Low-grade Dysplasia Patients Research Articles

Evaluation of femoral condyle volumes in patients with trochlear dysplasia: a pilot study

To examine the volumes of the medial and lateral femoral condyles and the trochlear groove, and to determine their relationship with trochlear dysplasia. Computed tomography images of the knees of 21 patients with trochlear dysplasia and 18 healthy individuals were analysed retrospectively. According to the modified Dejour classification, the degree of trochlear dysplasia was recorded, such as type A trochlea being low-grade dysplasia and types B, C, and D trochlea being high-grade dysplasia. Volume of the trochlear groove and medial and lateral femoral condyles were calculated using the three-dimensional (3D) volume-rendering method. The volumes of lateral condyle, medial condyle, and trochlear groove were statistically significantly lower in patients with trochlear dysplasia when compared to healthy participants. When compared according to Dejour types, all parameters were statistically significantly lower in both high- and low-grade dysplasia patients (p<0.05). The correlation between femoral condyle volumes and trochlear groove volume was low in the control group, but there was a moderate positive correlation in the patient group (r=0.50-0.75, p<0.05). In trochlear dysplasia, the volume of the trochlear groove decreases and hypoplasia may occur in both lateral femoral and medial femoral condyles. Therefore, hypoplasia of only one condyle should not be interpreted as trochlear dysplasia. A holistic approach to patients is required.

335. LONG TERM RISK FOR PROGRESSION TO NEOPLASIA FOR BARRETT’S ESOPHAGUS PATIENTS WITH VALIDATED LOW-GRADE DYSPLASIA OR INDEFINITE FOR DYSPLASIA

Abstract Barrett’s esophagus (BE) with low-grade dysplasia (LGD) confirmed by two pathologists has a high risk of progression to high-grade dysplasia and cancer why ablation or more intense surveillance is recommended. Recent studies suggest that the progression risks for indefinite for dysplasia (IND) and LGD are similar, but the management guidelines are still different. We did a retrospective analysis to calculate the long-term risk for patients with verified LGD and IND. All patients in the Ersta hospital BE-database in Stockholm who at least on one occasion during 1998 to 2012 were diagnosed with dysplasia. The first dysplastic specimen was re-evaluated by two highly experienced GI-pathologist. Clinical data was retrieved from the database and from patient medical records. Incidence rate (IR) was calculated for developing high-grade dysplasia (HGD) or cancer and IR ratio (IRR) was used as relative risk evaluation between the non-dysplastic Barrett’s Esophagus (NDBE) group and the LGD/IND groups and presented with 95% Confidence Intervals (CI). Of 1180 patients with BE, 455 (39%) were diagnosed with dysplasia. 32 were excluded and 3 had HGD. Of the remaining 420 patients, 266 (63%) could be downgraded to NDBE, 82 (20%) were diagnosed as LGD and 71 (17%) as IND. Total follow-up was 4592 person years. The median follow-up time was 12 years. 34 patients developed neoplasia. The yearly IR for HGD or cancer among patients downgraded to NDBE was found to be 0,3% compared to 1,8% for LGD and 1,4% for IND. There was a five-fold increased risk of HGD or cancer among LGD/IND as compared to NDBE. Patients with confirmed IND and LGD were found to have almost similarly elevated long-term risk for progression to neoplasia. Therefore, it seems reasonable that IND patients undergo the same surveillance regimen as non-treated LGD patients. Four patients (one with NDBE, two IND and one LGD) developed cancer more than 20 years after their initial BE diagnosis and therefore, it should be considered to keep BE patients in surveillance programs for a long period of time.

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Systematic review with meta-analysis: incidence and factors for progression to advanced neoplasia in inflammatory bowel disease patients with indefinite and low-grade dysplasia.

Due to limited research on the natural history of indefinite for dysplasia (IND) and low-grade dysplasia (LGD) in inflammatory bowel disease (IBD), the management of these patients is controversial. This systematic review and meta-analysis aimed to estimate the incidence and identify the risk factors for advanced neoplasia in IBD patients with IND and LGD. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched until 24 December, 2021, to identify studies that reported pathological results of follow-up colonoscopy or surgery in IBD patients with IND and LGD. The main outcomes were the incidence and risk factors for advanced neoplasia in IBD patients with IND and LGD. Based on the analysis of 38 studies, the pooled incidences of advanced neoplasia in IBD patients with IND and LGD were 9.9% (95% CI 4.4%-15.4%) and 10.7% (95% CI 7.0%-14.4%) respectively. The risk factors for advanced neoplasia in IND patients were primary sclerosing cholangitis (PSC) and aneuploidy. The risk factors for advanced neoplasia in LGD patients included male, PSC, previous IND, colonic stricture, index lesion ≥1cm, distal location, multifocal lesions, distal and flat lesions, nonpolypoid/flat lesions and invisible lesions. The incidence of advanced neoplasia was similar between IND and LGD in IBD patients, as high as one in ten, so more rigorous surveillance is also suggested in IND patients. Since the effects of most factors were derived from the pooled results of only two to three studies, further research was needed to confirm our results.

429 High Clinical Impact of Wide Area Transepithelial Sampling (WATS) Positive - Forceps Biopsy Negative Diagnoses of Barrett Esophagus and Associated Dysplasia: A Retrospective Cohort Study of 423 Patients

INTRODUCTION: Wide Area Transepithelial Sampling with 3-Dimensional Computer-Assisted Analysis (WATS) when used adjunctively to forceps biopsies (FB) has been demonstrated in multiple prospective studies to significantly increase detection of Barrett’s esophagus (BE) and associated neoplasia in patients undergoing either BE screening or surveillance. The clinical impact of WATS positive-FB negative diagnoses has never been evaluated. The aim of this IRB-approved clinical utility study was to determine changes in patient management when BE and/or dysplasia was detected by WATS but not by FB. METHODS: Between 2013-2018, we identified 423 consecutive patients from WATS clinical registries who had a WATS positive diagnosis of BE or dysplasia and a negative FB result; 317 patients were diagnosed with BE, 90 with low grade dysplasia (LGD) and 16 with high grade dysplasia (HGD) by WATS only. Physicians subsequently completed an extensive survey to determine if the positive WATS diagnosis resulted in a change in patient management such as enrolment in a surveillance program, endoscopic ablation/antireflux surgery, initiating proton pump inhibitors (PPIs) or increasing the patient’s dose of PPI. RESULTS: The clinical impact of WATS positive-FB negative diagnoses for patients with BE, LGD or HGD is summarized in Table 1. WATS had a direct impact on the clinical management of 97.8% of the 317 BE patients including enrolment in a surveillance program (96.2%), ablation/antireflux surgery (3.7%), or starting or increasing the dose of PPIs (60.2%). WATS impacted the management of 94.4% and 93.7% of LGD and HGD patients respectively. For instance, 30% and 50% respectively had ablation, 73.3% and 68.8% had increased frequency of or new enrollment in surveillance, and 56.7% and 62.5% had PPIs prescribed or the dose increased. Seven of 8 HGD patients not ablated were lost to follow up. One of 8 HGD patients not ablated developed invasive adenocarcinoma also identified with WATS upon follow-up endoscopy. CONCLUSION: The results of this study demonstrate that physicians have a high degree of confidence in WATS diagnoses even when the concurrent FB is negative. This is evidenced by the fact that physicians changed their patient management in 96.9% of all cases, often significantly with invasive treatments such as ablation, EMR, and even antireflux surgery in a small %age of patients. As an adjunct to FB, WATS has high clinical utility and adds value to the management of patients with BE and associated dysplasia.

Diagnosis, risk stratification, and management of ampullary dysplasia by DNA flow cytometric analysis of paraffin-embedded tissue

The limited accuracy of endoscopic biopsy in detecting high-grade dysplasia or adenocarcinoma within ampullary adenoma or dysplasia has been reported. The natural history of ampullary dysplasia is also unclear, and there are no established guidelines to determine which patients with ampullary dysplasia require resection versus surveillance endoscopy. DNA flow cytometry was performed on 47 ampullary biopsies with low-grade dysplasia, 18 high-grade dysplasia, and 23 negative for dysplasia, as well as 11 cases of ampullary adenocarcinoma. Abnormal DNA content (aneuploidy or elevated 4N fraction > 6%) was identified in 9 (82%) of adenocarcinoma, 13 (72%) of high-grade dysplasia, 7 (15%) of low-grade dysplasia, and none (0%) of non-dysplastic mucosa. One-, 2-, and 7-year detection rates of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with abnormal DNA content were 57%, 86%, and 88%, respectively, whereas low-grade dysplasia patients in the setting of normal DNA content had 1-, 2-, and 7-year detection rates of 10%, 10%, and 10%, respectively. The univariate and multivariate hazard ratios (HRs) for subsequent detection of high-grade dysplasia or adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 16.8 (p = <0.01) and 9.8 (p = <0.01), respectively. Among the 13 high-grade dysplasia patients with DNA content abnormality, 5 patients (38%) were subsequently found to have adenocarcinoma within a mean follow-up time of 3 months, whereas only 1 (20%) of the remaining 5 patients in the setting of normal DNA content developed adenocarcinoma in a month (HR = 2.6, p = 0.39). The overall 1- and 2-year detection rates of adenocarcinoma in all high-grade dysplasia patients (regardless of flow cytometric results) were 34% (95% confidence interval = 16–63%) and 47% (95% confidence interval = 23–79%), respectively. In conclusion, the majority of low-grade dysplasia patients (86%) in the setting of abnormal DNA content developed high-grade dysplasia or adenocarcinoma within 2 years and thus may benefit from resection, whereas those with normal DNA content may be followed with surveillance endoscopy. The presence of DNA content abnormality can also confirm a morphologic suspicion of high-grade dysplasia, which should be managed with resection, as nearly 50% of the high-grade dysplasia patients were found to have adenocarcinoma within 2 years.

PGI10 COST-EFFECTIVENESS ANALYSIS OF RADIO-FREQUENCY ABLATION IN PATIENTS WITH BARRETT’S ESOPHAGUS AND HIGH GRADE DYSPLASIA IN ITALY

Prognosis of Barret’s esophagus (BE) is generally good, although malignant progression may occur in a small number of patients from non-dysplastic BE (NDBE), to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and eventually esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is an established endoscopic technique recommended for eradication of BE. The aim of this analysis was to evaluate the cost-effectiveness of treating HGD patients with RFA in Italy. The analysis considered the Italian NHS perspective and the whole patients’ lifetime. Model structure was a Discrete-time Markov Model representing patients’ transition from NDBE, LGD, HGD and EAC. In the model, HGD patients are treated with either RFA (with endoscopic mucosal resection in selected patients) or esophagectomy, whereas LGD patients only receive endoscopic surveillance. Successfully operated patients move to a “cured” health-state and can progress again in the future. All patients with resecable EAC receive esophagectomy and are assumed free of relapse thereafter. Clinical and epidemiological inputs were derived from the published literature and expert opinions; Quality adjusted life years were used as primary health outcome. Cost data were derived using either micro-costing or national tariffs. Lastly, model structure, parameters and assumptions were validated by 5 prominent clinicians in Italy. Treating HGD patients with RFA in Italy was more effective and less expensive, compared to the standard of care. Probabilistic sensitivity analysis showed >95% of probability of RFA being the optimal strategy at a €20,000 threshold. This analysis showed that RFA is a dominant strategy for HGD patients in Italy. Italy has recently launched a National Plan for HTA of Medical Devices, setting criteria and procedures for determining coverage and reimbursement decisions for medical devices. Cost-effectiveness will play an increasing role as decision rule in the future requiring more studies to prove value for money of emerging technologies.

Does Multifocal Dysplasia in Barrett’s Esophagus Increase the Risk of Progression to Esophageal Adenocarcinoma?: Presidential Poster Award

Introduction: Barrett’s Esophagus (BE), is thought to be secondary to gastroesophageal reflux disease and progresses to esophageal adenocarcinoma (EAC) in a stepwise manner. Current guidelines utilize dysplasia to guide management, but there is conflicting evidence on the extent of dysplasia for risk stratification. Here, we evaluated the effect of multifocal dysplasia on the risk for EAC and hypothesized that multifocality in low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are risk factors for progression to EAC. Methods: This was a retrospective study of BE patients with, or with suspected, dysplasia presenting to an academic medical center for evaluation from 2006 to 2016. Information collected include: patient demographics; BE length; histology, including grade and presence of multifocal dysplasia; disease progression; PPI use; need for esophagectomy; and length of follow-up. All pathology specimens were read by expert GI pathologists as: no dysplasia (ND), indefinite for dysplasia (IND), LGD, or HGD. LGD or HGD was further categorized as unifocal or multifocal. Results: Of 305 BE patients with, or with suspected, dysplasia, 51 were excluded (33 ND, 18 IND). 254 BE patients were included in the final analysis: 112 LGD (unifocal=90, multifocal=22) and 142 HGD (unifocal=108, multifocal=34). In total, twenty-five patients with dysplastic BE (13 unifocal, 12 multifocal) developed EAC; all were diagnosed with intramucosal adenocarcinoma with either T1a or T1b lesions. Multifocality significantly increased the risk for progression to EAC (Table 2: RR 3.26, p=0.004), with the effect most pronounced in the subgroup with multifocal LGD as compared to those with unifocal LGD (RR 8.18, p=0.013). In patients with HGD, multifocality did not increase the risk for subsequent EAC (RR 2.31, p=0.079). Lastly, multifocal dysplasia associated with long segment BE (LSBE) significantly increased the risk for EAC (Table 3: RR 3.09, p=0.011), and HGD patients with LSBE were more at-risk for progression to EAC than that of LGD patients (RR 4.33, p=0.007). Conclusion: Multifocal dysplasia significantly increases the risk of progressing from BE to EAC and is especially important in BE patients with LGD. Identification of the extent of dysplasia is also essential in patients with LSBE, particularly those diagnosed with HGD. If confirmed, incorporating dysplasia multifocality into the BE management algorithm should be considered.335_A Figure 1 No Caption available.335_B Figure 2 No Caption available.335_C Figure 3. Short Segment (SS) BE is defined as <3 cm in length, while Long Segment (LS) BE is defined as > or = to 3 cm in length

Use of DNA flow cytometry in the diagnosis, risk stratification, and management of gastric epithelial dysplasia

The natural history of gastric epithelial dysplasia and the consequential surveillance strategies are not well defined in the West. To date, the diagnosis relies on morphology, and no reliable adjunct methods, either immunohistochemical or molecular, have reproducibly been able to confirm the diagnosis and/or risk stratify gastric epithelial dysplasia. Yet, such a tool would be useful in confirming the diagnosis, and developing objective and rational surveillance guidelines. DNA flow cytometry was performed using formalin-fixed paraffin-embedded gastric tissue from 23 cases of high-grade dysplasia and 38 cases of low-grade dysplasia. Twenty-four benign background mucosal samples from the same cohort (20 biopsies and 4 surgical resections from 16 low- and 8 high-grade dysplasia cases) were utilized as controls. The presence of DNA content abnormality (aneuploidy or elevated 4N fraction) correlated with increasing levels of dysplasia, as DNA content abnormality was detected in 18 (78%) of 23 high-grade dysplasia, 5 (13%) of 38 low-grade dysplasia, and none of 24 non-dysplastic samples. 1 and 4-year detection rates of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 80% (p = 0.003) and 100% (p = 0.005), respectively, whereas patients with low-grade dysplasia but with normal DNA content had 1, 4, and 12-year detection rates of 23, 32, and 54%, respectively. The univariate hazard ratio (HR) for subsequent detection of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality was 6.9 (p = 0.001). Older patients (HR = 1.1, p = 0.005) and those with familial adenomatous polyposis (HR = 9.7, p = 0.029) also had an increased risk for developing high-grade dysplasia or gastric adenocarcinoma in the univariate analysis, but only DNA content abnormality demonstrated a significantly elevated HR of 5.9 in the multivariate analysis (p = 0.005). While older age showed a minimally elevated risk (HR = 1.1, p = 0.013), no other potential risk factors, including male gender, ethnicity, polypoid endoscopic appearance, Helicobacter pylori infection, and intestinal metaplasia, were significantly associated with subsequent detection of high-grade dysplasia or gastric adenocarcinoma in the multivariate analysis. Among the 18 high-grade dysplasia cases with DNA content abnormality, 13 cases (72%) developed gastric adenocarcinoma within a mean follow-up time of 9 months, conferring a HR of 2.5; however, this did not reach statistical significance. In conclusion, the presence of DNA content abnormality can identify a subset of low-grade dysplasia patients who are at increased risk for subsequent detection of high-grade dysplasia or gastric adenocarcinoma. It can also provide confirmatory evidence to a morphologic impression or suspicion of high-grade dysplasia. The majority of gastric epithelial dysplasia patients with DNA content abnormality developed high-grade dysplasia or gastric adenocarcinoma within a year and thus may benefit from more thorough and rigorous endoscopic surveillance.

Economic evaluation of endoscopic radiofrequency ablation for the treatment of dysplastic Barrett's esophagus in Spain.

To assess the cost-effectiveness of introducing endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection in selected patients into the standard of care of Barrett's esophagus patients with high-grade dysplasia or low-grade dysplasia in Spain. The disease evolution was modeled via a semi-Markov model. The treatment strategies compared included endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection and the Standard of Care (esophagectomy or palliative chemoradiotherapy according to disease status for high-grade dysplasia and endoscopic surveillance for low-grade dysplasia). Efficacy rates, transition probabilities and utility values were obtained from the literature. Clinical management patterns and resource use were modeled according to Spanish clinical expert opinion. Costs were expressed in euros (€) from 2016 reflecting the Spanish National Health System perspective. Sensitivity analyses were performed to assess the robustness of the model. With respect to the Spanish Standard of Care, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection was a dominant strategy for high-grade dysplasia patients. When a willingness-to-pay threshold of €30,000 per quality-adjusted life-years gained was considered, this was cost-effective for low-grade dysplasia patients (€12,865 per quality-adjusted life-years gained). The sensitivity analyses supported the base case analysis results and pointed towards the main drivers of uncertainty in the model. From a health care decision-maker, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection is the intervention of choice for dysplasic Barrett's esophagus patients in Spain.

Development of Metachronous Tumors after Endoscopic Resection for Gastric Neoplasm according to the Baseline Tumor Grade at a Health Checkup Center.

Endoscopic resection (ER) procedure has been performed widely to treat gastric neoplasms. Here, we compared the long-term prognosis based on the clinical features of three types of recurred gastric neoplasms after ER, including low-grade dysplasia (LGD), high-grade dysplasia (HGD), and early gastric carcinoma (EGC). Between 2003 and 2014, subjects who were diagnosed with gastric neoplasm during screening endoscopy were included. The baseline clinicopathologic and tumor recurrence were analyzed. Of the 316 patients enrolled, 170 patients (53.8%) were categorized into the LGD group, 34 patients (10.8%) into the HGD group, and 112 patients (35.4%) into the EGC group. The median follow-up duration was 4.2 years. Among the total, 14 patients experienced a development of metachronous gastric cancer; 4 patients (2.3%) in the LGD group, 3 patients (8.3%) in the HGD group, and 7 patients (6.1%) in the EGC group. Metachronous gastric neoplasm had developed in 17 LGD patients (10.0%), 5 HGD patients (14.7%), and 14 EGC patients (12.5%). There was no significant difference in the incidence of metachronous gastric cancer and neoplasm among the three groups (p=0.15 and p=0.72, respectively). We identified that the incidence rates of gastric neoplasm and cancer after endoscopic treatment were not significantly different between the LGD, HGD, and EGC groups.

57 Significant Reduction in the Disease Progression in Barrett's Esophagus Low-Grade Dysplasia Patients Treated With Endoscopic Eradiation Therapy Compared With Surveillance Endoscopy: A Systematic Review and Meta-Analysis

57 Significant Reduction in the Disease Progression in Barrett's Esophagus Low-Grade Dysplasia Patients Treated With Endoscopic Eradiation Therapy Compared With Surveillance Endoscopy: A Systematic Review and Meta-Analysis

Current Controversies in Radiofrequency Ablation Therapy for Barrett's Esophagus.

Opinion StatementBarrett’s esophagus (BE) is the most important risk factor for esophageal adenocarcinoma. Through the sequence of no dysplasia to low-grade dysplasia (LGD) and high-grade dysplasia (HGD), eventually early cancer (EC) may develop. The risk of neoplastic progression is relatively low, 0.5–0.9 % per patient per year. However, once diagnosed, esophageal adenocarcinoma is often irresectable, and 5-year survival is only 15 %. Therefore, non-dysplastic BE patients are kept under endoscopic surveillance to detect early neoplasia in a curable stage. In case of LGD confirmed by an expert pathologist, risk of neoplastic progression is high. In these confirmed LGD patients, prophylactic ablation using radiofrequency ablation (RFA) of the Barrett’s segment has proven to significantly reduce risk of neoplastic progression. Once patients are diagnosed with HGD or EC, they have a clear indication for endoscopic treatment. The cornerstone for endoscopic management of early Barrett’s neoplasia is endoscopic resection of mucosal abnormalities. Endoscopic resection (ER) provides a large tissue specimen for accurate histological evaluation to select those patients for further endoscopic management, who have neoplasia limited to the mucosa, well to moderately differentiated and without lymph-vascular invasion. After ER, the remainder of the Barrett’s mucosa can be eradicated with RFA, to prevent occurrence of metachronous lesions.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists.

AIMTo evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists.METHODSStudies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTSInitial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett’s esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27).CONCLUSIONWhen LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett’s esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgen-stained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.

Clinical outcomes in patients with a diagnosis of "indefinite for dysplasia" in Barrett's esophagus: a multicenter cohort study.

Data are limited on the natural history of patients with Barrett's esophagus with a diagnosis of "indefinite for dysplasia" (IND). The aims of this study were to: (i) determine rates of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma, and compare these with rates for low grade dysplasia (LGD); and (ii) determine the proportion of patients whose histological IND diagnosis changed on follow-up endoscopy. Demographic, endoscopic, and histologic information of patients with diagnoses of IND and LGD and at least 12 months of follow-up were extracted from the database of a multicenter Barrett's esophagus study. Rates and times for progression to HGD and esophageal adenocarcinoma and regression to nondysplastic epithelium were calculated. Proportions of diagnoses upgraded to HGD/esophageal adenocarcinoma or downgraded to nondysplastic epithelium at first follow-up endoscopy were evaluated. Amongst 2264 patients, 83 with a diagnosis of IND (mean age 60 years, 95 % men, 95 % white; mean follow-up 5.6 years) and 79 with diagnosis of LGD were identified. In the IND group, annual incidences of esophageal adenocarcinoma and HGD were 0.21 % and 0.64 %, respectively, representing a combined incidence of 0.8 %. Mean time to progression was 4.72 years. Within the IND group 55 % patients showed regression to nondysplastic epithelium at first follow-up endoscopy and the overall regression rate was 80 %. Corresponding rates in LGD patients were similar. Lesions diagnosed as IND and LGD show similar biological behavior and can be treated as a single category with respect to surveillance and follow-up.

Coronary Artery Disease and Barrett’s Esophagus: Is There Any Association?

Introduction: Coronary artery disease (CAD) and Barrett’s esophagus (BE) share similar risk factor profile and CAD is highly prevalent in BE patients. In fact, CAD is the most common cause of mortality in BE patients. It is not known if CAD is associated with increased incidence of esophageal adenocarcinoma (EAC). Our aim was to identify patients with BE and CAD and see if there is any increased prevalence of dysplasia and EAC. Methods: All patients in our Barrett’s registry database from 2002 to 2013 with biopsy confirmed intestinal metaplasia were included. Variables such as age, gender, race, BMI, BE length, hiatal hernia size and biopsy findings were recorded. E-research services were utilized to identify patients with CAD, use of aspirin, NSAIDs and PPIs. Results: A total of 2341 subjects were included in the analysis. Average age was 60 ± 13 years and 75% were male and 95.8% were Caucasian. Average BMI was 29.7±6. Mean BE length was 3.23.5± cm and hiatal hernia size was 22.2± cm. CAD was identified in 110 (4.7%) patients. ASA use was documented in 413 (17.6%), and PPIs in 825 patients (35.2%). There were no significant differences in prevalence of dysplasia (Table 1). A total of 1034 subjects without high-grade dysplasia (HGD) or EAC at baseline, i.e. 836 with no dysplasia and 198 with low-grade dysplasia (LGD) were included in the follow-up. No dysplasia: During median follow-up of 47 [24, 90] months, 22% had progression (134 to LGD, 26 to HGD and 21 to EAC). After adjusting for age, gender, BE length and hernia size, CAD was associated with lower hazard of progression to HGD/EAC (HR=0.22; p= 0.038). Similarly, use of aspirin was associated with 55% lower risk of progression to HGD/EAC (HR=0.45, P=0.024) and use of PPIs with 23% lower risk (HR=0.77, p=0.4). LGD group: During median follow-up time of 30 [9, 56] months, 24% had progression (16 to HGD and 33 to EAC). CAD, use of asprin and PPIs was not associated with progression to HGD/EAC (HR=0.87, 0.64, 0.76 with p values of 0.79, 0.18 and 0.35, respectively).Table 1: Prevalence of Dysplasia in BE SubgroupsConclusion: CAD is not associated with any increased prevalence of dysplasia or cancer in BE patients. In fact, there is lower risk of progression in patients with no dysplasia at baseline. This may be perhaps due to concurrent aspirin and PPI use. However, the protective effect of CAD or ASA and PPIs was not observed in LGD patients with BE.

Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel

ObjectiveReported malignant progression rates for low-grade dysplasia (LGD) in Barrett's oesophagus (BO) vary widely. Expert histological review of LGD is advised, but limited data are available on its clinical value....

Management of low-grade dysplasia in Barrettʼs esophagus

This article discusses the various controversies that surround the management of low-grade dysplasia (LGD) in Barrett's esophagus. Data on the clinical course of LGD patients with regards to rates of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) are highly variable. Recent data suggest that the rate of progression to EAC may be similar to that of patients with nondysplastic Barrett's esophagus (0.4-0.5% per year). There is significant interobserver variability in the diagnosis of LGD even among expert gastrointestinal pathologists. Data on various endoscopic eradication therapies (EET) specifically in this patient population are limited. Eradication of LGD and intestinal metaplasia can be achieved by radiofrequency ablation as demonstrated in a randomized controlled trial. Although treatment appears to be durable for up to 3 years, progression to HGD and EAC can occur, highlighting the need for close endoscopic surveillance even after EET. There is a need to risk stratify Barrett's esophagus patients with LGD to identify patients most likely to progress using a reliable and objective system that incorporates clinical features, advanced imaging techniques and biomarkers. If such a high risk group could be identified, they may benefit from EET, whereas, the majority may be managed conservatively.

Circumferential and Focal Ablation of Barrett's Esophagus Containing Dysplasia

Dysplasia in a Barrett's esophagus (BE) is associated with an increased risk for developing esophageal adenocarcinoma. Ablation using the HALO system has shown promise for the treatment of BE with dysplasia. The objective of this study was to assess the safety and efficacy of a stepwise regimen of circumferential and focal ablation using the HALO system for the treatment of BE with dysplasia. BE patients with low-grade dysplasia (LGD) or high-grade dysplasia (HGD) were enrolled. Primary circumferential ablation was followed every 3 months by further circumferential ablation or focal ablation until complete endoscopic eradication of BE was achieved. At 3- or 6-month intervals, depending on baseline grade, targeted and four quadrant random biopsies were obtained to assess the histological response to ablation. A complete response (CR) is defined as all biopsies negative for intestinal metaplasia (IM) (CR-IM) or dysplasia (CR-D) at last available follow-up. A total of 63 patients were treated (57 men; median age 71 years; median BE length 5 cm), with worst grade of dysplasia being LGD (n=39) and HGD (n=24). Follow-up is available for 62 patients (median 24 months). Overall, CR-IM is 79% and CR-D is 89%. For the LGD cohort, CR-IM is 87% and CR-D is 95%. For the HGD cohort, CR-IM is 67% and CR-D is 79%. Stepwise circumferential and focal ablation of BE containing dysplasia appears to be a safe and effective intervention, achieving a CR for dysplasia in 95% and 79% of LGD and HGD patients, respectively.