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Biomedical subjects

H Messmann

Publications and source records attributed to H Messmann.

At least 37 records · Page 2Linked to original sources

[New endoscopic therapies for gastroesophageal reflux disease].

The growing data about new endoscopic therapies for gastroesophageal reflux disease (GERD) seem to indicate that these techniques might be effective at least in a part of patients suffering from GERD. However, up to now it is not clear which technique is the best. Randomized studies comparing the different techniques with each other and especially with surgical antireflux procedures (laparoscopic fundoplication) are needed. In addition, more data proving the long term effectiveness of these new techniques are necessary.

Biopolymers↗

Fluorescence endoscopy for the detection of low and high grade dysplasia in ulcerative colitis using systemic or local 5-aminolaevulinic acid sensitisation.

BACKGROUND AND AIMS: Longstanding ulcerative colitis (UC), especially in the presence of epithelial dysplasia, is associated with an increased risk of developing cancer. As dysplasia is not visible during routine endoscopy, at least 40-50 random biopsies in four quadrants every 10 cm are recommended. Fluorescence endoscopy after sensitisation with 5-aminolaevulinic acid (5-ALA) was assessed for the detection of dysplasia in ulcerative colitis by taking optical guided biopsies. 5-ALA is converted intracellularly into the sensitiser protoporphyrin IX which accumulates selectively in neoplastic tissue allowing the detection of dysplasia by typical red fluorescence after illumination with blue light. METHODS: In 37 patients with UC, 54 examinations were performed with fluorescence endoscopy after oral (20 mg/kg) or local (either with an enema or by spraying the mucosa with a catheter) sensitisation with 5-ALA. A total of 481 biopsies of red fluorescent (n=218) and non-fluorescent (n=263) areas of the colonic mucosa were taken. RESULTS: Forty two biopsies in 12 patients revealed either low grade (n=40) or high grade (n=2) dysplasia. Sensitivity of fluorescence for dysplastic lesions was excellent and ranged from 87% (95% confidence interval (CI) 0.73-1.00) to 100% (95% CI 1.00-1.00) after local sensitisation, in contrast with only 43% (95% CI 0.17-0.69) after systemic administration. Specificity did not differ for both forms of local sensitisation (enema 51% (95% CI 0.44-0.57) and spray catheter 62% (95% CI 0.51-0.73)); after systemic sensitisation specificity was 73% (95% CI 0.69-0.83). Negative predictive values of non-fluorescent mucosa for exclusion of dysplasia were very high; 89% after systemic sensitisation and 98-100% after local sensitisation. Positive predictive values were 13% and 14% after local sensitisation with enema and spray catheter, and 21% after oral sensitisation with 20 mg/kg ALA. The overall number of biopsies per examination was less than five from fluorescent positive areas. CONCLUSION: Fluorescence endoscopy after 5-ALA sensitisation is a possible tool to visualise dysplastic lesions in ulcerative colitis using 5-ALA sensitisation. Local sensitisation is a promising alternative approach compared with systemic administration of 5-ALA. A randomised controlled study is now indicated to compare the efficacy of endoscopic fluorescence detection with the standard technique of four quadrant random biopsies.

Adult↗

Fluorescence endoscopy and photodynamic therapy.

Fluorescence endoscopy is a new technique which allows a better detection of non-visible malignant or premalignant lesions or, those which are difficult to detect. Exogenously applied sensitisers accumulate selectively in malignant lesions and induce fluorescence after illumination with light of adequate wavelength. However, also endogenous fluorophores, different located in malignant or benign lesions, induce a different autofluorescence in these lesions. Tissue fluorescence can be detected by optical sampling of the mucosa using fluorescence spectroscopy or by generating real time fluorescence images with specialised camera systems. Compared to point fluorescence spectroscopy the latter technique enables the screening of large surface areas of mucosa. Meanwhile, fluorescence endoscopy is a widely used technique in urology employing 5-aminolaevulinic acid sensitisation. In gastroenterology, this technique seems promising for the detection of early cancers or dysplasia in patients with Barrett's oesophagus or ulcerative colitis. Using different sensitisers, photodynamic therapy seems to be a promising option for patients with advanced oesophageal cancer and in the palliative treatment of non-resectable bile duct cancer, furthermore for patients with early gastric cancer and dysplasia in Barrett's oesophagus. Probably, by laser light fractionation or a combination of different sensitisers, an enhanced effect can be expected.

Cholangiocarcinoma↗

Improving the use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for the gastrointestinal tract by esterification--an in vitro study.

Possible approaches to improve the diagnostic and therapeutic effects of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) are the esterification of ALA for enhanced uptake and the choice of wavelength for irradiation. The human colonic cell lines HT29 [G2] and CCD18 (fibroblasts) were incubated with 0.6 mM ALA, ALA-hexylester or -benzylester respectively, and for further assays with hypotaurine, in addition. PPIX-accumulation was analyzed by flow cytometry and fluorescence spectroscopy. PPIX formation kinetics were continuously recorded. Incubated cells were irradiated with an incoherent light source lambda = 400-700 nm or lambda = 590-700 nm, respectively. After PDT treatment, clonogenicity assays were performed to determine cell viability. Esterification leads to increased PPIX-accumulation, decreased time for production of detectable amounts of PPIX as well as increased response to PDT. Tumor specificity is always maintained or exceeds values for ALA alone. ALA enters the cells via beta transporter whereas esters by passive diffusion. Altering irradiation wavelengths showed the independence of wavelength rather than light dose. Results emphasize the role of heme metabolism for generating tumor specificity rather than the process of ALA-uptake, an important detail for future clinical application.

Aminolevulinic Acid↗

Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon.

Photodynamic diagnosis and especially therapy after sensitization with 5-aminolevulinic acid (ALA) is hampered by limitations of uptake and distribution of ALA due to its hydrophilic nature. Chemical modification of ALA into its more lipophilic esters seems to be promising to overcome these problems. The aim of the present study was to investigate the comparative kinetics of protoporphyrin IX (PPIX) fluorescence in rat colonic tissue after topical application of ALA and its esterified derivatives, ALA-hexylester (h-ALA), ALA-methylester (m-ALA) and ALA-benzylester (b-ALA). Fluorescence intensity induced by PPIX in normal colonic tissue was quantified using fluorescence microscopy at 1, 2, 4, 6 and 8 h after sensitization. Mucosa exhibited higher fluorescence levels compared to the underlying submucosa or smooth muscle. Peak fluorescence intensities were seen 4 h after local sensitization with 86.0 mol ml(-1) ALA (513 +/- 0.57 counts per pixel), 6.6 mol ml(-1) m-ALA (508 +/- 35.50) and 4.8 mol ml(-1) h-ALA (532 +/- 128.80), and 6 h after sensitization with 4.6 mol ml(-1) b-ALA (468 +/- 190.27). A 13-18 times lower concentration of ALA esters was required for fluorescence intensities reached with ALA alone. A similar degree of the fluorescence ratio between mucosa and muscularis (5-6:1) was detected for ALA and its derivatives. The time point of the maximum value of this ratio was consistent with peak fluorescence levels for ALA and each ALA-ester. The clinical feasibility and the advantages of topical ALA ester-based fluorescence for detection of malignant and premalignant lesions need further investigations.

Aminolevulinic Acid↗

[Endoscopic fluorescence diagnosis of esophageal carcinoma after sensitization with 5-aminolevulinic acid].

BACKGROUND: Barrett's esophagus is a complication of gastroesophageal reflux disease (GERD) characterized by specialized columnar epithelium that contains goblet cells and replaces the squamous epithelium of the distal esophagus. It is found in about 10% of patients with symptomatic reflux disease and more importantly has been associated with the development of esophageal cancer. Adenocarcinoma arises from dysplasia, which is usually not visible during routine endoscopy, therefore extensive random sampling of the entire Barrett's segment should be performed with biopsies in the 4 quadrants every 1 to 2 cm and of any macroscopic abnormality. CASE REPORT: We report the history of a 60-year-old man who was admitted to hospital because of an ulcer in Barrett's esophagus not healing despite conservative treatment. He has suffered from gastroesophageal reflux disease for more than 30 years and an antireflux surgical procedure had not resulted in regression of Barrett's esophagus. However, close surveillance could not reveal any dysplastic or malignant lesion. Endoscopic fluorescence detection (EFD) after sensitization with 30 mg/kg 5-aminolevulinic acid (5-ALA) in this patient demonstrated a selective red fluorescence in a macroscopically normal appearing area near the already known ulcer. Biopsies from this fluorescent area showed an adenocarcinoma. Esophagectomy confirmed the presence of intramucosal adenocarcinoma without lymph node metastases.

Adenocarcinoma↗

[Paraneoplastic Bazex acrokeratosis in adenocarcinoma of the stomach].

HISTORY AND EXAMINATION: A 58-year-old man presented with a sudden eruption of hyperkeratoses on hands and feet. Alcohol abuse had been present 10 years ago, together with a gastric ulcer. Physical examination was unremarkable, except for plantar bizarre hyperkeratoses especially at the sides of the feet as well as some rhagades with spread to the dorsum of the toes. Similar but less severe hyperkeratoses were found on the palms. INVESTIGATIONS: Laboratory investigation was essentially normal. X-rays of the thorax and sinuses as well as a sonography of the stomach revealed, except for a fatty liver, no pathological findings. Gastroscopy revealed a chronic active gastritis on the small curvature of the stomach. Only a second gastroscopy and biopsy revealed an adenocarcinoma of the stomach. DIAGNOSIS, THERAPY AND COURSE: According to the clinical presentation a paraneoplastic acrokeratosis (Bazex syndrome) was diagnosed. The patient was given high-dose chemotherapy with subsequent stem-cell transplantation and gastrectomy. The skin problems resolved after the first cycles of chemotherapy. CONCLUSION: If clinically a paraneoplastic acrokeratosis is suspected extensive search for a malignancy has to be initiated, including a gastroscopy, because rarely, but as in the present case, a carcinoma of the stomach can be the underlying cause.

Adenocarcinoma↗

Role of endoscopy in the staging of esophageal and gastric cancer.

Progress in instrumentation and clinical research continues to expand the potential utility of endoscopic ultrasound (EUS) in the treatment of esophageal and gastric cancer. This review focuses on the role of EUS in the staging and treatment planning of patients with esophageal and gastric cancer.

Endosonography↗

Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats.

We examined the clinical and histopathological features of the dextran sulfate sodium (DSS) induced acute and chronic colitis in rats as a model for studying basic biology of the inflamed colonic mucosa. Acute colitis was induced in male Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt. 54,000) in their drinking water. Chronic colitis was induced in 8 experimental groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles; CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10 days drinking water. The entire colons were examined histologically; dysplasia was graded as: indefinite/probably negative for dysplasia, indefinite/probably positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The earliest clinical findings in the acute colitis group over 4 days occurred on day 2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The maximal disease activity was noted on day 7 accompanied by a 53% mortality rate. The histological inflammation scores were significantly higher on day 7 than on day 4. All rats had extensive ulcerations predominantly in the rectum and cecum. The number of rats having ulcerations was markedly lower in the chronic colitis groups. The majority (75%) of the crypt lesions suspicious for dysplasia were classified as mucosa indefinite/probably negative for dysplasia. We classified 18 crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia (after eight cycles). No invasive carcinoma was observed. Most low-grade dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the rectum (44%) and colon transversum (33%). Our findings suggest that the DSS colitis model in rats may be an interesting model for studying the sequence chronic inflammation-dysplasia in human ulcerative colitis. Further long-term studies with the present DSS colitis model in rats might also prove it as a reliable model to study the sequence high-grade dysplasia and colitis associated-cancer.

Acute Disease↗

Early shifts of adrenal steroid synthesis before and after relief of short-term cholestasis.

BACKGROUND/AIMS: Chronic inflammatory diseases are characterised by a relative reduction of cortisol and adrenal androgens. The time point of appearance of these alterations is not known. Cholestasis may be a model of short-term inflammation to study early alterations of steroidogenesis. METHODS: We investigated 18 patients with cholestasis before and after therapeutic abolition of cholestasis (compared to nine control subjects, Co). RESULTS: Serum tumour necrosis factor (TNF) was increased in cholestatic patients as compared to Co (P at least <0.01). Co as compared to cholestatic patients without tumours had elevated levels of plasma adrenocorticotropic hormone (ACTH) and serum dehydroepiandrosterone sulfate (DHEAS) but serum cortisol levels were similar. Levels of ACTH and DHEAS in relation to serum IL-6 or TNF were higher in Co as compared to the cholestatic subgroup without tumours, whereas serum cortisol in relation to these cytokines was similar. In both subgroups of cholestatic patients, we observed the typical inflammation-dependent shift of adrenal hormones into the direction of cortisol in relation to DHEAS. Cholestatic patients with malignant tumours demonstrated an intermediate response pattern. CONCLUSIONS: Short-term cholestasis for 5-12 days induced marked alterations of adrenal steroidogenesis which partly resemble the changes observed in chronic inflammatory diseases.

Adrenal Glands↗

Squamous cell cancer of the oesophagus.

Squamous cell cancer is the most common neoplasm of the oesophagus worldwide, with an enormous variation in its global incidence. Several risk factors, such as achalasia, Plummer-Vinson syndrome, coeliac disease and nutritional factors, have been identified. The surveillance of patients, especially those with tylosis or caustic ingestion, has been recommended. Vital staining with iodine may improve the diagnosis of early cancer. The endoscopic management of early cancer and dysplasia by minimal invasive techniques such as photodynamic therapy or mucosal resection has become attractive for many of these patients with co-morbidity.

Carcinoma, Squamous Cell↗

[Surveillance of patients with Barrett's esophagus].

Barrett's esophagus is a major complication of gastroesophageal reflux disease and is associated with 30-125 fold increased risk of developing carcinoma. Because of the rising incidence of esophageal adenocarcinoma the malignant potential of Barrett's esophagus has been generally recognized. The definition of Barrett's esophagus has evolved over the last decades. It is now accepted that "Long-Barrett-Segment" (LBS) is used when intestinal-type epithelium, characterized by the presence of goblet cells, is detected in the distal esophagus > 3 cm in length. The term "Short-Barrett-Segment" (SBS) is defined by intestinal metaplasia detection < 3 cm in length in the distal esophagus. Recently, there has been focus on microscopic Barrett's esophagus, so called "Ultra-Short-Barrett's esophagus", with histological evidence of intestinal metaplasia without endoscopic appearance. The most significant predictor of the risk of malignancy in patients with Barrett's esophagus is the presence of dysplasia. Guidelines for surveillance are based on the diagnosis of dysplastic lesions. New methods (e. g. Methylene blue staining, endoscopic fluorescence detection, OCT) to improve the recognition of Barrett's esophagus and especially enhance the detection of premalignant and malignant lesions are under evaluation. So far, the standard biopsy protocol for patients with LBS includes biopsies in the 4 quadrants every 1-2 cm, whereas the appropriate surveillance intervals are dependent on the grade of dysplasia. Whether surveillance in patients with SBS has to be similar to that in patients with LBS is unclear and needs further evaluation.

Adenocarcinoma↗