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248 results on '"Haidry, R."'

1. Performance of endoscopic approaches for Zenker diverticulum management: a systematic review and meta-analysis

Author

Papaefthymiou, A., additional, Benjamin, N., additional, Telese, A., additional, Siggens, K., additional, Margaret, D., additional, Murino, A., additional, Johnson, G., additional, Murray, C., additional, Boz, M., additional, Muntzer, M., additional, Bisschops, R., additional, Pradeep, B., additional, Birchall, M., additional, and Haidry, R., additional

Published
2024
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5. The UK experience of zenker per-oral endoscopic myotomy (z-poem) for the treatment of zenker’s diverticulum

Author

Norton, B., additional, Siggens, K., additional, Papaefthymiou, A., additional, Telese, A., additional, Duku, M., additional, Murino, A., additional, Murray, C., additional, Johnson, G., additional, Mohammadi, B., additional, Mughal, M., additional, Bisschops, R., additional, Bhandari, P., additional, Birchall, M., additional, and Haidry, R., additional

Published
2024
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6. Strict endoscopic follow-up after endoscopic resection (R0) of high-risk T1 adenocarcinoma in Barrett's esophagus seems feasible: Preliminary results of a prospective, international, multicenter cohort study (PREFER)

Author

Chan, M. W., additional, Nieuwenhuis, E., additional, Jansen, M., additional, Nagengast, W. B., additional, Westerhof, J., additional, Neuhaus, H., additional, Beyna, T., additional, Koch, A., additional, Spaander, M., additional, Bourke, M. J., additional, Bisschops, R., additional, De Hertogh, G., additional, Weusten, B., additional, Alkhalaf, A., additional, Pech, O., additional, Seewald, S., additional, Haidry, R., additional, De Wulf, D., additional, Schlag, C., additional, Schoon, E. J., additional, Houben, M.H.M. G., additional, Messmann, H., additional, Dewint, P., additional, Fernández-Sordo, J. O., additional, Meijer, S., additional, Bergman, J., additional, and Pouw, R., additional

Published
2024
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9. Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus

Author

Fitzgerald, R.C., Noorani, A., Edwards, P.A.W., Grehan, N., Nutzinger, B., Hughes, C., Fidziukiewicz, E., MacRae, S., Northrop, A., Contino, G., Li, X., de la Rue, R., Katz-Summercorn, A., Abbas, S., Loureda, D., O'Donovan, M., Miremadi, A., Malhotra, S., Tripathi, M., Tavaré, S., Lynch, A.G., Eldridge, M., Secrier, M., Devonshire, G., Perner, J., Jammula, S., Davies, J., Crichton, C., Carroll, N., Safranek, P., Hindmarsh, A., Sujendran, V., Hayes, S.J., Ang, Y., Sharrocks, A., Preston, S.R., Oakes, S., Bagwan, I., Save, V., Skipworth, R.J.E., Hupp, T.R., O'Neill, J.R., Tucker, O., Beggs, A., Taniere, P., Puig, S., Underwood, T.J., Walker, R.C., Grace, B.L., Barr, H., Shepherd, N., Old, O., Lagergren, J., Davies, A., Chang, F., Goh, V., Ciccarelli, F.D., Sanders, G., Berrisford, R., Harden, C., Lewis, M., Cheong, E., Kumar, B., Parsons, S.L., Soomro, I., Kaye, P., Saunders, J., Lovat, L., Haidry, R., Igali, L., Scott, M., Sothi, S., Suortamo, S., Lishman, S., Hanna, G.B., Moorthy, K., Peters, C.J., Grabowska, A., Turkington, R., McManus, D., Coleman, H., Khoo, D., Fickling, W., Knight, William R.C., McEwen, Ricardo, Byrne, Ben E., Habib, Wais, Bott, Rebecca, Zylstra, Janine, Mahadeva, Ula, and Gossage, James A.

Published
2020
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11. Safety and efficacy of salvage endoscopic submucosal dissection for Barrett’s neoplasia recurrence after radiofrequency ablation

Author

Mesureur, L., additional, Deprez, P. H., additional, Bisschops, R., additional, Pouw, R., additional, Weusten, B., additional, Barret, M., additional, Dewint, P., additional, Tate, D. J., additional, Leclercq, P., additional, Seewald, S., additional, Barbaro, F., additional, Baldaque-Silva, F., additional, Omae, M., additional, Pioche, M., additional, Bourke, M. J., additional, Haidry, R., additional, and Lemmers, A., additional

Published
2023
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12. Hemospray use in pancreaticobiliary related gastrointestinal haemorrhage: Outcomes from an international multicentre registry

Author

Aslam, N., additional, Hussein, M., additional, Alzoubaidi, D., additional, O'donnell, M., additional, Varmpompitis, I., additional, Hengehold, T., additional, Fraile-Lopez, M., additional, Fernández-Sordo, J. O., additional, Wilhelm Rey, J., additional, Hayee, B., additional, Despott, E., additional, Murino, A., additional, Moreea, S., additional, Boger, P., additional, Dunn, J., additional, Maine, I., additional, Graham, D., additional, Early, D., additional, Latorre, M., additional, Ragunath, K., additional, Anderson, J., additional, Bhandari, P., additional, Götz, M., additional, Kiesslich, R., additional, Coron, E., additional, De Santiago, E. Rodriguez, additional, Gonda, T., additional, Seth, G., additional, Lovat, L., additional, and Haidry, R., additional

Published
2023
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14. Endoscopic Follow-up Of Radically Resected Submucosal Adenocarcinoma In Barrett’s Esophagus: Interim Results Of An Ongoing Prospective, International, Multicenter Cohort Registry (PREFER Trial)

Author

Chan, M. W., additional, Nieuwenhuis, E., additional, Jansen, M., additional, Koch, A., additional, Spaander, M.C. W., additional, Nagengast, W. B., additional, Westerhof, J., additional, Bisschops, R., additional, De Hertogh, G., additional, Bourke, M. J., additional, Neuhaus, H., additional, Weusten, B., additional, Alkhalaf, A., additional, Pech, O., additional, Seewald, S., additional, Haidry, R., additional, Schlag, C., additional, Schoon, E. J., additional, Houben, M.H.M. G., additional, De Wulf, D., additional, Messmann, H., additional, Dewint, P., additional, Meijer, S. L., additional, Bergman, J.J.G.H. M., additional, and Pouw, R. E., additional

Published
2023
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15. Endoscopic eradication therapy with multifocal cryoballoon ablation for Barrett’s esophagus related neoplasia: preliminary results from a prospective European multicenter study

Author

Frederiks, C. N., additional, Overwater, A., additional, Barret, M., additional, Maselli, R., additional, Bergman, J., additional, Pouw, R., additional, Bisschops, R., additional, Haidry, R., additional, Sehgal, V., additional, Beyna, T., additional, Neuhaus, H., additional, and Weusten, B., additional

Published
2023
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16. Wide-area transepithelial sampling with computer-assisted analysis to detect high grade dysplasia and cancer in Barrett's esophagus: a multicenter randomized study.

Author

Munster, S.N. van, Leclercq, P., Haidry, R., Messmann, H., Probst, A., Ragunath, K., Bhandari, P., Repici, A., Munoz-Navas, M., Seewald, S., Lemmers, A., Fernández-Esparrach, G., Pech, O., Schoon, E.J., Kariv, R., Neuhaus, H., Weusten, B.L., Siersema, P.D., Correale, L., Meijer, S.L., Hertogh, G. de, Bergman, J.J., Hassan, C., Bisschops, R., Munster, S.N. van, Leclercq, P., Haidry, R., Messmann, H., Probst, A., Ragunath, K., Bhandari, P., Repici, A., Munoz-Navas, M., Seewald, S., Lemmers, A., Fernández-Esparrach, G., Pech, O., Schoon, E.J., Kariv, R., Neuhaus, H., Weusten, B.L., Siersema, P.D., Correale, L., Meijer, S.L., Hertogh, G. de, Bergman, J.J., Hassan, C., and Bisschops, R.

Abstract

01 april 2023, Item does not contain fulltext, BACKGROUND: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB. METHODS: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques. RESULTS: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB (P = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively. CONCLUSIONS: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality.

Published
2023

17. Curriculum for bariatric endoscopy and endoscopic treatment of the complications of bariatric surgery: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement

Author

Boskoski, Ivo, Pontecorvi, Valerio, Ibrahim, M., Huberty, V., Maselli, R., Gölder, S. K., Kral, J., Samanta, J., Patai, Á. V., Haidry, R., Hollenbach, M., Pérez-Cuadrado-Robles, E., Silva, Matteo, Messmann, H., Tham, T. C., Bisschops, R., Boskoski I. (ORCID:0000-0001-8194-2670), Pontecorvi V., Silva M., Boskoski, Ivo, Pontecorvi, Valerio, Ibrahim, M., Huberty, V., Maselli, R., Gölder, S. K., Kral, J., Samanta, J., Patai, Á. V., Haidry, R., Hollenbach, M., Pérez-Cuadrado-Robles, E., Silva, Matteo, Messmann, H., Tham, T. C., Bisschops, R., Boskoski I. (ORCID:0000-0001-8194-2670), Pontecorvi V., and Silva M.

Abstract

Main recommendations Obesity is a chronic, relapsing, degenerative, multifactorial disease that is associated with many co-morbidities. The global increasing burden of obesity has led to calls for an urgent need for additional treatment options. Given the rapid expansion of bariatric endoscopy and bariatric surgery across Europe, the European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. This curriculum is set out in terms of the prerequisites prior to training, minimum number of procedures, the steps for training and quality of training, and how competence should be defined and evidenced before independent practice. 1 ESGE recommends that every endoscopist should have achieved competence in upper gastrointestinal endoscopy before commencing training in bariatric endoscopy and the endoscopic treatment of bariatric surgical adverse events. 2 Trainees in bariatric endoscopy and the endoscopic treatment of the complications of bariatric surgery should have basic knowledge of the definition, classification, and social impact of obesity, its pathophysiology, and its related co-morbidities. The recognition and management of gastrointestinal diseases that are more common in patients with obesity, along with participation in multidisciplinary teams where obese patients are evaluated, are mandatory. 3 ESGE recommends that competency in bariatric endoscopy and the endoscopic treatment of the complications of bariatric surgery can be learned by attending validated training courses on simulators initially, structured training courses, and then hands-on training in tertia

Published
2023

18. Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

Author

Noble, F., Lloyd, M. A., Turkington, R., Griffiths, E., OʼDonovan, M., OʼNeill, J. R., Mercer, S., Parsons, S. L., Fitzgerald, R. C., Underwood, T. J., Noorani, A., Fels Elliott, R., Abdullahi, Z., de la Rue, R., Bornschein, J., MacRae, S., Nutzinger, B., Grehan, N., Contino, G., Crawte, J., Edwards, P. A. W., Miremadi, A., Malhotra, S., Hayden, A., Walker, R., Peters, C., Hannah, G., Hardwick, R., Davies, J., Ford, H., Gilligan, D., Safranek, P., Hindmarsh, A., Sujendran, V., Carroll, N., McManus, D., Hayes, S. J., Ang, Y., Preston, S. R., Oakes, S., Bagwan, I., Skipworth, R. J. E., Save, V., Hupp, T. R., Puig, S., Bedford, M., Taniere, P., Whiting, J., Byrne, J., Kelly, J., Owsley, J., Crichton, C., Barr, H., Shepherd, N., Old, O., Lagergren, J., Gossage, J., Davies, A., Chang, F., Zylstra, J., Sanders, G., Berrisford, R., Harden, C., Bunting, D., Lewis, M., Cheong, E., Kumar, B., Saunders, J. H., Soomro, I. N., Vohra, R., Duffy, J., Kaye, P., Grabowska, A., Lovat, L., Haidry, R., Eneh, V., Igali, L., Welch, I., Scott, M., Sothi, S., Suortamo, S., Lishman, S., Beardsmore, D., Sutaria, R., Secrier, M., Eldridge, M.D., Bower, L., Lynch, A. G., and Tavaré, S.

Published
2017
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19. Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study)

Author

van Baar, A. C. G., Deviere, J., Hopkins, D., Crenier, L., Holleman, F., Galvao Neto, M. P., Becerra, P., Vignolo, P., Rodriguez Grunert, L., Mingrone, Geltrude, Costamagna, Guido, Nieuwdorp, M., Guidone, Caterina, Haidry, R. J., Hayee, B., Magee, C., Carlos Lopez-Talavera, J., White, K., Bhambhani, V., Cozzi, E., Rajagopalan, H., J. G. H. M. Bergman, J., Mingrone G. (ORCID:0000-0003-2021-528X), Costamagna G. (ORCID:0000-0002-8100-2731), Guidone C., van Baar, A. C. G., Deviere, J., Hopkins, D., Crenier, L., Holleman, F., Galvao Neto, M. P., Becerra, P., Vignolo, P., Rodriguez Grunert, L., Mingrone, Geltrude, Costamagna, Guido, Nieuwdorp, M., Guidone, Caterina, Haidry, R. J., Hayee, B., Magee, C., Carlos Lopez-Talavera, J., White, K., Bhambhani, V., Cozzi, E., Rajagopalan, H., J. G. H. M. Bergman, J., Mingrone G. (ORCID:0000-0003-2021-528X), Costamagna G. (ORCID:0000-0002-8100-2731), and Guidone C.

Abstract

Aims: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. Materials and Methods: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5–10.0% (58–86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). Results: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. Conclusions: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

Published
2022

20. Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: The randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial

Author

Mingrone, Geltrude, Van Baar, A. C. G., Deviere, J., Hopkins, D., Moura, E., Cercato, C., Rajagopalan, H., Lopez-Talavera, J. C., White, K., Bhambhani, V., Costamagna, Guido, Haidry, R., Grecco, E., Galvao Neto, M., Aithal, G., Repici, A., Hayee, B., Haji, A., Morris, A. J., Bisschops, R., Chouhan, M. D., Sakai, N. S., Bhatt, D. L., Sanyal, A. J., Bergman, J. J. G. H. M., Mingrone G. (ORCID:0000-0003-2021-528X), Costamagna G. (ORCID:0000-0002-8100-2731), Mingrone, Geltrude, Van Baar, A. C. G., Deviere, J., Hopkins, D., Moura, E., Cercato, C., Rajagopalan, H., Lopez-Talavera, J. C., White, K., Bhambhani, V., Costamagna, Guido, Haidry, R., Grecco, E., Galvao Neto, M., Aithal, G., Repici, A., Hayee, B., Haji, A., Morris, A. J., Bisschops, R., Chouhan, M. D., Sakai, N. S., Bhatt, D. L., Sanyal, A. J., Bergman, J. J. G. H. M., Mingrone G. (ORCID:0000-0003-2021-528X), and Costamagna G. (ORCID:0000-0002-8100-2731)

Abstract

Objective: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). Design: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. Results: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. Conclusions: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease

Published
2022

21. OVERSTITCHTM ENDOSCOPIC SUTURING SYSTEM FOR GASTROINTESTINAL APPLICATIONS: INITIAL RESULTS FROM A PROSPECTIVE MULTICENTER EUROPEAN REGISTRY

Author

Maselli, R., additional, Palma, R., additional, Traina, M., additional, Granata, A., additional, Juzgado, D., additional, Bisello, M., additional, Neuhaus, H., additional, Beyna, T., additional, Bansi, D., additional, Prades, L., additional, Bhandari, P., additional, Abdelrahim, M., additional, Haji, A., additional, Gubbiotti, A., additional, Haidry, R., additional, and Repici, A., additional

Published
2022
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22. ENDOSCOPIC FOLLOW-UP OF RADICALLY RESECTED SUBMUCOSAL ADENOCARCINOMA IN BARRETT’S ESOPHAGUS: EARLY RESULTS OF AN ONGOING PROSPECTIVE, INTERNATIONAL, MULTICENTER COHORT REGISTRY (PREFER TRIAL)

Author

Chan, M.W., additional, Nieuwenhuis, E.A., additional, Jansen, M., additional, Belghazi, K., additional, Nagengast, W.B., additional, Westerhof, J., additional, Koch, A.D., additional, Spaander, M.D.W., additional, Bisschops, R., additional, De Hertogh, G., additional, Bourke, M.J., additional, Neuhaus, H., additional, Weusten, B.L.A.M., additional, Alkhalaf, A., additional, Pech, O., additional, Schlag, C., additional, Seewald, S., additional, Houben, M.H.M.G., additional, Schoon, E.J., additional, Coron, E., additional, Haidry, R., additional, Messmann, H., additional, Meijer, S.L., additional, Bergman, J.J.G.H.M., additional, and Pouw, R.E., additional

Published
2022
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23. COMPUTER AIDED DIAGNOSIS FOR THE CHARACTERISATION OF DYSPLASIA IN BARRETT’S ESOPHAGUS WITH MAGNIFICATION ENDOSCOPY ON I-SCAN IMAGING

Author

Hussein, M., additional, Lines, D., additional, González-Bueno Puyal, J., additional, Bowman, N., additional, Sehgal, V., additional, Toth, D., additional, Everson, M., additional, Ahmad, O., additional, Kader, R., additional, Esteban, J.M., additional, Bischopps, R., additional, Banks, M., additional, Haefner, M., additional, Mountney, P., additional, Stoyanov, D., additional, Lovat, L., additional, and Haidry, R., additional

Published
2022
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24. Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction

Author

Bornschein, J, Wernisch, L, Secrier, M, Miremadi, A, Perner, J, MacRae, S, O'Donovan, M, Newton, R, Menon, S, Bower, L, Eldridge, MD, Devonshire, G, Cheah, C, Turkington, R, Hardwick, RH, Selgrad, M, Venerito, M, Malfertheiner, P, Fitzgerald, RC, Noorani, A, Elliott, RF, Edwards, PAW, Grehan, N, Nutzinger, B, Crawte, J, Chettouh, H, Contino, G, Li, X, Gregson, E, Zeki, S, De la Rue, R, Malhotra, S, Tavare, S, Lynch, AG, Smith, ML, Davies, J, Crichton, C, Carroll, N, Safranek, P, Hindmarsh, A, Sujendran, V, Hayes, SJ, Ang, Y, Preston, SR, Oakes, S, Bagwan, I, Save, V, Skipworth, RJE, Hupp, TR, O'Neill, JR, Tucker, O, Beggs, A, Taniere, P, Puig, S, Underwood, TJ, Noble, F, Owsley, J, Barr, H, Shepherd, N, Old, O, Lagergren, J, Gossage, J, Davies, A, Chang, F, Zylstra, J, Goh, V, Ciccarelli, FD, Sanders, G, Berrisford, R, Harden, C, Bunting, D, Lewis, M, Cheong, E, Kumar, B, Parsons, SL, Soomro, I, Kaye, P, Saunders, J, Lovat, L, Haidry, R, Eneh, V, Igali, L, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Hanna, GB, Peters, CJ, and Grabowska, A

Subjects
Oncology, Cancer Research, Esophageal Neoplasms, esophageal adenocarcinoma, gastroesophageal junction, SUBTYPES, Transcriptome, Molecular Cancer Biology, 0302 clinical medicine, Gene expression, Prospective Studies, BILE-ACIDS, SIGNATURE, Prognosis, Immunohistochemistry, Phenotype, medicine.anatomical_structure, 030220 oncology & carcinogenesis, OCCAMS Consortium, Adenocarcinoma, Esophagogastric Junction, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, Biology, CLASSIFICATION, Siewert classification, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Stomach Neoplasms, Internal medicine, gene expression profiling, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Esophagus, Science & Technology, Anatomical location, IDENTIFICATION, Gene Expression Profiling, gastric cancer, PATHWAYS, medicine.disease, Gene expression profiling, ESOPHAGUS, GASTRIC-CANCER
Abstract

Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed., What's new? Adenocarcinomas that arise at the junction between the esophagus and the stomach are currently classified based on location. Here, the authors looked at patterns of gene expression of these cancers. They found that gastro‐esophageal junction adenocarcinomas can be sorted into three biological subtypes, independent of location, based on gene expression. Group 1 cancers have boosted stomach‐specific genes that combat the effects of acid reflux. Group 2 tumors express genes characteristic to the intestinal tract, and the genes active in Group 3 relate to inflammation. The differences in biological pathway expression means that these differences could be used to improve treatment.

Published
2019

25. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrettʼs oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry

Author

Haidry, R J, Butt, M A, Dunn, J M, Gupta, A, Lipman, G, Smart, H L, Bhandari, P, Smith, L, Willert, R, Fullarton, G, Di Pietro, M, Gordon, C, Penman, I, Barr, H, Patel, P, Kapoor, N, Hoare, J, Narayanasamy, R, Ang, Y, Veitch, A, Ragunath, K, Novelli, M, Lovat, L B, Banks, Matthew, Sehgal, Vinay, Graham, David, Sweis, Rami, Miah, Haroon, Morris, Danielle, Morris, John, Boger, Philip, OʼToole, Dermot, Cheong, Edward, Direkze, Natalie, Dhar, Anjan, Nylander, David, and Mahon, Brinder

Published
2015
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32. Revising the European Society of Gastrointestinal Endoscopy (ESGE) research priorities: a research progress update

Author

Bhandari, P., Longcroft-Wheaton, G., Libanio, D., Pimentel-Nunes, P., Albeniz, E., Pioche, M., Sidhu, R., Spada, C., Anderloni, A., Repici, A., Haidry, R., Barthet, M., Neumann, H., Antonelli, G., Testoni, A., Ponchon, T., Siersema, P.D., Fuccio, L., Hassan, C., Dinis-Ribeiro, M., Bhandari, P., Longcroft-Wheaton, G., Libanio, D., Pimentel-Nunes, P., Albeniz, E., Pioche, M., Sidhu, R., Spada, C., Anderloni, A., Repici, A., Haidry, R., Barthet, M., Neumann, H., Antonelli, G., Testoni, A., Ponchon, T., Siersema, P.D., Fuccio, L., Hassan, C., and Dinis-Ribeiro, M.

Abstract

Contains fulltext : 235679.pdf (Publisher’s version ) (Closed access), BACKGROUND: One of the aims of the European Society of Gastrointestinal Endoscopy (ESGE) is to encourage high quality endoscopic research at a European level. In 2016, the ESGE research committee published a set of research priorities. As endoscopic research is flourishing, we aimed to review the literature and determine whether endoscopic research over the last 4 years had managed to address any of our previously published priorities. METHODS: As the previously published priorities were grouped under seven different domains, a working party with at least two European experts was created for each domain to review all the priorities under that domain. A structured review form was developed to standardize the review process. The group conducted an extensive literature search relevant to each of the priorities and then graded the priorities into three categories: (1) no longer a priority (well-designed trial, incorporated in national/international guidelines or adopted in routine clinical practice); (2) remains a priority (i. e. the above criterion was not met); (3) redefine the existing priority (i. e. the priority was too vague with the research question not clearly defined). RESULTS: The previous ESGE research priorities document published in 2016 had 26 research priorities under seven domains. Our review of these priorities has resulted in seven priorities being removed from the list, one priority being partially removed, another seven being redefined to make them more precise, with eleven priorities remaining unchanged. This is a reflection of a rapid surge in endoscopic research, resulting in 27 % of research questions having already been answered and another 27 % requiring redefinition. CONCLUSIONS: Our extensive review process has led to the removal of seven research priorities from the previous (2016) list, leaving 19 research priorities that have been redefined to make them more precise and relevant for researchers and funding bodies to target.

Published
2021

33. The Clinical Relevance of Manometric Esophagogastric Junction Outflow Obstruction Can Be Determined Using Rapid Drink Challenge and Solid Swallows

Author

Sanagapalli, S, McGuire, J, Leong, RW, Patel, K, Raeburn, A, Abdul-Razakq, H, Plumb, A, Banks, M, Haidry, R, Lovat, L, Sehgal, V, Graham, D, Sami, SS, Sweis, R, Sanagapalli, S, McGuire, J, Leong, RW, Patel, K, Raeburn, A, Abdul-Razakq, H, Plumb, A, Banks, M, Haidry, R, Lovat, L, Sehgal, V, Graham, D, Sami, SS, and Sweis, R

Abstract

INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO. METHODS: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated. RESULTS: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02). DISCUSSION: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol.

Published
2021

34. Outcomes of different treatment approaches after R0 endoscopic resection of high-risk T1 esophageal adenocarcinoma: An international multicentre retrospective cohort study.

Author

Chan, M. W., Haidry, R., Benjamin, N., Di Pietro, M., Hadjinicolaou, A. V., Barret, M., Doumbe-Mandengue, P., Seewald, S., Bisschops, R., Nafteux, P., Bourke, M. J., Gupta, S., Mundre, P., Lemmers, A., Vuckovic, C., Pech, O., Leclercq, P., Coron, E., Meijer, S., and Bergman, J.

Subjects
*ENDOSCOPIC surgery, *COHORT analysis, *ADENOCARCINOMA, *RETROSPECTIVE studies
Abstract

This article discusses the outcomes of different treatment approaches after R0 endoscopic resection (ER) of high-risk T1 esophageal adenocarcinoma (EAC). The study aimed to assess the outcomes following R0 ER for high-risk T1 EAC, specifically looking at the risk of lymph node metastases (N+). The study found that the majority of cases with surgical T1 had ER misclassified as R0, challenging previous studies that reported higher N+ rates. The results suggest that surgery is not a definitive curative approach and did not improve disease-specific mortality. Further research is needed to evaluate outcomes in patients treated endoscopically for high-risk T1 EAC. [Extracted from the article]

Published
2024
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35. Deep Neural Network for the Localisation of Early Neoplasia in Barrett’s Oesophagus with Targeted Biopsies

Author

Hussein, M, additional, Puyal, JG-B, additional, Lines, D, additional, Sehgal, V, additional, Toth, D, additional, Everson, M, additional, Lipman, G, additional, Ahmad, O, additional, Kader, R, additional, Esteban, JM, additional, Bisschops, R, additional, Banks, M, additional, Haefner, M, additional, Mountney, P, additional, Stoyanov, D, additional, Lovat, L, additional, and Haidry, R, additional

Published
2021
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36. Computer Aided Diagnosis for the Characterisation of Dysplasia in Barrett’s Oesophagus with Magnification Endoscopy

Author

Hussein, M, additional, Lines, D, additional, Puyal, JGB, additional, Bowman, N, additional, Sehgal, V, additional, Toth, D, additional, Everson, M, additional, Ahmad, O, additional, Kader, R, additional, Esteban, JM, additional, Bisschops, R, additional, Banks, M, additional, Haefner, M, additional, Mountney, P, additional, Stoyanov, D, additional, Lovat, L, additional, and Haidry, R, additional

Published
2021
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37. Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus

Author

Knight, William R.C., primary, McEwen, Ricardo, additional, Byrne, Ben E., additional, Habib, Wais, additional, Bott, Rebecca, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Gossage, James A., additional, Fitzgerald, R.C., additional, Noorani, A., additional, Edwards, P.A.W., additional, Grehan, N., additional, Nutzinger, B., additional, Hughes, C., additional, Fidziukiewicz, E., additional, MacRae, S., additional, Northrop, A., additional, Contino, G., additional, Li, X., additional, de la Rue, R., additional, Katz-Summercorn, A., additional, Abbas, S., additional, Loureda, D., additional, O'Donovan, M., additional, Miremadi, A., additional, Malhotra, S., additional, Tripathi, M., additional, Tavaré, S., additional, Lynch, A.G., additional, Eldridge, M., additional, Secrier, M., additional, Devonshire, G., additional, Perner, J., additional, Jammula, S., additional, Davies, J., additional, Crichton, C., additional, Carroll, N., additional, Safranek, P., additional, Hindmarsh, A., additional, Sujendran, V., additional, Hayes, S.J., additional, Ang, Y., additional, Sharrocks, A., additional, Preston, S.R., additional, Oakes, S., additional, Bagwan, I., additional, Save, V., additional, Skipworth, R.J.E., additional, Hupp, T.R., additional, O'Neill, J.R., additional, Tucker, O., additional, Beggs, A., additional, Taniere, P., additional, Puig, S., additional, Underwood, T.J., additional, Walker, R.C., additional, Grace, B.L., additional, Barr, H., additional, Shepherd, N., additional, Old, O., additional, Lagergren, J., additional, Davies, A., additional, Chang, F., additional, Goh, V., additional, Ciccarelli, F.D., additional, Sanders, G., additional, Berrisford, R., additional, Harden, C., additional, Lewis, M., additional, Cheong, E., additional, Kumar, B., additional, Parsons, S.L., additional, Soomro, I., additional, Kaye, P., additional, Saunders, J., additional, Lovat, L., additional, Haidry, R., additional, Igali, L., additional, Scott, M., additional, Sothi, S., additional, Suortamo, S., additional, Lishman, S., additional, Hanna, G.B., additional, Moorthy, K., additional, Peters, C.J., additional, Grabowska, A., additional, Turkington, R., additional, McManus, D., additional, Coleman, H., additional, Khoo, D., additional, and Fickling, W., additional

Published
2020
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40. OVERSTITCH SX ENDOSCOPIC SUTURING SYSTEM FOR GASTROINTESTINAL APPLICATIONS: A MULTICENTER EUROPEAN REGISTRY

Author

Maselli, R, additional, Palma, R, additional, Traina, M, additional, Granata, A, additional, Juzgado, D, additional, Bisello, M, additional, Neuhaus, H, additional, Beyna, T, additional, Bansi, D, additional, Prades, L, additional, Bhandari, P, additional, Abdelrahim, M, additional, Haji, A, additional, Haidry, R, additional, and Repici, A, additional

Published
2020
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41. WATS3D FOR THE DETECTION OF HIGH GRADE DYSPLASIA AND ADENOCARCINOMA IN BARRETT: EUROPEAN MULTI-CENTER, PROSPECTIVE, RANDOMIZED, TANDEM STUDY

Author

Bisschops, R, additional, Haidry, R, additional, Messmann, H, additional, Ragunath, K, additional, Bhandari, P, additional, Repici, A, additional, Munoz-Navas, M, additional, Seewald, S, additional, Lemmers, A, additional, Castells, A, additional, Pech, O, additional, Schoon, E, additional, Kariv, R, additional, Neuhaus, H, additional, Weusten, B, additional, Siersema, P, additional, Correale, L, additional, Fromowitz, F, additional, Hertogh, GD, additional, Bergman, J, additional, and Hassan, C, additional

Published
2020
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42. Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Author

Mourikis, TP, Benedetti, L, Foxall, E, Temelkovski, D, Nulsen, J, Perner, J, Cereda, M, Lagergren, J, Howell, M, Yau, C, Fitzgerald, RC, Scaffidi, P, Noorani, A, Edwards, PAW, Elliott, RF, Grehan, N, Nutzinger, B, Hughes, C, Fidziukiewicz, E, Bornschein, J, MacRae, S, Crawte, J, Northrop, A, Contino, G, Li, X, De la Rue, R, Katz-Summercorn, A, Abbas, S, Loureda, D, O'Donovan, M, Miremadi, A, Malhotra, S, Tripathi, M, Tavare, S, Lynch, AG, Eldridge, M, Secrier, M, Bower, L, Devonshire, G, Jammula, S, Davies, J, Crichton, C, Carroll, N, Safranek, P, Hindmarsh, A, Sujendran, V, Hayes, SJ, Ang, Y, Sharrocks, A, Preston, SR, Oakes, S, Bagwan, I, Save, V, Skipworth, RJE, Hupp, TR, O'Neill, JR, Tucker, O, Beggs, A, Taniere, P, Puig, S, Underwood, TJ, Walker, RC, Grace, BL, Barr, H, Shepherd, N, Old, O, Gossage, J, Davies, A, Chang, F, Zylstra, J, Mahadeva, U, Goh, V, Sanders, G, Berrisford, R, Harden, C, Lewis, M, Cheong, E, Kumar, B, Parsons, SL, Soomro, I, Kaye, P, Saunders, J, Lovat, L, Haidry, R, Igali, L, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Hanna, GB, Peters, CJ, Moorthy, K, Grabowska, A, Turkington, R, McManus, D, Khoo, D, Fickling, W, Ciccarelli, FD, Mourikis, Thanos P. [0000-0002-8026-8837], Foxall, Elizabeth [0000-0003-1995-5547], Scaffidi, Paola [0000-0002-3642-4193], and Apollo - University of Cambridge Repository

Subjects
EXPRESSION, SELECTION, 631/67, DATABASE, PROTEIN, 38/90, 631/67/69, 13/109, VARIANTS, 13/44, GERMLINE, MD Multidisciplinary, 38/23, 38/22, 38/88, Science & Technology, 631/67/1504/1477, article, Multidisciplinary Sciences, 13/31, BARRETTS-ESOPHAGUS, REPLICATION, PATTERNS, 38/77, Science & Technology - Other Topics, UPDATE, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Abstract

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.

Published
2019

43. Reply to Dong et al

Author

Walter, D., Berg, M.W. van den, Hirdes, M.M., Vleggaar, F.P., Repici, A., Deprez, P.H., Viedma, B.L., Lovat, L.B., Weusten, B.L., Bisschops, R., Haidry, R., Ferrara, E., Sanborn, K.J., O'Leary, E.E., Hooft, Jeanin E. van, Siersema, P.D., Walter, D., Berg, M.W. van den, Hirdes, M.M., Vleggaar, F.P., Repici, A., Deprez, P.H., Viedma, B.L., Lovat, L.B., Weusten, B.L., Bisschops, R., Haidry, R., Ferrara, E., Sanborn, K.J., O'Leary, E.E., Hooft, Jeanin E. van, and Siersema, P.D.

Abstract

Item does not contain fulltext

Published
2019

44. First Clinical Application of a Novel Duodenal Mucosal Ablation Device for Type 2 Diabetes Using Radiofrequency Vapor Ablation: A Video-Case.

Author

Papaefthymiou, A., Benjamin, N., Hoebel, P., Grunert, L., and Haidry, R.

Subjects
TYPE 2 diabetes, CATHETER ablation, CLINICAL medicine, ATRIAL flutter
Abstract

This article discusses the first clinical application of a new duodenal mucosal ablation device for the management of type 2 diabetes (T2D). The device, called the circumferential radiofrequency (RF) vapor ablation system, is currently being evaluated in a first-in-human clinical trial. The article presents a case study of a patient with poorly controlled T2D who underwent the procedure using a double-channel upper endoscope. The results from the ongoing clinical trial will provide valuable information about the safety and efficacy of this new intervention for T2D. [Extracted from the article]

Published
2024
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45. A multicentre retrospective cohort study to compare the safety and efficacy of zenker per-oral endoscopic myotomy, flexible diverticulotomy, and rigid diverticulotomy for the management of zenker's diverticulum.

Author

Norton, B., Siggens, K., Papaefthymiou, A., Telese, A., Duku, M., Murino, A., Murray, C., Johnson, G., Mohammadi, B., Mughal, M., Bisschops, R., Bhandari, P., Birchall, M., and Haidry, R.

Subjects
DIVERTICULUM, MYOTOMY, COHORT analysis
Abstract

A multicentre retrospective cohort study compared the safety and efficacy of three different treatments for Zenker's diverticulum (ZD): Zenker per-oral endoscopic myotomy (Z-POEM), flexible diverticulotomy (FD), and rigid surgical diverticulotomy (RD). The study found that all three treatments were effective in managing ZD, with equivalent rates of success during follow-up. However, the technical success of RD was significantly lower than the flexible techniques, which often resulted in an open myotomy associated with poor clinical outcomes. Therefore, the study suggests that minimally invasive flexible techniques, such as Z-POEM and FD, could be considered as the primary therapy for ZD due to their better access, control, high success rates, and low adverse events. [Extracted from the article]

Published
2024
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46. The landscape of selection in 551 Esophageal Adenocarcinomas defines genomic biomarkers for the clinic

Author

Frankell, AM, Jammula, S, Li, X, Contino, G, Killcoyne, S, Abbas, S, Perner, J, Bower, L, Devonshire, G, Cocks, E, Grehan, N, Mok, J, O'Donovan, M, MacRae, S, Eldridge, MD, Tavare, S, Fitzgerald, RC, Noorani, A, Edwards, PAW, Grehanl, N, Nutzinger, B, Hughes, CI, Fidziukiewicz, E, Northrop, A, De la Rue, R, Katz-Summercorn, A, Loureda, D, Miremadi, A, Malhotra, S, Tripathi, M, Lynch, AG, Eldridge, M, Secrier, M, Davies, J, Crichton, C, Carro, N, Safranek, P, Hindmarsh, A, Sujendran, V, Hayes, SJ, Ang, Y, Sharrocks, A, Preston, SR, Oakes, S, Bagwan, I, Save, V, Skipworth, RJE, Hupp, TR, ONeill, JR, Tucker, O, Beggs, A, Taniere, P, Puig, S, Underwood, T, Walker, RC, Grace, BL, Barr, H, Shepherd, N, Old, O, Lagergren, J, Gossage, J, Davies, A, Chang, F, Zylstra, J, Mahadeva, U, Goh, V, Ciccarelli, FD, Sanders, G, Berrisford, R, Harden, C, Lewis, M, Cheong, E, Kumar, B, Parsons, SL, Soomro, I, Kaye, P, Saunders, J, Lovat, L, Haidry, R, Igali, L, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Hanna, GB, Moorthy, K, Peters, CJ, Grabowska, A, Turkington, R, McManus, D, Coleman, H, Khoo, D, and Fickling, W

Subjects
Male, Oncology, Mutation rate, Esophageal Neoplasms, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Exome, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Mutation, GATA4, Incidence (epidemiology), Genomics, CANCER, Cell Cycle Gene, Gene Expression Regulation, Neoplastic, Cohort, Adenocarcinoma, Female, Life Sciences & Biomedicine, Silent mutation, medicine.medical_specialty, CARCINOMA, DNA Copy Number Variations, Biology, Article, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Genetics, Carcinoma, medicine, Humans, Gene, SIGNATURES, 030304 developmental biology, Science & Technology, Gene Expression Profiling, PATHWAYS, Cancer, SOMATIC MUTATIONS, 06 Biological Sciences, medicine.disease, COMPREHENSIVE MOLECULAR CHARACTERIZATION, PD-1 BLOCKADE, Gene expression profiling, PATTERNS, DRIVER, Cancer research, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, 030217 neurology & neurosurgery, ACQUIRED-RESISTANCE, Developmental Biology
Abstract

Esophageal Adenocarcinoma (EAC) is a poor prognosis cancer type with rapidly rising incidence. Our understanding of genetic events which drive EAC development is limited and there are few molecular biomarkers for prognostication or therapeutics. We have accumulated a cohort of 551 genomically characterised EACs (73% WGS and 27% WES) with clinical annotation and matched RNA-seq. Using a variety of driver gene detection methods, we discover 77 EAC driver genes (73% novel) and 21 non-coding driver elements (95% novel), and describe mutation and CNV types with specific functional impact. We identify a mean of 4.4 driver events per case derived from both copy number events and mutations. We compare driver mutation rates to the exome-wide mutational excess calculated using Non-synonymous vs Synonymous mutation rates (dNdS). We observe mutual exclusivity or co-occurrence of events within and between a number of EAC pathways (GATA factors, Core Cell cycle genes, TP53 regulators and the SWI/SNF complex) suggestive of important functional relationships. These driver variants correlate with tumour differentiation, sex and prognosis. Poor prognostic indicators (SMAD4, GATA4) are verified in independent cohorts with significant predictive value. Over 50% of EACs contain sensitising events for CDK4/6 inhibitors which are highly correlated with clinically relevant sensitivity in a panel EAC cell lines and organoids.

Published
2018

47. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry

Author

Haidry, R J, Butt, M A, Dunn, J M, Gupta, A, Lipman, G, Smart, H L, Bhandari, P, Smith, L, Willert, R, Fullarton, G, Di Pietro, M, Gordon, C, Penman, I, Barr, H, Patel, P, Kapoor, N, Hoare, J, Narayanasamy, R, Ang, Y, Veitch, A, Ragunath, K, Novelli, M, and Lovat, L B

Subjects
Adult, Male, Time Factors, Esophageal Neoplasms, Adenocarcinoma, Barrett Esophagus, Humans, Prospective Studies, Registries, BARRETT'S OESOPHAGUS, OESOPHAGEAL CANCER, Aged, Aged, 80 and over, Middle Aged, United Kingdom, Oesophagus, surgical procedures, operative, Treatment Outcome, ENDOSCOPIC PROCEDURES, Catheter Ablation, Disease Progression, Female, Esophagoscopy, Precancerous Conditions, Follow-Up Studies
Abstract

Background Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. Methods We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008–2010 and 2011–2013). Durability of successful treatment and progression to OAC were also evaluated. Results 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p

Published
2014

49. Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1

Author

Garcia, E, Hayden, A, Birts, C, Britton, E, Cowie, A, Pickard, K, Mellone, M, Choh, C, Derouet, M, Duriez, P, Noble, F, White, MJ, Primrose, JN, Strefford, JC, Rose-Zerilli, M, Thomas, GJ, Ang, Y, Sharrocks, AD, Fitzgerald, RC, Underwood, TJ, MacRae, S, Grehan, N, Abdullahi, Z, De la Rue, R, Noorani, A, Elliott, RF, De Silva, N, Bornschein, J, O’Donovan, M, Contino, G, Yang, T-P, Chettouh, H, Crawte, J, Nutzinger, B, Edwards, PAW, Smith, L, Miremadi, A, Malhotra, S, Cluroe, A, Hardwick, R, Davies, J, Ford, H, Gilligan, D, Safranek, P, Hindmarsh, A, Sujendran, V, Carroll, N, Turkington, R, Hayes, SJ, Preston, SR, Oakes, S, Bagwan, I, Save, V, Skipworth, RJE, Hupp, TR, O’Neill, JR, Tucker, O, Taniere, P, Owsley, J, Crichton, C, Schusterreiter, C, Barr, H, Shepherd, N, Old, O, Lagergren, J, Gossage, J, Davies, A, Chang, F, Zylstra, J, Sanders, G, Berrisford, R, Harden, C, Bunting, D, Lewis, M, Cheong, E, Kumar, B, Parsons, SL, Soomro, I, Kaye, P, Saunders, J, Lovat, L, Haidry, R, Eneh, V, Igali, L, Welch, I, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Beardsmore, D, Anderson, C, Smith, ML, Secrier, M, Eldridge, MD, Bower, L, Achilleos, A, Lynch, AG, and Tavare, S

Abstract

New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A, not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.

Published
2016

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