Real-World Safety and Efficacy of Fluid-Filled Dual Intragastric Balloon for Weight Loss.

BACKGROUND & AIMS: Reshape Duo is a saline-filled dual, integrated intragastric balloon (IGB) approved by the Food and Drug Administration for weight loss in patients with obesity. In a prospective, randomized trial, obese patients who received the balloon had significantly greater percent excess weight loss (%EWL) compared with patients treated with diet and exercise alone. However, there are limited data on the real-world efficacy of the Reshape balloon. METHODS: We performed a retrospective study of data collected from 2 academic centers and 5 private practices in which all patients paid for the IGB and follow-up visits out of pocket. The IGB was removed after 6 months. We collected data (demographic, medical, and laboratory) from 202 adults (mean age 47.8 ± 10.8 years; 83% female) with a baseline mean body mass index of 36.8 + 8.4 kg/m2 who had IGB insertion for weight loss therapy, along with counselling on lifestyle modifications focused on diet and exercise. Primary outcomes were percent total body weight loss (%TBWL) and %EWL at 1, 3, 6, 9, and 12 months after the procedure. RESULTS: Mean %TBWL at 1, 3, 6, 9 and 12 months was 4.8 ± 2.4%, 8.8 ± 4.3%, 11.4 ± 6.7%, 13.3 ± 7.8%, and 14.7 ± 11.8%, respectively. Data were available from 101 patients at 6 months and 12 patients at 12 months; 60.4% of patients achieved more than 10% TBWL and 55.4% had more than 25% EWL. Seventeen patients (8.4%) had esophageal tears during balloon insertion, with no intervention required. Thirteen patients (6.4%) had their IGB removed before the end of the 6-month treatment period. Nausea, vomiting, and abdominal pain were the most common adverse effects, occurring in 149 (73.8%), 99 (49%), and 51 (25.2%) patients. In one patient, the IGB migrated distally leading to small intestinal obstruction requiring surgical removal. CONCLUSION: In a retrospective analysis of real-world patients who received the Reshape Duo IGB, we found it to be a safe and efficacious endoscopic method for producing weight loss, with most patients achieving greater than 10% TBWL at 6 months.

Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial.

BACKGROUND & AIMS: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.

CA11-19: a tumor marker for the detection of colorectal cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) remains the second most frequent cause of cancer deaths in the United States. Blood tests using tumor-related antigens aid in diagnosing CRC. However, higher sensitivity and specificity are needed before an acceptable tumor antigen blood test for CRC is clinically useful. This study describes the diagnostic accuracy of an enzyme-linked immunosorbent assay for the CA11-19 serologic tumor antigen for the detection of CRC. METHODS: Serum specimens were obtained from 522 colonoscopy-confirmed subjects in institutional review board-approved studies. Specimens were blind coded. CA11-19 levels were determined by using enzyme-linked immunosorbent assay analysis. The results were tabulated for categories of normal, hyperplastic polyps, benign GI, adenomatous polyps, and CRC based on their final diagnosis. RESULTS: When a cutoff of 6.4 units/mL for normal is used, the CA11-19 level was elevated in 128 of 131 of CRC subjects, for an observed sensitivity of 98% (95% confidence interval, 93.1%-99.5%). Normal levels were found in 87% of normal subjects (90/103) and 83% of those with benign GI diseases (185/223). When combined, this yields an observed specificity of 84% (95% confidence interval, 80.0%-87.9%). CONCLUSION: CA11-19 is a serologic tumor marker for the diagnosis of CRC with a sensitivity of 98% and specificity of 84%. This high sensitivity means that this test will detect 43 of 44 cases of CRC presented. For those older than 50 years of age, it has a positive predictive value of 3.6% and a negative predictive value of 99.98%. Additional prospective studies are needed to further clarify the use of CA11-19 as an aid in the diagnosis of CRC.

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 Barrett's 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.

Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett's esophagus: results from the U.S. RFA Registry.

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. PATIENTS: Patients enrolled with BE. INTERVENTIONS: RFA. MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. RESULTS: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. LIMITATIONS: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. CONCLUSION: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race.

Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study.

Numerous histological mimics of high-grade dysplasia in Barrett's esophagus predispose to overdiagnosis and potential serious mismanagement, including unnecessary esophagectomy. This study investigates the prevalence and sources of this problem. Biopsies from 485 patients diagnosed with Barrett's high-grade dysplasia were screened for a multi-institutional, international Barrett's endoscopic ablation trial. Screening included review of the original diagnostic slides and an additional protocol endoscopy with an extensive biopsy sampling. Observer variability by the study pathologists was assessed through two blinded diagnostic rounds on 437 biopsies from 26 random study endoscopies. Study diagnostic reassessments revealed significantly lower rates of high-grade dysplasia. Only 248 patients (51%) were confirmed to have high-grade dysplasia. The remaining patients had inflamed gastric cardia without Barrett's (n=18; 7%), Barrett's without dysplasia (n=35; 15%), indefinite change (n=61; 26%), low-grade dysplasia (n=79; 33%), adenocarcinoma (n=43; 18%), and other (n=1; <1%), yielding an alarming total of 194 or 40% of patients who were overdiagnosed with Barrett's high-grade dysplasia. Study pathologists achieved a high-level agreement (90% three-way inter-observer agreement per biopsy, Kappa value 0.77) for high-grade dysplasia. Confounding factors promoting overdiagnosis included Barrett's inflammatory atypia (n=182), atypia limited to the basal metaplastic glands (n=147), imprecise criteria for low grade neoplasia (n=102), tangential sectioning artifact (n=59), and reactive gastric cardiac mucosa (n=38). A total of 194 patients (40%) were overdiagnosed with Barrett's high-grade dysplasia, as affirmed by the extensive screening process and high-level study pathologist agreement. The multiple diagnostic pitfalls uncovered should help raise pathologists' awareness of this problem and improve diagnostic accuracy.

Durability and predictors of successful radiofrequency ablation for Barrett's esophagus.

BACKGROUND & AIMS: After radiofrequency ablation (RFA), patients may experience recurrence of Barrett's esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication have been poorly described. METHODS: We used the US RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of intestinal metaplasia (IM). We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. RESULTS: Among 5521 patients, 3728 had biopsies 12 months or more after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. The average follow-up period was 2.4 years after CEIM. IM recurred in 334 (20%) and was nondysplastic or indefinite for dysplasia in 86% (287 of 334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared with patients without recurrence, patients with recurrence were more likely, based on bivariate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, the likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. CONCLUSIONS: BE recurred in 20% of patients followed up for an average of 2.4 years after CEIM. Most recurrences were short segments and were nondysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.

Prior fundoplication does not improve safety or efficacy outcomes of radiofrequency ablation: results from the U.S. RFA Registry.

BACKGROUND: Ongoing gastroesophageal reflux may impair healing and re-epithelialization after radiofrequency ablation (RFA) of Barrett's esophagus (BE). Because prior fundoplication may improve reflux control, our aim was to assess the relationship between prior fundoplication and the safety/efficacy of RFA. METHODS: We assessed the U.S. RFA Registry, a nationwide registry of BE patients receiving RFA at 148 institutions, to compare the safety and efficacy of ablation between those with prior fundoplication and those with medical management (proton pump inhibition). RESULTS: Among 5,537 patients receiving RFA, 301 (5.4 %) had prior fundoplication. Of fundoplication subjects, 1.0 % developed stricture and 1.0 % were hospitalized after RFA. Rates of stricture, bleeding, and hospitalization were not statistically different (p = ns) between patients with and without prior fundoplication. Complete eradication of intestinal metaplasia and complete eradication of dysplasia were achieved in 71 % and 87 % of fundoplication patients, and 73 % and 87 % of patients without fundoplication, respectively (p = ns for both). Patients with prior fundoplication needed similar numbers of RFA sessions for eradication compared with those without fundoplication. CONCLUSIONS: Radiofrequency ablation, with or without prior fundoplication, is safe and effective in eradicating BE. Prior fundoplication was associated with similar adverse event and efficacy rates when compared with medical management.

The effect of reactive atypia/inflammation on the laser-induced fluorescence diagnosis of non-dysplastic Barrett's esophagus.

BACKGROUND AND OBJECTIVES: Differential Normalized Fluorescence (DNF) technique has been used to distinguish high-grade dysplasia from non-dysplastic Barrett's esophagus. This technology may assist gastroenterologists in targeting biopsies, reducing the number of biopsies using the standard protocol. In the presence of reactive atypia/inflammation, it becomes difficult for the pathologist to differentiate non-dysplastic Barrett's esophagus from Barrett's esophagus with low-grade dysplasia. Before DNF technique may be used to guide target biopsies, it is critical to know whether reactive atypia/inflammation in non-dysplastic Barrett's may result in false positives. This study was conducted to determine whether DNF technique is adversely affected by the presence of reactive atypia/inflammation in non-dysplastic Barrett's esophagus resulting in false positives. STUDY DESIGN/MATERIALS AND METHODS: Four hundred ten-nanometer laser light was used to induce autofluorescence of Barrett's mucosa in 49 patients. The clinical study included 37 males and 12 females. This was a blinded retrospective data analysis study. A total of 303 spectra were collected and matched to non-dysplastic Barrett's biopsy results. One hundred seventy-five spectra were collected from areas with a pathology of non-dysplastic Barrett's esophagus with reactive atypia/inflammation. One hundred twenty-eight spectra were collected from areas with non-dysplastic Barrett's esophagus without reactive changes/inflammation. The spectra were analyzed using the DNF Index at 480 nm and classified as positive or negative using the threshold of -0.75 × 10(-3). RESULTS: Using DNF technique, 92.6% of non-dysplastic samples with reactive atypia/inflammation were classified correctly (162/175). 92.2% of non-dysplastic samples without reactive atypia/inflammation were classified correctly (118/128). Comparing the ratios of false positives among the two sample groups, there was not a statistically significant difference between the two groups. CONCLUSION: Using DNF technique for classification of non-dysplastic Barrett's mucosa does not result in false-positive readings due to reactive atypia/inflammation. Target biopsies guided by DNF technique may drastically reduce the number of pinch biopsies using the standard biopsy protocol.

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 Barrett's 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.

Detection of dysplasia in Barrett's esophagus with in vivo depth-resolved nuclear morphology measurements.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) show increased risk of developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to detect neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of patients with BE. METHODS: Consecutive patients undergoing routine surveillance upper endoscopy for BE were recruited at 2 endoscopy centers. A novel, endoscope-compatible a/LCI system measured the mean diameter and refractive index of cell nuclei in esophageal epithelium at 172 biopsy sites in 46 patients. At each site, an a/LCI measurement was correlated with a concurrent endoscopic biopsy specimen. Each biopsy specimen was assessed histologically and classified as normal, nondysplastic BE, indeterminate for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). The a/LCI data from multiple depths were analyzed to evaluate its ability to differentiate dysplastic from nondysplastic tissue. RESULTS: Pathology characterized 5 of the scanned sites as HGD, 8 as LGD, 75 as nondysplastic BE, 70 as normal tissue types, and 14 as indeterminate for dysplasia. The a/LCI nuclear size measurements separated dysplastic from nondysplastic tissue at a statistically significant (P < .001) level for the tissue segment 200 to 300 µm beneath the surface with an accuracy of 86% (147/172). A receiver operator characteristic analysis indicated an area under the curve of 0.91, and an optimized decision point gave 100% (13/13) sensitivity and 84% (134/159) specificity. CONCLUSIONS: These preliminary data suggest a/LCI is accurate in detecting dysplasia in vivo in patients with BE.

Biopsy depth after radiofrequency ablation of dysplastic Barrett's esophagus.

BACKGROUND: After endoscopic radiofrequency ablation (RFA) of dysplastic Barrett's esophagus (BE), endoscopic biopsy samples are obtained to assess response to therapy. Whether these biopsies are of adequate depth to assess efficacy is unknown. OBJECTIVE: To compare the depth of endoscopic biopsy samples after RFA with those of untreated controls and to determine the prevalence of subepithelial structures in endoscopic biopsy fragments. DESIGN: Secondary analysis of the AIM Dysplasia Trial, a multicenter, randomized, sham-controlled study. SETTING: Nineteen treatment centers. PATIENTS: Subjects with dysplastic BE, either status post RFA or ablation naïve (sham). MAIN OUTCOME MEASUREMENTS: The proportion of biopsy samples demonstrating subepithelial structures, stratified by tissue type (columnar vs squamous) in sham- and RFA-treated subjects. RESULTS: A total of 5648 biopsy fragments were analyzed from 113 subjects (78 RFA, 35 sham; mean 50.0 fragments per subject). Most fragments (4653, 82.4%) contained subepithelium. Squamous biopsy samples from RFA and sham subjects demonstrated subepithelium at similar rates (78.4% vs 79.1%, respectively, P = not significant [NS]). Columnar biopsy samples from RFA and sham subjects also included subepithelium at similar rates (99.0% vs 98.8%, respectively, P = NS). Regardless of treatment assignment, more columnar than squamous biopsy samples demonstrated subepithelium (98.8% vs 78.5%, P < .001). LIMITATIONS: Biopsy samples were not individually mounted. CONCLUSIONS: In both squamous and columnar tissue, endoscopic biopsy samples after RFA were as likely to demonstrate subepithelium as untreated controls. Almost 80% of all biopsy samples were adequate to evaluate for subsquamous intestinal metaplasia. The primary determinant of biopsy depth is the type of epithelium that underwent biopsy, with squamous less likely to yield subepithelium than columnar. Biopsy samples after RFA appear to be of adequate depth to assess response to therapy. (Clinical trial registration number NCT00282672.).

Does ablative therapy for Barrett esophagus affect the depth of subsequent esophageal biopsy as compared with controls?

BACKGROUND: Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are associated with high rates of complete eradication of Barrett esophagus (BE). However, if ablation were to induce fibrosis in the regenerated squamous epithelium, then postablation biopsies may not penetrate deeply enough to detect subsquamous intestinal metaplasia (SSIM) and, therefore, complete response rates could be over-estimated. GOALS: To assess the depth of esophageal biopsies from the squamous epithelium of ablation-naive controls and from the neosquamous epithelium of post-PDT and post-RFA patients to determine if prior ablation results in a reduced proportion of biopsies containing lamina propria (LP) as compared with controls. STUDY: Review of archived esophageal specimens from a prospective multicenter cohort study (post-RFA) and 2 retrospective consecutive case series (ablation-naive controls, post-PDT). SETTING: Eight US centers and 1 US gastrointestinal pathology laboratory. PATIENTS: Ablation-naive controls with GERD, dyspepsia, and/or BE. Post-PDT and post-RFA BE patients with biopsies more than 6 months after achieving complete eradication of BE. INTERVENTIONS: Review of endoscopic biopsies from ablation-naive controls, post-PDT patients, and post-RFA patients. MAIN OUTCOME MEASUREMENTS: One GI pathology lab processed all tissue and slides. One expert GI pathologist, blinded to cohort, graded the depth of each esophageal specimen as: partial epithelium, full epithelium, LP, muscularis mucosae, or submucosa. Each specimen was also evaluated for SSIM. RESULTS: There were 82 patients [ablation-naive (12), post-PDT (10), post-RFA (60)] with 899 biopsy specimens. The proportion of specimens containing "LP or deeper" was similar between groups: ablation-naive (88%), post-PDT (88%), post-RFA (91%) (P>0.05). No SSIM was detected in any group. CONCLUSIONS: There is no difference in esophageal biopsy depth between ablation-naive squamous epithelium and post-PDT/post-RFA neo-squamous epithelium, thus refuting the concern of ablation-induced mucosal resistance to procurement of adequate biopsy specimens. Most biopsies (88% to 91%) from both ablation cohorts were deep enough to detect SSIM, in that they included "LP or deeper."

The case for endoscopic treatment of non-dysplastic and low-grade dysplastic Barrett's esophagus.

Non-dysplastic mucosa (ND-) in Barrett's esophagus (BE) shows clonal molecular aberrations, loss of cell cycle control, and other features of "neoplasia." These changes occur prior to morphologic expression of neoplasia (dysplasia). Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses. Early "crypt dysplasia" is difficult to detect, and is often missed in routine biopsy specimens. Some studies show substantial progression rates of low-grade dysplasia (LGD), and crypt dysplasia, to esophageal adenocarcinoma (EAC). Dysplasia, even when fully developed, may, in certain circumstances, be difficult to differentiate from non-dysplastic (regenerating) BE. Radiofrequency ablation (RFA) is a safe and effective method for removing mucosa at risk of cancer. Given the difficulties of dysplasia assessment in mucosal biopsies, and the molecular characteristics of ND-BE, this technique should be considered for treatment of all BE patients, including those with ND or LGD. Post-ablation neo-squamous epithelium reveals no molecular abnormalities, and is biologically stable. Given that prospective randomized controlled trials of ablative therapy for ND-BE aiming at reducing EAC incidence and mortality are unlikely to be completed in the near future, endoscopic ablation is a valid management option. The success of RFA in achieving safe, uniform, reliable, and predictable elimination of BE allows surgeons to combine fundoplication with RFA. Currently, there is no type of treatment for dysplastic or non-dysplastic BE that achieves a complete response in 100% of patients, eliminates all risk of developing cancer, results in zero adverse events, is less expensive in terms of absolute costs than surveillance, is durable for 20+ years, or eliminates the need for surveillance. Regardless, RFA shows established safety, efficacy, durability, and cost-effective profiles that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE.

Evaluating screening age for colonoscopy: a quality assurance assessment.

OBJECTIVE: To evaluate colonoscopies in patients aged 40 to 49 and 50 to 59 years from multiple endoscopy surgery centers serving a wide geographical area. METHODS: An observational prospective multicenter quality assurance review was conducted in 49 Ambulatory Surgery Centers in 17 states with 315 gastroenterologists. Care of patients and routine of gastroenterologists continued as standard practice with patients attending for purposes of screening, surveillance, and symptoms. RESULTS: There were 1688 and 5090 consecutive qualified patients aged 40 to 49 and 50 to 59 years, respectively, receiving colonoscopies in a designated 4 week period. There was no significant difference (P=0.55) in the screening category between ages 40 to 49 (n=420) and 50 to 59 years (n=2705) in incidence of colon polyps although the older age group had more than 6 times the number of patients than the younger age group. Age group of 40 to 49-year-old males (21.5%) are at similar risk to 40 to 49-year-old females (21.1%) in development of carcinoma and adenoma polyps combined. Age group of 50 to 59-year-old males (31.3%) appear at greater risk (P<0.0001) than age 50 to 59-year-old females (18.4%) in development of carcinoma and adenoma polyps combined in the screening category. For surveillance and symptom categories significant differences (P<0.05) occurred between both age groups 40 to 49 and 50 to 59 years for males but not females in development of carcinoma and adenoma polyps combined. CONCLUSIONS: The equal risk of colon polyps in screening colonoscopies for age 40 to 49 and 50 to 59 years suggest reexamination of current recommendations for 50 years as the beginning age for screening colonoscopy. Further studies are needed to examine sex differences and cost effectiveness of screening colonoscopies beginning at age 40 years and to explore these factors as well in surveillance and symptom categories.

Withdrawal times and associated factors in colonoscopy: a quality assurance multicenter assessment.

OBJECTIVE: To evaluate the use and impact of the recommended withdrawal time of at least 6 minutes from the cecum in colonoscopy in multiple gastroenterology endoscopy ambulatory surgery centers serving a wide geographical area. METHODS: An observational prospective multicenter quality assurance review was conducted in 49 ambulatory surgery centers in 17 states with 315 gastroenterologists. There was no intervention with this quality assessment program as care of patients and the routine of gastroenterologists continued as standard practice. Multivariable analysis was applied to the database to examine factors affecting withdrawal time and polyp detection. RESULTS: There were 15,955 consecutive qualified patients receiving colonoscopies in a designated 4-week period. Gastroenterologists with average withdrawal times of 6 minutes or more in patients with no polyps were 1.8 times more likely to detect 1 or more polyps and had a significantly higher rate (P<0.0001) of polyp detection in patients with findings of polyps compared to gastroenterologists with average withdrawal times of less than 6 minutes in patients with no polyps. For patients with no pathology, the mean time of withdrawal was 6.98 (SD=4.34) minutes and for patients with pathology mean time of withdrawal was 11.27 (SD=6.71) minutes. Strongest predictors of withdrawal time of 6 minutes or more were presence of carcinoma (3.7 times more likely than those with no pathology), adenoma (2.0 times more likely than those with no pathology), and number of polyps visualized (1.7 times more likely for each polyp). CONCLUSIONS: This quality assurance assessment from standard colonoscopy practices of 315 gastroenterologists in 49 endoscopic ambulatory surgery centers serving a wide geographical area provides support for the merits of a colonoscopy withdrawal time from the cecum of 6 minutes or more to improve the detection of polyps.

Radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND: Barrett's 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 Barrett's esophagus and decrease the rate of neoplastic progression. METHODS: In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's 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 Barrett's 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 Barrett's 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.)

Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS: Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.