Carine Sondermeijer

Efficacy of Radiofrequency Ablation Combined With Endoscopic Resection for Barrett's Esophagus With Early Neoplasia

BACKGROUND & AIMS Radiofrequency ablation (RFA) is safe and effective for eradicating intestinal metaplasia and neoplasia in patients with Barretts esophagus. We sought to assess the safety and efficacy of RFA in conjunction with baseline endoscopic resection for high-grade intraepithelial neoplasia (HGIN) and early cancer. METHODS This multicenter, prospective cohort study included 24 patients (mean age, 65 years; median Barretts esophagus, 8 cm), with Barretts esophagus of < or =12 cm containing HGIN or early cancer, from 3 European tertiary-care medical centers. Visible lesions were endoscopically resected, followed by serial RFA. Focal escape endoscopic resection was used if Barrett tissue persisted despite RFA. Complete response, defined as all biopsies negative for intestinal metaplasia and neoplasia, was assessed during endoscopy with 4-quadrant biopsies taken every 1 cm of the original Barretts segment 2 months after the patient was last treated. RESULTS Twenty-three patients underwent pre-RFA endoscopic resection for visible lesions; 16 patients had early cancer and 7 patients had HGIN. The worst residual histology results, pre-RFA (after any endoscopic resection) were: HGIN (10 patients), low-grade intraepithelial neoplasia (11 patients), and intestinal metaplasia (3 patients). Neoplasia and intestinal metaplasia were eradicated in 95% and 88% of patients, respectively; after escape endoscopic resection in 2 patients, rates improved to 100% and 96%, respectively. Complications after RFA included melena (n = 1) and dysphagia (n = 1). After additional follow-up (median, 22 months; interquartile range, 17.2-23.8 months) no neoplasia recurred. CONCLUSIONS This European multicenter study to show that early neoplasia in Barretts esophagus can be effectively and safely treated with RFA, in combination with prior endoscopic resection of visible lesions.

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.

Properties of the Neosquamous Epithelium After Radiofrequency Ablation of Barrett's Esophagus Containing Neoplasia

OBJECTIVES:Endoscopic radiofrequency ablation (RFA) eradicates intestinal metaplasia and intraepithelial neoplasia associated with Barretts esophagus (BE), restoring an endoscopically normal neosquamous epithelium (NSE). We evaluated the post-RFA NSE for genetic abnormalities and buried glandular mucosa.METHODS:Eligible patients underwent RFA for BE containing early cancer and/or high-grade intraepithelial neoplasia with subsequent complete histological reversion to normal NSE. At baseline, the BE was sampled by brush cytology and biopsies. At least 2 months after RFA, the NSE was sampled by brush cytology, keyhole biopsies, and endoscopic resection. The untreated squamous epithelium was biopsied as a control. The baseline BE and post-RFA NSE were evaluated for immunohistochemical expression of Ki-67 and p53, and genetic abnormalities (DNA–fluorescent in situ hybridization: chromosome 1 and 9, p16 and p53). In addition, biopsy depth was compared for biopsies from the NSE and untreated squamous epithelium. The presence of buried glandular mucosa in NSE was assessed with primary and keyhole biopsy, and endoscopic resection.RESULTS:All pretreatment specimens from all 22 patients showed abnormalities on immunohistochemical staining and fluorescent in situ hybridization, whereas all post-RFA NSE specimens were normal. All the post-RFA biopsies from the NSE contained full epithelia, whereas 37% contained lamina propria, a finding no different from biopsies from untreated squamous epithelium (36% lamina propria). Deeper keyhole biopsies contained lamina propria in 51%. All endoscopic resection specimens contained submucosa, whereas no biopsy or endoscopic resection specimen contained buried glandular mucosa.CONCLUSIONS:Rigorous evaluation of the post-RFA NSE in patients who, at baseline, had BE containing early cancer high-grade intraepithelial neoplasia, showed neither persistent genetic abnormalities nor buried glandular mucosa.

Successful balloon-based radiofrequency ablation of a widespread early squamous cell carcinoma and high-grade dysplasia of the esophagus: a case report

BACKGROUND For selected patients with high-grade dysplasia (HGD) and/or early esophageal squamous cell cancer (ESCC), endoscopic therapy represents a nonsurgical treatment option. For widespread lesions, however, current endoscopic treatment modalities (eg, endoscopic resection, argon plasma coagulation, photodynamic therapy) are associated with considerable drawbacks, of which esophageal stricturing is the most significant. Balloon-based radiofrequency (RF) ablation (HALO System) is a promising technology for endoscopic treatment of Barretts esophagus, and may also play a role in treating widespread HGD and early ESCC. OBJECTIVE We describe a case report of balloon-based RF ablation for HGD and early ESCC. DESIGN Case report. SETTING Tertiary care institution, Academic Medical Center, Amsterdam, The Netherlands. PATIENT A 66-year-old male with a 35-mm large, flat-type ESCC with surrounding HGD. INTERVENTION Balloon-based RF ablation (HALO System). MAIN OUTCOME MEASUREMENTS Endoscopic and histological eradication of HGD and ESCC, and adverse events. RESULTS RF ablation resulted in complete endoscopic and histological eradication of HGD and ESCC without adverse events such as dysphagia or esophageal narrowing. LIMITATIONS Single patient report, limited follow-up. CONCLUSIONS This is the first report of balloon-based RF ablation for esophageal HGD and early ESCC. The treatment resulted in complete eradication of a 35-mm flat ESCC with no adverse events. This suggests that this ablation technique deserves further study for the management of widespread HGD or flat-type ESCC.

A comparative analysis by SAGE of gene expression profiles of esophageal adenocarcinoma and esophageal squamous cell carcinoma

Esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barrett’s esophagus (BE), the metaplastic epithelium that predisposes for EA, and compared the transcriptome of ESCC to normal esophageal squamous epithelium. For obtaining the transcriptomes tissue biopsies were used and serial analysis of gene expression (SAGE) was applied. Validation of results by RT-PCR and immunoblotting was performed using tissues of an additional 23 EA and ESCC patients. Over 58,000 tags were sequenced. Between EA and BE 1013, and between ESCC and normal squamous epithelium 1235 tags were significantly differentially expressed (p < 0.05). The most up-regulated genes in EA compared to BE were SRY-box 4 and Lipocalin2, whereas the most down-regulated genes in EA were Trefoil factors and Annexin A10. The most up-regulated genes in ESCC compared to normal squamous epithelium were BMP4, E-Cadherin and TFF3. The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified.

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.

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.

Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett's oesophagus: a multicentre randomised controlled trial

BACKGROUND For focal radiofrequency ablation of Barretts oesophagus, a simplified regimen (3 × 15 J/cm2, without cleaning) has proven to be as effective as the standard regimen (2 × 15 J/cm2, followed by cleaning, followed by 2 × 15 J/cm2). However, this simplified regimen seemed to be associated with a higher stenosis rate. Therefore, we lowered the radiofrequency energy and hypothesised that this new simplified regimen would be as effective and safe as the standard regimen. METHODS This randomised non-inferiority trial included patients with dysplastic Barretts oesophagus or residual Barretts oesophagus after endoscopic resection or circumferential radiofrequency ablation, in five European tertiary referral centres. Patients were randomly assigned (1:1) to the new simplified regimen (3 × 12 J/cm2, without cleaning) or the standard regimen, with variable block sizes of four, six, and eight patients, stratified by participating hospital. Focal radiofrequency ablation was done every 3 months, up to a maximum of three treatments, until all Barretts oesophagus was eradicated. The primary outcome was complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments, assessed in the intention-to-treat population. Non-inferiority was assessed on the basis of the difference between groups in the median percentage of Barretts oesophagus surface regression, with a non-inferiority margin of -15%. This study is registered with www.trialregister.nl, number NTR4994, and is completed. FINDINGS Between March 25, 2015, and July 25, 2016, 84 patients were randomly assigned to treatment: 44 to receive the simplified regimen and 40 to receive the standard regimen. One patient assigned to the simplified regimen and four assigned to the standard regimen were excluded because they weree found not to be eligible; therefore the final intention-to-treat population consisted of 43 patients in the simplified ablation group and 36 in the standard ablation group. Complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments was achieved in 32 (74%, 95% CI 59-87) patients treated with the simplified protocol, versus 30 (83%, 95% CI 67-94) patients treated with the standard protocol (p=0·34). Median Barretts oesophagus surface regression after two focal radiofrequency ablation sessions was 98% (IQR 95-100) in the simplified regimen group and 100% (97-100) in the standard regimen group. The difference between medians was 2% (95% CI -0·562 to 3·162); thus the simplified regimen was deemed non-inferior to the standard regimen. Stenoses requiring dilatation were observed in four (9%) of 43 patients in the simplified regimen group and four (11%) of 36 in the standard regimen group. Post-procedural bleeding requiring repeat endoscopy occurred in one (2%) patient in the simplified ablation group and three (8%) patients in the standard ablation group. One patient (2%) in the simplified treatment group died 36 days after the second radiofrequency ablation procedure, due to an unknown cause. INTERPRETATION Based on the results of this study, we conclude that the simplified regimen is the preferred regimen for focal radiofrequency ablation of Barretts oesophagus. FUNDING None.