Clinical Outcomes Following Recurrence of Intestinal Metaplasia After Successful Treatment of Barrett's Esophagus With Radiofrequency Ablation.

OBJECTIVES: Radiofrequency ablation (RFA) is an effective treatment for Barrett's esophagus (BE). However, recurrence of BE after initially successful RFA is common, and outcomes following recurrence not well described. We report the outcomes associated with recurrence following initially successful RFA. METHODS: We performed a retrospective cohort study of 306 patients treated with RFA for dysplastic BE. Complete eradication of intestinal metaplasia (CE-IM) was defined as complete histological and endoscopic remission of IM. Recurrence was defined as any presence of IM or dysplasia in the tubular esophagus or dysplasia in the gastric cardia subsequent to CE-IM. We examined rates and risk factors for recurrence, dysplastic recurrence, and invasive adenocarcinoma after CE-IM. We also describe the clinical course of patients following recurrence. RESULTS: Of the 306 eligible patients undergoing RFA, 218 achieved CE-IM and also had subsequent surveillance endoscopy. Of these, 52 (24%) experienced recurrence of IM or Barrett's-associated neoplasia over 540.6 person-years (incidence rate 9.6%/year). Thirty (58%) of these achieved second CE-IM; 4 (1.8% of total, 7.7% of recurrences) ultimately progressed to invasive adenocarcinoma (incidence rate 0.65%/year). Longer Prague M was a strong risk factor for invasive adenocarcinoma (rate ratio of 1.34/cm). Most dysplastic recurrences were in the cardia, and the majority were not visible but detected on random biopsies. CONCLUSIONS: Most patients with recurrent BE after initially successful RFA achieve second CE-IM; however, 1.8% progressed to invasive adenocarcinoma. Longer Prague M was predictive of invasive adenocarcinoma. Four-quadrant random biopsy of the cardia is advisable during surveillance endoscopy after CE-IM.

Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.

BACKGROUND: Radiofrequency ablation (RFA) is a safe and effective treatment for Barrett's esophagus (BE) that results in high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence is common after CEIM, and surveillance endoscopy is recommended. Neither the anatomic location nor the endoscopic appearance of these recurrences is well-described. OBJECTIVE: Describe the location of histologic specimens positive for recurrence after CEIM and the testing performance of endoscopic findings for the histopathologic detection of recurrence. DESIGN: Retrospective cohort. SETTING: Single referral center. PATIENTS: A total of 198 patients with BE with at least 2 surveillance endoscopies after CEIM. INTERVENTIONS: RFA, EMR, surveillance endoscopy. MAIN OUTCOME MEASUREMENTS: The anatomic location and histologic grade of recurrence. RESULTS: In a mean 3.0 years of follow-up, 32 (16.2%; 95% confidence interval [CI], 11.0%-22.0%) patients had recurrence of disease, 5 (2.5%; 95% CI, 0.3%-4.7%) of whom progressed beyond their worst before-treatment histology. Recurrence was most common at or near the gastroesophageal junction (GEJ). Recurrence>1 cm proximal to the GEJ always was accompanied by endoscopic findings, and random biopsies in these areas detected no additional cases. The sensitivity of any esophageal sign under high-definition white light or narrow-band imaging for recurrence was 59.4% (42.4%, 76.4%), and the specificity was 80.6% (77.2%, 84.0%). LIMITATIONS: Single-center study. CONCLUSION: Recurrent intestinal metaplasia often is not visible to the endoscopist and is most common near the GEJ. Random biopsies>1 cm above the GEJ had no yield for recurrence. In addition to biopsy of prior EMR sites and of suspicious lesions, random biopsies oversampling the GEJ are recommended.

Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus.

BACKGROUND & AIMS: The goal of radiofrequency ablation (RFA) for patients with Barrett's esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely. METHODS: We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia, total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation. RESULTS: CEIM was achieved in 80% of patients, and complete eradication of dysplasia was achieved in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%; P = .045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm; P = .03), had incomplete healing between treatment sessions (45% vs 15%; P = 0.004), and underwent more treatment sessions (4 vs 3; P = .007). Incomplete healing was associated independently with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), postprocedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients who developed strictures were more likely to use nonsteroidal anti-inflammatory drugs than those without strictures (70% vs 45%; P = .04), have undergone antireflux surgery (15% vs 3%; P = .04), or had erosive esophagitis (35% vs 12%; P = .01). CONCLUSIONS: RFA is highly effective and safe for treatment of BE with dysplasia or early stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. Nonsteroidal anti-inflammatory drug use, prior antireflux surgery, and a history of erosive esophagitis predicted stricture formation.

Intestinal metaplasia recurs infrequently in patients successfully treated for Barrett's esophagus with radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA. METHODS: We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence. RESULTS: Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54-1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55-1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence. CONCLUSIONS: In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ≈ 5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.

Focal endoscopic mucosal resection before radiofrequency ablation is equally effective and safe compared with radiofrequency ablation alone for the eradication of Barrett's esophagus with advanced neoplasia.

BACKGROUND: EMR is commonly performed before radiofrequency ablation (RFA) for nodular dysplastic Barrett's esophagus (BE). OBJECTIVE: To determine the efficacy and safety of EMR before RFA for nodular BE with advanced neoplasia (high-grade dysplasia [HGD] or intramucosal carcinoma [IMC]). DESIGN: Retrospective study. SETTING: University of North Carolina Hospitals, from 2006 to 2011. PATIENTS: 169 patients with BE with advanced neoplasia: 65 patients treated with EMR and RFA for nodular disease and 104 patients treated with RFA alone for nonnodular disease. INTERVENTIONS: EMR, RFA. MAIN OUTCOME MEASUREMENTS: Efficacy (complete eradication of dysplasia, complete eradication of intestinal metaplasia, total treatment sessions, RFA treatment sessions), safety (stricture formation, bleeding, and hospitalization). RESULTS: EMR followed by RFA achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia in 94.0% and 88.0% of patients, respectively, compared with 82.7% and 77.6% of patients, respectively, in the RFA-only group (P = .06 and P = .13, respectively). The complication rates between the 2 groups were similar (7.7% vs 9.6%, P = .79). Strictures occurred in 4.6% of patients in the EMR-before-RFA group. compared with 7.7% of patients in the RFA-only group (P = .53). LIMITATIONS: Retrospective study at a tertiary-care referral center. CONCLUSION: In patients treated with EMR before RFA for nodular BE with HGD or IMC, no differences in efficacy and safety outcomes were observed compared with RFA alone for nonnodular BE with HGD or IMC. EMR followed by RFA is safe and effective for patients with nodular BE and advanced neoplasia.

Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men.

BACKGROUND: Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence. METHODS: A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2. RESULTS: SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r(2) = 0.58). CONCLUSIONS: More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence. CLINICAL TRIALS REGISTRATION: NCT00775294.

Gastroesophageal reflux disease as an etiology of sleep disturbance in subjects with insomnia and minimal reflux symptoms: a pilot study of prevalence and response to therapy.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a well-recognized cause of impaired sleep in patients with frequent GERD symptoms, as well as those with sleep apnea. GERD's role in sleep disturbance of minimally symptomatic patients with poor sleep quality is less clear. AIM: We aimed to define the prevalence of GERD-related sleep disturbance in minimally-symptomatic subjects with demonstrated insomnia, and to assess the changes in sleep efficiency in these subjects after vigorous acid suppression. METHODS: We recruited subjects aged 18-75 years reporting at least 6 months of insomnia, and sleep difficulty at least three nights per week. Subjects with a BMI > 30, a history of snoring or ongoing use of proton pump inhibitor or H2 receptor antagonist were excluded. Subjects underwent concurrent sleep study with dual channel 24-h pH study. Sleep efficiency, defined as the percentage of time after sleep initiation that the subject actually slept, and spontaneous arousal index, defined as the number of arousals per hour, were calculated. Those with a sleep study demonstrating poor sleep quality (sleep efficiency of < 83%, and > 10 arousals/h for those aged < 45, and > 15 for those who were 45 or older) and no obstructive sleep apnea were treated with rabeprazole 20 mg PO BID x 14 days. After 14 days, the subjects underwent repeat sleep study with pH monitoring. The GERD Symptom Assessment Scale (GSAS), the Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) were administered to subjects at study inception and after 2 weeks of therapy. RESULTS: Twenty-four subjects reporting insomnia were enrolled, and 20 met criteria for disordered sleep and no OSA. Seventeen completed both the first and second studies, and 16 were adequate for analysis. Baseline GSAS demonstrated trivial or no reflux symptoms in the cohort (no subject scored > 8 out of 45 on GSAS, corresponding to a median rating of reflux symptoms of "not at all"). Four of 16 subjects (25%) demonstrated abnormal pH studies at baseline. All four had normalization of acid exposures on PPI. After 2 weeks of treatment, three of these four subjects had normalization of sleep efficiency, compared to 4 of 12 of the subjects with normal Johnson-DeMeester scores. Repeated measures analysis showed significant improvement in spontaneous arousal index between the first and second study for the whole group (P < 0.0035). Pre- and post-therapy ESS and FOSQ scores were not significantly different. CONCLUSIONS: Despite the lack of GERD symptoms, a significant minority of subjects with sleep disturbance have abnormal acid exposures. These preliminary data suggest that aggressive treatment of GERD in such patients may result in improvement in sleep efficiency.