Publications
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Lincoln AG, Benton SC, Piggott C, et al., 2023, Risk-stratified faecal immunochemical testing (FIT) for urgent colonoscopy in Lynch syndrome during the COVID-19 pandemic, BJS Open, Vol: 7, Pages: 1-8, ISSN: 2474-9842
BACKGROUND: Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing ('FIT') in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were limited. METHODS: An emergency service protocol was designed to improve colonoscopic surveillance access throughout the COVID-19 pandemic in England for people with Lynch syndrome when services were extremely restricted (1 March 2020 to 31 March 2021) and promoted by the English National Health Service. Requests for faecal immunochemical testing from participating centres were sent to the National Health Service Bowel Cancer Screening South of England Hub and a faecal immunochemical testing kit, faecal immunochemical testing instructions, paper-based survey, and pre-paid return envelope were sent to patients. Reports with faecal haemoglobin results were returned electronically for clinical action. Risk stratification for colonoscopy was as follows: faecal haemoglobin less than 10 µg of haemoglobin/g of faeces (µg/g)-scheduled within 6-12 weeks; and faecal haemoglobin greater than or equal to 10 µg/g-triaged via an urgent suspected cancer clinical pathway. Primary outcomes of interest included the identification of highest-risk Lynch syndrome patients and determining the impact of faecal immunochemical testing in risk-stratified colonoscopic surveillance. RESULTS: Fifteen centres participated from June 2020 to March 2021. Uptake was 68.8 per cent amongst 558 patients invited. For 339 eligible participants analysed, 279 (82.3 per cent) had faecal haemoglobin less than 10 µg/g and 60 (17.7 per cent) had faecal haemoglobin greater than or equal to 10 µg/g. In the latter group, the diagnostic accuracy of faecal immunochemical testing was 65.9 per cent and escalation to colonoscopy was facilitated (me
Monahan K, 2023, The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme, BMJ Oncology, ISSN: 2752-7948
Monje-Garcia L, Bill T, Farthing L, et al., 2023, From diagnosis of colorectal cancer to diagnosis of Lynch syndrome: The RM Partners quality improvement project, Colorectal Disease, ISSN: 1462-8910
AIM: The UK National Institute for Health and Care Excellence guideline DG27 recommends universal testing for Lynch syndrome (LS) in all newly diagnosed colorectal cancer (CRC) patients. However, DG27 guideline implementation varies significantly by geography. This quality improvement project (QIP) was developed to measure variation and deliver an effective diagnostic pathway from diagnosis of CRC to diagnosis of LS within the RM Partners (RMP) West London cancer alliance. METHOD: RM Partners includes a population of 4 million people and incorporates nine CRC multidisciplinary teams (MDTs), overseen by a Pathway Group, and three regional genetic services, managing approximately 1500 new CRC cases annually. A responsible LS champion was nominated within each MDT. A regional project manager and nurse practitioner were appointed to support the LS champions, to develop online training packages and patient consultation workshops. MDTs were supported to develop an 'in-house' mainstreaming service to offer genetic testing in their routine oncology clinics. Baseline data were collected through completion of the LS pathway audit of the testing pathway in 30 consecutive CRC patients from each CRC MDT, with measurement of each step of the testing pathway. Areas for improvement in each MDT were identified, delivered by the local champion and supported by the project team. RESULTS: Overall, QIP measurables improved following the intervention. The Wilcoxon signed rank test revealed significant differences with strong effect sizes on the percentile of CRC cases undergoing mismatch repair (MMR) testing in endoscopic biopsies (p = 0.008), further testing with either methylation or BRAF V600E (p = 0/03) and in effective referral for genetic testing (from 10% to 74%; p = 0.02). During the QIP new mainstreaming services were developed, alongside the implementation of systematic and robust testing pathways. These pathways were tailored to
Monahan KJ, Swinyard O, Latchford A, 2023, Biology of precancers and opportunities for cancer interception - lesson from colorectal cancer susceptibility syndromes, Cancer Prevention Research, Vol: 16, Pages: 421-427, ISSN: 1940-6207
Hereditary gastrointestinal cancer is associated with molecular and neoplastic precursors which have revealed much about sporadic carcinogenesis. Therefore, an appreciation of constitutional and somatic events linked to these syndromes have provided a useful model for the development of risk models and preventative strategies. In this review we focus of two of the best characterised syndromes, Lynch syndrome (LS) and familial adenomatous polyposis (FAP). Our understanding of the neoplasia-immune interaction in LS has contributed to the development of immune mediated therapies including cancer preventing vaccines and immunotherapy for cancer precursors. Chemoprevention in LS with aspirin and non-steroidal anti-inflammatory drugs has also translated into clinical cancer, however the efficacy of such agents in FAP remains elusive when cancer is applied as an endpoint in trials rather than the use of 'indirect' endpoints such as polyp burden, and requires further elucidation of biological mechanisms in FAP. Finally, we review controversies in gastrointestinal surveillance for LS and FAP, including limitations and opportunities of upper and lower GI endoscopy in the prevention and early detection of cancer.
Eckersley R, Monahan K, Suzuki N, 2023, P213 Endoscopic scar excision for previous R1 resection of advanced neoplasia in the rectum, BSG LIVE’23, 19–22 June, ACC Liverpool, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology
Maliki HA, Monahan KJ, 2023, O28 The diagnostic yield of colonoscopic surveillance following resection of early-age onset colorectal cancer (EOCRC), BSG LIVE’23, 19–22 June, ACC Liverpool, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology
Monje-Garcia L, Vairale J, Watt H, et al., 2023, O70 Psychological well-being of people living with a colorectal cancer predisposition syndrome: evidence from a systematic review, BSG LIVE’23, 19–22 June, ACC Liverpool, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology
Monje-Garcia L, 2023, P343 From diagnosis of colorectal cancer to diagnosis of lynch syndrome: the RM partners quality improvement project, BSG LIVE’23, 19–22 June, ACC Liverpool, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology
Monahan K, Shaw AC, Monje-Garcia LL, et al., 2023, P293 Finding the missing 95%: the English national lynch syndrome transformation project, BSG LIVE’23, 19–22 June, ACC Liverpool, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology
Dominguez-Valentin M, Haupt S, Seppälä TT, et al., 2023, Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database, EClinicalMedicine, Vol: 58, Pages: 1-12, ISSN: 2589-5370
BACKGROUND: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. METHODS: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. FINDINGS: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. INTERPRETATION: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. FUNDING: We ackno
Cavestro Giulia M, Mannucci A, Balaguer F, et al., 2023, Delphi initiative for early-onset colorectal cancer (DIRECt). International Management Guidelines., Clinical Gastroenterology and Hepatology, Vol: 21, Pages: 581-603.E33, ISSN: 1542-3565
BACKGROUND AND AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), comprised of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was employed to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. Based on current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors.The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
, 2023, 2022 CGA-IGC Annual Meeting: The collaborative group of the Americas on Inherited Gastrointestinal Cancer November 11-13, 2022 Abstracts, FAMILIAL CANCER, ISSN: 1389-9600
Sun M, Moquet J, Ellender M, et al., 2023, Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients, Familial Cancer, Vol: 22, Pages: 61-70, ISSN: 1389-9600
The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.
Georgiou D, Monje-Garcia L, Miles T, et al., 2023, A focused clinical review of lynch syndrome., Cancer Management and Research, Vol: 15, Pages: 67-85, ISSN: 1179-1322
Lynch syndrome (LS) is an autosomal dominant condition that increases an individual's risk of a constellation of cancers. LS is defined when an individual has inherited pathogenic variants in the mismatch repair genes. Currently, most people with LS are undiagnosed. Early detection of LS is vital as those with LS can be enrolled in cancer reduction strategies through chemoprophylaxis, risk reducing surgery and cancer surveillance. However, these interventions are often invasive and require refinement. Furthermore, not all LS associated cancers are currently amenable to surveillance. Historically only those with a strong family history suggestive of LS were offered testing; this has proved far too restrictive. New criteria for testing have recently been introduced including the universal screening for LS in associated cancers. This has increased the number of people being diagnosed with LS but has also brought about unique challenges such as when to consent for germline testing and questions over how and who should carry out the consent. The results of germline testing for LS can be complicated and the diagnostic pathway is not always clear. Furthermore, by testing only those with cancer for LS we fail to identify these individuals before they develop potentially fatal pathology. This review will outline these challenges and explore solutions. Furthermore, we consider the potential future of LS care and the related treatments and interventions which are the current focus of research.
Ahmad A, Wilson A, Haycock A, et al., 2022, Evaluation of a real-time computer-aided polyp detection system during screening colonoscopy: AI-DETECT study., Endoscopy, ISSN: 0013-726X
BACKGROUND: Polyp detection and resection during colonoscopy significantly reduce long-term colorectal cancer risk. Computer-aided detection (CADe) may increase polyp identification but has undergone limited clinical evaluation. Our aim was to assess the effectiveness of CADe at colonoscopy within a bowel cancer screening program (BCSP). METHODS: This prospective, randomized controlled trial involved all eight screening-accredited colonoscopists at an English National Health Service (NHS) BCSP center (February 2020 to December 2021). Patients were randomized to CADe or standard colonoscopy. Patients meeting NHS criteria for bowel cancer screening were included. The primary outcome of interest was polyp detection rate (PDR). RESULTS: 658 patients were invited and 44 were excluded. A total of 614 patients were randomized to CADe (n = 308) or standard colonoscopy (n = 306); 35 cases were excluded from the per-protocol analysis due to poor bowel preparation (n = 10), an incomplete procedure (n = 24), or a data issue (n = 1). Endocuff Vision was frequently used and evenly distributed (71.7 % CADe and 69.2 % standard). On intention-to-treat (ITT) analysis, there was a borderline significant difference in PDR (85.7 % vs. 79.7 %; P = 0.05) but no significant difference in adenoma detection rate (ADR; 71.4 % vs. 65.0 %; P = 0.09) for CADe vs. standard groups, respectively. On per-protocol analysis, no significant difference was observed in these rates. There was no significant difference in procedure times. CONCLUSIONS: In high-performing colonoscopists in a BCSP who routinely used Endocuff Vision, CADe improved PDR but not ADR. CADe appeared to have limited benefit in a BCSP setting where procedures are performed by experienced colonoscopists.
Ahmad A, Moorghen M, Wilson A, et al., 2022, Implementation of optical diagnosis with a "resect and discard" strategy in clinical practice: DISCARD3 study, Gastrointestinal Endoscopy, Vol: 96, Pages: 1021-1032.e2, ISSN: 0016-5107
Background and AimsOptical diagnosis (OD) of polyps can be performed with advanced endoscopic imaging. For high-confidence diagnoses, a “resect and discard” strategy could offer significant histopathology time and cost savings. The implementation threshold is a ≥90% OD-histology surveillance interval concordance. Here we assessed the OD learning curve and feasibility of a resect and discard strategy for ≤5-mm and <10-mm polyps in a bowel cancer screening setting.MethodsIn this prospective feasibility study, 8 bowel cancer screening endoscopists completed a validated OD training module and performed procedures. All <10-mm consecutive polyps had white-light and narrow-band images taken and were given high- or low-confidence diagnoses until 120 high-confidence ≤5-mm polyp diagnoses had been performed. All polyps had standard histology. High-confidence OD errors underwent root-cause analysis. Histology and OD-derived surveillance intervals were calculated.ResultsOf 565 invited patients, 525 patients were included. A total of 1560 <10-mm polyps underwent OD and were resected and retrieved (1329 ≤5 mm and 231 6-9 mm). There were no <10-mm polyp cancers. High-confidence OD was accurate in 81.5% of ≤5-mm and 92.8% of 6-9-mm polyps. Sensitivity for OD of a ≤5-mm adenoma was 93.0% with a positive predictive value of 90.8%. OD-histology surveillance interval concordance for ≤5-mm OD was 91.3% (209/229) for U.S. Multi-Society Task Force, 98.3% (225/229) for European Society of Gastrointestinal Endoscopy, and 98.7% (226/229) for British Society of Gastroenterology guidelines, respectively.ConclusionsA resect and discard strategy for high-confidence ≤5-mm polyp OD in a group of bowel cancer screening colonoscopists is feasible and safe, with performance exceeding the 90% surveillance interval concordance required for implementation in clinical practice. (Clinical trial registration number: NCT04710693.)
Monahan K, 2022, Exploring the utility and acceptability of Faecal Immunochemical Testing (FIT) as a novel intervention for the improvement of Colorectal Cancer (CRC) surveillance in individuals with Lynch Syndrome: A single-arm, prospective, multi-centre, non- randomised study, BMC Cancer, Vol: 22, Pages: 1-11, ISSN: 1471-2407
BackgroundLynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS.Methods/designIn this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 μg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway.16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome.DiscussionFIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT
Woodfield G, Belluomo I, Laponogov I, et al., 2022, Diagnostic performance of a non-invasive breath test for colorectal cancer: COBRA1 study, Gastroenterology, Vol: 163, Pages: 1447-1449.e8, ISSN: 0016-5085
, 2022, InSiGHT 2022 Abstract Publishing and Best Abstract Awards, FAMILIAL CANCER, Vol: 21, Pages: 557-636, ISSN: 1389-9600
Moller P, Seppala T, Dowty JG, et al., 2022, Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium, Hereditary Cancer in Clinical Practice, Vol: 20, Pages: 1-11, ISSN: 1731-2302
ObjectiveTo compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants.MethodsCRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands.ResultsIn the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups.ConclusionsProspectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.
Daca-Alvarez M, Marti M, Spinelli A, et al., 2022, Familial component of early-onset colorectal cancer: opportunity for prevention, BRITISH JOURNAL OF SURGERY, Vol: 109, Pages: 1319-1325, ISSN: 0007-1323
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Monahan KJ, Davies MM, Abulafi M, et al., 2022, Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG), Gut, Vol: 71, Pages: 1939-1962, ISSN: 0017-5749
Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.
Edwards P, Monahan KJ, 2022, Diagnosis and management of Lynch syndrome, Frontline Gastroenterology, Vol: 13, Pages: e80-e87, ISSN: 2041-4137
Lynch syndrome (LS) is a dominantly inherited cancer susceptibility syndrome defined by presence of pathogenic variants in DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or in deletions of the EPCAM gene. Although LS is present in about 1 in 400 people in the UK, it estimated that only 5% of people with this condition are aware of the diagnosis. Therefore, testing for LS in all new diagnoses of colorectal or endometrial cancers is now recommended in the UK, and gastroenterologists can offer ‘mainstreamed’ genetic testing for LS to patients with cancer. Because LS results in a high lifetime risk of colorectal, endometrial, gastric, ovarian, hepatobiliary, brain and other cancers, the lifelong care of affected individuals and their families requires a coordinated multidisciplinary approach. Interventions such as high-quality 2-yearly colonoscopy, prophylactic gynaecological surgery, and aspirin are proven to prevent and facilitate early diagnosis and prevention of cancers in this population, and improve patient outcomes. Recently, an appreciation of the mechanism of carcinogenesis in LS-associated cancers has contributed to the development of novel therapeutic and diagnostic approaches, with a gene-specific approach to disease management, with potential cancer-preventing vaccines in development. An adaptive approach to surgical or oncological management of LS-related cancers may be considered, including an important role for novel checkpoint inhibitor immunotherapy in locally advanced or metastatic disease. Therefore, a personalised approach to lifelong gene-specific management for people with LS provides many opportunities for cancer prevention and treatment which we outline in this review.
Ahmad A, Moorghen M, Wilson A, et al., 2022, LEARNING CURVE FOR OPTICAL DIAGNOSIS OF SMALL POLYPS AT SCREENING COLONOSCOPY (DISCARD3), Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A106-A106, ISSN: 0017-5749
Lincoln AG, Benton SC, Sasieni P, et al., 2022, Risk-stratified FIT for urgent colonoscopy in Lynch syndrome: A clinical service throughout the COVID-19 pandemic., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Ahmad A, Moorghen M, Wilson A, et al., 2022, OPTICAL DIAGNOSIS OF POLYPS < 10MM AND IMPACT ON SURVEILLANCE INTERVAL (DISCARD3), Publisher: BMJ PUBLISHING GROUP, Pages: A30-A30, ISSN: 0017-5749
Morley O, Mavrou A, Pawa N, et al., 2022, POST-COLORECTAL CANCER RESECTION COLONOSCOPY: FACTORS ASSOCIATED WITH COMPLIANCE, Publisher: BMJ PUBLISHING GROUP, Pages: A152-A153, ISSN: 0017-5749
Lincoln AG, Benton SC, Sasieni P, et al., 2022, Risk-stratified FIT for urgent colonoscopy in Lynch syndrome: A clinical service throughout the COVID-19 pandemic., Publisher: American Society of Clinical Oncology (ASCO), Pages: 10606-10606, ISSN: 0732-183X
<jats:p> 10606 </jats:p><jats:p> Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. Herein, we report results from a national emergency clinical service implemented during the COVID-19 pandemic which used FIT to prioritize colonoscopy in LS patients while endoscopy services were limited. Methods: Regional genetic and endoscopy services across England were invited to participate. Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 March 2021. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub’s Research Laboratory in Surrey. The Hub sent patients a FIT kit (OC-Sensor™ (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Lab reports with feecal haemoglobin (f-Hb) results were returned electronically for clinical action. LS patients were risk-stratified for colonoscopy based upon the following f-Hb thresholds: (1) f-Hb ≥10µg of Haemoglobin (Hb)/g (µg/g) faeces: triaged for colonoscopy via an urgent two-week wait (2WW) pathway, (2) f-Hb ≤10µg/g: schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits. Results: Fifteen centers across England participated in the clinical service from 9<jats:sup>th</jats:sup> June 2020 to 31<jats:sup>st</jats:sup> March 2021. An uptake rate of 64% was observed from this cohort (375/588 invites), though 21 cases were removed from analysis due to repeat FITs, insufficient sample, missing clinical data, or FIT completed after colonoscopy. Of the re
Perea J, Corchete LA, Monahan KJ, et al., 2022, EARLY-ONSET COLORECTAL CANCER: GEOGRAPHICAL DISPARITIES ACCORDING TO PHENOTYPE, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S269-S269, ISSN: 0016-5085
Perea J, Corchete LA, Monahan KJ, et al., 2022, 1144: EARLY-ONSET COLORECTAL CANCER: GEOGRAPHICAL DISPARITIES ACCORDING TO PHENOTYPE, Publisher: Elsevier BV, Pages: S-269, ISSN: 0016-5085
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