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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: 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.

Background & Aims: The aim of this study was to compare magnified still images obtained with high-resolution white light endoscopy, indigo carmine chromoendoscopy, acetic acid chromoendoscopy, and narrow-band imaging to determine the best technique for use in Barrett's esophagus., Methods: We obtained magnified images from 22 areas with the 4 aforementioned techniques. Seven endoscopists with no specific expertise in Barrett's esophagus or advanced imaging techniques and 5 international experts in this field evaluated these 22 areas for overall image quality, mucosal image quality, and vascular image quality. In addition, the regularity of mucosal and vascular patterns and the presence of abnormal blood vessels were evaluated, and this was correlated with histology., Results: The interobserver agreement for the 3 features of mucosal morphology with white light images ranged from kappa = 0.51 (95% confidence interval [CI]: 0.46-0.55) to kappa = 0.53 (95% CI: 0.50-0.57) for all observers, from kappa = 0.43 (95% CI: 0.33-0.54) to kappa = 0.53 (95% CI: 0.41-0.64) for experts, and from kappa = 0.51 (95% CI: 0.15-0.33) to kappa = 0.64 (95% CI: 0.58-0.70) for nonexperts. The interobserver agreement in these groups did not improve by adding one of the enhancement techniques. The yield for identifying early neoplasia with white light images was 86% for all observers, 90% for experts, and 84% for nonexperts. The addition of enhancement techniques did not improve the yield neoplasia., Conclusions: The addition of indigo carmine chromoendoscopy, acetic acid chromoendoscopy, or narrow-band imaging to white light images did not improve interobserver agreement or yield identifying early neoplasia in Barrett's esophagus.

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: Computed virtual chromoendoscopy (CVC) is a new imaging technique that enhances mucosal surface contrast and highlights the vascular pattern without the need for dye-spraying as in conventional chromoendoscopy. The aim of this prospective randomized pilot study with a crossover design was to compare CVC with conventional chromoendoscopy with acetic acid (CAA) for the detection of high grade intraepithelial neoplasia (HGIN) or early cancer in patients with Barrett's esophagus., Patients and Methods: 57 patients with Barrett's esophagus (mean length 3.8 cm) and a history of HGIN/early cancer or suspected HGIN/early cancer were randomly allocated to undergo either CAA or CVC. All patients were re-examined with the alternative procedure at 4 - 6 weeks after the initial endoscopy. The two procedures were performed by five endoscopists, who were blinded to the findings of the other examination. At each examination, targeted biopsies were taken from all detected lesions, followed by random four-quadrant biopsies., Results: In 24/57 patients, 30 lesions with HGIN/early cancer were detected. The sensitivity of targeted biopsies for HGIN/early cancer on a 'per lesion' basis was 87 % (26/30) for both CAA and CVC. The positive predictive value was 39 % (26/66) for CAA and 37 % (26/70) for CVC. In the 'per patient' analysis, sensitivity was 83 % (20/24) and 92 % (22/24) for CAA and CVC, respectively ( P = 0.617). Stepwise random four-quadrant biopsies identified only one patient with HGIN/early cancer that was missed by both, CAA and CVC., Conclusions: Computed virtual chromoendoscopy is a helpful adjunct for surveillance of Barrett's esophagus and appears to be as accurate as conventional chromoendoscopy in the detection of HGIN/early cancer.

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.

This report describes the case of a 62-year-old man with tonsillar carcinoma who had undergone esophagectomy due to an esophageal metastasis. Subsequently, a second metastasis occurred in the residual esophagus, and he presented for evaluation for local endoscopic therapy. The initial upper endoscopy revealed a type IIa - c lesion at 21 cm from the incisors, within a segment suspicious for Barrett's mucosa. As part of the complex treatment approach in this patient, endoscopic resection of the lesion was carried out using the suck-and-cut technique with ligation. Histology showed that the lesion was a metastasis from a squamous-cell carcinoma, with focal infiltration of the upper submucosal layer and vascular invasion consistent with the hypothesis of hematogenous spread from the preceding tonsillar carcinoma. The resection margins were tumor-free. At the time of writing, the patient had been recurrence-free for more than 9 months. In summary, the present paper describes a unique case of successful endoscopic resection of an esophageal metastasis associated with an antecedent tonsillar carcinoma.

Background: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking., Methods: The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients., Results: Between September 1996 and September 2002, 667 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barrett's neoplasia., Conclusions: The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barrett's neoplasia.

Background: Endoscopic resection has gained more and more importance in the treatment of early oesophageal neoplasia over the past few years. The choice of the different available techniques depends on the site, the macroscopic type of the tumour and the personal experience of the endoscopist., Methods: The "suck-and-cut" technique with ligation device or cap should be favoured over normal strip biopsy in the oesophagus because of the size of the resected specimen and the technical feasibility., Results: Endoscopic resection (ER) of high-grade intra-epithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus should be considered as the treatment of choice, due to excellent long-term results. First mid-term results of endoscopic therapy of early squamous cell neoplasia in the oesophagus show promising results; however, long-term results are awaited., Conclusion: ER of oesophageal neoplastic lesions is a safe and effective method but should be performed only by experienced endoscopists.

There has been a dramatic increase in recent years in the incidence of Barrett's esophagus and the esophageal adenocarcinoma associated with it. Adequate monitoring strategies and improved diagnostic procedures are therefore essential. Alongside conventional video endoscopy with four-quadrant biopsies, many additional diagnostic procedures are now available to improve monitoring. These allow early diagnosis of dysplastic areas and early carcinomas. Endoscopic therapy has gained more and more importance in the treatment of early esophageal neoplasias over the last few years. Localized lesions in the Barrett's segment should be treated by endoscopic resection (ER). Only in patients with not localized or multifocal superficial lesions photodynamic therapy (PDT) should be used. Between the different ER techniques the "suck and cut"-technique with ligation device or cap should be favoured to normal strip biopsy in the esophagus because of the size of the resected specimen and its technical feasibility. ER of high grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's esophagus should be considered as the treatment of choice. ER of early neoplasia in Barrett's esophagus is a safe and effective method but should only be performed by experienced endoscopists.