Anthony Infantolino

Radiofrequency Ablation in Barrett's Esophagus with Dysplasia

BACKGROUND Barretts esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barretts esophagus and decrease the rate of neoplastic progression. METHODS In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barretts esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barretts esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS In patients with dysplastic Barretts esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

BACKGROUND & AIMS Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barretts esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy.

BACKGROUND Capsule endoscopy (CE) of the small bowel has become a standard diagnostic tool, but there have been concerns regarding the risk of capsule retention in certain high-risk groups. The Agile patency system, an ingestible and dissolvable capsule with an external scanner, was developed to allow physicians to perform CE with greater confidence that the capsule will be safely excreted in patients at risk for capsule retention. OBJECTIVE Our purpose was to assess the ability of the device to help physicians identify which patients with known strictures may safely undergo CE. DESIGN Patients with known strictures ingested the new patency capsule and underwent periodic scanning until it was excreted. The intestinal tract was considered to be sufficiently patent if the capsule was excreted intact or if the capsule was not detected by the scanner at 30 hours after ingestion. If patency was established, then standard CE was performed. SETTING International multicenter study. PATIENTS A total of 106 patients with known strictures. INTERVENTION Agile patency system. MAIN OUTCOME MEASUREMENTS Performance and safety of Agile patency system. RESULTS A total of 106 patients ingested the patency capsule. Fifty-nine (56%) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41%). There were 3 severe adverse events. CONCLUSIONS These results suggest that the Agile patency system is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

A survey of oesophageal cancer: pathology, stage and clinical presentation

Background  Oesophageal adenocarcinoma is the sixth leading cause of cancer‐related mortality worldwide. Previously, oesophageal cancer was mainly squamous cell, presenting late with dysphagia and weight loss.

Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

A validation study of 3 grading systems to evaluate small-bowel cleansing for wireless capsule endoscopy : a quantitative index, a qualitative evaluation, and an overall adequacy assessment

BACKGROUND Capsule endoscopy (CE) is a powerful tool for evaluating the small bowel. Assessment of small-bowel cleansing for CE is an essential quality measure. OBJECTIVE Our purpose was to validate 3 new scales that grade small-bowel cleansing for CE. DESIGN Prospective, randomized, single-center study. SETTING Tertiary university hospital. INTERVENTION Five experienced capsule endoscopists read 40 CEs twice, separated by 1 month, to grade small-bowel cleansing on 3 scales-quantitative index (QI; 0-10), qualitative evaluation (QE; poor, fair, good, excellent), and overall adequacy assessment (OAA; inadequate, adequate). The QI and QE evaluated both the entire and distal small bowel. Investigators received no prior training in these scales. MAIN OUTCOME MEASUREMENTS Intraclass correlation coefficients to assess intraobserver (test-retest) and interobserver reliability. PATIENTS Forty patients who underwent 1 CE between June 2005 and May 2006 and who satisfied entry criteria. RESULTS Intraobserver reliability was moderate to substantial for the QI (0.60-0.66), moderate for the OAA (0.56), and fair to moderate for the QE (0.37-0.47). Interobserver scores were lower: QI and OAA moderate (0.47-0.52, 0.41, respectively) and slight to fair for the QE (0.20-0.24). QI scores for the entire and distal small bowel were highly correlated for each reader (0.57-0.87), and distal small-bowel scores were lower by 1.3 points, indicating poorer cleansing (P = .001). A dichotomized QE of excellent/good versus fair/poor had moderate to substantial intraobserver and interobserver reliability (0.58-0.66, 0.41-0.49, respectively). There was a strong and highly significant association among all 3 scales (P < .001 between QI and both QE and OAA). CONCLUSION We have described and validated 3 scales for grading small-bowel cleansing for CE. An evaluation of small-bowel cleansing should be routinely incorporated into the CE report.

Original ResearchFull Report: Clinical—Alimentary TractIncidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Quality of Life Following Radiofrequency Ablation of Dysplastic Barrett’s Esophagus

BACKGROUND AND STUDY AIMS The impact of the diagnosis and treatment of dysplastic Barretts esophagus on quality of life (QoL) is poorly understood. This study assessed the influence of dysplastic Barretts esophagus on QoL and evaluated whether endoscopic treatment of dysplastic Barretts esophagus with radiofrequency ablation (RFA) improves QoL. PATIENTS AND METHODS We analyzed changes in QoL in the AIM Dysplasia Trial, a multicenter study of patients with dysplastic Barretts esophagus who were randomly allocated to RFA therapy or a sham intervention. We developed a 10-item questionnaire to assess the influence of dysplastic Barretts esophagus on QoL. The questionnaire was completed by patients at baseline and 12 months. RESULTS 127 patients were randomized to RFA (n = 84) or sham (n = 43). At baseline, most patients reported worry about esophageal cancer (71 % RFA, 85 % sham) and esophagectomy (61 % RFA, 68 % sham). Patients also reported depression, impaired QoL, worry, stress, and dissatisfaction with the condition of their esophagus. Of those randomized, 117 patients completed the study to the 12-month end point. Compared with the sham group, patients treated with RFA had significantly less worry about esophageal cancer ( P=0.003) and esophagectomy ( P =0.009). They also had significantly reduced depression ( P=0.02), general worry about the condition of their esophagus ( P≤0.001), impact on daily QoL ( P=0.009), stress ( P=0.03), dissatisfaction with the condition of their esophagus ( P≤0.001), and impact on work and family life ( P=0.02). CONCLUSIONS Inclusion in the treatment group of this randomized, sham-controlled trial of RFA was associated with improvement in disease-specific health-related quality of life. This improvement appears secondary to a perceived decrease in the risk of cancer.

Prognostic significance of high-grade dysplasia in colorectal adenomas.

Aim  Colonoscopy to detect and remove polyps has contributed to a reduction in colorectal carcinoma. Three‐year follow up is recommended for patients considered to be at high risk (at least three adenomas, adenoma ≥ 1 cm, villous or high‐grade features). Our study focused on patients diagnosed with high‐grade dysplasia with regard to initial management and follow up.

Adenosquamous carcinoma in Barrett's esophagus presenting as pseudoachalasia

A case of pseudoachalasia resulting from adenosquamous carcinoma arising from the mucous epithelium of a Barretts esophagus is presented. This case represents an unusual combination of Barretts esophagus giving rise to an esophageal carcinoma with squamous as well as glandular features, rather than the usual adenocarcinoma and pseudoachalasia.