Publications
157 results found
Al Bakir I, Sebepos-Rogers GM, Burton H, et al., 2018, GENOMIC MEDICINE IN GASTROENTEROLOGY, PRESENT AND FUTURE: A NATIONWIDE SURVEY OF HIGHER SPECIALTY TRAINEES, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A271-A271, ISSN: 0017-5749
Cavazza A, Radia C, Harlow C, et al., 2018, COLORECTAL CANCER AND EXPERIENCE IN TESTING FOR LYNCH SYNDROME IN A WEST LONDON HOSPITAL, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A188-A189, ISSN: 0017-5749
Lawler M, Alsina D, Adams RA, et al., 2018, Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer, Gut, Vol: 67, Pages: 179-193, ISSN: 0017-5749
Objective Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.Design RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants.Results Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders.Conclusion Prioritising research activity and funding could have a significant impact on reducing CRC dis
Burn J, Alsina D, Hill J, et al., 2017, Response: A clinical consensus on improving the colonoscopic screening and surveillance of people with Lynch syndrome in England, British Medical Journal, Vol: 356, ISSN: 0959-8138
Aggarwal N, Donald ND, Malik S, et al., 2017, The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal Cancer: A Systematic Review and Meta-Analysis, Clinical and Translational Gastroenterology, Vol: 8, ISSN: 2155-384X
OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes,accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repairpathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair(DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations inthese genes are associated with high-penetrance CRC syndromes such as Lynch syndrome. However, the association of lowpenetrancepolymorphisms of DNA repair genes with CRC risk remains unclear.METHODS: A systematic literature review of PubMed, Embase, and HuGENet databases was conducted. Pre-specified criteriadetermined study inclusion/exclusion. Per-allele, pooled odds ratios disclosed the risk attributed to each variant. Heterogeneitywas investigated by subgroup analyses for ethnicity and tumor location; funnel plots and Egger’s test assessed publication bias.RESULTS: Sixty-one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses for 22 polymorphisms in 17genes revealed that six polymorphisms were significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5, XPC),double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup analyses revealed significant association ofOGG1 rs1052133 with rectal cancer risk. Egger’s test revealed no publication bias.CONCLUSIONS: Low-penetrance polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies should thereforeanalyze whole-genome polymorphisms and any synergistic effects on CRC risk.TRANSLATIONAL IMPACT: This knowledge may enhance CRC risk assessment and facilitate a more personalized approach tocancer prevention.
Aggarwal N, Donald ND, Malik S, et al., 2017, MDM2 T309G POLYMORPHISM AND RISK OF COLORECTAL CANCER, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A126-A127, ISSN: 0017-5749
Aggarwal N, Donald ND, Malik S, et al., 2017, THE ASSOCIATION OF LOW PENETRANCE VARIANTS IN DNA REPAIR GENES WITH COLORECTAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A126-A126, ISSN: 0017-5749
Donald N, Malik S, McGuire JL, et al., 2017, The association of low penetrance genetic risk modifiers with colorectal cancer in lynch syndrome patients: a systematic review and meta-analysis., Familial Cancer, Vol: 17, Pages: 43-52, ISSN: 1389-9600
Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition syndrome accounting for approximately 1000 cases of colorectal cancer (CRC) in the UK annually. LS is characterised by autosomal dominant inheritance and germline mutations in DNA mismatch repair genes. The penetrance is highly variable and the reasons for this have not been fully elucidated. This study investigates whether low penetrance genetic risk factors may result in phenotype modification in LS patients. To conduct a systematic literature review and meta-analysis to assess the association between low penetrance genetic risk modifiers and CRC in LS patients. A systematic review was conducted of the PubMed and HuGENet databases. Eligibility of studies was determined by pre-defined criteria. Included studies were analysed via the per-allele model and assessed by pooled odds ratios and establishing 95% confidence intervals. Study heterogeneity was assessed via Cochrane's Q statistic and I2 values. Publication bias was evaluated with funnel plots. Subgroup analysis was conducted on gender. Statistical software used was the Metafor package for the R programme version 3.1.3. Sixty-four polymorphisms were identified and sufficient data was available for analysis of ten polymorphisms, with between 279 and 1768 CRC cases per polymorphism. None demonstrated association with CRC risk in LS patients. However in sub-group analysis the polymorphism rs16892766 (8q23.3) was significant in males (OR 1.53, 95% CI 1.12-2.10). The variable phenotype presentation of the disease still remains largely unexplained, and further investigation is warranted. Other factors may also be influencing the high variability of the disease, such as environmental factors, copy number variants and epigenetic alterations. Investigation into these areas is needed as well as larger and more definitive studies of the polymorphisms analysed in this study.
Monahan KJ, Alsina D, Bach S, et al., 2017, Urgent improvements needed to diagnose and manage Lynch syndrome, BMJ-BRITISH MEDICAL JOURNAL, Vol: 356, ISSN: 1756-1833
Malik SS, Lythgoe M, Monahan KJ, 2016, METACHRONOUS CANCERS FOLLOWING SEGMENTAL OR EXTENDED COLECTOMY IN LYNCH SYNDROME: A SYSTEMATIC REVIEW & META-ANALYSIS, GUT, Vol: 65, Pages: A196-A197, ISSN: 0017-5749
Donald N, Malik S, McGuire J, et al., 2016, THE ASSOCIATION OF LOW PENETRANCE GENETIC RISK MODIFIERS WITH COLORECTAL CANCER IN LYNCH SYNDROME PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A193-A194, ISSN: 0017-5749
Monahan KJ, Hopkins L, 2016, Diagnosis and management of hereditary gastric cancer, Recent Results in Cancer Research, Vol: 205, Pages: 45-60, ISSN: 0080-0015
A positive family history is consistently reported as a risk factor for gastric cancer (GC), but the molecular basis for the familial aggregation is largely unknown. The risk associated with having one first-degree relative (FDR) with GC is approximately 1.3-3.5 fold increased. Hereditary cancer syndromes have been relatively well characterised, but their rarity largely precludes the development of trials of surveillance. In hereditary diffuse gastric cancer (HDGC), patients have a CDH1 mutation that results in a high penetrance of GC meaning that prophylactic gastrectomy is recommended, although this treatment results in significant psychosocial issues. The management of HDGC patients includes endoscopic surveillance, surgery and histological interpretation which require a high degree of selective expertise. Much of the remaining heritable risk of GC may be accounted for by low- and intermediate-penetrant genetic factors, i.e. common and rare variants, respectively. The advent of new methods such as next-generation sequencing has revealed a number of new candidate gene loci.
Donald ND, Malik S, McGuire JL, et al., 2016, Mo1160 The Association of Low Penetrance Genetic Risk Modifiers With Colorectal Cancer in Lynch Syndrome Patients: A Systematic Review and Meta-analysis, Publisher: Elsevier BV, Pages: S655-S655, ISSN: 0016-5085
Donald ND, Malik S, McGuire JL, et al., 2016, The Association of Low Penetrance Genetic Risk Modifiers With Colorectal Cancer in Lynch Syndrome Patients: A Systematic Review and Meta-analysis, 57th Annual Meeting and Residents Fellow Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / 52nd Annual Meeting on Digestive Disease Week (DDW) / Meeting of the American-Gastroenterological-Association (AGA), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S655-S655, ISSN: 0016-5085
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Graby J, Ramsey C, McPhail M, et al., 2015, The role of MRCP in potential gallstone disease when the biliary tree is normal on initial imaging, Clinical Radiology, Vol: 70, Pages: S3-S3, ISSN: 0009-9260
Mcgowan LA, Hopkins LA, Monahan KJ, 2015, Detection of neoplasia using dye spray chromoendoscopy in patients with a high risk of familial colorectal cancer, Gut, Vol: 64, Pages: A369-A370, ISSN: 1468-3288
Introduction Patients at high risk of familial colorectal cancer require surveillance colonoscopy to identify and remove polyps before malignant transformation can occur. Colonoscopy sensitivity rates vary and its effectiveness depends on user ability, adequate bowel preparation and procedure duration. Furthermore, the majority of polyps occur in the right colon and are characteristically flatter than those found in the left colon, rendering identification difficult. As such, recent guidelines have advocated the use of dye spray chromoendoscopy (DSC) to aid detection rates.1Our study assesses the use of chromoendoscopy at a district general hospital and whether polyp detection was higher in those undergoing surveillance colonoscopy when dye spray was used.Method High risk patients were selected from our local endoscopy database Scorpio®. High risk was defined by a diagnosis of Lynch Syndrome or High Moderate risk as per BSG guidelines (i.e. a lifetime risk of colorectal cancer of >10%).2We retrospectively measured polyp detection rate, procedure duration, adequacy of bowel preparation, withdrawal time, histopathology, and the use of 0.02% indigocarmine dye spray versus white light colonoscopy (WLI). Statistical analysis was performed using chi-square test and 2 tailed T test for binary and continuous variables respectively.Results 101 patients were included in this study (62 High Moderate risk and 39 Lynch Syndrome). WLI alone was performed for 77 patients, with DSC performed in 24. Significantly more polyps were detected by the use of dye spray, with an average polyp count of 0.49 for WLI versus 1.79 for DSC (P = 0.00332). There was a predominance of right sided lesions in this cohort. A longer withdrawal time may also be a factor in polyp detection rate. Table 1highlights our main findings.
Graby J, Goldman A, McPhail M, et al., 2015, PTU-306 The efficacy of mrcp in suspected gallstone disease when the biliary tree is normal on previous imaging, Gut, Vol: 64 Suppl 1, Pages: A195-A196, ISSN: 1468-3288
Huang-Doran I, Mason C, Mcphail M, et al., 2015, PTU-285 Early in-patient management of alcohol-related liver disease: results of a liver care bundle to improve quality of care, Gut, Vol: 64 Suppl 1, Pages: A186-A186, ISSN: 1468-3288
Malik SS, Monahan KJ, McPhail M, 2015, PWE-368 The association of genetic variation within the wnt signalling pathway with colorectal cancer: a meta-analysis, Gut, Vol: 64 Suppl 1, Pages: A372-A372, ISSN: 1468-3288
Kaur A, Monahan KJ, Schofield J, et al., 2015, PWE-346 Lynch syndrome and application of the rcpath colorectal cancer dataset in the United Kingdom, Gut, Vol: 64 Suppl 1, Pages: A362-A362, ISSN: 1468-3288
, 2014, Genetics for Health Professionals in Cancer Care, Publisher: Oxford University Press, ISBN: 9780199672844
Yusuf A, John Monahan K, 2014, Early detection of hereditary colorectal and gastric cancer, Genetics for Health Professionals in Cancer Care, Publisher: Oxford University Press, Pages: 165-172
Yusuf A, Monahan KJ, 2014, Genetics for Health Professionals in Cancer Care: From Principles to Practice(Chapter 19: Early detection of hereditary colorectal and gastric cancer), Genetics for Health Professionals in Cancer Care: From Principles to Practice, Editors: Jacobs, Robinson, Webb, Publisher: Oxford University Press, Pages: 165-172, ISBN: 9780191653483
Addresses the fundamental principles of cancer biology and basic genetics, enabling non-genetics healthcare staff to integrate genetics into practice Provides the reader with knowledge and practical skills about family history of cancer, including how to taking an accurate family history, assessing cancer risk, and communicating risk information to the patient, family and other health professionals Summary chapter at the ends of each section provide guided learning activities and suggested resources for further learningThe role of genetics is becoming increasingly important in all aspects of healthcare and particularly in the field of cancer care. Genetics for Health Professionals in Cancer Care: From Principles to Practice equips health professionals with the knowledge and skills required for all aspects of managing cancer family history. This includes taking an accurate cancer family history and drawing a family tree; understanding cancer biology, basic cancer genetics and the genes involved in hereditary breast, ovarian, prostate, colorectal, gastric and related gynaecological cancers and rare cancer predisposing syndromes; assessing cancer risk and communicating risk information; early detection and risk reducing measures available for those at increased risk and managing individuals with hereditary cancer.Drawing on experiences of health professionals, Genetics for Health Professionals in Cancer Care discusses the challenges raised and provides practical advice and insight into what happens when a patient is referred for genetic counselling and genetic testing, including the psychological, social and ethical issues faced by individuals and families with and at risk of hereditary cancer. The book also provides practical guidance on setting up a cancer family history clinic in primary and secondary care.Genetics for Health Professionals in Cancer Care is essential reading for healthcare professionals working with cancer patients and their families, and is a
McGuire J, McPhail M, Rajendran A, et al., 2014, PWE-010 The Association Of TGF-beta Signalling Pathway Gene Polymorphisms With Colorectal Cancer Risk: A Meta-analysis.
Background Approximately 35% of colorectal cancer risk is due to heritable factors. To date, a large fraction of this heritability remains unexplained. The TGFß signalling pathway has an increasingly implicated role in colorectal carcinogenesis, with highly penetrant-germline mutations of BMPR1A, SMAD4 and GREM1 causing known polyposis syndromes. We propose that common, low penetrance variation of TGFß signalling genes may account for much of the unexplained heritability of colorectal cancer, underlining the importance of this signalling pathway in the aetiology of colorectal cancer.
McGuire JL, McPhail M, Rajendran A, et al., 2014, Tu1902 The Association of TGFβ Signalling Pathway Gene Polymorphisms With Colorectal Cancer Risk: A Meta-Analysis, DDW 2014, Publisher: ScienceDirect
McGuire JL, McPhail M, Rajendran A, et al., 2014, The Association of TGFβ Signalling Pathway Gene Polymorphisms With Colorectal Cancer Risk: A Meta-Analysis, 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S868-S868, ISSN: 0016-5085
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Monahan KJ, Clark SK, British Society of Gastroenterology BSG Cancer Group, 2014, A national survey of hereditary colorectal cancer services in the UK., Frontline Gastroenterol, Vol: 5, Pages: 130-134, ISSN: 2041-4137
OBJECTIVES: The British Society of Gastroenterology (BSG) Cancer Group designed a survey to determine how we might understand and improve the service for patients at elevated risk of hereditary colorectal cancer (CRC). DESIGN AND SETTING: United Kingdom (UK) gastroenterologists, colorectal surgeons, and oncologists were invited by email to complete a 10 point questionnaire. This was cascaded to 1,793 members of the Royal College of Radiologists (RCR), Association of Cancer Physicians (ACP), the Association of Coloproctology of Great Britain and Ireland (ACPGBI), as well as BSG members. RESULTS: Three hundred and eighty-two members responded to the survey, an overall response rate of 21.3%. Although 69% of respondents felt there was an adequate service for these higher risk patients, 64% believed that another clinician was undertaking this work. There was no apparent formal patient pathway in 52% of centres, and only 33% of centres maintain a registry of these patients. Tumour block testing for Lynch Syndrome is not usual practice. Many appeared to be unaware of the BSG/ACPGBI UK guidelines for the management of these patients. CONCLUSIONS: There is wide variability in local management and in subsequent clinical pathways for hereditary CRC patients. There is a perception that they are being managed by 'another', unspecified clinician. National guidelines are not adhered to. We therefore recommend improved education, well defined pathways and cyclical audit in order to improve care of patients with hereditary CRC risk.
Adelson M, Pannick S, East J, et al., 2014, UK colorectal cancer patients are inadequately assessed for Lynch syndrome, Frontline Gastroenterology, Vol: 5, Pages: 31-35
Objective To establish whether colorectal cancer patients in two centres in the UK are screened appropriately for Lynch syndrome, in accordance with current international guidance.Design Patients newly diagnosed with colorectal cancer over an 18-month period were identified from the UK National Bowel Cancer Audit Programme. Their records and management were reviewed retrospectively.Setting Two university teaching hospitals, Imperial College Healthcare and Oxford Radcliffe Hospitals NHS Trusts.Outcomes These measured whether patients were screened for Lynch syndrome—and the outcome of that evaluation, if it took place—were assessed. The age, tumour location and family history of screened patients were compared to those of unscreened patients.Results Five hundred and fifty three patients with newly diagnosed colorectal cancer were identified. Of these, 97 (17.5%) satisfied the revised Bethesda criteria, and should have undergone further assessment. There was no evidence that those guidelines had been contemporaneously applied to any patient. In practice, only 22 of the 97 (22.7%) eligible patients underwent evaluation. The results for 14 of those 22 (63.6%) supported a diagnosis of Lynch syndrome, but only nine of the 14 (64.3%) were referred for formal mismatch repair gene testing. No factors reliably predicted whether or not a patient would undergo Lynch syndrome screening.Conclusions Colorectal teams in the UK do not follow international guidance identifying the patients who should be screened for Lynch syndrome. Patients and their families are consequently excluded from programmes reducing colorectal cancer incidence and mortality. Multidisciplinary teams should work with their local genetics services to develop reliable algorithms for patient screening and referral.
Brindley JH, Gordon H, Barrow E, et al., 2013, P718 THE INCIDENCE AND COST OF UNEXPECTED HOSPITAL ATTENDANCE FOLLOWING ELECTIVE OUTPATIENT FLEXIBLE SIGMOIDOSCOPY, UEGW, Publisher: SAGE Publications, ISSN: 2050-6414
INTRODUCTION: Outpatient flexible sigmoidoscopy is an increasingly utilised investigation shown to be effective in the detection and prevention of bowel cancer. The procedure is thought to entail a low risk of complications. However, recent literature suggests the complication rate of other endoscopic procedures may be up to 10 fold that traditionally quoted (1). The true complication rate of flexible sigmoidoscopy is of particular importance as the UK is introducing the Bowel Cancer Screening Programme (BCSP) by which all citizens will be offered the procedure at age 55.AIMS&METHODS: The aim of this study was to identify the morbidity and related healthcare costs of unexpected hospital attendance following outpatient flexible sigmoidoscopy. An observational study of A&E attendances and admissions occurring within 14 days of all outpatient flexible sigmoidoscopies which took place in 2011 was conducted. All procedures took place at West Middlesex University Hospital, London. Data was collected using the hospital's electronic records system, enterpriseCAMIS®. Cases were analysed to assess whether reattendance could be attributed to the procedure, and healthcare costs were determined.RESULTS: Of the 1137 outpatient flexible sigmoidoscopies performed, 18 patients (1.58%) presented to A&E within 14 days. Only 2 of these attendances were thought to be related to the procedure (0.18%). 1 case resulted in a 5 day admission due to bleeding post polypectomy. The second A&E attendance was also due to bleeding. The cost of the above admission was £4,682. Including the related A&E attendance, the total financial burden of related reattendance following flexible sigmoidoscopy was approximately £4,827 in 2011. This equates to an additional cost of £4.25 per procedure.CONCLUSION: This study suggests outpatient sigmoidoscopy is relatively safe, with complications necessitating reattendance occurring following 0.18% procedures. The financial
Qiu S, Hunt A, Beveridge I, et al., 2013, P1153 A DEDICATED FAMILY HISTORY OF COLORECTAL CANCER CLINIC IMPROVES ADHERENCE TO COLONOSCOPIC SCREENING GUIDELINES, UEGW, Publisher: SAGE Publications, ISSN: 2050-6414
INTRODUCTION: In 2010, the British Society of Gastroenterology (BSG) published guidelines for colonoscopic screening of people with family history (FH) of colorectal cancer (CRC). In the UK, most patients anxious about their FH of CRC are referred by primary care doctors to non-specialist hospitals. Previous studies indicate guideline adherence is poor. This could be due to a lack of dedicated genetic services to triage and counsel patients for appropriate screening. We compare guideline adherence before and after introducing a CRC FH clinic in a non-specialist hospital.AIMS&METHODS: Guideline adherence was assessed in a hospital with catchment population of ∼300,000. Data was collected from all colonoscopies in which FH was the primary indication over a 32-month period from guideline publication up to August 2012. The FH clinic was started in April 2011. Data from the 16 months periods before and after its initiation were compared.RESULTS: In total 146 screening colonoscopies were performed. Following the establishment of the dedicated FH Clinic there was a reduction in inappropriate colonoscopies (40% vs 11%, p=0.0004, X2) ; screening took place at a more appropriate age (11.80 vs 6.47 years early, p=0.013, t-test); and neoplasia detection rate was also significantly enhanced (18% vs 35%, p=0.03, X2).CONCLUSION: The BSG guidelines are based on robust evidence. Despite this, in the first 16 months after its publication, 40% of patients undergoing screening in our centre did not meet guideline criteria and were on average screened 11.8 years too early. These patients were exposed to the risk of colonoscopy earlier than recommended without justifiable benefits. Non adherence to guideline occurred at multiple levels from referral onwards. Clinicians often lacked awareness of the BSG guidelines and felt compelled to offer unnecessary screening to reassure anxious patients. After the introduction of FH clinics in our non-specialist centre, there was better evalu
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