Classification criteria for advanced adenomas of the colon by using probe-based confocal laser endomicroscopy: a preliminary study.

BACKGROUND: Probe-based confocal laser endomicroscopy may allow a strategy of "diagnose, resect, and discard" for small nonadvanced adenomas, but there are concerns about discarding polyps with advanced histology. OBJECTIVE: The aim of this study was to evaluate the potential use of probe-based confocal laser endomicroscopy to aid in distinguishing low-grade from advanced colon adenomas. DESIGN: Six observers, blinded to histopathology, scored 5 adenoma features and an overall diagnosis and confidence level for the diagnosis. SETTING: This study was conducted at single, tertiary care referral center. PATIENTS: Patients undergoing screening and surveillance colonoscopies and for whom an adenomatous polyp was removed were included. INTERVENTIONS: A sample of 27 advanced adenomas and 120 nonadvanced adenomas were used in the study. An initial classification system was created with 10 advanced and 10 nonadvanced adenomas. The remaining 127 adenomas were scored by each observer in the validation portion of the study. MAIN OUTCOME MEASURES: The primary outcome measured was the accurate classification of advanced and nonadvanced adenomas. RESULTS: Overall, across all 6 observers, the sensitivity in correctly classifying advanced adenomas was 43%, the negative predictive value was 89%, the specificity was 71%, and the positive predictive value was 19%. No single feature or combination of features as seen with probe-based confocal laser endomicroscopy consistently identified advanced adenomas. LIMITATIONS: Classification criteria were developed subjectively, and there was limited observer experience with probe-based confocal laser endomicroscopy use. CONCLUSIONS: Our initial attempt at creating classification criteria for probe-based confocal laser endomicroscopy did not consistently distinguish advanced from nonadvanced adenomas and, therefore, is not useful in applying a "diagnose, resect, and discard" strategy. However, further refinement of our probe-based confocal laser endomicroscopy classification scheme in future studies has potential to accurately detect advanced histology in colorectal polyps.

Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging for small colorectal polyps: a feasibility study.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) allows real-time in-vivo microscopic imaging of tissue. Narrow band imaging (NBI) can also classify colorectal lesions. Both systems may allow accurate optical diagnosis of small (6-9 mm) and diminutive (1-5 mm) polyps without histopathology. This study assesses the accuracy of pCLE and NBI for prediction of histology. METHODS: Participants underwent high-definition colonoscopy. The surface pit pattern of all polyps (1-9 mm) was determined in vivo using NBI. Confocal videos were obtained after administration of IV fluorescein. Recorded videos were subsequently analyzed offline, blinded to endoscopic characteristics, and histopathology. Confocal images were classified as neoplastic and non-neoplastic according to the Miami classification system. RESULTS: A total of 130 polyps (58 neoplastic, 72 non-neoplastic, mean size 4.6 mm) from 65 patients were assessed. Assuming histopathology as gold standard, pCLE had higher sensitivity than NBI (86% vs. 64%, P=0.008), with lower specificity (78% vs. 92%, p=0.027) and similar overall accuracy (82% vs. 79%, P=0.59). When 65 high-confidence cases were analyzed (polyps diagnosed identically with pCLE and NBI and with high-quality confocal videos), sensitivity and specificity were 94 and 97%. CONCLUSIONS: pCLE demonstrated higher sensitivity in predicting histology of small polyps compared with NBI, whereas NBI had higher specificity. When used in combination, the accuracy of pCLE and NBI was extremely high, approaching the accuracy of histopathology. Together, they may reduce the need for histological examination. However, further studies are warranted to evaluate the role of these techniques, especially in the population-based colon cancer screening.

Diagnostic accuracy of probe-based confocal laser endomicroscopy in detecting residual colorectal neoplasia after EMR: a prospective study.

BACKGROUND: Residual neoplasia after EMR of colorectal lesions is common. There is a critical need for imaging methods to accurately diagnose residual disease and to guide retreatment in real time. OBJECTIVE: The aim was to estimate and compare the accuracy of virtual chromoendoscopy (VCE) and probe-based confocal laser endomicroscopy (pCLE) for detection of residual neoplastic tissue at the site of prior EMR. DESIGN: Prospective, blind, pilot comparison of advanced endoscopic imaging (VCE and pCLE) by using matching histology as reference standard. SETTING: Three tertiary-care referral hospitals. PATIENTS: This study involved 92 participants who underwent follow-up colonoscopies for the evaluation of prior EMR sites within 1 year. INTERVENTION: The EMR scars were assessed during follow-up high-resolution colonoscopy by using VCE (narrow-band imaging/Fujinon Intelligent Color Enhancement [FICE]), and pCLE. Confocal videos of EMR scars were interpreted in real time and were also stored and reviewed offline, blinded to histopathology and endoscopic appearance. Tissue confirmation by biopsies or polypectomy/repeat EMR was performed in all cases. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and accuracy for VCE and pCLE alone and in combination against histopathology as the standard reference standard. RESULTS: Among 129 EMR scars, residual neoplasia was confirmed by histology in 29 sites (22%). For VCE, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72%, 77%, 49%, 91%, and 77%, respectively, and were 97%, 77%, 55%, 99%, and 81% for pCLE (P = .045 for sensitivity). When only EMR scars for which VCE and pCLE agreed on the diagnosis were analyzed (95/129 scars), the accuracy, sensitivity, specificity, PPV, and NPV of pCLE and VCE were 90%, 100%, 87%, 67%, and 100%, respectively. LIMITATIONS: Small sample size, lack of power, involvement of highly experienced pCLE experts. CONCLUSION: Confocal endomicroscopy significantly increases the sensitivity for detecting residual neoplasia after colorectal EMR compared with endoscopy alone. When confocal endomicroscopy is used in combination with VCE, the accuracy is extremely high, and sensitivity approaches that of histopathology. Together, they may reduce the need for histologic examination and allow a highly accurate on-table decision to treat again or not, thus avoiding unnecessary repeat procedures. ( CLINICAL TRIAL REGISTRATION NUMBER: 00874263.).

Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging in detection of dysplasia in duodenal polyps.

GOALS: To estimate the accuracy of probe-based confocal laser endomicroscopy (pCLE) and narrow band imaging (NBI), individually and in combination, for classification of duodenal polyps. BACKGROUND: Ex vivo pathologic diagnosis of duodenal polyps causes time delay, requiring separate procedures for diagnosis and therapy. It also involves small risk of pancreatitis in ampullary adenomas and can make subsequent endoscopic mucosal resection more difficult by "tacking down" mucosa. In vivo diagnosis with pCLE and NBI may avoid these complications and may guide immediate therapy. STUDY: During high-definition white light endoscopy, 1 endoscopist (M.B.W.) performed NBI and then, pCLE of duodenal sites. Matched tissue sampling or endoscopic mucosal resection was performed. Confocal videos were recorded, de-identified, and reviewed by same endoscopist, blinded to histopathology, 1 month later. Confocal features of dysplasia in Barrett esophagus were applied for detection of duodenal dysplasia. RESULTS: Of 65 sites from 36 participants, 24 lesions showed dysplasia, whereas 41 polyps and control sites were nondysplastic on histopathology, used as standard reference. The accuracy, sensitivity, and specificity of pCLE were 83%, 92%, and 78%, whereas that of NBI were 80%, 83%, and 78%, respectively. In subset of 49 lesions with similar pCLE and NBI diagnosis, the accuracy, sensitivity, and specificity, improved significantly and was found to be 92%, 95%, and 90%, respectively. CONCLUSIONS: Our study suggests that pCLE has superior sensitivity as compared with NBI for detection of dysplasia in duodenal polyps. Combined accuracy of pCLE and NBI approaches that of ex vivo pathology, which may help in avoiding biopsy sampling.

Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps.

BACKGROUND & AIMS: Probe-based confocal laser endomicroscopy (pCLE) allows in vivo imaging of tissue at micron resolution. Virtual chromoendoscopy systems, such as Fujinon intelligent color enhancement and narrow band imaging, also have potential to differentiate neoplastic colorectal lesions. The accuracy of these systems in clinical practice is, however, unknown. Our primary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy for classification of colorectal polyps using histopathology as a gold standard. A secondary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy using a modified gold standard that assumed that all polyps >/=10 mm had malignant potential and were considered neoplastic or high risk. METHODS: Patients underwent colonoscopy using high-resolution colonoscopes. The surface pit pattern was determined with NBI or FICE in all patients. Confocal images were recorded and subsequently analyzed offline, blinded to the endoscopic characteristics and histopathology. Each polyp was diagnosed as benign or neoplastic based on confocal features according to modified Mainz criteria. RESULTS: A total of 119 polyps (81 neoplastic, 38 hyperplastic) from 75 patients was assessed. The pCLE had higher sensitivity compared to virtual chromoendoscopy when considering histopathology as gold standard (91% vs 77%; P = .010) and modified gold standard (88% vs 76%; P = .037). There was no statistically significant difference in specificity between pCLE and virtual chromoendoscopy when considering histopathology or modified gold standard. CONCLUSIONS: Confocal endomicroscopy demonstrated higher sensitivity with similar specificity in classification of colorectal polyps. These new methods may replace the need for ex vivo histological confirmation of small polyps, but further studies are warranted.

Association between visual gaze patterns and adenoma detection rate during colonoscopy: a preliminary investigation.

OBJECTIVES: Eye gaze tracking (EGT) technology follows a person's gaze and records the resulting visual gaze pattern (VGP). Adenoma detection rate (ADR) is a validated measure of colonoscopy quality. Higher ADRs are associated with prolonged withdrawal times and other endoscopic maneuvers that allow a better visualization of the mucosa; however, the influence of VGP has yet to be explored. We aim to quantify the VGP for endoscopists observing colonoscopy videos and describe the association between VGP and ADR. Furthermore, we will evaluate the relationship between VGP and the endoscopists' years of experience. METHODS: Eleven endoscopists watched three videos while their VGP was recorded. The videos corresponded to 3 min of three different colonoscopy withdrawals. We divided the screen into a 3 × 3 grid of nine segments: eight peripheral and one central. We compared percent of gaze time (GT) in the central vs. peripheral segments using a paired t-test. VGP with ADR and years of practice were evaluated using Pearson's test. RESULTS: Subjects spent more GT in the screen's central segment (65 vs. 33%, P<0.001). ADR was significantly associated with increased percentage of central GT (r = 0.67, P = 0.024) and increased mean GT in the central segment (r = 0.70, P = 0.017). There was negative correlation between endoscopists' years of practice and the percentage of central GT (r = -0.67, P = 0.025), but no correlation between years of practice and percentage of peripheral GT (r = 0.24, P = 0.47). CONCLUSIONS: This reveals an association between a centrally focused VGP and ADR. Future steps include confirming in a larger sample and exploring if VGP can retrain low ADR endoscopists to perform higher quality colonoscopies.

Trainee participation is associated with increased small adenoma detection.

BACKGROUND: Previous studies examining the effect of fellow participation on adenoma detection rate in colonoscopy have yielded conflicting results, and factors such as adenoma size and location have not been rigorously evaluated. OBJECTIVE: To examine whether fellow participation during screening, surveillance, or diagnostic colonoscopy affects overall, size-specific, or location-specific adenoma or polyp detection rate. METHODS: This was a retrospective study of 2430 colonoscopies performed in our ambulatory surgical center between September 2006 and December 2007, comparing adenoma and polyp detection rates of colonoscopies performed by fellows with supervising staff endoscopists (n = 318) with colonoscopies performed by staff endoscopists without fellow participation (n = 2112). Study participants included patients who underwent screening, surveillance, or diagnostic colonoscopies in our GI suite. Logistic regression analysis was used to evaluate the association of fellow participation with adenoma and polyp detection. RESULTS: There was evidence of a higher rate of small (<5 mm) adenoma detection in colonoscopies with a fellow present (25% vs 17%, P = .001). This remained significant after multiple-testing adjustment (P ≤ .003 considered significant). Findings were similar, although not significant for small polyps (36% vs 29%, P = .007). There was a trend toward increased adenoma detection in colonoscopies with a fellow present compared with those without (30% vs 26%, P = .11). Multivariable adjustment for potentially confounding variables did not alter these associations. LIMITATIONS: The study had a retrospective design, and information regarding bowel preparation was not available for 37% of patients. CONCLUSION: Fellow involvement was associated with increased detection rates of small adenomas, providing evidence that the presence of a fellow during colonoscopy plays a role in enhancing the effectiveness of the examination.

The learning curve of in vivo probe-based confocal laser endomicroscopy for prediction of colorectal neoplasia.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is an emerging tool for in vivo imaging of the GI tract that requires the endoscopist to interpret microscopic images. The learning curve for interpretation of pCLE images is unknown. OBJECTIVE: To examine the learning curve of correctly identifying benign and neoplastic colorectal lesions by using pCLE and to evaluate the learning curve of obtaining high-quality images. DESIGN: Prospective, double-blind review of pCLE images of 76 colorectal lesions by using corresponding polypectomies as the reference standard. A training set of 20 images with known histology was first reviewed to standardize image interpretation, followed by blinded review of 76 unknown images. SETTING: Eleven endoscopists from 3 different endoscopy centers evaluated the images obtained by 1 endoscopist using the high-definition confocal probe. PATIENTS: Patients undergoing screening and surveillance colonoscopies. INTERVENTION: Intravenous fluorescein pCLE imaging of colorectal lesions followed by polypectomies. MAIN OUTCOME MEASUREMENTS: Accuracy of image interpretation with constructing learning curve for pCLE image interpretation and acquisition. RESULTS: Of the 76 colorectal lesions, 51 (67%) were neoplastic and 25 (33%) were benign, based on histopathology. Accuracy for the overall group was 63% for lesions 1 to 20, 64% for lesions 21 to 40, 79% for lesions 41 to 60, and 86% for lesions 61 to 76. The ability to obtain high-quality images was stable over the 76 cases. LIMITATIONS: Small sample size and use of offline video sequences. CONCLUSIONS: Accurate interpretation of pCLE images for predicting neoplastic lesions can be learned rapidly by a wide range of GI specialists. Furthermore, the ability to acquire high-quality pCLE images is also quickly learned.

High-definition colonoscopy detects colorectal polyps at a higher rate than standard white-light colonoscopy.

BACKGROUND & AIMS: Adenoma detection rates might be improved through use of high-definition colonoscopy, which can detect subtle mucosal changes. We investigated whether the use of high-definition white-light (HDWL) colonoscopy resulted in a higher rate of adenoma detection than standard-definition white-light (SDWL) colonoscopy in a clinical practice setting. METHODS: This retrospective study included 2430 patients who underwent colonoscopies from September 2006 to December 2007; 1226 received SDWL colonoscopy and 1204 received HDWL colonoscopy. We analyzed data from consecutive screening, surveillance, and diagnostic colonoscopies, comparing adenoma and overall polyp detection between procedures. Potentially confounding variables were controlled using multivariable logistic regression analysis. RESULTS: The adenoma detection rate was higher among patients who underwent HDWL compared with SDWL colonoscopies (28.8% vs 24.3%; P = .012), as was the polyp detection rate (42.2% vs 37.8%; P = .026). These findings remained after adjustments for potentially confounding variables (P = .018 and .022, respectively). CONCLUSIONS: In a general clinical practice setting, HDWL colonoscopy resulted in a higher adenoma detection rate compared with SDWL colonoscopy. The use of SDWL colonoscopy could reduce the number of missed adenomas and the subsequent risk for colorectal cancer.

Use of endoscopic distal attachment cap to enhance image stabilization in probe-based confocal laser endomicroscopy in colorectal lesions.

BACKGROUND AND STUDY AIMS: Colorectal cancer can be prevented through the use of colonoscopy with polypectomy. Most colon polyps are benign or low grade adenomas. However, currently all lesions need histopathologic analysis, which increases diagnostic costs and delays the final diagnosis. Confocal laser endomicroscopy (CLE) is a new technology that enables real-time endomicroscopy. However, there are challenges to maintaining a stable image with currently available systems. We conducted a small study to obtain a preliminary assessment of whether the use of an endoscopic distal attachment cap may enhance image quality of CLE in comparison with images obtained with free-hand acquisition. PATIENTS AND METHODS: Forty outpatients underwent colonoscopy for evaluation of colon polyps in a single academic medical center. Patients were assigned randomly to 1 of 2 study arms on the basis of whether an endoscopic distal attachment cap was used (n = 21, Cap Used) or not used (n = 19, No Cap) in the procedure. The quality of confocal images and probe stabilization was summarized. RESULTS: A total of 81 polyps were identified. The proportion of polyps with images of high quality was 74 % (28/38) in the Cap Used group and 79 % (30/38) in the No Cap arm. Image stability was also similar with and without a cap. Diagnostic accuracy was estimated to be slightly higher in the Cap Used group for probe-based confocal laser endomicroscopy (pCLE; 78 % vs 70 %). This was also true for white-light and narrow-band imaging. CONCLUSIONS: This preliminary study did not yield any evidence to support that the use of an endoscopic distal attachment cap improves the quality of images obtained during CLE.

Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis.

BACKGROUND: The integrity of the intestinal epithelium is critical for the absorption and retention of fluid and nutrients. The intestinal epithelium also provides a barrier between the intestinal bacteria and the body's immune surveillance. Therefore, intestinal epithelial barrier function is critically important, and disruption of the intestinal epithelium results in rapid repair of the damaged area. METHODS: We evaluated the requirement for protein kinase C iota (PKCι) in intestinal epithelial homeostasis and response to epithelial damage using a well-characterized mouse model of colitis. Mice were analyzed for the clinical, histological, and cellular effects of dextran sodium sulfate (DSS) treatment. RESULTS: Knockout of the mouse PKCι gene (Prkci) in the intestinal epithelium (Prkci KO mice) had no effect on normal colonic homeostasis; however, Prkci KO mice were significantly more sensitive to DSS-induced colitis and death. After withdrawal of DSS, Prkci KO mice exhibited a continued increase in apoptosis, inflammation, and damage to the intestinal microvasculature and a progressive loss of trefoil factor 3 (TFF3) expression, a regulatory peptide important for intestinal wound healing. Knockdown of PKCι expression in HT-29 cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3 restored wound healing in PKCι-depleted cells. CONCLUSIONS: Expression of PKCι in the intestinal epithelium protects against DSS-induced colitis. Our data suggest that PKCι reduces DSS-induced damage by promoting intestinal epithelial wound healing through the control of TFF3 expression.

Exploring the optimal fluorescein dose in probe-based confocal laser endomicroscopy for colonic imaging.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is an emerging method for in-vivo imaging of the gastrointestinal tract and requires a contrast agent. Fluorescein is the most commonly used agent. The optimal dose of fluorescein for pCLE in colon is unknown. OBJECTIVE: Exploration of optimal dose of fluorescein for pCLE in colon. DESIGN: Comparative, prospective pilot trail. SETTING: Tertiary-care center. PATIENTS: 18 participants underwent colonoscopy without complications. INTERVENTIONS: pCLE videos were recorded in normal cecum, using 10% fluorescein intravenously. MAIN OUTCOME MEASUREMENTS: For subjective analysis, pCLE videos were scored for quality, by 2 observers, independently and blinded to fluorescein dose. For objective analysis, signal-to-noise ratios (SNR) were calculated for each video by an expert. RESULTS: 6 fluorescein doses were used, including 0.5 mL, 1 mL, 2.5 mL, 5 mL, 7.5 mL and 10 mL and each dose was used in three patients. For each dose, median image quality score was 2.5, 2.0, 3.25, 4.0, 4.0 and 3.5 by first observer and 2.0, 3.0, 4.0, 5.0, 4.0 and 4.0 by second observer, respectively. The subjective quality scores increased from 0.5 mL to 5.0 mL, with no evidence of further improved quality at 7.5 mL and 10 mL doses. SNR were not significantly different between doses but trended higher for higher doses. LIMITATIONS: Small sample size. The results can not be applied to other parts of gastrointestinal tract i.e. duodenum, esophagus with different blood supply. CONCLUSION: This preliminary study suggests that the optimal dose of fluorescein for high quality pCLE imaging in colon is approximately 5.0 mL.

Endoscopic imaging for the detection of esophageal dysplasia and carcinoma.

Numerous endoscopic imaging modalities have been developed and introduced into clinical practice to enhance diagnostic capabilities. In the past, detection of dysplasia and carcinoma of the esophagus has been dependent on biopsies taken during standard white-light endoscopy. Recent important developments in biophonotics have improved visualization of these subtle lesions sufficiently for cellular details to be seen in vivo during endoscopy. These improvements allow diagnosis to be made in gastrointestinal endoscopy units, thereby avoiding the cost, risk, and time delay involved in tissue biopsy and resection. Chromoendoscopy, narrow-band imaging, high-yield white-light endoscopy, Fujinon intelligent color enhancement, and point enhancement such as confocal laser endomicroscopy are examples of enhanced imaging technologies that are being used in daily practice. This article reviews endoscopic-based imaging techniques for the detection of esophageal dysplasia and carcinoma from the perspective of routine clinical practice.