Imperial College London

DrKevinMonahan

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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k.monahan Website

 
 
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CRUKSt Marks HospitalNorthwick Park and St Marks Site

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Summary

 

Publications

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Ryan NAJ, Snowsill T, McKenzie E, Monahan KJ, Nebgen Det al., 2021, Should women with Lynch syndrome be offered gynaecological cancer surveillance?, BMJ, Vol: 374, Pages: 1-4, ISSN: 1759-2151

Journal article

Alexander J, Johnston B, Smith T, Yong KK, Marshall S, Fawkes J, Martin J, Seward E, Saunders B, Monahan Ket al., 2021, Low referral rates for genetic assessment of patients with multiple adenomas in United Kingdom Bowel Cancer Screening Programmes, Diseases of the Colon and Rectum, Vol: 64, Pages: 1058-1063, ISSN: 0012-3706

Background:Approximately one in twenty cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with ten or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. Objective:The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with ten or more adenomas.Design:A cross-sectional study was performed of prospectively collected data from the United Kingdom Bowel Cancer Screening Program between May 2007 & June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records and referrals to clinical genetics services were ascertained. Setting:Data were obtained from three centres in London, United Kingdom.Patients:A total of 17,450 subjects underwent colonoscopy following an abnormal faecal occult blood test. Main outcome measures:We quantified patients with ten or more adenomas and the proportion referred for genetic screening.Results:The adenoma detection rate was 50.6% amongst 17,450 patients who underwent colonoscopy (8,831 had one or more adenomas). 347 patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with less than 10 adenomas (76.9% vs. 53.4%; p<0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment.Limitations:All three screening centres were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population.Conclusions:In this study, almost one in fifty patients had ten or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient popula

Journal article

D'Souza N, Monahan K, Benton SC, Wilde L, Abulafi Met al., 2021, Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients, COLORECTAL DISEASE, ISSN: 1462-8910

Journal article

D'Souza N, Delisle TG, Chen M, Benton SC, Abulafi Met al., 2021, Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 804-810, ISSN: 0007-1323

Journal article

Win AK, Dowty JG, Reece JC, Lee G, Templeton AS, Plazzer J-P, Buchanan DD, Akagi K, Aksoy S, Alonso A, Alvarez K, Amor DJ, Ankathil R, Aretz S, Arnold JL, Aronson M, Austin R, Backman A-S, Bajwa-ten Broeke SW, Barca-Tierno V, Barwell J, Bernstein I, Berthet P, Betz B, Bignon Y-J, Boisjoli T, Bonadona V, Briollais L, Brunet J, Bucksch K, Buecher B, Buettner R, Burn J, Caldés T, Capella G, Caron O, Casey G, Chew MH, Choi Y-H, Church J, Clendenning M, Colas C, Cops EJ, Coupier I, Cruz-Correa M, de la Chapelle A, de Wind N, Dębniak T, Della Valle A, Delnatte C, Dhooge M, Dominguez-Valentin M, Drouet Y, Duijkers FA, Engel C, Esperon P, Evans DG, Falcón de Vargas A, Figueiredo JC, Foulkes W, Fourme E, Frebourg T, Gallinger S, Garre P, Genuardi M, Gerdes A-M, Gima LM, Giraud S, Goodwin A, Görgens H, Green K, Guillem J, Guillén-Ponce C, Guimbaud R, Guindalini RSC, Half EE, Hall MJ, Hampel H, Hansen TVO, Heinimann K, Hes FJ, Hill J, Ho JWC, Holinski-Feder E, Hoogerbrugge N, Hüneburg R, Huntley V, James PA, Jensen UB, John T, Juhari WKW, Kalady M, Kastrinos F, Kloor M, Kohonen-Corish MRJ, Krogh LN, Kupfer SS, Ladabaum U, Lagerstedt-Robinson K, Lalloo F, Lasset C, Latchford A, Laurent-Puig P, Lautrup CK, Leggett BA, Lejeune S, LeMarchand L, Ligtenberg M, Lindor N, Loeffler M, Longy M, Lopez F, Lowery J, Lubiński J, Lucassen AM, Lynch PM, Malińska K, Matsubara N, Mecklin J-P, Møller P, Monahan K, Morrison PJ, Nattermann J, Navarro M, Neffa F, Neklason D, Newcomb PA, Ngeow J, Nichols C, Nielsen M, Nixon DM, Nogues C, Okkels H, Olschwang S, Pachter N, Pai RK, Palmero EI, Pande M, Parry S, Patel SG, Pearlman R, Perne C, Pineda M, Poplawski NK, Pylvänäinen K, Qiu J, Rahner N, Ramesar R, Rasmussen LJ, Redler S, Reis RM, Ricciardiello L, Rogoża-Janiszewska E, Rosty C, Samadder NJ, Sampson JR, Schackert HK, Schmiegel W, Schulmann K, Schuster H, Scott R, Senter L, Seppälä TT, Shtoyerman R, Sijmons RH, Snyder C, Solomon IB, Soto JL, Southey MC, Spigelman A, Spirandelli F, Spurdle AB, Stet al., 2021, Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study, The Lancet Oncology, ISSN: 1470-2045

BackgroundExisting clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence.MethodsIn this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.Findings5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australas

Journal article

Ahmad A, Wilson A, Moorghen M, Dhillon AS, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan KJ, Vance M, Saunders BPet al., 2021, HIGH CONFIDENCE OPTICAL DIAGNOSIS OF SMALL POLYPS AT COLONOSCOPY VERSUS HISTOPATHOLOGY: MOVING TOWARDS A NEW GOLD STANDARD?, Publisher: MOSBY-ELSEVIER, Pages: AB89-AB89, ISSN: 0016-5107

Conference paper

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan KJ, Vance M, Dhillon AS, Saunders BPet al., 2021, LEARNING CURVE OF OPTICAL DIAGNOSIS WITH A RESECT AND DISCARD STRATEGY FOR SCREENING COLONOSCOPY: PRELIMINARY RESULTS FROM THE DISCARD3 STUDY, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S138-S138, ISSN: 0016-5085

Conference paper

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Dhillon A, Saunders Bet al., 2021, Patient Acceptability of Optical Diagnosis for Diminutive Polyps With a Resect And Discard Strategy In Bowel Cancer Screening Colonoscopy, ESGE Days 2021, Publisher: Georg Thieme Verlag KG

Conference paper

Awasthi A, Barbour J, Beggs A, Bhandari P, Blakeway D, Brookes M, Brown J, Brown M, Caldwell G, Clokie S, Colleypriest B, Conlin A, de Silva S, de Caestecker J, Deeks J, Dhar A, Dilworth M, Fogden E, Foley S, Ghosh D, Grellier L, Hart A, Hoque SS, Iacucci M, Iqbal T, James J, Jarvis M, Jayaprakash A, Keshav S, Magill L, Matthews G, Mawdsley J, McLaughlin S, Mehta S, Monahan K, Morton D, Murugesan S, Parkes M, Pestinger V, Probert C, Ramadas A, Rettino A, Sebastian S, Sharma N, Griffiths M, Stockton J, Subramanian V, Suggett N, Taniere P, Teare J, Verma AM, Wallis Yet al., 2021, Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-88, ISSN: 2050-4365

BackgroundChronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection.ObjectivesTo establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme.DesignModule 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later.SettingThirty-one UK hospitals.ParticipantsPatients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis.InterventionsAn optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy.Main outcomeIdentifying ulcerative colitis patients with neoplasia.ResultsModule 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interv

Journal article

Richardson-thibodeau J, Norton B, Monahan K, 2021, P72 The diagnostic yield of surveillance colonoscopy in post-colorectal cancer patients, Abstracts of the BSG Campus, 21–29 January 2021, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Ahmad A, Dhillon A, Wilson A, Suzuki N, Thomas-Gibson S, Humphries A, Haycock A, Monahan K, Vance M, Saunders Bet al., 2021, P1 Early evaluation of a computer assisted polyp detection system in bowel cancer screening, Abstracts of the BSG Campus, 21–29 January 2021, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

D'Souza N, Georgiou-Delisle T, Chen M, Benton S, Abulafi M, The NICE FIT Steering Groupet al., 2020, Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway; a diagnostic accuracy study, Gut, Vol: 70, Pages: 1130-1138, ISSN: 0017-5749

Objective To assess whether a faecal immunochemical test (FIT) could be used to select patients with suspected colorectal cancer (CRC) symptoms for urgent investigation.Design Multicentre, double-blinded diagnostic accuracy study in 50 National Health Service (NHS) hospitals across England between October 2017 and December 2019. Patients referred to secondary care with suspected CRC symptoms meeting NHS England criteria for urgent 2 weeks wait referral and triaged to investigation with colonoscopy were invited to perform a quantitative FIT. The sensitivity of FIT for CRC, and effect of relevant variables on its diagnostic accuracy was assessed.Results 9822 patients were included in the final analysis. The prevalence of CRC at colonoscopy was 3.3%. The FIT positivity decreased from 37.2% to 19.0% and 7.6%, respectively, at cut-offs of 2, 10 and 150 µg haemoglobin/g faeces (µg/g). The positive predictive values of FIT for CRC at these cut-offs were 8.7% (95% CI, 7.8% to 9.7%), 16.1% (95% CI 14.4% to 17.8%) and 31.1% (95% CI 27.8% to 34.6%), respectively, and the negative predictive values were 99.8% (95% CI 99.7% to 99.9%), 99.6% (95% CI 99.5% to 99.7%) and 98.9% (95% CI 98.7% to 99.1%), respectively. The sensitivity of FIT for CRC decreased at the same cut-offs from 97.0% (95% CI 94.5% to 98.5%) to 90.9% (95% CI 87.2% to 93.8%) and 70.8% (95% CI 65.6% to 75.7%), respectively, while the specificity increased from 64.9% (95% CI 63.9% to 65.8%) to 83.5% (95% CI 82.8% to 84.3%) and 94.6% (95% CI 94.1% to 95.0%), respectively. The area under the receiver operating characteristic curve was 0.93 (95% CI 0.92 to 0.95).Conclusion FIT sensitivity is maximised to 97.0% at the lowest cut-off (2 µg/g); a negative FIT result at this cut-off can effectively rule out CRC and a positive FIT result is better than symptoms to select patients for urgent investigations.Trial registration number ISRCTN49676259.

Journal article

Mohamed F, Kallioinen M, Braun M, Fenwick S, Shackcloth M, Davies RJet al., 2020, Author response to: NICE Guidelines: management of colorectal cancer metastases, BRITISH JOURNAL OF SURGERY, Vol: 107, Pages: E358-E358, ISSN: 0007-1323

Journal article

Monahan KJ, Lincoln A, East JE, Benton S, Burn J, DeSouza B, Hanson H, Lalloo F, McVeigh T, Rutter MD, Snape K, Thomas HJW, Sasieni Pet al., 2020, Management strategies for the colonoscopic surveillance of people with Lynch syndrome during the COVID-19 pandemic, Gut, ISSN: 0017-5749

Journal article

Mohamed F, Kallioinen M, Braun M, Fenwick S, Shackcloth M, Davies RJet al., 2020, Management of colorectal cancer metastases to the liver, lung or peritoneum suitable for curative intent: summary of NICE guidance, British Journal of Surgery, ISSN: 0007-1323

Journal article

Bromham N, Kallioinen M, Hoskin P, Davies RJet al., 2020, GUIDELINES Colorectal cancer: summary of NICE guidance, BMJ-BRITISH MEDICAL JOURNAL, Vol: 368, ISSN: 1756-1833

Journal article

Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J, Hereditary CRC guidelines eDelphi consensus groupet al., 2020, Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG), Gut, Vol: 69, Pages: 411-444, ISSN: 0017-5749

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Journal article

Rutter MD, East J, Rees CJ, Cripps N, Docherty J, Dolwani S, Kaye PV, Monahan KJ, Novelli MR, Plumb A, Saunders BP, Thomas-Gibson S, Tolan DJM, Whyte S, Bonnington S, Scope A, Wong R, Hibbert B, Marsh J, Moores B, Cross A, Sharp Let al., 2020, British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines, Gut, Vol: 69, Pages: 201-223, ISSN: 0017-5749

These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address:Which patients should commence surveillance post-polypectomy and post-cancer resection?What is the appropriate surveillance interval?When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant.two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either:two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10&thin

Journal article

Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, Chanchlani N, Walker GJ, Perry MH, McDonald TJ, Lees CW, Cummings JRF, Parkes M, Mansfield JC, Irving PM, Barrett JC, McGovern D, Goodhand JR, Anderson CA, Ahmad T, Patel V, Mazhar Z, Saich R, Colleypriest B, Tham TC, Iqbal TH, Kaushik V, Murugesan S, Singh S, Weaver S, Preston C, Butt A, Smith M, Basude D, Beale A, Langlands S, Direkze N, Parkes M, Torrente F, De La Revella Negro J, Ewen MacDonald C, Evans SM, Gunasekera AVJ, Thakur A, Elphick D, Shenoy A, Nwokolo CU, Dhar A, Cole AT, Agrawal A, Bridger S, Doherty J, Cooper SC, de Silva S, Mowat C, Mayhead P, Lees C, Jones G, Ahmad T, Hart JW, Gaya DR, Russell RK, Gervais L, Dunckley P, Mahmood T, Banim PJR, Sonwalkar S, Ghosh D, Phillips RH, Azaz A, Sebastian S, Shenderey R, Armstrong L, Bell C, Hariraj R, Matthews H, Jafferbhoy H, Selinger CP, Zamvar V, De Caestecker JS, Willmott A, Miller R, Sathish Babu P, Tzivinikos C, Bloom SL, Chung-Faye G, Croft NM, Fell JME, Harbord M, Hart A, Hope B, Irving PM, Lindsay JO, Mawdsley JE, McNair A, Monahan KJ, Murray CD, Orchard T, Paul T, Pollok R, Shah N, Bouri S, Johnson MW, Modi A, Dawa Kabiru K, Baburajan BK, Bhaduri B, Adebayo Fagbemi A, Levison S, Limdi JK, Watts G, Foley S, Ramadas A, MacFaul G, Mansfield J, Grellier L, Morris M-A, Tremelling M, Hawkey C, Kirkham S, Charlton CPJ, Rodrigues A, Simmons A, Lewis SJ, Snook J, Tighe M, Goggin PM, De Silva AN, Lal S, Smith MS, Panter S, Cummings F, Dharmisari S, Carter M, Watts D, Mahmood Z, McLain B, Sen S, Pigott AJ, Hobday D, Wesley E, Johnston R, Edwards C, Beckly J, Vani D, Ramakrishnan S, Chaudhary R, Trudgill NJ, Cooney R, Bell A, Prasad N, Gordon JN, Brookes MJ, Li A, Gore Set al., 2020, HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn’s disease, Gastroenterology, Vol: 158, Pages: 189-199, ISSN: 0016-5085

Background & AimsAnti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.MethodsWe performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn’s disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease.ResultsThe HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60–2.25; P = 5.88 × 10–13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35–2.98; P = 6.60 × 10–4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32–2.70) or infliximab (HR, 1.92; 95% CI, 1.57–2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37–2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57–2.58).ConclusionsIn an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the developmen

Journal article

Al Bakir I, Sebepos-Rogers G, Burton H, Monahan Ket al., 2019, Mainstreaming of genomic medicine in gastroenterology, present and future: a Nationwide Survey of UK Gastroenterology Trainees, BMJ Open, Vol: 9, ISSN: 2044-6055

Objective: Genomics and personalised medicine are increasingly relevant for patients with gastroenterological conditions. We aim to capture the current state of genomics training in gastroenterology to review current understanding, clinical experience and long-term educational needs of UK trainees.Design & Setting: A web-based nationwide survey of all UK gastroenterology specialty trainees was conducted in 2017.Results: 100 trainees (14% of UK gastroenterology trainees) completed this survey. Only 9% and 16% of respondents believe that their local training programme adequately prepares them for future clinical practice utilising genomic medicine and personalised medicine respectively. Barriers identified include the need for greater trainee education (95%), inadequate clinical guidance to base interventions on the results of genomic testing (53%), concerns over misinterpretation by patients (43%) and overuse/misuse of testing by clinicians (34%).Survey respondents felt prepared to perform HFE genotyping (98%), assess TPMT status (97%), and interpret HLA-subtyping for suspected coeliac disease (85%). However, only a minority felt prepared to perform the following investigations: polyposis screening (34%), hereditary pancreatitis screening (30%), testing for Lynch Syndrome (33%), and KRAS testing for colorectal cancer (20%).Most respondents would support holding dedicated training days on genomic medicine (83%), formal training provisions for the mainstreaming of genomic testing (64%), an update to the UK gastroenterology specialty training curriculum and examinations (57%), and better-defined referral pathways for local genomic services (91%).Conclusion: Most gastroenterology trainees in this survey feel ill-equipped to practice genomic and personalised medicine as consultants. We propose specific revisions to the UK gastroenterology specialty curriculum t

Journal article

Crosbie EJ, Ryan NAJ, Arends MJ, Bosse T, Burn J, Cornes JM, Crawford R, Eccles D, Frayling IM, Ghaem-Maghami S, Hampel H, Kauff ND, Kitchener HC, Kitson SJ, Manchanda R, McMahon RFT, Monahan KJ, Menon U, Moller P, Moslein G, Rosenthal A, Sasieni P, Seif MW, Singh N, Skarrott P, Snowsill TM, Steele R, Tischkowitz M, Evans DG, Sanchez AA, Bolton J, Church D, Donnelly K, Edmondson RJ, Gollop P, Goodman S, Hodgson S, Lalloo F, Lowry A, Mcvey RJ, Miles T, Monahan KJ, Stormoken A, Stringfellow H, Wallace A, Whyte L, Wilkinson N, Wilson G, Wilson J, Wood Net al., 2019, The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome, Genetics in Medicine, Vol: 21, Pages: 2390-2400, ISSN: 1098-3600

PURPOSE: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. METHODS: Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. RESULTS: Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. CONCLUSION: This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.

Journal article

Adams LK, Qiu S, Hunt AK, Monahan KJet al., 2019, A dedicated high‐quality service for the management of patients with an inherited risk of colorectal cancer, Colorectal Disease, Vol: 21, Pages: 879-885, ISSN: 1462-8910

Aim To demonstrate the quality improvement associated with the implementation of a specialist Family History of Bowel Cancer Service in secondary care. Method Outcomes assessed: 1. Adherence to the BSG Guidelines for colonoscopic surveillance of individuals with a family history of colorectal cancer; 2. Adherence to the Revised Bethesda Criteria for the identification of colorectal cancer patients with suspected Lynch Syndrome; 3. Identification of inherited colorectal cancer risk syndromes; 4. Colonoscopic Adenoma Detection Rate. Data was collected for a 21-month period prior and subsequent to the establishment of this service, for all patients who underwent colonoscopic surveillance for a family history of colorectal cancer and all patients newly diagnosed with colorectal cancer. Analysis compared the number of colonoscopies performed, not indicated by BSG guidelines; the average number of years patients were screened early; the adenoma detection rate; and the rate of MMR tumour testing, before and after the implementation of the service. Results Following the establishment of the service there was a reduction in number of colonoscopies not indicated by BSG guidelines, (39.6% vs 5.8%, p<0.001, chi squared test); surveillance colonoscopy took place at a more appropriate age (10.6 vs 5.9 years too early, p=0.01, t-test). There was an increased adenoma detection rate (17% vs 31.9%, p<0.01, chi-squared test), and increased tumour MMR testing (3.4% vs 91.8%, P<0.01, Chi squared test). Conclusion The introduction of a Family History of Bowel Cancer Service results in improved patient care through improved guideline adherence for colonoscopic surveillance and increased cancer detection rates.

Journal article

Cavazza A, Chandni R, Chris H, Monahan Ket al., 2019, An experience of implementation and outcomes of universal testing for Lynch Syndrome in the United Kingdom, Colorectal Disease, Vol: 21, ISSN: 1462-8910

AimColorectal cancer (CRC) is diagnosed in approximately 45 000 people annually in the UK, and it is estimated that Lynch syndrome (LS) accounts for 3.1% of these cases. In February 2017, National Institute for Health and Care Excellence (NICE guideline DG27 recommended universal testing of new cases of CRC for mismatch repair (MMR) status. The aim of this study was to implement universal testing for LS in CRC patients in a secondary care setting.MethodWe prospectively collected data on consecutive newly diagnosed CRC patients at our centre from November 2016 to August 2018, including evidence of MMR status determined by immunohistochemistry. We recorded clinicopathological data including age at diagnosis, stage, tumour site, reported histological findings and MMR tumour status. Statistical analysis was performed using the chi‐square test and the two‐tailed t‐test for binary and continuous variables, respectively.ResultsA cohort of 203 consecutive patients were diagnosed with CRC during this period. Universal MMR testing was performed for the 198 CRC patients in whom a diagnosis of adenocarcinoma was confirmed, with colonoscopic biopsy used as the source material in 68.6% of cases. Twenty‐three CRCs (11.6%) were MMR deficient (dMMR). Most dMMR CRCs (21/23) were early stage tumours (Dukes A or B, P = 0.002). In 39 Dukes B CRCs in patients under 70 years of age, the result of MMR testing influenced decision‐making about personalized treatment with 5‐fluorouracil based chemotherapy.ConclusionOur results demonstrate that universal testing of all new cases of CRC for features suggestive of LS is feasible and effective in the UK. Our data also indicate the importance of genetic testing and personalized oncological care.

Journal article

Norton B, Coultas J, Nicholas V, Wright T, Monahan Ket al., 2019, OUTCOMES OF COLONOSCOPIC SURVEILLANCE AND MOLECULAR PHENOTYPING IN PATIENTS WITH FAMILY HISTORY OF COLORECTAL CANCER, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A35-A36, ISSN: 0017-5749

Conference paper

Alexander J, Johnston B, Smith T, Fawkes J, Martin J, Seward E, Monahan Ket al., 2019, PATIENTS WITH MULTIPLE ADENOMAS IN BOWEL CANCER SCREENING PROGRAM ARE NOT REFERRED FOR GENETIC TESTING, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A188-A188, ISSN: 0017-5749

Conference paper

Lagrue D, Aggarwal N, Monahan K, 2019, THE ASSOCIATION OF TOLL-LIKE RECEPTOR (TLR) PATHWAY POLYMORPHISMS AND COLORECTAL CANCER RISK: A META-ANALYSIS, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A197-A197, ISSN: 0017-5749

Conference paper

Norton B, Wright T, Coultas J, Nicholas V, Monahan Ket al., 2019, COLONOSCOPIST KEY PERFORMANCE INDICATORS AND THE SURVEILLANCE OF PATIENTS WITH FAMILY HISTORY OF COLORECTAL CANCER, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A36-A37, ISSN: 0017-5749

Conference paper

Quaglia A, Aggarwa N, McPhail M, Monahan Ket al., 2019, META-ANALYSIS OF TUMOUR MICROSATELLITE-INSTABILITY, AS A PREDICTOR OF RESPONSE TO FLUOROURACIL-BASED ADJUVANT CHEMOTHERAPY FOR COLON CANCER, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A198-A198, ISSN: 0017-5749

Conference paper

Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ, Thomas A, Nice R, Perry MH, Bouri S, Chanchlani N, Heerasing NM, Hendy P, Lin S, Gaya DR, Cummings JRF, Selinger CP, Lees CW, Hart AL, Parkes M, Sebastian S, Mansfield JC, Irving PM, Lindsay J, Russell RK, McDonald TJ, McGovern D, Goodhand JR, Ahmad Tet al., 2019, Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 4, Pages: 341-353, ISSN: 2468-1253

Journal article

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