PubMed Health⌕ Search

Biomedical subjects

H Messmann

Publications and source records attributed to H Messmann.

At least 55 records · Page 3Linked to original sources
PubMed2001

Endoscopic fluorescence detection of low and high grade dysplasia in Barrett's oesophagus using systemic or local 5-aminolaevulinic acid sensitisation.

BACKGROUND AND AIMS: Barrett's oesophagus is associated with an increased risk of cancer. As dysplasia is not visible during routine endoscopy, random biopsies in the four quadrants every 1-2 cm are recommended. Endoscopic fluorescence detection (EFD) after sensitisation with 5-aminolaevulinic acid (5-ALA) with different modes and concentrations was assessed to optimise the technique for detection of dysplasia or early cancers. 5-ALA is converted intracellularly to protoporphyrin IX which accumulates in malignant tissue and can be detected by typical red fluorescence after illumination with blue light. METHODS: In 47 patients with Barrett's oesophagus, 10 with known dysplasia, 58 fluorescence endoscopies were performed after sensitisation with different concentrations of 5-ALA given orally (5, 10, 20, 30 mg/kg) or locally (500-1000 mg) by spraying the mucosa via a catheter. EFD was performed 4-6 hours after systemic and 1-2 hours after local sensitisation using a special light source delivering white or blue light. A total of 243 biopsies of red fluorescent (n=113) and non-fluorescent areas (n=130) were taken. RESULTS: In three patients, two early cancers and dysplasia, not visible during routine endoscopy, were detected by EFD. Thirty three biopsies revealed either low or high grade dysplasia. Sensitivity for detection of dysplastic lesions ranged from 60% after local sensitisation with 500 mg to 80%, 100%, and 100% after systemic application of 5-ALA 10, 20, and 30 mg/kg, respectively. However, specificity was best for local sensitisation (70%) while systemic administration revealed values between 27% and 56%. Using 5 mg/kg, no red fluorescence in dysplastic lesions was found. No severe side effects were noted. CONCLUSION: EFD is a promising tool to detect non-visible dysplastic lesions in Barrett's oesophagus using 5-ALA sensitisation. A randomised controlled study is now indicated to compare the efficacy of EFD with the standard technique of four quadrant random biopsies.

Administration, Oral↗
PubMed2001

The effects of 5-aminolevulinic acid esters on protoporphyrin IX production in human adenocarcinoma cell lines.

Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type-specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD.

Adenocarcinoma↗
PubMed2000

[Fluorescence endoscopy in gastroenterology].

Fluorescence endoscopy is a new technique which allows a better endoscopic detection of nonvisible or difficult detectable malignant or premalignant lesions. Exogenously applied sensitizers 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 tissues. Meanwhile fluorescence endoscopy is a widely spread technique in urology using 5-aminolevulinic acid sensitization. In gastroenterology this technique seems promising in the detection of early cancers or dysplasia in patients with Barrett's esophagus or ulcerative colitis. This paper describes the current status and future development of fluorescence endoscopy in gastroenterology.

Aminolevulinic Acid↗
PubMed2000

5-Aminolevulinic acid-induced protoporphyrin IX for the detection of gastrointestinal dysplasia.

The detection of gastrointestinal dysplasia is an unresolved problem. Fluorescence detection of these premalignancies after exogenous application of 5-aminolevulinic acid, which is converted to protoporphyrin IX and accumulates selectively in tumors, is an interesting approach. Illumination with light of appropriate wavelength allows the discrimination and detection of gastrointestinal neoplasia either by spectroscopy or fluorescence endoscopy because of a typical red fluorescence of protoporphyrin IX. Surveillance of patients with Barrett's esophagus and ulcerative colitis might benefit from this new technique.

Aminolevulinic Acid↗
PubMed1999

["Cardiomegaly and pneumonia"--a misdiagnosis in long-standing achalasia].

HISTORY: A 65-year-old woman was admitted to another hospital with suspected status asthmaticus. While there was progressive respiratory failure, the chest X-ray showed bilateral congestion and infiltration with widened mediastinum and cardiomegaly. The patient was transferred to the authors' hospital after two days on ventilatory support because of suspected left-ventricular failure and pulmonary congestion with pneumonia. 30 years previously she had undergone a myotomy for achalasia. INVESTIGATIONS: Imaging of the oesophagus with water-soluble contrast medium, computed tomography of the thorax and gastroscopy revealed a siphon-like megaoesophagus (which had been misinterpreted radiologically as cardiomegaly) with a slightly open lower oesophageal sphincter. The pulmonary symptoms were thought to be due to aspiration pneumonia. TREATMENT AND COURSE: As there were no other reasonable treatment options a transmediastinal oesophageal resection with gastric pull-through and collar anastomosis was performed. CONCLUSION: In long-standing achalasia a megaoesophagus can develop despite previous myotomy. It should be included in the differential diagnosis of radiologically demonstrated mediastinal enlargement.

Aged↗
PubMed1999

Endoscopic fluorescence detection of dysplasia in patients with Barrett's esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization.

BACKGROUND: Surveillance of patients with Barrett's esophagus or ulcerative colitis for dysplasia is confined to biopsy specimens taken randomly during endoscopy because dysplasia remains undetectable by visual inspection. We attempted to visualize dysplastic tissue during endoscopy after sensitization with 5-aminolevulinic acid (5-ALA) leading to accumulation and formation of protoporphyrin IX and induction of characteristic red fluorescence of the latter substance using blue light illumination. METHODS: Six patients with histologically proven low- or high-grade dysplasia (Barrett's esophagus 2, ulcerative colitis 1, Billroth-II stomach 1, rectal polyps 2) were treated with oral administration of different concentrations of 5-ALA (10 to 20 mg/kg) or by local instillation of 3 gm 5-ALA in the rectum. Endoscopic fluorescence detection was performed 1 to 6 hours after sensitization using a blue light source and compared with conventional white light endoscopy. Biopsies of fluorescent and nonfluorescent areas were compared with histologic findings. RESULTS: Normal duodenal mucosa and squamous epithelium showed more intense 5-ALA-induced background red fluorescence compared with normal mucosa in the stomach or Barrett's mucosa. Histologically, dysplasia was exclusively found in areas with red fluorescence. False-positive fluorescence was associated with microscopic inflammation of the mucosa or feces in the colon. CONCLUSIONS: 5-ALA-induced protoporphyrin IX fluorescence may be useful in the detection of dysplasia in the gastrointestinal tract by enhancement of endoscopic surveillance of patients at a high risk for dysplasia.

Adenomatous Polyps↗
PubMed1999

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light.

Despite of the approval of Photofrin in various countries, chemically defined sensitizers for photodynamic therapy (PDT) are still needed for the absorption of light in the infrared spectrum, which provides a maximal penetration of light into tissue. Therefore, both the efficacy and the mechanism of action of the clinically approved dye indocyanine green (ICG) and laser irradiation were investigated in vitro. For the investigation of phototoxic effects, HT-29 cells were incubated 24 h prior to irradiation by using different concentrations of ICG (10-500 microM). In each experiment, cells were irradiated using a continuous wave (cw)-diode laser (lambda(ex) = 805 nm, 30 J cm(-2), 40 mW cm(-2)). After laser irradiation, cell viability of dark control and of cells incubated with 500 microM ICG was 1.27+/-0.11 or 0.28+/-0.05 respectively. Using 100 microM ICG and D2O, cell viability was further decreased from 0.46+/-0.03 (H2O) to 0.11+/-0.01 (D2O). Using D2O and 100 microM ICG, the concentration of malondialdehyde, a marker of lipid peroxidation, increased from 0.89+/-0.10 nmol 10(-6) cells to 11.14+/-0.11 nmol 10(-6) cells. Using 100 microM ICG and laser irradiation sodium azide or histidine (50 mM), quenchers of singlet oxygen reduced the cell killing significantly. In contrast, when using mannitol, a quencher of superoxide anion and hydroxyl radical, cell killing was not inhibited. According to the present results, photoactivated ICG seems to kill colonic cancer cells due to the generation of singlet oxygen and the subsequent formation of lipid peroxides. Therefore, ICG might present a promising photosensitizer for PDT; first clinical results confirm these findings.

Cell Death↗
PubMed1998

[Photodynamic diagnosis of gastrointestinal precancerous lesions after sensitization with 5-aminolevulinic acid. A pilot study].

BASIC PROBLEM AND OBJECTIVE: Endoscopic diagnosis of gastrointestinal precancerous and cancerous lesions is difficult, often even impossible. This study was undertaken to find out whether premalignant or suspected malignant tumors can be diagnosed by preceding sensitization with 5-aminolaevulinic acid (ALA), which in tumors is transformed in increased amounts into photosensitizing protoporphyrin IX, the latter being recognized by its characteristic red fluorescence on exposure to blue light. PATIENTS AND METHODS: 20 patients with known mild or moderately severe dysplasias (Barrett's esophagus, n = 8; colorectal adenoma, n = 3; ulcerative colitis n = 2, and gastric polyps or mucosal changes suspicious of malignancy, n = 5. Two patients with squamous-cell carcinoma, who after radio- and chemotherapy were endoscopically free of tumor, were sensitized with different concentrations of ALA (orally: 5-30 mg/kg; or locally: 3 g in 100 ml 0.9% NaCl). Photodynamic diagnosis (PDD) took place 4-8 h after oral and ca. 1-2 h after local sensitization with blue light (D-light, Storz, Tuttlingen, Germany). RESULTS: Definite red fluorescence with demonstration of dysplasia was found in three of four patients with Barrett's esophagus. Biopies from nonfluorescent areas were free of dysplasia. Two gastric adenomas (10 mg/kg ALA with high-grade dysplasia were definitively endoscopically by their red fluorescence. In one patient mild dysplasia was found in a non-fluorescent area after radio- and chemotherapy of an esophageal carcinoma. Dysplasias were also seen in the rectal biopsy after local applications. CONCLUSIONS: PDD makes it possible for the first time to visualize precancerous lesions of the gastrointestinal tract after preceding ALA sensitization. PDD is a highly promising method for monitoring patients with gastrointestinal disease and an increased risk of cancer, and for clarifying the diagnosis of mucosal changes suspicious of malignancy.

Adenoma↗
PubMed1998

Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid.

BACKGROUND AND STUDY AIMS: Endoscopic diagnosis of dysplastic lesions and early cancers in chronic ulcerative colitis is a major problem. Identification of suspicious lesions is influenced by the macroscopic appearance of the colon, but also by the endoscopist's experience. In this study we evaluated the identification of dysplastic lesions by the naked eye in an animal model of colitis after 5-aminoaevulinic acid-induced photosensitization. METHODS: 80 male Wistar rats were examined. Acute and chronic colitis were induced by oral application of 5% dextrane sulfate sodium (DSS) in 1-7 cycles (1 cycle = seven days DSS and 10 days water). For sensitisation 5-aminolaevulinic acid (5-ALA) at different doses (0, 10, 25, 50, 75, 100, and 200 mg/kg) was used. The colonic fluorescence was examined under a blue light (390-436 nm) for excitation. Histological findings of fluorescent and non-fluorescent biopsy specimens were recorded. RESULTS: Using 100 mg/kg 5-ALA intravenously for photosensitization, all dysplastic lesions (5/5) showed fluorescence (sensitivity 100%). However, at this concentration of 5-ALA, 60 false positive lesions were found out of 76 specimens taken from lesions that were not dysplastic--only 16 specimens of non-dysplastic lesions did not fluoresce (specificity 21%). Using 75 and 50 mg/kg 5-ALA intravenously sensitivity decreased to 92% (36/39) and 42% (5/12), respectively, while specificity increased to 35% (29/82) and 62% (45/73). Using 50 mg/kg 5-ALA intravenously, fluorescence-positive biopsy specimens showed inflammation of the colon in 31% whereas only 12% contained normal mucosa (p < 0.01). The distribution of fluorescence-positive biopsy specimens with histologically confirmed inflammation was similar for different grades of inflammation after sensitisation with 75 and 100 mg/kg 5-ALA, whereas with 50 mg/kg 5-ALA fluorescence-positive biopsy specimens contained significantly (p < 0.05) more moderate, massive, or ulcerative inflammation (79%) than mild inflammation (21%). CONCLUSION: 5-ALA induced photosensitization gave a high sensitivity, but low specificity in identifying dysplastic lesions in DSS-induced colitis in rats. In this animal model inflammation is a major factor in disturbing the fluorescence localisation of dysplasia after sensitisation with 5-ALA.

Acute Disease↗
PubMed1998

Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial.

BACKGROUND AND STUDY AIMS: A second-look endoscopy is often performed to evaluate the efficacy of a prior injection therapy in patients with bleeding peptic gastric or duodenal ulcers. Although this strategy is widely established, it does not rely on unequivocal data from controlled studies. In a prospective, randomized, controlled multicenter trial we assessed the effect of programmed endoscopic follow-up examinations with eventual retreatment on the outcome of bleeding ulcers in these patients. PATIENTS AND METHODS: One hundred and five patients with gastric or duodenal peptic ulcers presenting with active (Forrest type I) or recent (Forrest type IIa and IIb) bleeding upon endoscopy within four hours after admission were included in the study. Emergency treatment consisted of the sequential injection of both epinephrine (1:10,000 v/v) and up to 2 ml of fibrin/thrombin around the ulcer base. Fifty-two patients were randomized to receive programmed endoscopic monitoring with eventual retreatment in cases of Forrest type I, IIa, or IIb ulcers beginning within 16-24 hours after the index bleed. Follow-up endoscopies were continued until the macroscopic appearance revealed a Forrest type IIc or III ulcer. Fifty-three patients in the control group were closely monitored, and only received a second endoscopy when there was clinical or biochemical evidence of recurrent bleeding. The groups did not differ with respect to age, sex, site and severity of bleeding. RESULTS: The numbers of patients with recurrent bleeding were similar whether they were endoscopically monitored or not (21% versus 17%, P=0.80 chi-squared test). In addition, there was no statistically significant difference between the two groups with respect to the number of blood units transfused, need for surgical intervention, hospital stay or number of deaths (Mann-Whitney U-test). Improving local ulcer stigmata was not related to a better outcome. CONCLUSIONS: Programmed endoscopic follow-up examinations with eventual retreatment in patients locally injected for an acute or recent hemorrhage from a gastric or duodenal ulcer did not influence their outcome when compared to patients receiving only a second endoscopic intervention upon evidence for recurrent hemorrhage. Scheduled control endoscopies cannot be recommended after an initial successful endoscopic treatment of peptic ulcer bleeding when selection of the patients for second-look endoscopy is directed by the Forrest criteria.

Aged↗
PubMed1998

Interleukins and their antagonists but not TNF and its receptors are released in post-ERP pancreatitis.

OBJECTIVE: Usually it is not possible to study the initial systemic response in patients with acute pancreatitis in the first hours after onset of the disease. We used postendoscopic retrograde pancreatography (ERP) pancreatitis as a model to study cytokine and anticytokine release in the early phase of human acute pancreatitis. METHODS: Post-ERP pancreatitis was defined as a threefold increase in serum amylase and at least two of the following clinical symptoms: abdominal pain, nausea, vomiting or peritonism 24 h after ERP. Serum levels of pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF), as well as endogenous antagonistic mediators of the systemic inflammatory response such as soluble tumour necrosis factor alpha receptors p55 (TNFR p55) and p75 (TNFR p75), and IL-1-receptor antagonist (IL-1-RA) and interleukin-2-receptor (IL-2R) as indicators of lymphocyte activation were measured before and 0, 1, 4, 12, 24 and 48 h after ERP. In nine patients with acute post-ERP pancreatitis, these parameters were monitored daily until C-reactive protein (CRP) was within normal ranges and were compared to patients without pancreatitis after ERP. RESULTS: IL-1beta was not detectable in five patients with and four patients without post-ERP pancreatitis. The values of the remaining patients in both groups were lower than 3.9 pg/ml. IL-8 and IL-1-RA serum concentrations peaked 12 h after ERP (132.9 and 3245.0 pg/ml respectively) compared to patients without post-ERP pancreatitis (25.8 and 389.9 pg/ml respectively). The IL-6 concentration increased to 81.6 pg/ml (8.0 pg/ml in control patients) 24 h after ERP, while the peak values for CRP were measured 72 h after ERP (164.0 versus 7.7 mg/l). IL-2R content was maximally elevated 144 h after ERP (688.8 versus 255.9 U/ml), while concentrations of TNF and its receptors showed no significant change over time. CONCLUSION: The initial response of the cytokine network to damage of the human pancreas leading to acute pancreatitis includes the release of IL-8 and the IL-1 antagonist IL-1-RA, while IL-1beta is not found in the systemic circulation. The TNF system does not seem to be involved as indicated by the lack of detectable changes in TNF and the soluble TNFR p55 and p75 serum concentrations. Lymphocyte activation as indicated by elevated IL-2R levels occurred days after the initial trauma. Even mild post-ERP pancreatitis leads to significant systemic release of cytokines and their biological counterparts.

Acute Disease↗
PubMed1998

Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.

Adult↗