Residual Intestinal Metaplasia Research Articles

The Utility of a Methylation Panel in the Assessment of Clinical Response to Radiofrequency Ablation for Barrett's Esophagus

Background: Radiofrequency ablation (RFA) is an effective treatment for dysplastic Barrett’s esophagus (BE), but recurrence can occur after initial response. Currently there is uncertainty about how to best define histological remission. A DNA methylation panel on esophageal samples was previously shown to have high diagnostic accuracy for BE. We aimed to investigate this biomarker panel in the assessment of response to RFA treatment. Methods: We retrospectively analyzed esophageal and gastroesophageal junction (GEJ) biopsies from patients with BE before and after RFA treatment. We quantified the extent of intestinal metaplasia (IM) based on number of glands with goblet cells (IM-Score) and expression of the intestinal factor trefoil factor-3 (TFF3-Score). Promoter methylation of 3 genes (ZNF345, TFP12, ZNF569) was measured by methylight (Meth-Score) throughout the RFA treatment pathway. Findings: We included 45 patients (11 non-dysplastic BE, 14 low-grade dysplasia, 20 high-grade dysplasia/intramucosal cancer). Meth-Scores were significantly higher in BE with and without dysplasia and GEJ with IM compared to GEJ without IM (P <·001). Meth-scores significantly correlated with the extent of IM at the GEJ measured both with IM-Scores (rho=66·0%, P<·001), and TFF3-Scores (rho=75·6%, P<·001). In patients with residual IM at the GEJ, RFA re-treatment brought about a 7·6-fold reduction in the methylation levels. The Meth-score had an area under the ROC curve of 95·1% (95%CI 91·1% - 99·1%) differentiating BE from normal GEJ. Interpretation: A DNA methylation panel can discriminate between the extent of histological IM in esophageal and junctional biopsies and could be used to objectively quantify residual disease following RFA. Funding Statement: This study was funded by a Medical Research Council core grant to RCF. WJ was funded by a Cancer Research UK multidisciplinary award (C47594/A21202). We would like to acknowledge clinical research infrastructure support from the Experimental Cancer Medicine Centre and the Cambridge Biomedical Research Centre. The funding bodies had no role in study design, patient recruitment, data collection, data analysis, data interpretation, writing of the manuscript or any other aspect pertinent to the study. Declaration of Interests: All of the authors disclose no conflict of interest. Ethics Approval Statement: The study was approved by the ethics committee at the local institution (LREC01/149). Informed consent for biomarker analysis was obtained from each patient before endoscopic treatment.

2130 Future of Endoscopy: Hybrid Argon Plasma Coagulation for Treatment of Intestinal Metaplasia of the Stomach

INTRODUCTION: Hybrid Argon Plasma Coagulation (Hybrid APC) is an advancement on standard APC technology; application of APC is preceded by high pressure needleless submucosal injection, with the same catheter. APC is indicated for the ablation of benign and dysplastic mucosal lesions such as vascular malformations and Barrett’s mucosa. Hybrid APC offers an advantage over efficacy and safety advantages over standard APC. The submucosal injection acts as a heat sink and disperses excess energy to ensure that the underlying layers (i.e.: muscularis propria) are unaffected. Only the mucosal layer is coagulated, in its entirety. CASE DESCRIPTION/METHODS: An 81 years-old Hispanic Male was found to have a 1.2 cm mucosal nodule along the incisura of the stomach (Figure 1). He underwent endoscopic ultrasound (EUS) of the lesion, which confirmed the presence of an isolated gastric nodule with no deep invasion of the muscularis propria, consistent with a T1N0Mx endoscopic staging. He subsequently underwent endoscopic submucosal dissection (ESD) of the lesion. Pathology of the specimen revealed multifocal high-grade dysplasia, arising in the background of extensive intestinal metaplasia. The deep margin was clear; however, the lateral resection margins showed focal involvement of intestinal metaplasia with low-grade dysplasia. In light of the diffuse mucosal dysplasia, the patient was successfully treated with widespread Hybrid APC of the residual intestinal metaplasia (Figures 2 and 3). DISCUSSION: Hybrid APC is an effective and efficient treatment modality for mucosal lesions. In one series of 50 patients; 96% achieved complete macroscopic remission of Barrett’s mucosa after a median of 3.5 APC sessions and 85% achieved complete histological remission. Hybrid APC is a promising technology as thermal injury depth is targeted and reduces deep injury as well as subsequent complications when it compared with Standard APC. Applications of hybrid APC will likely continue to grow as this modality is adopted into common parlance. This case is the first to describe the use of Hybrid APC for definitive treatment of intestinal metaplasia.

A Western Experience in the Use of a Novel CryoBalloon Focal Ablation System for the Management of Barrett’s Neoplasia

Introduction: Cryoablation poses an attractive alternative to radiofrequency ablation in patients with Barrett’s esophagus (BE), particularly those with residual intestinal metaplasia after multiple ablation sessions. The use of spray cryoablation, however, is not without challenges, including the need for simultaneous gastrointestinal venting, potential frosting of the endoscope optics, and dysfunction of the spray catheter. The CryoBalloon focal ablation system (CbFAS) was developed to maintain the advantages of cryoablation, but reduce the limitations of the spray system. We reported a U.S experience regarding the feasibility and safety of CbFAS (C2 Therapeutics, Redwood City, California, USA) in treating BE. Methods: A single-center, retrospective study of patients with dysplastic BE or early esophageal adenocarcinoma (EAC) treated with cryoablation using the CryoBalloon between 2016 and 2017. Our primary outcome was rate of technical success. Secondary outcomes included adverse events, complete remission of intestinal metaplasia (CR-IM), and complete remission of dysplasia (CR-D). Results: Forty-two patients were included and treated with 80 cryoablation sessions. The cohort had a mean age of 69.7±10.2 years (IQR: 66- 77) and was male predominant (83.3%). The majority of patients received prior endoscopic treatment (37/42, 88.1%). The mean length of the BE segment was 4±3.4 cm (IQR: 1-5). The majority of patients had high-grade dysplasia and/or intramucosal EAC 83.3%. Cryoablation was successfully performed in 78/80 (97.5%); one failure was due to device malfunction and another one due to the device not deploying due to a safety mechanism in a narrow esophagus. We did not encounter any major adverse events. Nine patients (21.5%) of patients developed mild adverse events including mild to moderate chest pain, mild esophageal strictures, and self-resolving sinus bradycardia. CR-IM and CR-D were achieved in 9.5% and 54.8%, respectively, during a mean follow-up of 7.5±5.7 months (IQR: 3-12). Conclusion: This is a large western experience with use of the CbFAS in treating BE with dysplasia or EAC. CryoBalloon CbFAS ablation was performed with a high rate of technical success and no significant adverse events. The CryoBalloon focal ablation system may be considered as a potential alternative to spray treatment when Cryoablation is indicated.378 Figure 1 No Caption available.

Early Barrett esophagus-related neoplasia in segments 1 cm or longer is always associated with intestinal metaplasia.

The assumption that intestinal metaplasia is a prerequisite for intraepithelial neoplasia/dysplasia and adenocarcinoma in the distal esophagus has been challenged by observations of adenocarcinoma without associated intestinal metaplasia. This study describes our experience of intestinal metaplasia in association with early Barrett neoplasia in distal esophagus and gastroesophageal junction. We reviewed the first endoscopic mucosal resection of 139 patients with biopsy-proven neoplasia. In index endoscopic mucosal resection, 110/139 (79%) cases showed intestinal metaplasia. Seven had intestinal metaplasia on prior biopsy specimens and three had intestinal metaplasia in subsequent specimens, totaling 120/139 (86%) patients showing intestinal metaplasia at some point supporting the theory of sampling error for absence of intestinal metaplasia in some cases. Those without intestinal metaplasia (13%) were enriched for higher stage disease (T1a Stolte m2 or above) supporting the assertion of obliteration of intestinal metaplasia by the advancing carcinoma. All cases of intraepithelial neoplasia and T1a Stolte m1 carcinomas had intestinal metaplasia (42/42). The average density of columnar-lined mucosa showing goblet cells was significantly less in shorter segments compared to those ≥3 cm (0.31 vs 0.51, P=0.0304). Cases where segments measured less than 1 cm were seen in a higher proportion of females and also tended to lack intestinal metaplasia. We conclude that early Barrett neoplasia is always associated with intestinal metaplasia; absence of intestinal metaplasia is attributable to sampling error or obliteration of residual intestinal metaplasia by neoplasia and those with segments less than 1 cm show atypical features for Barrett-related disease (absent intestinal metaplasia and female gender), supporting that gastroesophageal junction adenocarcinomas are heterogeneous.

Dedicated Transepithelial Brush Biopsies at the Esophago-Gastric Junction Detect Residual or Recurrent Intestinal Metaplasia Not Seen on White Light or Advanced Imaging After Endoscopic Ablation of Barrettʼs Esophagus

Dedicated Transepithelial Brush Biopsies at the Esophago-Gastric Junction Detect Residual or Recurrent Intestinal Metaplasia Not Seen on White Light or Advanced Imaging After Endoscopic Ablation of Barrettʼs Esophagus

PWE-077 Residual Intestinal Metaplasia after Successful Endoscopic Therapy for Barrett’s Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of The UK RFA Registry

<h3>Introduction</h3> Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. <h3>Methods</h3> Visible lesions were removed by EMR. Patients then underwent RFA 3 monthly. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Dysplasia recurrence was compared in patients who had complete reversal of BE and neoplasia (CR-IM) to those in whom dysplasia alone was eradicated (CR-D only). Residual BE was confirmed with visible columnar epithelium proximal to the OGJ with biopsies showing IM. <h3>Results</h3> 517 patients achieved CR-IM &amp; 96 patients achieved CR-D only after 12 months treatment . Sex &amp; ER rates were not significantly different between groups. The CR-D only group were older (mean age 70 vs 67, p &lt; 0.01) and had longer initial BE (mean length 6.2 cm vs 4.7 cm, p &lt; 0.0001). Mean residual BE length was 1.4 cm. At median follow up 32 months, more patients were disease free in the CR-IM group (96% vs 89%) and Kaplan Meier statistics demonstrated an improved predicted 6 year neoplasia free survival in the CR-IM group (90% vs 84% log rank p 0.0015). Most recurrences occurred within 3 years of follow up. <h3>Conclusion</h3> Endotherapy should aim to clear neoplasia and underlying metaplastic BE to improve long term outcome. Patients with CR-D but not CR-IM at the end of treatment have an increased risk of neoplasia recurrence. This may have implications for post treatment surveillance intervals. <h3>Disclosure of Interest</h3> None Declared

841 Residual Intestinal Metaplasia After Successful Endoscopic Therapy for Barrett's Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of the UK RFA Registry

Introduction Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. Methods Visible lesions were removed by EMR. Patients then underwent RFA 3 monthly. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Dysplasia recurrence was compared in patients who had complete reversal of BE and neoplasia (CR-IM) to those in whom dysplasia alone was eradicated (CR-D only). Residual BE was confirmed with visible columnar epithelium proximal to the OGJ with biopsies showing IM. Results 517 patients achieved CR-IM & 96 patients achieved CR-D only after 12 months treatment . Sex & ER rates were not significantly different between groups. The CR-D only group were older (mean age 70 vs 67, p Conclusion Endotherapy should aim to clear neoplasia and underlying metaplastic BE to improve long term outcome. Patients with CR-D but not CR-IM at the end of treatment have an increased risk of neoplasia recurrence. This may have implications for post treatment surveillance intervals. Disclosure of Interest None Declared

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

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 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. 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). After RFA, endoscopic inspection of the neo-SCJ with NBI in overview or zoom does not reliably predict presence or absence of intestinal metaplasia.

Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett’s esophagus

Endoscopic submucosal dissection (ESD) of early gastrointestinal tumors has been shown to achieve complete resection rates superior to endoscopic mucosal resection (EMR), but at the cost of higher risk. The aim of this study was to prospectively assess the feasibility and oncological results of ESD in patients with neoplastic Barrett's esophagus in conjunction with subsequent radiofrequency ablation (RFA). Patients with Barrett's esophagus who had visible lesions containing high grade intraepithelial neoplasia (HGIN) or mucosal adenocarcinoma (MAC) up to 3 cm in diameter were included in the study. ESD was performed using a new waterjet-assisted system (WESD) with a HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany). Primary outcome was the rate of complete tumor resection. RFA of residual intestinal metaplasia was offered to all patients with at least two negative follow-up endoscopies. Of 30 patients (m:f = 21:9; median age 60 years) with biopsy-proven MAC (n = 24) or HGIN (n = 6) with a median diameter of 2 cm, complete resection of the targeted area was achieved in 29 patients (96.7 %; 95 % confidence interval [CI] 82 % - 99 %); en bloc resection was achieved in 27 of these patients (90.0 %; 95 %CI 74 % - 97 %). Minor delayed bleedings occurred in two patients. One patient died due to a sudden cardiac death 7 days after an uneventful WESD. Specimen histology (n = 29) revealed no neoplasia in 3 patients, HGIN in 2, MAC in 21, and submucosal cancer in 3; complete resection was histologically confirmed in only 10 of the 26 patients with HGIN or adenocarcinoma (38.5 %; 95 %CI 22 % - 57 %). However, endoscopic follow-up (median 17 months) showed complete remission of neoplasia in 27 /28 (96.4 %; 95 %CI 81 % - 99 %) patients who underwent successful WESD and were alive at 30 days. One patient underwent EMR of residual tumor. All Barrett's tissue was eradicated by ESD alone in 15 cases and by additional RFA in 8 /10 cases (not done in three patients). ESD of Barrett's neoplasia is feasible and safe, but does not achieve sufficient R0 resection rates to warrant its recommended use over piecemeal EMR. In combination with RFA it can achieve complete eradication of neoplastic and non-neoplastic Barrett's epithelium. The discrepancy between insufficient oncological resection and good medium-term results needs to be studied further.

Columnar-Lined Esophagus Without Intestinal Metaplasia Has No Proven Risk of Adenocarcinoma

Intestinal metaplasia in the columnar-lined esophagus (CLE) has long been recognized as the most significant histologic risk indicator for esophageal adenocarcinoma. Recent concern has been expressed, however, that nonintestinalized metaplastic columnar epithelia (cardiac epithelium in the esophagus) may also indicate risk. Of 2586 consecutive patients undergoing endoscopy and biopsy in the Foregut Surgery Department, we selected (a) 214 patients with a visible CLE who had systemic 4-quadrant biopsies at 1 to 2 cm intervals, with the most proximal biopsy straddling the squamocolumnar junction, and (b) 109 patients without systematic biopsy who had dysplasia or adenocarcinoma. In the first group, 187 (87.4%) patients had intestinal metaplasia, and 27 (12.6%) had cardiac epithelium. Dysplasia or adenocarcinoma was present in 55 patients, all with intestinal metaplasia; its presence was significantly higher than in the cardiac epithelium group, none of whom had dysplasia or adenocarcinoma (P=0.01). In the second group with limited sampling, 49 had only tumor tissue in the biopsy. Of 60 patients with nontumor epithelium, only 34 (56.7%) had residual intestinal metaplasia. We conclude that systematic biopsies of CLE as described in this study separate patients into those with and without intestinal metaplasia in such a manner as to remove the possibility of false-negative diagnosis of intestinal metaplasia. When intestinal metaplasia is absent using this biopsy protocol, the patient is at no or extremely low risk for dysplasia and cancer. When biopsies have a lower level of sampling of the segment of CLE, the absence of intestinal metaplasia cannot be interpreted as a true negative for intestinal metaplasia. Inadequate sampling is a powerful reason why the near absolute association between intestinal metaplasia and adenocarcinoma is not seen in some studies.

Mo1528 Can Endoscopy With Narrow-Band Imaging Reliably Predict the Presence of Residual Intestinal Metaplasia at the Neosquamocolumnar Junction After Radiofrequency Ablation of Barrett's Esophagus?

Mo1528 Can Endoscopy With Narrow-Band Imaging Reliably Predict the Presence of Residual Intestinal Metaplasia at the Neosquamocolumnar Junction After Radiofrequency Ablation of Barrett's Esophagus?

Endoscopic resection and ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma

Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal adenocarcinoma. New endoscopic approaches allow treatment of these lesions with esophageal preservation. The aim of this study was to compare the outcome of endoscopic therapy with esophagectomy for high-grade dysplasia and intramucosal cancer. A retrospective review was performed of all patients treated for high-grade dysplasia or intramucosal adenocarcinoma from 2001 to April 2010. Endoscopic therapy was performed in 40 patients (high-grade dysplasia = 22, intramucosal cancer = 18) and esophagectomy in 61 patients (high-grade dysplasia = 13, intramucosal cancer = 48). Endotherapy consisted of 102 endoscopic resections and 79 mucosal ablations (median 3 interventions per patient). In the endotherapy group, intramucosal cancer was completely resected in all patients. At last assessment, 10 patients have been converted to intestinal metaplasia without dysplasia and 21 to no residual intestinal metaplasia. Five patients have follow-up biopsy procedures pending after recent ablation, and esophagectomy was performed in 3 patients for failed endotherapy. A laparoscopic Nissen fundoplication has been performed in 8 patients after eradication of intestinal metaplasia. Esophagectomy resected the mucosal disease with negative margins in all patients. Compared with esophagectomy, endotherapy was associated with significantly lower morbidity (39% vs 0; P < .0001) and similar survival (94% at 3 years in both groups; median follow-up 34 months after esophagectomy vs 17 months after endotherapy; P = .0026). Endoscopic therapy for high-grade dysplasia or intramucosal cancer has lower morbidity than an esophagectomy and similar survival during short-term follow-up, but required multiple procedures in most patients. Both therapies are appropriate options, but preservation of the esophagus allows the option of a fundoplication for reflux control, perhaps further improving long-term quality of life.

Treatment of ultralong-segment Barrett’s using focal and balloon-based radiofrequency ablation

Endoscopic radiofrequency ablation (ERFA) is being evaluated as definitive treatment for patients with Barrett's esophagus (BE). Guidelines have yet to be developed for the application of this technology to patients with ultralong-segment BE (ULBE, > or = 8 cm). This study reports a single institution's experience with ERFA of ULBE. A retrospective review of patients with ULBE undergoing ERFA from August 2005 to February 2009 was conducted. The entire segment of intestinal metaplasia (IM) was treated at each session using balloon- and/or plate-based devices (BARRX Medical, Inc., Sunnyvale, CA). Retreatments, endoscopic mucosal resection (EMR), dilations, and biopsies were performed based on endoscopic findings. Surveillance was conducted according to standard guidelines. Twenty-five patients (22 male) with a median age of 66 years [interquartile range (IQR) 57-74 years] were included. The length of BE treated was 10 cm (median; IQR 8-12 cm). Intramucosal carcinoma (IMC) was present in 3 patients, 15 had high-grade dysplasia (HGD), 6 had low-grade dysplasia (LGD), and 1 had IM without dysplasia. Complications for all 25 patients included hemorrhage (n = 1), stricture (n = 2), and nausea and vomiting (n = 2). Time from the initial procedure was such that 15 patients had postablation biopsies at least once. One patient with biopsies elected to undergo esophagectomy. Of these patients, 78.5% (11/14) had complete response (CR; no residual IM), two patients regressed from HGD to IM, and one patient with IMC had residual HGD and was treated with repeat EMR. The number of ablations in this group was 2.5 (median, IQR 2-3) during a median follow-up time of 20.3 months (IQR 10.4-29.2 months). ERFA is safe and feasible in patients with ULBE and can be applied to the entire length of IM during one session. Eradication of BE can be achieved with few repeat ablations and continued, vigilant surveillance.

Endoscopic Therapy for Barrett's Esophagus

Recent retrospective cohort data and a prospective randomized sham controlled trial have clearly documented the impact of endoscopic ablation therapy on dysplasia and Barrett's esophagus (BE). The clinical indications for ablation of BE includes high-grade dysplasia and intramucosal adenocarcinoma. The techniques of resection of mucosal irregularities and of ablation are reviewed, primarily thermal and photodynamic ablation. Ablation of BE with neoplasia has appropriately entered the clinical arena.

Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up

For patients with Barrett's esophagus (BE), life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma. Various endoscopic therapies have been used to eradicate BE. Recently circumferential radiofrequency ablation has been used with encouraging short-term results. To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE. Prospective, multicenter clinical trial (NCT00489268). Eight U.S. centers, between May 2004 and February 2007. Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia (IM). Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM. Follow-up biopsy specimens were obtained at 1, 3, 6, 12, and 30 months. Specimens were reviewed by a central pathology board. Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy (absolute indication) or endoscopic appearance suggestive of columnar-lined esophagus (relative indication). Subjects received esomeprazole for control of esophageal reflux. Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months, defined as complete remission-IM (CR-IM). At 12 months, CR-IM was achieved in 48 of 69 available patients (70% per protocol [PP], 69% intention to treat [ITT]). At 30 months after additional focal ablative therapy, CR-IM was achieved in 60 of 61 available patients (98% PP, 97% ITT). There were no strictures or buried glandular mucosa detected by the standardized biopsy protocol at 12 or 30 months, and there were no serious adverse events. This was an uncontrolled clinical trial with 2.5-year follow-up. Stepwise circumferential and focal ablation resulted in complete eradication of IM in 98% of patients at 2.5-year follow-up.

Predictors and Quantitative Assessment of Incomplete Response After Radiofrequency Ablation for Dysplastic Barrett's Esophagus: Analysis of Randomized Sham-Controlled Clinical Trial (The AIM Dysplasia Trial)

Background: Radiofrequency ablation (RFA) has been shown to completely eradicate dysplastic intestinal metaplasia (IM) in most patients, yet residual IM may persist in some. Aims: The primary endpoint for RFA therapy is complete response-IM (CR-IM, no histological evidence of IM). We sought to describe pt characteristics related to incomplete response-IM (IR-IM, any residual IM). We also assessed dysplasia grade, and extent/location of any residual IM. Methods: We enrolled 127 pts with dysplastic BE (63 HGD, 64 LGD) in a multi-center trial of RFA. Pts were randomized 2:1 (RFA vs. sham) then biopsied q 3 or 6 mo, with centralized path review. RFA was performed until CR-IM or max 4 sessions. Results: 52 pts (35 RFA, 17 sham) have evaluable 12 mo histology. This sub-analysis of the RF group compares CR-IM to IR-IM at 12 mo. The groups had similar hiatal hernia size. IR-IM had a longer pre-treatment period with dysplasia (p < 0.05). They were also older and had higher BMI, more years with BE, longer BE cm, and more multi-focal dysplasia, but given the small sample size of IR-IM, none of these was significant (table). All IR-IM pts had downgrading of dysplasia. For the 3 IR-IM pts with baseline HGD, the worst grade of residual IM was non-dysplastic (1), indefinite (1), or LGD (1). For the 3 IR-IM pts with baseline LGD, all were downgraded to non-dysplastic IM. Of the 6 IR-IM pts at 12 mo, 4 had a single-level IM focus, while 2 had multi-level disease. Five of 6 IR-IM pts had IM only within 1 cm of the top of gastric folds (TGF), while 1 pt had more proximal IM (4-5 cm from the TGF). One IR-IM pt had persistent GERD esophagitis, 1 had ibuprofen-induced ulceration, and 1 had a baseline stricture preventing focal balloon contact. Conclusions: All IR-IM had downgrading of dysplasia and substantial reduction of IM burden. IR-IM pts had a longer pre-treatment period with dysplasia than CR-IM. IR-IM also had insig increases in age, baseline BE length, BMI and % multi-focal. Follow-up RFA is planned for these pts, with the goal to eliminate residual disease. Tabled 1 CR-IM IR-IM Patients (n, %) 29 (83%) 6 (17%) Male (n, %) 24 (83%) 5 (83%) Age years (median, IQR) 64 (59-69) 70.5 (64-74) BMI (median, IQR) 26.5 (25-31) 28.9 (27-32) Years with BE / dysplasia (median) 3.4 / 0.6 6.0 / 2.2 ∗ p < 0.05 Baseline Prague (CM) median 1.5 / 4.0 4.5 / 6.5 Baseline multifocal dysplasia (n, %) 21 (72%) 6 (100%) Baseline HGD (n, %) 9 (31%) 3 (50%) RFA procedures (median) 4 4 12 mo fragments (n) 806 266 12 mo fragments with IM (n, % total) 0 (0%) 25 (9.3%) ∗ p < 0.05 Open table in a new tab

Is intestinal metaplasia a necessary precursor lesion for adenocarcinomas of the distal esophagus, gastroesophageal junction and gastric cardia?

Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed to arise in Barrett's esophagus with intestinal metaplasia. Whether adenocarcinoma can arise in columnar lined esophagus without intestinal metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate the relationship of size and stage of adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia to intestinal metaplasia and other types of columnar epithelium. Seventy-four patients who had esophagogastrectomy for adenocarcinomas in this region were examined histologically to assess the frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors without residual intestinal metaplasia were evaluated for the presence of other columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was present around all tumors. Residual intestinal metaplasia was present in 48 (65%) tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11 (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in all tumors that were less than 1 cm in maximum diameter and all intramucosal tumors. The prevalence of residual intestinal metaplasia decreased with increasing tumor size and stage. These data strongly support the contention that adenocarcinomas of this region, including those in the gastric cardia, arise in intestinal metaplastic epithelium. The absence of residual intestinal metaplasia in larger tumors is the result of tumor overgrowing the intestinal metaplasia from which it arose.

A Randomized Controlled Trial of Ablation of Barrett’s Esophagus With Electrocautery vs. Argon Plasma Coagulation: Long-Term Results

Background: Many modalities have been used to ablate Barrett’s esophagus (BE) including multipolar electrocoagulation (MPEC), argon plasma coagulation (APC), laser, heater probe, etc. However, long-term results and comparative effectiveness are not known. Aim: Our aim was to compare efficacy of achieving complete reversal (ie, endoscopic and histologic) between MPEC and APC in BE patients. Methods: Patients with BE, 2–6 cm long underwent 24-hour pH test on PPI therapy (rabeprazole 20 mg BID). Twenty-four-hour pH was performed by placing probe 5-cm above LES, after at least 7 days of PPI therapy. Patients were then randomized by BE length to undergo ablation with either MPEC or APC every 4–8 weeks till endoscopic reversal or maximum of 6 treatment sessions. If the patient developed reflux symptoms or had documented erosive esophagitis, PPI dose was increased. To document BE reversal, esophagus was sprayed with Lugol’s solution, and 4 quadrant jumbo biopsies every 2 cm were obtained. Biopsies were stained with H&E/alcian blue to detect residual intestinal metaplasia. Fisher’s exact test and logistic regression were done to study effect of BE length, pH scores, hernia size, PPI dose, and ablation modality in achieving BE reversal. Results: Thirty-five BE patients have been followed-up for at least 2 years after endoscopic ablation, 16 treated with MPEC, and 19 with APC. Mean age was 61 years (32–84 years), 34 males. Mean length of BE was 3.7 ± 1.7 cm. Median total time pH <4 was 0.6% (range 0–29.9%); median upright and supine values were 0.7% and 0% respectively. Acid exposure normalized in 26 patients (74%) on rabeprazole 20 mg BID. BE completely reversed in 24 patients (69%); 75% with MPEC, and 63% with APC (P = .49). Mean number of sessions required was 3.8 in MPEC and 3.4 in APC group (P = .48). There was no significant difference in either treatment type (MPEC vs. APC), pH results, BE length, PPI dose, or hernia size between patients with and without complete reversal. No GI bleed or perforations noted; one patient developed an esophageal stricture treated successfully with 1 dilation. Conclusions: In BE patients treated with MPEC or APC in combination with aggressive acid suppression, there are no significant predictors associated with achieving complete reversal of BE including BE length, 24-hour pH, hiatus hernia size, and PPI dose. At long-term follow-up (2 years), complete reversal of BE can be maintained in ∼ 70% of patients irrespective of technique, ie, MPEC vs. APC. Continued surveillance is still indicated in post-ablative setting.

A Randomized Controlled Trial of Ablation of Barrett's Esophagus With Electrocautery Vs. Argon Plasma Coagulation: Long Term Results

Many modalities have been used to ablate Barrett's esophagus (BE) including multipolar electrocoagulation(MPEC), argon plasma coagulation(APC), laser, heater probe, etc. However, long term results and comparative effectiveness are not known. Aim: Our aim was to compare efficacy of achieving complete reversal (i.e. endoscopic and histologic) between MPEC and APC in BE pts. Methods: Pts with BE, 2-6 cm long underwent 24 hr pH test on PPI therapy (rabeprazole 20 mg BID). 24 h pH was performed by placing probe 5 cm above LES, after at least 7 days of PPI therapy. Pts were then randomized by BE length to undergo ablation with either MPEC or APC every 4-8 weeks till endoscopic reversal or maximal of 6 treatment sessions. If pt developed reflux symptoms or had documented erosive esophagitis, PPI dose was increased. To document BE reversal, esophagus was sprayed with Lugol's solution and 4 quadrant jumbo biopsies every 2 cm were obtained. Biopsies were stained with H & E/alcian blue to detect residual intestinal metaplasia. Fisher's Exact test and logistic regression were done to study effect of BE length, pH scores, hernia size, PPI dose & ablation modality in achieving BE reversal. Results: 35 BE pts. have been followed for at least 2 yrs after endoscopic ablation, 16 treated with MPEC and 19 with APC. Mean age was 61 yrs (32-84 years), 34 males. Mean length of BE was 3.7 +/− 1.7 cm. Median total time pH <4 was 0.6% (range 0-29.9%); median upright & supine values were 0.7% and 0% respectively. Acid exposure normalized in 26 pts (74%) on rabeprazole 20mg BID. BE completely reversed in 24 pts (69%); 75% with MPEC and 63% with APC (p = 0.49). Mean no. of sessions required was 3.8 in MPEC and 3.4 in APC group (p = 0.48). There was no significant difference in either treatment type (MPEC vs. APC), pH results, BE length, PPI dose or hernia size between pts with and without complete reversal. No GI bleed or perforations noted; one pt developed an esophageal stricture treated successfully with 1 dilation. Conclusions: In BE pts. treated with MPEC or APC in combination with aggressive acid suppression, there are no significant predictors associated with achieving complete reversal of BE including BE length, 24 hr pH, hiatus hernia size and PPI dose. At long term f/u (2yrs), complete reversal of BE can be maintained in ~ 70% of pts irrespective of technique i.e. MPEC vs. APC. Continued surveillance is still indicated in post ablative setting. Funded by Eisai/Janssen.

Effect of multipolar electrocoagulation on EUS findings in Barrett's esophagus

Background: Restoration of squamous epithelium in patients with Barrett's epithelium may be achieved by treatment with a proton pump inhibitor plus selective electrocoagulation of the metaplastic epithelium. The effect of such treatment on esophageal wall thickness and morphology, as determined by EUS, is unknown. Methods: Patients with Barrett's esophagus were treated with omeprazole (40 mg by mouth, twice daily) and underwent selective multipolar electrocoagulation of the metaplastic segment monthly until complete squamous re-epithelialization or a maximum of 6 treatments was achieved. EUS was performed before and 6 months after the end of treatment. Four-quadrant large-forceps biopsy specimens were taken every 2 cm at the 6-month follow-up. Results: Twenty-five patients with Barrett's epithelium (mean length 3.1 cm, range 2-6 cm) were included. Complete endoscopic reversal was achieved in 24 patients. Residual intestinal metaplasia beneath squamous epithelium was observed in 1 patient. In 4 patients there was intestinalized mucosa at the neosquamocolunmar junction. The thickness of the treated distal esophageal wall decreased from 4.0 ± 0.1 mm to 3.7 ± 0.1 mm (mean ± SEM; p < 0.05, 2-tailed paired t test). Untreated (control) esophageal wall thickness at the level of the aortic arch (2.1 ± 0.1 mm vs. 2.2 ± 0.1 mm) and the mid-body gastric wall thickness (2.9 ± 0.1 mm vs. 3.1 ± 0.1 mm) did not change. Among the 6 patients with residual intestinal metaplasia there was no change in mean wall thickness (3.7 ± 0.2 mm vs. 3.8 ± 0.2 mm); among the 19 without metaplasia, thickness decreased from 4.1 ± 0.2 mm to 3.6 ± 0.2 mm; p < 0.01. Of 11 patients with a decrease in wall thickness, only 1 had residual intestinal metaplasia. No changes in the 5-layer sonographic pattern of the esophageal wall were observed. Conclusions: Multipolar electrocoagulation of Barrett's esophagus results in a slight decrease in thickness of the treated esophageal wall. A decrease in wall thickness by EUS was associated with the absence of intestinal metaplasia in follow-up biopsy specimens. (Gastrointest Endosc 2002;55:23-6.)