Biomedical subjects

Michael Vieth

Publications and source records attributed to Michael Vieth.

At least 37 records · Page 2Linked to original sources

PubMed2005

DAPK promotor methylation is an early event in colorectal carcinogenesis.

Death-associated protein kinase (DAPK) is frequently inactivated by promotor hypermethylation in various human cancers. At present, little is known about the significance of DAPK inactivation in colorectal carcinogenesis. We therefore, investigated macrodissected samples of 22 formalin-fixed and paraffin-embedded T1-carcinomas showing normal colon mucosa, intraepithelial neoplasia and carcinoma tissue on the same slice. Dissected carcinoma areas showed a higher frequency of DAPK promotor methylation (81.2%) compared to intraepithelial neoplasia (68.2%). Colon mucosa adjacent to intraepithelial neoplasia or carcinoma showed DAPK promotor methylation in only two of eight cases (25%). We suggest that DAPK promotor hypermethylation may play an important role in the early steps of tumor progression in colorectal carcinoma.

Adult↗

PubMed2005

Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis.

AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease, which is specifically expressed in cytotoxic lymphocytes, in different types of chronic inflammation of the gastric mucosa. METHODS: Gastric and duodenal biopsies of patients with Helicobacter pylori (H pylori)-associated active gastritis (Hp, n = 19), chemically induced reactive gastritis (CG, n = 17), autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10), and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG. RESULTS: Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P<0.001) and significantly decreased for HP (0.7%, P<0.05). Double staining with anti-CD3 and anti-CatW antibodies revealed that >90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P<0.01). The corresponding proportion of CatW/CD45-postive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P<0.05). CONCLUSION: The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.

Autoimmune Diseases↗

PubMed2005

Strictures, diaphragms, erosions or ulcerations of ischemic type in the colon should always prompt consideration of nonsteroidal anti-inflammatory drug-induced lesions.

AIM: To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA-induced erosions and ulcers of the stomach. METHODS: In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients (415 women, 196 men, average age 60.5 years) with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSAID-induced lesions whenever necroses of the ischemic type were found. Together with the histological report, we enclosed a questionnaire to investigate the use of medication. The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings. RESULTS: At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years (43.9%) or months (29.5%). The most common indication for the use of these drugs was pain (64.3%), and the most common indication for colonoscopy was bleeding (55.5%). Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon (79.9%). A separate analysis of age and sex distribution, endoscopic and histological findings for NSAIDs alone, ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups. CONCLUSION: This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective controlled study.

Adult↗

PubMed2005

Pyloric gland adenoma arising in Barrett's esophagus with mucin immunohistochemical and molecular cytogenetic evaluation.

Pyloric gland adenoma is a recently described and very rare entity. The occurrence of adenoma is very unusual in Barrett's epithelium of the esophagus. We report a case of esophageal polyp showing the features of pyloric gland adenoma, which was surrounded by so-called specialized columnar epithelium. Immunohistochemically, most tumor glands were strongly positive for MUC6, except in the superficial layer. MUC5AC was positive in almost all tumor cells, but MUC2 and CD10 were negative in the tumor. MIB-1-positive proliferating cells were distributed throughout the tumor. Microdissection and comparative genomic hybridization analyses revealed losses on 2p24-25.2, 2q14.1-ter, 5q31.3-32, 6q23-24, 8q23-24.2, 11q22.3-24 and 18q21.1-22. This is the first case of pyloric gland adenoma found to arise in Barrett's epithelium of the esophagus, showing its unstable and precancerous nature.

Adenoma↗

PubMed2005

A case of mucoepidermoid carcinoma with melanin pigmentation manifested in the palate.

This paper describes the first documented case of mucoepidermoid carcinoma (MEC) with melanin pigmentation manifested in the palate. Histopathological sections showed a neoplasm composed of epidermoid, mucous-producing and intermediate cells. Numerous large cells contained dark pigmented materials. Fontana Masson staining revealed dendritic melanocytes and melanin granules. HMB-45, Melan A and S-100 protein were all positive for melanocytes. Histopathological examination was not typical for malignant melanoma; the lesion was diagnosed as a low-grade MEC with melanin pigmentation.

Adult↗

PubMed2005

Long-term follow-up after complete ablation of Barrett's esophagus with argon plasma coagulation.

AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with histologically proven non-neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P = 0.0004). CONCLUSION: The long-term relapse rate of non-neoplastic BE following complete ablation with high-power APC is low (3% per year).

Adenocarcinoma↗

PubMed2005

Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn disease.

Nuclear factor-kappaB (NF-kappaB) is the main target of anti-inflammatory therapies in human chronic inflammatory bowel diseases (IBD), Crohn disease, and ulcerative colitis. This study investigates the molecular anti-inflammatory mechanisms of SB203580, an inhibitor of the mitogen-activated protein kinase p38. The murine trinitrobenzene sulfonic acid (TNBS)-induced colitis was used as an established model of human Crohn disease. Here we show that SB203580 improved the clinical condition, reduced intestinal inflammation, and suppressed mRNA levels of pro-inflammatory cytokines elevated upon induction of colitis. Besides p38 kinase activity, the "classical" IkappaB-dependent NF-kappaB pathway was strongly up-regulated during colitis induction, whereas the "alternative" was not. SB203580 treatment resulted in a drastic down-regulation of p38 and NF-kappaB activity. The molecular analysis of NF-kappaB activation revealed that Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK), a key component of a pathway leading to NF-kappaB induction, is also strongly inhibited by SB203580. In contrast, SB203580 had no effect on the colitis-induced activation of other potential NF-kappaB-activating kinases such as protein kinase C (PKC), mixed lineage kinase 3, and the oncogene product Cot/TPL2. Thus, the inhibitory effect of SB203580 on NF-kappaB activation is to a large extent mediated by RICK inhibition. RICK is the effector kinase of the intracellular receptor of bacterial peptidoglycan NOD. Because bacterial products are suggested to be the key pathogenic agents triggering IBD, inhibition of the NOD/RICK pathway may serve as a novel target of future therapies in human IBD.

Animals↗

PubMed2005

Acid challenge to the esophageal mucosa: effects on local nitric oxide formation and its relation to epithelial functions.

To evaluate the effect of esophageal acid exposure on epithelial function, transmucosal potential, histopathological markers of acute tissue damage, and local nitric oxide production were examined in healthy volunteers treated with proton pump inhibitors (group I), patients with treated reflux disease (group II), and patients with untreated erosive reflux disease (group III). The participants were randomized to esophageal perfusion with either saline or HCl. Denominators of acute acid exposure were balloon cells in superficial layers and superficial densification. The nitric oxide concentrations in groups I to III increased from < 1, 10.0+/-10.0, and 20.6+/-19.9 ppb, respectively, to 300+/-80, 1360+/-1080, and 920+/-700 ppb after HCl infusion (P < 0.001). Inducible nitric oxide synthase was consistently expressed in the epithelium. Blood flow was lower among reflux patients but did not correlate with acid exposure or nitric oxide. Nitric oxide is formed following acid perfusion and predominantly in gastroesophageal reflux disease.

Adult↗

PubMed2005

Acid challenge to the human esophageal mucosa: effects on epithelial architecture in health and disease.

The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.

Adult↗

PubMed2005

Pathology of early upper GI cancers.

Local endoscopic resection techniques for early neoplasms of the gastro-intestinal tract require exact description of the depth of infiltration for the decision of endoscopic versus surgical therapy. Subdivision of mucosal neoplasms is used only in the oesophagus. Mucosal oesophageal carcinoma (squamous cell carcinoma and adenocarcinoma) can be subdivided into m1-m3 and m1-m4. Distinction of high-grade intraepithelial neoplasia and mucosal carcinoma is without clinical relevance since the diagnosis of high-grade intraepithelial neoplasia should always first lead to a (diagnostic) endoscopic resection. The final histological diagnosis could then be made on the resection specimen. Diagnosis of low-grade intraepithelial neoplasia is often confused with regenerative changes. Histological diagnoses of early neoplasms are not the same worldwide and consensus should be improved further.

Adenocarcinoma↗

PubMed2005

Confocal laser endomicroscopy.

A miniaturized confocal microscope was developed that could be integrated in the distal tip of a conventional colonoscope. With this technique, denoted confocal endomicroscopy, subsurface analysis of the gut mucosa and in-vivo histology during ongoing endoscopy are possible in full resolution by point scanning laser analysis. The diagnostic spectrum of confocal endomicroscopy is expanding from screening and surveillance for colorectal cancer to Barrett's esophagus, Helicobacter pylori-associated gastritis, and gastric cancer. The new detailed images seen with confocal laser endomicroscopy allow a unique look on cellular structures at and below the surface of the gut. This review describes the optical and diagnostic possibilities of confocal laser endomicroscopy.

Acriflavine↗

PubMed2005

Islands of squamous epithelium and their surrounding mucosa in columnar-lined esophagus: a pathognomonic feature of Barrett's esophagus?

We examined 23 patients with columnar-lined esophagus (2 with long segment and 21 with short segment) endoscopically. After staining with Lugol's iodine solution, squamous islands were identified in the columnar mucosa in 18 (78%) of the 23 patients. When biopsy specimens were obtained from these islands, esophageal glands proper or their ducts were seen in 12 (67%) of the 18 cases. Because the identification of esophageal glands proper is a definite indicator that a piece of biopsy tissue is of esophageal origin, a diagnosis of columnar-lined esophagus could be made purely on the basis of the histological findings in these biopsy specimens of squamous islands. This was the case in 12 (52%) of the 23 patients examined in this study. Staining with Lugol's iodine solution, with subsequent biopsy of stained squamous islands, may assist in the diagnosis of short-segment columnar-lined esophagus. We also conclude, on the basis of our study, that columnar metaplasia of the esophagus cannot develop by direct outgrowth of epithelium from the ducts of esophageal glands proper. In addition, intestinal metaplasia was not always observed in the columnar mucosa around the duct orifices. From a practical point of view, biopsy specimens from columnar-lined mucosa of the esophagus do not always show intestinal metaplasia (specialized intestinal metaplasia).

Barrett Esophagus↗

PubMed2005

Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking. METHODS: The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients. RESULTS: Between September 1996 and September 2002, 667 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barrett's neoplasia. CONCLUSIONS: The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barrett's neoplasia.

Adenocarcinoma↗

PubMed2005

Prevalence of Barrett's esophagus in the general population: an endoscopic study.

BACKGROUND & AIMS: Barrett's esophagus (BE) is associated with esophageal adenocarcinoma, the incidence of which has been increasing dramatically. The prevalence of BE in the general population is uncertain because upper endoscopy is required for diagnosis. This study aimed to determine the prevalence of BE and possible associated risk factors in an adult Swedish population. METHODS: A random sample (n = 3000) of the adult population (n = 21,610) in 2 municipalities was surveyed using a validated gastrointestinal symptom questionnaire (response rate, 74%); a random subsample (n = 1000; mean age, 53.5 years; 51% female) underwent upper endoscopy. Endoscopic signs suggestive of columnar-lined esophagus (CLE) were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BE was diagnosed when specialized intestinal metaplasia was detected histologically in suspected CLE. RESULTS: BE was present in 16 subjects (1.6%; 95% confidence interval, 0.8-2.4): 5 with a long segment and 11 with a short segment. Overall, 40% reported reflux symptoms and 15.5% showed esophagitis; 103 (10%) had suspected CLE, and 12 (1.2%) had a visible segment > or = 2 cm. The prevalence of BE in those with reflux symptoms was 2.3% and in those without reflux symptoms was 1.2% (P = .18). In those with esophagitis, the prevalence was 2.6%; in those without, the prevalence was 1.4% (P = .32). Alcohol (P = .04) and smoking (P = .047) were independent risk factors for BE. CONCLUSIONS: BE was found in 1.6% of the general Swedish population. Alcohol and smoking were significant risk factors.

Adenocarcinoma↗

PubMed2005

A negative Helicobacter pylori serology test is more reliable for exclusion of premalignant gastric conditions than a negative test for current H. pylori infection: a report on histology and H. pylori detection in the general adult population.

OBJECTIVE: Corpus-dominant gastritis, gastric mucosal atrophy and intestinal metaplasia (IM) associated with Helicobacter pylori infection are all known potential risk markers for the development of gastric cancer. As the accuracy for finding cases at risk in the general population is unknown, we aimed to determine the prevalence of current and/or past H. pylori infection and associated gastric mucosal findings by means of histological survey of a random adult population. MATERIAL AND METHODS: A random Swedish sample (n = 3000, age 20-81 years) was surveyed using a validated gastrointestinal symptom questionnaire with 74% response rate. One-third of the responders were selected at random for esophago-gastro-duodenoscopy with biopsies and H. pylori serology. RESULTS: Of those endoscoped (n = 1000, mean age 53.5, 51% women), 43.0% were H. pylori+ by serology (seropositive), 33.9% had signs of current infection on either histology or culture (gold standard+), and 9.3% were seropositive, but gold standard negative. Corpus atrophy was found in 10% and IM in 13% when gold standard positive, and in a significantly higher number (17% and 21%, respectively) of those with only a serological sign of past infection. Among those who were seronegative, values were 1% and 2%, respectively. Corpus-dominant gastritis was found in 4.1%, all seropositive. CONCLUSION: One-third had an ongoing H. pylori infection, and a further 10% had signs of past infection. Corpus-dominant gastritis was found mostly among the former, while detection of those with corpus atrophy and IM also required a test for past infection. Seronegativity almost excludes precancerous conditions in a screening situation.

Adult↗

PubMed2005

High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report.

OBJECTIVE: Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. MATERIAL AND METHODS: A random sample (n =3000) of the adult population (20-81 years of age) of two Swedish municipalities (n =21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n = 1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. RESULTS: GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those with EE reported no GERS. Hiatus hernia and obesity remained significant risk factors for GERS and/or EE, with or without symptoms in a main effect model (OR up to 14 at EE). Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection (OR = 1.71 (1.23 2.38)). CONCLUSIONS: GERS and EE (of which one-third is asymptomatic) are highly prevalent in the Swedish adult population. H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux.

Adult↗

PubMed2005

Helicobacter pylori induces gastritis and intestinal metaplasia but no gastric adenocarcinoma in Mongolian gerbils.

OBJECTIVE: The Mongolian gerbil is considered as the model of choice when studying adenocarcinoma related to Helicobacter pylori infection. The purpose of this study was to compare two different H. pylori strains and elucidate whether adenocarcinomas developed in gerbils. MATERIAL AND METHODS: Male gerbils were separated into three groups: one control and two groups infected with two different strains of H. pylori, TN2GF4 and SS1. At 3, 6, 12 or 18 months after inoculation 5 animals from each group were sacrificed. The stomach was used for culture, and for histology. RESULTS: Inflammation was seen after 3 months in all the infected animals. In the controls no pathology was found at any time. Intestinal metaplasia was found in both the infected groups. Glands buried in the submucusal layer, changes that might be misinterpreted as adenocarcinoma, were found in 10% of the SS1 and in 65% of the TN2GF4 animals. Adenocarcinoma was not found in any of the gerbils. CONCLUSIONS: All studies claiming to have found H. pylori-induced adenocarcinomas in gerbils describe atypical glands penetrating into the muscularis propria and interpret these as invasive growths due to cancer. An alternative interpretation is that the deranged glandular structures grow in and below the submucosa. It is suggested that atypical glands in the muscularis layer are not enough as a diagnostic criterion for gastric adenocarcinoma. It is concluded that adenocarcinoma has not yet been shown convincingly to develop in Mongolian gerbils infected with H. pylori. Nevertheless, it is a model well suited for studying gastritis, gastric ulcer and premalignant changes such as metaplasia.

Adenocarcinoma↗

PubMed2005

Ciliated surface in the esophagogastric junction zone: a precursor of Barrett's mucosa or ciliated pseudostratified metaplasia?

We have previously reported squamous metaplasia-like change at the esophagogastric junction (EGJ). In the present study, we examined these lesions histologically and by immunohistochemistry and electron microscopy. Samples of EGJ mucosa, 3 cm long and comprising 1.5-cm long portions of both columnar and squamous mucosa, were obtained from 43 esophagectomy resection specimens. Squamous metaplasia-like change was observed in 21 (49%) of the 43 cases. The squamous metaplasia-like change was generally positive with immunohistochemical stains for tubulin and cytokeratins (CKs) 4, 7, 8, 13, and 18, and was generally negative with stains for CKs 10, 14, and 20. This pattern of immunoreactivity is very similar to that of bronchial mucosa. Also, many cilia were detected at the apices of the cells by electron microscopy in 5 (31%) of the 16 cases that were able to be examined. Therefore, squamous metaplasia-like change at the EGJ has both a similar appearance and a similar immunohistochemical profile to respiratory bronchial epithelium. These findings may suggest that squamous metaplasia-like change at the EGJ is not a precursor of Barrett's mucosa but rather is a form of pseudostratified metaplasia.

Aged↗