Subsquamous Intestinal Metaplasia Research Articles

An Endoscopic and Histologic Study on Healing of Radiofrequency Ablation Wounds in Patients With Barrett's Esophagus.

Radiofrequency ablation (RFA) of Barrett's esophagus (BE) inflicts a wound spanning 3 epithelial types (stratified squamous, Barrett's metaplasia, gastric epithelium), yet the esophageal injury heals almost completely with squamous epithelium. Knowledge of how this unique wound heals might elucidate mechanisms underlying esophageal metaplasia. We aimed to prospectively and systematically characterize the early endoscopic and histologic features of RFA wound healing. Patients with nondysplastic BE had endoscopy with systematic esophageal photographic mapping, biopsy, and volumetric laser endomicroscopy performed before and at 1, 2, and 4 weeks after RFA. Seven patients (6 men; mean age 56.1 ± 10.9 years) completed this study. Squamous re-epithelialization of RFA wounds did not only progress exclusively through squamous cells extending from the proximal wound edge but also progressed through islands of squamous epithelium sprouting throughout the ablated segment. Volumetric laser endomicroscopy revealed significant post-RFA increases in subepithelial glandular structures associated with the squamous islands. In 2 patients, biopsies of such islands revealed newly forming squamous epithelium contiguous with immature-appearing squamous cells arising from esophageal submucosal gland ducts. Subsquamous intestinal metaplasia (SSIM) was found in biopsies at 2 and/or 4 weeks after RFA in 6 of 7 patients. RFA wounds in BE are re-epithelialized, not just by squamous cells from the proximal wound margin but by scattered squamous islands in which esophageal submucosal gland duct cells seem to redifferentiate into the squamous progenitors that fuel squamous re-epithelialization. SSIM can be found in most patients during the healing process. We speculate that this SSIM might underlie Barrett's recurrences after apparently successful eradication.

Subskvamózní neoplazie po radiofrekvenční ablaci Barrettova jícnu

The term sub-squamous neoplasia or “buried carcinoma” refers to neoplastic processes developing in intestinal metaplasia lesions localised in the lamina propria below the squamous epithelium of the oesophagus. Sub-squamous intestinal metaplasia are located in the transition area between Barrett and squamous epithelium and also beneath neo-squamous epithelium that develops post endoscopic ablation. To date, less than 20 cases of sub squamous neoplasia following successful radiofrequency ablation of Barrett’s oesophagus have been reported in the MedLine database. Knowledge of these conditions is important for adequate follow-up and timely dia gnosis of this potentially fatal complication. Keywords: radiofrequency ablation – buried carcinoma – Barrett’s oesophagus – oesophageal adenocarcinoma

A human Barrett's esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts.

The pathogenesis of subsquamous intestinal metaplasia (SSIM), in which glands of Barrett's esophagus (BE) are buried under esophageal squamous epithelium, is unknown. In a rat model of reflux esophagitis, we found that columnar-lined esophagus developed via a wound-healing process involving epithelial-mesenchymal plasticity (EMP) that buried glands under ulcerated squamous epithelium. To explore a role for reflux-induced EMP in BE, we established and characterized human Barrett's organoids and sought evidence of EMP after treatment with acidic bile salts (AB). We optimized media to grow human BE organoids from immortalized human Barrett's cells and from BE biopsies from seven patients, and we characterized histological, morphological, and molecular features of organoid development. Features and markers of EMP were explored following organoid exposure to AB, with and without a collagen I (COL1) matrix to simulate a wound-healing environment. All media successfully initiated organoid growth, but advanced DMEM/F12 (aDMEM) was best at sustaining organoid viability. Using aDMEM, organoids comprising nongoblet and goblet columnar cells that expressed gastric and intestinal cell markers were generated from BE biopsies of all seven patients. After AB treatment, early-stage Barrett's organoids exhibited EMP with loss of membranous E-cadherin and increased protrusive cell migration, events significantly enhanced by COL1. Using human BE biopsies, we have established Barrett's organoids that recapitulate key histological and molecular features of BE to serve as high-fidelity BE models. Our findings suggest that reflux can induce EMP in human BE, potentially enabling Barrett's cells to migrate under adjacent squamous epithelium to form SSIM.NEW & NOTEWORTHY Using Barrett's esophagus (BE) biopsies, we established organoids recapitulating key BE features. During early stages of organoid development, a GERD-like wound environment-induced features of epithelial-mesenchymal plasticity (EMP) in Barrett's progenitor cells, suggesting that reflux-induced EMP can enable Barrett's cells to migrate underneath squamous epithelium to form subsquamous intestinal metaplasia, a condition that may underlie Barrett's cancers that escape detection by endoscopic surveillance, and recurrences of Barrett's metaplasia following endoscopic eradication therapy.

Allaying uncertainty in diagnosing buried Barrett's esophagus

Subsquamous intestinal metaplasia (SSIM) in the setting of Barrett's esophagus (BE) is a technically challenging diagnosis. While the risk for progression of BE involving the surface mucosa is well documented, the potential risk for development of advanced neoplasia associated with SSIM has been controversial. This study aimed to determine the effects of specimen adequacy, presence of dysplasia, and interobserver agreement for SSIM interpretation. Adult patients (n = 28) who underwent endoscopic therapy for BE with high-grade dysplasia or intramucosal carcinoma (HGD/IMC) between October 2005 and June 2013 were included. Initial evaluation (n = 140 slides) by an experienced gastrointestinal pathologist was followed by an interobserver study by 8 pathologists. Forty-seven (34%) slides had insufficient subsquamous tissue to assess for SSIM. SSIM was found in 19% of all slides and 29% of slides with sufficient subsquamous tissue. At least one slide had SSIM in 54% to 64% of patients. Subsquamous low grade dysplasia (LGD) was found in 4 (15%) slides with SSIM and subsquamous HGD/IMC was found in 5 (19%) slides with SSIM. At the patient level, 8 (53%) had no dysplasia, 4 (27%) had LGD and 3 (20%) had HGD/IMC. Overall agreement for SSIM by slide was 92% to 94% (κ = 0.73 to κ = 0.82, moderate to strong agreement), and by patient was 82% to 94% (κ = 0.65 to κ = 0.87, moderate to strong agreement). This study confirms the need for assessing specimen adequacy and assessing the prevalence of SSIM and is the first to assess interobserver agreement for SSIM and dysplasia within SSIM.

AGA Clinical Practice Update on Endoscopic Treatment of Barrett’s Esophagus With Dysplasia and/or Early Cancer: Expert Review

The purpose of this best practice advice article is to describe the role of Barrett's endoscopic therapy (BET) in patients with Barrett's esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients. The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee. BEST PRACTICE ADVICE 1: In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3-6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection. BEST PRACTICE ADVICE 2: Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia. BEST PRACTICE ADVICE 3: BET is the preferred treatment for BE patients with high-grade dysplasia (HGD). BEST PRACTICE ADVICE 4: BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a). BEST PRACTICE ADVICE 5: BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-μm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates. BEST PRACTICE ADVICE 6: In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5-10 mm proximal to the squamocolumnar junction and 3) 5-10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion. BEST PRACTICE ADVICE 7: Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities. BEST PRACTICE ADVICE 8: BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually. BEST PRACTICE ADVICE 9: BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies. BEST PRACTICE ADVICE 10: If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation. BEST PRACTICE ADVICE 11: Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy. BEST PRACTICE ADVICE 12: When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%. BEST PRACTICE ADVICE 13: After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years. BEST PRACTICE ADVICE 14: Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia. BEST PRACTICE ADVICE 15: The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation. BEST PRACTICE ADVICE 16: Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.

Covering the Cover

Covering the Cover

Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells

Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett esophagus (BE). This subsquamous intestinal metaplasia might be responsible for cancers that develop despite endoscopic surveillance and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo an epithelial-to-mesenchymal transition (EMT) that produces subsquamous intestinal metaplasia, we assessed EMT in BE cells exposed to acidic bile salts and in rat and human esophageal tissues. We compared markers of EMT and cell motility in trans-well and 3-dimensional organotypic culture systems among dysplastic BE epithelial cell lines, nondysplastic telomerase-immortalized BE cell lines (BAR-T), and BAR-T cells exposed acutely or for 20 weeks to acidic bile salts. Vascular endothelial growth factor (VEGF) A was inhibited with a neutralizing antibody or CRISPR-Cas9n and VEGF receptor 2 was inhibited with SU1498 or shRNA, and cells were analyzed by immunohistochemistry, quantitative polymerase chain reaction, or immunoblotting for markers of VEGF signaling and EMT; cell motility was assessed by trans-well assay. We used immunohistochemistry and quantitative polymerase chain reaction to assess EMT markers in the columnar-lined esophagus of rats with surgically induced reflux esophagitis and in esophagectomy specimens from patients with BE. We detected features of EMT (decreased cadherin 1 [CDH1]; increased fibronectin 1, vimentin, and matrix metalloproteinase 2; and increased motility) in dysplastic BE epithelial cell lines and in BAR-T cells exposed for 20 weeks, but not in unexposed BAR-T cells. Acute acidic bile salt exposure induced expression of zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) in BAR-T cells, which decreased their expression of CDH1 and increased motility; inhibitors of VEGF signaling blocked these effects. Columnar-lined esophagus of rats with reflux esophagitis had increased expression of ZEB1/2 and decreased expression of CDH1 compared with controls. Dysplastic BE tissues also had significantly increased levels of ZEB1 and significantly decreased levels of CDH1 compared with nondysplastic BE tissues. In BE cell lines, acidic bile salts induce EMT by VEGF signaling, which increases expression of ZEB1/2, repressors of CDH1. These observations suggest that reflux induces EMT in metaplastic BE tissues, which promotes development of subsquamous intestinal metaplasia.

332 - Reflux-Induced Epithelial Mesenchymal Transition: A Potential Mechanism for the Development of Sub-Squamous Intestinal Metaplasia in Barrett's Esophagus

332 - Reflux-Induced Epithelial Mesenchymal Transition: A Potential Mechanism for the Development of Sub-Squamous Intestinal Metaplasia in Barrett's Esophagus

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

Subsquamous intestinal metaplasia is common in treatment-naïve Barrett’s esophagus

Barrett's intestinal metaplasia may extend beneath normal squamous epithelium at the squamocolumnar junction (SCJ) and therefore escape surveillance biopsy sampling. The prevalence of subsquamous intestinal metaplasia (SSIM) in patients undergoing Barrett's esophagus (BE) surveillance is unknown. Our aim was to examine the prevalence and distribution of SSIM proximal to the SCJ in patients undergoing BE surveillance. We enrolled consecutive patients with biopsy specimen-proven BE. Biopsy specimens were obtained from the squamous epithelium at 5mm and 10mm above the SCJ. The primary outcomes were the proportion of patients with SSIM at each level. We further assessed factors associated with SSIM. We examined 515 squamous epithelial biopsy specimens from 106 BE patients (95% men; mean age, 66 years) with a mean Barrett's length of 3.0 cm. SSIM was present in 39% at 5mm (95% CI, 29.4-48.6) and 21% (95% CI, 11.7-32.1) at 10mm proximal to the SCJ. Among all biopsy specimens, 13% (95% CI, 10.6-16.6) contained SSIM: 17% (95% CI, 13-21.6) of biopsy samples at 5mm and 8% (95% CI, 4.3-12.2) at 10mm proximal to the SCJ. SSIM was more common in the anterior/right lateral position compared with the posterior/left lateral position (21% vs 11%, P= .001). None of the biopsy specimens showed dysplasia. Length of BE or duration of reflux symptoms were not associated with the presence of SSIM. This cross-sectional study found a surprisingly high proportion of SSIM in treatment-naïve patients proximal to the SCJ. These findings raise questions regarding BE management and the prevalence of SSIM in normal-appearing esophagus.

OC-027 Buried barrett’s dysplasia: rfa is not the only culprit: Abstract OC-027 Table 1

<h3>Introduction</h3> Buried Barrett’s’ or Subsquamous Intestinal Metaplasia (SSIM) refers to glands which are ‘buried’ underneath the squamous epithelium. Buried Barrett’s can pose significant diagnostic and surveillance challenges. Buried Barrett’s has mainly been reported in the post ablation context (APC, RFA, PDT). We aim to evaluate its prevalence in patients who are ablation naïve, and understand the reasons behind it. <h3>Method</h3> This is a prospective cohort study. We investigated our Barrett’s database for patients who were referred for endoscopic treatment (EMR) of Barrett’s neoplasia between June 2006 to June 2014. We assessed histology reports before and after endoscopic therapy (EMR), specifically looking for evidence of buried Barrett’s. Biopsy: Biopsies were first obtained from any suspicious looking area. Following this, biopsies were then obtained from the neosquamous area. Finally, random biopsies were obtained. These were sent in separate cassettes. Histopathology was reported by two independent GI pathologists and was prospectively recorded on a central pathology database. Buried Barrett’s was defined as any metaplastic or glandular tissue beneath the squamous epithelium. Pathology specimens were reported by 2 independent, accredited GI pathologists. <h3>Results</h3> Our study shows that in the pre-EMR cohort, there was an overall prevalence of 12.2% of buried Barrett’s and a 9.1% prevalence of buried Barrett’s with high grade neoplasia (HGD or IMC). Our results in the post EMR cohort shows an overall prevalence of 16.8% of buried Barrett’s with 6.1% prevalence of buried high grade neoplasia (HGD or IMC). This has significant implications for post EMR endoscopic assessment and surveillance. <h3>Conclusion</h3> Buried Barrett’s and Barrett’s cancer are seen in endotherapy naïve patients. This is likely to be related to intensive biopsies. EMR, despite being a non ablation technique, still results in buried Barrett’s and Barrett’s cancer. The overall prevalence of buried Barrett’s is higher than previously reported. We need to be aware of this while assessing Barrett’s patients. Buried Barrett’s glands after ablation (APC/RFA/PDT) are well reported. This is the first study to report on the prevalence of Barrett’s in endotherapy naïve patients and in the post EMR cohort. <h3>Disclosure of interest</h3> None Declared.

Esophageal neoplasia arising from subsquamous buried glands after an apparently successful photodynamic therapy or radiofrequency ablation for Barrett’s associated neoplasia

Objective. Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are effective non-surgical options for the treatment of Barrett’s esophagus (BE) associated neoplasia. Development of subsquamous intestinal metaplasia after successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of neoplasia arising from buried glands is a rare complication. Methods. This is a prospective case series of patients treated with PDT and/or RFA from 1999 to 2014 at University College London Hospital for neoplasia associated with BE, whose outcomes were analyzed retrospectively. Prior to any ablative therapy any visible nodularity was removed with endoscopic mucosal resection (EMR). After successful PDT and/or HALO RFA treatment, defined as a complete reversal of dysplasia and metaplasia, patients underwent endoscopic follow up using the Seattle protocol. Results. A total of 288 patients were treated, 91 with PDT between 1999 and 2010, 173 with RFA between 2007 and 2014, and 24 with both PDT and RFA for neoplasia associated with BE. Subsquamous neoplasia occurred in seven patients (7/288, 2%). The first patient developed subsquamous invasive adenocarcinoma and underwent curative surgery. Another five patients with subsquamous neoplasia (either high-grade dysplasia or intramucosal cancer) were treated successfully with EMR. The final patient developed subsquamous invasive esophagogastric junctional adenocarcinoma with liver metastases. Conclusion. Development of subsquamous neoplasia after an apparently successful PDT and/or RFA is a rare but recognized complication. Clinicians should be aware of this phenomenon and have a low threshold for performing an EMR. Thorough surveillance following successful PDT and/or RFA ensuring high-quality endoscopy is required.

Sa1896 Subsquamous Intestinal Metaplasia and Neoplasia After Radiofrequency Ablation for Barrett's Esophagus: A Systematic Review and Meta-Analysis

Sa1896 Subsquamous Intestinal Metaplasia and Neoplasia After Radiofrequency Ablation for Barrett's Esophagus: A Systematic Review and Meta-Analysis

PTU-041 Sub-squamous Columnar Neoplasia After Successful Radiofrequency Ablation For Barrett’s Related Neoplasia Is Rare But Highlights Requirement For Long Term Follow Up In These Patients

IntroductionRadiofrequency ablation (RFA) combined with endoscopic mucosal resection (EMR) has become the preferred treatment for BE related neoplasia. Success rates of 90% after treatment with a durability of up to...

Tumeurs et pseudotumeurs digestives dont on parle rarement. Cas no 3 : polype muqueux/sous-muqueux allongé

The purpose of this best practice advice article is to describe the role of Barrett’s endoscopic therapy (BET) in patients with Barrett’s esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients.The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee.In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3–6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection.Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia.BET is the preferred treatment for BE patients with high-grade dysplasia (HGD).BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a).BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-μm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates.In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5–10 mm proximal to the squamocolumnar junction and 3) 5–10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion.Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities.BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually.BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies.If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation.Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy.When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%.After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years.Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia.The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation.Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.

Subsquamous Extension of Intestinal Metaplasia Is Detected in 98% of Cases of Neoplastic Barrett's Esophagus

Subsquamous intestinal metaplasia (SSIM) has been observed after endotherapy in patients with neoplastic Barrett's esophagus (BE). However, it is not clear whether SSIM occurs in untreated patients. Incompletely eradicated SSIM could provide a source of recurrent disease. We assessed its prevalence in a large cohort of patients who had not received endoscopic therapy. Two experienced pathologists analyzed 138 samples of 506 resection specimens found to contain squamous epithelium from 110 patients with neoplastic BE treated by widespread endoscopic mucosal resection (92 men; mean age, 66 years). The maximum extent of SSIM was measured. Of the 138 samples analyzed, 124 (89.9%) were found to contain SSIM from 108 of the 110 patients (98.2%). The mean length of SSIM was 3.3 mm (range, 0.2-9.6 mm; 25% ≥ 5 mm); SSIM length correlated with BE length (P < .05). In 83 of 138 samples (60.1%), the SSIM consisted partially or entirely of neoplasias of different grades, with a mean subsquamous extension of 3.3 mm; the extension correlated with grade of neoplasia (P = .0001). Most patients with BE with neoplasia (of all grades) have subsquamous extension of intestinal metaplasia, including subsquamous extension of lesions at the squamocolumnar junction. Therefore, biopsy and resection of neoplastic BE should extend at least 1 cm into the squamous epithelium.

Subsquamous intestinal metaplasia after ablation of Barrettʼs esophagus

This article reviews reports on the prevalence of subsquamous intestinal metaplasia (SSIM) in patients with Barrett's esophagus, and the implications of SSIM in the neoplastic progression of Barrett's esophagus to esophageal adenocarcinoma. Endoscopic eradication therapy for dysplastic Barrett's esophagus has become an encouraging alternative to esophagectomy or continued endoscopic surveillance. However, the presence of SSIM before and after ablation is concerning because this tissue may have potential for malignant progression, is not visible by conventional endoscopy, and may evade detection by random esophageal biopsy sampling methods. Advances in endoscopic high-resolution three-dimensional optical coherence tomography recently have revealed SSIM in a majority of patients both before and after complete eradication of Barrett's esophagus by radiofrequency ablation. Studies suggest that although cells of Barrett's glands are highly proliferative, the cells of these buried glands are more dormant. Nevertheless, the malignant potential of SSIM cells remains undetermined. Novel endoscopic imaging demonstrates that SSIM is present in the majority of patients with Barrett's esophagus, both before and after ablative therapy. Although these subsquamous cells exhibit less proliferative activity than those of typical surface Barrett's glands, the malignant potential of the buried glands, especially when challenged by injurious factors, remains largely unknown. Future methods to detect subsurface dysplasia will be needed.

Markers suggest reduced malignant potential of subsquamous intestinal metaplasia compared with Barrett's esophagus

Esophageal subsquamous intestinal metaplasia (SSIM) is frequently observed in patients with Barrett's esophagus (BE) and can also be found in patients after endoscopic ablative treatments for dysplastic BE. While these 'buried glands' appear identical to BE glands, features of SSIM and its malignant potency have yet to be fully elucidated. To determine differences in malignant potential between nondysplastic BE and SSIM, the Automated Cellular Imaging System was used to assess and compare changes in DNA content between SSIM and BE. Samples were further immunostained for Ki67 and Lgr5 to gauge general proliferative and possible stem cell features, respectively, in SSIM cells compared with BE glands. No significant differences were found between SSIM and BE with regards to DNA ploidy aberrance. However, significant differences were noted between SSIM and BE upon immunohistochemical analysis. SSIM was found to be negative for both Ki67 and Lgr5 while BE was positive for both markers. SSIM cells appear to be relatively quiescent and behave differently from BE, suggesting a reduced proclivity toward cancer progression.

PTU-171 Buried Barrett’S Dysplasia (‘Bbad’) Study: Results from a long Term follow up Study of Barrett’S Neoplasia Cohort

IntroductionBuried Barrett’s’ or Subsquamous intestinal metaplasia (SSIM) refers to glands which are ‘buried’ underneath the squamous epithelium. High dose acid suppressive therapy and lack of acid exposure can result in...

285 Predictors of Subsquamous Intestinal Metaplasia (SSIM) in Patients With Prior Radiofrequency Ablation (RFA) for Treatment of Barrett's Esophagus: Results From the U.S. RFA Registry

Subsquamous intestinal metaplasia (SSIM) is defined as metaplastic columnar tissue found beneath an overlying layer of intact squamous epithelium. SSIM occurs in >25% of those with dysplastic Barrett's esophagus (BE), and in 5% or more of patients following radiofrequency ablation (RFA) for BE. We assessed the predictors of SSIM in a nationwide RFA registry.