Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

BACKGROUND AND AIMS: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC. METHODS: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire. RESULTS: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001). CONCLUSIONS: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research.

OBJECTIVES: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. METHODS: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. RESULTS: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p = 0.001). CONCLUSIONS: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

The prevalence of gastric heterotopia of the proximal esophagus is underestimated, but preneoplasia is rare - correlation with Barrett's esophagus.

BACKGROUND: The previously reported prevalence of gastric heterotopia in the cervical esophagus, also termed inlet patch (IP), varies substantially, ranging from 0.18 to 14%. Regarding cases with adenocarcinoma within IP, some experts recommend to routinely obtain biopsies from IP for histopathology. Another concern is the reported relation to Barrett's esophagus. The objectives of the study were to prospectively determine the prevalence of IP and of preneoplasia within IP, and to investigate the association between IP and Barrett's esophagus. METHODS: 372 consecutive patients undergoing esophagogastroduodenoscopy were carefully searched for the presence of IP. Biopsies for histopathology were targeted to the IP, columnar metaplasia of the lower esophagus, gastric corpus and antrum. Different definitions of Barrett's esophagus were tested for an association with IP. RESULTS: At least one IP was endoscopically identified in 53 patients (14.5%). Histopathology, performed in 46 patients, confirmed columnar epithelium in 87% of cases, which essentially presented corpus and/or cardia-type mucosa. Intestinal metaplasia was detected in two cases, but no neoplasia. A previously reported association of IP with Barrett's esophagus was weak, statistically significant only when short segments of cardia-type mucosa of the lower esophagus were included in the definition of Barrett's esophagus. CONCLUSIONS: The prevalence of IP seems to be underestimated, but preneoplasia within IP is rare, which does not support the recommendation to regularly obtain biopsies for histopathology. Biopsies should be targeted to any irregularities within the heterotopic mucosa. The correlation of IP with Barrett's esophagus hints to a partly common pathogenesis.

GERD assessment including pH metry predicts a high response rate to PPI standard therapy.

BACKGROUND: Inadequate response to proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) is reported in up to 40%. Patients with non erosive reflux disease (NERD) have lower response rates compared to patients with erosive reflux disease (ERD); pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD. Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg) for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry. METHODS: All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ) and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO). In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d. RESULTS: 31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71%) had abnormal acid exposure, 9 patients had normal pH metry (29%). Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities. 24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%). Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms. CONCLUSIONS: Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.

Helicobacter pylori infection and fundic gastric atrophy are not associated with esophageal squamous cell carcinoma: a case-control study.

OBJECTIVE: Recent studies from Asia and Northern Europe suggest that apart from alcohol intake and smoking, fundic gastric atrophy (FGA) may also increase the risk of esophageal squamous cell carcinoma (OSCC). However, because of the wide geographic variation of this cancer and the changing prevalence of the Helicobacter pylori infection, these findings need to be confirmed in other ethnic groups. The aim of this case-control study was to investigate whether H. pylori infection and FGA carry an increased risk for OSCC. PATIENTS AND METHODS: FGA was evaluated, by histology and serology, in 75 patients with OSCC, and 75 sex-matched and age-matched controls. Pepsinogen (PG) I levels 70 µg/ml or less and PG I/II ratio of 3 or less were indicative for FGA. H. pylori infection was defined as positivity to at least one test among histology, rapid urease test, and serology for both general anti-IgG and anti-CagA. RESULTS: Overall, the prevalence of H. pylori infection was identically high (70.7%) in both patients with OSCC and controls. FGA diagnosed by serology and histology was not associated with an increased risk for OSCC [odds ratio (OR)=1.17; 95% confidence interval (CI)=0.54-2.56 and OR=1.91; 95% CI=0.6-5.99, respectively]. ORs (95% CI) for hazardous alcohol consumption, smoking, and the presence of both risk factors were 5.75 (2.20-15.05), 22.18 (9.41-52.28), and 31.69 (8.39-119.67), respectively. CONCLUSIONS: Hazardous alcohol consumption and smoking increase synergistically the risk for developing OSCC. In our population neither H. pylori infection nor FGA was associated with an increased risk for OSCC.

Correlation of serum pepsinogens and gastrin-17 with atrophic gastritis in gastroesophageal reflux patients: a matched-pairs study.

BACKGROUND AND AIM: An algorithm (GastroPanel) for the non-invasive diagnosis of atrophic gastritis has been previously proposed, based on serum pepsinogen-I, gastrin-17, and Helicobacter pylori (H. pylori) antibodies. The aim of the present study was to evaluate whether serum markers correlate with and predict gastric atrophy in gastroesophageal reflux disease (GERD) patients. METHODS: The baseline data of the prospective ProGERD study, a study on the long-term course of GERD (n=6215 patients), served to select patients with atrophic gastritis diagnosed in biopsies from gastric antrum and corpus, and control cases without atrophy. A total of 208 pairs were matched for age, sex, GERD status (erosive vs non-erosive), presence of Barrett's esophagus, and histological H. pylori status were retrieved. Serum pepsinogen-I, gastrin-17, and H. pylori antibodies were determined using specific enzyme immunoassays. RESULTS: A significant negative correlation was found between the degree of corpus atrophy and the level of serum pepsinogen-I. A previously-reported negative correlation between the degree of antral atrophy and serum gastrin-17 could not be confirmed. The low sensitivity (0.32) and specificity (0.70) of the GastroPanel algorithm were mainly due to over diagnosis and under diagnosis of advanced atrophy in the antrum. CONCLUSION: The diagnostic validity of the GastroPanel algorithm to diagnose gastric atrophy non-invasively is not sufficient for general use in GERD patients.

Impact of high-resolution transabdominal ultrasound in the diagnosis of complications of Crohn's disease.

OBJECTIVE: Crohn's disease is associated with intestinal complications such as strictures, fistulas and abscesses. As the management of the patients is influenced by the presence or absence of complication, sensitive diagnostic modalities to detect these complications are needed. The aim of this prospective study was to evaluate the diagnostic accuracy of high-resolution transabdominal ultrasound in the diagnosis of complications of Crohn's disease. MATERIAL AND METHODS: From April 2003 to July 2009, 58 patients (31 women, 27 men; mean age 36.3 years, range 13-86 years) with known Crohn's disease were included in the study and investigated with high-resolution transabdominal ultrasound. The diagnosis of Crohn's disease was based on clinical, endoscopic, histological, radiological and operative findings. Patients with other forms of enteritis (e.g. infectious) were excluded from the study. Twenty of the 58 patients were investigated on a second occasion with other symptoms than at the first admission. The time duration between the two ultrasound investigations was at least 3 months. Consequently, a total of 78 ultrasound investigations were done in 58 patients. With respect to their clinical symptoms, all patients were further investigated within 2 weeks after ultrasound with magnetic resonance imaging, and/or computed tomography, and/or enteroclysis, and/or endoscopy with biopsy. Together with clinical data (Crohn's disease activity index) and surgical findings these investigations were used as reference procedure. RESULTS: The sensitivity, specificity, positive predictive and negative predictive values of ultrasound were as follows: 0.86, 0.90, 0.83 and 0.92 for stenoses; 0.78, 0.95, 0.86, and 0.91 for fistulas; 0.90, 0.99, 0.90 and 0.99 for abscesses, respectively. CONCLUSIONS: High-resolution transabdominal ultrasound done by experienced examiners has an excellent diagnostic accuracy in the diagnosis of complications in patients with Crohn's disease. Thus, it can be recommended as one of the primary investigative procedures for evaluation of Crohn's disease.

Interleukin-1beta and interleukin-8 expression correlate with the histomorphological changes in esophageal mucosa of patients with erosive and non-erosive reflux disease.

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-1beta (IL-1beta) 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-1beta and IL-8 were analyzed by real-time RT-PCR. RESULTS: ERD and NERD patients revealed significant higher levels of IL-1beta 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-1beta (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-1beta and IL-8 that correlates with histomorphological changes in esophageal mucosa.

Chronic mucosal inflammation of the gastric cardia in gastroesophageal reflux disease is not regulated by FOXP3-expressing T cells.

INTRODUCTION: Chronic inflammation at the cardia occurs in gastroesophageal reflux disease (GERD), as well as in the presence of Helicobacter pylori. Regulatory T cells have been demonstrated for H. pylori-induced gastritis, whereas their role has not been studied in GERD. METHODS: We prospectively analyzed the expression of FOXP3, a marker of various regulatory T cells, as well as the mucosal transcript levels of TGF-beta1 and IL-10. RNA and protein levels have been determined in cardiac biopsies of 70 patients stratified according to GERD (n = 22), controls (n = 17), and H. pylori (n = 31). RESULTS: GERD presented with chronic inflammation and reduced FOXP3-mRNA in the cardiac mucosa (-84%), whereas H. pylori-positive patients revealed a 25.1-fold increase of FOXP3 gene expression. These results were verified by the regulatory cytokines IL-10 and TGF-beta1, and by the immunohistochemical detection of intramucosal FOXP3-expressing T cells. CONCLUSION: Chronic inflammation at the cardia associated with either GERD or H. pylori differs concerning the presence of FOXP3-expressing T cells. In contrast to H. pylori, FOXP3-expressing T cells are not associated with GERD-associated carditis.

Naturally occurring regulatory T cells (CD4+, CD25high, FOXP3+) in the antrum and cardia are associated with higher H. pylori colonization and increased gene expression of TGF-beta1.

BACKGROUND: Helicobacter pylori causes gastric inflammation. Despite the induction of H. pylori-specific B- and T cells, the immune response is not sufficient to clear the infection. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. FOXP3 was shown to be expressed in a subset of Treg cells known as 'naturally occurring Treg cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. MATERIALS AND METHODS: The study included 76 patients stratified according to the presence of H. pylori. Gene expression levels of FOXP3, transforming growth factor (TGF)-beta1, and interleukin-10 were analyzed by quantitative real-time polymerase chain reaction in biopsies from gastric antrum, corpus, and cardia. FOXP3 expression was also analyzed by immunohistochemistry. Differences in expression levels were analyzed by comprehensive statistical analyses and correlated with clinical and histomorphologic parameters. RESULTS: H. pylori-positive patients revealed a 19- to 25-fold induction of FOXP3 transcript levels in antrum and cardia (p < .02). FOXP3 transcript levels correlated positively with inflammation (p < .04) and TGF-beta1 transcript levels (p < .001). Furthermore, a positive correlation between FOXP3(+) Treg cells and H. pylori colonization was demonstrated. CONCLUSION: This study demonstrates that H. pylori-induced gastritis is associated with a recruitment of naturally occurring FOXP3(+) Treg cells that correlates with the degree of bacterial colonization and mucosal TGF-beta1 expression. Together, these data support the hypothesis that naturally FOXP3(+) Treg cells play a role in the lifelong persistence of H. pylori infection in humans.

Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas.

Tissue inhibitor of metalloproteinase 3 (TIMP-3) promoter methylation has been linked to loss of TIMP-3 expression in various cancers. In this study, we analyzed TIMP-3 gene methylation using MethyLight assay and TIMP-3 mRNA expression using reverse transcription-polymerase chain reaction analysis in 22 esophageal cancers, 27 gastric carcinomas, and 7 cancer cell lines. We also analyzed TIMP-3 protein expression by immunohistochemistry and its association with clinicopathological characteristics in two cohorts of gastric cancer comprising a total of 347 patients. The TIMP-3 gene was more commonly methylated in adenocarcinomas of the esophagus (9/13) and stomach (9/15) than in the corresponding nonneoplastic mucosa of the esophagus (1/8; P = .024) and stomach (2/14; P = .021). In gastric cancer patients, TIMP-3 was decreased in a diffuse-type gastric cancer and in cancers with poor differentiation and was associated with poor survival (P = .04). In summary, we observed frequent TIMP-3 promoter methylation in adenocarcinomas of the esophagus and stomach and the loss of TIMP-3 expression seems to be of clinical and prognostic relevance in these cancers.

Gastroesophageal reflux disease leads to major alterations in lectin-binding in the columnar epithelium of the gastroesophageal junction.

OBJECTIVE: Chronic gastritis and esophagitis are associated with changes in glycosylation patterns. Lectins are carbohydrate-binding proteins that are used as sensitive tools in the analysis of glycosylation patterns. The aim was to investigate the binding patterns of lectins UEA-I, DBA, HPA and PNA at the squamocolumnar junction in relation to the existence of gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection. MATERIAL AND METHODS: Eighty-eight patients with either dyspeptic or gastroesophageal reflux-related symptoms were included in the study and stratified into four subgroups based on the presence of GERD and H. pylori infection. The binding patterns of lectins were examined immunohistochemically at the squamocolumnar junction, in squamous (SE) and columnar-lined epithelium (CLE). Staining patterns of lectins were semiquantitatively evaluated using an immunohistochemical score; data were analyzed using the non-parametric Mann-Whitney U-test. RESULTS: The presence of GERD led to significant changes in lectin-binding patterns. Lectin-binding was significantly reduced for UEA-I (p<0.0001), DBA (p<0.0001), PNA (p<0.01) and DBA (p<0.05) in CLE and SE of patients with GERD, respectively. H. pylori infection was associated with reduced PNA and DBA binding to the deep glandular mucosa of CLE (p<0.05) and surface SE (p<0.05), respectively. CONCLUSIONS: Distinct and complex changes in lectin-staining patterns are most prominent in CLE of patients with GERD. The functional relevance of changes in the glycosylation patterns needs further investigation.

Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells.

Helicobacter pylori infection is related to the development of diverse gastric pathologies, possibly by affecting epithelial junctional complexes that define cell polarity and play an essential role in transepithelial transport and cell-cell adhesion. Using primary gastric epithelial cell cultures, effects of H. pylori on the expression and localization of tight/adherence junction proteins and the resulting morphological changes and migratory capabilities were studied under in vivo-like conditions. Gastric epithelial cells were isolated from biopsies or gastrectomies and maintained in Quantum286 on collagen I-coated culture dishes or cover-slips. Cell cultures were characterized and further analyzed by western blot and immunofluorescent staining for ZO-1, p120ctn, and H. pylori CagA. Morphological changes and migratory response were monitored by time-lapse digital image microscopy. ZO-1 and p120ctn protein expression levels remain unaffected by H. pylori infection. Immunocytochemistry on H. pylori-infected primary cell monolayers focally showed disruption of intercellular ZO-1 staining and accumulation of ZO-1 in small vesicles. H. pylori infection recruited non-phosphorylated p120ctn to perinuclear vesicles. The fraction of phosphorylated p120ctn increased and could be detected in the nucleus, at the cell membrane, and at the leading edge of migrating cells. These alterations, triggered by H. pylori infection, are associated with an elongation phenotype and increased migration.

STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study.

BACKGROUND: Functional dyspepsia (FD) constitutes a complex picture with a variety of epigastric symptoms. No standard therapy is currently available for FD. OBJECTIVE: This multicenter, placebo-controlled, double-blind study evaluated the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh plant extract from Iberis amara. METHODS: Patients with FD were included. Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were required. A total of 315 patients were treated with 3 x 20 drops/day of either STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The principal outcome criterion was the change in a validated Gastrointestinal Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS: A total of 315 patients remained in the safety population. Of them, 158 were treated with STW 5 and 157 with placebo. The intention-to-treat population comprised 308 patients. Dropout number was similar in both groups. GIS showed improvement during the treatment period. The STW 5 group improved 6.9+/-4.8 points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not influence the results. Drug tolerability and safety were similar in both groups. CONCLUSION: This placebo-controlled study with an 8-wk treatment period documents the efficacy of STW 5 in FD.

Localization of TFF3 peptide in human esophageal submucosal glands and gastric cardia: differentiation of two types of gastric pit cells along the rostro-caudal axis.

TFF3 (trefoil factor family 3), which is a major secretory product of the gastric antrum and the intestine, but which is nearly absent in the gastric corpus, plays a key role in the maintenance of mucosal integrity. Here, we have systematically investigated TFF3 expression in the esophagus and gastric cardia by the use of reverse transcription/polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Synthesis of TFF3, but not TFF1 or TFF2, is detectable in esophageal submucosal glands. The stratified squamous epithelium is devoid of TFF synthesis. Prominent TFF3 expression starts at the Z-line with a sharply decreasing gradient toward the cardia. Immunohistochemistry has localized TFF3 to surface mucous cells of the proximal cardia. TFF3 distribution differs characteristically from that of TFF1 (secreted primarily by superficial surface mucous cells), whereas TFF3, together with the mucin MUC5AC, is also found in deeper lying cells toward the isthmus. This is the first report of TFF3 as a typical secretory peptide of esophageal submucosal glands and gastric cardia. The different expression patterns of TFF3 and TFF1 in the cardia suggest a stepwise maturation of surface mucous cells from TFF3/MUC5AC-positive cells close to the isthmus to TFF1/TFF3/MUC5AC-positive cells at the pit. The gradient of TFF3 expression along the gastric rostro-caudal axis defines two types of gastric pit cells: those secreting TFF3 in the cardia and the antrum and those nearly devoid of TFF3 synthesis in the corpus. This indicates the special requirement, particularly of the esophagogastric junction, for TFF3-triggered protection and repair.

Prevalence of H pylori associated "high risk gastritis" for development of gastric cancer in patients with normal endoscopic findings.

AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper-GI endoscopy. METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems. RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development--only a proper follow-up can provide this information.

Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases.

The secretory leukocyte protease inhibitor (SLPI) exerts antiproteolytic activity towards serine proteases, as well as anti-microbial and anti-inflammatory effects. To investigate its role in H. pylori-mediated diseases, SLPI expression was analyzed by RT-PCR, ELISA and immunohistochemistry in clinical samples and gastric tumor cell lines. Determination of the mucosal SLPI levels in 126 patients confirmed the previously reported downregulation of SLPI in H. pylori-infected patients. The lower SLPI levels in antral biopsies of H. pylori-positive subjects were associated with a 30-fold increase (p<0.01) in neutrophil elastase activity, and a significant negative correlation was demonstrated for both parameters (R=-0.63, p=0.0002). Eradication of the bacterium in a long-term study (5-7 years) led to a recovery of mucosal SLPI expression. In vitro experiments using four gastric tumor cell lines (AGS, MKN-28, MKN-45, NCI-N87) generally confirmed the clinical findings. While the co-incubation of these cell lines with H. pylori resulted in lower or unchanged SLPI protein levels, the corresponding SLPI mRNA amounts were upregulated by up to five-fold (p=0.006) in all cell lines. Taken together, these results indicate that the reduction in antral SLPI levels in H. pylori-infected subjects has a functional relevance for gastric mucosa and the H. pylori-induced decrease in SLPI is primarily regulated at the posttranslational level.

Sonographic diagnosis and endoscopic therapy of a biliopancreatic fistula complicating a pancreatic pseudocyst.

This is the first report of a case of biliopancreatic fistula complicating a pancreatic pseudocyst diagnosed correctly by transabdominal ultrasound. The diagnosis was confirmed by magnetic resonance and endoscopic retrograde cholangiopancreatography. The fistula was treated successfully with biliary stenting. The clinical and imaging features of this exceptional complication are presented along with a brief review of the topic.

Impact of the operator's experience on value of high-resolution transabdominal ultrasound in the diagnosis of choledocholithiasis: a prospective comparison using endoscopic retrograde cholangiography as the gold standard.

OBJECTIVE: Transabdominal ultrasound (US) is the most frequently used imaging method for the diagnosis of choledocholithiasis. The aim of this prospective study was to evaluate the diagnostic accuracy of high-resolution US in the diagnosis of common bile duct stones depending on the operator's experience and in comparison with endoscopic retrograde cholangiography (ERC) as the gold standard. MATERIAL AND METHODS: From April 2003 through November 2004, 126 patients referred because of clinically and biochemically suspected common bile duct stones were included in the study. Two patients were excluded because they refused to undergo ERC. Consequently, the study comprised 124 patients (86 F, 38 M, mean age 63.2 years, range 21-91 years). High-resolution US was performed (2-5 MHz sector scanner; Siemens Elegra, Erlangen, Germany) by operators who were unaware of the results of other imaging procedures. The definitive diagnosis was established by means of ERC. RESULTS: Thirty-five out of 124 patients were investigated by experienced examiners. Twenty-seven of 35 patients (77%) were found to have stones at ERC. Bile duct stones were correctly found by US in 22 out of 27 patients (sensitivity 82%, 95% CI: 63-92). Of the 8 patients without stones at ERC, one false-positive diagnosis was made with US (specificity 88%, 95% CI: 53-98). Correct diagnoses were made in 29 out of 35 (accuracy 83%, 95% CI: 67-92) patients investigated by experienced examiners. Eighty-nine out of 124 patients were investigated by less-experienced examiners. Fifty-four of 89 patients (61%) were found to have stones at ERC. Choledocholithiasis was found correctly in only 25 out of 54 patients (sensitivity 46%, 95% CI: 34-59). Of the 35 patients without stones at ERC, three false-positive diagnoses were made with US (specificity 91%, 95% CI: 78-97). In conclusion, correct diagnoses were observed in 57 of 89 patients (accuracy 64%, 95% CI: 54-73) investigated by less-experienced examiners (p<0.05 in comparison with the results of experienced examiners). CONCLUSIONS: High-resolution US carried out by experienced examiners has a high diagnostic accuracy in the diagnosis of choledocholithiasis. Therefore, good training and continued experience are prerequisites for successful sonographic detection of bile duct stones using US. Under these conditions, further expensive and invasive methods such as ERC, magnetic resonance cholangiopancreatography and endoscopic ultrasonography may not be necessary in cases with a clear sonographic diagnosis.