Diagnostic accuracy of a novel third generation esophageal capsule as a non-invasive detection method for Barrett's esophagus: A pilot study.

BACKGROUND AND AIM: Previous two generations of esophageal capsule did not show adequate detection rates for Barrett's esophagus (BE). We assessed the diagnostic accuracy of a novel third generation capsule with an improved frame rate of 35 frames per second for the detection of BE in a pilot study. METHODS: This was a blinded prospective pilot study conducted at a tertiary medical center. Patients with known BE (at least C0M > 1) who presented for endoscopic surveillance (May to October 2017) were included. All patients underwent novel esophageal capsule (PillCam™ UGI; Medtronic) ingestion using the simplified ingestion protocol followed by standard high-definition upper endoscopy (esophagogastroduodenoscopy [EGD]). Capsule endoscopy findings were interpreted by examiners blinded to endoscopy results and compared with endoscopic findings (gold standard). Following completion of both tests, a subjective questionnaire was provided to all patients regarding their experience. RESULTS: Twenty patients (95%males, mean age 66.3 [±7.9] years) with BE undergoing surveillance EGD were eligible. The mean BE length was 3.5 (±2.7) cm. Novel esophageal capsule detected BE in 75% patients when images were compared with endoscopy. Novel capsule detected BE in 82% patients when the BE length was ≥2 cm. The mean esophageal transit time was 0.59 s. On a subjective questionnaire, all 20 patients reported novel capsule as being more convenient compared with EGD. CONCLUSIONS: In this pilot, single-center study, novel esophageal capsule was shown to be not ready for population screening of BE. Studies integrating artificial intelligence into improved quality novel esophageal capsule should be performed for BE screening.

Surveillance of neo-squamous epithelium after ablation of Barrett's esophagus: is it better to use jumbo over standard biopsy forceps?

BACKGROUND AND AIMS: As obtaining adequate tissue on biopsy is critical for the detection of residual and recurrent intestinal metaplasia/dysplasia in Barrett's esophagus (BE) patients undergone Barrett's endoscopic eradication therapy (BET), we decided to compare the adequacy of biopsy specimens using jumbo versus standard biopsy forceps. METHODS: This is a two-center study of patients' post-radiofrequency ablation of dysplastic BE. After BET, jumbo (Boston Scientific©, Radial Jaw 4, opening diameter 2.8 mm) or standard (Boston Scientific©, Radial Jaw 4, opening diameter 2.2 mm) biopsy forceps were utilized to obtain surveillance biopsies from the neo-squamous epithelium. Presence of lamina propria and proportion of squamous epithelium with partial or full thickness lamina propria was recorded by two experienced gastrointestinal pathologists who were blinded. Squamous epithelial biopsies that contained at least two-thirds of lamina propria were considered 'adequate'. RESULTS: In a total of 211 biopsies from 55 BE patients, 145 biopsies (29 patients, 18 males, mean age 61 years, interquartile range [IQR] 33-83) were obtained using jumbo forceps and 66 biopsies (26 patients, all males, mean age 65 years, IQR 56-76) using standard forceps biopsies. Comparing jumbo versus standard forceps, the proportion of specimens with any subepithelial lamina propria was 51.7% versus 53%, P = 0.860 and the presence of adequate subepithelial lamina propria was 17.9% versus 9.1%, P = 0.096 respectively. CONCLUSIONS: Use of jumbo forceps does not appear to have added advantage over standard forceps to obtain adequate biopsy specimens from the neo-squamous mucosa post-ablation.

Lower Annual Rate of Progression of Short-Segment vs Long-Segment Barrett's Esophagus to Esophageal Adenocarcinoma.

BACKGROUND & AIMS: European guidelines recommend different surveillance intervals of non-dysplastic Barrett's esophagus (NDBE) based on segment length, as opposed to guidelines in the United States, which do recommend surveillance intervals based on BE length. We studied rates of progression of NDBE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with short-segment BE using the definition of BE in the latest guidelines (length ≥1 cm). METHODS: We collected demographic, clinical, endoscopy, and histopathology data from 1883 patients with endoscopic evidence of NDBE (mean age, 57.3 years; 83.5% male; 88.1% Caucasians) seen at 7 tertiary referral centers. Patients were followed for a median 6.4 years. Cases of dysplasia or EAC detected within 1 year of index endoscopy were considered prevalent and were excluded. Unadjusted rates of progression to HGD or EAC were compared between patients with short (≥1 and <3) and long (≥3) BE lengths using log-rank tests. A subgroup analysis was performed on patients with a documented Prague C&M classification. We used a multivariable proportional hazards model to evaluate the association between BE length and progression. Adjusted hazards ratios were calculated after adjusting for variables associated with progression. RESULTS: We found 822 patients to have a short-segment BE (SSBE) and 1061 to have long segment BE (LSBE). We found patients with SSBE to have a significantly lower annual rate of progression to EAC (0.07%) than of patients with LSBE (0.25%) (P = .001). For the combined endpoint of HGD or EAC, annual progression rates were significantly lower among patients with SSBE (0.29%) compared to compared to LSBE (0.91%) (P < .001). This effect persisted in multivariable analysis (hazard ratio, 0.32; 95% CI, 0.18-0.57; P < .001). CONCLUSION: We analyzed progression of BE (length ≥1 cm) to HGD or EAC in a large cohort of patients seen at multiple centers and followed for a median 6.4 years. We found a lower annual rate of progression of SSBE to EAC (0.07%/year) than of LSBE (0.25%/year). We propose lengthening current surveillance intervals for patients with SSBE.

Validation of Probe-based Confocal Laser Endomicroscopy (pCLE) Criteria for Diagnosing Colon Polyp Histology.

BACKGROUND: Validated probe-based confocal endomicroscopy (pCLE) criteria for distinguishing hyperplastic polyps (HPs) and tubular adenomas (TA) have not yet been developed. AIM: To develop pCLE criteria for distinguishing HP from TA and evaluate its performance characteristics among experts. METHODS: pCLE criteria for colon polyp histology were developed and tested in 2 phases prospectively. Phase I: 8 preliminary criteria were developed and tested internally. Criteria achieving an accuracy of >75% (epithelial surface: regular vs. irregular; goblet cells: increased vs. decreased; gland axis: horizontal vs. vertical; gland shape: slit/stellate vs. villiform; image scale: gray vs. dark) were evaluated in Phase II of study wherein external assessors evaluated these criteria in a separate set of pCLE videos. Accuracy and interobserver agreement (95% confidence intervals) were determined for colon histology prediction. RESULTS: Phase I (criteria development/internal testing): 8 criteria were assessed by 4 pCLE experts using 28 videos (14 HP/14 TA). Five of 8 pCLE criteria met selection for phase II (accuracy >75%). Phase II (external validation): 36 pCLE colon polyp videos (HP 16/TA 20) were evaluated by 8 external assessors. Overall accuracy in diagnosis of colon polyp histology was 84.9% (95% confidence interval, 81.7-87.7). Of predictions made with high confidence (75%), histology was predicted with an accuracy of 91%, sensitivity 83%, specificity 100%, negative predictive value 87% and positive predictive value 98%. Interobserver agreement was substantial (κ=0.73). CONCLUSIONS: We demonstrate the development and validation of pCLE criteria for prediction of colon polyp histology. Using these criteria, overall accuracy in differentiating TA from HP was high with substantial interobserver agreement.

A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples.

Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.

Impact of cap-assisted colonoscopy on detection of proximal colon adenomas: systematic review and meta-analysis.

BACKGROUND AND AIMS: Proximal colon adenomas can be missed during routine colonoscopy. Use of a cap or hood on the tip of the colonoscope has been shown to improve overall adenoma detection with variable rates. However, it has not been systematically evaluated for detection of proximal colon or right-sided adenomas where the cap may have maximum impact on adenoma detection rate (ADR). Our aim was to perform a systematic review and meta-analysis to evaluate the impact of cap-assisted colonoscopy (CC) on right-sided ADRs (r-ADRs) compared with standard colonoscopy (SC). METHODS: PubMed, EMBASE, SCOPUS, and Cochrane databases as well as secondary sources (bibliographic review of selected articles and major GI proceedings) were searched through October 1, 2016. Primary outcome was the pooled rate of r-ADR. Detection of flat adenoma, sessile serrated adenoma/polyp (SSA/P), and number of right-sided adenomas per patient were also assessed. Pooled odds ratio (OR) and 95% confidence intervals (CIs) were calculated using random-effect models. RESULTS: We screened 686 records and analyzed data from 4 studies (CC group, 2546 patients; SC group, 2547 patients) that met criteria for determination of r-ADRs, whereas 6 studies (CC group, 3159 patients; SC group, 3137 patients) were analyzed to estimate right-sided adenomas per patient. r-ADR was significantly higher with CC compared with SC (23% vs 17%; OR, 1.49; 95% CI, 1.08-2.05; I2 = 79%; P = .01). CC also improved detection rates of flat adenoma (OR, 2.08; 95% CI, 1.35-3.20; P < .01) and SSA/P (OR, 1.33; 95% CI, 1.01-1.74; P = .04). The total number of right-sided adenomas (CC: 1428 [60%] vs SC: 1127 [58%]) and number of right-sided adenomas per patient (CC, .71 ± .5, vs SC, .65 ± .62 [mean ± standard deviation]) were numerically higher for CC but were not statistically significant (P = .43). Approximately 17 CCs would be required to detect an additional patient with right-sided adenoma. CONCLUSIONS: Use of CC significantly improves the proximal colon ADR. In addition, flat adenoma and serrated colonic lesion detection rates are also significantly higher as compared with SC.

Low Risk of High-Grade Dysplasia or Esophageal Adenocarcinoma Among Patients With Barrett's Esophagus Less Than 1 cm (Irregular Z Line) Within 5 Years of Index Endoscopy.

BACKGROUND & AIMS: Many patients with a < 1 cm segment of columnar metaplasia in the distal esophagus, also called an irregular Z line, are encountered. These patients, often referred to as patients with Barrett's esophagus (BE), are enrolled in surveillance programs. However, little is known about their risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). We aimed to determine the incidence of HGD and EAC in patients with irregular Z line with intestinal metaplasia. METHODS: We performed a prospective, multicenter cohort study of patients who underwent endoscopic examination for BE at tertiary care referral centers in the United States and Europe. We analyzed data from 1791 patients (mean age, 56 ± 17 years) found to have non-dysplastic BE at the index endoscopy and after 1 year or more of follow-up. Patients were followed for a median of 5.9 years (interquartile range, 3.1-8.3 years). We calculated rates of progression to HGD or EAC between groups of patients with irregular Z line (n = 167) and those with BE of ≥ 1 cm (n = 1624). RESULTS: A higher proportion of patients in the irregular Z-line group were female (26.3%) than in the BE group (14.8% female BE) (P <.001). A lower proportion of patients in the irregular Z-line group were smokers (33.5%) than in the BE group (52.6% smokers). None of the patients with irregular Z line developed HGD or EAC during a median follow-up period of 4.8 years (interquartile range, 3.2-8.3 years). All 71 incident cases of HGD or EAC developed in patients with BE of ≥1 cm in length. On multivariate analysis, patients with irregular Z line and patients with BE of ≥ 1 cm did not differ significantly in age, race, or duration of follow-up. CONCLUSIONS: In a prospective, multicenter cohort study, we found that patients with irregular Z line do not develop HGD or esophageal cancer within 5 years after index endoscopy.

Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis.

BACKGROUND AND AIMS: Focal EMR followed by radiofrequency ablation (f-EMR + RFA) and stepwise or complete EMR (s-EMR) are established strategies for eradication of Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC)/intramucosal carcinoma (IMC). The objective of this study was to derive pooled rates of efficacy and safety of individual methods in a large cohort of patients with BE and to indirectly compare the 2 methods. METHODS: PubMed, Embase, Web of Science, Cochrane, and major conference proceedings were searched. A systematic review and pooled analysis were carried out to determine the following outcomes in patients with BE undergoing either f-EMR + RFA or s-EMR: (1) complete eradication rates of neoplasia (CE-N) and intestinal metaplasia (CE-IM); (2) recurrence rates of cancer (EAC), dysplasia, and IM; (3) incidence rates of adverse events. Mixed logistic regression was performed as an exploratory analysis to examine differences in outcomes between the 2 methods. RESULTS: Nine studies (774 patients) of f-EMR + RFA and 11 studies (751 patients) of s-EMR were included. Patients undergoing f-EMR + RFA had high BE eradication rates (CE-N, 93.4%; CE-IM, 73.1%), whereas strictures occurred in 10.2%, bleeding in 1.1%, and perforations in 0.2% of patients. Recurrence of EAC, dysplasia, and IM was 1.4%, 2.6%, and 16.1%, respectively, in this group. Patients undergoing s-EMR also showed high BE eradication rates (CE-N, 94.9%; CE-IM, 79.6%) but a higher rate of adverse events (strictures in 33.5%, bleeding in 7.5%, and perforation in 1.3%). Recurrence of EAC, dysplasia, and IM was 0.7%, 3.3%, and 12.1%, respectively, in the s-EMR group. Mixed logistic regression showed that patients undergoing s-EMR might be more likely to develop esophageal strictures (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.61-13.85; P = .005), perforation (OR, 7.00; 95% CI, 1.56-31.33; P = .01), and bleeding (OR, 6.88; 95% CI, 2.19-21.62; P = 0.001) compared with f-EMR + RFA. CONCLUSIONS: In patients with HGD/EAC, f-EMR followed by RFA seems to be equally effective as and safer than s-EMR.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists.

AIM: To evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists. METHODS: Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS: Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27). CONCLUSION: When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.