Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett's Esophagus: Lessons Learned.

BACKGROUND: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening. AIMS: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population. METHODS: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0-5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard. RESULTS: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD. CONCLUSIONS: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.

Increased risk of Barrett's oesophagus and related neoplasia in individuals with a positive family history.

BACKGROUND: Considering the poor prognosis of oesophageal adenocarcinoma (EAC), it is important to identify individuals at increased risk of developing EAC who may benefit from early detection and prevention strategies. We aimed to determine whether individuals with a positive family history of Barrett's oesophagus (BE) and EAC are at an increased risk of oesophageal neoplasia. METHODS: In a multi-centre case-control study, BE patients with or without related oesophageal neoplasia and randomly selected population controls filled out a questionnaire to collect information on family history and other risk factors for BE and EAC. Positive family history was defined as having ≥1 first-degree relative with BE or EAC whose diagnosis was histologically confirmed in the Dutch nationwide histopathology database. FINDINGS: We included 480 BE patients and 420 controls without BE who had a total of 6393 first-degree relatives. A pathologically confirmed positive family history was significantly higher in BE patients compared with controls (6.5% versus 0.9; p < 0.001). Positive family history was independently associated with an increased risk of BE (OR 5.04; 95% CI 1.45-17.58; p = 0.01) after adjusting for known risk factors, such as gastroesophageal reflux disease and body mass index, and family size. INTERPRETATION: We found that familial clustering of BE and EAC is present in 6.5% of Dutch BE patients. Subjects with ≥1 first-degree relative with BE or EAC have a 5-fold increased risk of BE and EAC. These findings emphasize the importance of a detailed family history in patients with BE or EAC to identify individuals at increased risk who may benefit from early detection strategies to prevent EAC-related mortality.

Rethinking gastroesophageal reflux disorder.

Gastroesophageal reflux disease (GERD) is a common clinical condition for which our understanding has evolved over the past decades. It is now considered a cluster of phenotypes with numerous anatomical and physiological abnormalities contributing to its pathophysiology. As such, it is important to first understand the underlying mechanism of the disease process for each patient before embarking on therapeutic interventions. The aim of our paper is to highlight the mechanisms contributing to GERD and review investigations and interpretation of these results. Finally, the paper reviews the available treatment modalities for this condition, ranging from medical intervention, endoscopic options through to surgery and its various techniques.

Esôfago de Barrett: o estado da arte / Barrett's Esophagus: the state of the art

Objetivo: Demonstrar fatores envolvidos nos distúrbios do sono em profissionais que fazem plantões. Métodos: Trata-se de estudo transversal, cuja amostra foi composta de 244 voluntários, plantonistas da área da saúde, sendo 191 do sexo feminino, que responderam a um questionário socioeconômico, associado à aplicação da Escala de Sonolência de Epworth e ao Índice de Qualidade do Sono de Pittsburgh. Os dados foram analisados pelos coeficientes de Spearman e de Kendall Tau, com distribuição de probabilidade gama. Resultados: Houve significância (p<0,05) com o Índice de Qualidade do Sono de Pittsburgh e a atividade física (+0,216), ergonomia (+0,148), filhos (-0,146), valor da remuneração (+0,112) e disfunção durante o dia (+0,352). Também houve significância com a Escala de Sonolência de Epworth e atividade física (+0,138), renda familiar (-0,118), trabalho semanal (-0,151), latência do sono (-0,106), duração do sono (-0,107), eficiência do sono (-0,139) e disfunção durante o dia (+0,170). Por fim, a eficiência do sono teve significiância com profissão (-0,209), tabagismo (+0,402), Escala de Sonolência de Epworth (-0,139) e dissonias com a obesidade (índice de massa corporal >30; razão de chance de 1,40; intervalo de confiança de 95% de 1,02-1,94). Conclusão: As medidas autorrelatadas são prontamente obtidas com questionários validados, como a Escala de Sonolência de Epworth e o Índice de Qualidade do Sono de Pittsburgh, encontrando-se correlações com renda familiar, ter ou não filhos, índice de massa corporal, atividade física, ergonomia, condições de trabalho, tabagismo e componentes biopsicossociais. Em virtude do caráter transversal deste estudo é indispensável mais estudos com maior follow-up

Objective: To demonstrate factors involved in sleep disorders in professionals who take shifts. Methods: This is a cross-sectional study whose sample consists of 244 volunteers, on-duty health workers, 191 females, who answered a socioeconomic questionnaire, associated with application of the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Data were analyzed with Spearman's and Kendall Tau coefficients, and gamma probability distribution. Results: There was significance (p<0,05) with the Pittsburgh Sleep Quality Index and physical activity (+0,216), ergonomics (+0,148), children (-0,146), the wage (+0,112), dysfunction during the day (+0,352). Also there was significance with the Epworth Sleepiness Scale and physical activity (+0,138), family income (-0,118), weekly workload (-0,151), sleep latency (-0,106), sleep duration (-0,107), sleep efficiency (-0,139), and dysfunction during the day (+0,170). Finally, sleep efficiency was significant with occupation (-0,209), smoking habits (+0,402), Epworth Sleepiness Scale (-0,139), dyssomnia with obesity (body index mass >30; OR of 1,40; CI 95% 1,02-1,94). Conclusion: Self-reported measures are readily obtained with validated questionnaires such as Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index, with correlations with family income, having children or not, body mass index, physical activity, ergonomics, working conditions, smoking habits, and biopsychosocial components. Due to the cross-sectional nature of this study, further research with longer follow-up is indispensable

Perioperative screening, management, and surveillance of Barrett's esophagus in bariatric surgical patients.

Obesity is a strong risk factor for Barrett's esophagus (BE), the only proven precursor lesion to esophageal adenocarcinoma (EAC). Bariatric surgery is currently the only reliable treatment that achieves long-term sustained weight loss; however, it can markedly affect the development of de novo BE, and the progression or regression of existing BE. Bariatric procedures may also have implications on future surgical management of any consequent EAC. In this review, we examine the current evidence and published guidelines for BE in bariatric surgery. Current screening practices before bariatric surgery vary substantially, with conflicting recommendations from bariatric societies. If diagnosed, the presence of BE may alter the type of bariatric procedure. A selective screening approach prevents unnecessary endoscopy; however, there is poor symptom correlation with disease. Studies suggest that sleeve gastrectomy predisposes patients to gastroesophageal reflux and de novo BE. Conversely, Roux-en-Y gastric bypass is associated with decreased reflux and potential improvement or resolution of BE. There are currently no guidelines addressing the surveillance for BE following bariatric surgery. BE is an important consideration in the management of bariatric surgical patients. Evidence-based recommendations are required to guide procedure selection and postoperative surveillance.

Recent insights into the biology of Barrett's esophagus.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), an aggressive cancer with a poor prognosis. Our understanding of the pathogenesis and Barrett's metaplasia is incomplete, and this has limited the development of new therapeutic targets and agents, risk stratification ability, and management strategies. This review outlines current insights into the biology of BE and addresses controversies surrounding cell of origin, cellular reprogramming theories, updates on esophageal epithelial barrier function, and the significance of goblet cell metaplasia and its association with malignant change. Further research into the basic biology of BE is vital as it will underpin novel therapies and improve our ability to predict malignant progression and help identify the minority of patients who will develop EAC.

Obesity and esophageal cancer: GERD, Barrett´s esophagus, and molecular carcinogenic pathways.

INTRODUCTION: Increases in the rates of esophageal adenocarcinoma (EAC) have paralleled rises in the prevalence of overweight and obesity. Despite not being fully understood, obesity-related EAC seems to have different carcinogenic pathways. AREAS COVERED: This comprehensive review will thoroughly evaluate the current literature, describing the underlying mechanisms that help understanding the strong association between obesity and esophageal cancer. EXPERT COMMENTARY: The risk of esophageal cancer among obese individuals could be partially explained by several factors: high prevalence of GERD; linear association between central adiposity and Barrett´s esophagus development; low levels of adiponectin and high levels of leptin that alter cell proliferation processes; insulin-resistant state that creates a tumorigenesis environment; and changes in the esophageal microbiota due to unhealthy dietary habits that promote carcinogenesis. In addition, a large proportion of obese patients are undergoing sleeve gastrectomy which can worsen GERD or cause de novo reflux, esophagitis, and Barrett´s metaplasia.

Columnar epithelium morphology after esophagectomy: clinical insight into the development of Barrett's esophagus.

BACKGROUND: The presence of Barrett's mucosa in the esophageal remnant is a result of post-esophagectomy anastomotic site exposure to gastric acid and is regarded as a human model of Barrett's esophagus onset. Here, we attempted to clarify the relationship between duodenogastric reflux and formation of columnar epithelium by following the changes over time after esophagectomy. METHODS: A total of 96 patients underwent esophagectomy due to superficial cancer from April 2000 to March 2018 were included in this study. Cases were divided into two groups according to the reconstruction technique after esophagectomy as either the gastric pull-up (Ga) group and ileocolonic interposition (Ic) group. Previously obtained endoscopic pictures of the cases were reviewed retrospectively and chronologically. RESULTS: There were 24 cases of columnar epithelium in the Ga group (42%) and 1 in the Ic group (2.6%) (P < 0.01) with 32 reflux cases (56%) in the Ga group and 1 (2.6%) in the Ic group (P < 0.01). Reflux precedes the development of columnar epithelium in both the Ga- and Ic groups. Multivariate analysis revealed surgical technique (odds ratio 10.6, 95% CI 1.2-97.5, P = 0.037) and reflux (odds ratio 4.5, 95% CI 1.3-15.6, P = 0.0017) as risk factors. CONCLUSIONS: The development of columnar epithelium was preceded by reflux comprising principally gastric acid and was strongly associated with a strong inflammatory state.

Clinical course of gastroesophageal reflux disease and impact of treatment in symptomatic young patients.

In symptomatic young patients with gastroesophageal reflux symptoms, early identification of progressive gastroesophageal reflux disease (GERD) is critical to prevent long-term complications associated with hiatal hernia, increased esophageal acid and nonacid exposure, release of proinflammatory cytokines, and development of intestinal metaplasia, endoscopically visible Barrett's esophagus, and dysplasia leading to esophageal adenocarcinoma. Progression of GERD may occur in asymptomatic patients and in those under continuous acid-suppressive medication. The long-term side effects of proton-pump inhibitors, chemopreventive agents, and radiofrequency ablation are contentious. In patients with early-stage disease, when the lower esophageal sphincter function is still preserved and before endoscopically visible Barrett's esophagus develops, novel laparoscopic procedures, such as magnetic and electric sphincter augmentation, may have a greater role than conventional surgical therapy. A multidisciplinary approach to GERD by a dedicated team of gastroenterologists and surgeons might impact the patients' lifestyle, the therapeutic choices, and the course of the disease. Biological markers are needed to precisely assess the risk of disease progression and to tailor surveillance, ablation, and management.

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.

Role of Multimodality Imaging in Gastroesophageal Reflux Disease and Its Complications, with Clinical and Pathologic Correlation.

Gastroesophageal reflux disease (GERD) is a common condition and impairs the quality of life for millions of patients, accounts for considerable health care spending, and is a primary risk factor for esophageal adenocarcinoma. There have been substantial advances in understanding the pathogenesis of GERD and its complications and much progress in diagnosis and management of GERD; however, these have not been comprehensively discussed in the recent radiology literature. Understanding the role of imaging in GERD and its complications is important to aid in multidisciplinary treatment of GERD. GERD results from prolonged or recurrent reflux of gastric contents into the esophagus. Common symptoms include heartburn or regurgitation. Prolonged reflux of gastric contents into the esophagus can cause erosive esophagitis. Over time, the inflammatory response related to esophagitis can lead to deposition of fibrous tissue and development of strictures. Alternatively, the esophageal mucosa can undergo metaplasia (Barrett esophagus), a precursor to dysplasia (which can lead to adenocarcinoma). Conventional barium esophagography has long been considered the primary imaging modality for the esophagus, and the fluoroscopic findings for diagnosis of GERD have been well established. Multimodality imaging has a clear role in detection and assessment of the complications of GERD, specifically reflux esophagitis and Barrett esophagus; differentiation of benign and malignant strictures; and detection, staging, and posttreatment surveillance of esophageal adenocarcinoma. Given the dramatic changes in utilization of abdominal imaging during the past 2 decades, with significantly declining volume of fluoroscopic procedures and concomitant increase in CT and MRI studies, it is crucial that modern radiologists appreciate the value of barium esophagography in the workup of GERD and recognize the key imaging features of GERD and its complications at CT and MRI.

Cellular Origins of Barrett's Esophagus: the Search Continues.

PURPOSE OF REVIEW: The cellular origins of Barrett's esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms. RECENT FINDINGS: Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands. Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett's esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett's esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.

Preclinical models for the study of Barrett's carcinogenesis.

Barrett's esophagus (BE) is clinically significant, as it is the only known precursor lesion for esophageal adenocarcinoma. To develop improved therapies for the treatment of BE, a greater understanding of the disease process at the molecular genetic level is needed. However, achieving a greater understanding will require improved preclinical models so that the disease process can be more closely studied and novel therapies can be tested. Our concise review highlights progress in the development of preclinical models for the study of BE and identifies the most suitable model in which to test novel therapies.

Natural History of Barrett's Esophagus.

Barrett's esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years.

Low-grade dysplasia diagnosis ratio and progression metrics identify variable Barrett's esophagus risk stratification proficiency in independent pathology practices.

BACKGROUND AND AIMS: The diagnosis of low-grade dysplasia (LGD) in Barrett's esophagus (BE) is subject to substantial interobserver variation. Our central aim in this study is to compare independent pathology practices using objective measures of BE risk stratification proficiency, including frequency of diagnosis and rate of progression, with high-grade dysplasia (HGD) or adenocarcinoma (EAC) after the first diagnosis of LGD. METHODS: We retrospectively evaluated over 29,000 endoscopic biopsy cases to identify 4734 patients under endoscopic biopsy surveillance for BE in a healthcare system with multiple independent pathology practices: a subspecialized GI pathology group (SSGI; 162 BE cases per pathologist annually), 3 high BE volume general surgical pathology practices (GSPs; >50 BE cases per pathologist annually), and multiple low BE volume GSPs (10.6 BE cases per pathologist annually). We measured LGD diagnosis frequencies and rates of diagnostic progression to HGD or EAC in patients diagnosed with LGD. RESULTS: The proportion of all BE cases diagnosed as LGD (LGD/BE diagnosis ratio) ranged from 1.1% to 6.8% in the different hospital settings (P < .001). The cumulative proportion of patients with HGD or EAC within 2 years of the first diagnosis of LGD was 35.3% in the SSGI and ranged from 1.4% to 14.3% in the GSPs (P < .001). LGD diagnosed by the GSP with the lowest LGD/BE diagnosis ratio had an adjusted risk of progression similar to LGD diagnosed by subspecialists (hazard ratio, .42; 95% CI, .06-3.03). However, when LGD was diagnosed by other generalists, the adjusted risk of progression was 79% to 91% lower than subspecialists (P < .001). When LGD was diagnosed in a low-volume GSP practice, the risk of progression was not significantly increased relative to patients with nondysplastic BE (hazard ratio, 1.3; 95% CI, .4-3.9). CONCLUSIONS: General surgical pathologists and subspecialists show highly significant differences with respect to LGD/BE ratio, risk of progression relative to nondysplastic BE, crude annual progression rates, and the cumulative 2-year progression rate after LGD. These metrics can be used to assess proficiency in BE risk stratification in historical cases. Some general practitioners were able to achieve results similar to subspecialists. General surgical pathologists with little annual experience evaluating BE biopsy specimens did not successfully risk stratify patients with BE.

Gastrointestinal pathologists' perspective on managing risk in the distal esophagus: convergence on a pragmatic approach.

Here, we discuss recent updates and a continuing controversy in the diagnosis and management of Barrett's esophagus, specifically the recommendation that the irregular Z-line not be biopsied, the diminished status of ultrashort-segment Barrett's esophagus, the evidence basis for excluding and including the requirement of goblet cells for the diagnosis of Barrett's esophagus, and the conclusion that histologically confirmed low-grade dysplasia is best managed with endoscopic ablation rather than surveillance. We reference the American Gastroenterological Association and College of Gastroenterology and the British Society of Gastroenterology guidelines throughout, with the thesis that the field is converging on the concept of applying scarce medical resources to the diagnosis, surveillance, and therapy of patients most likely to derive benefit.

Predictive Biomarkers of Gastroesophageal Reflux Disease and Barrett's Esophagus in World Trade Center Exposed Firefighters: a 15 Year Longitudinal Study.

Gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE), which are prevalent in the World Trade Center (WTC) exposed and general populations, negatively impact quality of life and cost of healthcare. GERD, a risk factor of BE, is linked to obstructive airways disease (OAD). We aim to identify serum biomarkers of GERD/BE, and assess the respiratory and clinical phenotype of a longitudinal cohort of never-smoking, male, WTC-exposed rescue workers presenting with pulmonary symptoms. Biomarkers collected soon after WTC-exposure were evaluated in optimized predictive models of GERD/BE. In the WTC-exposed cohort, the prevalence of BE is at least 6 times higher than in the general population. GERD/BE cases had similar lung function, D LCO , bronchodilator response and long-acting ß-agonist use compared to controls. In confounder-adjusted regression models, TNF-α ≥ 6 pg/mL predicted both GERD and BE. GERD was also predicted by C-peptide ≥ 360 pg/mL, while BE was predicted by fractalkine ≥ 250 pg/mL and IP-10 ≥ 290 pg/mL. Finally, participants with GERD had significantly increased use of short-acting ß-agonist compared to controls. Overall, biomarkers sampled prior to GERD/BE presentation showed strong predictive abilities of disease development. This study frames future investigations to further our understanding of aerodigestive pathology due to particulate matter exposure.