Article
Gastroenterology & Hepatology
Tarek Sawas, Shawn A. Zamani, Sarah Killcoyne, Andrew Dullea, Kenneth K. Wang, Prasad G. Iyer, Rebecca C. Fitzgerald, David A. Katzka
Summary: Existing Barrett's esophagus screening guidelines have limitations in detecting prevalent esophageal adenocarcinoma. An optimized approach is needed to identify individuals most suitable for esophageal adenocarcinoma screening, particularly one that does not rely on chronic reflux symptoms.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Sarmed S. Sami, James P. Moriarty, Jordan K. Rosedahl, Bijan J. Borah, David A. Katzka, Kenneth K. Wang, John B. Kisiel, Krish Ragunath, Joel H. Rubenstein, Prasad G. Iyer
Summary: In GERD-independent scenarios, most non-sEGD BE screening tests were cost-effective, with swallowable esophageal cell collection devices with biomarkers being the optimal choice. However, exhaled volatile organic compounds had the highest ICERs in all scenarios.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jan Bilski, Monika Pinkas, Dagmara Wojcik-Grzybek, Marcin Magierowski, Edyta Korbut, Agnieszka Mazur-Bialy, Gracjana Krzysiek-Maczka, Slawomir Kwiecien, Katarzyna Magierowska, Tomasz Brzozowski
Summary: Both obesity and esophageal adenocarcinoma (EAC) rates have seen a significant increase in recent years in the United States and Western Europe. Obesity plays a key role in the development of EAC, with increased body mass index correlating with higher risk. Pathologically altered visceral fat in obesity is believed to contribute to this process. Visceral obesity may promote EAC through direct effects on gastroesophageal reflux disease and Barrett's esophagus (BE), as well as through the release of pro-inflammatory adipokines and insulin resistance. Disrupted adipokine production, such as the imbalance of leptin and adiponectin, is implicated in the pathogenesis of BE and EAC. This review discusses the epidemiology, pathophysiology, and molecular alterations associated with obesity in BE and EAC, with a focus on the potential role of adipokines and myokines. The review also highlights the possible crosstalk of adipokines and myokines during exercise and suggests lifestyle interventions, specifically regular physical activity, as a promising strategy for preventing the development of BE and EAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ksenia Maslenkina, Liudmila Mikhaleva, Maxim Naumenko, Rositsa Vandysheva, Michail Gushchin, Dmitri Atiakshin, Igor Buchwalow, Markus Tiemann
Summary: Barrett's esophagus (BE) is a premalignant lesion that can develop into esophageal adenocarcinoma (EAC). The development of BE is caused by biliary reflux and involves various stem cell origins. The concept of healing has been replaced by the cytokine storm and inflammatory microenvironment, leading to intestinal metaplasia. This review discusses the roles of molecular pathways in the pathogenesis of BE and EAC, including NOTCH, hedgehog, NF-?B, and IL6/STAT3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Franz Ludwig Dumoulin, Fabian Dario Rodriguez-Monaco, Alanna Ebigbo, Ingo Steinbruck
Summary: Esophageal adenocarcinoma is the most common subtype of esophageal cancer in Western societies and its incidence is increasing. The development and validation of artificial intelligence systems in the field of gastroenterology may help address unresolved issues in the prevention and surveillance of this cancer.
Review
Biochemistry & Molecular Biology
Pelin Ergun, Sezgi Kipcak, Serhat Bor
Summary: Barrett's esophagus (BE) is a condition resulting from chronic gastroesophageal reflux disease, which may progress to esophageal adenocarcinoma (EAC). The histological dysplasia grade is commonly used as a biomarker, but its effectiveness is limited due to cost and lack of progression in many BE patients. Clinicians require multiple or more quantitative biomarkers for early diagnosis of EAC, which has high mortality. Epigenetic factors in the early stages of neoplastic transformation show promise as predictive biomarkers. This review summarizes current research on DNA methylations, histone modifications, and noncoding RNAs (miRNAs) during the progression from BE dysplasia to EAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Anshuman Panda, Mi Ryung Shin, Christina Cheng, Manisha Bajpai
Summary: Research on an in vitro BE carcinogenesis model showed that there is a clear threshold in the progression of BE to malignancy, with catastrophic transcriptomic changes during a window period leading to a point of no return for BE cells.
FRONTIERS IN GENETICS
(2021)
Article
Gastroenterology & Hepatology
Ritu R. Singh, Madhav Desai, Michael Bourke, Gary Falk, Vani Konda, Uzma Siddiqui, Alessandro Repici, Cesare Hassan, Prateek Sharma
Summary: This study explores the safety and effectiveness of Barrett's endoscopic therapy (BET) in patients with neoplastic Barrett's esophagus. The results reveal that BET significantly reduces the three-year mortality rate in patients with high-grade dysplasia or esophageal adenocarcinoma, but it also leads to esophageal strictures in 6.5% of treated patients.
GASTROINTESTINAL ENDOSCOPY
(2023)
Article
Gastroenterology & Hepatology
Swathi Eluri, Anna Paterson, Brianna N. Lauren, Maria O'Donovan, Pradeep Bhandari, Massimiliano di Pietro, Minyi Lee, Rehan Haidry, Laurence Lovat, Krish Ragunath, Chin Hur, Rebecca C. Fitzgerald, Nicholas J. Shaheen
Summary: This study assessed the application value of Cytosponge in BE patients after RFA. The results showed that Cytosponge testing is a cost-effective surveillance method and is strongly associated with residual BE after ablation.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ahmed Sam Beydoun, Kaleigh A. Stabenau, Kenneth W. Altman, Nikki Johnston
Summary: Esophageal adenocarcinoma (EAC) is increasing rapidly and has a poor prognosis, often preceded by Barrett's esophagus (BE). This review provides an overview of BE, EAC, and the progression from BE to EAC. The definition, diagnosis, epidemiology, and risk factors for both conditions are discussed, with special attention given to areas of debate. The progression from BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is conducted through serial endoscopic evaluation, with shorter intervals recommended for high-risk features.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Tarek Sawas, Saam Dilmaghani, Lovekirat Dhaliwal, Kenneth K. Wang, Prasad G. Iyer, David A. Katzka
Summary: The study found that compared to BE patients, EAC patients had significantly lower rates of heartburn, diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome. Therefore, optimal strategies for screening for prevalent EAC may need to be adjusted.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mourad Wagdy Ali, Jianhong Chen, Li Yan, Xiaoyu Wang, James Y. Dai, Thomas L. Vaughan, Graham Casey, Matthew F. Buas
Summary: Through genome-wide association studies (GWAS), 19 genetic susceptibility loci for esophageal adenocarcinoma (EAC) and its precursor Barrett's esophagus (BE) have been identified. Utilizing functional potential scores, a systematic informatics pipeline was developed to prioritize candidate functional variants. Two additional prioritized loci were experimentally interrogated, uncovering a functional variant and risk enhancer. The identification of candidate gene targets, including B lymphocyte kinase (BLK), nei like DNA glycosylase 2 (NEIL2), and cathepsin B (CTSB), suggests that altered expression of these genes may play a role in the genetic risk association at 8p23.1 with BE/EAC.
HUMAN MOLECULAR GENETICS
(2022)
Article
Medicine, General & Internal
Prateek Sharma, Gary W. W. Falk, Menaka Bhor, A. Burak Ozbay, Dominick Latremouille-Viau, Annie Guerin, Sherry Shi, Margaret M. M. Elvekrog, Paul Limburg
Summary: This study addresses the prevalence of GERD, BE, and BERN in the US, as well as the utilization patterns of upper endoscopy. The results show an increase in upper endoscopy utilization from GERD to BE to BERN, and a decrease in time between upper endoscopies as the disease stage progresses from BE to BERN.
Article
Genetics & Heredity
Manisha Bajpai, Anshuman Panda, Kristen Birudaraju, James Van Gurp, Amitabh Chak, Kiron M. Das, Parisa Javidian, Hana Aviv
Summary: Barrett's esophagus (BE) is a premalignant metaplasia in patients with chronic gastroesophageal reflux disease (GERD), which can progress to esophageal adenocarcinoma (EA). A novel chromosomal translocation t(10:16) was discovered, and a FISH-EA assay was designed to detect these chromosomal events.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Nan Yi, Hailiang Zhao, Juan He, Xike Xie, Liexin Liang, Guowen Zuo, Mingyue Xiong, Yunxiao Liang, Tingzhuang Yi
Summary: Almost 50% of esophageal adenocarcinoma (EAC) patients are progressed from Barrett's esophagus (BE). However, effective stratification and therapy methods for BE and EAC are still lacking. Differentially expressed genes (DEGs) between BE and EAC were identified through the analysis of two public datasets (GSE26886 and GSE37200), followed by bioinformatics analyses to explore potential biomarkers associated with BE-EAC. The results revealed a number of up- and down-regulated genes, which were highly involved in tumorigenesis according to the GO and KEGG enrichment analysis. In addition, the study identified several potential diagnostic and prognostic biomarkers in BE-EAC.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
E. Ococks, A. M. Frankell, N. Masque Soler, N. Grehan, A. Northrop, H. Coles, A. M. Redmond, G. Devonshire, J. M. J. Weaver, C. Hughes, K. Lehovsky, A. Blasko, B. Nutzinger, R. C. Fitzgerald, E. Smyth
Summary: The study analyzed the prognostic potential of postoperative ctDNA in EAC patients, finding that ctDNA-positive patients had a higher recurrence rate and significantly shorter cancer-specific survival after excluding CHIP. Postoperative ctDNA could be utilized for risk stratification and adjustment of chemotherapy intensity.
ANNALS OF ONCOLOGY
(2021)
Review
Medicine, Research & Experimental
Nastazja Dagny Pilonis, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Hereditary diffuse gastric cancer (HDGC) is a rare cancer syndrome associated with significant risks of gastric and lobular breast cancer, often presenting late in clinical settings. While most cases can be traced back to germline variants in the CDH1 gene, some families with clustering of DGC do not have a clear genetic cause. This review focuses on discussing key elements for assessing inherited DGC susceptibility, providing practical recommendations for surveillance and treatment of at-risk individuals and early-stage patients.
ANNUAL REVIEW OF MEDICINE, VOL 72, 2021
(2021)
Article
Oncology
Daniel R. S. Middleton, Blandina T. Mmbaga, Maria O'Donovan, Behnoush Abedi-Ardekani, Irene Debiram-Beecham, Gissela Nyakunga-Maro, Venance Maro, Martin Bromwich, Amini Daudi, Timothy Ngowi, Rehema Minde, Jackson Claver, Alex Mremi, Amos Mwasamwaja, Joachim Schuz, Rebecca C. Fitzgerald, Valerie McCormack
Summary: Esophageal sponge cytology is a well-accepted endoscopy alternative for adenocarcinoma with extensive data on accuracy, but its feasibility in asymptomatic community members, particularly in East Africa with high ESCC rates, has been less studied. In a study of 102 asymptomatic adults in Kilimanjaro, Tanzania, the safety, acceptability, and feasibility of Cytosponge sampling was demonstrated, paving the way for innovative etiology and early-detection research. Targeted sampling strategies and biomarker development will be crucial for the success of future initiatives.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
Jue-Sheng Ong, Suzanne C. Dixon-Suen, Xikun Han, Jiyuan An, Upekha Liyanage, Jean-Cluade Dusingize, Johannes Schumacher, Ines Gockel, Anne Boehmer, Janusz Jankowski, Claire Palles, Tracy O'Mara, Amanda Spurdle, Matthew H. Law, Mark M. Iles, Paul Pharoah, Andrew Berchuck, Wei Zheng, Aaron P. Thrift, Catherine Olsen, Rachel E. Neale, Puya Gharahkhani, Penelope M. Webb, Stuart MacGregor
Summary: A study using a larger set of variants associated with 25(OH)D re-evaluated the relationship between 25(OH)D and cancer, finding no relationship for most cancers except for ovarian cancer and basal cell carcinoma. After adjusting for pigmentation related variables, the association with basal cell carcinoma was attenuated.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Stacey J. Scott, Xiaodun Li, Sriganesh Jammula, Ginny Devonshire, Catherine Lindon, Rebecca C. Fitzgerald, Pier Paolo D'Avino
Summary: Polyloidy plays a significant role in promoting chromosomal instability, genome evolution, and heterogeneity in cancer cells. The study on esophageal adenocarcinoma (EAC) revealed that the likely origin of polyploidy is due to mitotic failure caused by problems in chromosomal attachments, shedding light on cancer evolution and diversification for potential classification and treatment improvements.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Gastroenterology & Hepatology
Swathi Eluri, Anna Paterson, Brianna N. Lauren, Maria O'Donovan, Pradeep Bhandari, Massimiliano di Pietro, Minyi Lee, Rehan Haidry, Laurence Lovat, Krish Ragunath, Chin Hur, Rebecca C. Fitzgerald, Nicholas J. Shaheen
Summary: This study assessed the application value of Cytosponge in BE patients after RFA. The results showed that Cytosponge testing is a cost-effective surveillance method and is strongly associated with residual BE after ablation.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Richard Phillips, Wladyslaw Januszewicz, Nastazja D. Pilonis, Maria O'Donovan, Tarek Sawas, David A. Katzka, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Patients with BE-IND have a high risk of neoplastic progression and need close monitoring. BE length is associated with neoplastic progression.
GASTROINTESTINAL ENDOSCOPY
(2021)
Article
Multidisciplinary Sciences
Stefan Antonowicz, Zsolt Bodai, Tom Wiggins, Sheraz R. Markar, Piers R. Boshier, Yan Mei Goh, Mina E. Adam, Haonan Lu, Hiromi Kudo, Francesca Rosini, Robert Goldin, Daniela Moralli, Catherine M. Green, Chris J. Peters, Nagy Habib, Hani Gabra, Rebecca C. Fitzgerald, Zoltan Takats, George B. Hanna
Summary: Volatile aldehydes enriched in the breath of esophageal adenocarcinoma patients may be related to impaired detoxification function, leading to genotoxicity, and potentially mitigated with antidiabetic drugs. Additionally, increased levels of specific aldehydes in breath are correlated with certain gene expressions, which could be used for early diagnosis.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Erik van Dijk, Tom van den Bosch, Kristiaan J. Lenos, Khalid El Makrini, Lisanne E. Nijman, Hendrik F. B. van Essen, Nico Lansu, Michiel Boekhout, Joris H. Hageman, Rebecca C. Fitzgerald, Cornelis J. A. Punt, Jurriaan B. Tuynman, Hugo J. G. Snippert, Geert J. P. L. Kops, Jan Paul Medema, Bauke Ylstra, Louis Vermeulen, Daniel M. Miedema
Summary: Intratumour heterogeneity (ITH) is associated with worse prognosis in cancer, and efficient frameworks to measure it are needed. Here the authors develop a method to estimate copy number heterogeneity, and propose that it is driven by chromosomal instability and can predict pan-cancer survival.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Rebecca C. Fitzgerald, Antonis C. Antoniou, Ljiljana Fruk, Nitzan Rosenfeld
Summary: Proactively detecting cancer at an early stage is crucial, but distinguishing inconsequential changes from life-threatening lesions can be challenging. Advancements in technology will aid real-time detection of personalized cancer signals. Risk-based detection and prevention should be cost effective and widely accessible.
Review
Multidisciplinary Sciences
David Crosby, Sangeeta Bhatia, Kevin M. Brindle, Lisa M. Coussens, Caroline Dive, Mark Emberton, Sadik Esener, Rebecca C. Fitzgerald, Sanjiv S. Gambhir, Peter Kuhn, Timothy R. Rebbeck, Shankar Balasubramanian
Summary: Early detection of cancer is crucial for improving survival rates, but unfortunately, a significant number of cases are diagnosed at an advanced stage. Overcoming various challenges is essential to achieve early detection for all cancers, including understanding high-risk individuals, elucidating the biology and trajectory of precancer and early cancer, and developing sensitive and specific detection technologies.
Article
Oncology
Xiaoyu Wang, Puya Gharahkhani, David M. Levine, Rebecca C. Fitzgerald, Ines Gockel, Douglas A. Corley, Harvey A. Risch, Leslie Bernstein, Wong-Ho Chow, Lynn Onstad, Nicholas J. Shaheen, Jesper Lagergren, Laura J. Hardie, Anna H. Wu, Paul D. P. Pharoah, Geoffrey Liu, Lesley A. Anderson, Prasad G. Iyer, Marilie D. Gammon, Carlos Caldas, Weimin Ye, Hugh Barr, Paul Moayyedi, Rebecca Harrison, R. G. Peter Watson, Stephen Attwood, Laura Chegwidden, Sharon B. Love, David MacDonald, John DeCaestecker, Hans Prenen, Katja Ott, Susanne Moebus, Marino Venerito, Hauke Lang, Rupert Mayershofer, Michael Knapp, Lothar Veits, Christian Gerges, Josef Weismueller, Matthias Reeh, Markus M. Noethen, Jakob R. Izbicki, Hendrik Manner, Horst Neuhaus, Thomas Roesch, Anne C. Boehmer, Arnulf H. Hoelscher, Mario Anders, Oliver Pech, Brigitte Schumacher, Claudia Schmidt, Thomas Schmidt, Tania Noder, Dietmar Lorenz, Michael Vieth, Andrea May, Timo Hess, Nicole Kreuser, Jessica Becker, Christian Ell, Ian Tomlinson, Claire Palles, Janusz A. Jankowski, David C. Whiteman, Stuart MacGregor, Johannes Schumacher, Thomas L. Vaughan, Matthew F. Buas, James Y. Dai
Summary: This study identified novel genetic susceptibility loci for esophageal adenocarcinoma and Barrett esophagus using an eQTL set-based genetic association approach, expanding the pool of genetic susceptibility loci.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Colin Y. C. Lee, Adriaan Olivier, Judith Honing, Anne-Marie Lydon, Susan Richardson, Maria O'Donovan, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Summary: Hereditary diffuse gastric cancer, caused by CDH1 gene mutations, is characterized by early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the recommended treatment. This study assessed different sampling strategies for detecting signet ring cell carcinoma and identified criteria for characterizing endoscopic lesions in hereditary diffuse gastric cancer.
Article
Oncology
Judith Honing, Rebecca C. Fitzgerald
Summary: Barrett's esophagus is a precancerous condition that can progress to esophageal adenocarcinoma. Surveillance is needed to detect progression, but current methods are limited. This commentary proposes incorporating new risk factors and tools, such as nonendoscopic triage and commercial biomarker panels, into clinical practice for better risk stratification.
CANCER PREVENTION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Kieran Foley, David Shorthouse, Eric Rahrmann, Lizhe Zhuang, Ginny Devonshire, Rebecca C. OCCAMS Consortium, Rebecca C. Fitzgerald, Benjamin A. Hall
Summary: Metastasis in oesophageal adenocarcinoma (OAC) is a crucial factor affecting survival. Radiological staging is commonly used to assess metastases, but its accuracy is limited. This study analyzed lymph node metastases and identified new roles of genes SMAD4 and KCNQ3 in metastasis. The findings suggest that both genes could serve as novel biomarkers for metastatic risk and offer potential new targets for drug treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
