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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 19 recordsLinked to original sources

Endoscopic measurement of Barrett's esophagus length is unreliable - a prospective comparative biopsy study.

BACKGROUND AND AIMS: Endoscopic assessment of the length and area of Barrett's esophagus (BE) has become crucial in assessing its spontaneous course as well as any effect of pharmacological or endoscopic treatment. Little, however, is known about the extent to which the endoscopic assessment of BE length and area correlates with the histopathological confirmation of BE epithelium. PATIENTS AND METHODS: 75 consecutive patients (mean age 60 years; 58 men, 17 women) were included in a prospective study on the basis of the endoscopic suspicion of BE. BE was endoscopically defined as gastric-type epithelium between the proximal cardiac folds and the Z line, on moderate air insufflation. Stepwise four-quadrant biopsies (4QB) were then taken, beginning at the proximal cardiac folds and then every 2 cm up to the Z line. RESULTS: Among the 75 study patients, BE was histologically verified in 57 cases (group 1) and not confirmed in any of the endoscopic biopsy samples in 18 cases (group 2). In group 1, the mean difference between the endoscopic and histological assessment of BE length was + 1 cm (range 0 - 5 cm); when determining the BE area histologically from 4QB the mean difference to the endoscopic determination was + 36 % (range 0 - 93 %). These differences were independent of the presence and degree of hiatal hernia or the presence of long or short BE. CONCLUSIONS: In the majority of patients, there is only a moderate correlation between the endoscopic and the histological extent of BE. However, we also found a substantial individual variability in endoscopic-histological correlation; therefore studies on the effects of treatment on BE must consider both the endoscopic and histopathological BE lengths.

Adult↗

The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only--what is the clinical significance?

BACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, with chronic reflux and Barrett's oesophagus being considered risk factors. Reliable detection of Barrett's oesophagus during upper endoscopy is therefore mandatory but requires both endoscopy and histology for confirmation. Appropriate management of patients with endoscopic suspicion but negative on histology, or vice versa, or of patients with no endoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS AND METHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50 years) referred for upper gastrointestinal endoscopy were included; 59% had reflux symptoms. The endoscopic aspect of the Z line and any suspicion of Barrett's oesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4), gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive for specialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for a final Barrett's oesophagus diagnosis. All patients with endoscopic and/or histological suspicion of Barrett's oesophagus were invited for a follow up endoscopy; the remaining cases (no endoscopic or histological suspicion of Barrett's oesophagus) were followed clinically. RESULTS: Of 235 patients positive for Barrett's oesophagus on endoscopy and/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5 months). 46% of patients with an endoscopic Barrett's oesophagus diagnosis but no histological confirmation (group A) showed the same distribution, a further 42% did not have Barrett's oesophagus, and 11% had confirmed Barrett's oesophagus on both endoscopy and biopsy on follow up. In the group with a histological Barrett's oesophagus diagnosis but negative on initial endoscopy (group B), follow up showed the same in 26% whereas 46% had no Barrett's oesophagus, and confirmed Barrett's oesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population, 16 patients had Barrett's oesophagus on initial endoscopy confirmed by histology which remained constant in 70% at follow up (group C). Of the remaining patients without an initial Barrett's oesophagus diagnosis on either endoscopy or histology (group D) and only clinical follow up (mean follow up period 38 months), one confirmed Barrett's oesophagus case was found among 100 patients re-endoscoped outside of the study protocol. However, no single case of dysplasia or cancer of the distal oesophagus was detected in any patient during the study period. CONCLUSIONS: Even in a specialised gastroenterology setting, reproducibility of presumptive endoscopic or histological diagnoses of Barrett's oesophagus at follow up were poor. Only 10-20% of cases with either endoscopic or histological suspicion of Barrett's oesophagus had established Barrett's oesophagus after 2.5 years of follow up. The risk of dysplasia in this population was very low and hence meticulous follow up may not be required.

Adolescent↗

Fatal outcome of lung transplantation in cystic fibrosis patients due to small-colony variants of the Burkholderia cepacia complex.

The aim of this study was to investigate the possible role of small-colony variant morphotypes of Burkholderia cepacia-like organisms in infectious complications in cystic fibrosis patients following lung transplantation. Respiratory tract specimens from 470 cystic fibrosis patients were screened over a 22-month period for Burkholderia cepacia-like organisms. Nineteen patients were positive for these organisms, eight of whom harboured small-colony-variant morphotypes. Three patients underwent bilateral lung transplantation during the study, two of whom harboured small-colony variants in addition to clonally identical wildtypes of Burkholderia multivorans and Burkholderia cepacia genomovar III prior to lung transplantation. Both patients developed fatal systemic infections post transplantation due to small-colony variants. In vitro testing revealed that small-colony variants exhibited increased serum resistance in comparison to wildtypes. The results of this study indicate that diagnostic efforts should be undertaken to carefully identify small-colony variants of Burkholderia cepacia complex, since they might be an indicator of poor post-transplantation outcome in patients with cystic fibrosis.

Adolescent↗

Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time and clinical sequelae. A prospective observational study.

BACKGROUND: In the diagnosis and treatment of biliary disorders, establishing percutaneous transhepatic biliary drainage (PTBD) is an invasive procedure that can potentially lead to infectious complications in both the short and long-term. We therefore prospectively analysed the time course and spectrum of biliary bacteria in patients undergoing PTBD. METHODS: Forty-nine patients (19 F, 30 M; mean age 64 years) with malignant (65%) or benign (35%) biliary disorders were included, 20 of whom had a newly established PTBD (group A), while the remaining 29 had already had their PTBD in situ (group B) for a mean of 8 months. Bacteriological analyses of bile and blood were carried out, and clinical symptoms and laboratory values were obtained. RESULTS: Biliary bacteria were found in 60% of cases during the initial PTBD placement, and 24 h later this rate had already increased to 85%; two or more microorganisms were found in 40% initially and in 70% after a few days. At later PTBD exchanges, bacteriobilia was found in 100%, with all patients harbouring multiple organisms. Whereas the initial spectrum was mixed, Escherichia coli and enterococci (97% each), Klebsiella (73%) and Bacteroides species (37%) later predominated; Candida increased initially from 15% to 80%, but later decreased to 30%. Clinical signs of cholangitis were observed in 30% initially (no sepsis), but decreased to 6% at later exchanges. CONCLUSIONS: Bacteriobilia is initially a frequent, and later a regular, event in PTBD; however, clinically significant complications are rare during the long-term course and limited to the initial, more invasive, phase of PTBD. A knowledge of the bacterial spectrum is important for selecting appropriate antibiotic coverage if complications arise and/or major interventions such as surgery are planned.

Adult↗

Biopsy surveillance is still necessary in patients with Barrett's oesophagus despite new endoscopic imaging techniques.

BACKGROUND AND AIMS: Endoscopic surveillance including stepwise four quadrant biopsies (4QB) is still regarded as the standard approach in patients with Barrett's oesophagus (BO). Several methods such as dye staining with methylene blue (MB) and tissue autofluorescence (AF) have been advocated to reduce the number of biopsies. We assessed their sensitivity and specificity compared with the standard approach-that is, endoscopy with 4QB-in the surveillance of a mixed BO population. PATIENTS AND METHODS: Thirty five consecutive BO patients (mean age 64.9 years; 30 men, five women) were included in the study. AF endoscopy was followed by high resolution video endoscopy (VE) plus tissue staining with 0.5% MB. Biopsies were taken from any suspicious area found on any of the above tests, in addition to 4QB every 2 cm. The results were classified as either positive or negative for the various tests used. Histopathological results were used as the reference standard. RESULTS: In the 35 study patients, a total of 345 biopsies showed low grade dysplasia (LGD) in 88 biopsies, high grade dysplasia (HGD) in 19 biopsies, and carcinoma in 12 biopsies. The sensitivity and specificity rates for AF and MB for the diagnosis of cancer or dysplasia versus BO mucosa without dysplasia were 21%/91% and 37%/91%, respectively. 4QB revealed five cancer/HGD areas and 76 LGD areas not detected by AF, MB, or VE. The additional yield of MB and AF over VE with 4QB concerned only one HGD area (in the vicinity of a cancer) and seven LGD areas. CONCLUSIONS: Due to their low sensitivity, AF and MB are not suitable techniques for reducing the high numbers of routine biopsies needed for finding additional foci of HGD or cancer. Careful endoscopic observation and stepwise four quadrant biopsy therefore still represent the gold standard for surveillance of Barrett's oesophagus.

Adenocarcinoma↗

Treatment of achalasia: the short-term response to botulinum toxin injection seems to be independent of any kind of pretreatment.

BACKGROUND: It has been suggested that intrasphincteric injection of botulinum toxin (BTX) may represent an alternative therapy to balloon dilatation in achalasia. The aim of the present study was to test the effectiveness of botulinum toxin injections in achalasia patients, as assessed using lower oesophageal sphincter pressure (LOSP) and symptom scores, and to compare the response in patients with different types of pretreatment (no previous treatment, balloon dilatation, myotomy, BTX injection). METHODS: Forty patients who presented with symptomatic achalasia were treated with BTX injection (48 injections in 40 patients). Some of the patients had received prior treatment (seven with myotomy, seven with dilatation and eight with BTX). The symptoms were assessed using a global symptom score (0-10), which was evaluated before treatment, 1 week afterwards, and 1 month afterwards. Manometry was also carried out before and after treatment. Three different selections of patients were studied: all patients; untreated patients; and patients with prior BTX, dilatation, or myotomy. RESULTS: After BTX injection, there was a significant reduction in LOSP (before, 38.2+/-11.3 mmHg; 1 week after, 20.5+/-6.9 mmHg; 1 month after, 17.8+/-6.8 mmHg; P < 0.001). The global symptom score and symptom subscores (dysphagia, regurgitation, chest pain) were significantly decreased after 1 week and 1 month. When the beneficial effects following BTX injection were compared (untreated vs. pretreated), neither changes in LOSP nor beneficial effects on the symptom scores significantly differed. After 6 months, 67.7% of all treated patients were still in symptomatic remission (subgroups: previously untreated patients, 61.5%, n = 26; prior dilatation, 71.4%, n = 7; prior myotomy, 71.4%, n = 7; prior BTX, 73.9%, n = 8). CONCLUSIONS: BTX injection offers an alternative treatment for achalasia which is safe and can be performed in an outpatient setting. The initial response to BTX, in terms of symptom scores and LOSP, appears to be independent of any prior treatment. A number of patients do not adequately respond to balloon dilatation or myotomy, which are the first-line treatment modalities in achalasia patients. BTX injection can be performed in these patients, and symptomatic benefit can be expected in the same percentages as with BTX injection in untreated patients.

Adult↗

Endoscopic treatment of a Zenker's diverticulum using argon plasma coagulation in a patient with massive cachexia and esophageal obstruction: a case report and review of literature.

A case report is presented of an 86-year-old man in a very poor general condition with a 10-year history of a Zenker's diverticulum as a cause of a complete obstruction of the esophagus with subsequent aphagia and massive cachexia. Because of high surgical risk and contraindications to general anesthesia, an approach with the flexible endoscope to perform cricopharyngeal myotomy was undertaken. Several attempts with the flexible endoscope by experienced investigators had been performed until the esophageal inlet was intubated and argon plasma coagulation could be applied in several sessions to divide the tissue bridge between the esophagus and the Zenker diverticulum to successfully restore the pharyngoesophageal passage.

Aged↗

Management of gastroesophageal reflux disease in primary care: results of a survey in 2 areas in Germany.

BACKGROUND: The incidence of gastroesophageal reflux disease (GERD) is increasing. Although guidelines have been issued on the diagnosis and treatment of GERD, the way in which these should be applied in everyday practice is unclear. The aim of the present survey was to interview private-practice physicians on their personal opinions concerning the management of GERD. METHODS: A questionnaire based on the case of a typical patient with reflux was sent out to a total of 918 private-practice physicians. The questions concerned general measures for avoiding reflux symptoms (dietary and lifestyle modifications), the diagnosis of GERD, and the type and dosage of antireflux treatment. RESULTS: A total of 255 questionnaires were evaluated (28 %), which had been returned by 151 family doctors, 63 internal medicine specialists, and 41 gastroenterologists. 70 % of the respondents carry out specific diagnostic tests (endoscopy in 98 % of cases) prior to treatment. Altering specific dietary and lifestyle factors (such as sleeping position) was considered useful by the majority of respondents. 99 % of the physicians administer some form of GERD therapy, and 88 % of the internists/gastroenterologists and 74 % of family doctors (P = 0.006) do so using a "step-down" approach (with proton-pump inhibitors as the initial strategy). With the "step-up" procedure, the initial recommendation includes primarily antacids, with a change to more effective drugs only when symptomatic relief is not achieved. CONCLUSIONS: The current guidelines on the diagnosis and treatment of GERD are largely adhered to, particularly by specialists. In addition to the well-established drug treatment, empirical recommendations on dietary and lifestyle measures still form part of the management of GERD, despite the lack of scientific evidence to support them.

Antacids↗

A score card for upper GI endoscopy: Evaluation of interobserver variability in examiners with various levels of experience.

BACKGROUND: In most European countries, training in GI endoscopy has largely been based on hands-on acquisition of experience in patients rather than on a structured training programme. With the development of training models systematic hands-on training in a variety of diagnostic and therapeutic endoscopy techniques was achieved. Little, however, is known about methods of objectively assessing trainees' performance. We therefore developed an assessment 'score card' for upper GI endoscopy and tested it in endoscopists with various levels of experience. The aim of the study was therefore to assess interobserver variations in the evaluation of trainees. METHODS: On the basis of textbook and expert opinions a consensus group of eight experienced endoscopists developed a score card for diagnostic upper GI endoscopy with biopsy. The score card includes an assessment of the single steps of the procedure as well as of the times needed to complete each step. This score card was then evaluated in a further conference including ten experts who blindly assessed videotapes of 15 endoscopists performing upper GI endoscopy in a training bio-simulation model (the 'Erlangen Endo-Trainer'). On the basis of their previous experience (i. e. the number of endoscopies performed) these 15 endoscopists were classified into four groups: very experienced, experienced, having some experience and inexperienced. Interobserver variability (IOV) was tested for the various score card parameters (Kendall's rank-correlation coefficient 0.0-0.5 poor, 0.5-1.0 good agreement). In addition, the correlation between the score card assessment and the examiners' experience levels was analysed. RESULTS: Despite poor IOV results for all the parameters tested (Kendall coefficient < 0.3), the assessment parameters correlated well when the examiners' different experience levels were taken into account (correlation coefficient 0.59-0.89, p < 0.05). The score card parameters were suitable for differentiating between the four groups of examiners with different levels of endoscopic experience. CONCLUSIONS: As expected with scores involving subjective assessment of performance, the variability between reviewers was substantial. Nevertheless, the assessment score was capable of distinguishing reliably between different experience levels in terms of a good individual observer consistency. The score card can therefore be used to document both training status and progress during endoscopy training courses using bio-simulation models, and this might be able to provide improved quality assurance in GI endoscopy training.

Animals↗

You get what you expect? A critical appraisal of imaging methodology in endosonographic cancer staging.

BACKGROUND AND AIMS: After an initial period of excellent results with newly introduced imaging procedures, the accuracy of most imaging methods declines in later publications. This effect may be due to various methodological factors involved in the research. Using the example of endoscopic ultrasound (EUS), this study aimed to elucidate one of the factors possibly concerned--namely, the extent to which the examiners are adequately blinded. METHODS: Well documented videotapes of EUS examinations of 101 patients with resected tumours of the oesophagus (n=32), stomach (n=33), or pancreas (n=36) were evaluated in three different ways: firstly, retrospective analysis under routine clinical conditions; secondly, evaluation of EUS videotapes in a strictly blinded fashion; and thirdly, evaluation of the same videotapes but with additional information from the video endoscopic appearance (oesophageal/gastric cancer) or from computed tomography results (pancreatic cancer). Histopathological T staging was used as the reference method. RESULTS: The accuracy of EUS in T staging was 73% under routine conditions. This value fell significantly to 53% for the blinded evaluation but increased again to 62% for the unblinded evaluation. The sensitivity of staging T1/T2 tumours was 72% (routine EUS), 59% (blinded EUS), and 70% (unblinded EUS). The respective values for advanced tumours were 85%, 74%, and 72%. CONCLUSIONS: The accuracy of EUS for T staging in clinical practice appears to be lower than has previously been reported. In addition, blinded analysis produced significantly poorer results, which improved when another test was added. It may be speculated that better results with routine EUS obtained in a clinical setting are due to additional sources of information.

Digestive System Neoplasms↗

Differential expression of CD95, Bcl-2, and Bax in rat gastric chief and parietal cells.

Apoptotic cell death is common in the inflamed gastric mucosa, but its role in the regulation of cell homeostasis in normal gastric mucosa is unknown. We investigated the expression of CD95, Bcl-2, and Bax and their roles in the regulation of apoptosis in normal rat gastric mucosa and in cultures of highly enriched rat chief and parietal cells by immunostaining, Western blotting, and FACS. In intact tissue CD95, Bcl-2, and Bax were localized predominantly in the glandular base region in chief cells. In freshly isolated cells, expression of CD95, Bcl-2, and Bax was much more pronounced in chief cells than in parietal cells. A lower intracellular Bcl-2/Bax ratio suggesting a higher susceptibility to apoptosis was noticed in chief rather than in parietal cells. In extended cultures of parietal and chief cells, Bax expression was upregulated and Bcl-2 expression was downregulated. These regulatory changes, presumably caused by in vitro effects, were not associated with an increase in spontaneous apoptosis. Treatment of chief and parietal cells with Fas-ligand induced apoptosis of all CD95 expressing cells. Expression of CD95, Bcl-2, and Bax predominantly in chief cells suggests that in this cell type regulation of apoptosis may differ from that in parietal cells. Binding of FasL with functionally active CD95 receptors on chief and parietal cells may be relevant for induction of apoptosis in inflamed gastric mucosa.

Animals↗

Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation.

Helicobacter pylori has been assigned as a class I carcinogen because of its relation to gastric adenocarcinoma. Chronic H. pylori infection may lead to severe gastritis, glandular atrophy (AT), and intestinal metaplasia (IM). Strains secreting the vacuolating toxin VacA and producing the cytotoxin-associated antigen CagA (type 1 strains), as well as the blood group antigen binding adhesin (BabA) targeting Lewis(b) antigens, have been associated previously with distal gastric adenocarcinoma (M. Gerhard et al., Proc. Natl. Acad. Sci. USA, 96: 12778-12783, 1999) and may therefore also be related to lesions preceding gastric cancer. Antral and corpus biopsies were collected from 451 patients; 151 were H. pylori positive, as determined by PCR. Gastric biopsies were histologically evaluated for activity of gastritis (G0-G3, granulocyte infiltration), chronicity of gastritis (L1-L3, lymphocyte infiltration), and the presence of IM and/or AT according to the Sydney classification. Simultaneously, the presence of bacterial genes encoding virulence and adherence factors (racAs1/s2, cagA, and babA2) was determined by PCR. The presence of cagA+ and vacAs1 (alone or combined) both correlated with activity and chronicity of gastritis (P < 0.05); however, the overall prevalence of these genes was 60 or 72%, respectively, and was thus relatively frequent. The babA2 gene, encoding the adhesin BabA, was detected in 38% of infected patients and was correlated with the activity of gastritis in antrum and corpus (P < 0.005). cagA+/vacAs1+ strains (suggesting the presence of type 1 strains) that were also babA2 positive were detected more frequently in patients with severe histological alterations (such as G3, IM, or AT) compared with subjects without these changes (P < 0.01). cagA+/vacAs1+ strains that were babA2 negative, however, lacked a significant correlation with severe histological changes, activity, or chronicity of gastritis in antrum and corpus. Adherence of H. pylori via BabA appears to be of importance for efficient delivery of VacA and CagA and may play a special role in the pathogenesis of severe histological changes.

Adhesins, Bacterial↗