Imperial College London

ProfessorGeorgeHanna

Faculty of MedicineDepartment of Surgery & Cancer

Head of Department of Surgery and Cancer
 
 
 
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Contact

 

+44 (0)20 7594 3396g.hanna

 
 
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Assistant

 

Ms Aoibheann Byrne +44 (0)20 7594 3396

 
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Location

 

Block B Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

530 results found

Rahman SA, Walker RC, Lloyd MA, Grace BL, van Boxel GI, Kingma BF, Ruurda JP, van Hillegersberg R, Harris S, Parsons S, Mercer S, Griffiths EA, O'Neill JR, Turkington R, Fitzgerald RC, Underwood TJ, OCCAMS Consortiumet al., 2020, Machine learning to predict early recurrence after oesophageal cancer surgery., Br J Surg, Vol: 107, Pages: 1042-1052

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

Journal article

Halliday LJ, Doran SLF, Sgromo B, Viswanath YKS, Tucker O, Patel B, Jambulingam PS, Dawas K, Mercer S, Baker C, Mughal M, Hanna GB, Moorthy Ket al., 2020, Variation in esophageal anastomosis technique-the role of collaborative learning., Dis Esophagus, Vol: 33

Centralization of care has improved outcomes in esophagogastric (EG) cancer surgery. However, specialist surgical centers often work within clinical silos, with little transfer of knowledge and experience. Although variation exists in multiple dimensions of perioperative care, the differences in operative technique are rarely studied. An esophageal anastomosis workshop was held to identify areas of common and differing practice within the operative technique. Surgeons showed videos of their anastomosis technique by open and minimally invasive surgery. Each video was followed by a discussion. Surgeons from 10 different EG cancer centers attended. Eight key technical differences and learning points were identified and discussed: the optimum diameter of the gastric conduit; avoiding ischemia in the gastric conduit; minimizing esophageal trauma; the use of an esophageal mucosal collar; omental wrapping; intraoperative leak testing; ideal diameter of the circular stapler and the growing use of linear stapled anastomoses. The workshop received positive feedback from participants and on 2 years follow-up, 40% stated that they believed that the learning of tips and techniques during the workshop has contributed to lowering their anastomotic leak rate. Many differences exist in surgical technique. The reasons for, and crucially the significance of, these differences must be discussed and examined. Workshops provide a forum for peer-to-peer collaborative learning to reflect on one's own practice and improve surgical technique. These changes can, in turn, generate incremental improvements in patient care and postoperative outcomes.

Journal article

Vadhwana B, Belluomo I, Boshier PR, Pavlou C, Spanel P, Hanna GBet al., 2020, Impact of oral cleansing strategies on exhaled volatile organic compound levels, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 34, ISSN: 0951-4198

Journal article

Tukanova K, Markar SR, Jamel S, Vidal-Diez A, Hanna GBet al., 2020, An international comparison of the utilisation of and outcomes from minimal access surgery for the treatment of common abdominal surgical emergencies, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 34, Pages: 2012-2018, ISSN: 0930-2794

Journal article

Jammula S, Katz-Summercorn AC, Li X, Linossi C, Smyth E, Killcoyne S, Biasci D, Subash VV, Abbas S, Blasko A, Devonshire G, Grantham A, Wronowski F, O'Donovan M, Grehan N, Eldridge MD, Tavaré S, Oesophageal Cancer Clinical and Molecular Stratification OCCAMS consortium, Fitzgerald RCet al., 2020, Identification of Subtypes of Barrett's Esophagus and Esophageal Adenocarcinoma Based on DNA Methylation Profiles and Integration of Transcriptome and Genome Data., Gastroenterology, Vol: 158, Pages: 1682-1697.e1

BACKGROUND & AIMS: Esophageal adenocarcinomas (EACs) are heterogeneous and often preceded by Barrett's esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed epigenetic analyses of BE and EAC tissues and combined these data with transcriptome and genomic data to identify mechanisms that control gene expression and genome integrity. METHODS: In a retrospective cohort study, we collected tissue samples and clinical data from 150 BE and 285 EAC cases from the Oesophageal Cancer Classification and Molecular Stratification consortium in the United Kingdom. We analyzed methylation profiles of all BE and EAC tissues and assigned them to subgroups using non-negative matrix factorization with k-means clustering. Data from whole-genome sequencing and transcriptome studies were then incorporated; we performed integrative methylation and RNA-sequencing analyses to identify genes that were suppressed with increased methylation in promoter regions. Levels of different immune cell types were computed using single-sample gene set enrichment methods. We derived 8 organoids from 8 EAC tissues and tested their sensitivity to different drugs. RESULTS: BE and EAC samples shared genome-wide methylation features, compared with normal tissues (esophageal, gastric, and duodenum; controls) from the same patients and grouped into 4 subtypes. Subtype 1 was characterized by DNA hypermethylation with a high mutation burden and multiple mutations in genes in cell cycle and receptor tyrosine signaling pathways. Subtype 2 was characterized by a gene expression pattern associated with metabolic processes (ATP synthesis and fatty acid oxidation) and lack methylation at specific binding sites for transcription factors; 83% of samples of this subtype were BE and 17% were EAC. The third subtype did not have changes in methylation pattern, compared with control tissue, but had a gene expression pattern t

Journal article

Abbassi-Ghadi N, Antonowicz S, McKenzie J, Kumar S, Huang J, Jones E, Strittmatter N, Petts G, Kudo H, court S, Hoare J, Veselkov K, Goldin R, Takats Z, Hanna Get al., 2020, De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma, Cancer Research, Vol: 80, Pages: 2764-2774, ISSN: 0008-5472

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.

Journal article

Markar SR, Ni M, Mackenzie H, Penna M, Faiz O, Hanna GBet al., 2020, The effect of time between procedures upon the proficiency gain period for minimally invasive esophagectomy, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 34, Pages: 2703-2708, ISSN: 0930-2794

Journal article

Markar SR, Arhi C, Wiggins T, Vidal-Diez A, Karthikesalingam A, Darzi A, Lagergren J, Hanna GBet al., 2020, Reintervention after antireflux surgery for gastroesophageal reflux disease in England, Annals of Surgery, Vol: 271, Pages: 709-715, ISSN: 0003-4932

BACKGROUND: After antireflux surgery, highly variable rates of recurrent gastroesophageal reflux disease (GERD) have been reported. OBJECTIVE: To identify the occurrence and risk factors of recurrent GERD requiring surgical reintervention or medication. METHODS: The Hospital Episode Statistics database was used to identify adults in England receiving primary antireflux surgery for GERD in 2000 to 2012 with follow-up through 2014, and the outcome was surgical reintervention. In a subset of participants, the Clinical Practice Research Datalink was additionally used to assess proton pump inhibitor therapy for at least 6 months (medical reintervention). Risk factors were assessed using multivariable Cox regression providing adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: Among 22,377 patients who underwent primary antireflux surgery in the Hospital Episode Statistics dataset, 811 (3.6%) had surgical reintervention, with risk factors being age 41 to 60 years (HR = 1.22, 95% CI 1.03-1.44), female sex (HR = 1.5; 95% CI 1.3-1.74), white ethnicity (HR = 1.71, 95% CI 1.06-2.77), and low hospital annual volume of antireflux surgery (HR = 1.32, 95% CI 1.04-1.67). Among 2005 patients who underwent primary antireflux surgery in the Clinical Practice Research Datalink dataset, 189 (9.4%) had surgical reintervention and 1192 (59.5%) used proton pump inhibitor therapy, with risk factors for the combined outcome being age >60 years (HR = 2.38, 95% CI 1.81-3.13) and preoperative psychiatric morbidity (HR = 1.58, 95% CI 1.25-1.99). CONCLUSION: At least 3.6% of patients may require surgical reintervention and 59.5% medical therapy following antireflux surgery in England. The influence of patient characteristics and hospital volume highlights the need for patient selection and surgical experience in successful antireflux surgery.

Journal article

Harris A, Butterworth J, Boshier PR, MacKenzie H, Tokunaga M, Sunagawa H, Mavroveli S, Ni M, Mikhail S, Yeh C-C, Blencowe NS, Avery KNL, Hardwick R, Hoelscher A, Pera M, Zaninotto G, Law S, Low DE, van Lanschot JJB, Berrisford R, Barham CP, Blazeby JM, Hanna GBet al., 2020, Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials., Ann Surg

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098. TRIAL REGISTRATION NUMBER: ISRCTN59036820, ISRCTN10386621.

Journal article

Ni M, Borsci S, Walne S, Mclister AP, Buckle P, Barlow JG, Hanna GBet al., 2020, The Lean and Agile Multi-dimensional Process (LAMP) - a new framework for rapid and iterative evidence generation to support health-care technology design and development, EXPERT REVIEW OF MEDICAL DEVICES, Vol: 17, Pages: 277-288, ISSN: 1743-4440

Journal article

Wiggins T, Markar S, Jamel S, Hakky S, Ahmed A, Hanna Get al., 2020, Assurance of surgical quality within multicentre randomised controlled trials for bariatric and metabolic surgery: a systematic review, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S31-S31, ISSN: 0960-8923

Conference paper

Tukanova K, Papi E, Jamel S, Hanna GB, McGregor AH, Markar SRet al., 2020, Assessment of chest wall movement following thoracotomy: a systematic review, JOURNAL OF THORACIC DISEASE, Vol: 12, Pages: 1031-+, ISSN: 2072-1439

Journal article

Goh YM, Antonowicz S, Boshier P, Hanna Get al., 2020, Metabolic biomarkers of squamous cell carcinoma of the aerodigestive tract: a systematic review and quality assessment, Oxidative Medicine and Cellular Longevity, Vol: 2020, Pages: 1-13, ISSN: 1942-0900

Introduction. Aerodigestive squamous cell carcinomas (ASCC) constitute a major source of global cancer deaths. Patients typically present with advanced, incurable disease, so new means of detecting early disease are a research priority. Metabolite quantitation is amenable to point-of-care analysis and can be performed in ASCC surrogates such as breath and saliva. The purpose of this systematic review is to summarise progress of ASCC metabolomic studies, with an emphasis on the critical appraisal of methodological quality and reporting. Method. A systematic online literature search was performed to identify studies reporting metabolic biomarkers of ASCC. This review was conducted in accordance with the recommendations of the Cochrane Library and MOOSE guidelines. Results. Thirty studies comprising 2117 patients were included in the review. All publications represented phase-I biomarker discovery studies, and none validated their findings in an independent cohort. There was heterogeneity in study design and methodological and reporting quality. Sensitivities and specificities were higher in oesophageal and head and neck squamous cell carcinomas compared to those in lung squamous cell carcinoma. The metabolic phenotypes of these cancers were similar, as was the kinetics of metabolite groups when comparing blood, tissue, and breath/saliva concentrations. Deregulation of amino acid metabolism was the most frequently reported theme. Conclusion. Metabolite analysis has shown promising diagnostic performance, especially for oesophageal and head and neck ASCC subtypes, which are phenotypically similar. However, shortcomings in study design have led to inconsistencies between studies. To support future studies and ultimately clinical adoption, these limitations are discussed.

Journal article

de Vries FEE, Hodgkinson JD, Claessen JJM, van Ruler O, Leo CA, Maeda Y, Lapid O, Obdeijn MC, Tanis PJ, Bemelman WA, Constantinides J, Hanna GB, Warusavitarne J, Vaizey C, Boermeester MAet al., 2020, Long-term outcomes after contaminated complex abdominal wall reconstruction, HERNIA, Vol: 24, Pages: 459-468, ISSN: 1265-4906

Journal article

Hodgkinson JD, de Vries FEE, Claessen JJM, Leo CA, Maeda Y, van Ruler O, Lapid O, Obdeijn MC, Tanis PJ, Bemelman WA, Constantinides J, Hanna GB, Warusavitarne J, Boermeester MA, Vaizey Cet al., 2020, The development and validation of risk-stratification models for short-term outcomes following contaminated complex abdominal wall reconstruction, HERNIA, Vol: 24, Pages: 449-458, ISSN: 1265-4906

Journal article

Campbell PJ, Getz G, Korbel JO, Stuart JM, Jennings JL, Stein LD, Perry MD, Nahal-Bose HK, Ouellette BFF, Li CH, Rheinbay E, Nielsen GP, Sgroi DC, Wu C-L, Faquin WC, Deshpande V, Boutros PC, Lazar AJ, Hoadley KA, Louis DN, Dursi LJ, Yung CK, Bailey MH, Saksena G, Raine KM, Buchhalter I, Kleinheinz K, Schlesner M, Zhang J, Wang W, Wheeler DA, Ding L, Simpson JT, O'Connor BD, Yakneen S, Ellrott K, Miyoshi N, Butler AP, Royo R, Shorser S, Vazquez M, Rausch T, Tiao G, Waszak SM, Rodriguez-Martin B, Shringarpure S, Wu D-Y, Demidov GM, Delaneau O, Hayashi S, Imoto S, Habermann N, Segre A, Garrison E, Cafferkey A, Alvarez EG, Maria Heredia-Genestar J, Muyas F, Drechsel O, Bruzos AL, Temes J, Zamora J, Baez-Ortega A, Kim H-L, Mashl RJ, Ye K, DiBiase A, Huang K-L, Letunic I, McLellan MD, Newhouse SJ, Shmaya T, Kumar S, Wedge DC, Wright MH, Yellapantula VD, Gerstein M, Khurana E, Marques-Bonet T, Navarro A, Bustamante CD, Siebert R, Nakagawa H, Easton DF, Ossowski S, Tubio JMC, De La Vega FM, Estivill X, Yuen D, Mihaiescu GL, Omberg L, Ferretti V, Sabarinathan R, Pich O, Gonzalez-Perez A, Weiner AT, Fittall MW, Demeulemeester J, Tarabichi M, Roberts ND, Van Loo P, Cortes-Ciriano I, Urban L, Park P, Bin Z, Pitkaenen E, Li Y, Saini N, Klimczak LJ, Weischenfeldt J, Sidiropoulos N, Alexandrov LB, Rabionet R, Escaramis G, Bosio M, Holik AZ, Susak H, Prasad A, Erkek S, Calabrese C, Raeder B, Harrington E, Mayes S, Turner D, Juul S, Roberts SA, Song L, Koster R, Mirabello L, Hua X, Tanskanen TJ, Tojo M, Chen J, Aaltonen LA, Ratsch G, Schwarz RF, Butte AJ, Brazma A, Chanock SJ, Chatterjee N, Stegle O, Harismendy O, Bova GS, Gordenin DA, Haan D, Sieverling L, Feuerbach L, Chalmers D, Joly Y, Knoppers B, Molnar-Gabor F, Phillips M, Thorogood A, Townend D, Goldman M, Fonseca NA, Xiang Q, Craft B, Pineiro-Yanez E, Munoz A, Petryszak R, Fullgrabe A, Al-Shahrour F, Keays M, Haussler D, Weinstein J, Huber W, Valencia A, Papatheodorou I, Zhu J, Fan Y, Torrents D, Bieg M, Chen K, Chong Z, Cibet al., 2020, Pan-cancer analysis of whole genomes, Nature, Vol: 578, Pages: 82-93, ISSN: 0028-0836

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

Journal article

Bornschein J, Wernisch L, Secrier M, Miremadi A, Perner J, MacRae S, O'Donovan M, Newton R, Menon S, Bower L, Eldridge MD, Devonshire G, Cheah C, Turkington R, Hardwick RH, Selgrad M, Venerito M, Malfertheiner P, Fitzgerald RC, Noorani A, Elliott RF, Edwards PAW, Grehan N, Nutzinger B, Crawte J, Chettouh H, Contino G, Li X, Gregson E, Zeki S, de la Rue R, Malhotra S, Tavare S, Lynch AG, Smith ML, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood TJ, Noble F, Owsley J, Barr H, Shepherd N, Old O, Lagergren J, Gossage J, Davies A, Chang F, Zylstra J, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Bunting D, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Eneh V, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Peters CJ, Grabowska Aet al., 2019, Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction, International Journal of Cancer, Vol: 145, Pages: 3389-3401, ISSN: 0020-7136

Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed.

Journal article

Turkington RC, Knight LA, Blayney JK, Secrier M, Douglas R, Parkes EE, Sutton EK, Stevenson L, McManus D, Halliday S, McCavigan AM, Logan GE, Walker SM, Steele CJ, Perner J, Bornschein J, MacRae S, Miremadi A, McCarron E, McQuaid S, Arthur K, James JA, Eatock MM, O'Neill R, Noble F, Underwood TJ, Harkin DP, Salto-Tellez M, Fitzgerald RC, Kennedy RD, Noorani A, Edwards PAW, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, Crawte J, Northrop A, Contino G, Li X, de la Rue R, O'Donovan M, Malhotra S, Tripathi M, Tavare S, Lynch AG, Eldridge M, Bower L, Devonshire G, Jammula S, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, Tucker O, Beggs A, Taniere P, Puig S, Owsley J, Barr H, Shepherd N, Old O, Lagergren J, Gossage J, Davies A, Chang F, Zylstra J, Mahadeva U, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Moorthy K, Peters CJ, Grabowska A, Coleman Het al., 2019, Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma, GUT, Vol: 68, Pages: 1918-1927, ISSN: 0017-5749

Journal article

Hodgkinson JD, Oke SM, Warusavitarne J, Hanna GB, Gabe SM, Vaizey CJet al., 2019, Incisional hernia and enterocutaneous fistula in patients with chronic intestinal failure: prevalence and risk factors in a cohort of patients referred to a tertiary centre, COLORECTAL DISEASE, Vol: 21, Pages: 1288-1295, ISSN: 1462-8910

Journal article

Tsai AY-C, Mavroveli S, Miskovic D, van Oostendorp S, Adamina M, Hompes R, Aigner F, Spinelli A, Warusavitarne J, Knol J, Albert M, Nassif G, Bemelman W, Boni L, Ovesen H, Austin R, Muratore A, Seitinger G, Sietses C, Lacy AM, Tuynman JB, Bonjer HJ, Hanna GBet al., 2019, Surgical Quality Assurance in COLOR III Standardization and Competency Assessment in a Randomized Controlled Trial, ANNALS OF SURGERY, Vol: 270, Pages: 768-774, ISSN: 0003-4932

Journal article

Markar SR, Vidal-Diez A, Patel K, Maynard W, Tukanova K, Murray A, Holt PJ, Karthikesalingam A, Hanna GBet al., 2019, Comparison of Surgical Intervention and Mortality for Seven Surgical Emergencies in England and the United States, ANNALS OF SURGERY, Vol: 270, Pages: 806-812, ISSN: 0003-4932

Journal article

Markar S, Lagergren P, Zaninotto G, Huddy J, Findlay J, Antonowicz S, Maynard N, Ariyathenam A, Sanders G, Jahoo S, McCormack O, Allum W, Klevebro F, Nilsson M, Henegouwen MVB, Gisbertz S, Van Hillegersberg R, Ruurda J, Lagarde S, Wijnhoven B, Elliott J, Van Lanschot J, Matthijsen R, Pera M, Alferi R, Castoro C, Reynolds J, Hanna Get al., 2019, AUGIS abstracts 2019, 22nd Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 5-5, ISSN: 0007-1323

Conference paper

Boshier PR, Swaray A, O'Sullivan A, Low DE, Hanna GB, Peters CJet al., 2019, Predictive models of survival after resection of oesophageal adenocarcinoma: a systematic review and multicentre validation of models, 22nd Annual Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: WILEY, Pages: 66-66, ISSN: 0007-1323

Conference paper

Arhi CS, Markar S, Burns EM, Bouras G, Bottle A, Hanna G, Aylin P, Ziprin P, Darzi Aet al., 2019, Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer, Diseases of the Esophagus, Vol: 32, Pages: 1-11, ISSN: 1120-8694

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68-0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67-0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21-0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.

Journal article

Curtis NJ, Conti JA, Dalton R, Rockall TA, Allison AS, Ockrim JB, Jourdan IC, Torkington J, Phillips S, Allison J, Hanna GB, Francis NKet al., 2019, 2D versus 3D laparoscopic total mesorectal excision: a developmental multicentre randomised controlled trial, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 33, Pages: 3370-3383, ISSN: 0930-2794

AimsThe role of laparoscopy in rectal cancer has been questioned. 3D laparoscopic systems are suggested to aid optimal surgical performance but have not been evaluated in advanced procedures. We hypothesised that stereoscopic imaging could improve the performance of laparoscopic total mesorectal excision (TME).MethodsA multicentre developmental randomised controlled trial comparing 2D and 3D laparoscopic TME was performed (ISRCTN59485808). Trial surgeons were colorectal consultants that had completed their TME proficiency curve and underwent stereoscopic visual testing. Patients requiring elective laparoscopic TME with curative intent were centrally randomised (1:1) to 2D or 3D using Karl Storz IMAGE1 S D3-Link™ and 10-mm TIPCAM®1S 3D passive polarising laparoscopic systems. Outcomes were enacted adverse events as assessed by the observational clinical human reliability analysis technique, intraoperative data, 30-day patient outcomes, histopathological specimen assessment and surgeon cognitive load.Results88 patients were included. There were no differences in patient or tumour demographics, surgeon stereopsis, case difficulty, cognitive load, operative time, blood loss or conversion between the trial arms. 1377 intraoperative adverse events were identified (median 18 per case, IQR 14–21, range 2–49) with no differences seen between the 2D and 3D arms (18 (95% CI 17–21) vs. 17 (95% CI 16–19), p = 0.437). 3D laparoscopy had non-significantly higher mesorectal fascial plane resections (94 vs. 77%, p = 0.059; OR 0.23 (95% CI 0.05–1.16)) but equal lymph node yield and circumferential margin distance and involvement. 30-day morbidity, anastomotic leak, re-operation, length of stay and readmission rates were equal between the 2D and 3D arms.ConclusionFeasibility of performing multicentre 3D laparoscopic multicentre trials of specialist performed complex procedures is shown. 3D imaging did not alter the nu

Journal article

Halliday L, Doganay E, Lada H, Wynter-Blyth V, Hanna G, Moorthy Ket al., 2019, Prehabilitation in oesophago-gastric cancer: the impact on post-operative outcomes, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY, Pages: 79-79, ISSN: 0007-1323

Conference paper

Wiggins T, Markar SR, MacKenzie H, Faiz O, Mukherjee D, Khoo DE, Purkayastha S, Beckingham I, Hanna GBet al., 2019, Optimum timing of emergency cholecystectomy for acute cholecystitis in England: population-based cohort study, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 33, Pages: 2495-2502, ISSN: 0930-2794

BackgroundCholecystectomy on index admission for acute cholecystitis is associated with improved patient outcomes. The timing of intervention is mainly driven by service provision. This population-based cohort study aimed to evaluate timing of emergency cholecystectomy in England.MethodsData from all consecutive patients undergoing surgery for acute cholecystitis on index admission in England from 1997 to 2012 were captured from the Hospital Episodes Statistics database. Data were analysed based on whether patients underwent surgery 0–3 days, 4–7 days or ≥ 8 days from admission. Outcome measures were rate of post-operative biliary complications, conversion to open and length of stay.ResultsForty-three thousand eight hundred and seventy patients underwent emergency cholecystectomy. 64.6% of patients underwent surgery between days 0 and 3 of admission, 24.3% between days 4–7 and 11.0% had surgery after day 8. Patients undergoing early surgery had significantly reduced rates of intra-operative laparoscopic conversion to open (0–3 days: 3.6%; 4–7 days: 4.0%; ≥ 8 days 4.7%, p = 0.001), post-operative ERCP (0–3 days: 1.1%; 4–7 days: 1.5%; ≥ 8 days 1.9%, p < 0.001) and bile duct injury (0–3 days: 0.6%; 4–7 days: 1.0%; ≥ 8 days 1.8%, p < 0.001). Early cholecystectomy was also associated with a shorter post-operative length of stay (LOS) [0–3 days group: median post-operative LOS 3 days (IQR: 1–6); 4–7 days group: 3 days (IQR 2–6); ≥ 8 days group: 4 days (IQR 2–9) (p < 0.001)]. High-volume centres undertook a significantly greater proportion of cholecystectomies within 3 days of presentation (high-volume: 67.3%; medium-volume: 64.8%; low-volume: 61.2%). In multivariate analysis greater time to surgery was independently associated with increased risk of post-operative ERCP and bil

Journal article

Mourikis TP, Benedetti L, Foxall E, Temelkovski D, Nulsen J, Perner J, Cereda M, Lagergren J, Howell M, Yau C, Fitzgerald RC, Scaffidi P, Noorani A, Edwards PAW, Elliott RF, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, Bornschein J, MacRae S, Crawte J, Northrop A, Contino G, Li X, de la Rue R, Katz-Summercorn A, Abbas S, Loureda D, O'Donovan M, Miremadi A, Malhotra S, Tripathi M, Tavare S, Lynch AG, Eldridge M, Secrier M, Bower L, Devonshire G, Jammula S, Davies J, Crichton C, Carroll N, Safranek P, Hindmarsh A, Sujendran V, Hayes SJ, Ang Y, Sharrocks A, Preston SR, Oakes S, Bagwan I, Save V, Skipworth RJE, Hupp TR, O'Neill JR, Tucker O, Beggs A, Taniere P, Puig S, Underwood TJ, Walker RC, Grace BL, Barr H, Shepherd N, Old O, Gossage J, Davies A, Chang F, Zylstra J, Mahadeva U, Goh V, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Peters CJ, Moorthy K, Grabowska A, Turkington R, McManus D, Khoo D, Fickling W, Ciccarelli FDet al., 2019, Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma, Nature Communications, Vol: 10, Pages: 1-17, ISSN: 2041-1723

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

Journal article

Curtis NJ, Dennison G, Brown CSB, Hewett PJ, Hanna GB, Stevenson ARL, Francis NKet al., 2019, Clinical evaluation of intraoperative near misses in laparoscopic rectal cancer surgery., Annals of Surgery, Pages: 1-7, ISSN: 0003-4932

OBJECTIVE: To investigate the frequency, nature, and severity of intraoperative adverse near miss events within advanced laparoscopic surgery and report any associated clinical impact. BACKGROUND: Despite implementation of surgical safety initiatives, the intraoperative period is poorly documented with evidence of underreporting. Near miss analyses are undertaken in high-risk industries but not in surgical practice. METHODS: Case video and data from 2 laparoscopic total mesorectal excision randomized controlled trials were analyzed (ALaCaRT ACTRN12609000663257, 2D3D ISRCTN59485808). Intraoperative adverse events were identified and categorized using the observational clinical human reliability analysis technique. The EAES classification was applied by 2 blinded assessors. EAES grade 1 events (nonconsequential error, no damage, or need for correction) were considered near misses. Associated clinical impact was assessed with early morbidity and histopathology outcomes. RESULTS: One hundred seventy-five cases contained 1113 error events. Six hundred ninety-eight (62.7%) were near misses (median 3, IQR 2-5, range 0-15) with excellent inter-rater and test-retest reliability (κ=0.86, 95% CI 0.83-0.89, P < 0.001 and κ=0.88, 95% CI 0.85-0.9, P < 0.001 respectively). Significantly more near misses were seen in patients who developed early complications (4 (3-6) vs. 3 (2-4), P < 0.001). Higher numbers of near misses were seen in patients with more numerous (P = 0.002) and more serious early complications (P = 0.003). Cases containing major intraoperative adverse events contained significantly more near misses (5 (3-7) vs. 3 (2-5), P < 0.001) with a major event observed for every 19.4 near misses. CONCLUSION: Intraoperative adverse events and near misses can be reliably and objectively captured in advanced laparoscopic surgery. Near misses are commonplace and closely associated with morbidity outcomes.

Journal article

Hanna GB, Boshier PR, Markar SR, Romano Aet al., 2019, Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis (vol 5, e182815, 2019), JAMA ONCOLOGY, Vol: 5, Pages: 1070-1070, ISSN: 2374-2437

Journal article

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