Thermal ablative therapies in the gastrointestinal tract.

PURPOSE OF REVIEW: Thermal ablatives therapies have seen an expanding role in gastrointestinal endoscopy during the last years. The aim of this review is to give an overview of the currently available techniques. RECENT FINDINGS: In the upper gastrointestinal tract, mainly in early Barrett's neoplasia, endoscopic ablation strategies ranging from RFA to Hybrid-APC are, together with resection strategies, the main part of the armamentarium. In the small intestine, argon plasma coagulation (APC) can be effectively used for the treatment of angiodysplasias. In the lower gastrointestinal tract, APC and RFA are mainly used. In tumour obstruction, thermal ablation is used to reopen the lumen. The selection of available techniques is still increasing. SUMMARY: The variety of ablation techniques enables the endoscopist to choose the appropriate ablation tool for each individual patient.

Hybrid APC in Combination With Resection for the Endoscopic Treatment of Neoplastic Barrett's Esophagus: A Prospective, Multicenter Study.

INTRODUCTION: The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation. METHODS: Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.6%) or primarily were included into this prospective trial in 9 European centers. Up to 5 ablation sessions were allowed for complete eradication of BE (initial complete eradication of intestinal metaplasia [CE-IM]), by definition including BE-associated neoplasia, documented by 1 negative endoscopy with biopsies. The main outcome was the rate of initial CE-IM in intention-to-treat (ITT) and per-protocol (PP) samples at 2 years. The secondary end points were the rate of recurrence-free cases (sustained CE-IM) documented by negative follow-up endoscopies with biopsies and immediate/delayed adverse events. RESULTS: One hundred fifty-four patients (133 men and 21 women, mean age 64 years) received a mean of 1.2 resection and 2.7 ablation sessions (range 1-5). Initial CE-IM was achieved in 87.2% of 148 cases in the PP analysis (ITT 88.4%); initial BE-associated neoplasia was 98.0%. On 2-year follow-up of the 129 successfully treated cases, 70.8% (PP) or 65.9% (ITT) showed sustained CE-IM; recurrences were mostly endoscopy-negative biopsy-proven BE epithelium and neoplasia in 3 cases. Adverse events were seen in 6.1%. DISCUSSION: Eradication and recurrence rates of Barrett's intestinal metaplasia and neoplasia by means of hybrid argon plasma coagulation at 2 years seem to be within expected ranges. Final evidence in comparison to radiofrequency ablation can only be provided by a randomized comparative trial.

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

Radiofrequency ablation for low-grade dysplasia in Barrett's esophagus: long-term outcome of a randomized trial.

BACKGROUND AND AIMS: A prior randomized study (Surveillance versus Radiofrequency Ablation study [SURF study]) demonstrated that radiofrequency ablation (RFA) of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) significantly reduces the risk of esophageal adenocarcinoma. Our aim was to report the long-term outcomes of this study. METHODS: The SURF study randomized BE patients with confirmed LGD to RFA or surveillance. For this retrospective cohort study, all endoscopic and histologic data acquired at the end of the SURF study in May 2013 until December 2017 were collected. The primary outcome was rate of progression to high-grade dysplasia (HGD)/cancer. All 136 patients randomized to RFA (n = 68) or surveillance (n = 68) in the SURF study were included. After closure of the SURF study, 15 surveillance patients underwent RFA based on patient preference and study outcomes. RESULTS: With 40 additional months (interquartile range, 12-51), the total median follow-up from randomization to last endoscopy was 73 months (interquartile range, 46-85). HGD/cancer was diagnosed in 1 patient in the RFA group (1.5%) and in 23 in the surveillance group (33.8%) (P = .000), resulting in an absolute risk reduction of 32.4% (95% confidence interval [CI], 22.4%-44.2%) with a number needed to treat of 3.1 (95% CI, 2.3-4.5). Seventy-five of 83 patients (90%; 95% CI, 82.1%-95.0%) treated with RFA for BE reached complete clearance of BE and dysplasia. BE recurred in 7 of 75 patients (9%; 95% CI, 4.6%-18.0%), mostly minute islands or tongues, and LGD in 3 of 75 (4%; 95% CI, 1.4%-11.1%). CONCLUSIONS: RFA of BE with confirmed LGD significantly reduces the risk of malignant progression, with sustained clearance of BE in 91% and LGD in 96% of patients, after a median follow-up of 73 months. (Clinical trial registration number: NTR1198.).

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Length of Barrett's oesophagus and cancer risk: implications from a large sample of patients with early oesophageal adenocarcinoma.

OBJECTIVE: Although it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate annual cancer transition rates for patients with long-segment (≥3 cm), short-segment (≥1 to <3 cm) and ultra-short-segment (<1 cm) Barrett's oesophagus. DESIGN: We used three data sources to estimate the annual cancer transition rates for each Barrett length category: (1) the distribution of long, short and ultra-short Barrett's oesophagus among a large German cohort with newly diagnosed T1 oesophageal adenocarcinoma; (2) population-based German incidence of oesophageal adenocarcinoma; and (3) published estimates of the population prevalence of Barrett's oesophagus for each Barrett length category. RESULTS: Among 1017 patients with newly diagnosed T1 oesophageal adenocarcinoma, 573 (56%) had long-segment, 240 (24%) short-segment and 204 (20%) ultra-short-segment Barrett's oesophagus. The base-case estimates for the prevalence of Barrett's oesophagus among the general population were 1.5%, 5% and 14%, respectively. The annual cancer transition rates for patients with long, short and ultra-short Barrett's oesophagus were 0.22%, 0.03% and 0.01%, respectively. To detect one cancer, 450 patients with long-segment Barrett's oesophagus would need to undergo annual surveillance endoscopy; in short segment and ultra-short segment, the corresponding numbers of patients would be 3440 and 12,364. Similar results were obtained when applying US incidence data. CONCLUSIONS: The large number of patients, who need to undergo endoscopic surveillance to detect one cancer, raises questions about the value of surveillance endoscopy in patients with short segment or ultra-short segment of Barrett's oesophagus.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.

BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10-8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. FINDINGS: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10-10), MSRA (rs17749155; p=5·2 × 10-10), LINC00208 and BLK (rs10108511; p=2·1 × 10-9), KHDRBS2 (rs62423175; p=3·0 × 10-9), TPPP and CEP72 (rs9918259; p=3·2 × 10-9), TMOD1 (rs7852462; p=1·5 × 10-8), SATB2 (rs139606545; p=2·0 × 10-8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10-8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10-8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10-6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. INTERPRETATION: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. FUNDING: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

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

BACKGROUND AND STUDY AIM: 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 AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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. GERMAN CLINICAL TRIALS REGISTER: DRKS00003369.

Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus.

BACKGROUND & AIMS: Barrett's esophagus-associated high-grade dysplasia is commonly treated by endoscopy. However, most guidelines offer no recommendations for endoscopic treatment of mucosal adenocarcinoma of the esophagus (mAC). We investigated the efficacy and safety of endoscopic resection in a large series of patients with mAC. METHODS: We collected data from 1000 consecutive patients (mean age, 69.1 ± 10.7 years; 861 men) with mAC (481 with short-segment and 519 with long-segment Barrett's esophagus) who presented at a tertiary care center from October 1996 to September 2010. Patients with low-grade and high-grade dysplasia and submucosal or more advanced cancer were excluded. All patients underwent endoscopic resection of mACs. Patients found to have submucosal cancer at their first endoscopy examination were excluded from the analysis. RESULTS: After a mean follow-up period of 56.6 ± 33.4 months, 963 patients (96.3%) had achieved a complete response; surgery was necessary in 12 patients (3.7%) after endoscopic therapy failed. Metachronous lesions or recurrence of cancer developed during the follow-up period in 140 patients (14.5%) but endoscopic re-treatment was successful in 115, resulting in a long-term complete remission rate of 93.8%; 111 died of concomitant disease and 2 of Barrett's esophagus-associated cancer. The calculated 10-year survival rate of patients who underwent endoscopic resection of mACs was 75%. Major complications developed in 15 patients (1.5%) but could be managed conservatively. CONCLUSIONS: Endoscopic therapy is highly effective and safe for patients with mAC, with excellent long-term results. In an almost 5-year follow-up of 1000 patients treated with endoscopic resection, there was no mortality and less than 2% had major complications. Endoscopic therapy should become the standard of care for patients with mAC.

BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia.

OBJECTIVES: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns.

BACKGROUND: A prerequisite for endoscopic treatment (ET) of not only mucosal, but also submucosal early adenocarcinoma of the esophagus (EAC) would be a rate of lymph node (LN) metastasis below the mortality rate of esophagectomy (2-5%). The aim of the present study was to evaluate the rate of LN metastasis in patients with pT1b sm1 EAC. METHODS: 1996-2010, 1,718 patients with suspicion of EAC were referred to the Department of Internal Medicine II at HSK Wiesbaden. In 123/1718 patients, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of sm1 EAC (ER/surgery) was made. Rate of LN metastasis was analyzed separately for low-risk (LR; G1-2, L0, V0) and high-risk lesions (HR; G3, L1, V1; ≥ 1 risk factor). LN metastasis was only evaluated in patients who had a proven maximum invasion depth of sm1 (ER and/or surgery), and who in case of ET had a follow-up (FU) by EUS of at least 24 months. RESULTS: Of the 72/123 patients included into the study, 49 patients had LR (68%) and 23 HR lesions (32%). In endoscopically treated LR patients (37/49), mean EUS-FU was 60 ± 30 mo (range 25-146); in HR patients undergoing ET (6/23), it was 63 ± 17 mo (46-86; p = 0.4). Mean number of resected LN was 27 ± 16 (12-62) in operated LR patients and 27 ± 10 (12-47) in HR-patients. The rate of LN metastasis was 2% in the LR (1 patient) and 9% in the HR group (2 patients; p = 0.24). Mortality of esophagectomy was 3%. CONCLUSIONS: The rate of LN metastasis in pT1b sm1 early adenocarcinoma with histological LR pattern was lower than the mortality rate of esophagectomy. ER may therefore be used alternatively to surgery in this group of patients.

Ablation of residual Barrett's epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).

BACKGROUND AND STUDY AIM: It is commonly assumed that ablation of any remaining Barrett's epithelium after endoscopic resection of early Barrett's neoplasia improves outcome by reducing the rate of metachronous lesions, but this has not yet been evaluated in a randomized trial. The aim of this study was to compare argon plasma coagulation (APC) with surveillance only for the management of residual Barrett's epithelium following endoscopic resection. PATIENTS AND METHODS: Patients in whom focal early Barrett's neoplasia (high grade intraepithelial neoplasia [HGIN] or mucosal cancer) had been curatively resected by endoscopy were randomly assigned to undergo ablation of the residual Barrett's segment by APC or surveillance only; pH-metry-adjusted proton pump inhibitor therapy was administered in both groups. The main outcome parameter was recurrence-free survival. Follow-up endoscopies with biopsies in cases of further residual Barrett's epithelium were carried out at 6-monthly intervals in both groups. RESULTS: A total of 63 patients (57 male [90.5%]) were included in the study (ablation group n=33; surveillance group n=30). For complete Barrett's ablation, a mean number of 4±1.6 APC sessions were required (range 2-7). The mean follow-up duration did not differ significantly between ablation (28.2±13.7 months, range 0-44) and surveillance patients (24.7±14.8 months, range 0-45; P=0.159). The number of secondary lesions was 1 in the ablation group (3%), and 11 in the surveillance group (36.7%), leading to significantly higher recurrence-free survival for the patients undergoing ablation (P=0.005). CONCLUSIONS: Thermal ablation of residual Barrett's epithelium leads to a significant reduction in neoplasia recurrence rate compared with a surveillance strategy during a limited follow-up of 2 years. A longer follow-up duration may have led to a relatively higher rate of secondary neoplasia in both groups of patients.

Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion.

BACKGROUND & AIMS: Patients with early-stage mucosal (T1a) esophageal adenocarcinoma (EAC) are increasingly treated by endoscopic resection. EACs limited to the upper third of the submucosa (pT1b sm1) could also be treated by endoscopy. We assessed the efficacy, safety, and long-term effects of endoscopic therapy for these patients. METHODS: We analyzed data from 66 patients with sm1 low-risk lesions (macroscopically polypoid or flat, with a histologic pattern of sm1 invasion, good-to-moderate differentiation [G1/2], and no invasion into lymph vessels or veins) treated by endoscopic therapy at the HSK Hospital Wiesbaden from 1996 through 2010. The efficacy of endoscopic therapy was assessed on the basis of rates of complete endoluminal remission (CER), metachronous neoplasia, lymph node events, and long-term remission (LTR). Safety was assessed on the basis of rate of complications. RESULTS: Remissions were assessed in 61 of the 66 patients; 53 of the 61 achieved CER (87%). Of patients with small focal neoplasias ≤2 cm, 97% achieved CER (for those with tumors ≥2 cm, 77%; P = .026). Metachronous neoplasias were observed in 10 of 53 patients (19%; 9 of the 10 underwent repeat endoscopic resection). One patient developed a lymph node metastasis (1.9%). Fifty-one patients achieved LTR (84%); 90% of those with focal lesions ≤2 cm achieved LTR after a mean follow-up period of 47 ± 29.1 months (range, 8-120 months). No tumor-associated deaths were observed, and the estimated 5-year survival rate was 84%. The rate of major complications from endoscopic resection was 1.5%, and no patients died. CONCLUSIONS: Endoscopic therapy appears to be a good alternative to esophagectomy for patients with pT1b sm1 EAC, on the basis of macroscopic and histologic analyses. The risk of developing lymph node metastases after endoscopic resection for sm1 EAC is lower than the risk of surgery.

Consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process.

BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS: We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Prospective, randomized, single-center trial comparing double-balloon enteroscopy and spiral enteroscopy in patients with suspected small-bowel disorders.

BACKGROUND: Double-balloon enteroscopy (DBE) is an established method in diagnostic and therapeutic small-bowel enteroscopy. OBJECTIVE: Spiral enteroscopy (SE) appears to be a promising new technique. A randomized, prospective study was conducted to compare both methods. DESIGN: Randomized, prospective study. SETTING: Single tertiary referral center. PATIENTS: Between September 2009 and March 2011, 26 patients with suspected mid-GI disorders completed the study. INTERVENTIONS: Patients were randomly assigned to DBE or SE. The oral examination was conducted first, with the deepest point reached being marked with India ink. An additional anal examination followed the day after, with the aim of reaching the ink mark. MAIN OUTCOME MEASUREMENTS: The primary endpoint of the study was the rate of complete enteroscopies achieved. RESULTS: The rate of complete enteroscopies with DBE was 12 times the rate achieved with SE (8% in the SE group and 92% in the DBE group; P = .002). With regard to the secondary study criteria, much longer examination times but greater depths of insertion were associated with DBE. There were no statistically significant differences in the diagnostic or therapeutic outcomes between the SE and DBE groups (diagnostic yield, P = .428; therapeutic yield, P = 1.0; Fisher exact test). One perforation occurred during an anal examination as a relevant adverse event in SE. LIMITATIONS: Single-center study, small sample size. CONCLUSION: SE does not represent an alternative to DBE with regard to the depth of insertion or the rate of complete enteroscopies achieved. However, SE is advantageous in that it involves significantly shorter examination times. Further technical improvements will be necessary before SE can compete with DBE for complete enteroscopies.

[Current status in Barrett's esophagus]. / Update Barrett-Ösophagus.

Barrett's esophagus has been an important issue in clinical medicine for many years. In the 70 s of the last century, the association between gastroesophageal reflux disease and BE was detected. Only ten years later, the association between BE and adenocarcinoma of the esophagus was reported. Starting in the 90s in Europe, endoscopic resection and ablation have seen an expanding role in the management of BE. In analogy with other diseases, patients are undergoing individualized surveillance and treatment strategies. In non-neoplastic Barrett's esophagus, surveillance intervals are clearly defined by national and European guidelines. Only in case of malignant transformation of BE which may range from low-grade dysplasia to high-grade dysplasia and early Barrett's cancer, endoscopic therapy is indicated. At present, there are emerging techniques of artificial intelligence. Due to these rapid developments in BE management, it is important to keep an eye on the current status of BE management.

eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.

BACKGROUND: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. METHODS: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. RESULTS: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). CONCLUSIONS: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. IMPACT: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.

Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett's esophagus at two high-volume centers.

BACKGROUND AND OBJECTIVE: Esophagectomy has previously been the gold standard for patients with mucosal adenocarcinoma in Barrett's esophagus (Barrett's carcinoma, BC). Because of the minimal invasiveness and excellent results obtained with endoscopic resection (ER), the latter has become an accepted alternative. However, few data have so far been published comparing the 2 treatment methods. METHODS: A total of 114 patients with mucosal BC who were treated surgically or endoscopically in 2 high-volume centers were included in this study. Between 1996 and 2009, 38 patients with mucosal BC received transthoracic esophageal resection with 2-field lymphadenectomy (median 29 lymph nodes removed; all pN0) in the Department of Surgery at the University of Cologne. Seventy-six patients with BC treated with ER followed by argon-plasma-coagulation of the remaining non-dysplastic Barrett's esophagus in the Department of Gastroenterology in Wiesbaden were matched according to the following criteria: age, gender, infiltration depth (pT1m1-3), differentiation grade (G1/2 vs. 3) and follow-up period. RESULTS: There were no significant differences between the 2 groups with regard to epidemiologic and tumor criteria. Complete remission (CR) was achieved in all patients in the surgery group and all but 1 patient in the ER group (98.7%; the patient died of other causes before CR was achieved). Major complications after surgery occurred in 32% of the patients, significantly more often than in the ER group (0% major complications, P < 0.001). The 90-day mortality rates were 0% in the ER group and 2.6% in the surgical group (1 of 38; P = 0.333). The median follow-up periods were 4.1 years in the ER group and 3.7 years in the surgical group. During this period, 1 patient in the ER group had a local recurrence and 4 had metachronous neoplasia (overall recurrence rate 6.6%). However, repeat endoscopic treatment was possible in all of the patients, and the long-term CR rates in the surgical and ER groups were 100% and 98.7%, respectively. No tumor-related mortality was observed in either group. CONCLUSIONS: For patients with mucosal BC, both surgery and ER are effective treatment modalities. Surgery is associated with a higher morbidity rate and shows a risk for procedure-related mortality. However, the recurrence rate is higher in patients treated with ER, so that thorough follow-up procedures are mandatory.

Incidence of macroscopically occult neoplasias in Barrett's esophagus: are random biopsies dispensable in the era of advanced endoscopic imaging?

OBJECTIVES: The gold standard for endoscopic surveillance of Barrett's esophagus (BE) includes targeted biopsies (TBs) from abnormalities as well as stepwise four-quadrant biopsies (4QBs) for detection of invisible high-grade intraepithelial neoplasias (HGINs) or early carcinomas (ECs). In a large mixed BE population, we investigated the rate of HGINs/ECs that are macroscopically occult to enhanced visualization with high-resolution endoscopy plus acetic acid chromoendoscopy. METHODS: From January 2007 to December 2009, 701 consecutive BE patients were enrolled in a prospective study at a tertiary referral center. Of these, 406 patients had a history of HGIN/EC (high-risk group) and 295 patients did not (low-risk group). RESULTS: In 701 patients, 459 TBs and 5,485 4QBs were obtained. Altogether, 92 patients with 132 lesions containing HGINs/ECs were detected. For the diagnosis of HGINs/ECs, patient-related sensitivity and specificity rates of endoscopic imaging with TBs were 96.7 and 66.5%, with a positive and negative predictive value of 30.4 and 99.3%, respectively. In the high-risk group, 4QBs identified three additional patients (3.3%) with macroscopically occult HGINs/ECs. In the low-risk group, no HGINs/ECs were identified with either biopsy approach. CONCLUSIONS: Advanced endoscopic imaging identifies the vast majority of BE patients with early neoplasias, and the additive effect of 4QB is minimal. Therefore, in low- and high-risk patients, limiting endoscopic surveillance to guided biopsies is justified in specialized high-volume centers with permanent quality control. However, we do not advocate abandoning 4QB outside this setting.