The impact of endoscopic treatment on health-related quality of life in patients with Barrett's neoplasia: a scoping review.

PURPOSE: The objective of this scoping review is to understand the extent, type of evidence, and overall findings in relation to the impact of endoscopic treatment (ET) on health-related quality of life (HR-QoL) in patients with Barrett's dysplasia and early oesophageal cancer. METHODS: A comprehensive search was conducted for literature between 2001 and 2022 in computerised databases (PubMed, Embase, Cochrane Library, and CINAHL Complete). Additionally, sources of unpublished literature were searched in Google Advanced Search. After title and abstract checking, full-text papers were retrieved. Data were extracted, synthesised, key information tabulated, and a narrative synthesis completed. RESULTS: Six studies were included in the final analysis. Twelve different survey tools were utilised across all studies. Study designs included three randomised controlled studies, two prospective observational studies, and a single retrospective observational study. The average age of study participants ranged from 60.3 to 71.0 years. Two studies evaluated HR-QoL as primary outcome measures, but most research evaluated HR-QoL as a secondary outcome. Health domains evaluated in the studies focussed on the biophysical and psychosocial aspects of quality of life. CONCLUSION: A small number of research studies have been conducted in this area. Due to the heterogeneity and small number of included studies, it was difficult to draw conclusions about the impact of specific ET types on HR-QoL. Overall, there were perceived psychological benefits while undergoing ET. Future research could target specific ET subtypes and measure HR-QoL at baseline and post-procedures in the short and long term.

Outcomes of patients with Barrett's oesophagus with low-grade dysplasia undergoing endoscopic surveillance in a tertiary centre: a retrospective cohort study.

BACKGROUND AND AIM: Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6-monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. METHODS: Endoscopy and pathology databases were searched over a 10-year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow-up times varied greatly, survival analysis techniques were employed. RESULTS: Fifty-nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non-guideline-adherent surveillance. A Cox model found only two predictors of progression: (i) guideline-adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non-guideline-adherent surveillance (95% confidence interval (CI) = 1.3-12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9-22.8; P = 0.003). CONCLUSION: Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline-recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined.

Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein.

OBJECTIVE: To investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. METHODS: We selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. RESULTS: In gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). CONCLUSION: The detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

Aberrant p53 expression is associated with neoplastic progression in Barrett oesophagus diagnosed as indefinite for dysplasia.

The aim of this study was to investigate the role of immunohistochemical (IHC) expression of p53 and other potential clinical parameters as prognostic markers for predicting neoplastic progression in Barrett oesophagus (BE) patients diagnosed as indefinite for dysplasia (IND). The study included patients with established BE of any extent who had a diagnosis of IND accompanied by concurrent p53 immunohistochemistry (IHC) stain at the index endoscopic procedure and at least one follow-up examination between 2000 and 2021. Correlation between disease progression from IND to higher-grade dysplasia [low-grade dysplasia (LGD), high-grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC)] and clinicopathological parameters were analysed. A total of 149 patients (99 males; mean age 63.3 ± 10.0 years, range = 35-89) were included in the final analysis. Median follow-up was 37.1 months [interquartile range (IQR) = 20.5-59.1 months]. Progression rates from IND to LGD and HGD were 12.1% (18 of 149) and 2.7% (four of 149), respectively. On multivariate analysis, the number of IND diagnoses was significantly associated with progression to both LGD and HGD (P = 0.016 and P < 0.001, respectively). Cox regression analysis showed that aberrant p53 expression was significantly associated with progression to LGD [hazard ratio (HR) = 4.87, 95% confidence interval (CI) = 1.91-12.45, P = 0.001] and HGD (HR = 21.81, 95% CI = 1.88-253.70, P = 0.014). Kaplan-Meier survival analysis also demonstrated that aberrant p53 expression was significantly associated with progression to LGD (P < 0.001) and HGD (P = 0.001). Our results suggest that frequency of IND diagnoses and status of p53 expression can help to stratify risk of neoplastic progression in BE patients with IND.

Colorectal cancer risk of flat low-grade dysplasia in inflammatory bowel disease: a systematic review and proportion meta-analysis.

BACKGROUND: To date, the optimal management of patients with inflammatory bowel disease (IBD) and flat low-grade dysplasia (fLGD) of the colon or rectum remains controversial. METHODS: A systematic review was reported in accordance with PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Patients diagnosed with fLGD on surveillance endoscopy were pooled from studies published between 2000 and 2020. Advanced neoplasia was defined by the presence of HGD, CRC or small bowel adenocarcinoma detected on subsequent surveillance endoscopy or from examination of resection specimens. We estimated the pooled annual incidence rate of colorectal cancer (CRC) and advanced neoplasia, and the risk factors associated with neoplastic progression. RESULTS: We identified 24 articles and 738 IBD patients were diagnosed with fLGD on endoscopy. Two hundred thirty-six patients (32%) underwent immediate surgery with surgical specimens demonstrating CRC in 8 patients (pooled prevalence, 8.66%; 95% CI 3.58-19.46) and HGD (high grade dysplasia) in 11 patients (pooled prevalence, 13.97%; 95% CI 5.65-30.65). Five hundred-two patients (68%) underwent endoscopic surveillance with 63 patients with fLGD progressing to advanced neoplasia during endoscopic surveillance (38 HGD, 24 CRC and one patient developing small bowel adenocarcinoma). The mean duration of follow-up after fLGD diagnosis was 71 months (10.9-212). The pooled incidence of CRC and advanced neoplasia was 0.5 (95% CI 0.23-0.77) and 1.71 per 100 patient-year (95% CI 0.88-2.54) respectively. The use of corticosteroids and location of fLGD in the distal colon were significantly associated with neoplastic progression. CONCLUSIONS: This study provides a summary incidence rate of CRC and advanced neoplasia in patients with IBD and fLGD to inform surgeons' and endoscopists' decision-making thus reducing potential ineffective treatments.

Endoscopic resection of gastric low-grade dysplasia with high risk factors is associated with decreased advanced neoplasia: a single-center retrospective cohort study.

BACKGROUND: The natural course of gastric low-grade dysplasia (LGD) remains unclear, and there are inconsistent management recommendations among guidelines and consensus. OBJECTIVE: This study aimed to investigate the incidence of advanced neoplasia in patients with gastric LGD and identify the related risk factors. METHODS: Cases of biopsy demonstrated LGD (BD-LGD) at our center from 2010 to 2021 were reviewed retrospectively. Risk factors related to histological progression were identified, and outcomes of patients based on risk stratification were evaluated. RESULTS: Ninety-seven (23.0%) of 421 included BD-LGD lesions were diagnosed as advanced neoplasia. Among 409 superficial BD-LGD lesions, lesion in the upper third of the stomach, H. pylori infection, larger size, and narrow band imaging (NBI)-positive findings were independent risk factors of progression. NBI-positive lesions and NBI-negative lesions with or without other risk factors had 44.7%, 1.7%, and 0.0% risk of advanced neoplasia, respectively. Invisible lesions, visible lesions (VLs) without a clear margin, and VLs with a clear margin and size ≤ 10 mm, or > 10 mm had 4.8%, 7.9%, 16.7%, and 55.7% risk of advanced neoplasia, respectively. In addition, endoscopic resection decreased the risk of cancer (P < 0.001) and advanced neoplasia (P < 0.001) in patients with NBI-positive lesions, but not in NBI-negative patients. Similar results were found in patients with VLs with clear margin and size > 10 mm. Moreover, NBI-positive lesions had higher sensitivity and lower specificity for predicting advanced neoplasia than VLs with a clear margin and size > 10 mm determined by white-light endoscopy (97.6% vs. 62.7%, P < 0.001; and 63.0% vs. 85.6%, P < 0.001, respectively). CONCLUSION: Progression of superficial BD-LGD is associated with NBI-positive lesions, as well as with VLs with a clear margin (size > 10 mm) if NBI is unavailable, and selective resection of those lesions offers benefits for patients by decreasing the risk of advanced neoplasia.

Low-grade dysplasia in Barrett's esophagus: A problematic diagnosis.

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed.

High interobserver variability and frequent overdiagnosis of dysplasia in fundic gland polyps can be improved by detecting atypia on the surface epithelium and an abrupt transition to non-neoplastic cells.

AIMS: Fundic gland polyps (FGPs) arise sporadically and in combination with familial adenomatous polyposis (FAP). Criteria for distinguishing low-grade dysplasia (LGD) from regenerative atypia in FGPs are not well established. The aims of study were to determine: (i) interobserver variability in diagnosing LGD in FGPs; (ii) bias in diagnosing LGD in FAP patients; and (iii) stringent criteria for LGD in FGPs. METHODS AND RESULTS: Five senior pathologists who were blinded to the clinical history reviewed 72 FAP-associated FGPs and 34 sporadic FGPs. Cases were classified as negative (score = 0) or positive (score = 1) for LGD. Each case was assigned a 'combined dysplasia score' (CDS) ranging from 0 to 5 to reflect all five opinions. Fleiss' kappa showed only moderate interobserver agreement (κ = 0.46). Forty-one FGPs were classified as negative for dysplasia by consensus (CDS = 0-1), including 10 (24%) originally diagnosed as LGD. In contrast, all 37 cases classified as LGD by consensus (CDS = 4-5) were originally diagnosed as LGD, indicating that overdiagnosis of dysplasia is more common than underdiagnosis (P = 0.0012). Cytological atypia in the surface epithelium and an abrupt transition between atypical and normal-appearing epithelium were the most sensitive (97% and 100%, respectively) and specific (100% and 98%, respectively) features of dysplasia (P < 0.0001 for both comparisons). Very good agreement was achieved when a diagnosis of dysplasia was based on the presence of both features (κ = 0.85). CONCLUSIONS: There is high interobserver variability and a tendency to overdiagnose LGD in FGPs. Strict criteria requiring both surface atypia and abrupt transition for LGD in FGPs result in low interobserver variability.

Prevalence of Extensive and Limited Gastric Intestinal Metaplasia and Progression to Dysplasia and Gastric Cancer.

BACKGROUND AND AIMS: Guidelines cite extensive gastric intestinal metaplasia (GIM) as a bigger risk factor for gastric cancer (GC) than limited GIM and an indication for endoscopic surveillance. Data on progression of extensive GIM to GC in the USA are limited. This study aimed to estimate the prevalence and progression rates of extensive GIM in a US cohort. METHODS: This retrospective study assessed the prevalence of extensive GIM between 1/1/1990 and 8/1/2019 at a large academic medical center. Multivariable regression was used to identify predictors of extensive GIM. Incidence of GC on follow-up was calculated as number of new diagnoses divided by person-years of follow-up. Presence of GIM on subsequent follow-up endoscopy was assessed. RESULTS: Of 1256 individuals with GIM, 352 (28%) had extensive GIM and 904 (72%) had limited GIM. On multivariable analysis, older age (OR 1.01, 95% CI 1.00-1.02) and Hispanic ethnicity (OR 1.55, 95% CI 1.11-2.16) were predictive of extensive GIM. The annual incidence of GC for GIM overall was 0.09%. There was no difference in progression to GC between extensive or limited GIM (IRR 0, 95% CI 0-2.6), or to advanced lesions overall (IRR 0.37, 95% CI 0.04-1.62). 70% of individuals had persistent GIM on follow-up biopsy, and 22% with limited GIM had extensive GIM on follow-up biopsy. CONCLUSIONS: 28% of individuals with GIM have the extensive subtype, and are more likely to be older and of Hispanic ethnicity. There was no difference in progression to GC between extensive and limited GIM. Further research is needed to better assess risk of GIM in the US context.

Reduced Esophageal Contractility Is Associated with Dysplasia Progression in Barrett's Esophagus: A Multicenter Cohort Study.

BACKGROUND: The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE. METHODS: This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression. RESULTS: Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)]. CONCLUSION: In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients.

Discordance Among Pathologists in the United States and Europe in Diagnosis of Low-Grade Dysplasia for Patients With Barrett's Esophagus.

BACKGROUND & AIMS: There is suboptimal inter-observer agreement, even among expert gastrointestinal pathologists, in the diagnosis of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE). We analyzed histopathologic criteria required for a diagnosis of LGD using the new subcategories of LGD with inflammatory and dysplastic features. We categorized each diagnosis based on the level of confidence and assessed inter-observer agreement among gastrointestinal pathologists from 5 tertiary centers in the United States and Europe. METHODS: In the first phase of the study, 3 pathologists held a consensus conference at which they discussed the diagnostic criteria for LGD. In the second phase, 79 slides from patients with BE (23 samples of non-dysplastic BE, 22 samples of LGD, and 34 samples of high-grade dysplasia) were identified, randomly assigned to 7 pathologists (4 from the United States and 3 from Europe), and interpreted in a blinded fashion. κ Values were calculated for inter-observer agreement. We performed multinomial logistic regression analysis to assess the weighting of histologic features with the diagnosis. RESULTS: The overall κ value for diagnosis was 0.43 (95% confidence interval [CI], 0.42-0.48). When categorized based on degree of dysplasia, the κ value was 0.22 (95% CI, 0.11-0.29) for non-dysplastic BE, 0.11 (95% CI, 0.004-0.15) for LGD, and 0.43 (95% CI, 0.36-0.46) for high-grade dysplasia. When all pathologists made a diagnosis with high confidence, the inter-observer agreement was substantial among the US pathologists (κ, 0.63; 95% CI, 0.61-0.66) and European pathologists (κ, 0.80; 95% CI, 0.74-0.97). The κ values for all diagnoses made by European pathologists were higher than those made by US pathologists. CONCLUSIONS: In an analysis of criteria used in histopathologic diagnosis of LGD, we did not observe improvement in level of agreement among experienced pathologists, even after accounting for inflammation. The level of inter-observer agreement increased with level of pathologist confidence. There was also a difference in reading of histopathology samples of BE tissues between US and European pathologists.

Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial.

BACKGROUND & AIMS: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.

Improved diagnostic stratification of digitised Barrett's oesophagus biopsies by p53 immunohistochemical staining.

AIMS: Interobserver agreement for dysplasia in Barrett's oesophagus (BO) is low, and guidelines advise expert review of dysplastic cases. The aim of this study was to assess the added value of p53 immunohistochemistry (IHC) for the homogeneity within a group of dedicated gastrointestinal (GI) pathologists. METHODS AND RESULTS: Sixty-single haematoxylin and eosin (HE) slide referral BO cases [20 low-grade dysplasia (LGD); 20 high-grade dysplasia (HGD); and 20 non-dysplastic BO reference cases] were digitalised and independently assessed twice in random order by 10 dedicated GI pathologists. After a 'wash-out' period, cases were reassessed with the addition of a corresponding p53 IHC slide. Outcomes were: (i) proportion of 'indefinite for dysplasia' (IND) diagnoses; (ii) interobserver agreement; and (iii) diagnostic accuracy as compared with a consensus 'gold standard' diagnosis defined at an earlier stage by five core expert BO pathologists after their assessment of this case set. Addition of p53 IHC decreased the mean proportion of IND diagnoses from 10 of 60 to eight of 60 (P = 0.071). Mean interobserver agreement increased significantly from 0.45 to 0.57 (P = 0.0021). The mean diagnostic accuracy increased significantly from 72% to 82% (P = 0.0072) after p53 IHC addition. CONCLUSION: Addition of p53 IHC significantly improves the histological assessment of BO biopsies, even within a group of dedicated GI pathologists. It decreases the proportion of IND diagnoses, and increases interobserver agreement and diagnostic accuracy. This justifies the use of accessory p53 IHC within our upcoming national digital review panel for BO biopsy cases.

Low Rate of Dysplasia Detection in Mucosa Surrounding Dysplastic Lesions in Patients Undergoing Surveillance for Inflammatory Bowel Diseases.

BACKGROUND & AIMS: When dysplastic lesions are encountered during surveillance colonoscopy of patients with inflammatory bowel disease (IBD), guidelines recommend collection of additional biopsies from the surrounding mucosa to ensure the lesion has been adequately circumscribed. We aimed to determine the rate of dysplasia in mucosa biopsies collected from tissues surrounding dysplastic lesions during IBD surveillance. METHODS: In a retrospective study, we collected endoscopy and pathology reports from 1065 patients undergoing colonoscopic surveillance for IBD from 2000 through 2015 at 3 centers in the Netherlands. We analyzed reports from all patients with dysplastic lesions from whom biopsies of surrounding mucosa were collected. Among 194 patients with 1 or more visible dysplastic lesions, mucosal biopsies were collected from tissues adjacent to 140 dysplastic lesions from 71 patients (63% male; 48% with ulcerative colitis, 42% with Crohn's disease, and 10% with indeterminate colitis). RESULTS: The mean number of surrounding mucosa biopsies collected per lesion was 3.4 (range, 1-6). Dysplasia was detected in 7 biopsies surrounding 140 areas of dysplasia (5.0%) and 5 biopsies surrounding 136 areas of low-grade dysplasia (3.7%). Dysplasia in biopsies of surrounding mucosa could be observed during 5 of 87 white light endoscopies and during 2 of 53 chromoendoscopies. In patients with dysplasia in mucosa surrounding lesions of low-grade dysplasia, post-resection surveillance did not reveal high-grade dysplasia or colorectal cancer. CONCLUSIONS: Dysplasia is detected in only 5% of biopsies collected from mucosa surrounding dysplastic lesions. This observation indicates that endoscopists accurately delineate the borders of dysplastic lesions during surveillance of patients with IBD. The lack of clinical consequences from routinely collecting biopsies from areas surrounding dysplastic lesions casts doubt on the usefulness and cost-effectiveness of this practice.

Adenocarcinoma risk in patients registered with Polish Barrett's Oesophagus Registry.

Barrett's Oesophagus (BO) is a complication of chronic gastro-oesophageal reflux disease (GORD) and is a major risk factor for oesophageal adenocarcinoma. Current guidelines are based on data showing a 0.5% annual malignancy progression rate. The Polish Barrett's Oesophagus Registry (POBOR) was established to characterize Polish patients with BO and estimate the risk of malignant progression. POBOR was established in 1999 after a dedicated training of endoscopists and histopathologists. Physicians registered patients using a dedicated registry form. After excluding patients known to have endoscopic treatment for BO, follow-up <1 year and adenocarcinoma found at index endoscopy we have linked patients personal identification numbers (PESEL) with the National Cancer Registry to identify those with a diagnosis of oesophageal or gastric cardia adenocarcinoma. In total, 843 patients were registered [609 men (72.2%), male to female ratio 2.6:1] with median age at diagnosis of 56 years (IQR:47-67). Long segment BE was found at index endoscopy in 294 patients (39.4%) whereas low grade dysplasia in 147 (17.4%). 112 patients (13.3%) fulfilled the exclusion criteria and the remaining 731 were followed for a median of 9.8 years (IQR: 9.3-10.0). After 6779 patient-years, 6 adenocarcinomas were diagnosed yielding an incidence rate of 0.89 per 1000 patients-years (95% confidence interval [CI 0.40-1.97]) which corresponds to annual malignancy progression rate of less than 0.1%. The malignancy rate in patients with low grade dysplasia was 3.70 per 1000 patient-years (95% CI 1.39-9.85). In Polish BO patients the risk of malignant progression was lower than previously reported. It was notably higher in patients with low grade dysplasia than in those with no dysplasia at index endoscopy, which may warrant strict surveillance in these patients.

Quality indicators for the management of Barrett's esophagus, dysplasia, and esophageal adenocarcinoma: international consensus recommendations from the American Gastroenterological Association Symposium.

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett's esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett's esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett's esophagus.

Predicting pre- and post-resectional histologic discrepancies in gastric low-grade dysplasia: A comparison of white-light and magnifying endoscopy.

BACKGROUND AND AIM: The aim of this study was to evaluate the validity of the parameters of conventional white-light endoscopy and magnifying endoscopy with narrow-band imaging (MENBI) for the prediction of discrepancies between pre- and post-resectional histology in cases of gastric adenoma with low-grade dysplasia (LGD) that were diagnosed based on endoscopically biopsied specimens. METHODS: The medical records of 266 lesions with gastric LGD that were diagnosed by endoscopic forceps biopsies were retrospectively reviewed. The Vienna classification was used for histologic diagnosis. These patients all underwent MENBI examinations followed by analyses of the incidence of histologic discrepancies and histologic heterogeneity. The relationship between white-light endoscopic/MENBI parameters and the presence of histologic discrepancies was also analyzed. RESULTS: Discrepancies between the pre- and post-resectional histologies were found in 74 cases (27.9%). Among those cases, the histology was upgraded in 71 cases, whereas the histology was downgraded in three cases. The presence of erythema and positive MENBI findings were independent factors for the prediction of upgraded histologic discrepancies (P-values = 0.008, < 0.001, respectively). A positive MENBI finding yielded the highest predictive value, with a multivariate adjusted odds ratio of 42.46. Histologic heterogeneity in post-resectional specimens was found in 40.8% of cases with upgraded histologic discrepancies. CONCLUSIONS: MENBI can provide more accurate information than white-light endoscopy for the prediction of pre- and post-resectional histologic discrepancies in biopsy-proven gastric LGD. Endoscopic resection is strongly recommended in cases with surface erythema on conventional white-light endoscopy or positive MENBI, irrespective of the lesion size.

Prior colorectal neoplasia is associated with increased risk of ileoanal pouch neoplasia in patients with inflammatory bowel disease.

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.

A Barrett's esophagus registry of over 1000 patients from a specialist center highlights greater risk of progression than population-based registries and high risk of low grade dysplasia.

Barrett's esophagus (BE) arising from chronic gastro-oesophageal reflux (GERD) is the main pathologic precursor of esophageal adenocarcinoma (EAC). The risk of progression to high-grade dysplasia (HGD) and EAC is unclear, and recent population studies from Denmark and Northern Ireland suggest that this has been overestimated in the past. No data exist from the Republic of Ireland. A detailed clinical, endoscopic, and pathologic database was established in one center as a proposed pilot for a national registry, and initial and follow-up data were abstracted by a data manager. One thousand ninety-three patients were registered, 60 patients with HGD were excluded, leaving 1033, with a median age of 59 and 2 : 1 male to female ratio, and 3599 person-years of follow-up. The overall incidence of HGD/EAC was 1.33% per year overall, 0.85% if the first year is excluded. Within the first year after index endoscopy, 18 cases of HGD or EAC were identified, and 30 following the first year. Low-grade dysplasia (LGD) on index endoscopy was associated with an incidence of progression of 6.5% per year, and 3.1% when tertiary referrals were excluded. These data provide important demographic and clinical information on the population of Irish patients with BE, with incidence rates of progression higher than recently published population-based registry series, perhaps relating to sampling and pathological assessment. Low-grade dysplasia on initial biopsy is a significant proxy marker of risk of progression.

A review of the current understanding and clinical utility of miRNAs in esophageal cancer.

BACKGROUND: MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that regulate the translation of RNAs. They have a role in biological and pathological process including cell differentiation, apoptosis, proliferation and metabolism. Since their discovery, they have been shown to have a potential role in cancer pathogenesis through their function as oncogenes or tumor suppressors. A substantial number of miRNAs show differential expression in esophageal cancer tissues, and so have been investigated for possible use in diagnosis. Furthermore, there is increasing interest in their use as prognostic markers and determining treatment response, as well as identifying their downstream targets and understanding their mode of action. METHODS: We analyzed the most recent studies on miRNAs in esophageal cancer and/or Barrett's esophagus (BE). The publications were identified by searching in PuBMed for the following terms: Barrett's esophagus and microRNA; esophageal cancer and microRNA. RESULTS: Four miRNAs (mi-R-25, -99a, -133a and -133b) showed good potential as diagnostic markers and interestingly five (mi-R-21, -27b, -126, - 143 and -145) appeared to be useful both as diagnostic and prognostic/predictive markers. CONCLUSION: The data so far on miRNAs in esophageal carcinogenesis is promising but further work is required to determine whether miRNAs can be used as biomarkers, not only in the clinical setting or added to individualized treatment regimes but also in non-invasive test by making use of miRNAs identified in blood.