[Show abstract][Hide abstract] ABSTRACT: The discovery of Helicobacter pylori (H. pylori) represents one of the most notable events in the field of experimental and clinical medicine with great impact to daily practice even to surgery. It has led to a paradigm shift in the treatment of peptic ulcer disease. For the time period of almost one century, several scientists had described spiral-shaped bacteria in the stomach of animals and humans. However, it lasted till the early 1980s when Robin Warren and Barry Marshall successfully cultured H. pylori and recognised its causal relationship to chronic gastritis and peptic ulcer disease. Since then, our knowledge about H. pylori and related diseases has been continuously growing. Today, the bacterium is known to be mainly responsible for the development of chronic gastritis, peptic ulcer disease, MALT lymphoma and is considered as the main risk factor for the development of gastric cancer - all this led to a switch in the basic aetiopathogenetic considerations. In particular, eradication of H. pylori helped to i) develop an aetiology-based therapeutic and preventive approach to the diseases listed above according and adapted to findings, stage and manifestation, and ii) define a new role of surgery in the treatment concept. In addition, more and more evidence is being gathered for a possible association between the bacterium and several extragastric diseases.
Zentralblatt für Chirurgie 08/2014; 139(4):399-405. · 0.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The benefits of combined systemic and liver-directed treatments in inoperable intermediate- or advanced-stage hepatocellular carcinoma (HCC) have yet to be defined. This paper presents the planned safety analyses for the first 40 patients randomized to radioembolization with yttrium-90 ((90) Y) resin microspheres followed by sorafenib (n=20) or sorafenib only (n=20) in the SORAMIC study.
Liver international: official journal of the International Association for the Study of the Liver 06/2014; · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Helicobacter pylori infection occurs in children and adults worldwide. Standard triple therapy of omeprazole, amoxicillin and clarithromycin (OAC) may not be optimal.AimTo evaluate quadruple therapy with bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride, given with omeprazole in H. pylori infected subjects who failed previous OAC eradication therapy.Methods
This was a multicenter, open-label, single-arm, multinational study. Helicobacter pylori-positive subjects who had failed ≥1 previous course of OAC therapy with or without up to three supplemental treatments in the previous year. Subjects were treated for 10 days with a combination formulation containing bismuth subcitrate potassium 140 mg, tetracycline hydrochloride 125 mg, and metronidazole 125 mg, three capsules four times daily (q.d.s.), and omeprazole 20 mg twice daily (b.d.). The primary endpoint was H. pylori eradication rate defined as one negative 13C-urea breath test ≥28 days post-treatment.ResultsHelicobacter pylori eradication rates ranged from 93.2% to 93.8% in the intent-to-treat population (n = 49), and from 94.7% to 95.0% in the PP population (n = 40). No clinically meaningful differences were observed when analysed by country. Metronidazole resistance was observed in 16/49 (32.7%) subjects and clarithromycin resistance in 31/49 (63.3%) subjects. Thirty-three subjects (67.3%) reported 87 adverse events, and only one (2%) discontinued the study for an adverse event.ConclusionsA quadruple regimen of bismuth, metronidazole and tetracycline plus omeprazole produces a high eradication rate in subjects previously failing H. pylori eradication regimens. This bismuth-based regimen offers an effective option as rescue therapy.
[Show abstract][Hide abstract] ABSTRACT: Background and Aim: In the beginning of May 2011 and finally terminated on July 26th 2011 an outbreak of infections with enterohaemorrhagic Escherichia (E.) coli (EHEC) strain O104:H4 occurred in Germany. The aim of this study is to analyse whether media coverage of the outbreak influenced the number of patients presenting with diarrhoea to the emergency room of a tertiary centre and to evaluate the influence of information on perception and rating of symptoms. Methods: Prospectively collected data in a tertiary centre on the number of patients presenting to the emergency room with diarrhea during the EHEC outbreak was correlated with retrospectively collected data about the media coverage of the outbreak on TV and compared to the number of patients that had presented with diarrhea during a comparative period in 2010. Results: A total of 1,625 patients presented to our emergency room during the observation period in 2011 between May 31st and June 13th, including 72 patients (4.4 %) presenting with the predominant symptom of diarrhoea, of whom six patients (0.4 %) reported haemorrhagic diarrhoea. In the comparative period in 2010, between May 31st and June 13th, twelve patients (1.6 %) presenting the symptom of diarrhea were treated in our emergency room. The analysis of the news reports in 2011 revealed a total of 1,150 reports broadcast in the ARD and a total of 173 reports broadcast in the regional news channel MDR between May 29th and June 11th. In 2010 not a single report regarding our search terms was broadcast in the corresponding time period. Conclusion: Our data suggest a clear positive correlation of the frequency of TV reports dealing with the epidemic disease outbreak and the rate of outpatient consultations in emergency rooms because of diarrhoea and could make an important contribution for future discussions.
Zeitschrift für Gastroenterologie 03/2014; 52(3):277-280. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Zeitschrift für Gastroenterologie 03/2014; 52(3):296-305. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present the first report on peroral endoscopic myotomy (POEM) in the treatment of jackhammer esophagus. A 34-year-old female patient was newly diagnosed with a jackhammer esophagus. After failure of medical treatment, the patient underwent POEM procedure for myotomy of the spastic segment. Postoperatively, a mild emphysema and pneumothorax occurred that required drainage and antibiotic therapy until full recovery. Discharge was possible after 5 days. Six months later, she presented with recurrent but mild pain due to a remnant spastic segment proximal to the myotomy. Endoscopic balloon dilation was performed twice within 6 weeks with full symptomatic relief of pain and mild symptoms of dysphagia.
Diseases of the Esophagus 01/2014; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease.
United European Gastroenterology Journal. 08/2013; 1(4):226-235.
[Show abstract][Hide abstract] ABSTRACT: Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain.
To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH.
Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated.
Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001).
These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH.
[Show abstract][Hide abstract] ABSTRACT: Background:Aberrant activation of the canonical WNT signaling is a feature of colorectal cancer (CRC). Van-Gogh-like 2 (VANGL2) belongs to the non-canonical WNT pathway whose activation inhibits canonical WNT signaling. In this study, we investigated the role of VANGL2 and its epigenetic regulation in CRC.Methods:Van-Gogh-like 2 expression and promoter methylation after 5-aza-2'-deoxycytidine (5-aza) treatment were evaluated in CRC cells. DNA samples from 418 sporadic CRCs were tested for VANGL2 promoter methylation and microsatellite instability (MSI). Proliferation, colony formation and activation of the WNT pathway were tested in cells after VANGL2 overexpression.Results:Van-Gogh-like 2 mRNA was significantly higher in 5-aza-treated RKO, LOVO and SW48, whereas no differences were found in SW480. Van-Gogh-like 2 was fully methylated in RKO, SW48, HCT116, DLD1 and Caco2; partially methylated in LOVO, LS174T and SW837; and unmethylated in SW480, SW620 and HT29. Higher expression of VANGL2 mRNA was found in the unmethylated cell lines. In CRC specimens (8.93% MSI), methylated VANGL2 was associated with MSI, higher grade, proximal colon location and BRAF mutation. Van-Gogh-like 2 overexpression in SW480 significantly decreased proliferation, colony formation and β-catenin levels.Conclusion:Van-Gogh-like 2 is frequently methylated in MSI-CRCs with BRAF mutation and may act as a tumour suppressor gene, counteracting WNT/β-catenin signaling.British Journal of Cancer advance online publication, 11 April 2013; doi:10.1038/bjc.2013.142 www.bjcancer.com.
British Journal of Cancer 04/2013; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Modern functional laboratories provide various techniques for the evaluation of esophageal diseases. For proton pump inhibitor (PPI) refractory reflux symptoms the differentiation of non-erosive gastroesophageal reflux disease and functional heartburn is essential for the choice of further treatment. The differentiation of the two clinical entities is based on functional diagnostic methods, such as catheter-based and catheter-free pH measurement as well as combined pH measurement and intraluminal impedance. Combined pH measurement and impedance monitoring detects individual reflux episodes and permits the diagnosis of additional functional esophageal diseases, such as supragastric belching. The technical innovation of high resolution manometry has led to a better understanding of esophageal pathophysiology and motility disorders and resulted in a new classification system of esophageal motility disorders (Chicago classification). The diagnosis of achalasia by high resolution manometry differentiates three distinct subtypes which has a direct therapeutic impact on the clinical management.
Der Internist 03/2013; 54(3):279-86. · 0.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are frequent disorders affecting quality of life. They often require long-term treatment. Abdominal symptoms of both disorders can overlap, making differential diagnosis and treatment challenging. The extracts of the herbal combination preparation STW 5 (Iberogast(®)) exert pharmacological effects in different gastrointestinal regions and can address symptoms of both FD and IBS. This review summarizes safety and efficacy data of 12 clinical trials using STW 5 in FD and IBS since 1990. Double-blind and randomized studies versus placebo or active control found statistically significant effects of STW 5 on patients' symptoms with a comparable efficacy to a standard prokinetic. Non-interventional and retrospective studies confirmed these effects. Various studies evaluated the tolerability profile of STW 5: the incidence of adverse drug reactions was 0.04 %. The worldwide spontaneous reporting system confirmed this profile. STW 5 has a favorable tolerability which is relevant for long-term treatment.
[Show abstract][Hide abstract] ABSTRACT: AIM: Noninvasive methods for assessment and follow-up of
hepatic fibrosis are important for the management of patients with
chronic liver disease. Our aim was to assess a new panel of surrogate
biomarkers for prediction of severe hepatic fibrosis in patients with
chronic liver disease of different aetiology.
METHODS: 118 patients [62 males (52.5%) and 56 females]
(47.5%) were prospectively enrolled with a mean age of 55.6 years
±14.9. The aetiology of chronic liver disease was hepatitis B virus
infection (n=12), hepatitis C virus infection (n=20), autoimmune
hepatitis (n=36), alcoholic steatohepatitis (n=10), non-alcoholic
steatohepatitis: (n=12), hepatocellular carcinoma (n=16). 12 patients
had no evidence of liver disease. Biomarkers of hepatic fibrosis and
liver function tests (α2-macroglobulin, haptoglobin, apolipoprotein
A1, total bilirubin, GGT, ALT, total cholesterol, AST, albumin,
CA19-9, CA125, CA 15-3, INR, platelet count, hyaluronic acid, nitric
oxide) were analyzed in serum. As reference for staging of fibrosis
we used FibroTest and FibroScan. Biomarkers were correlated to
hepatic fibrosis by univariate and multivariate analyses as well as
RESULTS: Univariate and multivariate analysis indicated that
platelet count, α2-macroglobulin, total bilirubin, GGT and total
cholesterol were the most relevant biomarkers related to the stage of
hepatic fibrosis. A new panel for prediction of severe hepatic fibrosis
was created using these relevant parameters. Applying this panel;
severe hepatic fibrosis was predicted with a sensitivity of 97.4%
and a specificity of 85.9% in comparison with FibroTest. Also a
sensitivity of 78.8% and specificity of 90.9% was obtained by the
panel in comparison to FibroScan.
CONCLUSION: The new noninvasive panel allows accurate
prediction of severe liver fibrosis in different types of chronic liver
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10-20% develop peptic ulcers and <3% progress to gastric cancer (GC). Th1-predominant immune responses have been suggested to underlie H. pylori-induced gastric diseases. However, the reason for a strong inter-individual variation of susceptibility and course of the disease is currently far from being understood. It has been shown that H. pylori stimulates the host's Toll-like receptor (TLR) 2/1 complex. Furthermore, the single nucleotide polymorphism (SNP) I602S of TLR1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR1 SNP with H. pylori-mediated gastric pathologies. MATERIALS AND METHODS: Subjects with different TLR1 genotypes were analyzed for their IFN-γ response of NK- and T-cells. We further genotyped 548 patients with gastric diseases for this SNP and compared patients with gastritis with those having ulcer, and patients with high-risk gastritis versus patients with GC. RESULTS: Homozygous 602S allele carriers exhibited impaired in vitro IFN-γ responses to the TLR2/1 agonist Pam(3) CSK(4) . The TLR1 I602S SNP is significantly associated with GC (p = .002) and gastric ulcer (p = .051). Odds ratios showed significantly reduced risk regarding GC and peptic ulcer for the homozygous mutated genotype. The odds ratios were 0.4 (95% CI, 0.22-0.72) and 0.588 (95% CI, 0.35-1.00), respectively. CONCLUSION: In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H. pylori-induced gastric diseases, probably via diminished Th1 responses.
[Show abstract][Hide abstract] ABSTRACT: Until now, it is uncertain if the so-called pH-only reflux episodes that consist of a pH drop without evidence of retrograde bolus movement in multichannel intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal hernia (HH) may allow reflux of small volumes to occur that can be detected by pH-metry but not by MII. The aim was to search for a mechanism that can explain pH-only reflux, 20 patients (12 females and 8 males, median age 52 years, interquartile range [IQR]: 40.5-60.75 years) were investigated with MII-pH off PPI. Impedance and pH-metry data were analyzed separately. The differences in detection rate of acid reflux between pH-metry and MII were correlated with the presence of HH. In an in vitro experiment, MII-pH probes were flushed with citric acid in plastic tubes of different size with capillary diameter and diameters of 2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six patients and absent in 14 patients. In patients with HH in comparison with patients with absent HH, the difference of acid reflux detection between pH-metry and MII is significantly higher (70%, IQR: 15-88% and 3.6%, IQR: 0-31%, respectively). In vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5-mm plastic tubes. Acid reflux episodes in patients with HH are more frequently detected by pH-metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon.
Diseases of the Esophagus 08/2012; · 1.64 Impact Factor