Imperial College London

MrDuncanSpalding

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Senior Lecturer in Hepato-Biliary Surgery
 
 
 
//

Contact

 

+44 (0)20 3313 3941d.spalding

 
 
//

Location

 

Hammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

115 results found

Das B, Fehervari M, Hamrang-Yousefi S, Jiao LR, Pai M, Jenkins JT, Spalding DRCet al., 2022, Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience, COLORECTAL DISEASE, ISSN: 1462-8910

Journal article

D'Alessio A, Pai M, Spalding D, Rajagopal P, Talbot T, Goldin R, Fulgenzi CAM, Ward C, Yip V, Dhillon T, Slater S, Sodergren M, Tait P, Habib N, Thomas R, Cortellini A, Sharma R, Pinato DJet al., 2022, PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma, Publisher: ELSEVIER, Pages: S108-S109, ISSN: 0168-8278

Conference paper

Alghazawi LOK, Entwistle OH, Fehervari M, Spalding Det al., 2022, Unusual cause of intraoperative haemorrhage: a lesson for patient counselling, BMJ CASE REPORTS, Vol: 15

Journal article

Fehervari M, Das B, Soleimani-Nouri P, Ahmad M, Fadel MG, Deputy M, Morgan C, Burke JR, Mason JD, Nott D, Spalding Det al., 2022, Can surgical skills be taught using technological advances online? A comparative study of online and face-to-face surgical skills training, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 36, Pages: 4631-4637, ISSN: 0930-2794

IntroductionOnline teaching has rapidly emerged as a viable alternative to traditional face-to-face education. How to teach surgical skills in the online environment, however, has not yet been fully established nor evaluated.MethodsAn international 1-day online surgical skills course consisting of lectures, pre-recorded virtual workshops, live demonstrations and along with surgical skills teaching in breakout rooms was organised. Based on existing learning theories, new methods were developed to deliver skills teaching online. Simultaneously, traditional in-person surgical skills teaching was also conducted and used as a benchmark. Skills development was assessed by trained demonstrators and self-reported competency scores were compared between the online and face-to-face event.Results553 delegates from 20 different countries attended the online course. Of these, 64 were trained in breakout rooms with a 1:5 demonstrator-to-delegate ratio whilst the remaining 489 delegates participated in didactic skills development sessions. In a separate face-to-face course, 20 delegates were trained with traditional methods. Demonstrators rated the competency of delegates for suturing, tendon repair and vascular anastomosis. There was no significant difference in the competency ratings of delegates receiving online teaching or face-to-face teaching (p = 0.253, p = 0.084, p = 1.00, respectively). The development of the same skills to “articulation” were not different between formats (p = 0.841, p = 0.792, p = 1.00, respectively). Post course self-rated competency scores improved for all technical skills (p < 0.001). Small group sessions, both online and face-to-face, received higher satisfaction ratings compared to large group sessions in terms of clarity of instructions, answers to questions and demonstrator feedback. Overall feedback on teaching quality, however, was e

Journal article

Kilic Y, Graham A, Tait NP, Spalding D, Vlavianos P, Jiao LR, Alsafi Aet al., 2022, Percutaneous biliary stone clearance: is there still a need? A 10-year single-centre experience, CLINICAL RADIOLOGY, Vol: 77, Pages: 130-135, ISSN: 0009-9260

Journal article

Tabiri S, Kamarajah SK, Nepogodiev D, Li E, Simoes J, Sravanam S, Owusu SA, Mahama H, Agyeman YN, Arthur J, Kunfah SM, Gyamfi FE, Owusu EA, Loffler MW, Wandoh P, Bhangu A, Siaw-Acheampong K, Argus L, Chaudhry D, Dawson BE, Glasbey JC, Gujjuri RR, Jones CS, Khatri C, Keatley JM, Lawday S, Mann H, Marson EJ, Mclean KA, Picciochi M, Taylor EH, Tiwari A, Simoes JFF, Trout IM, Venn ML, Wilkin RJW, Dajti I, Gjata A, Boccalatte L, Modolo MM, Cox D, Pockney P, Townend P, Aigner F, Kronberger I, Hossain K, VanRamshorst G, Lawani I, Ataide G, Baiocchi G, Buarque I, Gohar M, Slavchev M, Agarwal A, Brar A, Martin J, Olivos M, Calvache J, Perez Rivera CJ, Hadzibegovic AD, Kopjar T, Mihanovic J, Klat J, Novysedlak R, Christensen P, El-Hussuna A, Batista S, Lincango E, Emile SH, Mengesha MG, Hailu DS, Tamiru H, Kauppila J, Arnaud A, Albertsmeiers M, Lederhuber H, Loffler M, Metallidis S, Tsoulfas G, Lorena MA, Grecinos G, Mersich T, Wettstein D, Ghosh D, Kembuan G, Brouk P, Khosravi M, Mozafari M, Adil A, Mohan HM, Zmora O, Fiore M, Gallo G, Pata F, Pellino G, Satoi S, Ayasra F, Chaar M, Fakhradiyev IR, Jamal M, Elhadi M, Gulla A, Roslani A, Martinez L, Ramos De la Medina A, Outani O, Jonker P, Kruijff S, Noltes M, Steinkamp P, van der Plas W, Ademuyiwa A, Osinaike B, Seyi-olajide J, Williams E, Pejkova S, Augestad KM, Soreide K, Al Balushi Z, Qureshi A, Sayyed R, Daraghmeh MAM, Abukhalaf S, Cukier M, Gomez H, Shu S, Vasquez X, Parreno-Sacdalan MD, Major P, Azevedo J, Cunha M, Santos I, Zarour A, Bonci E-A, Negoi I, Efetov S, Litvin A, Ntirenganya F, AlAmeer E, Radenkovic D, Xiang FKH, Hoe CM, Yong JNC, Moore R, Nhlabathi N, Colino RB, Bravo AM, Minaya-Bravo A, Jayarajah U, Wickramasinghe D, Elmujtaba M, Jebril W, Rutegard M, Sund M, Isik A, Leventoglu S, Abbott TEF, Benson R, Caruna E, Chakrabortee S, Demetriades A, Desai A, Drake TD, Edwards JG, Evans JP, Ford S, Fotopoulou C, Griffiths E, Hutchinson P, Jenkinson MD, Khan T, Knight S, Kolias A, Leung E, McKay S, Norman L, Ots Ret al., 2022, Impact of Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection, BJS Open, Vol: 5, ISSN: 2474-9842

Journal article

da Costa AC, Spalding D, Cunha-Filho GDA, Santana MB, Pai M, Jiao LR, Habib Net al., 2022, HOW TO PERFORM LAPAROSCOPIC DISTAL PANCREATECTOMY USING THE CLOCKWISE TECHNIQUE, ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA-BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY, Vol: 35, ISSN: 0102-6720

Journal article

McKay SC, Pathak S, Wilkin RJW, Kamarajah SK, Wigmore SJ, Rees J, Dunne DFJ, Garcea G, Ahmad J, Carino NDL, Sultana A, Silva M, Lykoudis P, Nasralla D, Milburn J, Shah N, Kocher HM, Bhogal R, Baron RD, Navarro A, Halle-Smith J, Al-Sarireh B, Sen G, Jamieson NB, Briggs C, Stell D, Aroori S, Bowles M, Kanwar A, Harper S, Menon K, Prachalias A, Srinivasan P, Frampton AE, Jones C, Arshad A, Tait I, Spalding D, Young AL, Durkin D, Ghods-Ghorbani M, Sutcliffe RP, Roberts KJet al., 2021, Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience, HPB, Vol: 23, Pages: 1656-1665, ISSN: 1365-182X

Journal article

McLean KA, Kamarajah SK, Chaudhry D, Gujjuri RR, Raubenheimer K, Trout I, AlAmeer E, Creagh-Brown B, Harrison EM, Nepogodiev D, Roslani AC, Li E, Pata F, Ramos-De la Medina A, van Ramshorst GH, Sayyed R, Simoes J, Smart N, Bhangu A, Glasbey JC, Khaw RA, Ahmed W, Akhbari M, Baker D, Borakati A, Mills E, Murray V, Thavayogan R, Yasin I, Glasbey J, Ridley W, Sarrami M, Zhang G, Egoroff N, Pockney P, Richards T, Edwards M, Lee M, Pinkney T, Pearse R, Vohra R, Sohrabi C, Jamieson A, Nguyen M, Rahman A, English C, Tincknell L, Kakodkar P, Kwek I, Punjabi N, Burns J, Varghese S, Erotocritou M, McGuckin S, Vayalapra S, Dominguez E, Moneim J, Bhatia S, Kouli O, Salehi M, Tan HL, Yoong A, Zhu L, Seale B, Nowinka Z, Patel N, Chrisp B, Harris J, Maleyko I, Muneeb F, Gough M, James CE, Skan O, Chowdhury A, Rebuffa N, Khan H, Down B, Fatimah HQ, Siaw-Acheampong K, Benson RA, Bywater E, Dawson BE, Evans JP, Heritage E, Jones CS, Khatri C, Keatley JM, Knight A, Lawday S, Mann HS, Marson EJ, Mckay SC, Mills EC, Pellino G, Picciochi M, Taylor EH, Tiwari A, Simoes JFF, Trout IM, Venn ML, Wilkin RJW, Smart NJ, Minaya-Bravo A, Gallo G, Moug S, Di Saverio S, Vallance A, Vimalchandran D, Griffiths EA, Evans RPT, Townend P, Roberts K, McKay S, Isaac J, Satoi S, Edwards J, Coonar AS, Marchbank A, Caruana EJ, Layton GR, Patel A, Brunelli A, Ford S, Desai A, Gronchi A, Fiore M, Almond M, Tirotta F, Dumitra S, Kolias A, Price SJ, Fountain DM, Jenkinson MD, Hutchinson P, Marcus HJ, Piper RJ, Lippa L, Servadei F, Esene I, Freyschlag C, Neville I, Rosseau G, Schaller K, Demetriades AK, Robertson F, Alamri A, Shaw R, Schache AG, Winter SC, Ho M, Nankivell P, Biel JR, Batstone M, Ganly I, Vidya R, Wilkins A, Singh JK, Thekinkattil D, Sundar S, Fotopoulou C, Leung E, Khan T, Chiva L, Sehouli J, Fagotti A, Cohen P, Gutelkin M, Ghebre R, Konney T, Pareja R, Bristow R, Dowdy S, Rajkumar STS, Ng J, Fujiwara K, Stewart GD, Lamb B, Narahari K, McNeill A, Colquhoun A, McGrath J, Bromage S, Barod R, Kasiviset al., 2021, Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 1448-1464, ISSN: 0007-1323

Journal article

Plummer R, Sodergren M, Pinato D, Sarker D, Reebye V, Spalding D, Raulf N, Sinigaglia L, Talbot T, Cortellini A, D'Alessio A, Tchakov I, Habib R, Rossi J, Habib Net al., 2021, A PHASE 1 STUDY OF MYELOID MODULATING AGENT MTL-CEBPA IN COMBINATION WITH PEMBROLIZUMAB IN ADULT PATIENTS WITH ADVANCED SOLID TUMOURS, Publisher: BMJ PUBLISHING GROUP, Pages: A545-A545

Conference paper

Hashimoto A, Sarker D, Reebye V, Jarvis S, Sodergren MH, Kossenkov A, Sanseviero E, Raulf N, Vasara J, Andrikakou P, Meyer T, Huang K-W, Plummer R, Chee CE, Spalding D, Pai M, Khan S, Pinato DJ, Sharma R, Basu B, Palmer D, Ma Y-T, Evans J, Habib R, Martirosyan A, Elasri N, Reynaud A, Rossi JJ, Cobbold M, Habib NA, Gabrilovich DIet al., 2021, Upregulation of C/EBP alpha Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer, CLINICAL CANCER RESEARCH, Vol: 27, Pages: 5961-5978, ISSN: 1078-0432

Journal article

Glasbey J, Ademuyiwa A, Adisa A, AlAmeer E, Arnaud AP, Ayasra F, Azevedo J, Minaya-Bravo A, Costas-Chavarri A, Edwards J, Elhadi M, Fiore M, Fotopoulou C, Gallo G, Ghosh D, Griffiths EA, Harrison E, Hutchinson P, Lawani I, Lawday S, Lederhuber H, Leventoglu S, Li E, Gomes GMA, Mann H, Marson EJ, Martin J, Mazingi D, McLean K, Modolo M, Moore R, Morton D, Ntirenganya F, Pata F, Picciochi M, Pockney P, Ramos-De la Medina A, Roberts K, Roslani AC, Kottayasamy Seenivasagam R, Shaw R, Simões JFF, Smart N, Stewart GD, Sullivan R, Sundar S, Tabiri S, Taylor EH, Vidya R, Nepogodiev D, Bhangu A, Glasbey JC, McLean K, Nepogodiev D, Harrison E, Bhangu AA, Nepogodiev D, Siaw-Acheampong K, Benson RA, Bywater E, Chaudhry D, Dawson BE, Evans JP, Glasbey JC, Gujjuri RR, Heritage E, Jones CS, Kamarajah SK, Khatri C, Khaw RA, Keatley JM, Knight A, Lawday S, Li E, Mann HS, Marson EJ, McLean KA, Mckay SC, Mills EC, Pellino G, Picciochi M, Taylor EH, Tiwari A, Simoes JFF, Trout IM, Venn ML, Wilkin RJW, Bhangu A, Glasbey JC, Smart NJ, Minaya-Bravo A, Evans JP, Gallo G, Moug S, Pata F, Pockney P, Di Saverio S, Vallance A, Vimalchandran D, Griffiths EA, Kamarajah SK, Evans RPT, Townend P, Roberts K, McKay S, Isaac J, Satoi S, Edwards J, Coonar AS, Marchbank A, Caruana EJ, Layton GR, Patel A, Brunelli A, Ford S, Desai A, Gronchi A, Fiore M, Almond M, Tirotta F, Dumitra S, Kolias A, Price SJ, Fountain DM, Jenkinson MD, Hutchinson P, Marcus HJ, Piper RJ, Lippa L, Servadei F, Esene I, Freyschlag C, Neville I, Rosseau G, Schaller K, Demetriades AK, Robertson F, Alamri A, Shaw R, Schache AG, Winter SC, Ho M, Nankivell P, Rey Biel J, Batstone M, Ganly I, Vidya R, Wilkins A, Singh JK, Thekinkattil D, Sundar S, Fotopoulou C, Leung EYL, Khan T, Chiva L, Sehouli J, Fagotti A, Cohen P, Gutelkin M, Ghebre R, Konney T, Pareja R, Bristow R, Dowdy S, Shylasree TS, Kottayasamy Seenivasagam R, Ng J, Fujiwara K, Stewart GD, Lamb B, Narahari K, McNeill A, Colquhoun A, McGrath JS, Bromage S, Barod R, Kasivisvaet al., 2021, Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study, The Lancet Oncology, Vol: 22, Pages: 1507-1517, ISSN: 1470-2045

BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notif

Journal article

COVIDSurg Collaborative Co-authors, 2021, Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score, British Journal of Surgery, Vol: 108, Pages: 1274-1292, ISSN: 0007-1323

Since the beginning of the COVID-19 pandemic tens of millions of operations have been cancelled1 as a result of excessive postoperative pulmonary complications (51.2 per cent) and mortality rates (23.8 per cent) in patients with perioperative SARS-CoV-2 infection2. There is an urgent need to restart surgery safely in order to minimize the impact of untreated non-communicable disease.As rates of SARS-CoV-2 infection in elective surgery patients range from 1–9 per cent3–8, vaccination is expected to take years to implement globally9 and preoperative screening is likely to lead to increasing numbers of SARS-CoV-2-positive patients, perioperative SARS-CoV-2 infection will remain a challenge for the foreseeable future.To inform consent and shared decision-making, a robust, globally applicable score is needed to predict individualized mortality risk for patients with perioperative SARS-CoV-2 infection. The authors aimed to develop and validate a machine learning-based risk score to predict postoperative mortality risk in patients with perioperative SARS-CoV-2 infection.

Journal article

Pinato D, Cortellini A, Sukumaran A, Cole T, Pai M, Habib N, Spalding D, Sodergren M, Martinez M, Dhillon T, Tait P, Thomas R, Ward C, Kocher H, Yip V, Slater S, Sharma Ret al., 2021, PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma, BMC Cancer, Vol: 21, ISSN: 1471-2407

BackgroundAfter liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC.MethodsThe study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC.DiscussionThe results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcom

Journal article

Glasbey JC, Omar O, Nepogodiev D, Minaya-Bravo A, Bankhead-Kendall BK, Fiore M, Futaba K, Gabre-Kidan A, Gujjuri RR, Isik A, Kaafarani HMA, Kamarajah SK, Li E, Loeffler MW, McLean KA, Outani O, Ntirenganya F, Satoi S, Shaw R, Simoes JFF, Stewart GD, Tabiri S, Trout IM, Bhangu AA, Glasbey JC, Omar O, Bhangu AA, Siaw-Acheampong K, Benson RA, Bywater E, Chaudhry D, Dawson BE, Evans JP, Glasbey JC, Gujjuri RR, Heritage E, Jones CS, Kamarajah SK, Khatri C, Khaw RA, Keatley JM, Knight A, Lawday S, Li E, Mann HS, Marson EJ, McLean KA, Mckay SC, Mills EC, Nepogodiev D, Pellino G, Picciochi M, Taylor EH, Tiwari A, Simoes JFF, Trout IM, Venn ML, Wilkin RJW, Bhangu A, Glasbey JC, Smart NJ, Minaya-Bravo A, Evans JP, Gallo G, Moug S, Pata F, Pockney P, Di Saverio S, Vallance A, Vimalchandran D, Griffiths EA, Kamarajah SK, Evans RPT, Townend P, Roberts K, McKay S, Isaac J, Satoi S, Edwards J, Coonar AS, Marchbank A, Caruana EJ, Layton GR, Patel A, Brunelli A, Ford S, Desai A, Gronchi A, Fiore M, Almond M, Tirotta F, Dumitra S, Kolias A, Price SJ, Fountain DM, Jenkinson MD, Hutchinson P, Marcus HJ, Piper RJ, Lippa L, Servadei F, Esene I, Freyschlag C, Neville I, Rosseau G, Schaller K, Demetriades AK, Robertson F, Alamri A, Shaw R, Schache AG, Winter SC, Ho M, Nankivell P, Biel JR, Batstone M, Ganly I, Vidya R, Wilkins A, Singh JK, Thekinkattil D, Sundar S, Fotopoulou C, Leung E, Khan T, Chiva L, Sehouli J, Fagotti A, Cohen P, Gutelkin M, Ghebre R, Konney T, Pareja R, Bristow R, Dowdy S, Rajkumar STS, Ng J, Fujiwara K, Stewart GD, Lamb B, Narahari K, McNeill A, Colquhoun A, McGrath J, Bromage S, Barod R, Kasivisvanathan V, Klatte T, Simoes JFF, Abbott TEF, Abukhalaf S, Adamina M, Ademuyiwa AO, Agarwal A, Akkulak M, Alameer E, Alderson D, Alakaloko F, Albertsmeiers M, Alser O, Alshaar M, Alshryda S, Arnaud AP, Augestad KM, Ayasra F, Azevedo J, Bankhead-Kendall BK, Barlow E, Beard D, Benson RA, Blanco-Colino R, Brar A, Minaya-Bravo A, Breen KA, Bretherton C, Buarque IL, Burke J, Caruet al., 2021, Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 88-96, ISSN: 0007-1323

Journal article

Gavriilidis P, Sutcliffe RP, Roberts KJ, Pai M, Spalding D, Habib N, Jiao LR, Sodergren MHet al., 2020, No difference in mortality among ALPPS, two-staged hepatectomy, and portal vein embolization/ligation: A systematic review by updated traditional and network meta-analyses, HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, Vol: 19, Pages: 411-419, ISSN: 1499-3872

Journal article

Sarker D, Plummer R, Meyer T, Sodergren MH, Basu B, Chee CE, Huang K-W, Palmer DH, Ma YT, Evans TRJ, Spalding DRC, Pai M, Sharma R, Pinato DJ, Spicer J, Hunter S, Kwatra V, Nicholls JP, Collin D, Nutbrown R, Glenny H, Fairbairn S, Reebye V, Voutila J, Dorman S, Andrikakou P, Lloyd P, Felstead S, Vasara J, Habib R, Wood C, Saetrom P, Huber HE, Blakey DC, Rossi JJ, Habib Net al., 2020, MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial, Clinical Cancer Research, Vol: 26, Pages: 3936-3946, ISSN: 1078-0432

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

Journal article

Noor MS, Dennis J, Al-Hinai K, Arhi C, Spalding Det al., 2020, Quality Improvement Project: Improving the External Referrals Service of the Hepato-Pancreato-Biliary (HPB) Surgery in a Tertiary Centre, International Surgical Conference of the Association-of-Surgeons-in-Training, Publisher: WILEY, Pages: 187-187, ISSN: 0007-1323

Conference paper

Sarker D, Sodergren M, Plummer ER, Basu B, Meyer T, Huang K-W, Evans TRJ, Spalding D, Ma YT, Palmer DH, Chee CE, Pinato DJ, Reebye V, McVeigh D, Raulf N, Vasara J, Andrikakou P, Habib R, Blakey D, Habib NAet al., 2020, Phase Ib dose escalation and cohort expansion study of the novel myeloid differentiating agent MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X

Conference paper

da Costa AC, Sodergren M, Jayant K, Santa Cruz F, Spalding D, Pai M, Habib Net al., 2020, Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 26, Pages: 2040-2048, ISSN: 1007-9327

Journal article

Sarker D, Sodergren M, Plummer ER, Basu B, Meyer T, Huang K-W, Evans TRJ, Spalding D, Ma YT, Palmer DH, Chee CE, Pinato DJ, Reebye V, McVeigh D, Raulf N, Vasara J, Andrikakou P, Habib R, Blakey D, Habib NAet al., 2020, First-in-human phase I trial of small activating RNA (saRNA) oligonucleotide MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC), Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X

Conference paper

Sarker D, Plummer R, Basu B, Meyer T, Ma Y-T, Evans J, Palmer DH, Huang K-W, Chee E, Spalding D, Sodergren M, Habib Net al., 2019, First-in-human, first-in-class phase I study of MTL-CEBPA, a RNA oligonucleotide targeting the myeloid cell master regulator C/EBP-alpha, in patients with advanced hepatocellular cancer (HCC), 44th Congress of the European-Society-for-Medical-Oncology (ESMO), Publisher: OXFORD UNIV PRESS, Pages: 168-+, ISSN: 0923-7534

Conference paper

Dindyal S, Ross T, Adebayor D, Pai M, Spalding Det al., 2019, To what extent can a closed loop audit initiative successfully influence clinical care and improve safety of handover in a tertiary referral teaching hospital, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY, Pages: 94-94, ISSN: 0007-1323

Conference paper

Poovathoor AJ, Belete S, Afoke J, Spalding D, Punjabi Pet al., 2019, Cardiopulmonary exercise testing and major hepatobiliary surgery: An effective way to judge fitness for surgery?, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY, Pages: 68-69, ISSN: 0007-1323

Conference paper

Dindyal S, Siddique H, Pai M, Spalding Det al., 2019, Can a virtual clinic reduce waiting times and improve patient satisfaction in a tertiary referral teaching hospital, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY, Pages: 77-77, ISSN: 0007-1323

Conference paper

Patel BY, White L, Howard AM, Tait P, Thomas R, Habib N, Pai M, Spalding D, Gall T, Jiao Let al., 2019, A Retrospective Analysis of Portal Vein Embolisation In A Tertiary Hepato Pancreato Biliary Centre, International Surgical Conference of the Association-of-Surgeons-in-Training (ASIT), Publisher: WILEY, Pages: 74-74, ISSN: 0007-1323

Conference paper

Dindyal S, Wing V, Adebayo D, Pai M, Spalding Det al., 2019, Elective and emergency splenectomise at a tertiary referral teaching hospital - an audit of current practice, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY, Pages: 94-94, ISSN: 0007-1323

Conference paper

Wadsworth CA, Dixon PH, Taylor-Robinso SD, Kim JU, Zabron AA, Wong JH, Chapman MH, McKay SC, Spalding DR, Wasan HS, Pereira SP, Thomas HC, Whittaker JC, Williamson C, Khan SAet al., 2019, Polymorphisms in natural killer cell receptor protein 2D (NKG2D) as a risk factor for Cholangiocarcinoma, Journal of Clinical and Experimental Hepatology, Vol: 9, Pages: 171-175, ISSN: 0973-6883

Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. Methods: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. Results: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). Conclusion: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.

Journal article

Gall TMH, Gerrard G, Frampton AE, Castellano L, Ahmad R, Habib N, Spalding D, Pai M, Foroni L, Jiao LRet al., 2019, Can we predict long-term survival in resectable pancreatic ductal adenocarcinoma?, Oncotarget, Vol: 10, Pages: 696-706, ISSN: 1949-2553

Objective: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker. Methods: Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs. Results: Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival (p = 0.007). Group I patients (n = 21) had a higher frequency of the KRAS mutant mean variant allele (16.93% ± 11.04) compared to those in Group II (n = 13; 7.55% ± 5.76, p = 0.0078). Group I patients also trended towards having a KRAS c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as TP53, CDKN2A, and SMAD4. Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed. Conclusions: Medial resection margin status and the frequency of KRAS mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.

Journal article

Jayant K, Sodergren MH, Reccia I, Kusano T, Zacharoulis D, Spalding D, Pai M, Jiao LR, Huang KWet al., 2018, A systematic review and meta-analysis comparing liver resection with the rf-based device habib (TM)-4x with the clamp-crush technique, Cancers, Vol: 10, Pages: 1-17, ISSN: 2072-6694

Liver cancer is the sixth most common cancer and third most common cause of cancer-related mortality. Presently, indications for liver resections for liver cancers are widening, but the response is varied owing to the multitude of factors including excess intraoperative bleeding, increased blood transfusion requirement, post-hepatectomy liver failure and morbidity. The advent of the radiofrequency energy-based bipolar device Habib™-4X has made bloodless hepatic resection possible. The radiofrequency-generated coagulative necrosis on normal liver parenchyma provides a firm underpinning for the bloodless liver resection. This meta-analysis was undertaken to analyse the available data on the clinical effectiveness or outcomes of liver resection with Habib™-4X in comparison to the clamp-crush technique. The RF-assisted device Habib™-4X is considered a safe and feasible modality for liver resection compared to the clamp-crush technique owing to the multitude of benefits and mounting clinical evidence supporting its role as a superior liver resection device. The most intriguing advantage of the RF-device is its ability to induce systemic and local immunomodulatory changes that further expand the boundaries of survival outcomes following liver resection.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00502819&limit=30&person=true