Longitudinal outcomes of radiofrequency ablation versus surveillance endoscopy for Barrett's esophagus with low-grade dysplasia.

Radiofrequency ablation of Barrett's esophagus with low-grade dysplasia is recommended in recent American College of Gastroenterology guidelines, with endoscopic surveillance considered a reasonable alternative. Few studies have directly compared outcomes of radiofrequency ablation to surveillance and those that have are limited by short duration of follow-up. This study aims to compare the long-term effectiveness of radiofrequency ablation versus endoscopic surveillance in a large, longitudinal cohort of patients with Barrett's esophagus, and low-grade dysplasia.We conducted a retrospective analysis of patients with confirmed low-grade dysplasia at a single academic medical center from 1991 to 2014. Patients progressing to high-grade dysplasia or esophageal adenocarcinoma within one year of index LGD endoscopy were defined as missed dysplasia and excluded. Risk factors for progression were assessed via Cox proportional hazards model. Comparison of progression risk was conducted using a Kaplan-Meier analysis. Subset analyses were conducted to examine the effect of reintroducing early progressors and excluding patients diagnosed prior to the advent of ablative therapy. Of 173 total patients, 79 (45.7%) underwent radiofrequency ablation while 94 (54.3%) were untreated, with median follow up of 90 months. Seven (8.9%) patients progressed to high-grade dysplasia or adenocarcinoma despite ablation, compared with 14 (14.9%) undergoing surveillance (P = 0.44). This effect was preserved when patients diagnosed prior to the introduction of radiofrequency ablation were excluded (8.9% vs 13%, P = 0.68). Reintroduction of patients progressing within the first year of follow-up resulted in a trend toward significance for ablation versus surveillance (11.1% vs 23.8%, P = 0.053).In conclusion, progression to high-grade dysplasia or adenocarcinoma was not significantly reduced in the radiofrequency ablation cohort when compared to surveillance. Despite recent studies suggesting the superiority of radiofrequency ablation in reducing progression, diligent endoscopic surveillance may provide similar long-term outcomes.

Arsenic mediates cell proliferation and gene expression in the bladder epithelium: association with activating protein-1 transactivation.

Although the mechanism of action has not yet been defined, epidemiological studies have demonstrated an association between elevated arsenic levels in drinking water and the incidence of urinary bladder transitional cell carcinomas. In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of exposure. This was accompanied by the accumulation of inorganic trivalent arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. AP-1 transactivation by arsenic also occurred in bladders of transgenic mice containing an AP-1 luciferase reporter. Consistent with these in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding in a human bladder epithelial cell line. Gene expression studies using RNase protection assays, reverse transcription-PCR, and cDNA microarrays indicated that arsenite alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells likely contributes to its ability to cause cancer.

Disappearance of nitrite from the rat stomach: contribution of emptying and other factors.

To help understand how intragastric nitrosation forms N-nitroso compounds, nitriet disappearance from the rat stomach was measured after food containing nitrite was given. In preliminary experiments, nitrite disappearance from buffered aqueous solutions became more rapid as the pH was lowered from 5 to 1 and, at a given pH, was more rapid in a slurry of commercial rat food. The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents. When starved rats were given 5 g food with 1.82 mg nANO3/g, nitrate was not reduced to nitrite in the stomach. Five g food containing 154 mug NaNO2/g was administered similarly, and the total stomach (T) and glandular and nonglandular parts (G and NG) were analyzed after 1.5 hours. Weight and nitrite concentration of the stomach contents dropped linearly and the amount of nitrite dropped exponentially (with a half-life of 1.4 hr). Mean nitrite concentration in G was less than half that in NG. From similar experiments with phenol red, emptying accounted for 60% of nitrite loss from T. In G, nitrite concentration was reduced about 3 times due to dilution and 3 times due to other causes. Conditions in G, e.g., nitrite concentration, pH, and empyting time, were discussed in relation to carcinogenesis experiments with nitrite plus amines and amides.