Das Mikroskop im Gastrointestinaltrakt: Konfokale Endomikroskopie – klinischer Nutzen und wissenschaftlicher Einblick in die Tiefe

Zusammenfassung

Die Endomikroskopie erlaubt es erstmals, während der laufenden Endoskopie die Schleimhaut mikroskopisch zu untersuchen. Dafür ist die Applikation geeigneter Fluoreszenzfarbstoffe erforderlich. Indikation sind vor allem entzündliche und (prä-)neoplastische Erkrankungen, die durch ungezielte Biopsien häufig nur unvollständig erfasst werden können. Multiple Studien haben mittlerweile die Wertigkeit der Endomikroskopie im oberen und unteren Gastrointestinaltrakt etabliert. Folgestudien haben darüber hinausgehend die intravitale Mikroskopie des Gallengangs, der Leber und des Pankreas untersucht. Die Endomikroskopie ermöglicht außerdem erstmals die artefaktarme Untersuchung von Gewebe in dessen natürlicher Umgebung und weist damit einen völlig neuen Weg zu patientennaher Wissenschaft und molekularer Bildgebung. Sie verbindet somit die klinische Diagnostik mit der translationalen Wissenschaft.

Abstract

Endomicroscopy is a novel method that allows microscopy of the gastrointestinal mucosa during ongoing endoscopy. This necessitates the application of fluorescent contrast agents. Indications for endomicroscopy include inflammatory and (pre-)neoplastic diseases that are often only incompletely assessed by random biopsies. Multiple trials have established the value of endomicroscopy of the upper and lower gastrointestinal tract. Follow-up studies have evaluated intravital microscopy of the biliary tract, the liver or pancreas. Endomicroscopy for the first time enables microscopic imaging of the intact tissue virtually free of artifacts. This allows an unprecedented approach to the patient in gastrointestinal science and molecular imaging. CLE therefore links clinical patient care with translational science.

Schlüsselwörter

Endomikroskopie - molekulare Bildgebung - Colitis ulcerosa - Barrett-Ösophagus - kolorektales Adenom

Key words

endomicroscopy - molecular imaging - ulcerative colitis - Barrettʼs esophagus - colorectal adenoma

• Literatur

• 1 Kiesslich R, Burg J, Vieth M et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 2004; 127: 706-713
• 2 Goetz M, Deris I, Vieth M et al. Near-infrared confocal imaging during mini-laparoscopy: a novel rigid endomicroscope with increased imaging plane depth. J Hepatol 2010; 53: 84-90
• 3 Wallace MB, Meining A, Canto MI et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 2010; 31: 548-552
• 4 Goetz M, Fottner C, Schirrmacher E et al. In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases. Endoscopy 2007; 39: 350-356
• 5 Dunbar KB, Canto MI. Confocal laser endomicroscopy in Barrettʼs esophagus and endoscopically inapparent Barrettʼs neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc 2010; 72: 668
• 6 Kiesslich R, Galle PR, Neurath MF et al. Atlas of Endomicroscopy. Heidelberg: Springer Medizin Verlag; 2008
• 7 Tous R, Delgado J, Zinkl T et al. The Anatomy of an Optical Biopsy Semantic Retrieval System. IEEE MultiMedia 2012; 19: 16-27
• 8 Neumann H, Vieth M, Atreya R et al. Prospective evaluation of the learning curve of confocal laser endomicroscopy in patients with IBD. Histol Histopathol 2011; 26: 867-872
• 9 Pech O, Rabenstein T, Manner H et al. Confocal laser endomicroscopy for in vivo diagnosis of early squamous cell carcinoma in the esophagus. Clin Gastroenterol Hepatol 2008; 6: 89-94
• 10 Liu H, Li YQ, Yu T et al. Confocal laser endomicroscopy for superficial esophageal squamous cell carcinoma. Endoscopy 2009; 41: 99-106
• 11 Kiesslich R, Gossner L, Goetz M et al. In vivo histology of Barrettʼs esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol 2006; 4: 979-987
• 12 Dunbar KB, Okolo 3rd P, Montgomery E et al. Confocal laser endomicroscopy in Barrettʼs esophagus and endoscopically inapparent Barrettʼs neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc 2009; 70: 645-654
• 13 Pohl H, Rosch T, Vieth M et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrettʼs oesophagus. Gut 2008; 57: 1648-1653
• 14 Bajbouj M, Vieth M, Rosch T et al. Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrettʼs esophagus. Endoscopy 2010; 42: 435-440
• 15 Kiesslich R, Goetz M, Burg J et al. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology 2005; 128: 2119-2123
• 16 Ji R, Li YQ, Gu XM et al. Confocal laser endomicroscopy for diagnosis of Helicobacter pylori infection: a prospective study. J Gastroenterol Hepatol 2010; 25: 700-705
• 17 Guo YT, Li YQ, Yu T et al. Diagnosis of gastric intestinal metaplasia with confocal laser endomicroscopy in vivo: a prospective study. Endoscopy 2008; 40: 547-553
• 18 Zhang JN, Li YQ, Zhao YA et al. Classification of gastric pit patterns by confocal endomicroscopy. Gastrointest Endosc 2008; 67: 843-853
• 19 Li WB, Zuo XL, Zuo F et al. Characterization and identification of gastric hyperplastic polyps and adenomas by confocal laser endomicroscopy. Surg Endosc 2010; 24: 517-524
• 20 Li WB, Zuo XL, Li CQ et al. Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions. Gut 2011; 60: 299-306
• 21 Ji R, Zuo XL, Li CQ et al. Confocal endomicroscopy for in vivo prediction of completeness after endoscopic mucosal resection. Surg Endosc 2011; 25: 1933-1938
• 22 Polglase AL, McLaren WJ, Skinner SA et al. A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest Endosc 2005; 62: 686-695
• 23 Sanduleanu S, Driessen A, Gomez-Garcia E et al. In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. Clin Gastroenterol Hepatol 2010; 8: 371-378
• 24 Goetz M, Toermer T, Vieth M et al. Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical cresyl violet. Gastrointest Endosc 2009; 70: 959-968
• 25 Benedix F, Kuester D, Meyer F et al. [Influence of Mucinous and Signet-Ring Cell Differentiation on Epidemiological, Histological, Molecular Biological Features, and Outcome in Patients with Colorectal Carcinoma]. Zentralbl Chir 2012; Jan 24 [Epub ahead of print]
• 26 Bertolini J, Wittekind C. [Large Adenomas of the Colon and Rectum – Specific Features of the Diagnostics.]. Zentralbl Chir 2011; Dez 15; [Epub ahead of print]
• 27 Sumiyama K, Kiesslich R, Ohya TR et al. Endomicroscopy of intramuscular neuronal network using confocal laser endomicroscopy: a new diagnostic approach for enteral motility disorders. Gastrointest Endosc 2012; 75: 478-478
• 28 Kiesslich R, Goetz M, Lammersdorf K et al. Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology 2007; 132: 874-882
• 29 Neumann H, Vieth M, Atreya R et al. Assessment of Crohnʼs disease activity by confocal laser endomicroscopy. Inflamm Bowel Dis 2012; 18: 2261-2269
• 30 Kiesslich R, Duckworth CA, Moussata D et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 2012; 61: 1146-1153
• 31 Kiesslich R, Hoffman A, Goetz M et al. In vivo diagnosis of collagenous colitis by confocal endomicroscopy. Gut 2006; 55: 591-592
• 32 Zambelli A, Villanacci V, Buscarini E et al. Collagenous colitis: a case series with confocal laser microscopy and histology correlation. Endoscopy 2008; 40: 606-608
• 33 Meining A, Schwendy S, Becker V et al. In vivo histopathology of lymphocytic colitis. Gastrointest Endosc 2007; 66: 398-399 discussion 400
• 34 Meining A, Frimberger E, Becker V et al. Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy. Clin Gastroenterol Hepatol 2008; 6: 1057-1060
• 35 Loeser CS, Robert ME, Mennone A et al. Confocal endomicroscopic examination of malignant biliary strictures and histologic correlation with lymphatics. J Clin Gastroenterol 2011; 45: 246-252
• 36 Meining A, Phillip V, Gaa J et al. Pancreaticoscopy with miniprobe-based confocal laser-scanning microscopy of an intraductal papillary mucinous neoplasm (with video). Gastrointest Endosc 2009; 69: 1178-1180
• 37 Konda VJ, Aslanian HR, Wallace MB et al. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc 2011; 74: 1049-1060
• 38 Goetz M, Kiesslich R, Dienes HP et al. In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time. Endoscopy 2008; 40: 554-562
• 39 Foersch S, Heimann A, Ayyad A et al. Confocal Laser Endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo. PLoS One 2012; 7: e41760;
• 40 Haxel BR, Goetz M, Kiesslich R et al. Confocal endomicroscopy: a novel application for imaging of oral and oropharyngeal mucosa in human. Eur Arch Otorhinolaryngol 2010; 267: 443-448
• 41 Pogorzelski B, Hanenkamp U, Goetz M et al. Systematic intraoperative application of confocal endomicroscopy for early detection and resection of squamous cell carcinoma of the head and neck: a preliminary report. Arch Otolaryngol Head Neck Surg 2012; 138: 404-411
• 42 von Delius S, Feussner H, Wilhelm D et al. Transgastric in vivo histology in the peritoneal cavity using miniprobe-based confocal fluorescence microscopy in an acute porcine model. Endoscopy 2007; 39: 407-411
• 43 Sonn GA, Mach KE, Jensen K et al. Fibered confocal microscopy of bladder tumors: an ex vivo study. J Endourol 2009; 23: 197-201
• 44 Wiesner C, Jager W, Salzer A et al. Confocal laser endomicroscopy for the diagnosis of urothelial bladder neoplasia: a technology of the future?. BJU Int 2011; 107: 399-403
• 45 Tan J, Quinn MA, Pyman JM et al. Detection of cervical intraepithelial neoplasia in vivo using confocal endomicroscopy. BJOG 2009; 116: 1663-1670
• 46 Goetz M, Wang TD. Molecular imaging in gastrointestinal endoscopy. Gastroenterology 2010; 138: 828-833.e1
• 47 Mahmood U. Optical molecular imaging approaches in colorectal cancer. Gastroenterology 2010; 138: 419-422
• 48 Hsiung PL, Hardy J, Friedland S et al. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat Med 2008; 14: 454-458
• 49 Goetz M, Ziebart A, Foersch S et al. In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by targeting epidermal growth factor receptor. Gastroenterology 2010; 138: 435-446
• 50 Foersch S, Kiesslich R, Waldner MJ et al. Molecular imaging of VEGF in gastrointestinal cancer in vivo using confocal laser endomicroscopy. Gut 2010; 59: 1046-1055
• 51 Hoetker MS, Kiesslich R, Diken M et al. Molecular in vivo imaging of gastric cancer in a human-murine xenograft model: targeting epidermal growth factor receptor. Gastrointest Endosc 2012; 76: 612-620
• 52 Alencar H, Funovics MA, Figueiredo J et al. Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection–study in mice. Radiology 2007; 244: 232-238