Barrett's Neoplasia Research Articles

Mo1989 Stepwise Development of a Volumetric Laser Endomicroscopy Prediction Score for Barrett's Neoplasia Using Matched VLE-Histology Images of Endoscopic Resection Specimens

Mo1989 Stepwise Development of a Volumetric Laser Endomicroscopy Prediction Score for Barrett's Neoplasia Using Matched VLE-Histology Images of Endoscopic Resection Specimens

Tu1201 How Good Are Experts in Identifying Endoscopically Visible Early Barrett's Neoplasia on in vivo Volumetric Laser Endomicroscopy?

Tu1201 How Good Are Experts in Identifying Endoscopically Visible Early Barrett's Neoplasia on in vivo Volumetric Laser Endomicroscopy?

60 Increased Detection of Barrett's Esophagus-Associated Neoplasia Using Wide Area Transepithelial Sampling in Conjunction With 4-Quadrant Forceps Biopsies: Final Results From a Multi-Center, Prospective, Randomized Trial

60 Increased Detection of Barrett's Esophagus-Associated Neoplasia Using Wide Area Transepithelial Sampling in Conjunction With 4-Quadrant Forceps Biopsies: Final Results From a Multi-Center, Prospective, Randomized Trial

Computer-aided detection of early neoplastic lesions in Barrett's esophagus.

Early neoplasia in Barrett's esophagus is difficult to detect and often overlooked during Barrett's surveillance. An automatic detection system could be beneficial, by assisting endoscopists with detection of early neoplastic lesions. The aim of this study was to assess the feasibility of a computer system to detect early neoplasia in Barrett's esophagus. Based on 100 images from 44 patients with Barrett's esophagus, a computer algorithm, which employed specific texture, color filters, and machine learning, was developed for the detection of early neoplastic lesions in Barrett's esophagus. The evaluation by one endoscopist, who extensively imaged and endoscopically removed all early neoplastic lesions and was not blinded to the histological outcome, was considered the gold standard. For external validation, four international experts in Barrett's neoplasia, who were blinded to the pathology results, reviewed all images. The system identified early neoplastic lesions on a per-image analysis with a sensitivity and specificity of 0.83. At the patient level, the system achieved a sensitivity and specificity of 0.86 and 0.87, respectively. A trade-off between the two performance metrics could be made by varying the percentage of training samples that showed neoplastic tissue. The automated computer algorithm developed in this study was able to identify early neoplastic lesions with reasonable accuracy, suggesting that automated detection of early neoplasia in Barrett's esophagus is feasible. Further research is required to improve the accuracy of the system and prepare it for real-time operation, before it can be applied in clinical practice.

Sa1275 Patient Decision-Making and Clinical Outcomes Following Endoscopic Therapy or Esophagectomy for Barrett's Neoplasia

Sa1275 Patient Decision-Making and Clinical Outcomes Following Endoscopic Therapy or Esophagectomy for Barrett's Neoplasia

237 Feasibility of a Computer Algorithm for Detection of Early Barrett's Neoplasia Using Volumetric Laser Endomicroscopy

237 Feasibility of a Computer Algorithm for Detection of Early Barrett's Neoplasia Using Volumetric Laser Endomicroscopy

Su2076 How Good are Experts in Identifying Early Barrett's Neoplasia in Endoscopic Resection Specimens Using Volumetric Laser Endomicroscopy?

Su2076 How Good are Experts in Identifying Early Barrett's Neoplasia in Endoscopic Resection Specimens Using Volumetric Laser Endomicroscopy?

Su2052 NOTCH1 Is Overexpressed in Barrett's Epithelial Neoplasia and Can Be Inhibited by Curcumin

Su2052 NOTCH1 Is Overexpressed in Barrett's Epithelial Neoplasia and Can Be Inhibited by Curcumin

Adherence to therapy for Barrett's esophagus-associated neoplasia.

Multiple endoscopic sessions may be necessary for treatment and surveillance of Barrett's esophagus (BE)-associated neoplasia. Adherence to an endoscopic therapeutic regimen is important for longitudinal management of BE. The objective of this study was to identify the factors associated with adherence to therapy for BE-associated neoplasia. We retrospectively identified patients with BE whom were referred to a tertiary center for endoscopic mucosal resection (EMR) or radiofrequency ablation (RFA) between 2009 and 2012. Demographic and clinical data were extracted from the medical record. We had 69 subjects meet our inclusion criteria. Referral diagnosis was low-grade dysplasia in 9 (13%) subjects, high-grade dysplasia in 33 (48%) subjects and adenocarcinoma in 26 (38%) subjects. The majority (55%) lived more than 100 miles from the treatment center. The primary third-party payer was US Medicare for 54% of the subjects and private insurance for 36% of them; 45% of the subjects were seen in the clinic by the treating endoscopist, prior to endoscopic therapy and 71% underwent EMR as the initial treatment, while 29% underwent RFA without prior EMR. We found that 72% of subjects were adherent to therapy, including: 23 (33%) completing endoscopic therapy with documented post-treatment surveillance, 18 (26%) with ongoing endoscopic therapy, and 9 (13%) whom underwent esophagectomy. Subjects seen in gastroenterology clinical consultation were significantly more likely to demonstrate adherence than those referred for open access endoscopy (Lasso OR 2.31). Patients seen in a clinical consultation prior to endoscopic therapy for BE-associated neoplasia were more likely to demonstrate treatment adherence, compared to patients referred for open-access endoscopy. A clinic visit prior to therapy may define expectations regarding treatment course and increase the likelihood of patient adherence.

Advances in the endoscopic diagnosis and treatment of Barrett's neoplasia.

Barrett’s oesophagus is a well-recognised precursor of oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma is continuing to rise in the Western world with dismal survival rates. In recent years, efforts have been made to diagnose Barrett’s earlier and improve surveillance techniques in order to pick up cancerous changes earlier. Recent advances in endoscopic therapy for early Barrett’s cancers have shifted the paradigm away from oesophagectomy and have yielded excellent results.

Endoscopic Treatment of Early Barrett's Neoplasia: Expanding Indications, New Challenges.

Endoscopic therapy of early Barrett's neoplasia is nowadays the treatment of choice and recommended over surgery in most current guidelines. Recent data suggest radiofrequency ablation of low-grade intraepithelial neoplasia when confirmed by an expert pathologist. Endoscopic therapy of high-grade intraepithelial neoplasia and mucosal Barrett's adenocarcinoma consists of two steps: first endoscopic resection of all visible lesions, and second ablation of the remaining flat Barrett's mucosa to reduce the rate of recurrences and metachronous neoplasia. The preferred ablation method is radiofrequency ablation. In case of Barrett's adenocarcinoma with incipient submucosal invasion, endoscopic treatment can be considered curative when there are no further risk factors present.

Usefulness and Future Prospects of Confocal Laser Endomicroscopy for Gastric Premalignant and Malignant Lesions.

Confocal laser endomicroscopy (CLE) is a new technology enabling endoscopists to visualize tissue at the cellular level. CLE has the fundamental potential to provide a histologic diagnosis, and may theoretically replace or reduce the need for performing biopsy for histology. The clinical benefits of CLE are more obvious in esophageal disease, including Barrett’s esophagus. Currently, this technology has been adapted to the diagnosis and surveillance of Barrett’s esophagus and related neoplasia. Standard white light endoscopy is the primary tool for gastric cancer screening. Currently, the only method available to precisely diagnose these lesions is upper endoscopy with an appropriate biopsy. A recent study showed that CLE could characterize dysplasia or cancer and identify the risk factors for gastric cancer, such as intestinal metaplasia and the presence of Helicobacter pylori in vivo, although fewer studies on CLE were performed on the stomach than on Barrett’s esophagus and other esophageal diseases. However, the application of CLE to routine clinical endoscopy continues to be refined. This review focused on the usefulness and future prospects of CLE for gastric premalignant and malignant lesions.

In-class didactic versus self-directed teaching of the probe-based confocal laser endomicroscopy (pCLE) criteria for Barrett's esophagus.

Optimal teaching methods for disease recognition using probe-based confocal laser endomicroscopy (pCLE) have not been developed. Our aim was to compare in-class didactic teaching vs. self-directed teaching of Barrett's neoplasia diagnosis using pCLE. This randomized controlled trial was conducted at a tertiary academic center. Study participants with no prior pCLE experience were randomized to in-class didactic (group 1) or self-directed teaching groups (group 2). For group 1, an expert conducted a classroom teaching session using standardized educational material. Participants in group 2 were provided with the same material on an audio PowerPoint. After initial training, all participants graded an initial set of 20 pCLE videos and reviewed correct responses with the expert (group 1) or on audio PowerPoint (group 2). Finally, all participants completed interpretations of a further 40 videos. Eighteen trainees (8 medical students, 10 gastroenterology trainees) participated in the study. Overall diagnostic accuracy for neoplasia prediction by pCLE was 77 % (95 % confidence interval [CI] 74.0 % - 79.2 %); of predictions made with high confidence (53 %), the accuracy was 85 % (95 %CI 81.8 % - 87.8 %). The overall accuracy and interobserver agreement was significantly higher in group 1 than in group 2 for all predictions (80.4 % vs. 73 %; P = 0.005) and for high confidence predictions (90 % vs. 80 %; P < 0.001). Following feedback (after the initial 20 videos), the overall accuracy improved from 73 % to 79 % (P = 0.04), mainly driven by a significant improvement in group 1 (74 % to 84 %; P < 0.01). Accuracy of prediction significantly improved with time in endoscopy training (72 % students, 77 % FY1, 82 % FY2, and 85 % FY3; P = 0.003). For novice trainees, in-class didactic teaching enables significantly better recognition of the pCLE features of Barrett's esophagus than self-directed teaching. The in-class didactic group had a shorter learning curve and were able to achieve 90 % accuracy for their high confidence predictions.

Please provide us with a reasonable definition for curative R0 resection in Barrett's esophagus neoplasia; which one should we choose?

A resection is considered to be R0 when the pathological examination confirms that the edges of the resected specimen are free of disease. A resection is curative when the patient is cured by the endoscopic treatment without need for further surgery or chemoradiation therapy. In the colon for example, the definition of the curative R0 resection is quite simple: a strict R0 is defined by an 'en bloc' specimen with normal mucosa on the edges when examined histologically. The treatment is considered to be curative if the resection is R0 with an invasion depth less than 1000 µm in the submucosa, without lymphatic or venous emboli, without budding, and with a differentiated carcinoma. The situation is far more complex in the neoplasia developed on Barrett’s esophagus (BE) since different degrees of neoplasia are possible with different prognosis and treatment strategies. At present, we do not have any consensus on the definition of R0 and curative resections for BE neoplasia (Fig. 1 a). This editorial aims to discuss various definitions of the R0 resection and their clinical impact. We shall also discuss the literature available to choose the best criteria to define resection curativeness. Fig. 1 Schematic representation of the different R0 resections. a Neoplasia representation; b Colon-like R0; c Intestinal metaplasia R0; d LGD or less R0; e HGD or less R0; f Flat components R0. IM, intestinal metaplasia; LGD, low grade dysplasia; ...

Efficacy of viscous budesonide slurry for prevention of esophageal stricture formation after complete endoscopic mucosal resection of short-segment Barrett's neoplasia.

Complete endoscopic resection (CER) of short-segment Barrett's esophagus with high grade dysplasia (HGD) and early esophageal adenocarcinoma (EEA) is a precise staging tool and achieves durable disease control. The major drawback is development of post-endoscopic resection esophageal stricture (PERES). No effective therapy to prevent PERES has been described. Viscous budesonide slurry (VBS) may have a role in the prevention of PERES by suppressing the post-CER inflammatory process. The study aim was to evaluate the efficacy of VBS for the prevention of PERES. Prospective data were collected on patients referred for CER of HGD or EEA. After January 2012, patients routinely received VBS (two 0.5-mg/2-mL budesonide respules mixed with sucralose) twice daily for 6 weeks following each stage of the CER schedule. All patients received high dose proton pump inhibitor therapy for the duration of CER and the following 3 months. Patients had no other intervention to prevent PERES. A validated dysphagia score was used (0 - 4, no dysphagia to aphagia). Endoscopic dilation was performed for dysphagia. Patients receiving VBS were compared with historical controls. The primary endpoint was the need for dilation. Between January 2008 and January 2015, 104 of 116 eligible patients completed CER. The VBS group (n = 29) and non-VBS group (n = 75) had similar patient, disease, and procedural characteristics. Dilations were needed in 13.8 % vs. 37.3 % (P = 0.03), with a median of one vs. two procedures (P = 0.01), and median dysphagia score during CER of 0 vs. 1 (P = 0.02) in the VBS and non-VBS groups, respectively. No VBS-related adverse events were noted. In this pilot study VBS significantly reduced PERES and shortened the dilation program after CER.

Circumferential cryoablation in a strictured esophagus: a feasibility and dose-finding study in a porcine model after inducing stenosis by endoscopic mucosal resection.

In the treatment of early esophageal Barrett's neoplasia, radiofrequency ablation may be hindered by stenosis due to prior endoscopic resection (ER). The flexible balloon-based circumferential CryoBalloon Ablation System (CBAS) may overcome this problem by the conformability of the compliant balloon which might enable circumferential cryoablation in a stenosis. The aim of the current study was to evaluate the feasibility of the CBAS as well as the dose-response effect of cryoablation in a strictured esophagus model. In six pigs, a stenosis was induced by ER (3 cm in length, 75% of circumference) in the proximal, mid, and distal esophagus. After 28 days, cryoablation with the CBAS was performed, with the length of ablation time (6, 8, or 10 seconds) randomly assigned per stricture location within the esophagus. Four days post-ablation, the esophagi were harvested for histopathological assessment of the percentage of the total circumference affected by cryoablation and the maximum depth of necrosis. At 28 days, all 18 ER areas had transformed into strictures with ±50% of its original diameter remaining. In 9 of 18 strictures, more than one attempt for cryoablation was necessary due to displacement of the balloon. Histopathological evaluation showed a wide range in circumferential uniformity (0-100%) and maximum necrosis depth (epithelium to external proper muscle layer) of cryoablation, both independent of ablation times. Deepest ablation effects were seen at the center of the resection-induced scar. This first generation CryoBalloon Focal Ablation System was not feasible for ablation within severe stenoses, since it results in inconsistent circumferential uniformity of cryoablation with subsequent differences in depth of ablation. Further research with a next generation CBAS in a more realistic stricture model is warranted.

Long-term durability of radiofrequency ablation for Barrett's-related neoplasia.

Here, we examine data on the long-term durability of endoscopic therapy in patients with mucosal neoplasia in Barrett's esophagus. Short-term success is seen in most patients undergoing endoscopic therapy for Barrett's esophagus neoplasia, but long-term outcomes are only just becoming available. The incidence of esophageal adenocarcinoma (EAC) continues to rise with poor survival seen in the majority of patients. The only known precursor to EAC is Barrett's esophagus. Although the risk of progression from metaplastic Barrett's esophagus to neoplasia is low, surveillance is advocated as patients who progress to mucosal neoplasia carry a significantly higher risk of progressing to invasive EAC. Minimally invasive endoscopic therapy with endoscopic resection and radiofrequency ablation are now the gold standard treatments for patients with intramucosal neoplasia in Barrett's esophagus. After successful treatment, follow-up is still required as long-term durability is not 100% and recurrences are not rare. This review highlights the need for vigilant follow-up, but emphasizes the consensus that most patients have durable disease reversal.

Efficacy and safety of Hybrid-APC for the ablation of Barrett's esophagus.

After thermal ablation of Barrett's esophagus (BE), stricture formation is reported in 5 to over 10% of patients. The question arises whether submucosal fluid injection prior to ablation may lower the risk of stricture formation. The aim of the present study was to evaluate the efficacy and safety of the new technique of Hybrid-APC which combines submucosal injection with APC. Patients who had a residual BE segment of at least 1 cm after endoscopic resection of early Barrett's neoplasia underwent thermal ablation of BE by Hybrid-APC. Prior to thermal ablation, submucosal injection of sodium chloride 0.9% was carried out using a flexible water-jet probe (Erbejet 2; Erbe Elektromedizin, Tuebingen, Germany). Check-up upper GI endoscopy was carried out 3 months after macroscopically complete ablation including biopsies from the neo-Z-line and the former BE segment, and recording of stricture formation. From May 2011 to November 2012, a total of 60 patients (pt) were included in the study [55 pt male (92%); mean age 62 ± 9 years, range 42-79]. Ten patients were excluded from the study. In the remaining 50 pt, Hybrid-APC ablation and check-up endoscopy at 3 months were carried out. Forty-eight out of 50 pt (96%; ITT: 49/60, 82%) achieved macroscopically complete remission after a median of 3.5 APC sessions [SD 2.4; range 1-10]. Freedom from BE was histopathologically observed in 39/50 patients (78%). There was one treatment-related stricture (2%). Minor adverse events of Hybrid-APC were observed in 11 patients (22%). According to this pilot series, Hybrid-APC was effective and safe for BE ablation in a tertiary referral center. The rate of stricture formation was only 2%. Further studies are required to confirm the present results. DRKS00003369.

Comparison of endoscopic treatment modalities for Barrett’s neoplasia

There are few data comparing endoscopic treatment outcomes for Barrett's esophagus (BE). To compare treatment outcomes in BE patients treated with radiofrequency ablation (RFA), RFA after EMR, and porfimer sodium photodynamic therapy (Ps-PDT). Retrospective, observational study. Single tertiary center between 2001 and2013. A total of 342 BE patients treated with RFA (n= 119), EMR+RFA (n= 98), and Ps-PDT (n= 125). Rates of complete remission of intestinal metaplasia (CRIM), BE recurrence, and adverse events. Baseline BE high-grade dysplasia (HGD) and adenocarcinoma were more common in the Ps-PDT group (89%) compared with the EMR-RFA (70%) and RFA (37%) groups. At a median follow-up of 14.2 months, 173 patients (50.6%) achieved CRIM. CRIM was significantly more common in Ps-PDT patients compared with RFA (P< .001) and EMR-RFA (P< .001) patients on multivariable analysis. In patients who achieved CRIM, the rates of subsequent BE recurrence were relatively similar among the 3 groups. Although the rates of bleeding were similar, strictures were less common in RFA patients (2.4%) compared with EMR-RFA (13.3%, P= .001) and Ps-PDT (10.4%, P=.043) patients. This study of endoscopic treatment for Barrett's dysplasia and neoplasia found that complete remission was achieved more often and more rapidly after Ps-PDT with similar disease recurrence rates compared with EMR or RFA. Adverse events were more common after EMR and Ps-PDT. Further studies are required to determine which ablation and resection techniques are ideally suited for each BE patient.

Topical hemostatic powder promotes reepithelialization and reduces scar formation after extensive esophageal mucosal resection.

The development of techniques for endoscopic resection has provided new strategies for radical conservative treatment of superficial esophageal neoplasms, even those that are circumferential, such as Barrett's neoplasia. However, it is necessary to prevent the formation of scar tissue that can be responsible for esophageal strictures following circumferential resection. Preliminary data have suggested the possible efficacy of a hemostatic powder in the promotion of wound healing. The study aims to assess the effectiveness of Hemospray (Cook Medical) in a swine model of post-endoscopic esophageal stricture. Our prospective controlled study included 21 pigs. A 6-cm circumferential submucosal dissection of the esophagus (CESD) was performed in each pig. Group 1 (n = 11) only underwent CESD and Group 2 (n = 10) had repeated Hemospray applications after CESD. Clinical, endoscopic, and radiological monitoring were performed, blood levels of four inflammatory or pro-fibrotic cytokines were assessed, and histological analysis was performed. Median esophageal diameter was greater in the group treated with Hemospray (2 mm [1-3] vs. 3 mm [2-4], P = 0.01), and the rate of symptomatic esophageal stricture was 100% and 60% in Groups 1 and 2, respectively (P = 0.09). The thicknesses of esophageal fibrosis and inflammatory cell infiltrate were significantly lower in Group 2 than in Group 1 (P = 0.002 and 0.0003, respectively). The length of the neoepithelium was greater in Group 2 than in Group 1 (P = 0.0004). Transforming growth factor-β levels were significantly lower in Group 2 than in Group 1 (P = 0.01). The application of Hemospray after esophageal CESD reduces scar tissue formation and promotes reepithelialization, and therefore is a promising therapeutic approach in the prevention of post-endoscopic esophageal stricture.