Biomedical subjects

Michael Vieth

Publications and source records attributed to Michael Vieth.

At least 19 recordsLinked to original sources

PubMed2007

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.

Adult↗

PubMed2007

Curative endoscopic resection of early esophageal adenocarcinomas (Barrett's cancer).

BACKGROUND: In view of the increasing incidence of adenocarcinoma in Barrett's esophagus and the mortality and high morbidity rates associated with surgical therapy for this condition, safe and effective but less invasive methods of treatment are needed. OBJECTIVE: To evaluate efficacy and safety of endoscopic resection in these patients. DESIGN: Single-center prospective study. SETTING: Teaching hospital, conducted between October 1996 and September 2003. PATIENTS: A total of 100 consecutive patients (mean age, 62.1 +/- 10.9 years; range, 31-86 years) with low-risk adenocarcinoma of the esophagus (macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion without invasion into lymph vessels and veins; and histologic grades G1 and G2) arising in Barrett's metaplasia. INTERVENTIONS: Endoscopic resection with the suck-and-cut technique. MAIN OUTCOME MEASUREMENTS: Complete local remission. RESULTS: A total of 144 resections (1.47 per patient) were performed without technical problems. No major complications and only 11 minor ones (bleedings without decrease of Hb >2 g/dL; treated with injection therapy) occurred. Complete local remission was achieved in 99 of the 100 patients after 1.9 months (range, 1-18 months) and a maximum of 3 resections. During a mean follow-up period of 36.7 months, recurrent or metachronous carcinomas were found in 11% of the patients, but successful repeat treatment with endoscopic resection was possible in all of these cases. The calculated 5-year survival rate was 98%. Two patients died of other causes. LIMITATIONS: Nonblinded, nonrandomized study. CONCLUSIONS: Endoscopic resection is associated with favorable outcomes for low-risk patients with early esophageal adenocarcinoma (Barrett's carcinoma).

Adenocarcinoma↗

PubMed2006

Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study.

BACKGROUND: Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. METHODS: Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as "eosinophils present". Definite eosinophilic oesophagitis was defined as > or =20, probable as 15-19, and possible as 5-14 eosinophils/high-power field (HPF, at magnification x 40) in oesophageal biopsy specimens. RESULTS: Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for "eosinophils present". Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). CONCLUSIONS: Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.

Adult↗

PubMed2006

No prognostic impact of isolated lymphovascular invasion after radical resection of rectal cancer--results of a multicenter observational study.

BACKGROUND: The prognostic impact of isolated lymphovascular invasion (LVI) after radical resection of rectal cancer is controversially discussed. However, it could be relevant to decide for an adjuvant treatment. AIM: The aim of the analysis was, based on the data of an observational study, to determine the prognostic relevance of the isolated LVI. MATERIALS AND METHODS: Patients after radical resection of rectal cancer with no hemangioinvasion were subdivided in three groups: I-no LVI, no lymph node metastases (LNM); II-positive LVI, no LNM; III-positive LNM. Five-year local recurrence rate, distant metastases-free and disease-free survival were determined uni- and multivariate. RESULTS: Patients, n = 846, were studied (I, n = 471; II, n = 75; III, n = 300). The univariate comparison between the groups revealed the following 5-year results: local recurrence rate: 9.4 vs 10.0 vs 14.0%; distant metastases-free survival: 84.1 vs 82.5 vs 49.3%; disease-free survival: 83.2 vs 80.7 vs 45.5%. The differences between groups I and III were significant, but not between groups I and II. The determined higher disease-free survival rate in group II vs group III was significant (P = 0.041), but the differences in local recurrence rate and rate of distant metastases did not reach statistical significance. The multivariate analysis revealed no impact of the isolated LVI on the oncological outcome. CONCLUSION: The isolated LVI has no independent prognostic impact on the local recurrence rate and long-term survival after radical resection of rectal cancer. Based on this finding, no indication for an adjuvant treatment in these patients can be derived.

Aged↗

PubMed2006

Elevated risk for gastric adenocarcinoma can be predicted from histomorphology.

The number of patients with gastric cancer has more than doubled since 1985 in developing countries. Thus, the questions of whether it can be predicted from gastritis morphology, who is at risk and who has a lower risk of developing gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations, carcinoma, mucosa associated lymphoid tissue (MALT)-lymphoma and extragastric diseases only in some individuals. The frequency of ulcerations among H pylori-infected individuals is estimated to be 13%, gastric cancer about 1% and MALT lymphoma around 0.1%. In the literature a multistep model from chronic active H pylori-infection through multifocal atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and carcinoma has been described. But this model cannot be applied to all routine cases. Since risk factors such as metaplasia and atrophy are paracancerous rather than precancerous conditions, this raises the question whether there is a better morphological marker. Differences in topography, grade and activity of Helicobacter gastritis in the antrum and corpus might be good markers for identifying those who are at risk of developing gastric cancer. It is known that the so-called corpus dominant H pylori gastritis is found more frequently among individuals with early and advanced gastric cancer and within high risk populations. This is valid both for first-degree relatives of gastric cancer patients and for patients with gastric adenoma and hyperplastic polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more common in patients with advanced and early gastric cancer, first-degree relatives of patients with gastric cancer, patients with gastric adenoma and gastric hyperplastic polyps. Therefore, all these patients are at risk of developing gastric cancer. Next, the question of who is at risk of developing corpus-dominant gastritis is raised. It appears that patients with a low acid output more frequently develop gastric cancer. Eradication therapy is never performed too early but probably sometimes too late after the patients pass a "point of no return". Large prospective long term studies are necessary to prove this and identify new reliable markers for gastric cancer development.

Adenocarcinoma↗

PubMed2006

Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease.

OBJECTIVES: There is a controversy as to whether gastroesophageal reflux disease (GERD) exists as a spectrum of disease severity or as a categorial disease in three distinct groups: nonerosive (NERD) and erosive reflux disease (ERD) and Barrett's esophagus (BE). Aim of the study was to assess progression or regression of GERD over 2 yr in a large cohort of patients (N = 3,894) under routine clinical care in Germany, Austria, and Switzerland (ProGERD study). METHOD: Patients with predominant heartburn, with or without esophagitis, were recruited and classified according to endoscopic status at baseline, i.e., NERD, erosive reflux disease-Los Angeles (ERD-LA) grade A/B and ERD-LA grade C/D, and BE. After an initial treatment with esomeprazole, they were followed, regardless of their response. Medical therapy or endoscopy was initiated at the discretion of their primary care physician, in line with routine care. At 2 yr, endoscopy with biopsy was performed according to the protocol. RESULTS: After 2 yr, 25% of patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6% of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients had been off medication for at least 3 months. Patients with ERD-LA grade C/D were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade A/B and 0.5% for NERD. CONCLUSION: GERD does not seem to be a categorial disease. Progression and regression between grades was observed in this large cohort of patients under routine clinical care.

Barrett Esophagus↗

PubMed2006

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.

Adult↗

PubMed2006

Cholesterol glucosylation promotes immune evasion by Helicobacter pylori.

Helicobacter pylori infection causes gastric pathology such as ulcer and carcinoma. Because H. pylori is auxotrophic for cholesterol, we have explored the assimilation of cholesterol by H. pylori in infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glucosylation. Excessive cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells, such as macrophages and dendritic cells, and enhances antigen-specific T cell responses. A cholesterol-rich diet during bacterial challenge leads to T cell-dependent reduction of the H. pylori burden in the stomach. Intrinsic alpha-glucosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. We identify the gene hp0421 as encoding the enzyme cholesterol-alpha-glucosyltransferase responsible for cholesterol glucosylation. Generation of knockout mutants lacking hp0421 corroborates the importance of cholesteryl glucosides for escaping phagocytosis, T cell activation and bacterial clearance in vivo. Thus, we propose a mechanism regulating the host-pathogen interaction whereby glucosylation of a lipid tips the scales towards immune evasion or response.

Animals↗

PubMed2006

The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria.

BACKGROUND & AIMS: Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma, its diagnosis relying initially on recognition of a columnar-lined distal esophagus. We aimed to develop and validate explicit, consensus-driven criteria for the endoscopic diagnosis and grading of BE. METHODS: An international working group agreed on criteria and developed materials for their formal evaluation using video-endoscopic recordings gathered in a standardized manner in 29 patients. The criteria included assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualized BE segment as well as endoscopic landmarks. The recordings were scored according to these criteria by a separate international panel of 29 endoscopists. RESULTS: The Prague C & M Criteria give explicit guidance on the endoscopic recognition of BE and grading of its extent. The overall reliability coefficients (RC) for the assessment of the C & M extent of the endoscopic BE segment above the gastroesophageal junction were 0.95 and 0.94, respectively. The rates of exact agreement (for C & M values) for pairwise comparisons of individual patient values were 53% and 38%, respectively, whereas the values for agreement within a 2-cm interval were 97% and 95%, respectively. The overall RC for endoscopic recognition of BE >/=1 cm was 0.72, whereas for BE <1 cm, it was 0.22. The RCs for recognizing the location of the gastroesophageal junction and the diaphragmatic hiatus were 0.88 and 0.85, respectively. CONCLUSIONS: The Prague C & M Criteria have high overall validity for the endoscopic assessment of visualized BE lengths.

Barrett Esophagus↗

PubMed2006

In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy.

BACKGROUND & AIMS: Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy. Here, we have applied this technique to the in vivo diagnosis of Barrett's epithelium and associated neoplasia. METHODS: Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus. Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed. In vivo histology was compared with the histologic specimens. All digitally stored images were re-assessed by a blinded investigator by the confocal Barrett classification system to predict histology. Intraobserver and interobserver variations of the involved endoscopists were evaluated by using kappa statistics. RESULTS: Endomicroscopy allowed distinguishing between different types of epithelial cells and detected cellular and vascular changes in Barrett's epithelium at high resolution during ongoing endoscopy in 63 patients. Barrett's esophagus and associated neoplasia could be predicted with a sensitivity of 98.1% and 92.9% and a specificity of 94.1% and 98.4%, respectively (accuracy, 96.8% and 97.4%). The mean kappa value for interobserver agreement for the prediction of histopathological diagnosis was .843, whereas the intraobserver agreement showed a mean kappa value of .892. CONCLUSIONS: Fluorescence-aided endomicroscopy of Barrett's esophagus allows in vivo histology of the mucosal layer during ongoing endoscopy. Gastric and Barrett's epithelium and Barrett's-associated neoplastic changes can be diagnosed with high accuracy. Thus, endomicroscopy may be helpful in the management of patients with Barrett's esophagus.

Barrett Esophagus↗

PubMed2006

Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis-associated colorectal neoplasms.

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

Adenocarcinoma↗

PubMed2006

Angiotensin II receptor expression following intestinal transplantation in mice.

BACKGROUND: To further improve the success rate of intestinal transplantation there is a need to find early appearing indicators of rejection. The specific aim of this study was to compare Angiotensin (Ang) II type 1 receptor and Ang II type 2 receptor expression in relation to histological signs of rejection. METHODS: Mice of the C57BL6 strain with syngeneic intestinal grafts were compared to mice subjected to allogeneic intestinal transplantation with BalbC strain as donors. Local expression of Ang II type 1 and 2 receptor was evaluated using rt-PCR and Western blot and compared to histological picture in grafts and native intestine. RESULTS: The Ang II type 2 receptor protein expression was markedly up-regulated in the allogeneically transplanted graft from day 1 postoperatively. Histological signs of rejection were not seen until day 6. CONCLUSION: Intestinal allograft transplantation in mice is associated with a marked up-regulation of the Ang II type 2 receptor. However, the detailed role of the renin-angiotensin system in the immune rejection following intestinal transplantation remains to be clarified.

Animals↗

PubMed2006

Peptic ulcer disease in a general adult population: the Kalixanda study: a random population-based study.

The authors' aim in this study was to explore the prevalence, symptomatology, and risk factors for peptic ulcer in a general adult population. Between December 1998 and June 2001, the authors surveyed a random sample (n=3,000) of the adult population (n=21,610) in two communities in northern Sweden using a validated questionnaire, the Abdominal Symptom Questionnaire (response rate=74%). A subsample (n=1,001) of the responders was randomly invited to undergo esophagogastroduodenoscopy and symptom assessment (response rate=73%). The prevalence of peptic ulcer was 4.1% (20 gastric ulcers and 21 duodenal ulcers). Nausea and gastroesophageal reflux were significant predictors of peptic ulcer disease, but epigastric pain/discomfort was not. Six persons with gastric ulcer and two persons with duodenal ulcer were asymptomatic. Eight subjects with duodenal ulcer (38%) lacked evidence of current Helicobacter pylori infection. Five (25%) of the gastric ulcers and four (19%) of the duodenal ulcers were idiopathic (no use of aspirin or nonsteroidal antiinflammatory drugs, no H. pylori infection). Smoking, aspirin use, and obesity were risk factors for gastric ulcer; smoking, low-dose (<or=160 mg) aspirin use, and H. pylori infection were risk factors for duodenal ulcer. Peptic ulcer disease often coexists with atypical symptoms or no symptoms at all, and idiopathic duodenal ulcer may be more common than anticipated.

Adult↗

PubMed2006

Gastric-type well-differentiated adenocarcinoma and pyloric gland adenoma of the stomach.

Since 1985, when gastric-type well-differentiated adenocarcinomas were demonstrated in hyperplastic polyps of the stomach, we have studied phenotypic expression in gastrointestinal epithelial lesions. The recent discovery of MUC genes coding core proteins of mucin has improved research on the phenotypic expression of gastrointestinal neoplasms. The disease entity of gastric-type well-differentiated adenocarcinoma has recently been accepted, especially in Japan and Europe. This entity has often become a clinicopathological subject of discussion, because its biological behavior is possibly highly malignant, in spite of the difficulty in making endoscopic and histopathological diagnoses. Even under these circumstances, the term "gastric adenoma" usually means flat adenoma of the intestinal type. Gastric-type adenomas have been regarded as exceptional until recently. Although gastric-type adenomas could theoretically be classified into foveolar type and pyloric-gland type, foveolar-type adenoma is, in practice, difficult to distinguish from gastric-foveolar-type adenocarcinoma. In 2003, we first reported systematic clinicopathological analyses of pyloric gland adenoma, demonstrating its unstable and precancerous nature. In this article, we review and discuss the clinicopathological and molecular pathological aspects of gastric-type well-differentiated adenocarcinomas and pyloric gland adenomas, mainly based on our published and unpublished data.

Adenocarcinoma↗

PubMed2006

New pieces of the pathogenetic mosaic in inflammatory bowel disease.

Ulcerative colitis (UC) is a lifelong disease. Patients with UC have an approximately 20% risk of developing colorectal cancer. The risk of neoplasia increases with the duration of the disease. Why some patients develop colorectal cancer and others do not is still poorly understood. UC patients who develop cancer have an underlying process of genetic and epigenetic instability in the inflamed mucosa, as indicated previously using several experimental techniques. Rapid cell turnover and oxidative injury observed in UC mucosa is associated with accelerated telomere shortening, followed by an increased potential for the chromosomal ends to fuse, ending in chromatin damage and chromosomal instability. It has been reported that chromosomal losses are greater and telomeres are shorter in the biopsies of patients with long-standing UC. Telomere length is correlated with chromosomal instability in a variety of epithelial preneoplastic lesions. In the case of an inflammatory context for UC mucosa, this genetic (and also epigenetic) damage may be associated with cellular transformation and tumour progression. However, almost all studies have focussed on the hypothesis that the epithelial cells are the primary target in this scenario, leading to epithelial types of cancer. The elongated lifespan of fibroblasts, as reported in the paper by Getliffe et al. in this issue of European Journal of Gastroenterology and Hepatology, is probably indirectly connected to a lesser frequency of colorectal neoplasia in UC as part of a different immune response in these patients compared with individuals with early-onset UC.

Age of Onset↗

PubMed2006

Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of Helicobacter pylori infection.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastrointestinal mucosa exerting antimicrobial and anti-inflammatory effects. SLPI expression is generally induced during inflammation; however, Helicobacter pylori-mediated gastritis is associated with significantly decreased antral SLPI levels. The aim of the study was to investigate whether SLPI downregulation of gastric mucosa represents a specific phenomenon of H. pylori infection or is generally linked to gastric inflammation. METHODS: SLPI expression was retrospectively analysed by immunohistochemistry in 85 paraffin-embedded samples: H. pylori-induced (n=13), non-steroidal anti-inflammatory drug (NSAID)-enhanced (n=18), autoimmune (n=11), lymphocytic gastritis (n=26) and H. pylori-negative controls (n=17). The intensity of the staining was semiquantitatively analysed using an immunoreactivity score. Statistical analysis of differences was performed using an analysis of variance test. RESULTS: In comparison with the control group, the SLPI expression of antral mucosa in H. pylori-mediated and lymphocytic gastritis was significantly lower (P<0.001), whereas epithelial SLPI expression was not affected in NSAID-enhanced and autoimmune gastritis either in the antrum or corpus, respectively. Both the H. pylori-mediated and lymphocytic gastritis revealed a significantly lower expression of SLPI in infiltrating immune cells (P<0.01), whereas immune cells infiltrating the corpus in autoimmune gastritis showed higher SLPI levels than the immune cells of other groups (P<0.03). CONCLUSION: The local downregulation of SLPI in antral mucosa is specifically linked to H. pylori infection and is not a general phenomenon of gastric inflammation.

Adult↗

PubMed2006

Helicobacter pylori infection, but not low-dose aspirin, results in a local reduction of the secretory leukocyte protease inhibitor in gastroduodenal mucosa.

BACKGROUND: The secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein with mucosa-protective features. Helicobacter pylori and the usage of low-dose aspirin are two independent risk factors for the development of gastrointestinal diseases. Therefore, the effect of low-dose aspirin on gastrointestinal SLPI expression was analyzed in the context of H. pylori infection. MATERIAL AND METHODS: The study included 20 volunteers (H. pylori positive and negative: n = 10) who received 2 x 50 mg aspirin/day for 7 days. H. pylori-positive subjects underwent eradication therapy and repeated the protocol. Gastroduodenoscopy was performed at day 0, 1, 3, and 7, and biopsies were obtained each from antrum, corpus, and duodenal bulb. SLPI expression was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction of antral SLPI levels, ranging between 582 (day 0) and 941 pg/10 microg protein (day 7), was determined in H. pylori-positive compared to H. pylori-negative and -eradicated subjects (1600-2050 pg/10 microg protein, ANOVA: p = .001-.045). No differences concerning aspirin were observed within the groups. SLPI levels in corpus and duodenal mucosa were neither affected by H. pylori nor low-dose aspirin. There was an inverse correlation between SLPI and H. pylori-induced inflammation (activity: r = -0.575, -0.69 to -0.43, p < .0001; chronicity: r = -0.54, -0.66 to -0.39, p < .0001) in antral mucosa only, whereas other locations as well as the usage of low-dose aspirin did not show an association between SLPI and inflammation. CONCLUSIONS: H. pylori infection, but not the usage of low-dose aspirin, has a role in the down-regulation of antral SLPI levels.

Adult↗

PubMed2005

Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma.

PURPOSE: Vascular endothelial growth factor (VEGF)-D and its homolog VEGF-C influence lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3), and have been implicated in lymphatic tumor spread. Nodal dissemination of gastric adenocarcinomas critically determines clinical outcome and therapeutic options of affected patients. Therefore, we analyzed expression and prognostic significance of VEGF-D along with VEGF-C, and VEGFR-3 in gastric adenocarcinomas. MATERIALS AND METHODS: VEGF-C, VEGF-D, and VEGFR-3 were analyzed in 91 R(0)-resected primary gastric adenocarcinomas, corresponding noncancerous gastric mucosa, and lymph node metastases employing immunohistochemistry and/or in situ hybridization. Blood and lymph vessel densities were assessed after staining with CD31 and LYVE-1-specific antibodies. RESULTS: VEGF-D and VEGF-C were detected in 67.0% and 50.5% of gastric cancers, respectively. Healthy gastric mucosa was negative for VEGF-C and in 12.5% positive for VEGF-D. Presence of VEGF-D (P = .005) or VEGF-C (P = .006) was correlated with lymphatic metastases and decreased survival (VEGF-D, P < .05; VEGF-C, P < .05). VEGFR-3 was correlated with reduced carcinoma-specific survival (P < .05), and Cox multivariate regression analysis qualified VEGF-D and VEGFR-3, but not VEGF-C, as independent prognostic parameters. In lymph node-positive gastric cancers, presence of VEGF-D/VEGFR-3 was associated with poor survival, whereas absence of VEGF-D/VEGFR-3 defined a subgroup of patients with clearly favorable prognosis. CONCLUSION: VEGF-D and VEGFR-3 are novel independent prognostic marker molecules aiding to identify patients with poor prognosis after curative resection of gastric adenocarcinomas. Combined analysis of the VEGF-C/VEGF-D/VEGFR-3 system can be useful to identify patients with unfavorable clinical outcome and thereby may help to refine therapeutic decisions in gastric cancer.

Adenocarcinoma↗