Detection of Dysplastic Lesions by Fluorescence in a Model of Colitis in Rats After Previous Photosensitization with 5-Aminolaevulinic Acid

Messmann, Helmut; Kullmann, Frank; Wild, T. Cameron; Knüchel‐Clarke, Ruth; Rüschoff, Josef; Groß, Volker; Schölmerich, Jürgen; Holstege, Axel

doi:10.1055/s-2007-1001278

Cited by 48 publications

(25 citation statements)

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“…False positive fluorescence was mainly induced by inflammation. 8 In this study, we assessed the ability of FE to detect dysplasia in patients with UC. We tested local application of 5-ALA either by enema or by spraying the substance with a catheter on the mucosa, based on the assumption that local sensitisation is associated with fewer side effects.…”

Section: Discussionmentioning

confidence: 99%

“…8 The activity of UC is defined analogous to the UC scoring system. 9 Sensitisation and fluorescence endoscopy After conventional colon lavage, patients were sensitised orally with 20 mg/kg body weight 5-ALA (Medac GmbH, Hamburg, Germany) dissolved in orange juice, or locally either by enema (3 g 5-ALA dissolved in 250 ml NaCl 0.9% for one hour) or by spraying the 5-ALA solution onto the colonic mucosa with a spray catheter (5-PWL; Olympus, Hamburg, Germany).…”

Section: Patient Populationmentioning

confidence: 99%

“…5 Promising results for FE of bronchial 6 and bladder 7 tumours after 5-ALA sensitisation have been reported. For the first time, we have demonstrated previously in an animal colitis model that it may be possible to detect dysplastic lesions even with the "naked eye" in a dose dependent manner after sensitisation with 5-ALA. 8 The aim of this study was to assess the feasibility of detecting or excluding dysplasia in patients with chronic ulcerative colitis (UC) by FE using various sensitisation modes.…”

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confidence: 99%

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

Messmann

2003

Gut

101

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Patient Populationmentioning

confidence: 99%

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confidence: 99%

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

Messmann

2003

Gut

101

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“…The potential for malignant degeneration of some chronic diseases like Barrett's oesophagus, ulcerative colitis and familial polyposis is well known. However, early cancers are difficult to diagnose, as they can hide in normal or unspecifically inflamed mucosa [37,38,39,40,41,42,43,44,45,46,47,48]. At present, assessment of endoscopic findings is subjectively made by the investigator.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Fluorescence detection of small gastrointestinal tumours: principles, technique, first clinical experience

Orth

Russ

Steiner

et al. 2000

Langenbeck's Archives of Surgery

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Photodynamic therapy (PDT) is a form of cancer treatment based on the selective accumulation of a photosensitizer in neoplastic tissue. The fluorescent properties of a photosensitizer permit diagnostic localization of primary tumours and/or metastasis. Occult lesions are hard to detect and can easily be missed during routine laparoscopy. Fluorescence observation offers additional optical information and the ability to detect these occult tumours. Clinically, we used 5-aminolevulinic acid for peritoneal staining and tumour demarcation via tumour-specific fluorescence induced by protoporphyrin IX. For laparoscopic observations, a "D-Light" system was used; the conventional white light source was equipped with an optical blocking filter that transmits at the excitation wavelength (380-450 nm) and blocks all other parts of the spectrum. With the aid of a suitable observation filter, the relevant fluorescence was detectable. With the help of this fluorescence we increased the capacity to detect occult tumours, that were missed with white-light observation (9/26). In the gastrointestinal tract, we used a krypton laser at 405 nm for PP IX fluorescence induction. Although there were high sensitivity rates for neoplasms (81% peritoneal carcinomas, 60% gastric cancer), no exact histopathological statement could be achieved at because of false-positive fluorescence, mainly caused by inflammation (6/32). Current clinical goals and the future perspectives of photodynamic diagnostic are discussed.

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“…Ideally, the investigator will discern subtle mucosal changes and decide immediately, according to their fluorescence characteristic, whether the lesions require further treatment. Although showing high sensitivity rates of >90 %, the described ideal clinical situation is hampered by false-positive fluorescence, mainly caused by inflammation [21].…”

Section: Current Clinical Applicationsmentioning

confidence: 99%

Blue light illumination for minimally-invasive fluorescence detection of tumours: technology, clinical experience and future perspectives

Gahlen

Prosst

Herfarth

2000

Minimally Invasive Therapy & Allied Technologies

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Endoscopic detection and differentiation of benign, precancerous and malignant tissue is difficult, especially in gastroenterology. Photodynamic techniques utilising tumour-specific fluorescence, e.g. induced by aminolevulinic acid (AM) / protoporphyrin IX (PplX), have been used to visualise and assess lesions. Originally requiring sophisticated laser technology, innovative excitation light sources have been recently developed for photodynamic diagnosis (PDD) to facilitate and broaden its clinical use. The characteristics of one of these devices, the D-Light (Karl Storz, Germany), are described. Current clinical applications and future perspectives of PDD are discussed.

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Detection of Dysplastic Lesions by Fluorescence in a Model of Colitis in Rats After Previous Photosensitization with 5-Aminolaevulinic Acid

Abstract: 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.

Cited by 48 publications

References 0 publications

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

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

Fluorescence detection of small gastrointestinal tumours: principles, technique, first clinical experience

Blue light illumination for minimally-invasive fluorescence detection of tumours: technology, clinical experience and future perspectives

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