Search

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (©2022 American Association for Cancer Research.)

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., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

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., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available., (© 2016 International Society for Diseases of the Esophagus.)

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., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10(-5) ) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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.

Background: Detecting early neoplasias in Barrett's oesophagus (BE) is challenging. Recent publications have been focusing on improving the detection of such lesions during Barrett's surveillance. However in a recently published Danish register study calculating the risk for cancer-development in BE two-thirds of the diagnosed tumors were identified during the first examination or in the first year. This means that index endoscopy might be more effective than surveillance in detecting early neoplasia in BE. , Methods: In the period from January 2010 to April 2011, all patients who consecutively presented with a diagnosis of early neoplastic changes in BE were recorded prospectively., Analysis: The analysis included data for 121 patients. In patients with short-segment BE (SSBE), neoplasia was only diagnosed in 6 % of cases in the surveillance examination, compared with 44 % of cases in long-segment BE (LSBE). The neoplastic lesion was identified visually in 43 patients (36 %) during the external EGD. Type II tumours were detected in 40 % (39/98) and were correctly assessed as neoplastic in 25 % of cases (24/98)., Conclusions: 1. in patients with SSBE almost all early tumours are diagnosed by index endoscopy and not by Barrett's surveillance; 2. around 40 % of all early neoplasias are endoscopically invisible and are only diagnosed using four-quadrant biopsies; 3. the macroscopic tumour type has a substantial influence on the detection rate for neoplasia. If efforts to increase the detection rate for early neoplasia in BE are focused solely on the Barrett's surveillance method, then only a minority of patients - 20 % in the present group - will benefit from the measure. German clinical trials register, DRKS00 004 168., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

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., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Modern high-resolution video endoscopes allow detailed examination of the esophageal mucosa and diagnosis of early neoplastic changes in the gastrointestinal tract. Whereas Barrett's esophagus is a precancerous condition that can develop into adenocarcinoma, there is no defined precancerous lesion for squamous cell carcinoma. Various diseases are associated with the development of esophageal squamous cell carcinoma. Chromoendoscopy has become an established method in the diagnostic work-up for better visualization of early neoplasia. If Barrett's esophagus is present, acetic acid spraying or virtual chromoendoscopy can be used to accentuate the display of superficial gyriform structures in the mucosa. The gold standard for detecting squamous cell carcinoma is still the use of Lugol solution. When early neoplasia is suspected, diagnostic endoscopic resection should be performed. This allows precise histological assessment of the tumor. Early diagnosis of neoplastic changes in the esophagus provides patients not only with the option of curative therapy but also with a good quality of life through preservation of the esophagus.

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., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Endoscopic treatment is increasingly being accepted for early Barrett's cancer (EBC), as it is associated with few complications, excellent long-term results, and almost no mortality. This study investigated current standards and treatment strategies for EBC in eight countries in Western Europe., Methods: A standardized questionnaire with questions on the endoscopic diagnosis, staging, and treatment of EBC was developed and sent to 107 university gastroenterology departments. The data were analyzed anonymously., Results: The response rate was 49 % (52/107). For work-up of early Barrett's neoplasia, 67 % of hospitals use high-resolution endoscopes, with routine four-quadrant and targeted biopsies of visible lesions in 94 % of the cases. Narrow-band imaging and chromoendoscopy are used in 67 % of the cases, and other advanced imaging and staining techniques in 65 %. Before treatment, 63 % of the respondents recommended conventional endosonography, 6 % miniprobe endosonography, and 19 % both. Endoscopic resection is carried out at 98 % of the hospitals. Argon plasma coagulation is used for ablation in 52 % of the cases and radiofrequency ablation in 27 %. An 80-year-old patient with localized mucosal EBC would be treated endoscopically in all of the hospitals. Endoscopic therapy was recommended for 50-year-old patients with mucosal EBC by 87 % of the hospitals; esophageal resection was recommended for multifocal EBC by 15 % in 80-year-old patients, by 63 % in 50-year-old patients and by 44 % in patients with incipient submucosal infiltration., Conclusions: About two-thirds of the university hospitals use high-resolution endoscopy and advanced imaging. Endoscopic therapy is the accepted standard for treating localized mucosal Barrett's cancer in Western Europe; esophageal resection is recommended by the majority (63 %) for a young patient with multifocal EBC., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Endoscopic resection (ER) has become the most important endoscopic treatment method of early cancers of the upper GI tract. ER serves as a therapeutic but also as a diagnostic tool by providing a specimen for histologic assessment. In expert hands ER is easy to performe and has a very low complication rate. Long-term results in early esophageal and gastric cancer are excellent., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Background: Endoscopic therapy (ET) has become a less risky alternative to open surgery in mucosal Barrett's cancer (BC) because of the very low risk of lymph node (LN) metastasis. Recently published surgical series demonstrated that even in case of minimal submucosal invasion of BC, the risk for LN metastasis is very low. In consequence, also these patients might be eligible for curative ET. The aim of this study was to prospectively evaluate the efficacy and safety of endoscopic resection (ER) in these patients., Methods: From September 1996 to September 2003, the suspicion or definite diagnosis of submucosal BC was made in 80 patients referred to our department. Of those, 21 patients (20 male [95.2%], mean age 62 +/- 9 yr, range 47-78) fulfilled the definition of "low-risk" submucosal cancer: invasion of the upper submucosal third (sm1), absence of infiltration into lymph vessels/veins, histological grade G1/2, and macroscopic type I/II. ET was carried out using ER with the suck-and-cut technique with or without an additive ablation of non-neoplastic remnants of Barrett's esophagus., Results: One of the 21 patients was referred to surgery directly after the detection of sm1 invasion at the beginning of the study. One patient died (not tumor-related) before completion of ET. Using definitive ET, complete remission (CR) was achieved in 18 of 19 patients (95%) after a mean of 5.3 months (range 1-18) and a mean of 2.9 resections (range 1-9). Only one minor complication (bleeding without drop in hemoglobin level >2 g/dL) occurred (5% of patients). During a mean follow-up (FU) of 62 months (range 45-89), recurrent or metachronous carcinomas were found in 5 patients (28%). Repeat ET was carried out successfully using ER (4 patients) and argon plasma coagulation (1 patient). In one of the 19 patients (5%), tumor freedom had not been achieved after a total of 2 ER. This patient died of a heart attack before surgery could be performed. The calculated 5-yr survival rate of all 21 patients was 66%. No tumor-related death occurred., Conclusions: As in mucosal BC, ER is associated with favorable outcomes even in case of "low-risk" submucosal BC. Further and larger clinical trials are required before a general recommendation for ER as the treatment of choice in "low-risk" submucosal BC can be given.

Objective: Endoscopic therapy is increasingly being used in the treatment of high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma (BC) in patients with Barrett's oesophagus. This report provides 5 year follow-up data from a large prospective study investigating the efficacy and safety of endoscopic treatment in these patients and analysing risk factors for recurrence., Design: Prospective case series., Setting: Academic tertiary care centre., Patients: Between October 1996 and September 2002, 61 patients with HGIN and 288 with BC were included (173 with short-segment and 176 with long-segment Barrett's oesophagus) from a total of 486 patients presenting with Barrett's neoplasia. Patients with submucosal or more advanced cancer were excluded., Interventions: Endoscopic therapy., Main Outcome Measures: Rate of complete remission and recurrence rate, tumour-associated death., Results: Endoscopic resection was performed in 279 patients, photodynamic therapy in 55, and both procedures in 13; two patients received argon plasma coagulation. The mean follow-up period was 63.6 (SD 23.1) months. Complete response (CR) was achieved in 337 patients (96.6%); surgery was necessary in 13 (3.7%) after endoscopic therapy failed. Metachronous lesions developed during the follow-up in 74 patients (21.5%); 56 died of concomitant disease, but none died of BC. The calculated 5 year survival rate was 84%. The risk factors most frequently associated with recurrence were piecemeal resection, long-segment Barrett's oesophagus, no ablative therapy of Barrett's oesophagus after CR, time until CR achieved >10 months and multifocal neoplasia., Conclusions: This study showed that endoscopic therapy was highly effective and safe, with an excellent long-term survival rate. The risk factors identified may help stratify patients who are at risk for recurrence and those requiring more intensified follow-up.

The advent of endoscopic resection (ER) techniques has enabled gastroenterologists to remove premalignant or neoplastic lesions throughout the gastrointestinal tract. This review discusses the indications and the several techniques of ER in early carcinomas of the esophagus and stomach. Before ER is performed an accurate evaluation of patients and careful staging of lesions is mandatory. After ER of the neoplasia histological assessment of the entire specimen with detailed histological analysis of layer infiltration is crucial. First long-term follow-up studies of large numbers of patients confirm the excellent effectiveness of ER for well-differentiated mucosal lesions without lymphangitic invasions., (2009 S. Karger AG, Basel)

Background & Aims: Confocal laser endomicroscopy has been shown to allow direct histologic imaging of gastrointestinal tumors in vivo. This study was designed to assess the potential of endomicroscopy for predicting histology in vivo during routine endoscopy in patients with early squamous cell cancer., Methods: Twenty-one consecutive patients with suspected early squamous cell cancer who had been referred for endoscopic therapy to a tertiary-care academic medical center were included in this prospective study. After staining with 0.5% Lugol's solution and injection of 500 mg fluorescein sodium, unstained mucosal areas were examined using confocal imaging. Images of each scanned lesion were acquired and stored digitally, and in vivo diagnosis was performed during ongoing endoscopy. Biopsy specimens were taken from every lesion. The confocal images were reviewed by 2 endoscopists, who were blinded to the histology and endoscopic appearance., Results: Confocal images were acquired from 43 lesions in 21 patients. Twenty-seven of the 43 lesions (63%) were proven to be squamous cell cancer on histology. All squamous cell cancers were diagnosed correctly by endomicroscopy and 2 lesions were falsely diagnosed as neoplastic. The overall accuracy was 95%, and the sensitivity and specificity were 100% and 87%, respectively. Intraobserver agreement was almost perfect (kappa = 0.95) and interobserver agreement was substantial (kappa = 0.79)., Conclusions: Confocal laser endomicroscopy is able to provide virtual histology of early squamous cell cancers with a high degree of accuracy and can facilitate rapid diagnosis during routine endoscopy.

Background and Study Aims: The macroscopic appearance of early gastric cancers, classified according to the Japanese criteria, has been shown to be an important prognostic factor for local endoscopic therapy. No prospective data about the distribution of macroscopic types and their location in early Barrett's neoplasia are available, however. The present study was conducted to evaluate the clinical applicability of this macroscopic classification and to analyze the relative proportions of the different gross types in early Barrett's neoplasms and the correlation between the macroscopic classification and the stage or grade of differentiation., Patients and Methods: A total of 344 patients with 380 Barrett's neoplastic lesions who were referred between October 1996 and September 2005 for endoscopic therapy of early Barrett's high-grade intraepithelial neoplasia and carcinoma were prospectively included in the study. Routine endoscopy prior to endoscopic resection in our center included assessment of the macroscopic type (according to the Japanese classification) and documentation of the radial location of the neoplastic lesions. Images were recorded which were later assessed by six independent reviewers; intra- and interobserver agreement for the assessment of the macroscopic type were calculated using kappa statistics., Results: The distribution of the lesions by gross type was as follows: type I, n = 49 (13 %); type IIa, n = 139 (37 %); type IIb, n = 106 (28 %); type IIc, n = 17 (4 %); type IIa + c, n = 62 (16 %); type III, n = 7 (2 %). Type IIb lesions seem to be the most favorable type with regard to differentiation and T category ( P < 0.05). The mean kappa value for the interobserver agreement was 0.86 and the mean kappa value for the intraobserver agreement was 0.89. Most lesions were found at the 12 o'clock and 3 o'clock positions., Conclusions: Assessment of the macroscopic type may provide important information about the possibility of endoscopic treatment. The harder-to-detect flat lesions are by far the most frequent macroscopic type of neoplastic lesion in Barrett's esophagus.

Background and Study Aims: Endoscopic resection of esophageal squamous-cell neoplasia with curative intent is considered to be a safe and effective alternative treatment to radical surgery in cases where the neoplasia is intraepithelial or limited to the mucosal layer. These patients are at risk for recurrent malignancy in the preserved esophagus, however. We conducted a prospective study to evaluate the efficacy and safety of endoscopic resection and to analyze variables associated with recurrence in patients with mucosal or intraepithelial squamous-cell neoplasia., Patients and Methods: Between December 1997 and September 2005, 65 patients (mean age +/- standard deviation [SD] 62.9 +/- 9.5 years), 12 with high-grade intraepithelial neoplasia (HGIN) and 53 with mucosal squamous-cell cancer, were included in our study and were treated using endoscopic resection. Details of patient and tumor characteristics were documented prospectively. All patients were included in a staging protocol including high-resolution endoscopy with Lugol staining, endoscopic ultrasound, computed tomography, and abdominal ultrasound. Endoscopic resection was performed using a ligation technique. The data acquired were subjected to univariate and multivariate analysis., Results: A total of 179 resections were performed (mean number of resections +/- SD per patient, 2.8 +/- 1.8): 11/12 patients with HGIN (91.7%), and 51/53 patients with mucosal cancer (96.2%) achieved a complete response during a mean follow-up period of 39.3 +/- 22.8 months; three patients were still under therapy at the end of the study period. Recurrence of malignancy after achieving a complete response was observed in 16 patients (26%), but these patients all achieved another complete response after further endoscopic treatment. Independent risk factors for recurrence was multifocal carcinoma (RR 4.1, P = 0.018). Tumor-related deaths occurred in two patients (3%), and eight patients died as a result of co-morbidity. Complications were seen in 15/65 patients (23%, all esophageal stenoses). The 7 year survival rate calculated for all groups was 77%., Conclusions: According to the results of long-term follow-up in this study, endosocopic resection appears to be an effective and safe method of curative treatment in patients with HGIN and mucosal squamous-cell carcinomas of the esophagus. Multifocal carcinoma and T1m1 tumors seem to be highly associated with recurrence.