Use Of Confocal Laser Endomicroscopy Research Articles

Comments on the use of confocal laser endomicroscopy in diagnosing protein-losing enteropathy.

Comments on the use of confocal laser endomicroscopy in diagnosing protein-losing enteropathy.

Intraoperative confocal laser endomicroscopy for brain tumors - potential and challenges from a neuropathological perspective.

Confocal laser endomicroscopy (CLE) represents a new non-invasive in vivo imaging technique that holds considerable promise in neurosurgery and neuropathology. CLE is based on the principle of optical sectioning which uses pinholes placed in the light path to selectively image photons of a specific focal plane by filtering out photons above and below the focal plane. Potential indications of CLE in neurosurgery and neuropathology include intraoperative tumor diagnosis and staging as well as assessment of tumor resection margins notably in the case of diffusely infiltrating gliomas. CLE-based tumor analysis in near-real time may also have a significant impact on future tumor resection strategies. We here discuss the technical features of CLE, its potential for wide-field imaging, its role in comparison to established histological techniques for intraoperative tumor assessment and its position in digital pathology and telepathology. Based on our group's experience with a commercially available confocal laser endomicroscope (ZEISS CONVIVO), we critically address the current state of intraoperative CLE in brain tumor surgery, the applicability of classical histological criteria and the strategies required to further improve the diagnostic accuracy of CLE. We finally discuss how a widespread use of CLE in neurosurgery may modify the role of neuropathologists in intraoperative consultation, generating both new opportunities and new challenges.

Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn’s disease: a pilot study

Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission. In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months). At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts≥i2). The Rutgeerts score was significantly correlated with the Watson score (ρ= 0 .73; P< .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P= .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P= .036). CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.

Use of confocal laser endomicroscopy with a fluorescently labeled fatty acid to diagnose colorectal neoplasms.

Endoscopic treatment for early colorectal cancer closely correlates with patient prognosis. However, endoscopic differentiation between carcinomas and non-neoplastic lesions remains difficult. Here, we topically stained colorectal neoplasms with a fatty acid analogue (BODIPY-FA) and quantified the fluorescent signals using confocal laser endomicroscopy (CLE) and fluorescence microscopy. We also analyzed protein expression in colorectal cancer tissues. We found that expression of fatty acid synthase was elevated, while the expression of fatty acid transporters was reduced in colorectal cancer. In colorectal cancer mouse models and patients, the BODIPY-FA signals were higher in normal epithelia than in carcinomas or colonic intraepithelial neoplasias. BODIPY-FA staining revealed both the arrangement of intestinal glands and the intracellular structures under CLE screening. In a double-blind trial, CLE images stained with BODIPY-FA exhibited greater consistency (κ = 0.68) and overall validity (74.65%) than those stained using intravenous fluorescein sodium (κ = 0.43, 55.88%) when the results were compared with histological diagnoses. These findings suggest that topical use of BODIPY-FA with CLE is a promising imaging approach for early colorectal neoplasm screening.

Correlation Between Confocal Laser Endomicroscopy (Cellvizio®) and Histological Grading of Upper Tract Urothelial Carcinoma: A Step Forward for a Better Selection of Patients Suitable for Conservative Management

BackgroundDespite the recent growing interest in the conservative management of upper tract urothelial carcinoma (UTUC), the diagnostic process is still a challenge for the risk of tumor undergrading. Real-time confocal laser endomicroscopy (CLE) provides in vivo microscopic images of tissues using a low-energy laser light source. ObjectiveTo describe our initial experience with CLE for the real-time characterization of UTUC. Design, setting, and participantsFourteen flexible ureteroscopies (f-URS) were performed at our center with CLE for UTUC. Lesions were preoperatively identified at computed tomography-intravenous urography. Cellvizio system was used during f-URS to perform CLE on the targeted lesions. Biopsies were then performed. Interventionf-URS with CLE. Outcome measurements and statistical analysisSurgeon’s CLE readings (low-grade/high-grade/carcinoma in situ [CIS]) were documented in the operation notes. A dedicated genitourinary pathologist—blinded to the surgeon reading—examined all specimens. A third person collected prospectively the CLE readings and the histopathological reports. Cohen’s Kappa analysis was performed to test interobserver agreement. Results and limitationsThe mean diameter of tumors at computed tomography scan was 26mm (range, 5–50mm). In eight patients, CLE allowed to obtain images compatible with low-grade UTUC, in five patients with high-grade UTUC, and in one case with CIS. We found correspondence between the CLE images and the final histopathological results in seven out of seven cases of low-grade UTUC (100%), in five out of six cases of high-grade UTUC (83%), and in one out of one case of CIS (100%). Substantial agreement was found at interobserver agreement (k=0.64) between CLE and histological reading. No complications and/or limitations related to the use of CLE were recorded. ConclusionsCLE is a promising new technology in providing a reliable real-time histological characterization of UTUC lesions. Ideal targets might be UTUC patients potentially candidates for conservative management. Patient summaryWe believe that a conservative treatment for low-grade upper tract urothelial carcinoma is an option that must be considered. The diagnostic process is still lacking of accurate tools. In this study, we find that confocal laser endomicroscopy, using the Cellvizio system, seems to help the clinician to have a real-time histological characterization of upper tract urothelial carcinoma lesions. This could better select patients for a conservative treatment.

Usefulness of confocal laser endomicroscopy to diagnose ulcerative colitis-associated neoplasia.

Chromoendoscopy, narrow-band imaging (NBI), and confocal laser endomicroscopy (CLE) have been introduced in ulcerative colitis (UC)-associated neoplasia surveillance. We aimed to determine the ability of CLE to differentiate among UC-associated neoplasia (differentiated type or undifferentiated type), sporadic adenoma, and circumscribed regenerative lesions. Of 665 patients with UC, we carried out probe-based CLE (pCLE) on 12 patients with suspected UC-associated neoplasia in addition to magnifying chromoendoscopy with crystal violet and NBI. We compared pCLE findings with pathological diagnoses. pCLE could differentiate UC-associated differentiated cancer from other pathologies such as solitary adenoma and non-neoplastic circumscribed regenerative lesions on the basis of back-to-back orientation of crypts (P = 0.048), and UC-associated undifferentiated cancer from other pathologies on the basis of dark trabecular architecture (P = 0.015). Sensitivity, specificity, and accuracy of combination of back-to-back orientation of crypts and dark trabecular architecture for carcinoma or dysplasia were 100%, 83%, and 92%, respectively. In vivo microscopic observation with pCLE was helpful to evaluate the suspected UC-associated neoplasia.

Confocal laser endomicroscopy in the diagnosis of colorectal diseases: image interpretation criteria

Confocal laser endomicroscopy is a rapidly emerging area of gastroenterology that bridges endoscopy and histological examination. This newest technique has enabled endoscopists to assess the microstructure of gastrointestinal mucosa in vivo during the endoscopic procedure ("virtual biopsy"), and has stimulated growing interest to its application in clinical practice. During colonoscopy, the use of confocal laser endomicroscopy is justified for assessment of post-resection margins after excision of epithelial neoplasms, for differential diagnosis of polyps and assessment of the colon in patients with inflammatory bowel disorders. This article presents the interpretation criteria of confocal images in various colon diseases and the published data on the diagnostic value of the method.

Application and Efficacy of Super-Magnifying Endoscopy for the Lower Intestinal Tract.

Endoscopy plays a significant role in the diagnosis, management, and surveillance of colorectal cancer (CRC) and inflammatory bowel diseases (IBDs). Moreover, magnifying endoscopy and image-enhanced endoscopy has a crucial role in the clinical setting. Recently, a super-magnifying endoscope has been developed, and two devices, confocal laser endomicroscopy (CLE) and an endocytoscopy system (ECS), which allow in vivo microscopic inspection of the microstructural mucosal features of the gastrointestinal tract, are currently available. Studies on the use of ECS in CRC were reported by a Japanese group. Additionally, a few studies on the use of ECS in IBD have been reported. CLE has been shown to be reliable in assessing the activity of the disease in IBDs in both ulcerative colitis and Crohn’s disease. Various published studies evaluated the use of CLE during colonoscopy to distinguish colorectal polyp pathology and neoplasia. However, these studies are heterogeneous, and further evidence is necessary to confirm the efficacy of CLE.

CURRENT DIAGNOSTIC BRONCHOSCOPY FOR EARLY CENTRAL LUNG CANCER (Review of literature)

The article tells about the evolution in the development of endoscopic diagnostic methods for early central lung cancer, from rigid bronchoscopes to modern high-resolution video endoscopes. The current multimodal diagnostic methods are described, including the recent data on the use of confocal laser endomicroscopy and endocytoscopy which allow to detect lesions caused by intramucosal cancer in the tracheobronchial tree as well as to study the cellular-level morphology in vivo. Long-term clinical experience of the P.A. Herzen Moscow Oncology Research Institute in the diagnosis of central lung cancer is presented.

Use of confocal laser endomicroscopy to assess the adequacy of endoscopic treatment of gastrointestinal neoplasia: a systematic review and meta-analysis.

Evaluation of the adequacy of endoscopic mucosal resection (EMR) of gastrointestinal lesions remains challenging by use of conventional endoscopy. Confocal laser endomicroscopy (CLE) is a novel imaging technique, designed to provide in vivo histology, and facilitate diagnosis with real-time intervention. We undertook a systematic review of the available literature, exploring the role of CLE in assuring completeness of EMR of gastrointestinal lesions. The number of pertinent studies is very limited, including only 1 randomized controlled study and 2 prospective comparative case series. Per-lesion meta-analysis showed that the sensitivity of CLE for detection of residual neoplasia was 91% (95% confidence interval, 82.5%-96%) with specificity of 69% (95% confidence interval, 61%-77%), with significant heterogeneity noted in all outcomes. In conclusion, the evidence underpinning the usefulness of CLE in ensuring adequate EMR of gastrointestinal neoplasia is currently very weak, with limited promising results related to gastric and colorectal polyp resections.

Covering the Cover

Covering the Cover

Su1503 Definition of a Standardized Program of Training and Credentialing for the Use of Confocal LASER Endomicroscopy in Gastrointestinal Applications: a Consensus Report

Su1503 Definition of a Standardized Program of Training and Credentialing for the Use of Confocal LASER Endomicroscopy in Gastrointestinal Applications: a Consensus Report

Use of confocal laser endomicroscopy to predict relapse of ulcerative colitis

BackgroundAssessment of inflammatory activity in patients with ulcerative colitis (UC) is crucial to the prediction of relapse. Confocal laser endomicroscopy (CLE) is an accurate tool for assessing inflammatory activity in UC patients. This study aimed to evaluate whether CLE could be used to predict UC relapse reliably.MethodsIn total, forty-three patients with documented UC were analyzed in this study. Patients identified as having obvious active inflammation by conventional colonoscopy were excluded. The mucosa of each patient’s sigmoid colon and rectum was assessed by CLE before targeted biopsies were taken. The patients were then followed up for at least 12 months to evaluate relapse according to the Simple Clinical Colitis Activity Index. The correlation between CLE classification and UC relapse was evaluated.ResultsSeventeen of 20 patients with histologically confirmed normal or chronic inflammation were diagnosed as having non-active inflammation by real-time CLE and 22 of 23 patients with histologically confirmed acute inflammation were diagnosed as having active inflammation by CLE. The sensitivity, specificity, and accuracy of CLE in real-time diagnosis of active inflammation were 95.7%, 85%, and 90.7%, respectively. The agreement between CLE and conventional histology was excellent (kappa value = 0.812). Two of 18 (11.1%) patients who were classified as having non-active inflammation by CLE relapsed, while 16 of 25 (64%) patients classified as having as active inflammation relapsed. The relapse rate of patients with active inflammation was significantly higher than of those with non-active inflammation (P < 0.001).ConclusionsCLE is comparable to conventional histology in predicting relapse in patients with UC.

Evaluation of New Morphometric Parameters of Neoangiogenesis in Human Colorectal Cancer Using Confocal Laser Endomicroscopy (CLE) and Targeted Panendothelial Markers

The tumor microcirculation is characterized by an abnormal vascular network with dilated, tortuous and saccular vessels. Therefore, imaging the tumor vasculature and determining its morphometric characteristics represent a critical goal for optimizing the cancer treatment that targets the blood vessels (i.e. antiangiogenesis therapy). The aim of this study was to evaluate new vascular morphometric parameters in colorectal cancer, difficult to achieve through conventional immunohistochemistry, by using the confocal laser endomicroscopy method. Fresh biopsies from tumor and normal tissue were collected during colonoscopy from five patients with T3 colorectal carcinoma without metastasis and were marked with fluorescently labeled anti-CD31 antibodies. A series of optical slices spanning 250 µm inside the tissue were immediately collected for each sample using a confocal laser endomicroscope. All measurements were expressed as the mean ± standard error. The mean diameter of tumor vessels was significantly larger than the normal vessels (9.46±0.4 µm vs. 7.60±0.3 µm, p = 0.0166). The vessel density was also significantly higher in the cancer vs. normal tissue samples (5541.05±262.81 vs. 3755.79±194.96 vessels/mm3, p = 0.0006). These results were confirmed by immunohistochemistry. In addition, the tortuosity index and vessel lengths were not significantly different (1.05±0.016 and 28.30±3.27 µm in normal tissue, vs. 1.07±0.008 and 26.49±3.18 µm in tumor tissue respectively, p = 0.5357 and p = 0.7033). The daughter/mother ratio (ratio of the sum of the squares of daughter vessel radii over the square of the mother vessel radius) was 1.15±0.09 in normal tissue, and 1.21±0.08 in tumor tissue (p = 0.6531). The confocal laser endomicroscopy is feasible for measuring more vascular parameters from fresh tumor biopsies than conventional immunohistochemistry alone. Provided new contrast agents will be clinically available, future in vivo use of CLE could lead to identification of novel biomarkers based on the morphometric characteristics of tumor vasculature.

Confocal Laser Endomicroscopy and Molecular Imaging in Barrett Esophagus and Stomach

Detection of premalignant lesions in the upper gastrointestinal tract may facilitate endoscopic treatment and improve survival. Despite technological advances in white light endoscopy, its ability to detect premalignant lesions remains limited. Early detection could be improved by using advanced endoscopic imaging techniques, such as magnification endoscopy, narrow band imaging, i-scanning, flexible spectral imaging color enhancement, autofluorescence imaging, and confocal laser endomicroscopy (CLE), as these techniques may increase the rate of detection of mucosal abnormalities and allow optical diagnosis. The present review focuses on advanced endoscopic imaging techniques based on the use of CLE for diagnosing premalignant lesions in Barrett esophagus and stomach.

Advanced Endoscopic Imaging

Advanced Endoscopic Imaging

Confocal laser endomicroscopy in inflammatory bowel diseases: Dream or reality?

Confocal laser endomicroscopy (CLE) is a newly introduced procedure that provide real-time, high-resolution imaging of the gastrointestinal mucosa during endoscopy, allowing the visualization of the pathology of the mucosal epithelium with its cellular and subcellular structures. Recently, the use of CLE was reported in the study of colonic mucosa in patients with inflammatory bowel diseases and in particular in patients affected by ulcerative colitis. CLE has the potential to have an important role in management of inflammatory bowel diseases (IBD) patients as it can be used to assess the grading of colitis and in detection of microscopic colitis in endoscopically silent segments. Moreover, CLE can be used in surveillance programs especially in high-risk patients. Finally, CLE has been effectively used in diagnosing a biliary dysplasia/neoplasia in patients with primary sclerosing cholangitis, a pathological condition frequently associated with IBD, with a coexisting bile duct stricture.

Sa1603 Accuracy of Endoscopic Based Confocal Laser Endomicroscopy of Donor Duodenum in Early Detection of Pancreas Rejection in a Recipient of Simultaneous Duodenum-Drained Pancreas - Kidney Transplantation

Sa1603 Accuracy of Endoscopic Based Confocal Laser Endomicroscopy of Donor Duodenum in Early Detection of Pancreas Rejection in a Recipient of Simultaneous Duodenum-Drained Pancreas Kidney Transplantation Marek Stobinski*, Janusz Milewski, Aleksandra Poplawska, Marek Durlik, Agnieszka Serwacka, Andrzej Rydzewski, Grazyna Rydzewska Dpt. of Internal Medicine and Gastroenterology, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warszawa, Poland; Dpt. of Gastroenterological and Transplantation Surgery, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warszawa, Poland; Dpt. of Internal Medicine and Nefrology, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warszawa, Poland Background and aims: Confocal laser endomicroscopy (CLE) is a new, powerful technic, allows to get in vivo histology. This technology is widely investigated in different gastrointestinal diseases and becomes an alternative to conventional histology. Percutaneous transplanted pancreas biopsy under imaging control is the method of choice in monitoring of organ rejection, however adequate samples are obtained in 73-89% of biopsy attempts. Recently we described also usefulness of transplanted duodenum biopsies for graft rejection monitoring. However histology technique is time consuming, so the aim of the present study was to investigate usefulness of CLE in monitoring of acute pancreas rejection, and it’s influence on potential clinical decision. Patients and methods: During first 2 weeks after SPK procedure 18 patients were examined with CLE technique and histological biopsies from transplanted and own duodenum were also taken for confirmation of endoscopic changes. No difficulties to reach anastomosis with CLE were observed. Results: In the group of 18 patients after SPK transplantation we found in 2 cases endoscopic changes in transplanted duodenum, expressed as destruction of the villi and dispersed globlet cells in comparison to their own healthy duodenum. No macroscopic changes in transplanted duodenum in those patients were observed. In both cases histological examination confirmed acute organ rejection. Patients were operated and graft was removed. Conclusion: In our pilot study we demonstrated for the first time, that CLE is a promising and effective method to detect acute phase GvHD and also for follow up in those patients group. The procedure is easy acceptable and safe for patients and clinical decision based on the information obtained after examination could be made quickly. Further studies are needed to confirmed clinical usefulness of this technique in monitoring of patients after SPK transplantation. Sa1604 Mucosal Healing in Patients With Ulcerative Colitis Assessed by Confocal Laser Endomicroscopy Cristian Gheorghe, Razvan Iacob*, Bogdan Cotruta, Ion Bancila, Gabriel Becheanu, Mona Dumbrava, Liana Gheorghe Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania; Gastroenterology and Hepatology, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania Background & Aim: The ultimate therapeutic goal in patients with ulcerative colitis (UC) is represented by mucosal healing. Recently, confocal LASER endomicroscopy (CLE) has emerged to allow in vivo histological evaluation during ongoing endoscopy. Considering that histologic remission should be part of sustained deep remission, we have conducted a pilot study to investigate the ability of CLE to differentiate between normal mucosa and residual inflammation. Methods: Rectal CLE has been performed using 5 ml 10% fluorescein iv and targeted biopsies have been analysed by the pathologist. Mucosal inflammation was investigated by CLE assessing crypt architecture and interstitial and cryptal fluorescein leakage. The image processing was performed using ImageJ, a public domain Java software. All images have been captured using the same LASER power setting, at the superficial and medium-depth level. Semiautomatic computer estimation of interstitial and cryptal fluorescein leakage (ICFL) has been performed on stacks of images, by evaluating mean luminosity of pixels corresponding to crypts and interstitium, on a scale ranging from 0-255. ICFL in patients with UC in histological remission has been compared to patients with active ulcerative colitis and to patients with irritable bowel syndrome undergoing screening colonoscopy for colorectal cancer, using Student’s T Test. Results: A total of 184 CLE images have been analysed. Only minor cryptal abnormalities have been noted for patients with ulcerative colitis in remission, whereas for patients with active ulcerative colitis a wide range of cryptal alterations have been registered, from crypt distortion to crypt destruction and crypt abcess. ICFL was 94 21 for patients with ulcerative colitis in histological remission, 106 12.6 for IBS controls (p 0.24 -NS) and 178.6 21.6 for patients with active UC (p 0.0001). Conclusion: CLE is an emerging endoscopic technique for real-time assessment of deep mucosal remission during ongoing endoscopic examination, in patients with UC. The semiautomatic quantification of interstitial and cryptal fluorescein leakage can be objectively used to diagnose in vivo deep mucosal remission in patients with UC. Abstracts

A Review on the Use of Confocal Laser Endomicroscopy in the Bile Duct

Background. Current methods to diagnose malignant biliary strictures are of low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) is a new approach that can be used to evaluate in vivo histopathology of the GI tract. This paper is of studies evidencing pCLE's application in the diagnosis of indeterminate biliary strictures. Methods. This paper examined peer-reviewed studies conducted between January 2000 and November 2011. A PubMed search for relevant articles was performed using the following keywords:“pCLE”, “confocal”, “endomicroscopy”, “probe-based confocal laser endomicroscopy”, “and “bile duct”. Further individual review was done to assess the screened articles' relevance to the topic. Results. After individual review, 6 studies were included; with a cumulative sample size of 165, with 75 subjects identified as having a malignancy. These studies included tertiary care centers in Germany, France, and USA, including one multicenter trial. 3 studies assessed pCLE's specificity (range 67%–88%) ,sensitivity (range 83%–98), and accuracy (range 81%–86%). Conclusion. Confocal endomicroscopy is a novel and promising modality for the biliary tree. Further studies need to be conducted both to establish its usefulness for the diagnosis of indeterminate biliary strictures and to understand the histological meaning of the imaging patterns that are observed.

Confocal Laser Endomicroscopy

Confocal laser endomicroscopy (CLE) is a newly developed endoscopic technique that enables imaging of the mucosal layer during endoscopy at a subcellular level of resolution. The method can therefore be used for the assessment of changes in vascular architecture, connective tissue, and cellular components in the mucosa, enabling endoscopists to collect real-time in vivo histological images or “virtual biopsies” of the gastrointestinal (GI) mucosa during endoscopy. Confocal microscopy consists of focusing a laser beam (such as an argon-ion laser that generates an excitation wavelength of 488 nm, blue laser light) onto the plane of interest and filtering the returned light by means of a small pinhole which rejects out-of-focus light. The illumination and detection systems are in the same focal plane and are termed “confocal”. After passing the pinhole, the fluorescent light is detected by a photodetection device (a photomultiplier tube or avalanche photodiode), transforming the light signal into an electrical one that is recorded by a computer. All detected signals from the illuminated spot are captured and measured. As the laser scans over the plane of interest, a whole image is obtained pixel-by-pixel and line-by-line, whereas the brightness of a resulting image pixel corresponds to the relative intensity of detected fluorescent light. The gray-scale image created is an optical section representing one focal plane within the examined specimen. Because confocal images depend on fluorescence, a fluorescent dye (contrast agent) is required to make objects visible. The contrast agents can be applied systemically (fluorescein, tetracycline) or topically (acriflavine, cresyl violet) by using a spraying catheter. Of these, intravenous fluorescein sodium (10%) and topically applied acriflavine (0.2%) have been most commonly used in humans. CLE can be performed currently with 2 devices: (1) integrated into an endoscope (Pentax, Tokio, Japan, herein termed eCLE) and (2) as a stand-alone probe (herein termed pCLE) capable of passage through the accessory channel of most endoscopes (Cellvizio, Mauna Kea Technologies, Paris, France). In this special issue on CLE, we have invited a few papers that address the current potential indications for pCLE imaging in clinical gastroenterology and its potential impact in the future, particularly in the screening or surveillance of GI neoplasia. A paper in this special issue by H. Bertani et al. reviews the role of pCLE in Barrett's esophagus for detection of esophageal dysplasia and carcinoma from a clinical practice perspective. Another paper by Mascolo et al. evaluates the accuracy of pCLE in the detection of aberrant crypt foci (ACF), comparing in double-blind manner the microendoscopic and histopathological features resulting from colonic biopsy. By pCLE, the authors identified specific crypt architecture modifications associated with changes in cellular infiltration and vessels architecture, highlighting a good correspondence between pCLE features and histology. A paper by V. Ussui and B. Wallace reviews the role of CLE as applied to colorectal polyps detected during colonoscopy. It describes the importance of probe-based confocal endomicroscopy on colorectal polyps with a particular emphasis on distinguishing hyperplastic from neoplastic polyps. One paper of this special issue, by F. Salvatori et al., reviews the current data on the clinical application of CLE in the study of colonic mucosa in patients with ulcerative colitis. Finally, a paper, by R. Cannizzaro et al. describes the use of CLE to analyze the angiogenic process in colo4rectal and gastric cancer patients and the possibility of a translational approach combining the confocal imaging with the diagnosis in vivo and the specific molecular profile of the patient with the targeted antiangiogenic treatment. Giovanni D. De Palma Michael B. Wallace Marc Giovannini