Background Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been ...extensively evaluated. Objective To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade dysplasia (HGD) and early carcinoma (EC) in BE. Design International, prospective, multicenter, randomized, controlled trial. Setting Five tertiary referral centers. Patients A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC. Interventions All patients were examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were recorded before biopsy samples were obtained. The order of HD-WLE and NBI was randomized and performed by 2 independent, blinded endoscopists. All suspicious lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These locations were examined by pCLE, and a presumptive diagnosis of benign or neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken from all locations and were reviewed by a central pathologist, blinded to endoscopic and pCLE data. Main Outcome Measurements Diagnostic characteristics of pCLE. Results The sensitivity and specificity for HD-WLE were 34.2% and 92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or pCLE ( P = .002 and P < .001, respectively). The sensitivity and specificity for HD-WLE or NBI were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%, respectively, for HD-WLE, NBI, or pCLE ( P = .01 and P = .02, respectively). Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI, respectively, resulting in detection of all HGD/EC patients, although not statistically significant. Limitations Academic centers with enriched population. Conclusions pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE. This may allow better informed decisions to be made for the management and subsequent treatment of BE patients. (Clinical trial registration number: NCT00795184 .)
Background Volumetric laser endomicroscopy (VLE) produces high-resolution, cross-sectional surface, and subsurface images for detecting neoplasia, targeting biopsies, and guiding real-time treatment. ...Objective To evaluate the safety and feasibility of the Nvision VLE system. Design Prospective, multicenter study. Setting Tertiary-care medical centers. Patients One hundred patients with suspected Barrett’s esophagus, including 52 patients with prior endotherapy. Interventions The first-generation Nvision VLE Imaging System, a balloon-centered, rotating optical probe provided images of the mucosa and submucosa through a 6-cm segment length and 360° scan of the distal esophagus. Main Outcome Measurements Acquisition of a complete, 6-cm scan from the distal esophagus, demographic and procedural data, and final histologic diagnosis. Results VLE imaging was successfully performed in 87 cases. After VLE imaging, biopsy specimens were obtained in 77 patients and mucosal resection was performed in 20 patients. The final pathologic diagnoses of the patients studied were adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29 patients), and normal squamous cells (18 patients). VLE was not completed in 13 of 100 (13%) because of optical probe and console issues. There were 2 minor adverse events (mucosal lacerations not requiring therapy). Limitations This was a feasibility study with a first-generation device. There was no direct histopathologic correlation with the VLE images or any comparative analysis with white-light endoscopy or narrow-band imaging findings. Conclusion VLE is a safe procedure for patients with suspected or confirmed Barrett’s esophagus. Real-time VLE images enabled visualization of the mucosa and submucosa in 87% of cases. Further studies are needed to evaluate the in vivo diagnostic accuracy and clinical utility of VLE.
Background Confocal laser endomicroscopy (CLE) is a rapidly emerging method for in vivo imaging of the GI tract. Objective To determine the preliminary evaluation accuracy and interobserver agreement ...of probe-based CLE (pCLE) in Barrett's esophagus (BE). Design Prospective, double-blind review of pCLE images of 40 sites of BE tissue by using matching biopsies 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 20 unknown images. Setting Eleven experts in BE imaging from 4 different endoscopy centers from the United States and Europe evaluated the images. Patients This study involved nonconsecutive patients undergoing BE surveillance or evaluation of high-grade intraepithelial neoplasia or early adenocarcinoma. Intervention Intravenous fluorescein pCLE imaging of each site within the BE segment, followed by matching biopsy. Main Outcome Measurements Sensitivity, specificity, and agreement for the pCLE diagnosis of high-grade intraepithelial neoplasia or carcinoma. Results In the validation set (n = 20), 11 cases had high-grade intraepithelial neoplasia or invasive carcinoma. The sensitivity for the diagnosis of neoplasia for the 11 endoscopists was 88% (range 6 of 11 to 11 of 11), and the specificity was 96% (range 7 of 9 to 9 of 9). There was substantial agreement on the pCLE diagnosis (86%, kappa 0.72; 95% confidence interval, 0.58-0.86). Endomicroscopists with prior pCLE experience had an overall sensitivity of 91% (all 10 of 11), specificity of 100% (all 9 of 9), and almost perfect agreement (92%, kappa 0.83; 95% confidence interval, 0.64-1.0). Limitations Small sample size and use of offline video sequences. Conclusion Results suggest that pCLE for the diagnosis of neoplasia in BE has very high accuracy and reliability.
Background Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy ...(CRYO) demonstrates promising preliminary data. Objective To assess the safety and efficacy of CRYO in BE with HGD. Design Multicenter, retrospective cohort study. Setting Nine academic and community centers; treatment period, 2007 to 2009. Patients Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. Interventions CRYO with follow-up biopsies. Main Outcome Measurements Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. Results Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). Limitations Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. Conclusions CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.
Background The role of EUS among patients with Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or suspected mucosal carcinoma is controversial. Objective To define the role of EUS in ...detecting advanced disease among patients with BE. Design Systematic review and meta-analysis. Setting MEDLINE, Embase, Web of Science, and Cochrane Central databases. Patients Patients with BE and HGD or esophageal adenocarcinoma (EAC) who were referred for endoscopic evaluation and underwent EUS. Interventions EUS. Main Outcome Measurements Pooled proportion of patients with advanced EAC identified by EUS among patients with BE who are referred for HGD or EAC (with or without visible lesions). Forest plots were used to contrast effect sizes in each of the studies and random effect models when tests of heterogeneity were significant ( I2 > 50% or P < .1 for the Q statistic). Results Of 1278 articles, 47 were reviewed in full text, and 11 articles met the inclusion criteria, including a total of 656 patients. Based on a random-effects model, the proportion of patients with advanced disease detected on EUS was 14% (95% confidence interval, 8%-22%; P < .0001). In a subanalysis, the pooled proportion of patients with advanced disease on EUS in the absence of nodules was 4% (95% confidence interval, 2%-6%, P < .0001). Limitations Significant heterogeneity among studies. Conclusions EUS will result in a change in the therapeutic approach among in a significant minority of patients with BE who are referred for HGD or EAC.
Background and Aims Endoscopic therapy is the standard treatment for high-grade dysplasia and some cases of T1a esophageal adenocarcinoma (EAC), but it is not appropriate for deeply invasive disease. ...Data on the value of EUS for patient selection for endoscopic or surgical resection are conflicting. We investigated the outcome of esophageal EUS for the staging and treatment selection of patients with treatment-naive, premalignant Barrett’s esophagus (BE) and suspected superficial EAC. Methods We retrospectively reviewed consecutive patients who underwent EUS for staging of treatment-naive, suspected premalignant BE and superficial EAC from January 2006 to June 2014. All patients referred for endoscopic therapy routinely underwent EUS. Patients with esophageal masses, squamous cell cancers, previous neoadjuvant therapy, or unrelated pathologies were excluded. Each patient’s final diagnosis was verified by EMR, esophagectomy, or forceps biopsy sampling. Test characteristics of EUS were calculated. Results Three hundred thirty-five patients (mean age, 68 years; 86% male) with BE, a Prague C mean of 2.8 cm, and a Prague M mean of 4.5 cm were staged (pT0, 78% 6% nondysplastic, 24% low-grade dysplasia, 42% high-grade dysplasia; pT1a, 14%; pT1b, 7%; and pT2, 1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for patient selection to endoscopic (T1aN0 or less) or surgical therapy with EUS TN staging were 50%, 93%, 40%, 95%, and 90%, respectively. Comparable rates were achieved for patients with nodular BE. Overstaging occurred in 7% of patients, and EUS selected 11% for incorrect treatment modalities compared with pathologic staging. Conclusions This study confirms the limited value of EUS suggested in the latest American College of Gastroenterology guidelines for BE management.
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.
Background Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated ...efficacy in this setting in early studies. Objective To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Design Multicenter, retrospective cohort study. Setting Ten academic and community medical centers between 2006 and 2009. Patients Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Interventions Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Main Outcome Measurements Complete eradication of luminal cancer and adverse events. Results Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Limitations Retrospective study design, short follow-up. Conclusions Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.
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