New aspects of modern endoscopy

The prognosis for patients with malignancies of the ga-strointestinal-tract is strictly dependent on early detec-tion of premalignant and malignant lesions. However, small, flat or depressed neoplastic lesions remain dif-ficult to detect with these technologies thereby limiting their value for polyp and cancer screening. At the same time computer and chip technologies have undergone major technological changes which have greatly im-proved endoscopic diagnostic investigation. New imag-ing modalities and techniques are very notable aspects of modern endoscopy. Chromoendoscopy or filter-aided colonoscopy(virtual chromoendoscopy) with high defi-nition endoscopes is able to enhance the detection and characterization of lesions. Finally, confocal laser en-domicroscopy provides histological confirmation of the presence of neoplastic changes. The developing tech-niques around colonoscopy such as the retro-viewing colonoscope, the balloon-colonoscope or the 330-de-grees-viewing colonoscope try to enhance the efficacy by reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon capsule endoscopy is limited to identifying cancer and not necessarily small adenomas. Preliminary attempts have been made to introduce this technique in clinical routine.     

Third‐generation autofluorescence endoscopy for the detection of early neoplasia in Barrett's esophagus: a pilot study

In Barrett's esophagus (BE), second‐generation autofluorescence imaging (AFI‐II) improves targeted detection of high‐grade intra‐epithelial neoplasia (HGIN) and early cancer (EC), yet suffers from high false‐positive (FP) rates. The newest generation AFI (AFI‐III) specifically targets fluorescence in malignant cells and may therefore improve detection of early neoplasia and reduce FP rate. The aim was to compare AFI‐III with AFI‐II for endoscopic detection of early neoplasia in BE. BE patients with endoscopically inconspicuous neoplasia underwent two diagnostic endoscopies (AFI‐II/AFI‐III) in a single session. End‐points: number of patients and lesions with HGIN/EC detected with AFI‐II and AFI‐III after white‐light endoscopy (WLE) and the value of reinspection of AFI‐positive areas with WLE and narrow‐band imaging. Forty‐five patients were included (38 males, age 65 years). Nineteen patients showed HGIN/EC. AFI‐II inspection after WLE increased detection of HGIN/EC from 9 to 15 patients (47 to 79%); AFI‐III increased detection from 9 to 17 patients (47 to 89%). WLE plus random biopsies diagnosed 13/19 (68%) HGIN/EC patients. One hundred and four abnormal AFI areas were inspected; 23 (22%) showed HGIN/EC. AFI‐II increased detection of HGIN/EC from 10 to 18 lesions (43 to 78%). AFI‐III increased detection from 10 to 20 lesions (43–87%). FP rate was 86% for AFI‐II and AFI‐III. Reinspection with WLE or narrow‐band imaging reduced FP rate to 21% and 22%, respectively, but misclassified HGIN/EC lesions as unsuspicious in 54% and 31%, respectively. This first feasibility study on third‐generation AFI again showed improved targeted detection of HGIN/EC in BE. However, the results do not suggest AFI‐III performs significantly better than conventional AFI‐II.     

Characterization of tissue autofluorescence in Barrett''s esophagus by confocal fluorescence microscopy

High grade dysplasia and early cancer in Barrett's esophagus can be distinguished in vivo by endoscopic autofluorescence point spectroscopy and imaging from non-dysplastic Barrett's mucosa. We used confocal fluorescence microscopy for ex vivo comparison of autofluorescence in non-dysplastic and dysplastic Barrett's esophagus. Unstained frozen sections were obtained from snap-frozen Barrett's esophagus biopsy samples and scanned with confocal fluorescence microscopy (458 nm excitation; 505-550 nm [green] and > 560 nm [red] emission). Digital micrographs were taken from areas with homogenous and specific histopathology. Visual inspection and statistical analysis were used to evaluate the image datasets. Dysplastic and non-dysplastic Barrett's esophagus epithelia fluoresced mainly in the green spectrum and the main sources of autofluorescence were the cytoplasm and lamina propria. High-grade dysplasia was differentiated from non-dysplastic Barrett's esophagus by microstructural tissue changes. However, there were no specific changes in either the locations or average intensities of intrinsic green and red autofluorescence at the epithelial level that could differentiate between dysplastic and non-dysplastic Barrett's esophagus epithelia, ex vivo. Detectable differences in autofluorescence between BE and dysplasia/cancer in vivo are probably not caused by specific changes in epithelial fluorophores but are likely due to other inherent changes (e.g. mucosal thickening and increased microvascularity) attenuating autofluorescence from the collagen-rich submucosa. Furthermore, confocal fluorescence microscopy provides 'histology-like' imaging of Barrett's tissues and may offer a unique opportunity to exploit microstructural tissue changes occurring during neoplastic transformation for in vivo detection of high-grade dysplasia in Barrett's patients using newly developed confocal fluorescence microendoscopy devices.     

Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease: a pilot study

Background: Patients are at increased risk of disease recurrence after surgical treatment of Crohn’s disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown.

Methods: This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included. Colon capsule endoscopy was performed 4–8 weeks (d1) and 4–8 months (d2) postoperatively together with ileo-colonoscopy at d2 using a modified Ruttgeerts index for evaluating disease activity.

Results: Twenty-two patients were included into this study. At d1, significant disease activity (Ruttgeerts index ≥2) was detected in 3/16 (19%) of the patients. At d2, half of the patients (6/12) showed active disease, whereas ileo-colonoscopy revealed significant inflammation in 5/15 (33%). All patients rated as having active disease by ileo-colonoscopy had been revealed by PICE as well. These findings influenced the medical treatment in every case.

Conclusion: Pan-intestinal capsule endoscopy seems to be feasible in the postoperative surveillance of Crohn's disease. Disease activity is reliably detected. Especially, the findings in the small bowl might be a significant advantage in comparison to ileo-colonoscopy, as they can have significant impact on clinical management. Further studies with a larger number of patients are needed to confirm these findings and might lead to a replacement of the flexible ileo-colonoscopy with pan-intestinal capsule endoscopy in this indication in the future.     

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM: To investigate whether autofluorescence imaging(Af I) endoscopy can distinguish non-erosive reflux disease(NERD) from functional heartburn(fh).METHODS: In this prospective observational trial, 127 patients presenting with typical reflux symptoms for 6 mo were screened. All the participants underwent endoscopy, during which white light imaging(WLI) was followed by Af I. finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during Af I endoscopy. Ambulatory 24-h multichannel intraluminal impedance and ph monitoring was also performed. After standard proton-pump inhibitor(PPI) tests, subjects were divided into an NERD group and an fh group and the diagnostic performance of Af I endoscopy to differentiate NERD from fh was evaluated.RESULTS: Of 84 endoscopy-negative patients, 36(42.9%) had a normal ph/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. finally 10 patients were diagnosed with fh and the others with NERD. Altogether, 68(81.0%) of the 84 patients were positive on Af I endoscopy. In the NERD group, there were 67(90.5%) patients with abnormal esophageal findings on Af I endoscopy while only 1(10%) patient was positive on Af I endoscopy in the fh group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5%(95%CI: 81.5%-96.1%) and 90.0%(95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of Af I in differentiating between NERD and fh were 90.5%(95%CI: 84.2%-96.8%), 98.5%(95%CI: 92.1%-99.9%) and 56.3%(95%CI: 30.0%-80.2%), respectively.CONCLUSION: Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and fh.     

Endoscopic fluorescence detection of low and high grade dysplasia in Barrett's oesophagus using systemic or local 5-aminolaevulinic acid sensitisation

BACKGROUND AND AIMS: Barrett's oesophagus is associated with an increased risk of cancer. As dysplasia is not visible during routine endoscopy, random biopsies in the four quadrants every 1-2 cm are recommended. Endoscopic fluorescence detection (EFD) after sensitisation with 5-aminolaevulinic acid (5-ALA) with different modes and concentrations was assessed to optimise the technique for detection of dysplasia or early cancers. 5-ALA is converted intracellularly to protoporphyrin IX which accumulates in malignant tissue and can be detected by typical red fluorescence after illumination with blue light. METHODS: In 47 patients with Barrett's oesophagus, 10 with known dysplasia, 58 fluorescence endoscopies were performed after sensitisation with different concentrations of 5-ALA given orally (5, 10, 20, 30 mg/kg) or locally (500-1000 mg) by spraying the mucosa via a catheter. EFD was performed 4-6 hours after systemic and 1-2 hours after local sensitisation using a special light source delivering white or blue light. A total of 243 biopsies of red fluorescent (n=113) and non-fluorescent areas (n=130) were taken. RESULTS: In three patients, two early cancers and dysplasia, not visible during routine endoscopy, were detected by EFD. Thirty three biopsies revealed either low or high grade dysplasia. Sensitivity for detection of dysplastic lesions ranged from 60% after local sensitisation with 500 mg to 80%, 100%, and 100% after systemic application of 5-ALA 10, 20, and 30 mg/kg, respectively. However, specificity was best for local sensitisation (70%) while systemic administration revealed values between 27% and 56%. Using 5 mg/kg, no red fluorescence in dysplastic lesions was found. No severe side effects were noted. CONCLUSION: EFD is a promising tool to detect non-visible dysplastic lesions in Barrett's oesophagus using 5-ALA sensitisation. A randomised controlled study is now indicated to compare the efficacy of EFD with the standard technique of four quadrant random biopsies.     

Autofluorescence imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia: a phase II study

Background and Aim: Few prospective studies examining the efficacy of autofluorescence imaging (AFI) screening for esophageal cancer have been reported. This study aimed to investigate the diagnostic value of AFI endoscopy for the screening of squamous mucosal high‐grade neoplasia of the esophagus, performed by experienced and less‐experienced endoscopists. Methods: Patients with a history of esophageal neoplasia or head and neck cancer underwent AFI endoscopic screening, followed by chromoendoscopy using iodine staining as the reference standard. The primary outcome was the sensitivity of AFI for detecting new squamous mucosal high‐grade neoplasias. The secondary outcome was the positive predictive value (PPV) of AFI. Results: Of a total 364 patients who underwent endoscopic examination, 43 new mucosal high‐grade neoplasias were detected. The sensitivities of AFI in the experienced and less‐experienced endoscopist groups were 71% (95% confidence interval [CI]: 55–87%) and 50% (95% CI: 32–68%), respectively. The PPV of AFI in the experienced and the less‐experienced endoscopist groups were 25% (95% CI: 16–34%) and 26% (95% CI: 15–37%), respectively. The sensitivity of AFI in lesions ≤ 10 mm (31%, 5/16 lesions) was significantly lower than that in lesions > 10 mm (78%, 21/27 lesions) (P = 0.003). Conclusions: The sensitivity of AFI for the detection of new squamous mucosal high‐grade neoplasias, and its PPV, were both low. Based on these results, a randomized study to compare AFI with standard techniques is not justified.     

Autofluorescence imaging endoscopy for identification and assessment of inflammatory ulcerative colitis

AIM:To validate the clinical relevance of autofluores-cence imaging(AFI)endoscopy for the assessment of inflammatory ulcerative colitis(UC).METHODS:A total of 572 endoscopic images were se-lected from 42 UC patients:286 taken with white light imaging(WLI)and 286 with AFI from the same sites.WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore(MES),and for seven characteristic endoscopic features.Likewise,AFI photographs were scored according to relative abundance o...     

Magnifying endoscopy of gastric epithelial dysplasia based on the morphologic characteristics

AIM: To investigate the difference in magnifying endoscopic findings of gastric epithelial dysplasias (GEDs) according to the morphologic characteristics.METHODS: This study included 46 GED lesions in 45 patients who underwent magnifying endoscopy using narrow band imaging (ME-NBI) before endoscopic resection. During ME-NBI, the microvascular and microsurface (MS) patterns and the presence of light blue crest (LBC) and white opaque substance were investigated. GEDs were categorized as adenomatous, foveolar, and hybrid types, and their mucin phenotype was evaluated.RESULTS: Of the 46 lesions, 27 (59%) were categorized as adenomatous, 15 (32%) as hybrid, and the remaining 4 (9%) as foveolar. All adenomatous GEDs showed the round pit and/or tubular MS patterns, all foveolar GEDs showed the papillary pattern, and hybrid GEDs showed mixed patterns (P < 0.001). LBC was more frequently observed in adenomatous GEDs than in hybrid or foveolar GEDs (52%, 33%, 0%, respectively), although this difference was not significant (P = 0.127). The papillary MS pattern was associated with MUC5AC and MUC6 expression, and the round pit and/or tubular MS patterns were associated with CD10 expression.CONCLUSION: The MS pattern in ME-NBI findings is useful for predicting the morphologic category and mucin phenotype of GEDs, and ME-NBI findings may guide decisions regarding GED treatment.     

Reduction of miss rates of colonic adenomas by zoom chromoendoscopy

Background and aims The aim of this study was to determine the detection rate of polyps using zoom chromoendoscopy (ZE) compared with standard video colonoscopy.Patients and methods End-to-end colonoscopies were performed in 50 patients by two different endoscopists blinded for each other’s results. Lesions detected during initial standard colonoscopy (C1) were biopsied or removed by snare resection. The second colonoscopy (C2) was done with a zoom colonoscope spraying the whole colon with indigocarmine (0.4%). In addition, detected mucosal lesions were documented prior to ZE and then classified according to the pit pattern classification before biopsy or removal. The retrieval time for each procedure was determined. Results: The average retrieval time for C1 was 13±9 min (9–24) and 28±11 min (16–38, p<0.05) for ZE. During C1, 56 lesions were detected in 26 of 50 patients (34 hyperplastic and 22 adenomatous). During C2, 19 additional polyps were documented prior to ZE (15% tandem miss rate), and 20 further lesions were detected with ZE (21% additional polyp detection rate compared to C1 and C2 without ZE). Of the 39 additional lesions removed during C2 after ZE, 29 were hyperplastic and 10 were adenomatous. Most adenomas detected during the second investigation were found in patients in whom adenomatous polyps had already been removed during the initial colonoscopy (9 of 26 patients vs 1 of 24 patients, p<0.02). No carcinoma was detected. The pit pattern classification allowed a correct differentiation between hyperplastic and adenomatous polyps (accuracy 93%, sensitivity 90%, specificity 97%).Conclusion Using zoom chromoendoscopy, the rate of detecting colonic polyps can be increased at the cost of a longer retrieval time.     

Photodiagnostic techniques for the endoscopic detection of premalignant gastrointestinal lesions

Considerable attention is given to the clinical diagnosis of gastrointestinal (GI) malignancies as they remain the second leading cause of cancer‐associated deaths in developed countries. Detection and intervention at an early stage of preneoplastic development significantly improve patient survival. High‐risk assessment of asymptomatic patients is currently performed by strict endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy. However, poor sensitivity associated with frequent surveillance programs incorporating conventional screening tools, such as white light endoscopy and multiple random biopsy, is a significant limitation. Recent advances in biomedical optics are illuminating new ways to detect premalignant lesions of the GI tract with endoscopy. The present review presents a summary report on the newest developments in modern GI endoscopy, which are based on novel optical endoscopic techniques: fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, light scattering spectroscopy, optical coherence tomography, chromoendoscopy, confocal fluorescence endoscopy and immunofluorescence endoscopy. Relying on the interaction of light with tissue, these ‘state‐of‐the‐art’ techniques potentially offer an improved strategy for diagnosis of early mucosal lesions by facilitating targeted excisional biopsies. Furthermore, the prospects of real‐time ‘optical biopsy’ and improved staging of lesions may significantly enhance the endoscopist's ability to detect subtle preneoplastic mucosal changes and lead to curative endoscopic ablation of these lesions. Such advancements within this specialty will be rewarded in the long term with improved patient survival and quality of life.     

Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells.Molecular imaging has several advantages including minimal damage to tissues,repetitive visualization,and utility for conducting quantitative analyses.Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible.Molecular imaging during gastrointestinal endoscopy requires thedevelopment of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio.Additionally,a high-resolution endoscope with an accurate wide-field viewing capability must be developed.Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.     

Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study

AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.     

Colon capsule endoscopy: Detection of colonic polyps compared with conventional colonoscopy and visualization of extracolonic pathologies

BACKGROUND:

Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine.

OBJECTIVE:

To assess the PillCam Colon 2 (Given Imaging Ltd, Israel) capsule with regard to feasibility, sensitivity and specificity for the detection of colonic pathologies and additional recorded extracolonic findings.

METHODS:

CCE was performed before CC in patients indicated for CC for known or suspected colonic disease. The results of both techniques were compared with regard to polyp detection. Additionally, bowel preparation and extracolonic pathologies were analyzed.

RESULTS:

Twenty-four patients (mean age 51.1 years) were included in the analysis. Visualization of the colon was complete in 23 CCs and 17 CCEs. No adverse events or major technical failures occurred. CC detected 47 polyps and CCE detected 43 polyps of any size (per-finding sensitivity 90.9%, specificity 67.6%). The accuracy of CCE in detecting polyp carriers was 81.5% (per-patient analysis). On average, the colon was adequately cleansed in 90.1% of patients. CCE identified esophageal, gastric and small bowel pathologies in seven (24%), nine (38%) and 14 (58%) patients, respectively.

CONCLUSIONS:

CCE proved to be technically feasible and safe. Acceptable sensitivity and moderate specificity levels in polyp detection were recorded. Bowel preparation was adequate in most patients. Because extracolonic pathologies were effectively visualized, new indications for the PillCam Colon 2 may be defined.     

Detection of abnormal lesions recorded by capsule endoscopy: A prospective study comparing endoscopist''s and nurse''s accuracy

BACKGROUND AND STUDY AIM: Capsule endoscopy is a non-invasive technique for small bowel examination but its evaluation is time consuming. The aim of this study was to assess whether, following adequate training, an endoscopy nurse is capable of picking up all significant images without reducing the diagnostic accuracy of the procedure. PATIENTS AND METHODS: Between April 2003 and December 2004, a total of 41 consecutive capsule endoscopy studies were blindly reviewed by both an endoscopy nurse and an endoscopist. The two operators had to select all significant images independently and to complete a structured questionnaire. Thirty-nine capsule endoscopy examinations (two studies discharged for premature battery failure) were evaluated. The agreement between the two operators was calculated by kappa statistics (coefficient of agreement). RESULTS: Agreement was excellent for all kind of selected lesions (mean kappa>0.85); the agreement was complete (kappa=1) for site identification, active bleeding, stenosis and negative studies. The greater disagreement (kappa=0.77) was found in cases of subtle mucosal abnormalities (i.e. reduction of villi), which were over-estimated by the nurse. CONCLUSIONS: The preview recordings made by the nurse may increase the cost/effectiveness of the study, by considerably reducing the time needed for the endoscopist to make the final report (about 5-10 min), without compromising final diagnosis.