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Endoscopic therapies have become the standard of care for most cases of Barrett's esophagus with high-grade dysplasia or intramucosal adenocarcinoma. Despite a rapid and dramatic evolution in treatment paradigms, esophagectomy continues to occupy a place in the therapeutic armamentarium for superficial esophageal neoplasia. The managing physician must remain cognizant of the limitations of endoscopic approaches and consider surgical resection when they are exceeded. Esophagectomy, performed at experienced centers for appropriately selected patients with early-stage disease can be undertaken with the expectation of cure as well as low mortality, acceptable morbidity, and good long-term quality of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Endoscopic resection has proven highly effective and safe in the removal of focal early neoplastic lesions in Barrett's esophagus and is considered the cornerstone of endoscopic treatment. Several techniques are available for endoscopic resection in Barrett's esophagus. The most widely used technique for piecemeal resection of early Barrett's neoplasia is the ligate-and-cut technique. Newer techniques such as endoscopic submucosal dissection may also play a role in the treatment of neoplastic Barrett's esophagus. Treatment of early Barrett's neoplasia should be centralized and limited to expert centers with a high-volume load and sufficient expertise in the detection and treatment of esophageal neoplasia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Per WHO, 2000 classification, pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma, and are primarily located in the pancreatic body/tail of females. The incidence of MCN and associated malignancy in males, since, standardization of MCN diagnostic-criteria is unknown., Methods: MCN resections from 2000 to 2014 at eight institutions of the Central-Pancreas-Consortium were included, and divided into early (2000-2007) and late (2008-2014) time-periods. Primary aim was to characterize MCN and associated adenocarcinoma/high-grade-dysplasia (AC/HGD) in males versus females over time., Results: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had MCNs: 310 (89%) female, 39 (11%) male. Patients were equally divided between early (n = 173) and late (n = 176) time-periods. MCN in male-patients decreased over time (early: 15%, late: 7%; P = 0.036), as did pancreatic head/neck location (early: 22%, late: 11%; P = 0.01). MCN-associated AC/HGD was more frequent in males versus females (39 vs. 12%; P < 0.001). The overall rate of MCN-associated AC/HGD remained stable (early: 17%, late: 13%; P = 0.4), and was identical in males (39%) over both time-periods. Males with AC/HGD had more LN-positive disease versus females (57 vs. 22%; P = 0.039)., Conclusions: As the diagnostic-criteria of MCN have standardized over time, MCN diagnosis has decreased in males and head/neck location. Despite this, MCN-associated adenocarcinoma/high-grade dysplasia has been stable and remains high in males. Any male with suspected MCN, regardless of location, should undergo resection., (© 2017 Wiley Periodicals, Inc.)

Introduction: Recent studies have indicated a lower incidence rate of oesophageal adenocarcinoma (OAC) in individuals with Barrett's oesophagus (BO) than most earlier studies. Our objective was to assess the risk of OAC in a Swedish unselected cohort of individuals with BO., Methods: This population-based cohort study included all Swedish residents diagnosed with BO in 2006-2013, identified through the Swedish Patient Registry. The cohort members were followed from the date of first BO diagnosis until the first occurrence of OAC, high-grade dysplasia (HGD), death, emigration or end of study period. The main outcome was incidence rates with 95% confidence intervals (CIs) of OAC., Results: Among 7932 participants with BO and 18,415 person-years of follow-up, the overall incidence of OAC was 1.47 (95% CI 0.91-2.02) per 1000 person-years. When stratified into follow-up periods after BO diagnosis, the incidence rate of OAC was 15.53 (4.77-26.29) from 7 to 30 d, 4.10 (0.82-7.38) from 31 to 100 d, 1.87 (0.00-3.99) from 101 d to 6 months, 1.44 (0.18-2.70) from >6 months to 1 year, 0.94 (0.36-1.53) from >1 year to 3 years and 2.17 (1.14-3.21) from >3 years to the end of follow-up. The median follow-up time was 2.13 person-years., Conclusion: This population-based study indicates that OAC is primarily diagnosed during the first months following an initial diagnosis of BO. This could justify a changed surveillance strategy of BO with a repeated thorough endoscopy shortly after initial BO diagnosis to identify prevalent early OAC or HGD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or intramucosal cancer (IMC) on endoscopic forceps biopsies are referred to endoscopic therapy even though forceps biopsies do not reflect the disease extent accurately. Endoscopic mucosal resection (EMR) and endoscopic ultrasound (EUS) are frequently used for staging prior to endoscopic therapy. Our aims were to evaluate: (1) if endoscopic forceps biopsies correlated with EMR histology in these patients; (2) the utility of EUS compared to EMR; and (3) if accuracy of EUS varied based on grade of differentiation of tumor., Methods: This is a retrospective review of patients referred to endoscopic therapy of BE with HGD or early esophageal adenocarcinoma (EAC) who underwent EMR from 2006 to 2011. Age, race, sex, length of Barrett's segment, hiatal hernia size, number of endoscopies and biopsy results and EUS findings were abstracted., Results: A total of 151 patients underwent EMR. In 50 % (75/151) of patients, EMR histology was consistent with endoscopic forceps biopsy findings. EMR resulted in change in diagnosis with upstaging in 21 % (32/151) and downstaging in 29 % (44/151). In patients with HGD on EMR, EUS staging was T0 in 74.1 % (23/31) but upstaged in 25.8 % (8/31). In patients with IMC on EMR, EUS findings were T1a in 23.6 % (9/38), upstaged in 18.4 % (7/38) and downstaged in 57.8 % (22/38). EUS accurately identified EMR histology in all submucosal cancers. Grade of differentiation was reported in 24 cancers on EMR histology. There was no correlation between grade and EUS staging., Conclusions: EUS is of limited utility in accurate staging of BE patients with HGD or early EAC. Endoscopic forceps biopsy correlated with EMR findings in only 50 % of patients. Irrespective of the endoscopic forceps biopsy results, all BE patients with visible lesions should be referred to EMR.

Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a distinct type of biliary tumor. We herein discuss the possible mechanisms underlying the development of multiple tumors in patients with IPNBs through a case presentation and literature review. A 64-year-old woman initially underwent extended right hepatectomy for IPNB in the right hepatic duct. Although the surgical margin of the common bile duct was tumor-free, recurrence was detected in the intrapancreatic bile duct 26 months later. Both tumors had similar histopathological characteristics (intestinal-type IPNB with high-grade dysplasia, but no invasive cancer). A literature review identified 9 additional cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in the extrahepatic bile duct. Although multicentric tumors have been suggested in such cases, the intrabiliary dissemination of tumor cells appears to be more likely, as the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor.

Background: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD)., Objective: The purpose of this study was to investigate the molecular effects of endotherapy., Methods: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals., Results: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes., Conclusion: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

Barrett's oesophagus is a precursor lesion for oesophageal adenocarcinoma, which generally has a poor prognosis. Patients diagnosed with Barrett's oesophagus therefore undergo regular endoscopic surveillance to detect neoplastic lesions at a curable stage. The efficacy of endoscopic surveillance of Barrett's oesophagus patients is, however, hampered by difficulties to detect early neoplasia endoscopically, biopsy sampling error, inter-observer variability in histological assessment and the relatively low overall progression rate. Efficacy and cost-effectiveness of Barrett's surveillance may be improved by using endoscopic and clinical characteristics to risk-stratify Barrett's patients to high- and low-risk categories. Recent national and international surveillance guidelines have incorporated Barrett's length and presence of low-grade dysplasia in the advised surveillance intervals. In this review we will discuss endoscopic characteristics that may be associated with neoplastic progression in Barrett's oesophagus and that may be used to tailor surveillance in Barrett's patients.

Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines-ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4-all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC.

Introduction: The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett's esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett's neoplasia., Methods: All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett's esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors., Results: Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett's segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%., Conclusion: In this early experience, ESD yielded a moderate curative resection rate in Barrett's neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett's neoplasia.

Background and Aims: The safety and efficacy of radiofrequency ablation (RFA) in treatment of Barrett's esophagus (BE)-associated dysplasia has been well established. The effectiveness of focal and balloon RFA devices has not been compared. Therefore, the aim of our study was to assess the effectiveness of focal and balloon RFA devices in the treatment of BE by calculating absolute and percentage change in BE length with RFA therapy by comparing pre- and post-treatment BE length., Patients and Methods: This is a retrospective cross-sectional study of patients who underwent at least one treatment with either focal and/or balloon RFA devices who were identified from two tertiary centers. Patients' demographics, hiatal hernia, pre- and post-treatment BE length, prior use of endoscopic therapies and number of sessions were recorded., Results: Sixty-one patients who had undergone 161 RFA treatment sessions met inclusion criteria. There was no significant difference in percentage change in BE length with greater number of RFA sessions. RFA with a focal device resulted in greater percentage reduction in BE length compared to the balloon system (73% vs. 39%, p < 0.01). After adjusting for initial BE length, pre-treatment BE length, hernia status, prior endoscopic mucosal resection (EMR), prior RFA, and prior EMR/RFA sessions, RFA with a focal device at each session remained an independent predictor for a significant reduction in BE extent as compared to the balloon system., Conclusion: The focal RFA device alone was more effective in treatment of BE compared to the balloon system, with a greater reduction in extent of BE. The focal RFA device for endoscopic eradication therapy of BE should be considered the preferred technique.

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies, this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.

Background: We present long-term follow-up data on patients with esophageal high-grade dysplasia and/or carcinoma in situ who were treated with laparoscopic transgastric esophageal mucosal resection (LTEMR)., Methods: Patient demographics, operative outcomes, and follow-up results were tabulated., Results: LTEMR was performed in 11 patients (9 male, 2 female). The median age was 54 (44 to 75) years. The 30-day morbidity or mortality was zero. The median follow-up was 5.2 (2 to 12) years. Upper endoscopy was performed at 3, 6, and 12 month, and yearly thereafter. All patients regenerated squamous epithelium at 6 months. One patient developed a recurrence of Barrett's epithelium 2 years after resection. No recurrences of high-grade dysplasia or carcinoma were observed in any of the patients. Two patients developed an esophageal stricture; both were treated successfully with endoscopic balloon dilation and have suffered no further sequelae., Conclusions: LTEMR is safe and effective alternative method to treat patients with Barrett's esophagus with high-grade dysplasia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making., Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE are described., Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17). Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA., Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA., Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional pathology in the assessment of BE.

Esophageal adenocarcinoma (EAC) has increased dramatically in the past 3 decades, making its precursor lesion Barrett's esophagus (BE) an important clinical problem. Effective interventions are available, but overall outcomes remain unchanged. Most of the BE population remains undiagnosed; most EACs are diagnosed late, and most BE patients will never progress to cancer. These epidemiologic factors make upper endoscopy an inefficient and ineffective strategy for BE diagnosis and risk stratification. In the current review, biomarkers for diagnosis, risk stratification, and predictors of response to therapy in BE are discussed., (Published by Elsevier Inc.)

In this paper, the authors review recent topics of interest in relation to squamous dysplasia and squamous cell carcinoma in situ in Japan, and also the differences in diagnostic criteria for squamous cell carcinoma in situ between Japanese and Western pathologists. Photomicrographs of high-grade squamous dysplasia in Western textbooks of surgical pathology are judged in Japan to be squamous cell carcinoma in situ. Squamous cell carcinoma in situ can be histologically subdivided by the appearance of the basement membrane into the simple replacement type, showing a linear pattern, and the bulky outgrowth type, showing a wavy pattern. Squamous cell carcinoma in situ may also be classified into a total layer type, in which the entire epithelium is replaced by tumor cells, and a basal layer type in which the basal half is replaced by tumor cells. It is frequently observed that minute squamous cell carcinomas of the basal layer type, but not the total layer type, show signs of early stromal invasion into the lamina propria mucosae. These histologic findings strongly indicate that the basal layer type is not low-grade dysplasia but squamous cell carcinoma in situ. [ABSTRACT FROM AUTHOR]

Some topics related mainly to histopathologic aspects of gastroesophageal reflux disease and columnar-lined esophagus (CLE) are reviewed and discussed briefly in order to understand CLE and Barrett’s adenocarcinoma (BA). The esophagogastric junction (EGJ) is considered in Japan to be the lower limit at which longitudinal vessels can be seen within the lower segment of the esophagus by endoscopy. This definition has been endorsed by the Japan Esophageal Society. In Western countries, the proximal end of the gastric folds is considered to represent the EGJ. Histologic diagnosis of biopsy specimens from CLE is also discussed in relation to the presence of esophageal glands proper. The differences in the histopathologic criteria for BA between Western countries and Japan are also described. [ABSTRACT FROM AUTHOR]

Background and Objective: Even when advanced cross-sectional imaging modalities have been employed, endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMN) is often required in order to assess the final character and extent of lesions. The current study addresses the use of SpyGlass single-operator peroral pancreatoscopy in suspected IPMN., Design: A prospective, non-randomized exploratory cohort study., Setting: Single-center., Patients and Intervention: A prospective study-cohort of 44 consecutive patients in a single tertiary referral center who underwent ERCP and peroral pancreatoscopy, was prospectively collected between July 2007 and March 2013 because of a radiological signs of IPMN. These IPMN-findings were discovered incidentally in 44% of the cases., Main Outcome Measurements: Diagnostic accuracy (specificity & sensitivity) and complications., Results: The targeted region of the pancreatic duct was reached with the SpyGlass system in 41 patients (median age 65 years, 41% female). Three patients were excluded from analysis because of failed deep cannulation of the pancreatic duct. Brush cytology was taken in 88% and direct biopsies in 41%. IPMN with intermediate or high-grade dysplasia was the main final diagnosis (76%) in 22 patients who had surgery. Out of the 17 patients with a final diagnosis of MD-IPMN, 76% were correctly identified by pancreatoscopy. Of the 9 patients with a final diagnosis of BD-IPMN, the pancreatoscopy identified 78% of the cases correctly.The incidence of post-ERCP pancreatitis was 17%. Pancreatoscopy was found to have provided additional diagnostic information in the vast majority of the cases and to affect clinical decision-making in 76%., Limitations: Single-center study., Conclusions: Single-operator peroral pancreatoscopy contributed to the clinical evaluation of IPMN lesions and influenced decision-making concerning their clinical management. The problem of post-procedural pancreatitis needs further attention., (Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Gastric high-grade dysplasia is an important premalignant lesion in gastric epithelial cells and has a high possibility of transforming to adenocarcinoma. Therefore, biopsy-proven high-grade dysplasia should be treated with en bloc resection methods such as endoscopic mucosal resection or endoscopic submucosal dissection (ESD). We report the case of a 63-year-old male patient, diagnosed with gastric high-grade dysplasia at the angle and lesser curvature side of the lower body. The patient was initially treated with ESD, although histopathology subsequently showed horizontal margin involvement. Since the lesion was diffusely edematous and margins were uncertain because of the previous ESD treatment, we chose to treat the patient with laparoscopy-assisted endoscopic full-thickness resection (EFTR). EFTR is a recently developed procedure, which uses both endoscopic and laparoscopic techniques to resect the full-thickness of the tissue. The final pathologic report revealed high-grade dysplasia and a focal intramucosal carcinoma of 0.8×0.7 cm. We conclude that EFTR can be an effective alternative treatment in gastric high-grade dysplasia unsuitable for ESD.

The benzoazepinoqunolinone derivative, 5-amino-6-hydroxy-8 H -benzo[6,7]azepino[5,4,3- de ]quinolin-7-one (ABAQ), which is produced in a mixture of glucose and tryptophan incubated at 37 °C under physiological conditions in the presence or absence of hydroxyl radicals caused by the Fenton reaction, is a novel aromatic mutagen. In the current study, we determined the tumor-initiating potency of ABAQ using an inflammation-relate, two-stage mouse colon carcinogenesis model. Male Crj: CD-1 (ICR) mice were treated with the single intragastric administration (100 or 200 mg/kg body weight) of ABAQ followed by subsequent 1-week oral exposure to 2% dextran sodium sulfate (DSS) in drinking water. The ABAQ treatment alone resulted in high-grade dysplasia, which is a precursor to colorectal cancer, in the colon. Following the administration of DSS after ABAQ treatment, the incidence and frequency of high-grade dysplastic lesions increased; the values were highest in the mice treated with 200 mg/kg body weight of ABAQ followed by DSS. The lesions expressing β-catenin in their nuclei and cytoplasm exhibited high proliferation activity without the expression of programmed cell death 4. These findings indicate that ABAQ has a tumor-initiating activity in the mouse colon, with or without inflammation, although the potential pro-inflammatory effect of high doses of ABAC should be investigated.

Background: Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE)., Objective: To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia., Design: Multicenter, randomized, controlled trial., Setting: Academic medical centers., Patients: Adult patients with BE undergoing routine surveillance or referred for early neoplasia., Intervention: Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard., Main Outcome Measurements: Diagnostic yield, performance characteristics, clinical impact., Results: A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients., Limitations: Tertiary-care referral centers and expert endoscopists limit generalizability., Conclusion: Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. (, Clinical Trial Registration Number: NCT01124214.)., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Esophagectomy is the conventional treatment for Barrett's esophagus with high-grade dysplasia and intramucosal cancer. Endotherapy is an alternative treatment., Objective: To compare the efficacy and safety of these 2 treatments., Design: PubMed, Web of Science, EMBASE, Cochrane Library and momentous meeting abstracts were searched. Studies comparing endotherapy with esophagectomy were included in the meta-analysis. Pooling was conducted in a random-effects model., Setting: Tertiary-care facility., Patients: Seven studies involving 870 patients were included., Intervention: Endotherapy and esophagectomy., Main Outcome Measurements: Neoplasia remission rate, neoplasia recurrence rate, overall survival rate, neoplasia-related death, and major adverse events., Results: Meta-analysis showed that there was no significant difference between endotherapy and esophagectomy in the neoplasia remission rate (relative risk [RR] 0.96; 95% CI, 0.91-1.01); overall survival rate at 1 year (RR 0.99; 95% CI, 0.94-1.03), 3 years (RR 1.03; 95% CI, 0.96-1.10), and 5 years (RR 1.00; 95% CI, 0.93-1.06); and neoplasia-related mortality (risk difference [RD] 0; 95% CI, -0.02 to 0.01). Endotherapy was associated with a higher neoplasia recurrence rate (RR 9.50; 95% CI, 3.26-27.75) and fewer major adverse events (RR 0.38; 95% CI, 0.20-0.73)., Limitations: Relatively small number of retrospective studies available, different types of endoscopic treatments were used., Conclusion: Endotherapy and esophagectomy show similar efficacy except in the neoplasia recurrence rate, which is higher after endotherapy. Prospective, randomized, controlled trials are needed to confirm these results., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Endoscopic surveillance for non-dysplastic Barrett's esophagus (BE) is contentious and its cost effectiveness unclear., Objective: To perform an economic analysis of endoscopic surveillance strategies., Design: Cost-utility analysis by using a simulation Markov model to synthesize evidence from large epidemiologic studies and clinical data for surveillance, based on international guidelines, applied in a coordinator-managed surveillance program., Setting: Tertiary care hospital, South Australia., Patients: A total of 2040 patient-years of follow-up., Intervention: (1) No surveillance, (2) 2-yearly endoscopic surveillance of patients with non-dysplastic BE and 6-monthly surveillance of patients with low-grade dysplasia, (3) a hypothetical strategy of biomarker-modified surveillance., Main Outcome Measurements: U.S. cost per quality-adjusted life year (QALY) ratios., Results: Compared with no surveillance, surveillance produced an estimated incremental cost per QALY ratio of $60,858. This was reduced to $38,307 when surveillance practice was modified by a hypothetical biomarker-based strategy. Sensitivity analyses indicated that the likelihood that surveillance alone was cost-effective compared with no surveillance was 16.0% and 60.6% if a hypothetical biomarker-based strategy was added to surveillance, at an acceptability threshold of $100,000 per QALY gained., Limitations: Treatment options for BE that overlap those for symptomatic GERD were omitted., Conclusion: By using best available estimates of the malignant potential of BE, endoscopic surveillance of patients with non-dysplastic BE is unlikely to be cost-effective for the majority of patients and depends heavily on progression rates between dysplasia grades. However, strategies that modify surveillance according to cancer risk might be cost-effective, provided that high-risk individuals can be identified and prioritized for surveillance., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus., Objective: To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma., Design: A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo., Setting: Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit., Patients: Tissue from 62 patients was included in the study., Interventions: Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically., Main Outcome Measurement: Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma., Results: ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated., Limitations: Measurements were taken from ex vivo tissue., Conclusion: ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Background: Despite advances in endoscopic treatment, many colonic adenomas are still referred for surgical resection. There is a paucity of data on the suitability of these lesions for endoscopic treatment., Objective: To analyze the results of routine repeat colonoscopy in patients referred for surgical resection of colon polyps without biopsy-proven cancer., Design: Retrospective review., Setting: University hospital., Patients: Patients referred to a colorectal surgeon for surgical resection of a polyp without biopsy-proven cancer., Interventions: Repeat colonoscopy., Main Outcome Measurements: The rate of successful endoscopic treatment., Results: There were 38 lesions in 36 patients; 71% of the lesions were noncancerous and were successfully treated endoscopically. In 26% of the lesions, previous removal was attempted by the referring physician but was unsuccessful. The adenoma recurrence rate was 50%, but all recurrences were treated endoscopically and none were cancerous. Two patients were admitted for overnight observation. There were no major adverse events., Limitations: Single center, retrospective., Conclusions: In the absence of biopsy-proven invasive cancer, it is appropriate to reevaluate patients referred for surgical resection by repeat colonoscopy at an expert center., (Published by Mosby, Inc.)

Background & Aims: Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) substantially reduces the risk of colorectal cancer in patients with inflammatory bowel disease (IBD), subsequent pouch neoplasia can develop. There are few data on the incidence of and risk factors for neoplasia, so there is no consensus on the need for pouch surveillance. We aimed to determine the cumulative incidence of pouch neoplasia in patients with IBD and identify risk factors for developing pouch neoplasia., Methods: We searched the Dutch Pathology Registry (PALGA) to identify all patients with IBD and IPAA in The Netherlands from January 1991 to May 2012. We calculated the cumulative incidence of pouch neoplasia and performed a case-control study to identify risk factors. Demographic and clinical variables were analyzed with univariable and multivariable Cox regression analyses., Results: We identified 1200 patients with IBD and IPAA; 25 (1.83%) developed pouch neoplasia, including 16 adenocarcinomas. Respective cumulative incidences at 5, 10, 15, and 20 years were 1.0%, 2.0%, 3.7%, and 6.9% for pouch neoplasia and 0.6%, 1.4%, 2.1%, and 3.3% for pouch carcinoma. A history of colorectal neoplasia was the only risk factor associated with pouch neoplasia. Hazard ratios were 3.76 (95% confidence interval, 1.39-10.19) for prior dysplasia and 24.69 (95% confidence interval, 9.61-63.42) for prior carcinoma., Conclusions: The incidence of pouch neoplasia in patients with IBD without a history of colorectal neoplasia is relatively low. Prior dysplasia or colon cancer is associated with an approximate 4- and 25-fold increase in risk, respectively, of developing pouch neoplasia., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of mucinous pancreatic cysts (MPCs) is challenging due to the poor sensitivity of cytology provided by EUS-guided-FNA (EUS-FNA)., Objective: To quantify the test characteristics of molecular (DNA) analysis in suspected low-risk MPCs., Design: A prospective cohort study performed in between 2008 and 2011., Setting: Academic referral center., Patients: Consecutive patients who underwent EUS-FNA of suspected MPCs., Intervention: EUS-FNA and molecular (DNA) analysis of cyst fluid., Main Outcome Measurements: The sensitivity and specificity of molecular analysis in the diagnosis of MPCs using the criterion standard of surgical pathology in resected cysts., Results: Patients with suspected MPCs underwent EUS-FNA and cyst fluid DNA analysis. Surgical resection was performed in 48 patients (17%), confirming a mucinous pathology in 38 (79%). In this group, molecular analysis had a sensitivity of 50% and a specificity of 80% in identifying MPCs (accuracy of 56.3%). The combination of molecular analysis with cyst fluid carcinoembryonic antigen (CEA) and cytology resulted in higher MPC diagnostic performance than either one of its individual components, with a sensitivity, specificity, and accuracy of 73.7%, 70%, and 72.9%, respectively. There was no significant difference in accuracy between molecular analysis and CEA/cytology in this group., Limitations: Single-center experience., Conclusion: Molecular analysis aids in the diagnosis of MPCs when cytology is nondiagnostic or cyst fluid is insufficient for CEA or its level is indeterminate. Our results do not support the routine use of molecular analysis, which should be used selectively after review of imaging findings and cyst fluid studies. Further studies are needed to assess DNA's performance in malignant cysts., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: The management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear., Aim: The aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD., Methods: 997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan-Meier estimates and incidence rates calculated., Results: Of the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18-71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio=3.6; 95% confidence interval, CI (1.3-10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia., Conclusions: The frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Despite the increasing number of patients undergoing endoscopic therapy for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC), there are few data to guide clinical decision making and research initiatives in the area of posttreatment follow-up., Objectives: We aimed to define expert practice patterns regarding follow-up after endoscopic treatment of BE with HGD and IMC., Design: Electronic survey., Subjects: Forty-eight endoscopists in the United States with expertise in BE endotherapy based on high-impact publications and national reputation., Intervention: A 21-item Web-based survey inquiring about post-BE endotherapy follow-up practices., Results: Of 48 expert endoscopists, 42 completed the survey. After successful treatment of BE with HGD or IMC, all experts perform surveillance upper endoscopy, most commonly at 3-month intervals in the first posttreatment year, every 6 months during the second year, and annually thereafter. None of the experts perform surveillance EUS after treatment of HGD, and only 19% perform EUS after treatment of IMC. After cancer eradication, only 36% of experts refer patients for CT, and 24% refer patients for positron emission tomography. Thirty-eight percent of experts refer patients for a surgical opinion when IMC extends into the muscularis mucosa; 100% refer when IMC extends into submucosa., Limitations: Not a consensus document; only U.S. experts included., Conclusions: This study reports the follow-up practices of expert endoscopists after successful endotherapy for BE with HGD and IMC. Additional research is necessary to establish optimal surveillance intervals, the role of follow-up EUS, CT, and positron emission tomography, as well as the surgical implications of low-risk IMC extending into the muscularis mucosa., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background/objectives: Morphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN., Methods: This retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated., Results: According to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5-87.4, p = 0.003)., Conclusions: In mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Endoscopic management of Barrett's esophagus (BE) has evolved over the past decade; however, the practice patterns for managing BE among gastroenterologists remain unclear., Objective: To assess practice patterns for management of BE among gastroenterologists working in various practice settings., Design: A random questionnaire-based survey of practicing gastroenterologists in the United States. The questionnaire contained a total of 10 questions pertaining to practice setting, physician demographics, and strategies used for managing BE., Setting: Survey of gastroenterologists working in various practice settings., Intervention: Questionnaire., Main Outcome Measurements: Practice patterns for endoscopic imaging and management of BE., Results: The response rate was 45% (236/530). The majority (85%) were gastroenterologists in community practice, 72% were aged 41 to 60 years, 80% had >10 years of experience, and 81% had attended postgraduate courses and/or seminars on BE management. A total of 78% did not use the Prague C & M classification, and about a third used advanced endoscopic imaging routinely (37%) or in selected cases (31%). For nondysplastic BE, 86% practiced surveillance, 12% performed ablation, and 3% did no intervention. For BE with low-grade dysplasia, 56% practiced surveillance, 26% performed endoscopic ablation in all low-grade dysplasia cases, and 18% performed endoscopic ablation in only selected patients with low-grade dysplasia. The majority of respondents (58%) referred their patients with high-grade dysplasia to centers with BE expertise, 13% performed endoscopic ablation in all patients with high-grade dysplasia, 25% performed endoscopic ablation in selected cases only, and 3% referred these patients for surgery. The most frequently used endoscopic eradication therapy was radiofrequency ablation (39%) followed by EMR (17%)., Limitations: The sample may be unrepresentative, participation in the study was voluntary, and responses may be skewed toward following the guidelines., Conclusion: Results from this survey show that the majority of practicing gastroenterologists in the United States practice surveillance endoscopy in patients with nondysplastic BE and provide endoscopic therapy for those with high-grade dysplasia. The Prague C & M classification and advanced imaging techniques are used by less than a third of gastroenterologists. Practice patterns did not appear to be affected by respondent age or duration of clinical practice., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background & Aims: Endoscopic therapy can improve long-term outcomes of patients with superficial esophageal adenocarcinoma (EAC), producing fewer complications than esophagectomy. However, there have been few population-based studies to compare long-term outcomes of patients who received these treatments. We used a large national cancer database to evaluate the outcomes of patients with superficial EAC who underwent endoscopic therapy or surgery., Methods: We used the Surveillance Epidemiology and End Results database to identify 1618 patients with Tis or T1 N0M0 EAC from 1998-2009. Patients were grouped on the basis of whether they received endoscopic therapy (n = 306) or surgery (n = 1312). Multivariate logistic regression was performed to identify factors associated with endoscopic therapy. We collected survival data through the end of 2009; overall survival and esophageal cancer-specific survival were compared after controlling for relevant covariates., Results: The use of endoscopic therapy increased progressively from 3% in 1998 to 29% in 2009. Factors associated with use of endoscopic therapy included age older than 65 years, diagnosis in 2006-2009 vs 1998-2001, and the absence of submucosal invasion. Overall survival after 5 years was higher in the surgery group than in the endoscopic therapy group (70% vs 58%, respectively). After adjusting for patient and tumor factors, patients treated by endoscopy had similar overall survival times (hazard ratio, 1.21; 95% confidence interval, 0.92-1.58) and esophageal cancer-specific survival times (hazard ratio, 0.74; 95% confidence interval, 0.49-1.11)., Conclusion: In a population-based analysis, the use of endoscopic therapy for superficial EAC tended to increase from 1998-2009. Long-term survival of patients with EAC did not appear to differ between those who received endoscopic therapy and those treated with surgery., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length., Methods: We analyzed data from a large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n = 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (≤3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE., Results: The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P = .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P = nonsignificant)., Conclusions: In patients with BE without dysplasia, length of BE was associated with progression to HGD or EAC. The results support the development of a risk stratification scheme for these patients based on length of BE segment., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: In patients with Barrett's esophagus (BE), radiofrequency ablation (RFA) safely and effectively eradicates dysplasia and intestinal metaplasia. We aimed to determine the efficacy and durability of RFA for patients with dysplastic and nondysplastic BE., Methods: We performed a systematic review and meta-analysis of studies identified in PubMed and EMBASE that reported the proportion of patients treated with RFA who had complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM), and the proportion of patients with recurrent IM after successful treatment. Pooled estimates of CE-D, CE-IM, IM recurrence, and adverse events were calculated., Results: We identified 18 studies of 3802 patients reporting efficacy and 6 studies of 540 patients reporting durability. Ten were prospective cohort studies, 9 were retrospective cohort studies, and 1 was a randomized trial. CE-IM was achieved in 78% of patients (95% confidence interval [CI], 70%-86%) and CE-D was achieved in 91% (95% CI, 87%-95%). After eradication, IM recurred in 13% (95% CI, 9%-18%). Progression to cancer occurred in 0.2% of patients during treatment and in 0.7% of those after CE-IM. Esophageal stricture was the most common adverse event and was reported in 5% of patients (95% CI, 3%-7%). Confidence in most summary estimates was limited by a high degree of heterogeneity, which did not appear to be caused by single outlier studies., Conclusions: Treatment of BE with RFA results in CE-D and CE-IM in a high proportion of patients, with few recurrences of IM after treatment and a low rate of adverse events. Despite the large amount of study heterogeneity, these data provide additional information for patients and providers to make informed treatment decisions., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Colorectal cancer (CRC) and advanced precancers can be detected noninvasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance., Methods: In a blinded, multicenter, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n = 93), advanced adenoma (AA) (n = 84), or sessile serrated adenoma ≥1 cm (SSA) (n = 30); controls included nonadvanced polyps (n = 155) or no colonic lesions (n = 641). Samples were analyzed by using an automated multi-target sDNA assay to measure β-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or SSA ≥1 cm)., Results: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant P value). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity., Conclusions: We developed an automated, multi-target sDNA assay that detects CRC and premalignant lesions with levels of accuracy previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible noninvasive approach to general CRC screening., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry., Methods: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events., Results: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol., Conclusion: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data.

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.

Background & Aims: Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE)., Methods: We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer., Results: Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively (P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC., Conclusions: Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Early cancer (high-grade dysplasia [HGD] and intramucosal carcinoma [ImCa]) associated with Barrett's esophagus (BE) may have a circumferential spatial predilection., Objective: To describe the esophageal circumferential location of early cancer in BE., Design and Setting: Retrospective study, single tertiary referral center., Patients and Intervention: One hundred nineteen patients were referred for endoscopic eradication therapy for early cancer associated with BE. Endoscopic images and reports and pathology were reviewed., Main Outcome Measurements: Circumferential location designation of early cancer in BE by using a clock-face orientation., Results: One hundred nineteen of 131 patients referred for endoscopic eradication therapy had a location designation for their advanced histology (91.9%). There were a total of 57 patients (47.9%) with HGD and 62 patients (52.1%) with ImCa. There was a significantly higher rate of early cancer (HGD or ImCa) in the right hemisphere (12 to 6 o'clock location) compared with the left hemisphere (84.9% vs 15.1%, P < .0001). The highest percentage of early cancer was found in the 12 to 3 o'clock quadrant (64.7%); 71.9% of HGD and 58.1% of ImCa lesions were located in the 12 to 3 o'clock quadrant., Limitations: Retrospective design, single center., Conclusions: Early cancer associated with BE is far more commonly found in the right hemisphere of the esophagus (12 to 6 o'clock) with the highest rate in the 12 to 3 o'clock quadrant. These findings support enhanced scrutiny of the right hemisphere of the esophagus during surveillance and endoscopic treatment of patients with BE., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Liquid nitrogen endoscopic spray cryotherapy can safely and effectively eradicate high-grade dysplasia in Barrett's esophagus (BE-HGD). Long-term data on treatment success and safety are lacking., Objective: To assess the long-term safety and efficacy of spray cryotherapy in patients with BE-HGD., Design: Single-center, retrospective study., Setting: Tertiary-care referral center., Patients: A total of 32 patients with BE-HGD of any length., Intervention: Patients were treated with liquid nitrogen spray cryotherapy every 8 weeks until complete eradication of HGD (CE-HGD) and intestinal metaplasia (CE-IM) was found by endoscopic biopsy. Surveillance endoscopy with biopsies was performed for at least 2 years., Main Outcome Measurements: CE-HGD, CE-IM, durability of response, disease progression, and adverse events., Results: CE-HGD was 100% (32/32), and CE-IM was 84% (27/32) at 2-year follow-up. At last follow-up (range 24-57 months), CE-HGD was 31/32 (97%), and CE-IM was 26/32 (81%). Recurrent HGD was found in 6 (18%), with CE-HGD in 5 after repeat treatment. One patient progressed to adenocarcinoma, downgraded to HGD after repeat cryotherapy. BE segment length ≥3 cm was associated with a higher recurrence of IM (P = .004; odds ratio 22.6) but not HGD. No serious adverse events occurred. Stricture was seen in 3 patients (9%), all successfully dilated., Limitations: Retrospective study design, small sample size., Conclusion: In patients with BE-HGD, liquid nitrogen spray cryotherapy has an acceptable safety profile and success rate for eliminating HGD and IM and is associated with a low rate of recurrence or progression to cancer with long-term follow-up., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background & Aims: Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes., Methods: We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors., Results: Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA., Conclusions: Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Probe-based confocal laser endomicroscopy (pCLE) is a novel imaging technique which utilizes a low-power laser light passed through a fiber-optic bundle, within a miniprobe that is advanced into the working channel, to obtain microscopic images of the mucosa. This allows the endoscopist to evaluate the microarchitecture of the gastrointestinal epithelium in real time. At this time pCLE cannot replace histopathology, but it can provide diagnostic information as well as guide therapeutic management in patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). We describe a retrospective case series in which four patients with BE and biopsy-proven HGD underwent endoscopy with pCLE to direct real-time endoscopic ablation therapy and/or endoscopic mucosal resection (EMR), which was performed in conjunction with pCLE. All four patients had pCLE showing features of HGD. After either EMR or radiofrequency ablation (RFA), pCLE was again used to evaluate the margins after therapy to assure accuracy. In one case, pCLE had features of dysplasia at the margin and further repeat EMR was immediately performed. Another case had a normal-appearing esophagus, but pCLE found features of BE in discrete areas and targeted biopsies were performed, which confirmed BE. This patient subsequently underwent RFA therapy of the residual areas of BE. In conclusion, in patients with BE and dysplasia, pCLE is an effective tool used to target biopsies, guide endoscopic therapy and assess the accuracy of EMR or RFA.

High-grade dysplasia (HGD) in Barrett's esophagus (BE) is the critical step before invasive esophageal adenocarcinoma. Although its natural history remains unclear, an aggressive therapeutic approach is usually indicated. Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium. In healthy patients with reasonable life expectancy, vagal-sparing esophagectomy, with associated low mortality and low early and late postoperative morbidity, is considered the treatment of choice for BE with HGD. Patients unfit for surgery should be managed in a less aggressive manner, using endoscopic ablation or endoscopic mucosal resection of the entire BE segment, followed by lifelong surveillance. Patients eligible for surgery who present with a long BE segment, multifocal dysplastic lesions, severe reflux symptoms, a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment, either surgical or endoscopic.

Esophageal adenocarcinoma and its precursor, Barrett's esophagus, are rapidly rising in incidence. This review serves to highlight the role of pharmacologic, endoscopic, and surgical intervention in the management of Barrett's esophagus, which requires acid suppression and endoscopic assessment. Treatment with a proton pump inhibitor may decrease acid exposure and delay the progression to dysplasia. Patients who require aspirin for cardioprotection or other indications may also benefit in terms of a protective effect against the development of esophageal cancer. However, without other indications, aspirin is not indicated solely to prevent cancer. A careful endoscopic examination should include assessment of any visible lesions in a Barrett's segment. An expert gastrointestinal pathologist should confirm neoplasia in the setting of Barrett's esophagus. For those patients with high-grade dysplasia or intramucosal carcinoma, careful consideration of endoscopic therapy or surgical therapy must be given. All visible lesions in the setting of dysplasia should be targeted with focal endoscopic mucosal resection for both accurate histopathologic diagnosis and treatment. The remainder of the Barrett's epithelium should be eradicated to address all synchronous and metachronous lesions. This may be done by tissue acquiring or nontissue acquiring means. Radiofrequency ablation has a positive benefit-risk profile for flat Barrett's esophagus. At this time, endoscopic therapy is not indicated for nondysplastic Barrett's esophagus. Esophagectomy is still reserved for selected cases with evidence of lymph node metastasis, unsuccessful endoscopic therapy, or with high-risk features of high-grade dysplasia or intramucosal carcinoma.

Colorectal carcinomas (CRC) usually arise in colorectal adenomas (CRA) displaying high-grade dysplasia (HGD) or carcinoma in situ (CIS). The aim was to assess the frequency of adenomas displaying HGD or CIS in a cohort of consecutive CRA with submucosal invasive carcinoma. Ninety-two consecutive adenomas were investigated. Sub-mucosal invasion was present in the 39 adenomas with HGD (42%) and in 58% (53/92) of the adenomas with CIS (p<0.05). Sections from 49 adenomas were stained with the DNA-specific Feulgen reaction and for the proliferation marker Ki-67. Five consecutive high power fields (HPFs) were evaluated using a x40 objective. Marked Feulgen reaction was recorded in 91.8% or in 101 of the 110 HPFs studied in adenomas with HGD, but in none of the 135 HPFs studied in adenomas with CIS (p<0.05). Intense Ki-67 expression (>/=75%) was present in 98.2% or in 108 of the 110 HPFs studied in adenomas with HGD, but only in 1.4% or in 2 of the 135 HPFs in adenomas with CIS (p<0.05). Hence, HGD cells and CIS cells can be differentiated not only morphologically but also chemically by the semi-quantitative appreciation of their DNA content and immunohistochemically by the apparent difference in cell proliferation. Although submucosal invasion occurred significantly more frequently in adenomas with CIS than in those with HGD, as many as 42% of the adenomas with submucosal invasion displayed HGD at histology. Despite morphological, chemical and immunohistochemical dissimilarities, these 2 non-invasive neoplasias might have similar biological behaviour in terms of progression towards submucosal invasion.

Barrett's esophagus is a known risk factor for the development of adenocarcinoma of the esophagus and esophagogastric junction. Based on the length of the columnar segment at endoscopy, Barrett's esophagus has been arbitrarily separated into two broad categories: long-segment and short-segment. The rapid rise in the incidence of esophageal adenocarcinoma has generated sustained research interest in this lesion. Studies have shown that although the prevalence of short-segment Barrett's esophagus is higher than that of long-segment Barrett's esophagus, the risk of developing dysplasia and adenocarcinoma may actually be lower in those patients with short segment Barrett's esophagus. Nonetheless, both dysplasia and esophageal adenocarcinoma have been reported in patients with short-segment Barrett's esophagus, making this arbitrary distinction clinically unimportant. The current surveillance guidelines remain the same for both short- and long-segment Barrett's esophagus. Another key issue is differentiating short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. The latter is distinct from esophageal intestinal metaplasia (ie, Barrett's esophagus) and probably does not warrant surveillance.