Progress in Endoscopic Imaging of Gastrointestinal Tumors

European Review for Medical and Pharmacological Sciences 2010; 14: 272-276 Progress in endoscopic imaging of gastrointestinal tumors

G. COSTAMAGNA, M. MARCHESE

Operative Unit of Endoscopic Digestive Surgery, Catholic University of the Sacred Heart, Rome (Italy)

Abstract. – State of the Art: New technolo- ommended, but it remains questionable whether gies in the form of high-magnification or “zoom” this time-consuming approach is clinically effec- endoscopy complemented by chromoscopic tive. This need led to intensified efforts to devel- agents or Narrow Band Imaging permit early detection of neoplastic lesions, particularly flat and de- op an “ideal” technique that could objectively de- pressed types. Detailed characteristics of the mu- tect the maximum number of cases of cancer cosal surface can be obtained, enabling an in vivo with a minimum number of biopsies (Table I). “optical biopsy” to make an instant diagnosis at endoscopy, previously possible only by using his- Red Flag Techniques With tological or cytological analysis. Advances in fiber “Virtual” Chromoendoscopy optics, light sources, detectors, and molecular biol- ogy have led to the development of several novel “Red flag” methods involve special techniques methods for tissue evaluation in situ. that are added to standard white-light endoscopy in Perspectives: Promising imaging techniques order to increase the sensitivity for detecting early include fluorescence endoscopy, optical coher- neoplasia in a broadfield imaging examination1,2. ence tomography, confocal microendoscopy, Olympus Narrow Band Imaging (NBI), Fujji- molecular imaging, and light scattering and Ra- non Intelligent Colour Enhancement system man spectroscopy. (FICE), and Pentax i-scan are applied to a new Conclusions: These techniques probably are able to replace conventional biopsy in the near generation of high-resolution endoscopes, allow- future, but the endoscopists should become in- ing the endoscopist to easily switch between the creasingly more familiar with histopathologic “Virtual chromoendoscopy-mode” and the nor- findings. mal “High resolution-mode” with no need for special equipment or dyes. Key Words: NBI works through the application of a special Gastrointestinal tumors, Narrow band imaging, Fu- optical filter to the white light source, enabling to jjinon intelligent colour enhancement, I-Scan, Autoflu- “narrow” the wavelength of the light and to em- orescence imaging, Spectroscopy, Confocal laser en- phasize both the mucosal “pit-pattern” and the domicroscopy, Endocytoscopy, Optical coherence to- 3 mography. vascular network . The FICE system is based on a computed spectral estimation technology that processes the reflected photons to reconstruct virtual images with a choice of different wavelengths. This leads to enhancement of the tissue Introduction microvasculature as a result of the differential optical absorption of light by haemoglobin in the The detection of small premalignant lesions is mucosa4. I−Scan (Pentax, Tokyo, Japan) is an en- largely dependent upon the experience of the endoscopic postprocessing light filter technology doscopist and the identification of subtle mucosal using sophisticated software algorithms with on- changes with standard white light endoscopes. line image mapping technology embedded in the Once the lesion has been detected, visible suspi- high-definition EPKi processor. This technology cious areas are targeted biopsied or endoscopi- enables resolution above HDTV standard, which cally removed to obtain a definitive diagnosis. In can provide detailed analysis based on vessel (V- addition, in diseases like ulcerative colitis or Bar- mode), pattern (P-mode), or surface architecture rett’s oesophagus (BE) random biopsies are rec- (SE-mode)5.

272 Corresponding Author: Guido Costamagna, MD; e-mail: [email protected] Progress in endoscopic imaging of gastrointestinal tumors

Table I. Novel imaging techniques in digestive endoscopy.

“Red flag” techniques Chromoendoscopy – Lugol’s Solution Detection of early squamous carcinoma – Methylene Blue Detection of Barrett’s esophagus – Indigo Carmine Detection of gastroduodenal malignancies – Acetic Acid Detection of Barrett’s esophagus

Virtual chromoendoscopy Enhancement of surface and vascular (NBI, FICE, I-Scan) patterns Fluorescence endoscopy Wide-area surveillance of gastrointestinal mucosa

Functional imaging Light-scattering spectroscopy Subcellular morphological examination Raman spectroscopy Molecular histopathologic examination

Virtual histology Confocal microscopy Cross-sectional histopathologic examination of mucosal neoplasia Endocytoscopy Iintracellular changes of mucosal neoplasia Optical coherence tomography Cross-sectional histopathologic examination of mucosal neoplasia

Prior studies have demonstrated the value of uses the variation in scattered light across a full virtual chromoendoscopy in the evaluation of pa- spectrum to measure the size and density of nu- tients with upper GI lesions including BE dyspla- clei in the epithelial layer. This is a highly accu- sia6, and the classification of colorectal lesions7-9. rate method which correlates directly with histo- However, a few recent studies have shown con- logic changes of dysplasia15. flicting results with no improvement in adenoma Some authors suggest that it may be ideal if detection rates10-12. AFI and NBI could be used back-to-back in a complimentary fashion with a multi-modal sys- Functional Imaging tem that incorporate high-resolution videoendo- While NBI, FICE, and i-Scan rely on im- scope (HRE), NBI and AFI: high-resolution proved anatomic resolution and contrast, other imaging should be used for a standard examina- methods focuses on functional imaging. During tion, AFI to detect suspicious lesions in selected progression from normal tissue to neoplasia, tis- patients and NBI for a close inspection of these sue undergoes both architectural and biochemical areas16. changes which lead to alterations in its interac- tion with light, producing spectral signatures use- Virtual Histology ful to differentiate between various tissues. In vivo confocal laser endomicroscopy (CLE) Autofluorescence imaging (AFI) detects subtle is a newly developed diagnostic tool that allows changes in the concentration of specific chemi- immediate optical histology of the mucosal layer cals in tissue that have the ability to fluoresce during ongoing endoscopy. The quality of the when activated by specific wavelengths of light. new, detailed images obtained with CLE might As an example, most changes noted in BE with be the start of a new era. AFI rely on loss of collagen in dysplastic tissue Confocal laser microscope can be integrated resulting in reduced green and increased red flu- into the distal tip of a conventional video endo- orescence13. scope (Pentax EC-3870CIFK; Pentax, Tokyo, Raman spectroscopy is based on detecting Japan), or a miniaturized probe, using a single characteristic spectral “fingerprints” of mole- optical-mode fibre acting as both the illumination cules in the tissue based on the molecular vibra- point source and the detection pinhole can be tions in response to light energy14. Reflectance used as “baby-scope” (Optiscan Pty. Ltd., Not- spectroscopy qualifies the colours and the inten- ting Hill, Victoria, Australia, and Cellvizio, Mau- sity of reflected light, altered by the tissue naKea Technologies, Fort Washington, PA, through absorption of certain wavelengths such USA)17. as haemoglobin, thus defining vascularity and The grey-scale image created is an optical sec- oxygenation status. Light scattering spectroscopy tion representing one focal plane within the ex-

273 G. Costamagna, M. Marchese amined specimen. Series of confocal images Conclusions within successive planes can be used to reconstruct three-dimensional structures in a virtual Current limitations of standard endoscopic specimen18. practice are rapidly being overcome by advanced Several prospective studies have already been methods described in this review. Unfortunately, published confirming the high level of diagnostic lack of such studies does not allow clear recom- accuracy of CLE. The diagnostic spectrum of mendations about the clinical use of these CLE is currently expanding from screening and promising technologies. surveillance for colorectal cancer19 towards Bar- At this time, clinicians should resist the temp- rett’s esophagus20, Helicobacter pylori-associated tation to use these very promising, but experi- gastritis21, and gastric cancers22. Several other mental, technologies in making patient manage- clinical applications – such as coeliac disease23,24, ment decisions, and a detailed “japanese-like” microscopic colitis25, squamous-cell carcinoma26, evaluations is mandatory in western Countries, to and architectural evaluation of the liver during la- achieve an early diagnosis of all gastrointestinal paroscopy27 – have also been proposed. cancers. In the future, the endoscopists should Endocytoscopy (EC) provides, in combina- become increasingly more familiar with tion with chromoagents, in vivo histologic im- histopathologic findings, in order to draw the full ages with the use of an ultra high magnification potential benefits of these new techniques. (450-1125 times) catheter which is passed through the working channel of the endoscope. Unlike CLE, EC provides images in colour but is limited to the most superficial cell layer. En- References docytoscopy imaging may correlate closely with histopathology in differentiating between neo- 1) P. E ISENDRATH J. Deviere. “Red flag” techniques in plastic and non-neoplastic lesions as well as Barrett’s esophagus: minor additional benefit or a adenomas and invasive cancer28, with an esti- waste of time? Endoscopy 2006; 38: 929-931. mated sensitivity and specificity of 79 and 90% 2) DACOSTA RS, WILSON BC, MARCON NE. Optical tech- respectively29. niques for the endoscopic detection of dysplastic Optical coherence tomography (OCT) per- colonic lesions. Curr Opin Gastroenterol 2005; 21: forms a cross-sectional, high-resolution, tomo- 70-79. graphic imaging of the microstructure of mucos- 3) LARGHI A, LECCA PG, COSTAMAGNA G. High-resolution narrow band imaging endoscopy. Gut 2008; 57: al tissues by measuring back-scattered or back- 976-986. reflected infrared light, similar to that of B- mode ultrasound imaging30. Most of the so far 4) CORIAT R, CHRYSSOSTALIS A, ZEITOUN JD, DEYRA J, GAU- DRIC M, PRAT F, C HAUSSADE S. Computed virtual published studies aimed at evaluating OCT chromoendoscopy system (FICE): a new tool for imaging to detect dysplasia and early cancer at upper endoscopy? Gastroenterol Clin Biol 2008; different levels of the gastrointestinal tract31. Un- 32: 363-369. fortunately, attempts to identify OCT patterns 5) HOFFMAN A, BASTING N, GOETZ M, TRESCH A, MUDTER characteristics for dysplasia within BE, especial- J, BIESTERFELD S, GALLE PR, NEURATH MF, KIESSLICH R. ly the high-grade type, have been substantially High-definition endoscopy with i-Scan and Lugol’s 32,33 solution for more precise detection of mucosal disappointing . Whether no data are currently breaks in patients with reflux symptoms. En- available about its use in the stomach, small bow- doscopy 2009; 41: 107-112. 34,35 el and colon , more promising are the results 6) KARA MA, PETERS FP, ROSMOLEN WD, KRISHNADATH KK, regarding the discrimination between non-neo- TEN KATE FJ, FOCKENS P, B ERGMAN JJ. High-resolution plastic and neoplastic tissue when bilio-pancreat- endoscopy plus chromoendoscopy or narrow- ic strictures of unknown etiology are identified band imaging in Barrett’s esophagus: a prospec- during an endoscopic retrograde cholangiopan- tive randomized crossover study. Endoscopy 2005; 37: 929-936. creatography (ERCP) procedure36,37. The ability of OCT imaging to recognize the 7) POHL J, NGUYEN-TAT M, PECH O, MAY A, RABENSTEIN T, ELL C. Computed virtual chromoendoscopy for villous pattern and submucosal inflammatory classification of small colorectal lesions: a changes, could be used to identify and stage celi- prospective comparative study. Am J Gastroen- ac disease38, and to differentiate patients with terol 2008; 103: 562-569. Crohn’s disease from those with ulcerative 8) HIRATA M, TANAKA S, OKA S, KANEKO I, YOSHIDA S, colitis39. YOSHIHARA M, CHAYAMA K. Magnifying endoscopy

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