Lorenza Alvarez Herrero

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial

Objective After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barretts 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<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. Conclusions In patients with BO ≤5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Endoscopic Tri-Modal Imaging Is More Effective Than Standard Endoscopy in Identifying Early-Stage Neoplasia in Barrett's Esophagus

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 Barretts 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.

Randomized trial on endoscopic resection-cap versus multiband mucosectomy for piecemeal endoscopic resection of early Barrett's neoplasia

BACKGROUND Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barretts 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 Barretts 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 Barretts 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 Barretts neoplasia. ( CLINICAL TRIAL REGISTRATION NUMBER NTR1435.).

Do we still need EUS in the workup of patients with early esophageal neoplasia? A retrospective analysis of 131 cases

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 25 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.

Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program

BACKGROUND AND STUDY AIMS Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program. PATIENTS AND METHODS The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications. RESULTS A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barretts esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2 - 4 specimens). Complete endoscopic removal was achieved in 111 /120 cases (92.5 %). Six perforations occurred (5.0 %): five were effectively treated endoscopically (clips, covered stent), and one patient underwent esophagectomy. There were 11 acute mild bleedings (9.2 %), which were managed endoscopically. Perforations occurred in ER-cap procedures performed by four participants (7.1 % ER-cap vs. 0 % MBM; P = 0.18), and in 1.7 % of the first 10 endoscopic resections and 8.3 % of the second 10 endoscopic resections per endoscopist (P = 0.26). CONCLUSION In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0 % perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.

Validation of the Prague C&M classification of Barrett’s esophagus in clinical practice

BACKGROUND AND STUDY AIMS The Prague C&M classification for Barretts esophagus has found widespread acceptance but has only been validated by Barretts 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 Barretts experts and community hospital endoscopists when using this classification to describe Barretts 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 Barretts 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 Barretts 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 Barretts esophagus and 80 % for hiatal hernia length. Barretts experts and community hospital endoscopists showed no differences in agreement. Shorter Barretts segments (≤ 5 cm) had lower agreement compared with longer segments (> 5 cm). CONCLUSIONS Agreement was good for Barretts esophagus and reasonable for hiatal hernia length. These findings strengthen the value of the Prague C&M classification to describe Barretts esophagus and hiatal hernia length. Although absolute agreement during real-time endoscopy was high, one should anticipate that Barretts values may vary by 1 - 2 cm between two endoscopies.

Circumferential Balloon-based Radiofrequency Ablation of Barrett's Esophagus With Dysplasia Can Be Simplified, yet Efficacy Maintained, by Omitting the Cleaning Phase

BACKGROUND & AIMS The current procedure for circumferential balloon-based radiofrequency ablation (c-RFA) for the removal of dysplastic Barretts 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.

Esophageal motility and impedance characteristics in patients with Barrett's esophagus before and after radiofrequency ablation

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.

Narrow band imaging does not reliably predict residual intestinal metaplasia after radiofrequency ablation at the neo-squamo columnar junction

BACKGROUND AND STUDY AIMS After radiofrequency ablation (RFA) of Barretts 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.

981 A Pilot Trial of Endoscopic Radiofrequency Ablation for the Eradication of Esophageal Squamous Intraepithelial Neoplasia and Early Squamous Cell Carcinoma Limited to the Mucosa

We present the case of a 71-year-old female with a five month history of dysphagia, weight loss and heartburn. Preoperative investigation with barium swallow and upper endoscopy demonstrated a large lower esophageal pulsion divertictulum. A laparoscopic transhiatal resection of the esophageal diverticulum was performed with Heller myotomy and crural repair. Intraoperative endoscopy helps to identify the diverticulum in the mediastinum, to ensure complete resection of the diverticulum, to ensure an adequate esophageal myotomy, and to perform an air leak test. A Heller myotomy is performed to treat the esophageal dysmotility. A fundoplication is not performed due to poor esophageal motility.