[Gastro-highlights 2012]. / Gastro-Highlights 2012.

The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

[Highlights in gastroenterology 2011]. / Gastro-Highlights 2011. Zusammenfassung der Referate anlässlich des gastroenterologischen Symposiums am Universitätsspital Zürich vom 10. September 2011 unter der Leitung von Professor Michael Fried.

«Gastro-Highlights¼, an annual symposium dedicated to continuing education, took place at the University Hospital Zürich for the sixteenth time this autumn. In this well-attended event, major new findings in the fields of gastroenterology and hepatology that were published in the past year or recently presented at the «Digestive Disease Week (DDW)¼ were summarized for practising gastroenterologists and internists.

[Highlights in gastroenterology 2010]. / Gastro-Highlights 2010.

This summer saw the fifteenth edition of «Gastro-Highlights¼, a well-attended symposium dedicated to continuing education that takes place each year at the University Hospital in Zurich. Major new findings in the fields of gastroenterology and hepatology that were achieved in the past year and were recently presented at the «Digestive Disease Week (DDW)¼ were summarized here for practising gastroenterologists and internists.

[Intestinal perforation after preoperative colonic tattooing with India ink]. / Darmperforation nach präoperativer kolonoskopischer Tuschemarkierung.

Since the ability to palpate the bowel is lost in laparoscopic colon surgery preoperative marking of lesions is required to avoid "blind" resection. Endoscopic tattooing with India ink is the agent of choice because of its simplicity and the long-lasting stain. Only few complications have been reported using this technique. We present a case with localized necrosis and retroperitoneal perforation after endoscopic tattooing. Due to the formation of a local inflammatoric pseudotumor laparoscopic resection was impossible and open right hemicolectomy was necessary. Fever, abdominal pain and signs of local peritonitis after endoscopic tattooing should remind clinicians of this rare complication.

Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses.

Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.

Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis.

Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently known cationic trypsinogen gene mutations. The R117H mutation was detected in seven patients (six patients of two clinically classified HP families, one patient with clinically classified IJCP) and the A16V mutation in one IJCP patient. No cationic trypsinogen gene mutations were found in the remaining 96 patients with chronic and recurrent acute pancreatitis of various etiologies. Our results demonstrate the need for genetic testing to exclude HP, particularly in the presence of an atypical or unknown family history. In addition, cationic trypsinogen gene mutations are no predisposing factor in patients with chronic and recurrent acute pancreatitis of different etiologies.

[Helicobacter pylori and skin diseases--a (still) intact myth?]. / Helicobacter pylori und Hauterkrankungen--ein (noch) ungebrochener Mythos?

Helicobacter pylori plays a key role in the aetiology of peptic ulcer, gastric cancer and gastric MALT-lymphoma. Based on a number of reports, a possible relationship of Helicobacter pylori infection to a variety of different dermatoses has been suggested, including urticaria, rosacea, acne-rosacea, atopic dermatitis, alopecia areata, Sjögren's syndrome, Schönlein-Henoch purpura, and Sweet syndrome. Larger case-control studies, however, do not confirm this relationship. Therefore, Helicobacter pylori eradication therapy cannot be generally recommended in these dermatoses.

Quasispecies development of Helicobacter pylori observed in paired isolates obtained years apart from the same host.

Helicobacter pylori isolates show greater genetic diversity than other bacterial species studied, but the basis for this phenomenon is unknown. Whether detectable genomic mutation appears within an H. pylori population during persistent colonization was investigated. Paired H. pylori populations obtained across 7- to 10-year intervals from 13 patients were characterized by use of methods including polymerase chain reaction (PCR) genotyping for cagA, vacA, iceA, recA, and IS605; random arbitrarily primed DNA (RAPD)-PCR and amplified fragment length polymorphism (AFLP) analysis; and ELISA, to determine Lewis phenotypes. Genotyping, including recA sequence analysis, revealed that initial and follow-up populations represented the same population in 11 patients (85%). Nevertheless, distinct dissimilarities were shown within each of these 11 pairs by both RAPD-PCR and AFLP analyses. During follow-up, Lewis-y levels, but not Lewis-x levels, decreased significantly. The changes detected by RAPD-PCR and AFLP indicate that genetic drift occurs within H. pylori populations over the course of years of colonization of a single host.

Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils.

BACKGROUND & AIMS: Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma. METHODS: Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay. RESULTS: Gastric epithelial cell turnover was no different after infection with the wild-type, cagA(-), or vacA(-) strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles. CONCLUSIONS: In H. pylori-infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms.

Phenotypic diversity in Lewis expression of Helicobacter pylori isolates from the same host.

Populations of Helicobacter pylori cells show a stable expression of Lewis surface antigens, although phase variation may occur among individual organisms grown in vitro. We searched for variation in Lewis phenotypes among H. pylori cells of minimally in vitro-passaged isolates. Lewis expression in 180 clonal H. pylori populations from the primary culture of 20 gastric biopsy samples from 12 patients, and that in 160 isolates from primary cultures from 16 experimentally infected rodents, were examined by enzyme immunoassays. Substantial differences in Lewis expression were found among the isolates from 9 (75%) of 12 patients. These differences were unrelated to overall genetic diversity as determined by polymerase chain reactions for random amplified polymorphic DNA or cagA status, and they persisted during subsequent in vitro passage. In contrast, Lewis expression was highly uniform in H. pylori isolates from different rodents infected for up to 20 weeks. Variation in H. pylori Lewis expression in genetically closely related organisms in human subjects may provide a pool of bacterial phenotypes for the continuous selection of optimally host-adapted populations suitable for persistence.

Host specificity of Helicobacter pylori strains and host responses in experimentally challenged nonhuman primates.

BACKGROUND & AIMS: The specificity of colonization by Helicobacter pylori and complex host-bacterium interactions cannot be readily examined in humans. The aim of this study was to perform such analyses in rhesus monkeys. METHODS: Four animals that had been cured of natural H. pylori colonization were challenged with a mixture of 7 strains of human origin, and bacteria recovered during periodic videogastroscopy were DNA fingerprinted. RESULTS: Three animals carried mixtures of several strains for 4 months, after which strain J166 predominated. In the fourth animal, only strain J238 was isolated from the earliest phase of colonization through 7 months, but strain J166 again became predominant by 10 months after the challenge. Gastritis scores and plasma gastrin and anti-H. pylori immunoglobulin G titers reached levels observed in naturally colonized animals by 4 months after the challenge; however, no plasma immunoglobulin A response was observed up to 10 months. CONCLUSIONS: These results show that (1) natural colonization does not elicit protective immunity against subsequent H. pylori challenge; (2) individuals differ in susceptibility to different H. pylori strains during initial stages of colonization; and (3) certain strains are better suited than others for long-term survival in different hosts. These observations show the complexity of H. pylori-host interactions.

Experimental infection of Mongolian gerbils with wild-type and mutant Helicobacter pylori strains.

Experimental Helicobacter pylori infection was studied in Mongolian gerbils with fresh human isolates that carry or do not carry cagA (cagA-positive or cagA-negative, respectively), multiply passaged laboratory strains, wild-type strain G1.1, or isogenic ureA, cagA, or vacA mutants of G1.1. Animals were sacrificed 1 to 32 weeks after challenge, the stomach was removed from each animal for quantitative culture, urease test, and histologic testing, and blood was collected for antibody determinations. No colonization occurred after >/=20 in vitro passages of wild-type strain G1.1 or with the ureA mutant of G1.1. In contrast, infection occurred in animals challenged with wild-type G1.1 (99 of 101 animals) or the cagA (25 of 25) or vacA (25 of 29) mutant of G1.1. Infection with G1.1 persisted for at least 8 months. All 15 animals challenged with any of three fresh human cagA-positive isolates became infected, in contrast to only 6 (23%) of 26 animals challenged with one of four fresh human cagA-negative isolates (P < 0.001). Similar to infection in humans, H. pylori colonization of gerbils induced gastric inflammation and a systemic antibody response to H. pylori antigens. These data confirm the utility of gerbils as an animal model of H. pylori infection and indicate the importance of bacterial strain characteristics for successful infection.

Simultaneous expression of type 1 and type 2 Lewis blood group antigens by Helicobacter pylori lipopolysaccharides. Molecular mimicry between h. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms.

Previous structural investigations performed on the lipopolysaccharides (LPSs) from the human gastric pathogen Helicobacter pylori have revealed that these cell surface glycan molecules express type 2 partially fucosylated, glucosylated, or galactosylated N-acetyllactosamine O antigen chains (O-chains) of various lengths, which may or may not be terminated at the nonreducing end by Lewis X (Lex) and/or Ley blood group epitopes in mimicry of human cell surface glycoconjugates and glycolipids. Subsequently, serological experiments with commercially available Lewis-specific monoclonal antibodies also have recognized the presence of Lex and Ley blood group antigens in H. pylori but, in addition, have indicated the presence of type 1 chain Lea, Leb, and Led (H-type 1) blood group epitopes in some H. pylori strains. To confirm their presence, structural studies and additional serological experiments were undertaken on H. pylori strains suspected of carrying type 1 chain epitopes. These investigations revealed that the O-chain region of H. pylori strain UA948 carried both Lea (type 1) and Lex (type 2) blood group determinants. The O-chain from H. pylori UA955 LPS expressed the terminal Lewis disaccharide (type 1 chain) and Lex and Ley antigens (type 2). The O-chain of H. pylori J223 LPS carried the type 1 chain precursor Lec, the H-1 epitope (Led, type 1 chain) and an elongated nonfucosylated type 2 N-acetyllactosamine chain (i antigen). Thus, O-chains from H. pylori LPSs can also express fucosylated type 1 sequences, and the LPS from a single H. pylori strain may carry O-chains with type 1 and 2 Lewis blood groups simultaneously. That monoclonal antibodies putatively specific for the Leb determinant can detect glycan substructures (Le disaccharide, Lec, and Led) of Leb indicates their nonspecificity. The expression of both type 1 and 2 Lewis antigens by H. pylori LPSs mimics the cell surface glycomolecules present in both the gastric superficial (which expresses mainly type 1 determinants) and the superficial and glandular epithelium regions (both of which express predominantly type 2 determinants). Therefore, each H. pylori strain may have a different niche within the gastric mucosa, and each individual LPS blood group antigen may have a dissimilar role in H. pylori adaptation.

Epithelial attachment alters the outcome of Helicobacter pylori infection.

Genetically defined in vivo models are needed to assess the importance of target cell attachment in bacterial pathogenesis. Gastric colonization by Helicobacter pylori in human populations is common and persistent, and has various outcomes including peptic ulcers and cancer. The impact of attachment on the course of infection was examined in transgenic mice expressing a human receptor for H. pylori in their gastric epithelium. Persistent infection by a clinical isolate occurred at comparable microbial densities in transgenic and nontransgenic littermates. However, microbial attachment in transgenic mice resulted in production of autoantibodies to Lewisx carbohydrate epitopes shared by bacteria and acid-secreting parietal cells, chronic gastritis, and parietal cell loss. This model should help identify bacterial and host genes that produce attachment-related pathology.

Helicobacter pylori Lewis expression is related to the host Lewis phenotype.

BACKGROUND & AIMS: Lewis antigens occur in human gastric epithelium and in Helicobacter pylori lipopolysaccharide; their expression is polymorphic in both. Autoimmune mechanisms induced by bacterial Lewis expression have been proposed to cause gastritis. The aim of this study was to examine the relationship between bacterial and host gastric Lewis expression, as determined by the erythrocyte Lewis(a/b) phenotype, and between gastric histopathology and bacterial Lewis expression. METHODS: H. pylori Lewis expression was determined by enzyme immunoassays, erythrocyte Lewis phenotype was assessed by agglutination tests, and gastric histopathology was scored blindly. RESULTS: The host Lewis phenotype was (a+b-) in 15, (a-b+) in 34, and (a-b-) in 17 patients, therefore expressing Lewis x, y, or neither as their major gastric epithelial Lewis type 2 antigen. H. pylori from patients with Lewis(a+b-) expressed Lewis x more than y (1147 +/- 143 vs. 467 +/- 128 optical density units [ODU]; P = 0.006), isolates from patients with Lewis(a-b+) expressed Lewis x less than y (359 +/- 81 vs. 838 +/- 96 ODU; P = 0.0001), and isolates from Lewis(a-b-) patients expressed Lewis x and y approximately equally. Gastritis was unrelated to H. pylori Lewis expression. CONCLUSIONS: In mimicking host gastric epithelium, H. pylori cells not only express Lewis x and y, but the relative proportion of expression corresponds to the host Lewis phenotype, suggesting selection for host-adapted organisms.

[Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer]. / Wirkungsvergleich von Lansoprazol/Amoxicillin mit Omeprazol/Amoxicillin zur Eradikation von Helicobacter pylori bei Patienten mit Duodenalulkus.

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.