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

558 results found

Tarazi M, Jamel S, Mullish BH, Markar SR, Hanna GBet al., 2021, Impact of gastrointestinal surgery upon the gut microbiome: a systematic review, Surgery, ISSN: 0039-6060

BackgroundThere is evidence from preclinical models that the gut microbiome may impact outcomes from gastrointestinal surgery, and that surgery may alter the gut microbiome. However, the extent to which gastrointestinal surgery modulates the gut microbiome in clinical practice is currently poorly defined. This systematic review aims to evaluate the changes observed in the gut microbiome after gastrointestinal surgery.MethodsA systematic review and meta-analysis were conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, Web of Science, and CENTRAL for comparative studies meeting the predetermined inclusion criteria. The primary outcome was the difference between pre and postoperative bacterial taxonomic composition and diversity metrics among patients receiving gastrointestinal surgery.ResultsIn total, 33 studies were identified including 6 randomized controlled trials and 27 prospective cohort studies reporting a total of 968 patients. Gastrointestinal surgery was associated with an increase in α diversity and a shift in β diversity postoperatively. Multiple bacterial taxa were identified to consistently trend toward an increase or decrease postoperatively. A difference in microbiota across geographic provenance was also observed. There was a distinct lack of studies showing correlation with clinical outcomes or performing microbiome functional analysis. Furthermore, there was a lack of standardization in sampling, analytical methodology, and reporting.ConclusionThis review highlights changes in bacterial taxa associated with gastrointestinal surgery. There is a need for standardization of microbial analysis methods and reporting of results to allow interstudy comparison. Further adequately powered multicenter studies are required to better assess variation in microbial changes and its potential associations with clinical outcomes.

Journal article

Boshier PR, Klevebro F, Jenq W, Puccetti F, Muthuswamy K, Hanna GB, Low DEet al., 2021, Long-term variation in skeletal muscle and adiposity in patients undergoing esophagectomy., Dis Esophagus, Vol: 34

This study seeks to define long-term variation in body composition in patients undergoing esophagectomy for cancer and to associate those changes with survival. Assessment of skeletal muscle, visceral (VAT) and subcutaneous adipose tissue (SAT) was performed using computed tomography (CT) images routinely acquired: at diagnosis; after neoadjuvant therapy, and; >6 months after esophagectomy. In cases where multiple CT scans were performed >6 months after surgery, all available images were assessed. Ninty-seven patients met inclusion criteria with a median of 2 (range 1-10) postoperative CT images acquired between 0.5 and 9.7 years after surgery. Following surgical treatment of esophageal cancer, patients lost on average 13.3% of their skeletal muscle, 64.5% of their VAT and 44.2% of their SAT. Sarcopenia at diagnosis was not associated with worse overall survival (66.3% vs. 68.5%; P = 0.331). Sarcopenia 1 year after esophagectomy was however associated with lower 5-year overall survival (53.8% vs. 87.5%; P = 0.019). Survival was lower in those patients who had >10% decrease in skeletal muscle index (SMI; 33.3% vs. 72.1%; P = 0.003) and >40% decrease in SAT 1 year after surgery (40.4% vs. 67.4%; P = 0.015). On multivariate analysis, a decline in SMI 1 year after surgery was predictive of worse survival (HR 0.38, 95%CI 0.20-0.73; P = 0.004). This study provides new insight relating to long-term variation in body composition in patients undergoing esophagectomy for cancer. Findings provide further evidence of the importance of body composition, in particular depletion of skeletal muscle, in predicting survival following esophagectomy.

Journal article

Kamal F, Kumar S, Edwards MR, Veselkov K, Belluomo I, Kebadze T, Romano A, Trujillo-Torralbo M-B, Shahridan Faiez T, Walton R, Ritchie AI, Wiseman DJ, Laponogov I, Donaldson G, Wedzicha JA, Johnston SL, Singanayagam A, Hanna GBet al., 2021, Virus-induced volatile organic compounds are detectable in exhaled breath during pulmonary infection., American Journal of Respiratory and Critical Care Medicine, Vol: 204, Pages: 1075-1085, ISSN: 1073-449X

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation trigger is important to guide appropriate therapy but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection aetiology. METHODS: We used serial sampling within in vitro and in vivo studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas-chromatography mass spectrometry (GC-MS) techniques were used to measure VOC production from infected airway epithelial cell cultures and in exhaled breath samples of healthy subjects experimentally challenged with rhinovirus A16 and COPD subjects with naturally-occurring exacerbations. RESULTS: We identified a novel VOC signature comprising of decane and other related long chain alkane compounds that is induced during rhinovirus infection of cultured airway epithelial cells and is also increased in the exhaled breath of healthy subjects experimentally challenged with rhinovirus and of COPD patients during naturally-occurring viral exacerbations. These compounds correlated with magnitude of anti-viral immune responses, virus burden and exacerbation severity but were not induced by bacterial infection, suggesting they represent a specific virus-inducible signature. CONCLUSION: Our study highlights the potential for measurement of exhaled breath VOCs as rapid, non-invasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.

Journal article

Patel NM, Puri A, Sounderajah V, Ferri L, Griffiths E, Low D, Maynard N, Mueller C, Pera M, Henegouwen MIVB, Watson D, Zaninotto G, Hanna GB, Markar SRet al., 2021, Quality of life and symptom assessment in paraesophageal hernias: a systematic literature review of reporting standards, DISEASES OF THE ESOPHAGUS, Vol: 34, ISSN: 1120-8694

Journal article

Belluomo I, Boshier PR, Myridakis A, Vadhwana B, Markar SR, Spanel P, Hanna GBet al., 2021, Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath, NATURE PROTOCOLS, Vol: 16, Pages: 3419-3438, ISSN: 1754-2189

Journal article

Lin G-P, Vadhwana B, Belluomo I, Boshier PR, Spanel P, Hanna GBet al., 2021, Cross Platform Analysis of Volatile Organic Compounds Using Selected Ion Flow Tube and Proton-Transfer-Reaction Mass Spectrometry, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 32, Pages: 1215-1223, ISSN: 1044-0305

Journal article

Moloney K, Janda M, Frumovitz M, Leitao M, Abu-Rustum NR, Rossi E, Nicklin JL, Plante M, Lecuru FR, Buda A, Mariani A, Leung Y, Ferguson SE, Pareja R, Kimmig R, Tong PSY, McNally O, Chetty N, Liu K, Jaaback K, Lau J, Ng SYJ, Falconer H, Persson J, Land R, Martinelli F, Garrett A, Altman A, Pendlebury A, Cibula D, Altamirano R, Brennan D, Ind TE, De Kroon C, Tse KY, Hanna G, Obermair Aet al., 2021, Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 647-655, ISSN: 1048-891X

Journal article

Markar SR, Vidal-Diez A, Holt PJ, Karthikesalingam A, Hanna GBet al., 2021, An International Comparison of the Management of Gastrointestinal Surgical Emergencies in Octogenarians-England Versus United States A National Population-based Cohort Study, Joint Meeting of the Royal-Society-of-Medicine / Annual Meeting of the Society-of-Academic-and-Research-Surgery, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 924-932, ISSN: 0003-4932

Conference paper

Woodfield G, Belluomo I, Boshier PR, Waller A, Fayyad M, von Wagner C, Cross AJ, Hanna GBet al., 2021, Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study, BMJ Open, Vol: 11, Pages: 1-10, ISSN: 2044-6055

Objectives To examine the feasibility and acceptability of breath research in primary care.Design Non-randomised, prospective, mixed-methods cross-sectional observational study.Setting Twenty-six urban primary care practices.Participants 1002 patients aged 18–90 years with gastrointestinal symptoms.Main outcome measures During the first 6 months of the study (phase 1), feasibility of patient enrolment using face-to-face, telephone or SMS-messaging (Short Message Service) enrolment strategies, as well as processes for breath testing at local primary care practices, were evaluated. A mixed-method iterative study design was adopted and outcomes evaluated using weekly Plan-Do-Study-Act cycles, focus groups and general practitioner (GP) questionnaires.During the second 6 months of the study (phase 2), patient and GP acceptability of the breath test and testing process was assessed using questionnaires. In addition a ‘single practice’ recruitment model was compared with a ‘hub and spoke’ centralised recruitment model with regards to enrolment ability and patient acceptability.Throughout the study feasibility of the collection of a large number of breath samples by clinical staff over multiple study sites was evaluated and quantified by the analysis of these samples using mass spectrometry.Results 1002 patients were recruited within 192 sampling days. Both ‘single practice’ and ‘hub and spoke’ recruitment models were effective with an average of 5.3 and 4.3 patients accrued per day, respectively. The ‘hub and spoke’ model with SMS messaging was the most efficient combined method of patient accrual. Acceptability of the test was high among both patients and GPs. The methodology for collection, handling and analysis of breath samples was effective, with 95% of samples meeting quality criteria.Conclusions Large-scale breath testing in primary care was feasible and acceptable. This study provides a practical fra

Journal article

Huddy JR, Ni MZ, Barlow J, Hanna GBet al., 2021, Qualitative analysis of stakeholder interviews to identify the barriers and facilitators to the adoption of point-of-care diagnostic tests in the UK., BMJ Open, Vol: 11, Pages: 1-9, ISSN: 2044-6055

OBJECTIVES: This study investigated the barriers and facilitators to the adoption of point-of-care tests (POCTs). DESIGN: Qualitative study incorporating a constant comparative analysis of stakeholder responses to a series of interviews undertaken to design the Point-of-Care Key Evidence Tool. SETTING: The study was conducted in relation to POCTs used in all aspects of healthcare. PARTICIPANTS: Forty-three stakeholders were interviewed including clinicians (incorporating laboratory staff and members of trust POCT committees), commissioners, industry, regulators and patients. RESULTS: Thematic analysis highlighted 32 barriers in six themes and 28 facilitators in eight themes to the adoption of POCTs. Six themes were common to both barriers and facilitators (clinical, cultural, evidence, design and quality assurance, financial and organisational) and two themes contained facilitators alone (patient factors and other (non-financial) resource use). CONCLUSIONS: Findings from this study demonstrate the complex motivations of stakeholders in the adoption of POCT. Most themes were common to both barriers and facilitators suggesting that good device design, stakeholder engagement and appropriate evidence provision can increase the likelihood of a POCT device adoption. However, it is important to realise that while the majority of identified barriers may be perceived or mitigated some may be absolute and if identified early in device development further investment should be carefully considered.

Journal article

Butterworth JW, Boshier PR, Mavroveli S, Van Lanschot JBB, Sasako M, Reynolds J, Hanna GBet al., 2021, Challenges to quality assurance of surgical interventions in clinical oncology trials: A systematic review, EJSO, Vol: 47, Pages: 748-756, ISSN: 0748-7983

Journal article

Curtis NJ, Dennison G, Brown CSB, Hewett PJ, Hanna GB, Stevenson ARL, Francis NKet al., 2021, Clinical evaluation of intraoperative near misses in laparoscopic rectal cancer surgery., Annals of Surgery, Vol: 273, Pages: 778-784, 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

Hodgkinson JD, Worley G, Warusavitarne J, Hanna GB, Vaizey CJ, Faiz ODet al., 2021, Evaluation of the Ventral Hernia Working Group classification for long-term outcome using English Hospital Episode Statistics: a population study, HERNIA, Vol: 25, Pages: 977-984, ISSN: 1265-4906

Journal article

Antonowicz S, Bodai Z, Wiggins T, Markar SR, Boshier PR, Goh YM, Adam ME, Lu H, Kudo H, Rosini F, Goldin R, Moralli D, Green CM, Peters CJ, Habib N, Gabra H, Fitzgerald RC, Takats Z, Hanna GBet al., 2021, Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723

Journal article

Markar SR, Penna M, Gisbertz S, Hanna GB, van Berge Henegouwen MI, Cuesta MAet al., 2021, What comes next after the surgical randomized clinical trial?, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: E59-E59, ISSN: 0007-1323

Journal article

Wen Q, Boshier P, Myridakis A, Belluomo I, Hanna GBet al., 2020, Urinary volatile organic compound analysis for the diagnosis of cancer: a systematic literature review and quality assessment, Metabolites, Vol: 11, Pages: 17-17, ISSN: 2218-1989

The analysis of urinary volatile organic compounds (VOCs) is a promising field of research with the potential to discover new biomarkers for cancer early detection. This systematic review aims to summarise the published literature concerning cancer-associated urinary VOCs. A systematic online literature search was conducted to identify studies reporting urinary VOC biomarkers of cancers in accordance with the recommendations of the Cochrane Library and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Thirteen studies comprising 1266 participants in total were included in the review. Studies reported urinary VOC profiles of five cancer subtypes: prostate cancer, gastrointestinal cancer, leukaemia/lymphoma, lung cancer, and bladder cancer. Forty-eight urinary VOCs belonging to eleven chemical classes were identified with high diagnostic performance. VOC profiles were distinctive for each cancer type with limited cross-over. The metabolic analysis suggested distinctive phenotypes for prostate and gastrointestinal cancers. The heterogenicity of study design, methodological and reporting quality may have contributed to inconsistencies between studies. Urinary VOC analysis has shown promising performance for non-invasive diagnosis of cancer. However, limitations in study design have resulted in inconsistencies between studies. These limitations are summarised and discussed in order to support future studies.

Journal article

Halliday LJ, Doganay E, Wynter-Blyth VA, Hanna GB, Moorthy Ket al., 2020, The Impact of Prehabilitation on Post-operative Outcomes in Oesophageal Cancer Surgery: a Propensity Score Matched Comparison, JOURNAL OF GASTROINTESTINAL SURGERY, Vol: 25, Pages: 2733-2741, ISSN: 1091-255X

Journal article

Markar SR, Zaninotto G, Castoro C, Johar A, Lagergren P, Elliott JA, Gisbertz SS, Mariette C, Alfieri R, Huddy J, Sounderajah V, Pinto E, Scarpa M, Klevebro F, Sunde B, Murphy CF, Greene C, Ravi N, Piessen G, Brenkman H, Ruurda JP, Van Hillegersberg R, Lagarde S, Wijnhoven B, Pera M, Roig J, Castro S, Matthijsen R, Findlay J, Antonowicz S, Maynard N, McCormack O, Ariyarathenam A, Sanders G, Cheong E, Jaunoo S, Allum W, Van Lanschot J, Nilsson M, Reynolds JV, van Berge Henegouwen MI, Hanna GBet al., 2020, Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study., Ann Surg

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Journal article

Aksenov AA, Laponogov I, Zhang Z, Doran SLF, Belluomo I, Veselkov D, Bittremieux W, Nothias LF, Nothias-Esposito M, Maloney KN, Misra BB, Melnik AV, Smirnov A, Du X, Jones KL, Dorrestein K, Panitchpakdi M, Ernst M, van der Hooft JJJ, Gonzalez M, Carazzone C, Amézquita A, Callewaert C, Morton JT, Quinn RA, Bouslimani A, Orio AA, Petras D, Smania AM, Couvillion SP, Burnet MC, Nicora CD, Zink E, Metz TO, Artaev V, Humston-Fulmer E, Gregor R, Meijler MM, Mizrahi I, Eyal S, Anderson B, Dutton R, Lugan R, Boulch PL, Guitton Y, Prevost S, Poirier A, Dervilly G, Le Bizec B, Fait A, Persi NS, Song C, Gashu K, Coras R, Guma M, Manasson J, Scher JU, Barupal DK, Alseekh S, Fernie AR, Mirnezami R, Vasiliou V, Schmid R, Borisov RS, Kulikova LN, Knight R, Wang M, Hanna GB, Dorrestein PC, Veselkov Ket al., 2020, Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data, Nature Biotechnology, Vol: 39, Pages: 169-173, ISSN: 1087-0156

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.

Journal article

Klevebro F, Boshier PR, Savva K, Waller A, Hage L, Ni M, Hanna GB, Low DEet al., 2020, Severe Dumping Symptoms Are Uncommon Following Transthoracic Esophagectomy But Significantly Decrease Health-Related Quality of Life in Long-Term, Disease-Free Survivors, JOURNAL OF GASTROINTESTINAL SURGERY, Vol: 25, Pages: 1941-1947, ISSN: 1091-255X

Journal article

Hanna GB, Mackenzie H, Miskovic D, Ni M, Wyles S, Aylin P, Parvaiz A, Cecil T, Gudgeon A, Griffith J, Robinson JM, Selvasekar C, Rockall T, Acheson A, Maxwell-Armstrong C, Jenkins JT, Horgan A, Cunningham C, Lindsay I, Arulampalam T, Motson RW, Francis NK, Kennedy RH, Coleman MG, Lapco programet al., 2020, Laparoscopic colorectal surgery outcomes improved after national training program (LAPCO) for specialists in England, Annals of Surgery, Pages: 1-1, ISSN: 0003-4932

OBJECTIVE: To examine the impact of The National Training Programme for Laparoscopic Colorectal Surgery (Lapco) on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training. SUMMERY BACKGROUND DATA: Lapco provided competency-based supervised clinical training for specialist colorectal surgeons in England. METHODS: We compared the rate of laparoscopic surgery, mortality and morbidity for colorectal cancer resections by Lapco delegates and non-Lapco surgeons in 3-year periods preceding and following Lapco using difference in differences analysis. The changes in the rate of post-Lapco laparoscopic surgery with the Lapco sign-off competency assessment and in-training global assessment scores were examined using risk-adjusted cumulative sum to determine their predictive clinical validity with predefined competent scores of 3 and 5 respectively. RESULTS: 108 Lapco delegates performed 4586 elective colorectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% (95% CI, 18.5 to 23.3, p<0.001) with a relative decrease in 30-day mortality by -1.6% (95% CI, -3.4 to -0.2, p = 0.039) and 90-day mortality by -2.3% (95% CI, -4.3 to -0.4, p = 0.018). The change point of risk-adjusted cumulative sum was 3.12 for competency assessment tool and 4.74 for global assessment score whereas laparoscopic rate increased from 44% to 66% and 40% to 56% respectively. CONCLUSIONS: Lapco increased the rate of laparoscopic colorectal cancer surgery and reduced mortality and morbidity in England. In-training competency assessment tools predicted clinical performance after training.

Journal article

Knight WRC, McEwen R, Byrne BE, Habib W, Bott R, Zylstra J, Mahadeva U, Gossage JA, Fitzgerald RC, Noorani A, Edwards PAW, Grehan N, Nutzinger B, Hughes C, Fidziukiewicz E, MacRae S, Northrop A, Contino G, Li X, de la Rue R, Katz-Summercorn A, Abbas S, Loureda D, O'Donovan M, Miremadi A, Malhotra S, Tripathi M, Tavaré S, Lynch AG, Eldridge M, Secrier M, Devonshire G, Perner J, 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, Lagergren J, Davies A, Chang F, Goh V, Ciccarelli FD, Sanders G, Berrisford R, Harden C, Lewis M, Cheong E, Kumar B, Parsons SL, Soomro I, Kaye P, Saunders J, Lovat L, Haidry R, Igali L, Scott M, Sothi S, Suortamo S, Lishman S, Hanna GB, Moorthy K, Peters CJ, Grabowska A, Turkington R, McManus D, Coleman H, Khoo D, Fickling Wet al., 2020, Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus, European Journal of Surgical Oncology, ISSN: 0748-7983

BackgroundPrognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival.MethodsPatients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals.Results262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas’ Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p < 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p < 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31–0.93, HR 0.42 95% CI 0.21–0.82).ConclusionThis study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.

Journal article

Curtis NJ, Foster JD, Miskovic D, Brown CSB, Hewett PJ, Abbott S, Hanna GB, Stevenson ARL, Francis NKet al., 2020, Association of Surgical Skill Assessment With Clinical Outcomes in Cancer Surgery, JAMA SURGERY, Vol: 155, Pages: 590-598, ISSN: 2168-6254

Journal article

Markar SR, Ni M, Gisbertz SS, van der Werf L, Straatman J, van der Peet D, Cuesta MA, Hanna GB, van Berge Henegouwen MIet al., 2020, Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice, JOURNAL OF CLINICAL ONCOLOGY, Vol: 38, Pages: 2130-+, ISSN: 0732-183X

Journal article

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

Muthuswamy K, Fisher R, Mavroveli S, Petrou F, Khawar S, Amlani A, Hanna GB, Hadjiminas D, Thiruchelvam P, Leff Det al., 2020, Assessment of technical skills in axillary lymph node dissection, Annals of Surgery, ISSN: 0003-4932

Objective A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated.Summary and Background Data The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. MethodsA cross-sectional multi-center observational study was carried out between July 2017 to August 2018. Following model development, 30 surgeons ofvarying experience (n=9 ‘experts’, n=11 ‘senior residents’ and n=10 ‘junior residents’) were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by two attending breast surgeons, blinded to operator identity, using a video-based assessment tool and an end product assessment tool.ResultsStatistically significant differences between groups were observed across all operative sub-phases on theaxillary clearance assessment tool (p<0.001). Significant differences between groups were observed for overall procedure quality (p<0.05) and total number of lymph nodes harvested (p<0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (p=0.864) and long thoracic nerve injury R1 ALND Structured abstract(p=0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7).ConclusionsVideo based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery orFaculty administered assessments.

Journal article

Kamarajah SK, Phillips AW, Hanna GB, Low DE, Markar SRet al., 2020, Is Local Endoscopic Resection a Viable Therapeutic Option for Early Clinical Stage T1a and T1b Esophageal Adenocarcinoma?: A Propensity-Matched Analysis., Ann Surg

OBJECTIVE: The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus esophagectomy in node-negative cT1a and cT1b esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: The role of ER in the management of subsets of clinical T1N0 esophageal adenocarcinoma is controversial. METHODS: Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2545) and T1bN0 (n = 1281) esophageal adenocarcinoma that received either ER (cT1a, n = 1581; cT1b, n = 335) or esophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching and Cox analyses were used to account for treatment selection bias. RESULTS: ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b esophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to esophagectomy [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.70-1.04, P = 0.1]. The corresponding 5-year survival for ER and esophagectomy were 70% and 74% (P = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, P = 0.3). The corresponding 5-year survival for ER and esophagectomy were 53% versus 61% (P = 0.3), respectively. CONCLUSIONS: This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 esophageal adenocarcinoma. However, 15% of patients with cT1b esophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from esophagectomy with lymphadenectomy.

Journal article

Kamarajah SK, Phillips AW, Hanna GB, Low D, Markar SRet al., 2020, Definitive Chemoradiotherapy Compared to Neoadjuvant Chemoradiotherapy With Esophagectomy for Locoregional Esophageal Cancer: National Population-Based Cohort Study., Ann Surg

AIM: Ongoing randomized controlled trials seek to evaluate the potential organ-preservation strategy of definitive chemoradiotherapy as a primary treatment for esophageal cancer. This population-based cohort study aimed to assess survival following definitive chemoradiotherapy (DCR) with or without salvage esophagectomy (SALV) in the treatment of esophageal cancer. PATIENTS AND METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2015, was used to identify patients with nonmetastatic esophageal cancer receiving either DCR (n = 5977) or neoadjuvant chemoradiotherapy with planned esophagectomy (NCRS) (n = 13,555). Propensity score matching and multivariable analyses were used to account for treatment selection bias. Subset analyses compared patients receiving SALV after DCR with NCRS. RESULTS: Comparison of baseline demographics of the unmatched cohort revealed that patients receiving NCRS were younger, had a lower burden of medical comorbidities, lower proportion of squamous cell carcinoma (SCC), and more positive lymph nodes. Following matching, NCRS was associated with significantly improved survival compared with DCR [hazard ratio (HR): 0.60, 95% confidence Interval (CI): 0.57-0.63, P < 0.001], which persisted in subset analyses of patients with adenocarcinoma (HR: 0.60, 95% CI: 0.56-0.63, P < 0.001) and SCC (HR: 0.58, 95% CI: 0.53-0.63, P < 0.001). Of 829 receiving SALV after DCR, 823 patients were matched to 1643 NCRS. There was no difference in overall survival between SALV and NCRS (HR: 1.00, 95% CI: 0.90-1.11, P = 1.0). CONCLUSIONS: Surgery remains an integral component of the management of patients with esophageal cancer. Neoadjuvant therapy followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with locoregional esophageal cancer.

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

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