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ObjectiveRadiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting.DesignEndoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included.ResultsAfter ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk.ConclusionIn a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value.Netherlands trial register numberNL7039.

Introduction After endoscopic resection (ER) of neoplasia in Barrett’s esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. Methods Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. Results Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11–51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. Conclusion In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Contains fulltext : 245204.pdf (Publisher’s version ) (Open Access) AIM: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma. METHODS: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow-up. A prediction model to identify risk factors for metastases was developed and internally validated. RESULTS: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2-3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy-eight patients had metastases. The risk of metastases was increased for tumors with 2-3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10-5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37-6.10). The prediction model demonstrated a good discriminative ability (c-statistic 0.81). CONCLUSION: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice.

Summary Preliminary data show higher stricture rates after radiofrequency ablation (RFA) for early esophageal squamous neoplasia compared with Barrett's esophagus. We studied the effects of Lugol stain (LS) directly prior to RFA on stricture formation in squamous epithelium. Of 16 pigs, the distal half of the esophagus was LS, followed by circumferential RFA (single application 12 J/cm2) in the unstained and stained esophagus. Pigs were euthanized at day 0 (n = 4), 3 (n = 4), or 28 (n = 8). Histology was evaluated in four areas: blank-control (no RFA, no LS), blank-RFA (no LS), LS+RFA, and LS-control (no RFA). Stenosis severity in LS+RFA and blank-RFA at 28 days was assessed by the ratio of the mucosal diameter at the RFA area to the diameter 2 cm proximal of this zone. Histology showed submucosal edema in 50% of LS+RFA versus 0% in blank-RFA. Severity and depth of inflammation (day 3) was equal in LS+RFA and blank-RFA. Severity and depth of fibrosis (day 28) appeared more severe in LS+RFA. Consequently, stenosis was present in 100% (LS+RFA) versus 12.5% (blank-RFA). The stenosis-severity ratio was 0.40 (interquartile range 0.29–0.45) in LS+RFA versus 0.73 (interquartile range 0.64–0.78) in blank-RFA (P = 0.012). Limitations of this study were the difference in uptake of LS between pigs and humans, the difference in esophageal anatomy between pigs and humans, and between the proximal and distal esophagus within pigs. In conclusion, in the porcine squamous esophagus, stenosis rate and severity after RFA increased when preceded by LS. LS may be contributing in the altered response of squamous epithelium to RFA as compared with Barrett's esophagus.

Background and study aims: After radiofrequency ablation (RFA) of Barrett’s esophagus, it may be difficult to determine whether complete eradication of intestinal metaplasia at the neosquamocolumnar junction (neo-SCJ) in the cardia has been achieved. It is claimed that narrow band imaging (NBI) may predict the presence of intestinal metaplasia, which would enable immediate treatment. The aim of the current study was to evaluate whether inspection of the neo-SCJ with NBI after RFA results in reliable detection of intestinal metaplasia. Patients and methods: Patients with a normal-appearing neo-SCJ who were scheduled for RFA were included in the study. Two expert endoscopists obtained images from the neo-SCJ in overview (high resolution white light and NBI mode) and from four areas using NBI zoom, followed by corresponding biopsies. Four other blinded expert endoscopists evaluated the images for the presence of intestinal metaplasia and type of mucosal pattern (round, small tubular, large tubular, villous). Endpoints were sensitivity and specificity for identifying patients and areas with intestinal metaplasia. Results: From 21 patients overview images from 21 neo-SCJs and NBI zoom images from 83 neo-SCJ areas were obtained. Intestinal metaplasia was present in five overview images (24 %) and nine zoom images (11 %). Using the overview images, sensitivity and specificity for identifying patients with intestinal metaplasia were 65 % (95 % confidence interval [CI] 38 – 86) and 46 % (95 %CI 33 – 60), respectively. For individual zoom images, sensitivity was 71 % (95 %CI 54 – 85) and specificity was 37 % (95 %CI 32 – 43). Conclusions: After RFA, endoscopic inspection of the neo-SCJ with NBI in overview or zoom does not reliably predict presence or absence of intestinal metaplasia.

Radiofrequency ablation (RFA) is safe and effective for eradication of Barrett’s esophagus after endoscopic resection (ER) of neoplasia. Widespread ER, however, is likely to induce stenosis, hampering subsequent circumferential RFA. A ‘single step’ procedure with ER and circumferential RFA in the same session may avoid this problem. Two variants are possible: circumferential RFA of Barrett’s esophagus including the lesion followed by ER of the ablated lesion (‘RFA→ER’), or ER of the lesion directly followed by circumferential RFA of remaining Barrett’s esophagus including the resection wound (‘ER→RFA’). First aim was to evaluate perforation risk of ‘ER→RFA’ using increasing RFA energies. Second aim was to compare stenosis rate after ‘ER→RFA’ versus ‘RFA→ER’. In Experiment 1, 24 areas in six pigs underwent widespread ER directly followed by circumferential RFA with increasing energies (2 x 10, 2 x 12-6 x 12 J/cm(2)) in the esophagus. In Experiment 2, eight pigs each had four treatment areas randomized: ‘ER→RFA’, RFA alone, ER alone, and ‘RFA→ER’. No acute perforations occurred when ablating ER wounds. Two delayed perforations occurred: one in experiment 1, another in experiment n2 at the ‘ER→RFA’ area. The remaining seven pigs in experiment 2 showed stenosis in all ‘ER→RFA’ and ‘RFA→ER’ areas versus 5/7 RFA alone areas, and 0/7 ER alone areas. In conclusion, the ‘single step’ variant ‘ER→RFA’ is not safe in this porcine model and seems therefore not ethical to evaluate in humans at this stage. Given the high rate of stenosis after ‘RFA→ER’ and RFA alone, one might question the validity of the porcine model for this type of experiments.

Background and study aims: The Prague C&M classification for Barrett’s esophagus has found widespread acceptance but has only been validated by Barrett’s experts scoring video sequences. To date, validation has been lacking for its application in routine practice during real-time endoscopy. The aim of this study was to evaluate agreement between Barrett’s experts and community hospital endoscopists when using this classification to describe Barrett’s esophagus and hiatal hernia length during real-time endoscopy. Patients and methods: Patients underwent two consecutive endoscopies performed by different endoscopists. The study was performed in two cohorts: one cohort was seen by Barrett’s experts and the other cohort by community hospital endoscopists. Landmarks were recorded according to the Prague classification. Outcomes were interobserver agreement (assessed with intraclass correlation coefficient [ICC]), absolute agreement, and relative agreement. Results: A total of 187 patients were included, with median extent of C3M5 (IQR C1 – 7 M4 – 9) for Barrett’s esophagus and 3 cm (IQR 2 – 5) for hiatal hernia length. ICC was 0.91 (95 % confidence interval [CI] 0.88 – 0.93) for maximum length, 0.92 (95 %CI 0.90 – 0.94) for circumferential extent, and 0.59 (95 %CI 0.49 – 0.68) for hiatal hernia length. Absolute agreement within ≤ 1 cm was 74 % (95 %CI 68 – 80) for circumference, 68 % (95 %CI 62 – 75) for length, and 63 % (95 %CI 56 – 70) for hiatal hernia length. Relative agreement was 91 % for Barrett’s esophagus and 80 % for hiatal hernia length. Barrett’s experts and community hospital endoscopists showed no differences in agreement. Shorter Barrett’s segments (≤ 5 cm) had lower agreement compared with longer segments (> 5 cm). Conclusions: Agreement was good for Barrett’s esophagus and reasonable for hiatal hernia length. These findings strengthen the value of the Prague C&M classification to describe Barrett’s esophagus and hiatal hernia length. Although absolute agreement during real-time endoscopy was high, one should anticipate that Barrett’s values may vary by 1 – 2 cm between two endoscopies.

INTRODUCTION Radiofrequency ablation (RFA) is a valuable treatment option in Barrett's esophagus resulting in eradication of dysplasia and conversion of all Barrett's epithelium into normal squamous epithelium. In Barrett's esophagus, esophageal impedance monitoring is hampered by low baseline impedance values. Whether these low baselines are caused by an intrinsically low impedance of cylindrical epithelium or by the excessive reflux itself is hitherto unknown. Data on esophageal motility after RFA are scarce. Our aim was to examine the effect of RFA on esophageal motility and esophageal baseline impedance in patients with Barrett's esophagus. METHODS In 10 patients, conventional esophageal manometry and 24-h pH-impedance measurements were performed before and after RFA. The number and type of reflux episodes were assessed and baseline impedance values were measured in all recording segments. In another five patients, high-resolution manometry was performed before and after RFA. RESULTS Complete regression of all Barrett's epithelium was achieved in all 15 patients after 3 ± 1 RFA sessions. Overall, no significant motility changes were found after RFA. Patients had excessive acid exposure times before and after RFA [25 (17-42) and 16 (9-24)%, respectively]. Baseline esophageal impedance values were low, with the lowest values in the distal recording segments. RFA increased baseline impedance in all recording segments in the upright position; in the supine position, the effect just failed to reach statistically significant levels. CONCLUSION RFA did not alter esophageal motility significantly. Low esophageal baseline impedance levels in patients with Barrett's esophagus reflect, at least in part, intrinsic impedance properties of cylindrical epithelium, as baselines increased after conversion into neosquamous epithelium.

Background and study aims: Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett's esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome. Methods: We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. "Poor initial responseo" was defined as < 50 % regression of the Barrett's esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis. Results: There were 278 patients included (median Barrett's segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 - 433.2); endoscopic resection scar regeneration with Barrett's epithelium (OR 4.7; 95 %CI 1.1 - 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 - 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 - 1.4). Conclusions: Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett's epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett's esophagus for a longer time, or a narrow esophagus.

Background: EUS is often used for locoregional staging of early esophageal neoplasia. However, its value compared with that of endoscopic examination and diagnostic endoscopic resection (ER) may be questioned because diagnostic ER allows histological assessment of submucosal invasion and other risk factors for lymph node metastasis, eg, poor differentiation/lymphovascular invasion. Objective: To evaluate how often patients were excluded from endoscopic treatment of esophageal neoplasia based on EUS findings. Design: Retrospective cohort study. Setting: Tertiary care institution. Patients: Patients with early esophageal neoplasia. Interventions: EUS, diagnostic ER. Main Outcome Measurements: Number of patients excluded from endoscopic treatment based on EUS results. Results: A total of 131 patients were included (98 men, 33 women; age 66 +/- 13 years). In 105 of 131 patients (80%), EUS findings were unremarkable. In 23 of 105 patients (24%), diagnostic ER showed submucosal invasion (n = 17), deep resection margins positive for cancer (n = 2, confirmed at surgery), or poor differentiation/lymphovascular invasion (n = 6). In 26 of 131 patients (20%), EUS findings raised the suspicion of submucosal invasion and/or lymph node metastasis. In the 14 of 26 patients (54%) with abnormal EUS findings, endoscopy results were unremarkable. Diagnostic ER showed submucosal invasion in 7 of 14 (50%) patients, whereas no lymph node metastasis risk factors were found in 7 of 14 patients (50%), who subsequently underwent curative endoscopic treatment. In 12 of 26 patients (46%) with abnormal EUS, endoscopy also raised doubts on whether curative endoscopic treatment could be achieved. After diagnostic ER, no risk factors for lymph node metastasis were found in 3 of 12 patients (25%). Limitation: Retrospective study. Conclusions: This study shows that EUS has virtually no clinical impact on the workup of early esophageal neoplasia and strengthens the role of diagnostic ER as a final diagnostic step. (Gastrointest Endosc 2011;73:662-8.)

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is an important diagnostic, staging, and therapeutic tool for patients with Barrett's esophagus (BE)-associated neoplasia. We analyzed the histopathologic characteristics of specimens collected during EMR compared with biopsy specimens from patients with BE and assessed interobserver variability in pathologists' assessment of EMR and biopsy specimens. METHODS: We evaluated EMR (n = 251) and biopsy (n = 269) specimens collected from patients with BE at 2 tertiary referral centers. A detailed histologic analysis was performed for each EMR and biopsy specimen to determine the grade of dysplasia, depth of the specimen, proportion of specimen with dysplasia, and quality of samples. Interobserver agreement for both biopsy and EMR specimens (among 4 experienced pathologists) was calculated by using kappa statistics. RESULTS: Histologic analysis showed that submucosa was present in the majority of EMRs, compared with biopsy specimens (88% vs 1%, P < .0001). Almost all biopsy specimens (99%) included lamina propria. However, the muscularis mucosa was observed in only 58% of biopsy specimens. For both EMR and biopsy specimens, the highest grade of dysplasia comprised < or =25% of the total area in >50% of the specimens. Interobserver agreement on the diagnosis of dysplasia was significantly greater for EMR specimens than biopsy specimens (low-grade dysplasia, 0.33 vs 0.22, P < .001; high-grade dysplasia, 0.43 vs 0.35, P = .018). CONCLUSIONS: Submucosa can be examined in most samples collected from EMR; the distribution of neoplasia is focal within biopsy and EMR specimens. There is more interobserver agreement among pathologists in the analysis of EMR samples than biopsy specimens for the diagnosis of dysplasia

Background Several classifications of mucosal morphology have been proposed in Barrett oesophagus using narrow-band imaging (NBI). We evaluated a simplified classification in which only the regularity of mucosal and vascular patterns were evaluated. Aim To assess the inter and intraobserver agreement and the correlation with histology of a simplified NBI classification of mucosal morphology in Barrett oesophagus combining the experience of two referral centres. Methods Two hundred NBI images [57 high-grade intraepithelial neoplasia (HGIN)/early cancer (EC)] were evaluated twice by four NBI-experienced and four nonexperienced endoscopists in the field of NBI. Endoscopists assessed each image for: quality, suspicion for dysplasia, and regularity of mucosal and vascular patterns. Observer agreement was assessed using kappa statistics. Results Overall interobserver agreement for the items evaluated was 'moderate' and varied between 0.42 and 0.44. Overall intraobserver agreement was 'moderate' to 'substantial' (kappa 0.60-0.62). There were no significant differences in agreement between expert and nonexpert endoscopists. Endoscopist correctly identified 71% of the images containing HGIN/EC. Of the areas without HGIN/EC, 68% were correctly identified as not suspicious. Again, there were no significant differences between experts and nonexperts. Conclusion Our proposed, simplified classification for Barrett mucosal morphology has a moderate interobserver and a moderate to substantial intraobserver agreement. The lack of differences in agreements between expert and nonexpert endoscopists suggests a short learning curve. The disappointing rate for correctly indentifying HGIN/EC, questions, however, whether detailed inspection of Barrett oesophagus with NBI can replace histological sampling. Eur J Gastroenterol Hepatol 21: 1068-1075 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Endoscopic submucosal dissection (ESD) is technically demanding. A viscous gel for submucosal lifting might induce mechanical submucosal dissection facilitating easier and safer ESD. In 12 female pigs (median 64 kg), ESDs of simulated lesions were performed at the posterior wall and greater curvature in the gastric body (one ESD per location) with randomly assigned injection fluids: gel or control fluid (0.9 % saline with hydroxypropyl methylcellulose 3 mg/ml [7:1] and indigo carmine droplets). Additionally, 10 cc gel was injected into the submucosa at the anterior wall without ESD to assess effects of inappropriate injection. Pigs were euthanized at day 0, 3 or 28. In four additional pigs (euthanized day 3 or 28) 10 cc gel was injected into the muscularis propria (MP) after four endoscopic mucosal resections in the gastric body. Both fluid groups showed equal ESD-procedure times (28 [gel] vs. 26 min [control]) and complications. Gel-ESDs required less accessory interchanges (3.5 vs. 5.5; p = 0.01). Mechanical dissection after circumferential incision was achieved in 25 % of gel-ESDs; none in control-ESDs. The severity of inflammation and fibrosis was equal in both fluid groups. Normal architecture and vital mucosa were found after inappropriate submucosal injection. MP-injections resulted in one transmural hematoma (day 3), and intramuscular encapsulation in 25 % of the sites (day 28). A pig’s stomach differs from the human stomach. The mechanical dissection properties of the gel may reduce the need for submucosal dissection during ESD. The gel is safe when advertently injected in the submucosa and MP. The porcine model appeared suboptimal to evaluate the true mechanical dissection properties of the gel.

BACKGROUND: The currently recommended regimen for focal radiofrequency ablation (RFA) of Barrett's esophagus (BE) comprises 2 applications of energy, cleaning of the device and ablation zone, and 2 additional applications of energy. A simplified regimen may be of clinical utility if it is faster, easier, and equally safe and effective.OBJECTIVE: To compare the efficacy of 2 focal RFA regimens.SETTING: Three tertiary referral centers.PATIENTS: Consecutive patients scheduled for focal RFA of BE with flat type BE with at least 2 BE islands or mosaic groups of islands were enrolled.INTERVENTIONS: BE areas were paired: 1 area was randomized to the "standard" regimen (2 × 15 J/cm(2)-clean-2 × 15 J/cm(2)) or to the "simplified" regimen (3 × 15 J/cm(2)-no clean), allocating the second area automatically to the other regimen. The percentage of surface area regression of each area was scored at 2 months by the endoscopist (blinded).OUTCOME MEASURE: Proportion of completely removed BE areas at 2 months. Calculated sample size was 46 pairs of BE areas using a noninferiority design. Noninferiority was defined as RESULTS: Forty-five equivalent pairs of BE areas were included in 41 patients. The proportion of completely removed BE areas at 2 months after focal RFA was 30 (67%) for standard and 33 (73%) for simplified. Noninferiority was demonstrated by a 7% difference (95% CI, -10.6 to +20.9).LIMITATIONS: Tertiary referral centers.CONCLUSIONS: The results of this multicenter randomized trial suggest that a simplified 3 × 15 J/cm(2) focal ablation regimen is not inferior to the standard regimen, regarding the endoscopic removal of residual Barrett islands.

BACKGROUND & AIMS: The current procedure for circumferential balloon-based radiofrequency ablation (c-RFA) for the removal of dysplastic Barrett's esophagus (BE) is labor intensive, comprising 2 ablation passes with a cleaning step to remove debris from the ablation zone and electrode. We compared the safety and efficacy of 3 different c-RFA ablation regimens.METHODS: We performed a prospective trial of consecutive patients with flat-type BE with high-grade dysplasia. Fifty-seven patients (45 men; age, 64 ± 15 y; 28 with prior endoscopic resection) were assigned randomly to groups that underwent c-RFA with a double application of RFA (12 J/cm(2)). The standard group received c-RFA, with device removal and cleaning, followed by c-RFA; the simple-with-cleaning group underwent c-RFA, with device cleaning without removal, followed by c-RFA; and the simple-no-cleaning group received 2 applications of c-RFA, and the device was not removed or cleaned. The primary outcome was surface regression of BE 3 months later, graded by 2 blinded expert endoscopists. Calculated sample size was 57 patients, based on a noninferiority design.RESULTS: Median BE surface regression at 3 months was 83% in the standard group, 78% in the simple-with-cleaning group, and 88% in the simple-no-cleaning group (P = .14). RF ablation time was 20 minutes (interquartile range [IQR], 18-25 min) for the standard group, 13 minutes (IQR, 11-15 min) for the simple-with-cleaning group, and 5 minutes (IQR, 5-9 min) for the simple-no-cleaning group (P < .01). The median number of introductions (RFA devices/endoscope) for the standard group was 7, vs 4 for the simple groups (P < .01).CONCLUSIONS: This randomized, prospective study suggests that c-RFA is easier and faster, but equally safe and effective, when the cleaning phase between ablations is omitted or simplified. Trialregister.nl, NTR 2495.

Background and study aim: Endoscopic resection with radiofrequency ablation (RFA) 6 weeks later safely and effectively eradicates Barrett’s esophagus with high grade dysplasia (HGD) and early cancer. After widespread endoscopic resection, related scarring may hamper balloon-based circumferential RFA (c-RFA). However c-RFA immediately followed by endoscopic resection in the same session might avoid the impact of scarring and reduce laceration and stenosis risk. We aimed to assess the feasibility of such an approach. Patients and methods: Patients with Barrett’s esophagus ≥ 3 cm and ≥ 1 visible lesion (HGD/early cancer) were included. Visible lesions were marked with cautery, and c-RFA (12 J/cm2) was delivered using two applications and a cleaning step, followed by resection of the delineated area. Outcome measures were surface regression of Barrett’s esophagus at 3 months, need for subsequent c-RFA, complications, and quality of resection specimens. Results: 24 patients (20 men, 4 women; mean age 68 years, standard deviation [SD] 12; Barrett’s esophagus median length C6M8) underwent single-session c-RFA + endoscopic resection, providing a median of 4 (interquartile range [IQR] 2 – 6) resection specimens (early cancer 18 patients; HGD 6). Complications included 1 perforation, 4 bleedings, and 5 stenoses; all were managed endoscopically. Specimens allowed assessment of neoplasia depth, differentiation, and lymphatic/vascular invasion. Median Barrett’s esophagus surface regression at 3 months was 95 %. No patient required a second c-RFA procedure and 40 % required repeat endoscopic resection for visible lesions. Complete response for neoplasia was achieved in 100 % and complete response for intestinal metaplasia (CR-IM) in 95 %. Conclusions: c-RFA followed by endoscopic resection in the same session is feasible, but technically demanding and associated with a substantial rate of complications and repeat endoscopic resection. This approach should be reserved for selected cases in expert centers, with endoscopic resection and RFA 6 – 8 weeks later remaining the standard combined approach.

Background and study aims: The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns. Patients and methods: NBI images from macroscopically normal areas in patients with Barrett's esophagus were retrieved from endoscopy databases and were randomized for review by seven endoscopists (three experts, four nonexperts). A simplified binary classification of NBI mucosal and vascular patterns was used: (1) regular pattern (nondysplastic Barrett's esophagus); (2) irregular pattern (dysplastic Barrett's esophagus). Agreement in relation to surface patterns and predicted histology (dysplasia vs. no dysplasia) was calculated using. statistics.Results: A total of 252 NBI images from 75 patients with Barrett's esophagus were assessed: 93 showed intestinal metaplasia, 91 low-grade dysplasia, and 68 high-grade dysplasia/esophageal adenocarcinoma. The median score for image quality was 4 (very good). Interobserver agreement for mucosal and vascular patterns and dysplasia prediction was fair: K = 0.40 (95% CI: 0.370.42), 0.36 (95% CI: 0.33-0.38), and 0.39 (95% CI: 0.36-0.41) respectively, with comparable results for experts and nonexperts. Intraobserver agreement was substantially better among experts than among nonexperts, with mucosal K = 0.63 vs. 0.49, vascular K = 0.58 vs. 0.43, and predicted histology K= 0.68 vs. 0.54 (all P Conclusions: Using a consensus-driven simplified classification of NBI surface patterns for Barrett's esophagus, the interobserver agreement was fair with suboptimal sensitivity and specificity. Significant improvements in NBI interpretation are needed prior to the routine use of NBI surface patterns for the assessment of Barrett's esophagus.

Objective: After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. Methods: A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). Results: CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p

Background and study aims: Radiofrequency ablation (RFA) with or without prior endoscopic resection safely and effectively removes early neoplasia in Barrett's esophagus. We speculated that this approach might also be suited for early squamous neoplasia of the esophagus. The aim of the study was to assess our initial experiences with RFA for high grade intraepithelial neoplasia (HGIN) and esophageal squamous cell cancer (ESCC) limited to the mucosa. Patients and methods: This was a prospective case series study in two tertiary centers. Patients with at least one unstained lesion (USL) of the esophagus using Lugol's chromoendoscopy and squamous HGIN/ESCC upon biopsy were included. In the case of nonflat USLs, endoscopic resection was performed for staging and to render the mucosa flat. After endoscopic resection and subsequent circumferential RFA, chromoendoscopy was repeated every 3 months with focal RFA of residual USLs. Follow-up chromoendoscopy was repeated at 6 months and annually thereafter. The main outcome measure was complete histological response for any squamous intraepithelial neoplasia or ESCC. Results: A total of 13 patients (10 HGIN, three ESCC) were included. Following endoscopic resection in nine patients, the median extent of USLs was 4 cm and 50 % of circumference. All 13 patients achieved a complete response after a median of 2 RFA sessions (IQR 1 - 3 sessions). RFA-related complications included two mucosal lacerations (at the endoscopic resection scar) and one intramural hematoma, none requiring therapy. Endoscopic resection-/RFA-related complications were three stenoses. Dilation resulted in perforation in one patient (managed with a covered stent). There were no recurrences (median follow-up 17 months [IQR 11 - 22 months]). Conclusions: This study suggests that RFA with or without prior endoscopic resection for esophageal squamous HGIN and mucosal ESCC is feasible and effective.

Introduction: Multiband mucosectomy (MBM) is a relatively new technique for endoscopic resection in Barrett's esophagus. This ligate-cut technique uses a modified variceal band ligator allowing for six consecutive resections without prior submucosal lifting. The aim was to evaluate the safety of MBM and its efficacy for complete endoscopic removal of delineated target areas in Barrett's esophagus. Methods: Prospective registration of all MBM procedures in Barrett's esophagus was carried out between November 2004 and October 2009 in two hospitals. Prior to MBM, the target area was delineated with coagulation markings, followed by endoscopic resection until the delineated area was completely resected. Primary end points were acute (during procedure) plus early complications (< 30 days) and the rate of complete endoscopic resection of the delineated target area. Results: A total of 243 MBM procedures, with 1060 resections, were performed in 170 patients. MBM was performed for focal lesions (n = 113), for Barrett's esophagus removal as part of a (stepwise) radical endoscopic resection protocol (n = 117), and as escape treatment after radiofrequency ablation (n = 13). The only acute complication was bleeding (in 3 %, endoscopically managed); no perforations occurred despite absence of submucosal lifting. Early complications consisted of delayed bleeding (in 2 %, endoscopically managed) and stenosis, which occurred in 48 % of patients treated in a (stepwise) radical resection protocol; patients treated for focal lesions or in escape treatment showed no stenosis. Complete endoscopic resection was achieved in 91 % of the focal lesions, in 86 % of cases treated under the (stepwise) radical endoscopic resection protocol, and 100 % for escape treatment after radiofrequency ablation. Conclusion: MBM is a safe and effective technique for the removal of delineated target areas in Barrett's esophagus.

Background: Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barrett's esophagus. ER-cap requires submucosal lifting and positioning of a snare in the cap, making it technically demanding and laborious. Multiband mucosectomy (MBM) uses a modified variceal band ligator and requires no submucosal lifting or positioning of a snare. Objective: To compare ER-cap and MBM for piecemeal ER of early Barrett's neoplasia. Design: Randomized, controlled trial. Setting: Tertiary-care and community-care centers. Patients: This study involved 84 patients (64 men; median age 70 years) undergoing piecemeal ER of Barrett's neoplasia. Intervention: Piecemeal ER was performed by using ER-cap (n = 42) or MBM (n = 42). Main Outcome Measurements: Safety, efficacy, procedure time, costs. Results: Procedure time (34 vs 50 minutes; P = .02) and costs (€240 vs €322; P < .01) were significantly less with MBM compared with ER-cap. MBM resulted in smaller resection specimens than ER-cap (18 ×13 mm vs 20 × 15 mm; P < .01). Maximum thicknesses of specimens and resected submucosa were not significantly different. There were no clinically relevant bleeding episodes. Four perforations occurred, 3 with ER-cap, 1 with MBM (P = not significant). Limitations: Potential bias because of different levels of experience among participating endoscopists. Conclusion: Piecemeal ER with MBM is faster and cheaper than with ER-cap. Despite the lack of submucosal lifting, MBM appears not to be associated with more perforations. Although MBM results in slightly smaller specimens, the clinical relevance of this may be limited because depth of resections does not differ between both techniques. MBM may thus be preferred for piecemeal ER of early Barrett's neoplasia. (Clinical trial registration number: NTR1435.)

Background: Radiofrequency ablation (REA) is safe and effective for eradicating Barrett's esophagus (BE) and BE-associated early neoplasia. Most REA studies have limited the baseline length of BE ( = 10 ern containing neoplasia. Design: Prospective trial. Setting: Two tertiary-care centers. Patients: This study involved consecutive patients with BE >= 10 cm with early neoplasia. Intervention: Focal ER for visible abnormalities, followed by a maximum of 2 circumferential and 3 focal REA procedures every 2 to 3 months until complete remission. Main Outcome Measurements: Complete remission, defined as endoscopic resolution of BE and no intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia) in biopsy specimens. Results: Of the 26 patients included, 18 underwent ER for visible abnormalities before RFA. The ER specimens showed early cancer in 11, high-grade intraepithelial neoplasia (HGIN) in 6, and low-grade intraepithelial neoplasia (LGIN) in 1. The worst residual histology, before RFA and after any ER, was HGIN in 16 patients and LGIN in 10 patients. CR-neoplasia and CR-IM were achieved in 83% (95% confidence interval [CI], 63%-95%) and 79% (95% CI, 58%-93%), respectively. None of the patients had fatal or severe complications and 15% (95% CI, 4%-35%) had moderate complications. During a mean (+/- standard deviation) follow-up of 29 (+/- 9.1) months, no neoplasia recurred. Limitations: Tertiary-care center, short follow-up. Conclusion: ER for visible abnormalities, followed by RFA of residual BE is a safe and effective treatment for BE >= 10 cm containing neoplasia, with a low chance of recurrence of neoplasia or BE during follow-up. (Gastrointest Endosc 2011;73:682-90.)

Background & Aims Endoscopic tri-modal imaging (ETMI) incorporates high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow band imaging (NBI). A recent uncontrolled study found that ETMI improved the detection of high-grade dysplasia (HGD) and early carcinoma (Ca) in Barrett's esophagus (BE). The aim was to compare ETMI with standard video endoscopy (SVE) for the detection of HGD/Ca with the use of a randomized cross-over design. Methods Patients referred for work-up of inconspicuous HGD/Ca were eligible and underwent both SVE and ETMI in randomized order within an interval of 6–12 weeks. During ETMI, inspection with HRE was followed by AFI. Detected lesions were inspected in detail with NBI and biopsied, followed by random biopsies. During SVE, any visible lesion was biopsied followed by random biopsies. Results Eighty-seven patients with BE underwent ETMI and SVE. No significant difference was observed in overall histologic yield between ETMI and SVE. ETMI had a significantly higher targeted yield compared with SVE because of AFI. However, the yield of targeted biopsies of ETMI was significantly inferior to the overall yield of SVE. Detailed inspection with NBI reduced the false-positive rate of HRE + AFI from 71% to 48% but misclassified 17% of HGD/Ca lesions as not suspicious. Conclusions ETMI statistically significant improves the targeted detection of HGD/Ca compared with SVE. Subsequent characterization of lesions with NBI appears to be of limited value. At this stage, ETMI cannot replace random biopsies for detection of lesions or targeted biopsies for characterization of lesions in a high-risk population.

BACKGROUND: Most risk estimations for lymph node metastasis in adenocarcinoma of the esoph-agus and cardia (AEC) with invasion into the muscularis mucosae (m3) or submucosa are based on surgical series. This study aimed to correlate the lymph node metastasis rate with m3 and sub-mucosal infiltration depth of AEC in endo-scop-ic resection specimens. METHODS: Patients undergoing endoscopic resection for AEC between January 2000 and March 2008 at two centers were included if the endo-scopic resection specimen showed m3 or sub-mucosal cancer. Infiltration into the muscularis mucosae was defined as m3. Submucosal inva-sion was classified as sm1 (≤ 500 µm) or sm2 / 3 (> 500 µm). Exclusion criteria were chemotherapy or radiotherapy and nonradical endoscopic resection. RESULTS: 82 patients included 57 with m3, 12 with sm1, and 13 with sm2 / 3 cancers. Of the tumors, 13 were poorly differentiated and five showed lymphovascular invasion. After initial endoscopic resection, seven patients underwent surgery and 75 endoscopic therapy. No lymph node metastases were found in 158 lymph nodes of the esophagectomy specimens and none of the endoscopically treated patients were diagnosed with lymph node metastasis during a median follow-up of 26 months (interquartile range [IQR] 14–41). CONCLUSION: This study suggests that lymph node metastasis risk for m3 and submucosal AEC may be lower than has been assumed on the basis of surgical series, and that current guidelines are -valid regarding suitability of m3 AECs for endo-scopic therapy. It may also suggest that selected patients with submucosal cancers are also eligi-ble for endoscopic management. Confirmation of these results is needed in larger series with longer follow-up.

Introduction Autofluorescence endoscopy (AFE) is a novel technique that identifies early neoplasia in Barrett9s oesophagus (BE) by highlighting differences in tissue autofluoresence (AF). It has high sensitivity but is associated with false positive rates up to 80%. We aimed to develop numerical measures of AF to reduce the false positive rates of AFE. Methods Images of AFE lesions in patients with BE were prospectively collected. Blinded anonymised images were de-gamma corrected and average grayscale values in the red, green and blue channels of the abnormal and background normal area were quantified. The autofluoresence intensity (ratio of average red to green channel greyscale value of lesion compared to background), colour contrast index (between lesion and background), hue, saturation and lightness (of the lesion) were calculated. A decision tree based on the training set was developed with the J48 algorithm in WEKA3.2.4, using a 10-fold cross validation strategy. The performance of the model developed was assessed on an independently collected test dataset. Results There were 82 images (37 high grade dysplasia/cancer) in the training set and 164 images (51 high grade dysplasia/cancer) in the test set. The decision tree classifier developed utilised only autofluoresence intensity and colour contrast index and had a sensitivity of 97%, specificity of 77%, and negative predictive value of 98% in detecting high grade dysplasia/cancer in the independent test set. The false positive rate of AFE was reduced from 70% to 16%. Conclusion Numerical analysis of colour fluorescence and contrast is a reliable, objective and accurate method of reducing the false positive rate of AFE and can be easily incorporated into real time endoscopy. Competing interests V Subramanian: None declared, J Mannath: None declared, D Boerwinkel: None declared, L Alvarez-Herrero: None declared, W Curvers: None declared, C Hawkey: None declared, J Bergman Grant/Research Support from: Olympus Medical, K Ragunath Grant/Research Support from: Olympus Medical.

Radiofrequency Ablation /Endoscopic Resection for Barrett’s Esophagus With High-Grade Dysplasia and/or Early Cancer: Durability of the Post-Treatment Neosquamous Epithelium At 5-Year Follow-Up Kai Yi N. Phoa, Roos E. Pouw, Frederike G. Van Vilsteren, Carine Sondermeijer, Lorenza Alvarez Herrero, Fiebo J. Ten Kate, Mike Visser, Mark I. Van Berge Henegouwen, Bas L. Weusten, Rosalie C. Mallant-Hent, Jacques J. Bergman Gastroenterology, Academic Medical Center, Amsterdam, Netherlands; Gastroenterology, St Antonius hospital, Nieuwegein, Netherlands; Pathology, Academic Medical Center, Amsterdam, Netherlands; Surgery, Academic Medical Center, Amsterdam, Netherlands; Gastroenterology, Flevoziekenhuis, Almere, Netherlands Background: Radiofrequency ablation (RFA) is safe and effective for complete eradication of Barrett’s esophagus (BE) with high-grade dysplasia (HGD) and/or early cancer (EC), and may be safely preceded by focal endoscopic resection (ER) to remove visible lesions. Less is known regarding the long-term (5-year) durability of the neosquamous epithelium (NSE) that repopulates the esophagus after RFA. Aim: In a prospective cohort of BE patients with HGD/EC, all of whom achieved complete epithelial reversion after RFA /focal ER at 1-year follow-up, we assessed the 5-year durability of the treatment response. Methods: At study entry, patients had BE 10cm with HGD or EC( T1sm1) confirmed by an expert pathologist. We removed visible lesions with focal ER, followed by repeat biopsy to establish the post-ER diagnosis. We performed RFA at 2-month intervals until all Barrett’s mucosa was visibly eradicated. Annually thereafter we performed high-resolution endoscopy with NBI, taking biopsies (4Q/2cm) from the NSE above the top of the gastric folds. Additionally, biopsies were obtained distal to the neosquamocolumnar junction (gastric cardia, analyzed separately). During and after treatment patients received high-dose PPI maintenance medication. Primary outcomes: 1) complete histological remission of HGD/EC (CR-neo), 2) complete histological remission of intestinal metaplasia (CR-IM) in esophageal biopsies. Secondary outcome: presence of IM in biopsies from the gastric cardia. Results: Twenty-three patients were analyzed (17 men, mean age 63.4, median BE C4M7). Entry ER was performed in 13 patients for lesions showing: EC (n 4), HGD (n 6) or LGD (n 3). Worst grade post-ER (pre-RFA): HGD(n 20), LGD(n 3). All patients achieved CR-neo/CR-IM at 1-year (2 required focal escape ER). Three patients exited the study at 16, 28 and 44 mo due to unrelated comorbidity. All were CR-neo/CR-IM at last follow-up. Median follow-up (n 23) since study entry was 52 mo (IQR 44-55). Follow-up endoscopy with biopsies was performed a median of 5 (IQR 4-5) times per patient (mean 77 38 biopsies per pt (61 NSE, 17 cardia)). All patients (n 23, 100%) demonstrated sustained CR-neo and CR-IM at every biopsy session during follow-up. None of the 1780 NSE biopsies demonstrated subsquamous IM. In 37 of the 379 gastric cardia biopsies (9 pts) focal non-dysplastic IM was detected (not treated). Conclusion: We have previously reported that RFA /focal ER for BE with HGD and/or EC is safe and effective, resulting in 100% CR-neo and CRIM at 1-year. The results of the present long-term follow-up of this cohort suggest that the histologically normal NSE achieved after treatment at 1-year is further durable at 5-year follow-up. No patient in this cohort developed invasive cancer or sustained BE-related morbidity. The clinical relevance of focal IM in a normal appearing cardia remains unknown.

Introduction Auto-fluorescence imaging (AFI) endoscopy is a novel imaging technique that can identify neoplastic tissue by highlighting differences in tissue fluorescence properties and detect early neoplasia not detectable by conventional white light endoscopy. Normal areas appear “green” and abnormal areas are highlighted as “red” when using AFI endoscopy. Although it has a high sensitivity, it is associated with high false positive rates up to 80%.1 Methods To determine if auto-fluorescence index, defined as the ratio of the intensity of red and green tone between normal and abnormal AFI areas in patients with Barrett9s oesophagus (BO), can improve the specificity and accuracy of AFI endoscopy. Images of patients with both AFI true and false positive areas of BO were selected from two prospectively collected data sets using the Olympus Lucera-Hyperpro video endoscopy systems and GIF Q240FZ and GIFQ260FZ gastroscopes and used as training and test data sets, respectively. Biopsies from these areas had been confirmed by two specialist GI pathologists to have no dysplasia or high-grade dysplasia/carcinoma. Lesions with indefinite or low grade dysplasia were excluded. The images were de-gamma corrected, split into component channels and the mean intensity of the red and green tone at the abnormal area and background (normal areas) were quantified blinded using Image J software (NIH). Statistical analysis was done using SPSS V.17 (SPSS Inc). An optimal cut off was developed from the training set and applied blinded to the test set in order to determine the usefulness of the AFI index. Results There were 82 images from of AFI abnormalities in the training set. Of these 19 had high-grade dysplasia (HGD), 18 had carcinoma (CA), 38 had intestinal metaplasia (IM) and seven were from areas of gastric mucosa. The test set comprised of 40 images from 27 patients of which 24 had IM, six had HGD and 10 had CA. The area under the receiver operating curve (AUROC) for the auto-fluorescence index ratio (AFI ratio) in the training set was 0.9 (SE=0.3) with an optimal cut off of 1.3. Using an AFI ratio of 1.3 on the 40 images in the test set only one AF area with IM and 1 area with CA were misclassified. The sensitivity of AFI in the test set was 94% (95% CI 80 to 98), specificity was 96% (95% CI 86 to 99), the likelihood ratio of a positive test was 22.5 (95% CI 5.8 to 85). Using the AFI index reduces the false positive rate in the test set from 60% to 6%. Conclusion The AFI ratio shows promise as a tool to improve the diagnostic capabilities of AFI endoscopy. AFI index of >1.3 resulted in a 10-fold reduction in the false positive rate of AFI endoscopy.

This review discusses the application of 2 novel imaging techniques in Barrett's esophagus: autofluorescence imaging and narrow band imaging (NBI). Autofluorescence as well as NBI may help to direct endoscopic therapy for early neoplasia in Barrett's esophagus; their value in daily practice, however, seems to be limited and needs further evaluation.