Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett's esophagus.

BACKGROUND: Several types of forceps are available for use in sampling Barrett's esophagus (BE). Few data exist with regard to biopsy quality for histologic assessment. OBJECTIVE: To evaluate sampling quality of 3 different forceps in patients with BE. DESIGN: Single-center, randomized clinical trial. PATIENTS: Consecutive patients with BE undergoing upper endoscopy. INTERVENTIONS: Patients randomized to have biopsy specimens taken with 1 of 3 types of forceps: standard, large capacity, or jumbo. MAIN OUTCOME MEASUREMENTS: Specimen adequacy was defined a priori as a well-oriented biopsy sample 2 mm or greater in diameter and with at least muscularis mucosa present. RESULTS: A total of 65 patients were enrolled and analyzed (standard forceps, n = 21; large-capacity forceps, n = 21; jumbo forceps, n = 23). Compared with jumbo forceps, a significantly higher proportion of biopsy samples with large-capacity forceps were adequate (37.8% vs 25.2%, P = .002). Of the standard forceps biopsy samples, 31.9% were adequate, which was not significantly different from specimens taken with large-capacity (P = .20) or jumbo (P = .09) forceps. Biopsy specimens taken with jumbo forceps had the largest diameter (median, 3.0 mm vs 2.5 mm [standard] vs 2.8 mm [large capacity]; P = .0001). However, jumbo forceps had the lowest proportion of specimens that were well oriented (overall P = .001). LIMITATIONS: Heterogeneous patient population precluded dysplasia detection analyses. CONCLUSIONS: Our results challenge the requirement of jumbo forceps and therapeutic endoscopes to properly perform the Seattle protocol. We found that standard and large-capacity forceps used with standard upper endoscopes produced biopsy samples at least as adequate as those obtained with jumbo forceps and therapeutic endoscopes in patients with BE.

Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett's esophagus.

OBJECTIVES: Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS: We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS: A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8). CONCLUSIONS: In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

Resistance training improves femoral artery endothelial dysfunction in aged rats.

Although endurance exercise improves age-associated endothelial dysfunction, few studies have examined the effects of resistance training and the potential molecular mechanisms involved in altering vascular reactivity with age. Young (9 months) and aged (20 months) male, Fisher 344 rats were divided into four groups: Young Sedentary (YS, n = 14), Young Trained (YT, n = 10), Aged Sedentary (AS, n = 12), and Aged Trained (AT, n = 10). Resistance training consisted of climbing a 1 m wire ladder, at an 85 degrees angle, 3 days/week for 6 weeks with increasing weight added to the tail. Endothelial function in femoral arteries was determined by constructing acetylcholine dose-response curves on a wire myograph. Femoral artery phospho-Ser1179-eNOS, eNOS and Hsp90 expression were evaluated by Western blot. Acetylcholine-induced vasorelaxation was significantly (P < 0.05) impaired in AS compared to YS and YT but not AT compared to YS and YT. Phospho-Ser1179-eNOS and eNOS were elevated (P < 0.05) in aged animals but not changed with resistance training. Resistance training increased Hsp90 levels in both young and old animals. Therefore, resistance training improves age-associated endothelial dysfunction in femoral arteries without changes in eNOS phosphorylation and expression. Increased Hsp90 expression, a regulator of eNOS activity and coupling, suggests a potential mechanism for this improvement.

Inhibition of BCL2 expression and activity increases H460 sensitivity to the growth inhibitory effects of polyphenon E.

The anti-cancer properties of the green tea-derived mixture Polyphenon E (Poly E) have been demonstrated in a variety of cell culture and animal models. We recently discovered that the H460 lung cancer cell line is markedly resistant to the growth inhibitory effects of Poly E compared with SW480 colon and Flo-1 esophageal cancer cells. We investigated the mechanism of H460 resistance by comparing gene expression profiles of Poly E-sensitive and -resistant cells. Unsupervised hierarchical clustering revealed that Poly E-sensitive cells clustered separately from Poly E-resistant cells, and 6,242 genes were differentially expressed between the two groups at the 0.01 level of significance. We discovered that BCL2 gene and protein expression were significantly higher in H460 cells compared with SW480 and Flo-1 cells (10.60-fold higher gene expression; P < 0.0001). Inhibition of BCL2 expression and activity, using siRNA and the small molecule inhibitor HA14-1 respectively, restored sensitivity to Poly E and induced BCL2-related apoptosis by decreasing mitochondrial membrane potential and inducing PARP cleavage. Our results suggest that increased BCL2 expression may contribute to H460 resistance to the growth inhibitory effects of Poly E. If validated in additional laboratory and clinical models, BCL2 could ultimately be used as a marker of Poly E resistance.