Brigitte Mayinger

Endoscopic light-induced autofluorescence spectroscopy for the diagnosis of colorectal cancer and adenoma.

To evaluate the new, bio-optical method of light-induced autofluorescence spectroscopy for the endoscopic in-vivo diagnosis of (pre)-cancerous lesions of the colorectum, 311 endogenous fluorescence spectra were obtained from normal, adenomatous and cancerous colorectal tissue in 11 patients with cancer, six patients with familial adenomatous polyposis, and six patients with multiple adenomatous polyps. A light source delivered either white or violet-blue light for excitation of tissue autofluorescence via a flexible endoscope. Endogenous fluorescence spectra emitted by the tissue were picked up with a fiberoptic probe and analysed with a spectrograph. Biopsies were taken for definitive classification of the spectra. Rectal cancer (n=11) as well as adenomas with severe dysplasia (n=19) showed specific differences between the emitted fluorescence spectra as compared with normal mucosa and hyperplastic polyps. Having applied a mathematical algorithm to the spectra, a sensitivity of 96% and a specificity of 93% were obtained for the diagnosis of rectal cancer. The equivalent values for the diagnosis of dysplastic ademomas were 98 and 89%, respectively. Light-induced autofluorescence spectroscopy is a new and promising bio-optical procedure for the endoscopic in-vivo diagnosis of colorectal cancer and dysplasia.

Evaluation of in vivo endoscopic autofluorescence spectroscopy in gastric cancer

BACKGROUND The aim of this study was to evaluate light-induced autofluorescence spectroscopy for the in vivo diagnosis of gastric cancer. METHODS A total of 344 endogenous fluorescence spectra were obtained from normal (164) and cancerous gastric mucosa (180) in 15 patients with pure adenocarcinoma and in 16 patients with gastric cancer containing signet-ring cells. A special light source capable of delivering either white or violet-blue light for the excitation of tissue autofluorescence via the endoscope was used. Endogenous fluorescence spectra emitted by the tissue were collected with a fiberoptic probe and analyzed with a spectrograph. RESULTS Gastric adenocarcinoma exhibits specific changes in the emitted fluorescence spectra as compared with normal gastric mucosa. By algorithmic classification of the spectra, a sensitivity of 84%, specificity of 87%, a likelihood ratio for a positive test of 6.5 and for a negative test of 0.18 were obtained for the diagnosis of pure adenocarcinoma of the stomach. However, gastric cancer with signet-ring cells exhibits great variation in emitted autofluorescence spectra as compared with normal mucosa. The sensitivity for the diagnosis of all carcinomas containing signet-ring cells was 55%, specificity 85%, the likelihood ratio for a positive test was 3.7 and for a negative test, 0.53. The diagnostic value decreases with increasing numbers of signet-ring cells and tumor grade. CONCLUSIONS Light-induced autofluorescence spectroscopy is a new and promising bio-optical technique for the endoscopic in vivo diagnosis of gastric adenocarcinoma. The poor diagnostic accuracy for signet-ring cell carcinoma may be explained by the diffuse and frequent submucosal growth of this tumor and the presence of collagen fibers.

Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience

Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience

Endoscopic photodynamic diagnosis: oral aminolevulinic acid is a marker of GI cancer and dysplastic lesions☆☆☆★★★

BACKGROUND Dysplasia and early cancer of the upper gastrointestinal (GI) tract often are undetected at white-light endoscopy. We describe oral administration of 5-aminolevulinic acid for the in vivo photodynamic diagnosis of premalignant and malignant lesions during endoscopy. METHODS Four patients with known gastric adenoma (n = 1), macroscopically undetected but histologically proven esophageal squamous cell cancer (n = 1), suspected early cancer of the esophagus (n = 1), and multiple duodenal adenomas (n = 1) were sensitized with 5-aminolevulinic acid administered orally (15 mg/kg body weight). Photodynamic diagnosis was conducted after a retention time of 6 to 7 hours with a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected through the gastroscope with an image-intensifying camera. RESULTS All malignant lesions exhibited red or bluish fluorescence during photodynamic diagnosis. Fluorescence-negative mucosal areas proved to be histologically benign. CONCLUSION Fluorescence induced with 5-aminolevulinic acid might be useful for the endoscopic detection of dysplasia and early carcinoma in the upper GI tract. Further investigations are needed to evaluate the sensitivity and specificity of photodynamic diagnosis for different tumor entities.

Evaluation of sensitivity and inter- and intra-observer variability in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus with enhanced magnification endoscopy

Objective. Magnification endoscopy with acetic acid or dye for diagnosis of Barretts esophagus is presently undergoing clinical evaluation. Current studies report good accuracy in predicting specialized intestinal metaplasia. To date, however, there is no definitive information on the inter- and intra-observer variability of these methods applied to the diagnosis of normal and dysplastic Barretts mucosa. Material and methods. Sixty patients with endoscopically suspected Barretts esophagus were investigated prospectively with the zoom endoscope after contrast enhancement of the mucosa with 1.5% acetic acid. Two hundred and twenty-three enlarged and histologically investigated areas of gastric, cardiac, normal and dysplastic Barretts mucosa were photodocumented and in randomized sequence presented to 4 endoscopists in a blinded manner (2 with and 2 without experience of zoom endoscopy for evaluation). The reference for the first evaluation (A1) was standard endoscopic photographs of the respective, histologically confirmed mucosal entity. In a second evaluation (A2), the pictures were again interpreted by the same blinded investigators, but this time a modified pit-pattern classification as proposed by Sharma et al. was employed as the evaluation reference. Results. The diagnostic sensitivity for specialized intestinal metaplasia and dysplasia in Barretts esophagus calculated for the A1 evaluation ranged – investigator dependently – from 54.9% to 80.7% and for A2 from 42.2% to 81.5%. The inter- and intra-observer variability for the evaluation procedure A1 and A2 was high (all kappa values <0.4). In particular, the inexperienced investigators demonstrated high intra-observer variability and low sensitivity in comparison with the experienced investigators. Conclusions. The diagnosis of Barretts mucosa using enhanced magnification endoscopy after acetic acid instillation is associated with a high level of interobserver variability. One reason is a frequent mismatch between cardiac mucosa and non-dysplastic Barretts mucosa.

Isolierter ACTH-Mangel als seltene Ursache rezidivierender Synkopen und Hypoglykämien

ZusammenfassungAnamnese und klinischer Befund: Ein 63-jähriger Patient wurde wegen einer Synkope, assoziiert mit Hypoglykämie und Hypotonie, notfallmäßig stationär aufgenommen. Klinisch auffällig waren ein blasses, wachsartiges Hautkolorit sowie eine deutliche Antriebsstörung. Zum Aufnahmezeitpunkt und während des weiteren stationären Aufenthalts wirkte der Patient verlangsamt und adynam. Untersuchungen: Nach Ausschluss einer kardiovaskulären oder neurologischen Genese der rezidivierenden Synkopen erfolgte eine weiterführende endokrinologische Diagnostik. Dabei zeigte sich ein Cortisolmangel mit fehlendem Anstieg des Cortisols im ACTH-Test. Der ACTH-GnRH-TRH-Test erbrachte einen isolierten Ausfall der corticotropen Hormone. Im CRH-Test zeigte sich kein Anstieg der ACTH– und Cortisolwerte. Der Insulinhypoglykämietest dokumentierte eine isolierte ACTH-Insuffizienz mit konsekutivem Cortisolmangel. Im Computertomogramm (CT) des Abdomens konnte eine Nebennierenraumforderung ausgeschlossen werden. Das CT des Schädels war unauffällig. In der Kernspintomographie der Hypophyse wurde der Verdacht auf eine Volumenminderung der Hypophyse geäußert. Therapie und Verlauf:Unter Therapie mit Hydrocortison 20 mg und Fludrocortison 0,05 mg oral täglich besserte sich die klinische Symptomatik umgehend. Unter Substitutionstherapie war der Patient deutlich leistungsfähiger, die Antriebsarmut war behoben. Die systolischen Blutdruckwerte lagen im Schnitt über 120 mm Hg. Hypoglykämische Episoden traten nicht mehr auf. Schlußfolgerung: Bei der Konstellation einer hypotonen Kreislaufsituation mit Hypoglykämie und fehlender Pigmentierung sollte an die seltene Ursache einer sekundären Nebennierenrindeninsuffizienz gedacht werden.AbstractHistory and Clinical Findings: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patients behavior was slowed down and adynamic. Investigations: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. Treatment and Course: Under therapy with hydrocortisone 20 mg and fludrocortisone 0,05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycaemic episodes. Conclusion: Secondary insufficiency of the adrenal gland should be considered as a rare cause hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin.

Farbtexturbasierte optische Biopsie auf hochauflösenden endoskopischen Farbbildern des Ösophagus

In diesem Beitrag stellen wir zwei neue Verfahren zur Farbtexturklassifikation in endoskopischen Bildern vor. Diese multispektralen Texturmerkmale basieren auf Summen- und Differenzhistogrammen sowie Statistischen Geometrischen Merkmalen. Die Anwendbarkeit dieser Farbtexturmerkmale zur automatischen Klassifikation von hochaufgelosten Bildern der Schleimhaut des Osophagus wird nachgewiesen. Es zeigt sich, dass durch die Verwendung dieser kombinierten Farbtexturmerkmale signifikante Klassifikationsverbesserungen erzielt werden konnen.

Lineare Farbkorrektur zur automatischen Gewebeerkennung in der Endoskopie des Ösophagus

Der vorliegende Beitrag untersucht mehrere Varianten eines analytischen, auf Referenzfarbwerten beruhenden, linearen Farbkalibrierverfahrens mit verschiedenen Matrixformen und vorverarbeitenden Normierungen. Die erforderlichen Transformationsmatrizen werden mit Hilfe der Singularwertzerlegung geschatzt. Ihr Einfluss auf Klassifikationsraten einer farbtexturbasierten Gewebeklassifikation werden bewertet und mit bekannten Farbkonstanzverfahren verglichen. Das vorgestellte Verfahren leistet einen Beitrag zu einer verbesserten automatischen Erkennung von Geweben, die langfristig Unterstutzung fur den praktizierenden Endoskopiker bieten und auch in Wissenschaft und Forschung Einsatz finden kann.

3452 Endoscopic photodynamic diagnosis for the detection of dysplasia and squamous cell cancer of the esophagus.

Introduction: Dysplasia and early cancer of esohagus are often difficult to prove under white-light endoscopy. The present article describes the early detection of these lesions with the help of photodynamic diagnosis (PDD) following photosensibilisation with oral 5-aminolevulinic acid (5-ALA). Methods: Twelve patients with histological proved esophageal squamous cell cancer were sensitized with 5-ALA [10 mg/kg body weight (n=7), 15 mg/kg body weight (n=5)] orally. Three hours (n=2) or six hours (n=10) later patients underwent endoscopic fluorescence detection using a special light source capable of delivering either white light for conventional endoscopy or violet-blue light for endoscopic fluorescence detection. Red fluorescence was recorded via the gastroscope using an image-intensifying camera. Results: In total 48 biopsies were taken, 21 from non-fluorescing mucosa and 27 from red-fluorescing mucosa. Nine of ten biopsies taken from histological proved malignant areas showed red fluorescence. 20 of 38 histological benign biopsies were classified as fluorescence-negative using PDD. Using histology as gold-standard, sensitivity for PDD was 90.0 % versus 20.0 % for white-light endoscopy, while specificity for PDD was only 52.6 % versus 92.1 % for endoscopic white light image. Discussion: With a sensitivity of 90 % PDD is an appropriate method to detect (pre-)cancerous lesions potentially at an earlier stage in comparison with white-light endoscopy (sens. 20 %). Though PDD has a lower specificity (52.6 % versus 92.1 % with white-light), especially high risk patients might profit from this procedure.

7126 Light-induced autofluorescence spectroscopy for the diagnosis of esophageal cancer.

Introduction: Autofluorescence spectroscopy using violet-blue excitation light is being investigated for in-vivo diagnosis of esophageal cancer during routine-endoscopy. Methods: Fluorescence spectra were collected from squamous cell cancer (N = 7 patients) and adenocarcinoma of the esophagus (N = 3 patients) and compared with collected spectra of the corresponding healthy esophageal mucosa. Following the spectrographic measurements biopsies were taken to get a definitive classification of histopathological status. A special light source capable of delivering either white or violet-blue light was used for the excitation of tissue autofluorescence via the endoscope. Endogenous fluorescence spectra emitted by the tissue were collected with a fiberoptic probe and analyzed with a spectrograph. Results: Over 100 spectra of cancerous and benign esophageal mucosa were evaluated. As compared with normal mucosa esophageal squamous cell cancer and adenocarcinoma of the esophagus were associated with special changes in the emitted fluorescence spectra. Discussion: Fluorescence spectroscopy with a slightly modified conventional light source might be useful for the endoscopic in-vivo detection of esophageal cancer. Further series trials need to be done to investigate the sensitivity and specificity of this new method.