Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma

Cook, Michael B.; Thrift, Aaron P.

doi:10.1016/j.giec.2020.08.001

Cited by 31 publications

(30 citation statements)

References 176 publications

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“…Despite improved risk factor identification and a BE surveillance program, temporal epidemiological data show that there has been no change in the proportion of people diagnosed into each stage of EAC since the 1970s [9]. Patients with EAC face a poor prognosis, with 5-year survival of less than 20% [10,11]. Detection at an early stage significantly improves survival, exemplified by the 48% 5-year survival rate for localized EAC [11].…”

Section: Introductionmentioning

confidence: 99%

“…Patients with EAC face a poor prognosis, with 5-year survival of less than 20% [10,11]. Detection at an early stage significantly improves survival, exemplified by the 48% 5-year survival rate for localized EAC [11]. Hence, there is an urgent need to improve early EAC risk stratification and diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…For BE patients who have undergone endoscopy with biopsy, TissueCypher and BarreGEN predicts EAC risk using a 15-marker immunohistochemistry panel and gene mutational load, respectively [2]. While these tests will assist BE diagnosis and risk stratification, >90% of EAC patients do not have prior diagnosis of BE [11]. Therefore, there is an unmet need for biomarkers that detect EAC and high grade dysplastic (HGD) BE in a high-risk population.…”

Section: Introductionmentioning

confidence: 99%

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EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma

Webster¹,

Wuethrich²,

Shanmugasundaram³

et al. 2021

Preprint

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Esophageal adenocarcinoma (EAC) detection relies on endoscopy-biopsy diagnosis, with routine endoscopic surveillance recommended for Barrett’s esophagus (BE) patients. Here, we examine the utility of blood biomarkers in patient risk stratification by translating the EAC blood biomarker Jacalin lectin binding complement C9 (JAC-C9) into a novel microfluidic immunoassay, the EndoScreen Chip. Cohort evaluation (n=46) showed elevated serum total C9 and JAC-C9 in EAC. Logistic regression modeling demonstrated that addition of C9 and JAC-C9 to patient risk factors (age, body mass index and heartburn/reflux history) improved EAC prediction from AUROC of 0.838 to 0.931. Serum JAC-C9 strongly predicted EAC (vs BE OR= 4.6, 95% CI: 1.6-15.6, p = 0.014; vs Healthy OR=4.1, 95% CI:1.2-13.7, p = 0.024) while total C9 was moderately predictive for BE (vs EAC OR=1.4; 95% CI: 1.0-1.8, p = 0.032; vs Healthy OR=0.8; 95% CI: 0.6-1.0, p = 0.039). This translational study demonstrates the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma

Webster¹,

Wuethrich²,

Shanmugasundaram³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Despite improved risk factor identification and a BE surveillance program, temporal epidemiological data show that there has been no change in the proportion of people diagnosed into each stage of EAC since the 1970s [4]. Patients with EAC face a poor prognosis, with 5-year survival of less than 20% [9,10]. Detection at an early stage significantly improves survival, exemplified by the 48% 5-year survival rate for localized EAC [10].…”

Section: Introductionmentioning

confidence: 99%

“…Patients with EAC face a poor prognosis, with 5-year survival of less than 20% [9,10]. Detection at an early stage significantly improves survival, exemplified by the 48% 5-year survival rate for localized EAC [10]. Hence, there is an urgent need to improve early EAC risk stratification and diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Development of EndoScreen Chip, a Microfluidic Pre-Endoscopy Triage Test for Esophageal Adenocarcinoma

Webster

Wuethrich

Shanmugasundaram

et al. 2021

Cancers

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The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6–15.6, p = 0.014; vs. Healthy OR = 4.1, 95% CI: 1.2–13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers.

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Epidemiology of Digestive Diseases

Timmer

2023

Handbook of Epidemiology

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Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma

Cited by 31 publications

References 176 publications

EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma

EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma

Development of EndoScreen Chip, a Microfluidic Pre-Endoscopy Triage Test for Esophageal Adenocarcinoma

Epidemiology of Digestive Diseases

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