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1. Reply to Eker et al. Comment on Kilian et al. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. J. Clin. Med. 2023, 12, 2704.

Author

Kilian, Alexandra, Latino, Giuseppe, White, Andrew, Ratjen, Felix, McDonald, Jamie, Whitehead, Kevin, Gossage, James, Krings, Timo, Lawton, Michael, Kim, Helen, and Faughnan, Marie

Abstract

We are grateful to Eker et al. for their thoughtful analysis and response to our publication titled Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT [...].

Published
2023

2. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT

Author

Kilian, Alexandra, Latino, Giuseppe A, White, Andrew J, Ratjen, Felix, McDonald, Jamie, Whitehead, Kevin J, Gossage, James R, Krings, Timo, Lawton, Michael T, Kim, Helen, Faughnan, Marie E, and Group, The Brain Vascular Malformation Consortium HHT Investigator

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pediatric Research Initiative, Hematology, Congenital Structural Anomalies, Rare Diseases, Orphan Drug, Prevention, Pediatric, Clinical Research, Brain Disorders, Neurosciences, hereditary hemorrhagic telangiectasia, pediatrics, brain vascular malformation, embolization, gamma knife, surgery, intracranial hemorrhage, screening, Biomedical and clinical sciences
Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterized by the development of vascular malformations (VMs) in organs such as the brain and lungs, as well as telangiectases on mucosal surfaces. Prophylactic treatment of organ VMs may prevent potential complications, such as hemorrhage. However, brain VM treatment-surgical resection, embolization, and/or radiosurgery-is not recommended for all patients due to the associated risks. Given the scarcity of data regarding HHT-related brain VM presentation and treatment trends in pediatric patients, we aim to describe the clinical presentations and the patterns of treatment of HHT-related brain VMs in a pediatric cohort, and compare pediatric trends to those of adults. Demographic and clinical data were analyzed in 114 pediatric patients with HHT-related brain VMs and compared with a cohort of 253 adult patients enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. Our data demonstrated that a higher proportion of pediatric patients with HHT-related brain VMs were symptomatic at presentation (p = 0.004). Moreover, a higher proportion of pediatric patients presented with intracranial hemorrhage (p < 0.001) and seizure (p = 0.002) compared to adult patients. Surgical resection was the most common brain VM treatment modality in both children and adults. We conclude that pediatric patients may be more likely to present with symptoms and complications from brain VMs, supporting the case for screening for brain VMs in children with HHT.

Published
2023

4. Statistical analysis plan for the biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2) study: An international randomised controlled multicentre trial

Author

Wempe, Carola, Storck, Michael, Brix, Tobias, Strauss, Christian, Sadjadi, Mahan, Weiss, Raphael, Booke, Hendrik, Loomann, Lisa, Amini, Wida, Meschede, Dana, Göbel, Ulrich, Haaker, Jan Gerrit, Brenner, Thorsten, Espeter, Florian, Rahmel, Tim, Adamzik, Michael, Brandenburger, Timo, Putensen, Christian, Bode, Christian, Kruse, Philippe, Wild, Lennart, Rosenberger, Peter, Bernard, Alice, Jung-König, Mona, Larmann, Jan, Reutershan, Jörg, Arndt, Christian, Vojnar, Benjamin, Spieth, Peter M., Schneider, Antoine, Monard, Céline, Mura, Benedetta, Villa, Gianluca, Laici, Cristiana, Siniscalchi, Antonio, Capozzi, Chiara, Sita, Marco, Cattin, Lucia, de Rosa, Silvia, Spadaro, Savino, Franco, D'Arcangelo Benito, Ostermann, Marlies, Gossage, James, Verzelloni, Alessandra, Scaramuzzi, Marco, Glass, Adam, Silversides, Jon, Lonsdale, Elliot, Forni, Lui G., Haider, Syeda, Rossiter, Adam, Welters, Ingeborg, Hoste, Eric, Hollmann, Markus W., Ripollés-Melchor, Javier, Fernández-Valdes-Bango, Paula, Parise-Roux, Diego, Martin González, Maria Carmen, Bathal, Irene Romero, Jáuregui, Maider Puyada, Navarro-Perez, Rosalía, De Soto, Inés, García-Álvarez, Raquel, Sánchez, Elena Murcia, Suarez-de-la-Rica, Alejandro, Lalande, Robin, von Groote, Thilo, Danzer, Moritz Fabian, Meersch, Melanie, Zarbock, Alexander, and Gerß, Joachim

Published
2024
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5. Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation

Author

Fitzgerald, Rebecca C., Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Loreno, Christine, Redmond, Aisling M., Abbas, Sujath, Freeman, Adam, Smyth, Elizabeth C., O'Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Cheah, Calvin, Coles, Hannah, Millington, Curtis, Devonshire, Ginny, Eldridge, Matthew, Secrier, Maria, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Hardwick, Richard H., Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Contino, Gianmarco, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Chan, David, Cheong, Ed, Kumar, Bhaskar, Sreedharan, L., Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Scott, Michael, Sothi, Sharmila, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Coleman, Helen, Petty, Russell D., Bartlet, Freddie, O'Neill, J. Robert, Yébenes Mayordomo, Marcos, Mitulović, Goran, Al Shboul, Sofian, Bedran, Georges, Faktor, Jakub, Hernychova, Lenka, Uhrik, Lukas, Gómez-Herranz, Maria, Kocikowski, Mikołaj, Vojtěšek, Bořivoj, Arends, Mark J., Hupp, Ted, and Alfaro, Javier Antonio

Published
2024
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6. Genotype-Phenotype Correlations in Children with HHT.

Author

Kilian, Alexandra, Latino, Giuseppe A, White, Andrew J, Clark, Dewi, Chakinala, Murali M, Ratjen, Felix, McDonald, Jamie, Whitehead, Kevin, Gossage, James R, Lin, Doris, Henderson, Katharine, Pollak, Jeffrey, McWilliams, Justin P, Kim, Helen, Lawton, Michael T, Faughnan, Marie E, and the Brain Vascular Malformation Consortium HHT Investigator Group

Subjects
the Brain Vascular Malformation Consortium HHT Investigator Group, ACVRL1, ENG, Hereditary hemorrhagic telangiectasia, SMAD4, arteriovenous malformation, genotype–phenotype correlation, pediatrics, genotype-phenotype correlation, Clinical Sciences
Abstract

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype-phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype-phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0-18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype-defined as both pulmonary AVMs and brain VMs-was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype-phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.

Published
2020

7. Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia

Author

Faughnan, Marie E, Gossage, James R, Chakinala, Murali M, Oh, S Paul, Kasthuri, Raj, Hughes, Christopher CW, McWilliams, Justin P, Parambil, Joseph G, Vozoris, Nicholas, Donaldson, Jill, Paul, Gitanjali, Berry, Pamela, and Sprecher, Dennis L

Subjects
Biochemistry and Cell Biology, Biological Sciences, Rare Diseases, Hematology, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Female, Hemorrhage, Humans, Indazoles, Male, Middle Aged, Pyrimidines, Sulfonamides, Telangiectasia, Hereditary Hemorrhagic, Telangiectasia, Hereditary, Epistaxis, Anemia, Tyrosine kinase inhibitor, Clinical Sciences, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology
Abstract

Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

Published
2019

9. Serial ctDNA detection using a personalized, tumor-informed assay in esophageal adenocarcinoma patients following resection

Author

Ococks, Emma, Sharma, Shruti, Tian Ng, Alvin Wei, Aleshin, Alexey, Fitzgerald, Rebecca C., Smyth, Elizabeth, Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Fidziukiewicz, Elwira, Redmond, Aisling M., Northrop, Alex, Abbas, Sujath, Smyth, Elizabeth C., O’Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Grantham, Amber, Cheah, Calvin, Coles, Hannah, Flint, Connor, Eldridge, Matthew, Secrier, Maria, Devonshire, Ginny, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Hardwick, Richard H., Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O’Neill, J. Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Contino, Gianmarco, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Chan, David, Cheong, Ed, Kumar, Bhaskar, Sreedharan, L., Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Scott, Michael, Sothi, Sharmila, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Coleman, Helen, and Petty, Russell D.

Published
2021
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11. Management of paraesophageal hiatus hernia

Author

Gerdes, Stephan, Schoppmann, Sebastian F, Bonavina, Luigi, Boyle, Nicholas, Mueller-Stich, Beat P, Gutschow, Christian A, Gisbertz, Suzanne Sarah, Kockerling, Ferdinand, Lehmann, Thorsten G, Lorenz, Dietmar, Granderath, Frank Alexander, Rosati, Riccardo, Wullstein, Christoph, Lundell, Lars, Cheong, Edward, Nafteux, Philippe, Olmi, Stefano, Monig, Stefan, Biebl, Matthias, Leers, Jessica, Zehetner, Joerg, Kristo, Ivan, Berrisford, Richard George, Skrobic, Ognjan M, Simic, Aleksandar P, Pera, Manuel, Grimminger, Peter Philipp, Gockel, Ines, Zarras, Konstantinos, Nieuwenhuijs, Vincent Bernard, Gossage, James A, Henegouwen, Mark I van Berge, Stein, Hubert J, Markar, Sheraz R, Hueting, Willem Eduard, Targarona, Eduardo M, Johansson, Jan, Macaulay, Graeme D, Wijnhoven, Bas PL, Benedix, Frank, Attwood, Stephen E, Hoelscher, Arnulf Heinrich, Priego, Pablo, Fuchs, Karl-Hermann, Luyer, Misha DP, Griffiths, Ewen A, Sovik, Torgeir Thorson, Theodorou, Dimitrios, Sgromo, Bruno, Salo, Jarmo A, Singhal, Rishi, Thorell, Anders, Zaninotto, Giovanni, Itenc, Marko, D'journo, Xavier Benoit, Fullarton, Grant M, Horbach, Thomas, Surgery, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and CCA - Cancer Treatment and quality of life

Subjects
REPAIR, MESH, Hiatus hernia, Mesh, Science & Technology, Fundoplication, Surgical technique, GUIDELINES, Paraesophageal hernia, REFLUX, Surgery, Delphi survey, RECURRENCE, Life Sciences & Biomedicine
Abstract

Aims There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. Methods We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as “recommended” or “discouraged” if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled “acceptable” (neither recommended nor discouraged). Results Seventy-two surgeons with a median (IQR) experience of 23 (14–30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15–36) and 40 (28–60) pHH-surgeries, respectively. After Delphi round 2, “recommended” strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified “discouraged” strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fixation technique) were “acceptable”. Conclusions This multinational European Delphi survey represents the first expert-led process to identify recommended strategies for the management of pHH. Our work may be useful in clinical practice to guide the diagnostic process, increase procedural consistency and standardization, and to foster collaborative research.

Published
2023

12. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Author

Noorani, Ayesha, Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Hughes, Caitriona, Fidziukiewicz, Elwira, Bornschein, Jan, MacRae, Shona, Crawte, Jason, Contino, Gianmarco, Li, Xiaodun, Rue, Rachel de la, O’Donovan, Maria, Miremad, Ahmad, Malhotra, Shalini, Tripathi, Monika, Tavaré, Simon, Lynch, Andy G., Eldridge, Matthew, Secrier, Maria, Bower, Lawrence, Devonshire, Ginny, Perner, Juliane, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O’Neill, J. Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Underwood, Timothy J., Noble, Fergus, Owsley, Jack, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Igali, Laszlo, Scott, Michael, Sothi, Sharmila, Suortamo, Sari, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Grabowska, Anna, Turkington, Richard, Sawas, Tarek, Killcoyne, Sarah, Iyer, Prasad G., Wang, Kenneth K., Smyrk, Thomas C., Kisiel, John B., Qin, Yi, Ahlquist, David A., Rustgi, Anil K., Costa, Rui J., Gerstung, Moritz, Fitzgerald, Rebecca C., and Katzka, David A.

Published
2018
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13. Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: Gene–phenotype correlations

Author

Nishida, Takeo, Faughnan, Marie E, Krings, Timo, Chakinala, Murali, Gossage, James R, Young, William L, Kim, Helen, Pourmohamad, Tony, Henderson, Katharine J, Schrum, Stacy D, James, Melissa, Quinnine, Nancy, Bharatha, Aditya, terBrugge, Karel G, and White, Robert I

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Congenital Structural Anomalies, Hematology, Pediatric, Brain Disorders, Neurosciences, Stroke, Clinical Research, Rare Diseases, Activin Receptors, Type II, Adolescent, Adult, Aged, Antigens, CD, Arteriovenous Fistula, Child, Child, Preschool, Endoglin, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Intracranial Arteriovenous Malformations, Male, Middle Aged, Mutation, Receptors, Cell Surface, Smad4 Protein, Telangiectasia, Hereditary Hemorrhagic, Young Adult, hereditary hemorrhagic telangiectasia, brain arteriovenous malformation, genotype, intracranial hemorrhage, Clinical Sciences, Clinical sciences
Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2-50) and 18 ± 21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT.

Published
2012

14. Extended Wireless pH Monitoring Significantly Increases Gastroesophageal Reflux Disease Diagnoses in Patients With a Normal pH Impedance Study

Author

Zeki, Sebastian S, primary, Miah, Ismail, additional, Visaggi, Pierfrancesco, additional, Wolak, Anna, additional, deSilva, Minerva, additional, Dunn, Jason M, additional, Davies, Andrew, additional, Gossage, James, additional, Botha, Abrie, additional, Sui, Guiping, additional, Jafari, Jafar, additional, and Wong, Terry, additional

Published
2023
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15. Long Term Survival of Heritable Pulmonary Arterial Hypertension Associated with Hereditary Hemorrhagic Telangiectasia: A Case Series.

Author

Jamindar, Parth, Pope, Michael, and Gossage, James

Subjects
HEREDITARY hemorrhagic telangiectasia, PULMONARY arterial hypertension, GENETIC disorders, ARTERIOVENOUS malformation, PULMONARY hypertension, TELANGIECTASIA
Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disease characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. Multiple genetic mutations have been linked to this rare disease, including ENG, ALK1 (ACVRL1), and MADH4. Pulmonary hypertension is a potential complication of HHT, with the most common phenotypes being World Health Organization (WHO) group 1 heritable pulmonary arterial hypertension (PAH), which is typically associated with ALK1 mutation; WHO group 2 pulmonary hypertension due to high output heart failure from hepatic arteriovenous malformations and/or anemia; and WHO group 2 due to high pulmonary artery wedge pressure. There is scarce evidence to help guide treatment of heritable PAH in HHT, and observational literature suggests that patients with HHT and heritable PAH have a worse prognosis compared to patients with idiopathic PAH. We describe the diagnosis, pulmonary hemodynamics, and detailed treatment courses of three patients with ALK1-associated HHT and PAH, who all exhibited objective clinical improvement with parenteral prostacyclins and oral agents. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Preoperative risk factors for conversion from laparoscopic to open cholecystectomy: a validated risk score derived from a prospective U.K. database of 8820 patients

Author

Fenwick, Stephen, Elmasry, Mohamed, Nunes, Quentin, Kennedy, David, Khan, Raja B., Khan, Muhammad A.S., Magee, Conor J., Jones, Steven M., Mason, Denise, Parappally, Ciny P., Mathur, Pawan, Saunders, Michael, Jamel, Sara, Haque, Samer U.l., Zafar, Sara, Shiwani, Muhammad H., Samuel, Nehemiah, Dar, Farooq, Jackson, Andrew, Lovett, Bryony, Dindyal, Shiva, Winter, Hannah, Rahman, Saquib, Wheatley, Kevin, Nieto, Tom, Ayaani, Soofiyah, Youssef, Haney, Nijjar, Rajwinder S., Watkin, Helen, Naumann, David, Emeshi, Sophie, Sarmah, Piyush B., Lee, Kathryn, Joji, Nikita, Heath, Jonathan, Teasdale, Rebecca L., Weerasinghe, Chamindri, Needham, Paul J., Welbourn, Hannah, Forster, Luke, Finch, David, Blazeby, Jane M., Robb, William, McNair, Angus G.K., Hrycaiczuk, Alex, Charalabopoulos, Alexandros, Kadirkamanathan, Sritharan, Tang, Cheuk-Bong, Jayanthi, Naga V.G., Noor, Nigel, Dobbins, Brian, Cockbain, Andrew J., Nilsen-Nunn, April, de Siqueira, Jonathan, Pellen, Mike, Cowley, Jonathan B., Ho, Wei-Min, Miu, Victor, White, Timothy J., Hodgkins, Kathryn A., Kinghorn, Alison, Tutton, Matthew G., Al-Abed, Yahya A., Menzies, Donald, Ahmad, Anwar, Reed, Joanna, Khan, Shabuddin, Monk, David, Vitone, Louis J., Murtaza, Ghulam, Joel, Abraham, Brennan, Stephen, Shier, David, Zhang, Catherine, Yoganathan, Thusidaran, Robinson, Steven J., McCallum, Iain J.D., Jones, Michael J., Elsayed, Mohammed, Tuck, Liz, Wayman, John, Carney, Kate, Aroori, Somaiah, Hosie, Kenneth B., Kimble, Adam, Bunting, David M., Fawole, Adeshina S., Basheer, Mohammed, Dave, Rajiv V., Sarveswaran, Janahan, Jones, Elinor, Kendal, Chris, Tilston, Michael P., Gough, Martin, Wallace, Tom, Singh, Shailendra, Downing, Justine, Mockford, Katherine A., Issa, Eyad, Shah, Nayab, Chauhan, Neal, Wilson, Timothy R., Forouzanfar, Amir, Wild, Jonathan R.L., Nofal, Emma, Bunnell, Catherine, Madbak, Khaliel, Rao, Sudhindra T.V., Devoto, Laurence, Siddiqi, Najaf, Khawaja, Zechan, Hewes, James C., Gould, Laura, Chambers, Alice, Rodriguez, Daniel U., Sen, Gourab, Robinson, Stuart, Bartlett, Francis, Rae, David M., Stevenson, Thomas E.J., Sarvananthan, Kas, Dwerryhouse, Simon J., Higgs, Simon M., Old, Oliver J., Hardy, Thomas J., Shah, Reena, Hornby, Steve T., Keogh, Ken, Frank, Lucinda, Al-Akash, Musallam, Upchurch, Emma A., Frame, Richard J., Hughes, Michael, Jelley, Clare, Weaver, Simon, Roy, Sudipta, Sillo, Toritseju O., Galanopoulos, Giorgios, Cuming, Tamzin, Cunha, Pedro, Tayeh, Salim, Kaptanis, Sarantos, Heshaishi, Mohamed, Eisawi, Abdalla, Abayomi, Michael, Ngu, Wee S., Fleming, Katie, Bajwa, Dalvir S., Chitre, Vivek, Aryal, Kamal, Ferris, Paul, Silva, Michael, Lammy, Simon, Mohamed, Sarah, Khawaja, Amir, Hussain, Adnan, Ghazanfar, Mudassar A., Bellini, Maria I., Ebdewi, Hamdi, Elshaer, Mohamed, Gravante, Gianpiero, Drake, Benjamin, Ogedegbe, Arikoge, Mukherjee, Dipankar, Arhi, Chanpreet, Giwa, Lola, Iqbal, Nusrat, Watson, Nicholas F., Aggarwal, Smeer K., Orchard, Philippa, Villatoro, Eduardo, Willson, Peter D., Mok, Kam W.J., Woodman, Thomas, Deguara, Jean, Garcea, Giuseppe, Babu, Benoy I., Dennison, Alistair R., Malde, Deep, Lloyd, David, Slavin, John P., Jones, Robert P., Ballance, Laura, Gerakopoulos, Stratos, Jambulingam, Periyathambi, Mansour, Sami, Sakai, Naomi, Acharya, Vikas, Sadat, Mohammed M., Karim, Lawen, Larkin, David, Amin, Khalid, Khan, Amarah, Law, Jennifer, Jamdar, Saurabh, Smith, Stella R., Sampat, Keerthika, O'shea, Kathryn M., Manu, Mangta, Asprou, Fotini M., Malik, Nabeela S., Chang, Jessica, Johnstone, Marianne, Lewis, Michael, Roberts, Geoffrey P., Karavadra, Babu, Photi, Evangelos, Hewes, James, Rodriguez, Dan, O'Reilly, Derek A., Rate, Anthony J., Sekhar, Hema, Henderson, Lucy T., Starmer, Benjamin Z., Coe, Peter O., Tolofari, Sotonye, Barrie, Jenifer, Bashir, Gareth, Sloane, Jake, Madanipour, Suroosh, Halkias, Constantine, Trevatt, Alexander E.J., Borowski, David W., Hornsby, Jane, Courtney, Michael J., Virupaksha, Suvi, Seymour, Keith, Robinson, Sarah, Hawkins, Helen, Bawa, Sadiq, Gallagher, Paul V., Reid, Alistair, Wood, Peter, Finch, Jonathan G., Finch, J.Guy, Parmar, Jitesh, Stirland, Euan, Gardner-Thorpe, James, Al-Muhktar, Ahmed, Peterson, Mark, Majeed, Ali, Bajwa, Farrukh M., Martin, Jack, Choy, Alfred, Tsang, Andrew, Pore, Naresh, Andrew, David R., Al-Khyatt, Waleed, Santosh Bhandari, Christopher Taylor, Chambers, Adam, Subramanium, Dhivya, Toh, Simon K.C., Carter, Nicholas C., Mercer, Stuart J., Knight, Benjamin, Vijay, Vardhini, Alagaratnam, Swethan, Sinha, Sidhartha, Khan, Shahab, El-Hasani, Shamsi S., Hussain, Abdulzahra A., Bhattacharya, Vish, Kansal, Nisheeth, Fasih, Tani, Jackson, Claire, Siddiqui, Midhat N., Chishti, Imran A., Fordham, Imogen J., Siddiqui, Zohaib, Bausbacher, Harald, Geogloma, Ileana, Gurung, Kabita, Tsavellas, George, Basynat, Pradeep, Shrestha, Ashish K., Basu, Sanjoy, Chhabra, Alok, Harilingam, Mohan, Rabie, Mohamed, Akhtar, Mansoor, Kumar, Pradeep, Jafferbhoy, Sadaf F., Hussain, Najam, Raza, Soulat, Haque, Manzarul, Alam, Imran, Aseem, Rabiya, Patel, Shakira, Asad, Mehek, Booth, Michael I., Ball, William R., Wood, Christopher P.J., Pinho-Gomes, Ana C., Kausar, Ambareen, Obeidallah, Mohammed, Varghase, Joseph, Lodhia, Joshil, Bradley, Donal, Rengifo, Carla, Lindsay, David, Gopalswamy, Sivakumar, Finlay, Ian, Wardle, Stacy, Bullen, Naomi, Iftikhar, Syed Y., Awan, Altaf, Ahmed, Javed, Leeder, Paul, Fusai, Guiseppe, Bond-Smith, Giles, Psica, Alicja, Puri, Yogesh, Hou, David, Noble, Fergus, Szentpali, Karoly, Broadhurst, Jack, Date, Ravindra, Hossack, Martin R., Goh, Yan L., Turner, Paul, Shetty, Vinutha, Riera, Manel, Macano, Christina A.W., Sukha, Anisha, Preston, Shaun R., Hoban, Jennifer R., Puntis, Daniel J., Williams, Sophie V., Krysztopik, Richard, Kynaston, James, Batt, Jeremy, Doe, Matthew, Goscimski, Andrzej, Jones, Gareth H., Hall, Claire, Carty, Nick, Ahmed, Jamil, Panteleimonitis, Sofoklis, Gunasekera, Rohan T., Sheel, Andrea R.G., Lennon, Hannah, Hindley, Caroline, Reddy, Marcus, Kenny, Ross, Elkheir, Natalie, McGlone, Emma R., Rajaganeshan, Rajasundaram, Hancorn, Kate, Hargreaves, Anita, Prasad, Raj, Longbotham, David A., Vijayanand, Dhakshinamoorthy, Wijetunga, Imeshi, Ziprin, Paul, Nicolay, Christopher R., Yeldham, Geoffrey, Read, Edward, Gossage, James A., Rolph, Rachel C., Ebied, Husam, Phull, Manraj, Khan, Mohammad A., Popplewell, Matthew, Kyriakidis, Dimitrios, Hussain, Anwar, Henley, Natasha, Packer, Jessica R., Derbyshire, Laura, Porter, Jonathan, Appleton, Shaun, Farouk, Marwan, Basra, Melvinder, Jennings, Neil A., Ali, Shahda, Kanakala, Venkatesh, Ali, Haythem, Lane, Risha, Dickson-Lowe, Richard, Zarsadias, Prizzi, Mirza, Darius, Puig, Sonia, Al Amari, Khalid, Vijayan, Deepak, Sutcliffe, Robert, Marudanayagam, Ravi, Hamady, Zayed, Prasad, Abheesh R., Patel, Abhilasha, Durkin, Damien, Kaur, Parminder, Bowen, Laura, Byrne, James P., Pearson, Katherine L., Delisle, Theo G., Davies, James, Tomlinson, Mark A., Johnpulle, Michelle A., Slawinski, Corinna, Macdonald, Andrew, Nicholson, James, Newton, Katy, Mbuvi, James, Farooq, Ansar, Mothe, Bhavani S., Zafrani, Zakhi, Brett, Daniel, Francombe, James, Spreadborough, Philip, Barnes, James, Cheung, Melanie, Al-Bahrani, Ahmed Z., Preziosi, Giuseppe, Urbonas, Tomas, Alberts, Justin, Mallik, Mekhlola, Patel, Krashna, Segaran, Ashvina, Doulias, Triantafyllos, Sufi, Pratik A., Yao, Caroline, Pollock, Sarah, Manzelli, Antonio, Wajed, Saj, Kourkulos, Michail, Pezzuto, Roberto, Wadley, Martin, Hamilton, Emma, Jaunoo, Shameen, Padwick, Robert, Sayegh, Mazin, Newton, Richard C., Hebbar, Madhusoodhana, Farag, Sameh F., Hebbar, Madhu, Spearman, John, Hamdan, Mohammed F., D'Costa, Conrad, Blane, Christine, Giles, Mathew, Peter, Mark B., Hirst, Natalie A., Hossain, Tanvir, Pannu, Arslan, El-Dhuwaib, Yesar, Morrison, Tamsin E.M., Taylor, Greg W., Thompson, Ronald L.E., McCune, Ken, Loughlin, Paula, Lawther, Roger, Byrnes, Colman K., Simpson, Duncan J., Mawhinney, Abi, Warren, Conor, McKay, Damian, McIlmunn, Colin, Martin, Serena, MacArtney, Matthew, Diamond, Tom, Davey, Phil, Jones, Claire, Clements, Joshua M., Digney, Ruairi, Chan, Wei M., McCain, Stephen, Gull, Sadaf, Janeczko, Adam, Dorrian, Emmet, Harris, Andrew, Dawson, Suzanne, Johnston, Dorothy, McAree, Barry, Ghareeb, Essam, Thomas, George, Connelly, Martin, McKenzie, Stephen, Cieplucha, Krzysztos, Spence, Gary, Campbell, William, Hooks, Gareth, Bradley, Neil, Hill, Arnold D.K., Cassidy, John T., Boland, Michael, Burke, Paul, Nally, Deirdre M., Khogali, Elmoataz, Shabo, Wael, Iskandar, Edrin, McEntee, Gerry P., O'Neill, Maeve A., Peirce, Colin, Lyons, Emma M., O'Sullivan, Adrian W., Thakkar, Rohan, Carroll, Paul, Ivanovski, Ivan, Balfe, Paul, Lee, Matthew, Winter, Des C., Kelly, Michael E., Hoti, Emir, Maguire, Donal, Karunakaran, Priyadarssini, Geoghegan, Justin G., Martin, Sean T., Cross, Keith S., Cooke, Fiachra, Zeeshan, Saquib, Murphy, James O., Mealy, Ken, Mohan, Helen M., Nedujchelyn, Yuwaraja, Ullah, Muhammad F., Ahmed, Irfan, Giovinazzo, Francesco, Milburn, James, Prince, Sarah, Brooke, Eleanor, Buchan, Joanna, Khalil, Ahmed M., Vaughan, Elizabeth M., Ramage, Michael I., Aldridge, Roland C., Gibson, Simon, Nicholson, Gary A., Vass, David G., Grant, Alan J., Holroyd, David J., Jones, Angharad, Sutton, Cherith M.L.R., O'Dwyer, Patrick, Nilsson, Frida, Weber, Beatrix, Williamson, Tracey K., Lalla, Kushik, Bryant, Alice, Carter, Ross, Forrest, Craig R., Hunter, David I., Nassar, Ahmad H., Orizu, Mavis N., Knight, Katrina, Qandeel, Haitham, Suttie, Stuart, Belding, Rowena, McClarey, Andrew, Boyd, Alan T., Guthrie, Graeme J.K., Lim, Pei J., Luhmann, Andreas, Watson, Angus J.M., Richards, Colin H., Nicol, Laura, Madurska, Marta, Harrison, Ewen, Boyce, Kathryn M., Roebuck, Amanda, Ferguson, Graeme, Pati, Pradeep, Wilson, Michael S.J., Dalgaty, Faith, Fothergill, Laura, Driscoll, Peter J., Mozolowski, Kirsty L., Banwell, Victoria, Bennett, Stephen P., Rogers, Paul N., Skelly, Brendan L., Rutherford, Claire L., Mirza, Ahmed K., Lazim, Taha, Lim, Henry C.C., Duke, Diana, Ahmed, Talat, Beasley, William D., Wilkinson, Marc D., Maharaj, Geta, Malcolm, Cathy, Brown, Timothy H., Shingler, Guy M., Mowbray, Nicholas, Radwan, Rami, Morcous, Paul, Wood, Simon, Kadhim, Abbas, Stewart, Duncan J., Baker, Andrew L., Tanner, Nicola, Shenoy, Hrishikesh, Sutcliffe, Robert P., Hollyman, Marianne, Hodson, James, Bonney, Glenn, Vohra, Ravi S., and Griffiths, Ewen A.

Published
2016
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17. Management of paraesophageal hiatus hernia:recommendations following a European expert Delphi consensus

Author

Gerdes, Stephan, Schoppmann, Sebastian F., Bonavina, Luigi, Boyle, Nicholas, Müller-Stich, Beat P., Gutschow, Christian A., Gisbertz, Suzanne Sarah, Köckerling, Ferdinand, Lehmann, Thorsten G., Lorenz, Dietmar, Granderath, Frank Alexander, Rosati, Riccardo, Wullstein, Christoph, Lundell, Lars, Cheong, Edward, Nafteux, Philippe, Olmi, Stefano, Mönig, Stefan, Biebl, Matthias, Leers, Jessica, Zehetner, Joerg, Kristo, Ivan, Berrisford, Richard George, Skrobić, Ognjan M., Simić, Aleksandar P., Pera, Manuel, Grimminger, Peter Philipp, Gockel, Ines, Zarras, Konstantinos, Nieuwenhuijs, Vincent Bernard, Gossage, James A., van Berge Henegouwen, Mark i., Stein, Hubert J., Markar, Sheraz R., Hueting, Willem Eduard, Targarona, Eduardo M., Johansson, Jan, Macaulay, Graeme D., Wijnhoven, Bas P.L., Benedix, Frank, Attwood, Stephen E., Hölscher, Arnulf Heinrich, Priego, Pablo, Fuchs, Karl Hermann, Luyer, Misha D.P., Griffiths, Ewen A., Søvik, Torgeir Thorson, Theodorou, Dimitrios, Sgromo, Bruno, Salo, Jarmo A., Gerdes, Stephan, Schoppmann, Sebastian F., Bonavina, Luigi, Boyle, Nicholas, Müller-Stich, Beat P., Gutschow, Christian A., Gisbertz, Suzanne Sarah, Köckerling, Ferdinand, Lehmann, Thorsten G., Lorenz, Dietmar, Granderath, Frank Alexander, Rosati, Riccardo, Wullstein, Christoph, Lundell, Lars, Cheong, Edward, Nafteux, Philippe, Olmi, Stefano, Mönig, Stefan, Biebl, Matthias, Leers, Jessica, Zehetner, Joerg, Kristo, Ivan, Berrisford, Richard George, Skrobić, Ognjan M., Simić, Aleksandar P., Pera, Manuel, Grimminger, Peter Philipp, Gockel, Ines, Zarras, Konstantinos, Nieuwenhuijs, Vincent Bernard, Gossage, James A., van Berge Henegouwen, Mark i., Stein, Hubert J., Markar, Sheraz R., Hueting, Willem Eduard, Targarona, Eduardo M., Johansson, Jan, Macaulay, Graeme D., Wijnhoven, Bas P.L., Benedix, Frank, Attwood, Stephen E., Hölscher, Arnulf Heinrich, Priego, Pablo, Fuchs, Karl Hermann, Luyer, Misha D.P., Griffiths, Ewen A., Søvik, Torgeir Thorson, Theodorou, Dimitrios, Sgromo, Bruno, and Salo, Jarmo A.

Abstract

Aims: There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. Methods: We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as “recommended” or “discouraged” if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled “acceptable” (neither recommended nor discouraged). Results: Seventy-two surgeons with a median (IQR) experience of 23 (14–30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15–36) and 40 (28–60) pHH-surgeries, respectively. After Delphi round 2, “recommended” strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified “discouraged” strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fixation technique) were “acceptable”. Conclusions: This multina

Published
2023

20. Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/Perioperative Quality Initiative (POQI) consensus statement on intraoperative and postoperative interventions to reduce pulmonary complications after oesophagectomy

Author

Singh, Pritam, Gossage, James, Markar, Sheraz, Pucher, Philip H, Wickham, Alex, Weblin, Jonathan, Chidambaram, Swathikan, Bull, Alexander, Pickering, Oliver, Mythen, Monty, Maynard, Nick, Grocott, Mike, Underwood, Tim, Levett, Denny, West, Malcolm, and Noble, Fergus

Subjects
Esophagectomy, Postoperative Care, Postoperative Complications, Quality of Life, Humans, Surgery, Ireland, United Kingdom
Abstract

Background Pulmonary complications are the most common morbidity after oesophagectomy, contributing to mortality and prolonged postoperative recovery, and have a negative impact on health-related quality of life. A variety of single or bundled interventions in the perioperative setting have been developed to reduce the incidence of pulmonary complications. Significant variation in practice exists across the UK. The aim of this modified Delphi consensus was to deliver clear evidence-based consensus recommendations regarding intraoperative and postoperative care that may reduce pulmonary complications after oesophagectomy. Methods With input from a multidisciplinary group of 23 experts in the perioperative management of patients undergoing surgery for oesophageal cancer, a modified Delphi method was employed. Following an initial systematic review of relevant literature, a range of anaesthetic, surgical, and postoperative care interventions were identified. These were then discussed during a two-part virtual conference. Recommendation statements were drafted, refined, and agreed by all attendees. The level of evidence supporting each statement was considered. Results Consensus was reached on 12 statements on topics including operative approach, pyloric drainage strategies, intraoperative fluid and ventilation strategies, perioperative analgesia, postoperative feeding plans, and physiotherapy interventions. Seven additional questions concerning the perioperative management of patients undergoing oesophagectomy were highlighted to guide future research. Conclusion Clear consensus recommendations regarding intraoperative and postoperative interventions that may reduce pulmonary complications after oesophagectomy are presented.

Published
2022

22. Anastomotic leak following oesophagectomy: research priorities from an international Delphi consensus study

Author

Kamarajah, Sivesh K, Mohamed, Imran, Nepogodiev, Dmitri, Evans, Richard PT, Hodson, James, Griffiths, Ewen A, Singh, Pritam, Committee, Steering, Alderson, Derek, Bundred, James, Evans, Richard, Gossage, James, Jefferies, Benjamin, Mckay, Siobhan, Siaw-Acheampong, Kobby, van Hillegersberg, Richard, Vohra, Ravinder, Wanigsooriya, Kasun, Whitehouse, Tony, Bekele, A, Achiam, Mp, Ahmed, H, Ainsworth, A, Akhtar, K, Akkapulu, N, Al-Khyatt, W, Alasmar, M, Alemu, Bn, Alfieri, R, Alkhaffaf, B, Alvarez, Ls, Amahu, V, Andreollo, Na, Arias, F, Ariyarathenam, A, Arndt, A, Athanasiou, A, Azagra, Js, Baban, C, Babor, R, Baili, E, Balla, A, Beenen, E, Bendixen, M, Bennett, J, Bergeat, D, Bernardes, Aj, Bernardi, D, Berrisford, R, Bianchi, A, Bjelovic, M, Blencowe, N, Boddy, A, Bogdan, S, Bolger, J, Bonavina, L, Bouras, G, Bouwense, S, Bowrey, D, Bragg, D, Bright, Tn, Broderick, S, Buduhan, G, Byrne, B, Carey, D, Carroll, P, Carrott, P, Casaca, R, Castro, Rg, Catton, J, Cerdeira, Mp, Chang, Ac, Charalabopoulos, A, Chaudry, A, Choh, C, Ciprian, B, Ciubotaru, C, Coe, P, Colak, E, Colino, Rb, Colucci, N, Costa, Pm, Daniela, K, Das, N, Davies, A, Davies, N, de Manzoni, G, del Val, Id, Dexter, S, Dolan, J, Donlon, N, Donohoe, C, Duffy, J, Dwerryhouse, S, Egberts, Jh, Ekwunife, C, Elhadi, A, Elhadi, M, Elliott, Ja, Elnagar, H, Elnagar, F, Faraj, Ha, Farooq, N, Fearon, N, Fekaj, E, Forshaw, M, Freire, J, Gacevski, G, Gaedcke, J, Giacopuzzi, S, Gijón, Mm, Gisbertz, S, Golcher, H, Gordon, A, Gossage, J, Griffiths, E, Grimminger, P, Guner, A, Gutknecht, S, Harustiak, T, Hedberg, J, Heisterkamp, J, Hii, M, Hindmarsh, A, Holm, J, Hornby, S, Isik, A, Izbicki, J, Jagadesham, V, Jaunoo, S, Johansson, J, Johnson, Ma, Johnston, B, Kapoulas, S, Kauppi, J, Kauppila, Jh, Kechagias, A, Kelly, M, Kelty, C, Kennedy, A, Khan, M, Khattak, S, Kidane, B, Kjaer, Dw, Klarenbeek, B, Korkolis, Dp, Koshy, Rm, Krantz, S, Lagarde, S, Larsen, Mh, Lau, Pc, Leeder, Pc, Leite, Js, Liakakos, T, Madhavan, A, Mahdi, Si, Mahendran, Ha, Mahmoodzadeh, H, Majbar, A, Manatakis, D, Markar, S, Martijnse, I, Matei, B, Matos da Costa, P, Mccormack, K, Mcnally, S, Meriläinen, S, Merrett, N, Migliore, M, Mingol, F, Mitton, D, Mogoanta, Ss, Mönig, Sp, Moorthy, K, Muhinga, M, Mwachiro, M, Naeem, A, Nasir, I, Navidi, M, Negoi, I, Negoiţă, V, Niazi, Sk, Nilsson, M, Pazdro, A, Pera, M, Perez, Cj, Perivoliotis, K, Peters, C, Phillips, Aw, Powell, A, Prove, L, Pucher, Ph, Rahman, S, Räsänen, Jv, Read, M, Reeh, M, Reim, D, Reynolds, J, Robb, Wb, Robertson, K, Rodica, B, Rosero, G, Rosman, C, Saadeh, L, Santos, Eg, Saunders, J, Sayyed, R, Schizas, D, Scurtu, Rr, Sekhniaidze, D, Serralheiro, Pa, Sevinç, B, Sgromo, B, Shakeel, O, Siemsen, M, Skipworth, R, Smith, B, Soares, A, Spillane, J, Steliga, Ma, Sundbom, M, Sydiuk, A, Takahashi, Aml, Talbot, M, Tan, B, Tareen, Ma, Tewari, N, Tez, M, Theodorou, D, Tita, A, Toledo, E, Townend, Pj, Triantafyllou, T, Trugeda, M, Tucker, O, Turner, P, Turrado, V, Underwood, T, Vaccari, S, Valmasoni, M, van Berge Henegouwen, M, van Boxel, G, van den Berg, Jw, van der Sluis, P, van Hillegersberg, R, van Lanschot, Jjb, van Workum, F, Vickers, J, Videira, J, Viswanath, Y, Vohra, R, Voon, K, Wadley, M, Walker, R, Wallner, B, Walsh, Tn, Weindelmayer, J, Welch, N, Wheatley, T, Wijnhoven, B, Wong, Lf, Yanni, F, Yeung, J, Zacharakis, Null, and Moenig, Stefan Paul

Subjects
medicine.medical_specialty, Leak, Biomedical Research, Delphi Technique, Steering committee, medicine.medical_treatment, Delphi method, Anastomotic Leak, 030230 surgery, Esophagectomy, Evidence-Based Medicine, Humans, Surveys and Questionnaires, Research, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, medicine, computer.programming_language, ddc:617, business.industry, General surgery, 030220 oncology & carcinogenesis, Surgery, business, computer, Delphi
Abstract

Background The Oesophago-Gastric Anastomosis Audit (OGAA) is an international collaborative group set up to study anastomotic leak outcomes after oesophagectomy for cancer. This Delphi study aimed to prioritize future research areas of unmet clinical need in RCTs to reduce anastomotic leaks. Methods A modified Delphi process was overseen by the OGAA committee, national leads, and engaged clinicians from high-income countries (HICs) and low/middle-income countries (LMICs). A three-stage iterative process was used to prioritize research topics, including a scoping systematic review (stage 1), and two rounds of anonymous electronic voting (stages 2 and 3) addressing research priority and ability to recruit. Stratified analyses were performed by country income. Results In stage 1, the steering committee proposed research topics across six domains: preoperative optimization, surgical oncology, technical approach, anastomotic technique, enhanced recovery and nutrition, and management of leaks. In stages 2 and stage 3, 192 and 171 respondents respectively participated in online voting. Prioritized research topics include prehabilitation, anastomotic technique, and timing of surgery after neoadjuvant chemo(radio)therapy. Stratified analyses by country income demonstrated no significant differences in research priorities between HICs and LMICs. However, for ability to recruit, there were significant differences between LMICs and HICs for themes related to the technical approach (minimally invasive, width of gastric tube, ischaemic preconditioning) and location of the anastomosis. Conclusion Several areas of research priority are consistent across LMICs and HICs, but discrepancies in ability to recruit by country income will inform future study design.

Published
2020

23. Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia

Author

Kasthuri, Raj S., Montifar, Megan, Nelson, Jeffrey, Kim, Helen, Lawton, Michael T., Faughnan, Marie E., Chakinala, Murali, Clancy, Marianne S., Faughnan, Marie E., Gossage, James R., Henderson, Katherine, Iyer, Vivek, Kasthuri, Raj S., Kim, Helen, Krings, Timo, Lawton, Michael T., Lin, Doris, Mager, Hans‐Jurgen, McWilliams, Justin P., McDonald, Jamie, Pawlikowska, Ludmila, Pollak, Jeffrey, Ratjen, Felix, Swanson, Karen, terBrugge, Karel, Vethanayagam, Dilini, White, Andrew, White, Robert I., Jr, Wilcox, Pearce, and Young, William L.

Published
2017
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25. Hemorrhage Rates From Brain Arteriovenous Malformation in Patients With Hereditary Hemorrhagic Telangiectasia

Author

Kim, Helen, Nelson, Jeffrey, Krings, Timo, terBrugge, Karel G., McCulloch, Charles E., Lawton, Michael T., Young, William L., Faughnan, Marie E., Chakinala, Murali, Gossage, James R., Henderson, Katharine, Iyer, Vivek, Kasthuri, Raj, Lin, Doris, Mager, Johannes Jurgen, McWilliams, Justin, McDonald, Jamie, Pawlikowska, Ludmila, Pollak, Jeffrey, Ratjen, Felix, Swanson, Karen, Vethanayagam, Dilini, White, Andrew, White, Robert I., Jr, and Wilcox, Pearce

Published
2015
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27. sj-pdf-1-vmj-10.1177_1358863X20974452 – Supplemental material for Screening for pulmonary and brain vascular malformations is the North American standard of care for patients with hereditary hemorrhagic telangiectasia (HHT): A survey of HHT Centers of Excellence

Author

Kilian, Alexandra, Clancy, Marianne S, Olitsky, Scott, Gossage, James R, and Faughnan, Marie E

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, FOS: Clinical medicine, fungi, otorhinolaryngologic diseases, Cardiology, 110323 Surgery
Abstract

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X20974452 for Screening for pulmonary and brain vascular malformations is the North American standard of care for patients with hereditary hemorrhagic telangiectasia (HHT): A survey of HHT Centers of Excellence by Alexandra Kilian, Marianne S Clancy, Scott Olitsky, James R Gossage and Marie E Faughnan in Vascular Medicine

Published
2020
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28. The Influence of Comorbidity on Health-Related Quality of Life After Esophageal Cancer Surgery

Author

Backemar, Lovisa, Johar, Asif, Wikman, Anna, Zylstra, Janine, Gossage, James, Davies, Andrew, Lagergren, Jesper, Lagergren, Pernilla, Backemar, Lovisa, Johar, Asif, Wikman, Anna, Zylstra, Janine, Gossage, James, Davies, Andrew, Lagergren, Jesper, and Lagergren, Pernilla

Abstract

Background Esophageal cancer surgery reduces patients’ health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients. Methods This prospective cohort study included esophageal cancer patients having undergone curatively intended esophagectomy at St Thomas’ Hospital London in 2011–2015. Clinical data were collected from patient reports and medical records. Well-validated cancer-specific and esophageal cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25) were used to assess HRQoL before and 6 months after esophagectomy. Number of comorbidities, American Society of Anesthesiologists physical status classification (ASA), and specific comorbidities were analyzed in relation to HRQoL aspects using multivariable linear regression models. Mean score differences with 95% confidence intervals were adjusted for potential confounders. Results Among 136 patients, those with three or more comorbidities at the time of surgery had poorer global quality of life and physical function and more fatigue compared with those with no comorbidity. Patients with ASA III–IV reported more problems with the above HRQoL aspects and worse social function and pain compared with those with ASA I–II. Cardiac comorbidity was associated with worse global quality of life and dyspnea, while pulmonary comorbidities were related to coughing. Patients assessed both before and 6 months after surgery (n = 80) deteriorated in most HRQoL aspects regardless of comorbidity status, but patients with several comorbidities had worse physical function and fatigue and more trouble with coughing compared with those with fewer comorbidities. Conclusion Comorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL.

Published
2020
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29. Pan-cancer analysis of whole genomes

Author

Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, Zhang, Jiashan, Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, and Zhang, Jiashan

Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).

Published
2020

30. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia

Author

Circulatory Health, Team Medisch, Cardiologie, Faughnan, Marie E, Mager, Johannes J, Hetts, Steven W, Palda, Valerie A, Lang-Robertson, Kelly, Buscarini, Elisabetta, Deslandres, Erik, Kasthuri, Raj S, Lausman, Andrea, Poetker, David, Ratjen, Felix, Chesnutt, Mark S, Clancy, Marianne, Whitehead, Kevin J, Al-Samkari, Hanny, Chakinala, Murali, Conrad, Miles, Cortes, Daniel, Crocione, Claudia, Darling, Jama, de Gussem, Els, Derksen, Carol, Dupuis-Girod, Sophie, Foy, Patrick, Geisthoff, Urban, Gossage, James R, Hammill, Adrienne, Heimdal, Ketil, Henderson, Katharine, Iyer, Vivek N, Kjeldsen, Anette D, Komiyama, Masaki, Korenblatt, Kevin, McDonald, Jamie, McMahon, Jack, McWilliams, Justin, Meek, Mary E, Mei-Zahav, Meir, Olitsky, Scott, Palmer, Sara, Pantalone, Rose, Piccirillo, Jay F, Plahn, Beth, Porteous, Mary E M, Post, Marco C, Radovanovic, Ivan, Rochon, Paul J, Rodriguez-Lopez, Josanna, Sabba, Carlo, Serra, Marcelo, Shovlin, Claire, Sprecher, Dennis, White, Andrew J, Winship, Ingrid, Zarrabeitia, Roberto, Circulatory Health, Team Medisch, Cardiologie, Faughnan, Marie E, Mager, Johannes J, Hetts, Steven W, Palda, Valerie A, Lang-Robertson, Kelly, Buscarini, Elisabetta, Deslandres, Erik, Kasthuri, Raj S, Lausman, Andrea, Poetker, David, Ratjen, Felix, Chesnutt, Mark S, Clancy, Marianne, Whitehead, Kevin J, Al-Samkari, Hanny, Chakinala, Murali, Conrad, Miles, Cortes, Daniel, Crocione, Claudia, Darling, Jama, de Gussem, Els, Derksen, Carol, Dupuis-Girod, Sophie, Foy, Patrick, Geisthoff, Urban, Gossage, James R, Hammill, Adrienne, Heimdal, Ketil, Henderson, Katharine, Iyer, Vivek N, Kjeldsen, Anette D, Komiyama, Masaki, Korenblatt, Kevin, McDonald, Jamie, McMahon, Jack, McWilliams, Justin, Meek, Mary E, Mei-Zahav, Meir, Olitsky, Scott, Palmer, Sara, Pantalone, Rose, Piccirillo, Jay F, Plahn, Beth, Porteous, Mary E M, Post, Marco C, Radovanovic, Ivan, Rochon, Paul J, Rodriguez-Lopez, Josanna, Sabba, Carlo, Serra, Marcelo, Shovlin, Claire, Sprecher, Dennis, White, Andrew J, Winship, Ingrid, and Zarrabeitia, Roberto

Published
2020

31. P107 PREDICTION OF A POSITIVE CIRCUMFERENTIAL RESECTION MARGIN IN ADENOCARCINOMA OF THE ESOPHAGUS

Author

Goh Vicky, Jacques Audrey, Yip Connie, Griffin Nyree, Landau David, Kelly Mark, Van Hemelrijck Mieke, R C Knight William, R Davies Andrew, Zylstra Janine, R Baker Cara, Wulaningsih Wahyu, Largergren Jesper, Gaya DrAndrew, Maisey Nick, and A Gossage James

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Gastroenterology, medicine, Adenocarcinoma, Circumferential resection margin, General Medicine, Radiology, Esophagus, medicine.disease, business
Abstract

Aim To determine if a positive circumferential resection margin (CRM) can be predicted in patients with esophageal adenocarcinoma undergoing neo-adjuvant chemotherapy prior to surgery Methods 223 patients were included in this study. Multivariable analyses of clinico-pathological and computed tomography (CT) imaging predictors were performed to evaluate the likelihood of a positive CRM at initial staging and following neoadjuvant chemotherapy, with prediction models constructed. Area under curve (AUC) with 95% confidence interval (CI) from 1000 bootstrapping was assessed. Results Advanced clinical T-stage (T3-4) (odds ratio, OR 2.93 95%CI 1.03-9.48) and poor tumor differentiation (OR 2.84, 95%CI 1.39-6.01) were independently associated with an increased risk of a positive CRM. Non response to chemotherapy as estimated by CT independently corresponded with an increased risk of CRM positivity (OR 3.38 95% CI 1.43-8.50). Additional CT evidence of local invasion/pleural thickening and higher CT tumor volume (14cm3) improved the performance of a prediction model, including all above parameters; with AUC (c-index) of 0.76 (0.68-0.83). Conclusion Combining advanced clinical T-stage, poor tumor differentiation, CT non-response to chemotherapy, higher CT tumor volume and local invasion may be helpful in selecting patients for intensification of neo-adjuvant treatment prior to resection.

Published
2019

32. Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Author

Griffiths, Ewen A, Hodson, James, Vohra, Ravi S, Marriott, Paul, Katbeh, Tarek, Zino, Samer, Nassar, Ahmad HM, Vohra, Ravinder S, Kirkham, Amanda J, Pasquali, Sandro, Johnstone, Marianne, Spreadborough, Philip, Alderson, Derek, Fenwick, Stephen, Elmasry, Mohamed, Nunes, Quentin M, Kennedy, David, Khan, Raja Basit, Khan, Muhammad AS, Magee, Conor J, Jones, Steven M, Mason, Denise, Parappally, Ciny P, Mathur, Pawan, Saunders, Michael, Jamel, Sara, Haque, Samer Ul, Zafar, Sara, Shiwani, Muhammad Hanif, Samuel, Nehemiah, Dar, Farooq, Jackson, Andrew, Lovett, Bryony, Dindyal, Shiva, Winter, Hannah, Fletcher, Ted, Rahman, Saquib, Wheatley, Kevin, Nieto, Tom, Ayaani, Soofiyah, Youssef, Haney, Nijjar, Rajwinder S, Watkin, Helen, Naumann, David, Emesih, Sophie, Sarmah, Piyush B, Lee, Kathryn, Joji, Nikita, Lambert, Joel, Heath, Jonathan, Teasdale, Rebecca L, Weerasinghe, Chamindri, Needham, Paul J, Welbourn, Hannah, Forster, Luke, Finch, David, Blazeby, Jane M, Robb, William, McNair, Angus GK, Hrycaiczuk, Alex, Charalabopoulos, Alexandros, Kadirkamanathan, Sritharan, Tang, Cheuk-Bong, Jayanthi, Naga VG, Noor, Nigel, Dobbins, Brian, Cockbain, Andrew J, Nilsen-Nunn, April, de Siqueira, Jonathan, Pellen, Mike, Cowley, Jonathan B, Ho, Wei-Min, Miu, Victor, White, Timothy J, Hodgkins, Kathryn A, Kinghorn, Alison, Tutton, Matthew G, Al-Abed, Yahya A, Menzies, Donald, Ahmad, Anwar, Reed, Joanna, Khan, Shabuddin, Monk, David, Vitone, Louis J, Murtaza, Ghulam, Joel, Abraham, Brennan, Stephen, Shier, David, Zhang, Catherine, Yoganathan, Thusidaran, Robinson, Steven J, McCallum, Iain JD, Jones, Michael J, Elsayed, Mohammed, Tuck, Liz, Wayman, John, Carney, Kate, Aroori, Somaiah, Hosie, Kenneth B, Kimble, Adam, Bunting, David M, Fawole, Adeshina S, Basheer, Mohammed, Dave, Rajiv V, Sarveswaran, Janahan, Jones, Elinor, Kendal, Chris, Tilston, Michael P, Gough, Martin, Wallace, Tom, Singh, Shailendra, Downing, Justine, Mockford, Katherine A, Issa, Eyad, Shah, Nayab, Chauhan, Neal, Wilson, Timothy R, Forouzanfar, Amir, Wild, Jonathan RL, Nofal, Emma, Bunnell, Catherine, Madbak, Khaliel, Rao, Sudhindra TV, Devoto, Laurence, Siddiqi, Najaf, Khawaja, Zechan, Hewes, James C, Gould, Laura, Chambers, Alice, Rodriguez, Daniel Urriza, Sen, Gourab, Robinson, Stuart, Bartlett, Francis, Rae, David M, Stevenson, Thomas EJ, Sarvananthan, Kas, Dwerryhouse, Simon J, Higgs, Simon M, Old, Oliver J, Hardy, Thomas J, Shah, Reena, Hornby, Steve T, Keogh, Ken, Frank, Lucinda, Al-Akash, Musallam, Upchurch, Emma A, Frame, Richard J, Hughes, Michael, Jelley, Clare, Weaver, Simon, Roy, Sudipta, Sillo, Toritseju O, Galanopoulos, Giorgios, Cuming, Tamzin, Cunha, Pedro, Tayeh, Salim, Kaptanis, Sarantos, Heshaishi, Mohamed, Eisawi, Abdalla, Abayomi, Michael, Ngu, Wee Sing, Fleming, Katie, Bajwa, Dalvi S, Chitre, Vivek, Aryal, Kamal, Ferris, Paul, Silva, Michael, Lammy, Simon, Mohamed, Sarah, Khawaja, Amir, Hussain, Adnan, Ghazanfar, Mudassar A, Bellini, Maria Irene, Ebdewi, Hamdi, Elshaer, Mohamed, Gravante, Gianpiero, Drake, Benjamin, Ogedegbe, Arikoge, Mukherjee, Dipankar, Arhi, Chanpreet, Giwa, Lola, Iqbal, Nusrat, Watson, Nicholas F, Aggarwal, Smeer Kumar, Orchard, Philippa, Villatoro, Eduardo, Willson, Peter D, Mok, Kam Wa Jessica, Woodman, Thomas, Deguara, Jean, Garcea, Giuseppe, Babu, Benoy I, Dennison, AR, Malde, Deep, Lloyd, David, Satheesan, Steve, Al-Taan, Omer, Boddy, Alexander, Slavin, John P, Jones, Robert P, Ballance, Laura, Gerakopoulos, Stratos, Jambulingam, Periyathambi, Mansour, Sami, Sakai, Naomi, Acharya, Vikas, Sadat, Mohammed M, Karim, Lawen, Larkin, David, Amin, Khalid, Khan, Amarah, Law, Jennifer, Jamdar, Saurabh, Smith, Stella R, Sampat, Keerthika, O'shea, Kathryn M, Manu, Mangta, Asprou, Fotini M, Malik, Nabeela S, Chang, Jessica, Lewis, Michael, Roberts, Geoffrey P, Karavadra, Babu, Photi, Evangelos, Hewes, James, Rodriguez, Dan, O'Reilly, Derek A, Rate, Anthony J, Sekhar, Hema, Henderson, Lucy T, Starmer, Benjamin Z, Coe, Peter O, Tolofari, Sotonye, Barrie, Jenifer, Bashir, Gareth, Sloane, Jake, Madanipour, Suroosh, Halkias, Constantine, Trevatt, Alexander EJ, Borowski, David W, Hornsby, Jane, Courtney, Michael J, Virupaksha, Suvi, Seymour, Keith, Robinson, Sarah, Hawkins, Helen, Bawa, Sadiq, Gallagher, Paul V, Reid, Alistair, Wood, Peter, Finch, JG, Finch, J Guy, Parmar, J, Stirland, E, Gardner-Thorpe, James, Al-Muhktar, Ahmed, Peterson, Mark, Majeed, Ali, Bajwa, Farrukh M, Martin, Jack, Choy, Alfred, Tsang, Andrew, Pore, Naresh, Andrew, David R, Al-Khyatt, Waleed, Bhandari, Christopher Taylor Santosh, Chambers, Adam, Subramanium, Dhivya, Toh, Simon KC, Carter, Nicholas C, Tate, Sophie, Pearce, Belinda, Wainwright, Denise, Mercer, Stuart J, Knight, Benjamin, Vijay, Vardhini, Alagaratnam, Swethan, Sinha, Sidhartha, Khan, Shahab, El-Hasani, Shamsi S, Hussain, Abdulzahra A, Bhattacharya, Vish, Kansal, Nisheeth, Fasih, Tani, Jackson, Claire, Siddiqui, Midhat N, Chishti, Imran A, Fordham, Imogen J, Siddiqui, Zohaib, Bausbacher, Harald, Geogloma, Ileana, Gurung, Kabita, Tsavellas, George, Basynat, Pradeep, Shrestha, Ashish Kiran, Basu, Sanjoy, Harilingam, Alok Chhabra Mohan, Rabie, Mohamed, Akhtar, Mansoor, Kumar, Pradeep, Jafferbhoy, Sadaf F, Hussain, Najam, Raza, Soulat, Haque, Manzarul, Alam, Imran, Aseem, Rabiya, Patel, Shakira, Asad, Mehek, Booth, Michael I, Ball, William R, Wood, Christopher PJ, Pinho-Gomes, Ana C, Kausar, Ambareen, Obeidallah, Moh'd Rami, Varghase, Joseph, Lodhia, Joshil, Bradley, Donal, Rengifo, Carla, Lindsay, David, Gopalswamy, Sivakumar, Finlay, Ian, Wardle, Stacy, Bullen, Naomi, Iftikhar, Syed Yusuf, Awan, Altaf, Ahmed, Javed, Leeder, Paul, Fusai, Guiseppe, Bond-Smith, Giles, Psica, Alicja, Puri, Yogesh, Hou, David, Noble, Fergus, Szentpali, Karoly, Broadhurst, Jack, Date, Ravindra, Hossack, Martin R, Goh, Yan Li, Turner, Paul, Shetty, Vinutha, Riera, Manel, Macano, Christina AW, Sukha, Anisha, Preston, Shaun R, Hoban, Jennifer R, Puntis, Daniel J, Williams, Sophie V, Krysztopik, Richard, Kynaston, James, Batt, Jeremy, Doe, Matthew, Goscimski, Andrzej, Jones, Gareth H, Hall, Claire, Carty, Nick, Ahmed, Jamil, Panteleimonitis, Sofoklis, Gunasekera, Rohan T, Sheel, Andrea RG, Lennon, Hannah, Hindley, Caroline, Reddy, Marcus, Kenny, Ross, Elkheir, Natalie, McGlone, Emma R, Rajaganeshan, Rajasundaram, Hancorn, Kate, Hargreaves, Anita, Prasad, Raj, Longbotham, David A, Vijayanand, Dhakshinamoorthy, Wijetunga, Imeshi, Ziprin, Paul, Nicolay, Christopher R, Yeldham, Geoffrey, Read, Edward, Gossage, James A, Rolph, Rachel C, Ebied, Husam, Phull, Manraj, Khan, Mohammad A, Popplewell, Matthew, Kyriakidis, Dimitrios, Hussain, Anwar, Henley, Natasha, Packer, Jessica R, Derbyshire, Laura, Porter, Jonathan, Appleton, Shaun, Farouk, Marwan, Basra, Melvinder, Jennings, Neil A, Ali, Shahda, Kanakala, Venkatesh, Ali, Haythem, Lane, Risha, Dickson-Lowe, Richard, Zarsadias, Prizzi, Mirza, Darius, Puig, Sonia, Al Amari, Khalid, Vijayan, Deepak, Sutcliffe, Robert, Marudanayagam, Ravi, Hamady, Zayed, Prasad, Abheesh R, Patel, Abhilasha, Durkin, Damien, Kaur, Parminder, Bowen, Laura, Byrne, James P, Pearson, Katherine L, Delisle, Theo G, Davies, James, Tomlinson, Mark A, Johnpulle, Michelle A, Slawinski, Corinna, Macdonald, Andrew, Nicholson, James, Newton, Katy, Mbuvi, James, Farooq, Ansar, Mothe, Bhavani Sidhartha, Zafrani, Zakhi, Brett, Daniel, Francombe, James, Barnes, James, Cheung, Melanie, Al-Bahrani, Ahmed Z, Preziosi, Giuseppe, Urbonas, Tomas, Alberts, Justin, Mallik, Mekhlola, Patel, Krashna, Segaran, Ashvina, Doulias, Triantafyllos, Sufi, Pratik A, Yao, Caroline, Pollock, Sarah, Manzelli, Antonio, Wajed, Saj, Kourkulos, Michail, Pezzuto, Roberto, Wadley, Martin, Hamilton, Emma, Jaunoo, Shameen, Padwick, Robert, Sayegh, Mazin, Newton, Richard C, Hebbar, Madhusoodhana, Farag, Sameh F, Spearman, John, Hamdan, Mohammed F, D'Costa, Conrad, Blane, Christine, Giles, Mathew, Peter, Mark B, Hirst, Natalie A, Hossain, Tanvir, El-Dhuwaib, Arslan Pannu Yesar, Morrison, Tamsin EM, Taylor, Greg W, Thompson, Ronald LE, McCune, Ken, Loughlin, Paula, Lawther, Roger, Byrnes, Colman K, Simpson, Duncan J, Mawhinney, Abi, Warren, Conor, McKay, Damian, McIlmunn, Colin, Martin, Serena, MacArtney, Matthew, Diamond, Tom, Davey, Phil, Jones, Claire, Clements, Joshua M, Digney, Ruairi, Chan, Wei Ming, McCain, Stephen, Gull, Sadaf, Janeczko, Adam, Dorrian, Emmet, Harris, Andrew, Dawson, Suzanne, Johnston, Dorothy, McAree, Barry, Ghareeb, Essam, Thomas, George, Connelly, Martin, McKenzie, Stephen, Cieplucha, Krzysztos, Spence, Gary, Campbell, William, Hooks, Gareth, Bradley, Neil, Hill, Arnold DK, Cassidy, John T, Boland, Michael, Burke, Paul, Nally, Deirdre M, Khogali, Elmoataz, Shabo, Wael, Iskandar, Edrin, McEntee, Gerry P, O'Neill, Maeve A, Peirce, Colin, Lyons, Emma M, O'Sullivan, Adrian W, Thakkar, Rohan, Carroll, Paul, Ivanovski, Ivan, Balfe, Paul, Lee, Matthew, Winter, Des C, Kelly, Michael E, Hoti, Emir, Maguire, Donal, Karunakaran, Priyadarssini, Geoghegan, Justin G, McDermott, Frank, Martin, Sean T, Cross, Keith S, Cooke, Fiachra, Zeeshan, Saquib, Murphy, James O, Mealy, Ken, Mohan, Helen M, Nedujchelyn, Yuwaraja, Ullah, Muhammad Fahad, Ahmed, Irfan, Giovinazzo, Francesco, Milburn, James, Prince, Sarah, Brooke, Eleanor, Buchan, Joanna, Khalil, Ahmed M, Vaughan, Elizabeth M, Ramage, Michael I, Aldridge, Roland C, Gibson, Simon, Nicholson, Gary A, Vass, David G, Grant, Alan J, Holroyd, David J, Jones, M Angharad, Sutton, Cherith MLR, O'Dwyer, Patrick, Nilsson, Frida, Weber, Beatrix, Williamson, Tracey K, Lalla, Kushik, Bryant, Alice, Carter, C Ross, Forrest, Craig R, Hunter, David I, Nassar, Ahmad H, Orizu, Mavis N, Knight, Katrina, Qandeel, Haitham, Suttie, Stuart, Belding, Rowena, McClarey, Andrew, Boyd, Alan T, Guthrie, Graeme JK, Lim, Pei J, Luhmann, Andreas, Watson, Angus JM, Richards, Colin H, Nicol, Laura, Madurska, Marta, Harrison, Ewen, Boyce, Kathryn M, Roebuck, Amanda, Ferguson, Graeme, Pati, Pradeep, Wilson, Michael SJ, Dalgaty, Faith, Fothergill, Laura, Driscoll, Peter J, Mozolowski, Kirsty L, Banwell, Victoria, Bennett, Stephen P, Rogers, Paul N, Skelly, Brendan L, Rutherford, Claire L, Mirza, Ahmed K, Lazim, Taha, Lim, Henry CC, Duke, Diana, Ahmed, Talat, Beasley, William D, Wilkinson, Marc D, Maharaj, Geta, Malcolm, Cathy, Brown, Timothy H, Al-Sarireh, Bilal, Shingler, Guy M, Mowbray, Nicholas, Radwan, Rami, Morcous, Paul, Wood, Simon, Kadhim, Abbas, Stewart, Duncan J, Baker, Andrew L, Tanner, Nicola, Shenoy, Hrishikesh, Hafiz, Shazia, De Marchi, Joshua A, Singh-Ranger, Deepak, Hisham, Elzanati, Ainley, Paul, O'Neill, Stephen, Terrace, John, Napetti, Sara, Hopwood, Benjamin, Rhys, Thomas, Kanavati, Osama, Coats, Maria, Aleksandrov, Danail, Kallaway, Charlotte, Yahya, Salama, Templeton, Alexa, Trotter, Martin, Lo, Christina, Dhillon, Ajit, Heywood, Nick, Aawsaj, Yousif, Hamdan, Alhafidz, Reece-Bolton, Obuobi, McGuigan, Andrew, Shahin, Yousef, Aymon, Luther, Ali Alison, Nicholson, James A, Rajendran, Ilayaraja, Boal, Matthew, Ritchie, Judith, Grp, CholeS Study, Collaborative, West Midlands Res, Segaran, A, and Collaborative, West Midlands Research

Subjects
medicine.medical_specialty, medicine.medical_treatment, 030230 surgery, Article, 03 medical and health sciences, 0302 clinical medicine, Case mix index, Laparoscopic, length of stay, male, middle aged, postoperative complications, Medicine, Cholecystectomy, Prospective cohort study, Grading (education), humans, Laparoscopic cholecystectomy, business.industry, General surgery, adult, cholecystectomy, difficulty grading, laparoscopic, operative difficulty, surgery, aged, cholecystectomy, laparoscopic, conversion to open surgery, female, multivariate analysis, prospective studies, ROC curve, Difficulty grading, Cohort, 030211 gastroenterology & hepatology, Surgery, business, Operative difficulty, Grading scale, Abdominal surgery
Abstract

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p p Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty.

Published
2018

34. Quantification metrics for telangiectasia using optical coherence tomography.

Author

Cardinell, Jillian L., Ramjist, Joel M., Chen, Chaoliang, Shi, Weisong, Nguyen, Nhu Q., Yeretsian, Tiffany, Choi, Matthew, Chen, David, Clark, Dewi S., Curtis, Anne, Kim, Helen, Faughnan, Marie E., Yang, Victor X. D., the Brain Vascular Malformation Consortium HHT Investigator Group, Chakinala, Murali, Clancy, Marianne S., Faughnan, Marie, Gossage, James R., Henderson, Katharine, and Iyer, Vivek

Subjects
HEREDITARY hemorrhagic telangiectasia, TELANGIECTASIA, BLOOD flow
Abstract

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)—a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion images. Preliminary results from these lesions are presented in this paper alongside representative OCT images. This study provides a new objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost-effective, and efficient imaging modality with quantitative metrics describing morphology and blood flow. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Identification of Subtypes of Barrett’s Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data

Author

Jammula, SriGanesh, primary, Katz-Summercorn, Annalise C., additional, Li, Xiaodun, additional, Linossi, Constanza, additional, Smyth, Elizabeth, additional, Killcoyne, Sarah, additional, Biasci, Daniele, additional, Subash, Vinod V., additional, Abbas, Sujath, additional, Blasko, Adrienn, additional, Devonshire, Ginny, additional, Grantham, Amber, additional, Wronowski, Filip, additional, O’Donovan, Maria, additional, Grehan, Nicola, additional, Eldridge, Matthew D., additional, Tavaré, Simon, additional, Fitzgerald, Rebecca C., additional, Noorani, Ayesha, additional, Edwards, Paul A.W., additional, Nutzinger, Barbara, additional, Hughes, Caitriona, additional, Fidziukiewicz, Elwira, additional, Bornschein, Jan, additional, MacRae, Shona, additional, Crawte, Jason, additional, Northrop, Alex, additional, Contino, Gianmarco, additional, de la Rue, Rachel, additional, Miremadi, Ahmad, additional, Malhotra, Shalini, additional, Tripathi, Monika, additional, Lynch, Andy G., additional, Eldridge, Matthew, additional, Secrier, Maria, additional, Bower, Lawrence, additional, Perner, Juliane, additional, Jammula, Sriganesh, additional, Davies, Jim, additional, Crichton, Charles, additional, Carroll, Nick, additional, Safranek, Peter, additional, Hindmarsh, Andrew, additional, Sujendran, Vijayendran, additional, Hayes, Stephen J., additional, Ang, Yeng, additional, Preston, Shaun R., additional, Oakes, Sarah, additional, Bagwan, Izhar, additional, Save, Vicki, additional, Skipworth, Richard J.E., additional, Hupp, Ted R., additional, O’Neill, J. Robert, additional, Tucker, Olga, additional, Beggs, Andrew, additional, Taniere, Philippe, additional, Puig, Sonia, additional, Underwood, Timothy J., additional, Noble, Fergus, additional, Owsley, Jack, additional, Barr, Hugh, additional, Shepherd, Neil, additional, Old, Oliver, additional, Lagergren, Jesper, additional, Gossage, James, additional, Davies, Andrew, additional, Chang, Fuju, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Goh, Vicky, additional, Ciccarelli, Francesca D., additional, Sanders, Grant, additional, Berrisford, Richard, additional, Harden, Catherine, additional, Lewis, Mike, additional, Cheong, Ed, additional, Kumar, Bhaskar, additional, Parsons, Simon L., additional, Soomro, Irshad, additional, Kaye, Philip, additional, Saunders, John, additional, Lovat, Laurence, additional, Haidry, Rehan, additional, Igali, Laszlo, additional, Scott, Michael, additional, Sothi, Sharmila, additional, Suortamo, Sari, additional, Lishman, Suzy, additional, Hanna, George B., additional, Moorthy, Krishna, additional, Peters, Christopher J., additional, Grabowska, Anna, additional, and Turkington, Richard, additional

Published
2020
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41. Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia.

Author

Thompson, K. P., Nelson, J., Kim, H., Weinsheimer, S. M., Marchuk, D. A., Lawton, M. T., Krings, T., Faughnan, M. E., Brain Vascular Malformation Consortium HHT Investigator Group, Chakinala, Murali, Clancy, Marianne S., Faughnan, Marie E., Gossage, James R., Hetts, Steven W., Iyer, Vivek, Kasthuri, Raj S., Kim, Helen, Krings, Timo, Lawton, Michael T., and Lin, Doris

Subjects
HEREDITARY hemorrhagic telangiectasia, CEREBRAL arteriovenous malformations, INTRACRANIAL hemorrhage, TREATMENT effectiveness, ARTERIOVENOUS malformation, HUMAN abnormalities
Abstract

Background: Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up.Methods: 1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit.Results: Presence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0-2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26-0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27-0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09-0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21-1.08, p = 0.004).Conclusion: Most HHT-brain VM patients had good functional capacity (mRS scores 0-2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation

Author

O'Neill, J. Robert, Yébenes Mayordomo, Marcos, Mitulović, Goran, Al Shboul, Sofian, Bedran, Georges, Faktor, Jakub, Hernychova, Lenka, Uhrik, Lukas, Gómez-Herranz, Maria, Kocikowski, Mikołaj, Save, Vicki, Vojtěšek, Bořivoj, Arends, Mark J., Fitzgerald, Rebecca C., Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Loreno, Christine, Redmond, Aisling M., Abbas, Sujath, Freeman, Adam, Smyth, Elizabeth C., O'Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Cheah, Calvin, Coles, Hannah, Millington, Curtis, Devonshire, Ginny, Eldridge, Matthew, Secrier, Maria, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Hardwick, Richard H., Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Contino, Gianmarco, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Chan, David, Cheong, Ed, Kumar, Bhaskar, Sreedharan, L., Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Scott, Michael, Sothi, Sharmila, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Coleman, Helen, Petty, Russell D., Bartlet, Freddie, Hupp, Ted, and Alfaro, Javier Antonio

Abstract

Efforts to address the poor prognosis associated with esophageal adenocarcinoma (EAC) have been hampered by a lack of biomarkers to identify early disease and therapeutic targets. Despite extensive efforts to understand the somatic mutations associated with EAC over the past decade, a gap remains in understanding how the atlas of genomic aberrations in this cancer impacts the proteome and which somatic variants are of importance for the disease phenotype. We performed a quantitative proteomic analysis of 23 EACs and matched adjacent normal esophageal and gastric tissues. We explored the correlation of transcript and protein abundance using tissue-matched RNA-seq and proteomic data from seven patients and further integrated these data with a cohort of EAC RNA-seq data (n = 264 patients), EAC whole-genome sequencing (n = 454 patients), and external published datasets. We quantified protein expression from 5879 genes in EAC and patient-matched normal tissues. Several biomarker candidates with EAC-selective expression were identified, including the transmembrane protein GPA33. We further verified the EAC-enriched expression of GPA33 in an external cohort of 115 patients and confirm this as an attractive diagnostic and therapeutic target. To further extend the insights gained from our proteomic data, an integrated analysis of protein and RNA expression in EAC and normal tissues revealed several genes with poorly correlated protein and RNA abundance, suggesting posttranscriptional regulation of protein expression. These outlier genes, including SLC25A30, TAOK2, and AGMAT, only rarely demonstrated somatic mutation, suggesting post-transcriptional drivers for this EAC-specific phenotype. AGMAT was demonstrated to be overexpressed at the protein level in EAC compared to adjacent normal tissues with an EAC-selective, post-transcriptional mechanism of regulation of protein abundance proposed. Integrated analysis of proteome, transcriptome, and genome in EAC has revealed several genes with tumor-selective, posttranscriptional regulation of protein expression, which may be an exploitable vulnerability.

Published
2024
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44. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Author

Sawas, Tarek, primary, Killcoyne, Sarah, additional, Iyer, Prasad G., additional, Wang, Kenneth K., additional, Smyrk, Thomas C., additional, Kisiel, John B., additional, Qin, Yi, additional, Ahlquist, David A., additional, Rustgi, Anil K., additional, Costa, Rui J., additional, Gerstung, Moritz, additional, Fitzgerald, Rebecca C., additional, Katzka, David A., additional, Noorani, Ayesha, additional, Edwards, Paul A.W., additional, Grehan, Nicola, additional, Nutzinger, Barbara, additional, Hughes, Caitriona, additional, Fidziukiewicz, Elwira, additional, Bornschein, Jan, additional, MacRae, Shona, additional, Crawte, Jason, additional, Contino, Gianmarco, additional, Li, Xiaodun, additional, Rue, Rachel de la, additional, O’Donovan, Maria, additional, Miremad, Ahmad, additional, Malhotra, Shalini, additional, Tripathi, Monika, additional, Tavaré, Simon, additional, Lynch, Andy G., additional, Eldridge, Matthew, additional, Secrier, Maria, additional, Bower, Lawrence, additional, Devonshire, Ginny, additional, Perner, Juliane, additional, Jammula, Sriganesh, additional, Davies, Jim, additional, Crichton, Charles, additional, Carroll, Nick, additional, Safranek, Peter, additional, Hindmarsh, Andrew, additional, Sujendran, Vijayendran, additional, Hayes, Stephen J., additional, Ang, Yeng, additional, Preston, Shaun R., additional, Oakes, Sarah, additional, Bagwan, Izhar, additional, Save, Vicki, additional, Skipworth, Richard J.E., additional, Hupp, Ted R., additional, O’Neill, J. Robert, additional, Tucker, Olga, additional, Beggs, Andrew, additional, Taniere, Philippe, additional, Puig, Sonia, additional, Underwood, Timothy J., additional, Noble, Fergus, additional, Owsley, Jack, additional, Barr, Hugh, additional, Shepherd, Neil, additional, Old, Oliver, additional, Lagergren, Jesper, additional, Gossage, James, additional, Davies, Andrew, additional, Chang, Fuju, additional, Zylstra, Janine, additional, Mahadeva, Ula, additional, Goh, Vicky, additional, Ciccarelli, Francesca D., additional, Sanders, Grant, additional, Berrisford, Richard, additional, Harden, Catherine, additional, Bunting, David, additional, Lewis, Mike, additional, Cheong, Ed, additional, Kumar, Bhaskar, additional, Parsons, Simon L., additional, Soomro, Irshad, additional, Kaye, Philip, additional, Saunders, John, additional, Lovat, Laurence, additional, Haidry, Rehan, additional, Eneh, Victor, additional, Igali, Laszlo, additional, Scott, Michael, additional, Sothi, Sharmila, additional, Suortamo, Sari, additional, Lishman, Suzy, additional, Hanna, George B., additional, Peters, Christopher J., additional, Grabowska, Anna, additional, and Turkington, Richard, additional

Published
2018
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46. Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.

Author

Thompson, K. P., Nelson, J., Kim, H., Pawlikowska, L., Marchuk, D. A., Lawton, M. T., Faughnan, Marie E., the Brain Vascular Malformation Consortium HHT Investigator Group, Chakinala, Murali, Clancy, Marianne S., Gossage, James R., Henderson, Katharine, Iyer, Vivek, Kasthuri, Raj S., Kim, Helen, Krings, Timo, Lawton, Michael T., Lin, Doris, Mager, Hans-Jurgen, and Marchuk, Douglas A.

Subjects
HEREDITARY hemorrhagic telangiectasia, DEATH forecasting, MORTALITY, ARTERIOVENOUS malformation, GASTROINTESTINAL hemorrhage, RESEARCH, RESEARCH methodology, RETROSPECTIVE studies, CELL receptors, MEDICAL cooperation, EVALUATION research, ARTERIOVENOUS fistula, COMPARATIVE studies, RESEARCH funding, LONGITUDINAL method
Abstract

Background: Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark's centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status.Results: 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37-6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46-4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15-3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60-60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths).Conclusions: Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients. [ABSTRACT FROM AUTHOR]

Published
2021
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47. A longitudinal assessment of psychological distress after oesophageal cancer surgery

Author

Hellstadius, Ylva, Lagergren, Jesper, Zylstra, Janine, Gossage, James, Davis, Andrew, M Hultman, Christina, Lagergren, Pernilla, Wikman, Anna, Hellstadius, Ylva, Lagergren, Jesper, Zylstra, Janine, Gossage, James, Davis, Andrew, M Hultman, Christina, Lagergren, Pernilla, and Wikman, Anna

Abstract

Background: Psychological distress is common among patients with oesophageal cancer. However, little is known about the course and predictors of psychological distress among patients treated with curative intent. Therefore, the aim of this study was to explore the prevalence, course and predictors of anxiety and depression in patients operated for oesophageal cancer, from prior to surgery to 12 months post-operatively. Methods: A prospective cohort of patients with oesophageal cancer (n ¼ 218) were recruited from one high-volume specialist oesophago-gastric treatment centre (St Thomas’ Hospital, London, UK). Anxiety and depression were assessed prior to surgery, 6 and 12 months post-operatively. Mixed-effects modelling was performed to investigate changes over time and to estimate the association between clinical and socio-demographic predictor variables and anxiety and depression symptoms. Results: The proportion of patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12 months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12-month follow-up. Anxiety symptoms remained stable over time whereas depression symptoms appeared to increase from pre-surgery to 6 months, levelling off between 6 and 12 months. Younger age, female sex, living alone and more severe self-reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety symptoms. In-hospital complications, greater limitations in activity status and more severe selfreported dysphagia were predictive of higher depression. Conclusions: Many patients report psychological distress during the first year following oesophageal cancer surgery. Whether improving the experience of swallowing difficulties may also reduce distress among these patients warrants further study.

Published
2017
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48. Extent of lymphadenectomy and prognosis after esophageal cancer surgery

Author

Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, Davies, Andrew, Lagergren, Jesper, Mattsson, Fredrik, Zylstra, Janine, Chang, Fuju, Gossage, James, Mason, Robert, Lagergren, Pernilla, and Davies, Andrew

Abstract

IMPORTANCE: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95%CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95%CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95%CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mort

Published
2017

49. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

Author

Secrier, Maria, Li, Xiaodun, de Silva, Nadeera, Eldridge, Matthew D., Contino, Gianmarco, Bornschein, Jan, MacRae, Shona, Grehan, Nicola, O'Donovan, Maria, Miremadi, Ahmad, Yang, Tsun-Po, Bower, Lawrence, Chettouh, Hamza, Crawte, Jason, Galeano-Dalmau, Núria, Grabowska, Anna, Saunders, John, Underwood, Tim, Waddell, Nicola, Barbour, Andrew P., Nutzinger, Barbara, Achilleos, Achilleas, Edwards, Paul A.W., Lynch, Andy G., Tavaré, Simon, Fitzgerald, Rebecca C., Noorani, Ayesha, Elliott, Rachael Fels, Weaver, Jamie, Ross-Innes, Caryn, Smith, Laura, Abdullahi, Zarah, de la Rue, Rachel, Cluroe, Alison, Malhotra, Shalini, Hardwick, Richard, Ford, Hugo, Smith, Mike L., Davies, Jim, Turkington, Richard, Hayes, Stephen J., Ang, Yeng, Preston, Shaun R., Oakes, Sarah, Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J. Robert, Tucker, Olga, Taniere, Philippe, Noble, Fergus, Owsley, Jack, Lovat, Laurence, Haidry, Rehan, Eneh, Victor, Crichton, Charles, Barr, Hugh, Shepherd, Neil, Old, Oliver, Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Zylstra, Janine, Sanders, Grant, Berrisford, Richard, Harden, Catherine, Bunting, David, Lewis, Mike, Cheong, Ed, Kumar, Bhaskar, Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Collier, Pamela, Igali, Laszlo, Welch, Ian, Scott, Michael, Sothi, Shamila, Suortamo, Sari, Lishman, Suzy, Beardsmore, Duncan, Francies, Hayley E., Garnett, Mathew J., Pearson, John V., Nones, Katia, Patch, Ann-Marie, Grimmond, Sean M., Achilleos, Achilleas [0000-0001-7157-8991], Apollo - University of Cambridge Repository, and Davies, J

Subjects
0301 basic medicine, Male, Esophageal Neoplasms, Sequence analysis, medicine.medical_treatment, CD8 Antigens, Antineoplastic Agents, Adenocarcinoma, Poly(ADP-ribose) Polymerase Inhibitors, medicine.disease_cause, Receptor tyrosine kinase, DNA sequencing, Targeted therapy, Cohort Studies, 03 medical and health sciences, Genetic Heterogeneity, 0302 clinical medicine, Cell Line, Tumor, Genetics, medicine, Humans, Aged, Mutation, biology, Genetic heterogeneity, Genome, Human, Cancer, Receptor Protein-Tyrosine Kinases, DNA, Neoplasm, Sequence Analysis, DNA, medicine.disease, 3. Good health, Homologous Recombination Pathway, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, DNA Damage
Abstract

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

Published
2016

50. Management and Reconstruction of a Gastroesophageal Junction Adenocarcinoma Patient Three Years after Pancreaticoduodenectomy: A Surgical Puzzle

Author

Dellaportas, Dionysios, Gossage, James A., and Davies, Andrew R.

Subjects
Article Subject
Abstract

Introduction. With the improving survival of cancer patients, the development of a secondary primary cancer is an increasingly common phenomenon. Extensive surgery during initial treatment may pose significant challenges to surgeons managing the second primary cancer. Case Presentation. A 69-year-old male, who had a pancreaticoduodenectomy three years ago for pancreatic head adenocarcinoma, underwent an uneventful extended total gastrectomy for gastroesophageal junctional adenocarcinoma. The reconstruction controversies and considerations are highlighted. Discussion. Genetic, environmental, and lifestyle factors are common for several gastrointestinal malignancies. However, the occurrence of a second unfavorable cancer such as gastroesophageal adenocarcinoma after pancreatic head cancer treatment is extremely uncommon. This clinical scenario possesses numerous difficulties for the surgeon, since surgical resection is the mainstay of treatment for both malignancies. Gastrointestinal reconstruction becomes challenging and requires careful planning and meticulous surgical technique along with sound intraoperative judgement.

Published
2016
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