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
Diana L. Snyder, Michael D. Crowell, Allon Kahn, W. Leroy Griffing, Sarah Umar, Francisco C. Ramirez
Summary: This study is the largest on the prevalence of BE in women with SSc, revealing a prevalence of 12.8%. Women with SSc with BE were more likely to show features of a scleroderma esophagus on HRM. The high prevalence and incidence of dysplasia found suggest that women with SSc should be included in screening recommendations for BE.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Hsin-Yu Fang, Stefan Stangl, Sabrina Marcazzan, Marcos J. Braz Carvalho, Theresa Baumeister, Akanksha Anand, Julia Strangmann, Julia Slotta Huspenina, Timothy C. Wang, Roland M. Schmid, Marcus Feith, Helmut Friess, Vasilis Ntziachristos, Gabriele Multhoff, Dimitris Gorpas, Michael Quante
Summary: This study evaluated the use of a highly specific Hsp70-specific contrast agent in guided fluorescence molecular endoscopy biopsy, showing promising potential to improve tumor surveillance in BE patients, especially in cases with dysplasia and EAC.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Gastroenterology & Hepatology
Sho Fukuda, Kenta Watanabe, Tatsuki Yoshida, So Takahashi, Shusei Fujimori, Yohei Horikawa, Taiga Komatsu, Kenji Shirane, Yosuke Shimodaira, Tamotsu Matsuhashi, Katsunori Iijima
Summary: Although the prevalence of USSBE is quite high (36.4%), the incidence of EAC in USSBE is very low (0.0068%/year). Accordingly, USSBE can be excluded from targets for endoscopic surveillance in Japan.
DIGESTIVE ENDOSCOPY
(2022)
Article
Gastroenterology & Hepatology
Amir-Houshang Omidvari, William D. Hazelton, Brianna N. Lauren, Steffie K. Naber, Minyi Lee, Ayman Ali, Claudia Seguin, Chun Yin Kong, Ellen Richmond, Joel H. Rubenstein, Georg E. Luebeck, John M. Inadomi, Chin Hur, Iris Lansdorp-Vogelaar
Summary: This study highlights the importance of considering comorbidity status and sex when determining the optimal age to discontinue surveillance in patients with NDBE. Men are generally recommended a later age for the last surveillance, while women are recommended to discontinue surveillance at a younger age.
Article
Gastroenterology & Hepatology
Majid Alsahafi, Hebah Mimish, Fatma Salem, Mohammed Hijazi, Emad Aljahdli, Hani Jawa, Salim Bazarah, Rana Bokhary, Yousef Qari, Mahmoud Mosli
Summary: BE was reported endoscopically in 0.64% and histologically confirmed in 0.32% of this cohort of Saudi patients. Male gender was the only factor associated with BE.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Review
Oncology
Ksenia S. Maslyonkina, Alexandra K. Konyukova, Darya Y. Alexeeva, Mikhail Y. Sinelnikov, Liudmila M. Mikhaleva
Summary: Barrett's esophagus is a chronic and widespread disease that can progress to neoplastic transformation, which is often overlooked due to lack of standardized approaches in diagnosis. Research suggests that molecular, genetic, and epigenetic alterations in the esophagus occur earlier than cancerous transformation, providing insight into potential preventative strategies.
Article
Gastroenterology & Hepatology
Vidhi Patel, Madhusudhan R. Sanaka, Yi Qin, John McMichael, James Bena, Claire Beveridge, John Barron, Siva Raja, Jamak Modaresi Esfeh, Prashanthi N. Thota
Summary: This retrospective cohort study demonstrates that immunosuppressant use is associated with neoplastic progression in Barrett's esophagus (BE) patients, while solid organ transplantation (SOT) is not. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.
JOURNAL OF GASTROINTESTINAL SURGERY
(2023)
Article
Oncology
Mary E. Sehl, Jill E. Henry, Anna M. Storniolo, Steve Horvath, Patricia A. Ganz
Summary: The study found associations between earlier age at menarche and higher BMI with elevated DNA methylation-based age estimates in healthy breast tissues, indicating that cumulative estrogen exposure drives breast epigenetic aging. This suggests that epigenetic clock measures may help advance understanding of the relationship between accelerated breast tissue aging and increased breast cancer incidence in younger women.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2021)
Article
Medicine, General & Internal
Purva Jain, Alexandra M. Binder, Brian Chen, Humberto Parada, Linda C. Gallo, John Alcaraz, Steve Horvath, Parveen Bhatti, Eric A. Whitsel, Kristina Jordahl, Andrea A. Baccarelli, Lifang Hou, James D. Stewart, Yun Li, Jamie N. Justice, Andrea Z. LaCroix
Summary: This study investigated the association between epigenetic age acceleration (EAA), a biomarker associated with aging, and healthy longevity among older women. The findings suggest that EAA may be a valid biomarker associated with healthy longevity among older women and may be used for risk stratification and risk estimation of future functional and cognitive aging.
Article
Oncology
Benita K. Glamour, Omar Alaber, Gino Cioffi, Apoorva K. Chandar, Jill Barnholtz-Sloan, Wendy Brock, Gary W. Falk, Marcia Canto, Jean S. Wang, Prasad G. Iyer, Nicholas J. Shaheen, William M. Grady, Julian A. Abrams, Prashanthi N. Thota, Amitabh Chak, Andrew E. Blum
Summary: The study suggests a genetic basis for familial Barrett's associated neoplasia, and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.
Article
Gastroenterology & Hepatology
Kentaro Ishikawa, Kenichiro Okimoto, Tomoaki Matsumura, Yosuke Hirotsu, Kenji Amemiya, Takashi Kishimoto, Naoki Akizue, Yuki Ohta, Keiko Saito, Daisuke Maruoka, Motoi Nishimura, Kazuyuki Matsushita, Hitoshi Mochizuki, Makoto Arai, Jun Kato, Osamu Yokosuka, Masao Omata, Naoya Kato
Summary: The study clarified the malignant potential of patients with CLE without intestinal metaplasia and/or less than 1 cm, suggesting the need for follow-up in these patients similar to those with BE.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Christopher Douville, Helen R. Moinova, Prashanthi N. Thota, Nicholas J. Shaheen, Prasad G. Lyer, Marcia Irene Canto, Jean S. Wang, John A. Dumot, Ashley Faulx, Kenneth W. Kinzler, Nickolas Papadopoulos, Bert Vogelstein, Sanford D. Markowitz, Chetan Bettegowda, Joseph E. Willis, Amitabh Chak
Summary: RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in patients with Barrett's esophagus. It identifies specific chromosome changes that occur early in the disease and others that occur late and mark disease progression. The clinical implications of this approach can now be tested in prospective trials.
Article
Biochemistry & Molecular Biology
Takuya Shijimaya, Tomomitsu Tahara, Jumpei Yamazaki, Yasushi Matsumoto, Naohiro Nakamura, Yu Takahashi, Takashi Tomiyama, Toshiro Fukui, Tomoyuki Shibata, Makoto Naganuma
Summary: The molecular mechanisms of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in Japanese patients are still unclear. A study conducted on Japanese patients, mostly with short-segment BE (SSBE), found that methylation levels of the N33, DPYS, and SLC16A12 genes were higher in the ADJ and T groups compared to the N group.
MOLECULAR CARCINOGENESIS
(2023)
Article
Gastroenterology & Hepatology
Jing Dong, Catriona Grant, Barry Vuong, Norman Nishioka, Anna Huizi Gao, Matthew Beatty, Grace Baldwin, Aaron Baillargeon, Ara Bablouzian, Patricia Grahmann, Nitasha Bhat, Emily Ryan, Amilcar Barrios, Sarah Giddings, Timothy Ford, Emilie Beaulieu-Ouellet, Seyed Hamid Hosseiny, Irene Lerman, Wolfgang Trasischker, Rohith Reddy, Kanwarpal Singh, Michalina Gora, Daryl Hyun, Lucille Queneherve, Michael Wallace, Herbert Wolfsen, Prateek Sharma, Kenneth K. Wang, Cadman L. Leggett, John Poneros, Julian A. Abrams, Charles Lightdale, Samantha Leeds, Mireille Rosenberg, Guillermo J. Tearney
Summary: TCE can be used at multiple sites, administered to unsedated patients by non-expert physicians or nurses, and rapidly and safely evaluate the microscopic structure of the esophagus.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Kit Curtius, Joel H. Rubenstein, Amitabh Chak, John M. Inadomi
Summary: The study aimed to determine whether Barrett's esophagus is the origin of all incident esophageal adenocarcinomas, and found that almost all cases of OAC could be attributed to Barrett's esophagus based on a computational model and population data.
Article
Gastroenterology & Hepatology
Kit Curtius, Misha Kabir, Ibrahim Al Bakir, Chang Ho Ryan Choi, Juanda L. Hartono, Michael Johnson, James E. East, James O. Lindsay, Roser Vega, Siwan Thomas-Gibson, Janindra Warusavitarne, Ana Wilson, Trevor A. Graham, Ailsa Hart
Summary: This study identified that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing advanced neoplasia. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator can support treatment decision-making.
Review
Gastroenterology & Hepatology
Kit Curtius, Samir Gupta, C. Richard Boland
Summary: Lynch syndrome is an autosomal dominant familial condition caused by a pathogenic variant in a DNA mismatch repair gene, predisposing carriers to various cancers. This review aims to discuss the pathogenesis, clinical presentation, differential diagnosis, and clinical strategies for detection and management of Lynch syndrome. Lynch syndrome tumors have a unique pathogenesis resulting in hypermutation, microsatellite instability, and high immunogenicity. Understanding the pathogenesis of Lynch syndrome informs current strategies for detection and clinical management, and guides future areas for clinical innovation.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Gregory D. Sepich-Poore, Caitlin Guccione, Lucie Laplane, Thomas Pradeu, Kit Curtius, Rob Knight
Summary: The presence and role of microbes in human cancers have been reconsidered and should be taken seriously. Careful consideration of microbial experimental idiosyncrasies is needed when utilizing cancer's metagenome for diagnostics, prognostics, and therapeutics. Reconsidering cancer clonality as a multispecies process holds key implications for understanding metastasis and predicting therapeutic resistance.
Article
Multidisciplinary Sciences
Qingli Guo, Eszter Lakatos, Ibrahim Al Bakir, Kit Curtius, Trevor A. Graham, Ville Mustonen
Summary: Clinical archives of patient material are predominantly composed of FFPE blocks. However, sequencing DNA derived from FFPE material is known to have artifacts. In this study, a computational algorithm called FFPEsig is introduced to rectify these artifacts and enable accurate mutational signature analysis.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Pradipt Ghosh, Vinicius J. Campos, Daniella T. Vo, Caitlin Guccione, Vanae Goheen-Holland, Courtney Tindle, Guilherme S. Mazzini, Yudou He, Ludmil B. Alexandrov, Scott M. Lippman, Richard R. Gurski, Das Soumita, Rena Yadlapati, Kit Curtius, Debashis Sahoo
Summary: This study used artificial intelligence-guided network approach to study the initiation and progression of esophageal adenocarcinomas (EACs). They identified a driver of cellular transformation in EACs and suggested that a racially influenced immunological basis and the presence of benign ethnic neutropenia may affect the progression from Barrett's metaplasia to EAC.
Article
Genetics & Heredity
James V. Talwar, David Laub, Meghana S. Pagadala, Andrea Castro, McKenna Lewis, Georg E. Luebeck, Bryan R. Gorman, Cuiping Pan, Frederick N. Dong, Kyriacos Markianos, Craig C. Teerlink, Julie Lynch, Richard Hauger, Saiju Pyarajan, Philip S. Tsao, Gerald P. Morris, Rany M. Salem, Wesley K. Thompson, Kit Curtius, Maurizio Zanetti, Hannah Carter
Summary: Autoimmunity and cancer are two different aspects of immune dysfunction, characterized by breakdowns in self-tolerance and impaired immune surveillance, respectively. This study shows that MHC-I autoimmune-risk alleles are associated with a delayed age of melanoma diagnosis and decreased risk of developing melanoma. The findings suggest that these alleles modulate melanoma risk that is not accounted for by current risk scores.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Gastroenterology & Hepatology
Roshani V. Patel, Kit Curtius, Ripple Man, Jordan Fletcher, Victoria Cuthill, Susan K. Clark, Alexander C. von Roon, Andrew Latchford
Summary: This study analyzed data from 249 patients with familial adenomatous polyposis (FAP) and found that 76% of patients developed at least one pouch body adenoma, with 16% developing an advanced pouch body lesion. The cumulative incidence of advanced lesions in the pouch body and cuff after 10 years was 2.8% and 6.4%, respectively. The presence of adenomas before the 10-year point was associated with an increased risk of subsequent development of advanced lesions. These findings can guide personalized surveillance for FAP patients.
Editorial Material
Microbiology
Caitlin Guccione, Daniel McDonald, Rebecca Fielding-Miller, Kit Curtius, Rob Knight
NATURE MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Bingxin Lu, Kit Curtius, Trevor A. Graham, Ziheng Yang, Chris P. Barnes
Summary: Phylogenetic trees based on copy number profiles from multiple samples of a patient are helpful to understand cancer evolution. We developed a new maximum likelihood method, CNETML, to infer phylogenies from such data. CNETML is the first program to jointly infer the tree topology, node ages, and mutation rates from total copy numbers of longitudinal samples. Our simulations show that CNETML performs well on copy numbers relative to ploidy and slightly violated model assumptions.
Article
Biochemical Research Methods
Brian Johnson, Yubo Shuai, Jason Schweinsberg, Kit Curtius
Summary: Measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. However, using DNA sequencing datasets at single-cell resolution, researchers can reconstruct past evolution and gain a better understanding of dynamics prior to detectable disease.
Meeting Abstract
Gastroenterology & Hepatology
Steven D. Ma, Caitlin Guccione, Kristen Linnemeyer, Madeline Greytak, Aws Hasan, Joshua Rubin, Philip Weissbrod, Bernd Schnabl, Kit Curtius, Rena Yadlapati
Meeting Abstract
Gastroenterology & Hepatology
Steven D. Ma, Caitlin Guccione, Kristen Linnemeyer, Madeline Greytak, Aws Hasan, Joshua Rubin, Philip Weissbrod, Bernd Schnabl, Kit Curtius, Rena Yadlapati
Meeting Abstract
Surgery
Talita Oliveira, McKenna Lewis, Laura Smyth, Richard Turkington, Amy Jayne McKnight, Victoria Cairnduff, Damian McManus, Brian Johnston, Helen Coleman, Kit Curtius
BRITISH JOURNAL OF SURGERY
(2021)
Meeting Abstract
Gastroenterology & Hepatology
Mehmet Yalchin, Kit Curtius, Salpie Nowinski, Morgan Moorghen, Chris Kimberley, Kane Smith, Ann-Marie Baker, Ibrahim Al-Bakir, Ailsa Hart, Trevor Graham