Increased detection of Barrett's esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial.

BACKGROUND AND AIMS: Wide-area transepithelial sampling (WATS) with computer-assisted 3-dimensional analysis is a sampling technique that combines abrasive brushing of the Barrett's esophagus (BE) mucosa followed by neural network analysis to highlight abnormal-appearing cells. METHODS: We performed a randomized trial of referred BE patients undergoing surveillance at 16 medical centers. Subjects received either biopsy sampling followed by WATS or WATS followed by biopsy sampling. The primary outcome was rate of detection of high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) using WATS in conjunction with biopsy sampling compared with biopsy sampling alone using standard histopathologic criteria. Secondary aims included evaluating neoplasia detection rates based on the procedure order (WATS vs biopsy sampling first), of each procedure separately, and the additional time required for WATS. RESULTS: One hundred sixty patients (mean age, 63.4 years; 76% men; 95% white) completed the trial. The median circumferential and maximal BE extents were 1.0 cm (interquartile range: .0-5.0) and 4.0 cm (interquartile range, 2.0-8.0), respectively. The diagnostic yield for biopsy sampling alone was as follows: HGD/EAC, 7 (4.4%); low-grade dysplasia (LGD), 28 (17.5%); nondysplastic BE (NDBE), 106 (66.25%); and no BE, 19 (11.9%). The addition of WATS to biopsy sampling yielded an additional 23 cases of HGD/EAC (absolute increase, 14.4%; 95% confidence interval, 7.5%-21.2%). Among these 23 patients, 11 were classified by biopsy sampling as NDBE and 12 as LGD/indefinite for dysplasia (IND); 14 received biopsy sampling first and 9 WATS first (not significant) and most (n = 21; 91.7%) had a prior dysplasia history. WATS added an average of 4.5 minutes to the procedure. CONCLUSION: Results of this multicenter, prospective, randomized trial demonstrate that the use of WATS in a referral BE population increases the detection of HGD/EAC. (Clinical trial registration number: NCT03008980.).

Inter-Observer Agreement among Pathologists Using Wide-Area Transepithelial Sampling With Computer-Assisted Analysis in Patients With Barrett's Esophagus.

OBJECTIVES: The histopathological diagnosis of Barrett's esophagus (BE)-associated dysplasia has poor inter-observer agreement. The wide-area transepithelial sampling (WATS) procedure uses a minimally invasive brush biopsy technique for acquiring wide-area sampling of BE tissue followed by computer-assisted analysis. In this study, our aim was to assess inter-observer agreement among pathologists in the diagnosis of Barrett's-associated dysplasia using the WATS computer-assisted analysis technique. METHODS: WATS slides with varying degrees of BE dysplasia were randomly selected and distributed to four pathologists. Each pathologist graded the slides as nondysplastic, low-grade dysplasia (LGD), or high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) and completed a standardized case report form (CRF) for each slide. RESULTS: In all, 149 BE slides were evaluated in a blinded manner by 4 pathologists. The slides included the following: no dysplasia (n=109), LGD, and HGD/EAC (n=40). The overall mean kappa value for all 3 diagnoses for the 4 observers was calculated at 0.86 (95% confidence interval (CI) 0.75-0.97). The kappa values (95% CI) for HGD/EAC, IND/LGD, and no dysplasia were 0.95 (0.88-0.99), 0.74 (0.61-0.85), and 0.88 (0.81-0.94), respectively. CONCLUSIONS: The diagnosis of BE and associated dysplasia using the WATS technique has very high inter-observer agreement. This appears to be significantly higher as compared with previously published data using standard histopathology.

15-deoxy-Delta12,14-prostaglandin J2 impairs phosphatidylcholine synthesis and induces nuclear accumulation of thiol-modified cytidylyltransferase.

Synthesis of phosphatidylcholine, the major phospholipid of animal cell membranes, requires the key enzyme cytidylyltransferase (CCTalpha). Cysteine sulfhydryls within CCTalpha are needed for full catalytic activity. Here we show that prostaglandin 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) inactivates CCTalpha by inducing generation of reactive oxidant species and the appearance of a cross-linked CCTalpha dimer in cells. N-Acetyl-l-cysteine reduced oxidative stress, prevented CCTalpha cross-linking, and restored CCT function in 15d-PGJ2-treated cells. 15d-PGJ2 modified critical cysteine residues within CCTalpha as determined by mutagenesis studies and by incorporation of biotin-15d-PGJ2 into CCTalpha. These effects of 15d-PGJ2 were associated with CCTalpha accumulation within the nucleus. The data indicate that bioactive prostanoids significantly impair membrane phospholipid production by promoting cysteine cross-bridging within CCTalpha.

Pseudodyskinesis--a novel mechanism for abnormal motion of the heart's diaphragmatic wall.

We report a case of pseudodyskinesis, where there is dyssynchronous contraction of the heart's diaphragmatic wall despite normal wall thickening. This finding has previously been reported in a small group of patients with liver disease, and has been attributed to elevation of the diaphragm as a result of hepatomegaly and ascites. Our case demonstrates similar findings in a patient without liver disease, in whom the diaphragm was elevated secondary to volume loss in the chest. Our case supports the assertion that diaphragmatic elevation, regardless of cause, is indeed responsible for this probably common echocardiographic finding.