{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:16:17Z","timestamp":1779210977864,"version":"3.51.4"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Surg Endosc"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The risk of progression from non-dysplastic Barrett\u2019s esophagus (NDBE) to high grade dysplasia or esophageal adenocarcinoma (HGD\/EAC) is low but variable. Biomarker assays can aid with risk stratification to optimize surveillance for NDBE. The role of diagnostic esophageal testing in prognosticating progression is unclear. The aim of this study was to evaluate whether esophageal physiology parameters correlate with a validated biomarker for BE risk progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Patients with NDBE, including histology confirmed intestinal metaplasia\u2009&lt;\u20091\u00a0cm, had their pathology specimen analyzed using a validated tissue systems pathology test with 9 biomarkers (TSP-9). This assay uses immunohistochemistry and digital pathology analysis to provide a 5-year risk of progression to HGD\/EAC. These patients also underwent esophageal pH-monitoring and high-resolution impedance manometry (HRIM). Correlation analyses were performed between TSP-9 risk percent and esophageal testing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A total of 59 patients [52.5% male; mean\u00a0(SD) age 59 (14)] were included (40 NDBE, 19\u2009&lt;\u20091\u00a0cm IM) between 2021 and 2023. The median (IQR) TSP-9 value for 5-year risk of progression was low at 2.0% (2.0\u20133.0%). There were 8 (13.6%) statistical outliers with higher risk ranging from 5.0 to 10.0%. Risk of progression in the entire cohort was directly correlated with physiology testing parameters including DeMeester score (<jats:italic>R<\/jats:italic>\u2009=\u20090.30), acid exposure time (AET) (<jats:italic>R<\/jats:italic>\u2009=\u20090.34), duration of longest reflux episode on pH-monitoring (<jats:italic>R<\/jats:italic>\u2009=\u20090.30), and % incomplete bolus clearance on HRIM (<jats:italic>R<\/jats:italic>\u2009=\u20090.35) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 for all).<\/jats:p>\n            <jats:p>In a subgroup of 19 patients with\u2009&lt;\u20091\u00a0cm IM, risk of progression had a stronger correlation with DeMeester score (<jats:italic>R<\/jats:italic>\u2009=\u20090.65), AET (<jats:italic>R<\/jats:italic>\u2009=\u20090.67), supine AET (<jats:italic>R<\/jats:italic>\u2009=\u20090.70), number of reflux episodes on pH-monitoring (<jats:italic>R<\/jats:italic>\u2009=\u20090.50) and % incomplete bolus clearance on HRIM (<jats:italic>R<\/jats:italic>\u2009=\u20090.68) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 for all).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>There was a direct correlation between 5-year risk of progression to HGD\/EAC using TSP-9 and distal esophageal acid exposure and poor esophageal clearance among patients with NDBE that was even stronger in those with\u2009&lt;\u20091\u00a0cm of IM. These findings suggest that esophageal physiology testing may have value in predicting risk progression in BE.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00464-025-11930-y","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T16:30:55Z","timestamp":1751905855000},"page":"5046-5056","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distal esophageal acid exposure and poor esophageal clearance correlate with probability of progression in Barrett\u2019s esophagus\u00a0as determined by the tissue systems pathology test"],"prefix":"10.1007","volume":"39","author":[{"given":"Sven E.","family":"Eriksson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnathan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inanc S.","family":"Sarici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-9164","authenticated-orcid":false,"given":"Shahin","family":"Ayazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"242\u2013256","key":"11930_CR1","volume":"79","author":"LG Gordon","year":"2014","unstructured":"Gordon LG, Mayne GC, Hirst NG, Bright T, Whiteman DC, Follow-Up ACSC, Watson DI (2014) Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett\u2019s esophagus. Gastrointest Endosc 79(242\u2013256):e246","journal-title":"Gastrointest Endosc"},{"key":"11930_CR2","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1038\/ajg.2011.130","volume":"106","author":"KW Jung","year":"2011","unstructured":"Jung KW, Talley NJ, Romero Y, Katzka DA, Schleck CD, Zinsmeister AR, Dunagan KT, Lutzke LS, Wu T-T, Wang KK (2011) Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett\u2019s esophagus: a population-based study. Off J Am Coll Gastroenterol ACG 106:1447\u20131455","journal-title":"Off J Am Coll Gastroenterol ACG"},{"key":"11930_CR3","first-page":"47","volume":"47","author":"MG Brandt","year":"2004","unstructured":"Brandt MG, Darling GE, Miller L (2004) Symptoms, acid exposure and motility in patients with Barrett\u2019s esophagus. Can J Surg 47:47","journal-title":"Can J Surg"},{"issue":"907\u2013931","key":"11930_CR4","volume":"87","author":"S Wani","year":"2018","unstructured":"Wani S, Qumseya B, Sultan S, Agrawal D, Chandrasekhara V, Harnke B, Kothari S, McCarter M, Shaukat A, Wang A (2018) Endoscopic eradication therapy for patients with Barrett\u2019s esophagus\u2013associated dysplasia and intramucosal cancer. Gastrointest Endosc 87(907\u2013931):e909","journal-title":"Gastrointest Endosc"},{"key":"11930_CR5","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/ajg.2008.31","volume":"104","author":"S Wani","year":"2009","unstructured":"Wani S, Puli SR, Shaheen NJ, Westhoff B, Slehria S, Bansal A, Rastogi A, Sayana H, Sharma P (2009) Esophageal adenocarcinoma in Barrett\u2019s esophagus after endoscopic ablative therapy: a meta-analysis and systematic review. Off J Am Coll Gastroenterol ACG 104:502\u2013513","journal-title":"Off J Am Coll Gastroenterol ACG"},{"key":"11930_CR6","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1136\/gut.2009.176701","volume":"59","author":"PJ De Jonge","year":"2010","unstructured":"De Jonge PJ, van Blankenstein M, Looman CW, Casparie MK, Meijer GA, Kuipers EJ (2010) Risk of malignant progression in patients with Barrett\u2019s oesophagus: a Dutch nationwide cohort study. Gut 59:1030\u20131036","journal-title":"Gut"},{"issue":"869\u2013877","key":"11930_CR7","volume":"17","author":"Y Peters","year":"2019","unstructured":"Peters Y, Honing J, Kievit W, Kestens C, Pestman W, Nagtegaal ID, van der Post RS, Siersema PD (2019) Incidence of progression of persistent nondysplastic Barrett\u2019s esophagus to malignancy. Clin Gastroenterol Hepatol 17(869\u2013877):e865","journal-title":"Clin Gastroenterol Hepatol"},{"key":"11930_CR8","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1158\/1055-9965.EPI-15-1164","volume":"25","author":"RJ Critchley-Thorne","year":"2016","unstructured":"Critchley-Thorne RJ, Duits LC, Prichard JW, Davison JM, Jobe BA, Campbell BB, Zhang Y, Repa KA, Reese LM, Li J (2016) A tissue systems pathology assay for high-risk Barrett\u2019s esophagus. Cancer Epidemiol Biomark Prev 25:958\u2013968","journal-title":"Cancer Epidemiol Biomark Prev"},{"key":"11930_CR9","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1158\/1055-9965.EPI-16-0640","volume":"26","author":"RJ Critchley-Thorne","year":"2017","unstructured":"Critchley-Thorne RJ, Davison JM, Prichard JW, Reese LM, Zhang Y, Repa K, Li J, Diehl DL, Jhala NC, Ginsberg GG (2017) A tissue systems pathology test detects abnormalities associated with prevalent high-grade dysplasia and esophageal cancer in Barrett\u2019s esophagus. Cancer Epidemiol Biomark Prev 26:240\u2013248","journal-title":"Cancer Epidemiol Biomark Prev"},{"key":"11930_CR10","first-page":"14309","volume":"10","author":"JM Davison","year":"2022","unstructured":"Davison JM, Goldblum JR, Duits LC, Khoshiwal AM, Bergman JJ, Falk GW, Diehl DL, Khara HS, Smolko C, Arora M (2022) A tissue systems pathology test outperforms the standard of care variables in predicting progression in patients with Barrett\u2019s esophagus. Clin Trans Gastroenterol 10:14309","journal-title":"Clin Trans Gastroenterol"},{"key":"11930_CR11","doi-asserted-by":"publisher","first-page":"48","DOI":"10.4103\/2153-3539.163987","volume":"6","author":"JW Prichard","year":"2015","unstructured":"Prichard JW, Davison JM, Campbell BB, Repa KA, Reese LM, Nguyen XM, Li J, Foxwell T, Taylor DL, Critchley-Thorne RJ (2015) TissueCypher\u2122: a systems biology approach to anatomic pathology. J Pathol Inform 6:48","journal-title":"J Pathol Inform"},{"key":"11930_CR12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/0016-5085(93)90008-Z","volume":"105","author":"DS Levine","year":"1993","unstructured":"Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ (1993) An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett\u2019s esophagus. Gastroenterology 105:40\u201350","journal-title":"Gastroenterology"},{"key":"11930_CR13","doi-asserted-by":"publisher","first-page":"e14058","DOI":"10.1111\/nmo.14058","volume":"33","author":"R Yadlapati","year":"2021","unstructured":"Yadlapati R, Kahrilas PJ, Fox MR, Bredenoord AJ, Prakash Gyawali C, Roman S, Babaei A, Mittal RK, Rommel N, Savarino E (2021) Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0\u00a9. Neurogastroenterol Motility 33:e14058","journal-title":"Neurogastroenterol Motility"},{"key":"11930_CR14","doi-asserted-by":"publisher","first-page":"1458138","DOI":"10.3389\/fonc.2024.1458138","volume":"14","author":"A Barchi","year":"2025","unstructured":"Barchi A, Dell\u2019Anna G, Massimino L, Mandarino FV, Vespa E, Viale E, Passaretti S, Annese V, Malesci A, Danese S (2025) Unraveling the pathogenesis of Barrett\u2019s esophagus and esophageal adenocarcinoma: the \u201comics\u201d era. Front Oncol 14:1458138","journal-title":"Front Oncol"},{"issue":"2772\u20132779","key":"11930_CR15","volume":"20","author":"PG Iyer","year":"2022","unstructured":"Iyer PG, Codipilly DC, Chandar AK, Agarwal S, Wang KK, Leggett CL, Latuche LR, Schulte PJ (2022) Prediction of progression in Barrett\u2019s esophagus using a tissue systems pathology test: a pooled analysis of international multicenter studies. Clin Gastroenterol Hepatol 20(2772\u20132779):e2778","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"2696\u20132706","key":"11930_CR16","volume":"20","author":"VR Muthusamy","year":"2022","unstructured":"Muthusamy VR, Wani S, Gyawali CP, Komanduri S, Bergman J, Canto MI, Chak A, Corley D, Falk GW, Fitzgerald R (2022) AGA clinical practice update on new technology and innovation for surveillance and screening in Barrett\u2019s esophagus: expert review. Clin Gastroenterol Hepatol 20(2696\u20132706):e2691","journal-title":"Clin Gastroenterol Hepatol"},{"key":"11930_CR17","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1111\/j.1572-0241.2002.05902.x","volume":"97","author":"B Avidan","year":"2002","unstructured":"Avidan B, Sonnenberg A, Schnell TG, Chejfec G, Metz A, Sontag SJ (2002) Hiatal hernia size, Barrett\u2019s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. Off J Am Coll Gastroenterol ACG 97:1930\u20131936","journal-title":"Off J Am Coll Gastroenterol ACG"},{"key":"11930_CR18","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1111\/j.1572-0241.2004.30228.x","volume":"99","author":"HB El-Serag","year":"2004","unstructured":"El-Serag HB, Aguirre TV, Davis S, Kuebeler M, Bhattacharyya A, Sampliner RE (2004) Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett\u2019s esophagus. Off J Am Coll Gastroenterol ACG 99:1877\u20131883","journal-title":"Off J Am Coll Gastroenterol ACG"},{"key":"11930_CR19","doi-asserted-by":"publisher","first-page":"2681","DOI":"10.1007\/s00432-021-03544-3","volume":"147","author":"Y Chen","year":"2021","unstructured":"Chen Y, Sun C, Wu Y, Chen X, Kailas S, Karadsheh Z, Li G, Guo Z, Yang H, Hu L (2021) Do proton pump inhibitors prevent Barrett\u2019s esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis. J Cancer Res Clin Oncol 147:2681\u20132691","journal-title":"J Cancer Res Clin Oncol"},{"key":"11930_CR20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/01.sla.0000167864.46462.9f","volume":"242","author":"S \u00d6berg","year":"2005","unstructured":"\u00d6berg S, Wenner J, Johansson J, Walther B, Will\u00e9n R (2005) Barrett esophagus: risk factors for progression to dysplasia and adenocarcinoma. Ann Surg 242:49\u201354","journal-title":"Ann Surg"},{"key":"11930_CR21","doi-asserted-by":"publisher","first-page":"9083","DOI":"10.1158\/0008-5472.CAN-09-2518","volume":"69","author":"HY Zhang","year":"2009","unstructured":"Zhang HY, Hormi-Carver K, Zhang X, Spechler SJ, Souza RF (2009) In benign Barrett\u2019s epithelial cells, acid exposure generates reactive oxygen species that cause DNA double-strand breaks. Can Res 69:9083\u20139089","journal-title":"Can Res"},{"key":"11930_CR22","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/j.1365-2036.2004.02127.x","volume":"20","author":"L Gerson","year":"2004","unstructured":"Gerson L, Boparai V, Ullah N, Triadafilopoulos G (2004) Oesophageal and gastric pH profiles in patients with gastro-oesophageal reflux disease and Barrett\u2019s oesophagus treated with proton pump inhibitors. Aliment Pharmacol Ther 20:637\u2013643","journal-title":"Aliment Pharmacol Ther"},{"key":"11930_CR23","first-page":"1263","volume":"84","author":"S Fiorucci","year":"1989","unstructured":"Fiorucci S, Santucci L, Farroni F, Pelli MA, Morelli A (1989) Effect of omeprazole on gastroesophageal reflux in Barrett\u2019s esophagus. Am J Gastroenterol 84:1263","journal-title":"Am J Gastroenterol"},{"key":"11930_CR24","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1111\/j.1572-0241.1998.00331.x","volume":"93","author":"M Coenraad","year":"1998","unstructured":"Coenraad M, Masclee AA, Straathof JW, Ganesh S, Griffioen G, Lamers CB (1998) Is Barrett\u2019s esophagus characterized by more pronounced acid reflux than severe esophagitis? Off J Am Coll Gastroenterol ACG 93:1068\u20131072","journal-title":"Off J Am Coll Gastroenterol ACG"},{"key":"11930_CR25","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1007\/s10620-020-06098-5","volume":"65","author":"R Yadlapati","year":"2020","unstructured":"Yadlapati R, Triggs J, Quader F, Eluri S, Bhatia S, Kaizer A, Pandolfino JE, Komanduri S, Gyawali P, Shaheen NJ (2020) Reduced esophageal contractility is associated with dysplasia progression in Barrett\u2019s esophagus: a multicenter cohort study. Dig Dis Sci 65:3631\u20133638","journal-title":"Dig Dis Sci"},{"issue":"897\u2013909","key":"11930_CR26","volume":"79","author":"S Singh","year":"2014","unstructured":"Singh S, Manickam P, Amin AV, Samala N, Schouten LJ, Iyer PG, Desai TK (2014) Incidence of esophageal adenocarcinoma in Barrett\u2019s esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 79(897\u2013909):e894","journal-title":"Gastrointest Endosc"},{"key":"11930_CR27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1136\/gutjnl-2013-305372","volume":"63","author":"RC Fitzgerald","year":"2014","unstructured":"Fitzgerald RC, Di Pietro M, Ragunath K, Ang Y, Kang J-Y, Watson P, Trudgill N, Patel P, Kaye PV, Sanders S (2014) British Society of Gastroenterology guidelines on the diagnosis and management of Barrett\u2019s oesophagus. Gut 63:7\u201342","journal-title":"Gut"},{"issue":"335\u2013359","key":"11930_CR28","volume":"90","author":"B Qumseya","year":"2019","unstructured":"Qumseya B, Sultan S, Bain P, Jamil L, Jacobson B, Anandasabapathy S, Agrawal D, Buxbaum JL, Fishman DS, Gurudu SR (2019) ASGE guideline on screening and surveillance of Barrett\u2019s esophagus. Gastrointest Endosc 90(335\u2013359):e332","journal-title":"Gastrointest Endosc"},{"key":"11930_CR29","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1053\/j.gastro.2019.09.051","volume":"158","author":"P Sharma","year":"2020","unstructured":"Sharma P, Shaheen NJ, Katzka D, Bergman JJ (2020) AGA clinical practice update on endoscopic treatment of Barrett\u2019s esophagus with dysplasia and\/or early cancer: expert review. Gastroenterology 158:760\u2013769","journal-title":"Gastroenterology"},{"key":"11930_CR30","doi-asserted-by":"publisher","first-page":"559","DOI":"10.14309\/ajg.0000000000001680","volume":"117","author":"NJ Shaheen","year":"2022","unstructured":"Shaheen NJ, Falk GW, Iyer PG, Souza RF, Yadlapati RH, Sauer BG, Wani S (2022) Diagnosis and management of Barrett\u2019s esophagus: an updated ACG guideline. Off J Am Coll Gastroenterol ACG 117:559\u2013587","journal-title":"Off J Am Coll Gastroenterol ACG"}],"container-title":["Surgical Endoscopy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00464-025-11930-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00464-025-11930-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00464-025-11930-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T01:20:59Z","timestamp":1757208059000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00464-025-11930-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["11930"],"URL":"https:\/\/doi.org\/10.1007\/s00464-025-11930-y","relation":{},"ISSN":["0930-2794","1432-2218"],"issn-type":[{"value":"0930-2794","type":"print"},{"value":"1432-2218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"19 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Jennifer M. Kolb is consultant for Castle Biosciences. Drs. Sven E. Eriksson, Johnathan Nguyen, Inanc S. Sarici, Ping Zheng, and Shahin Ayazi have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}