Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Standardizing Scoring Conventions for Crohn's Disease Endoscopy: An International RAND/UCLA Appropriateness Study.

BACKGROUND AND AIMS: Endoscopic assessment of disease activity is integral for evaluating treatment response in patients with Crohn's disease (CD). We aimed to define appropriate items for evaluating endoscopic activity and conventions for consistent endoscopic scoring rules in CD. METHODS: A 2-round modified RAND/University of California at Los Angeles Appropriateness Method study was conducted. A panel of 15 gastroenterologists used a 9-point Likert scale to rate the appropriateness of statements pertaining to the Simple Endoscopic Score for CD, Crohn's Disease Endoscopic Index of Severity, and additional items relevant to endoscopy scoring in CD. Each statement was voted as appropriate, uncertain, or inappropriate based on the median panel rating and presence of disagreement. RESULTS: Panelists voted that it is appropriate for all ulcers to contribute to endoscopic scoring in CD, including aphthous ulcers, ulcerations at a surgical anastomosis, and anal canal ulcers (scored in the rectum). Endoscopic healing should reflect an absence of ulcers. Narrowing should be defined as a clear decrease in luminal diameter; stenosis should be defined by an impassable narrowing, and if occurring at the junction of 2 segments, scored in the distal segment. Scarring and inflammatory polyps were considered inappropriate for including in the affected area score. The optimal method for defining ulcer depth remains uncertain. CONCLUSIONS: We outlined scoring conventions for the Simple Endoscopic Score for CD and Crohn's Disease Endoscopic Index of Severity, noting that both scores have limitations. Therefore, we identified priorities for future research and steps for developing and validating a more representative endoscopic index in CD.

Endoscopic management of patients with high-risk colorectal colitis-associated neoplasia: a Delphi study.

BACKGROUND AND AIMS: Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis-associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions. METHODS: A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. RESULTS: Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (< 20 mm, >20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN. CONCLUSIONS: This is the first step in developing international consensus-based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies.

Interobserver agreement of the modified Paris classification and histology prediction of colorectal lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: SCENIC (International Consensus Statement on Surveillance and Management of Dysplasia in IBD) guidelines recommend that visible dysplasia in patients with longstanding inflammatory bowel disease (IBD) should be endoscopically characterized using a modified Paris classification. This study aimed to determine the interobserver agreement (IOA) of the modified Paris classification and endoscopists' accuracy for pathology prediction of IBD visible lesions. METHODS: One hundred deidentified endoscopic still images and 30 videos of IBD visible colorectal lesions were graded by 10 senior and 4 trainee endoscopists from 5 tertiary care centers. Endoscopists were asked to assign 4 classifications for each image: the standard Paris classification, modified Paris classification, pathology prediction, and lesion border. Agreement was measured using Light's kappa coefficient. Consensus of ratings was assessed according to strict majority. RESULTS: The overall Light's kappa for all study endpoints was between .32 and .49. In a subgroup analysis between junior and senior endoscopists, Light's kappa continued to be less than .6 with a slightly higher agreement among juniors. Lesions with the lowest agreement and no consensus were mostly classified as Is, IIa, and mixed Paris classification and sessile and superficial elevated for modified Paris classification. Endoscopist accuracy for prediction of dysplastic, nondysplastic, and serrated pathology was 77%, 56%, and 30%, respectively. There was a strong association (P < .001) between the given morphology classification and the predicted pathology with Ip lesions carrying a much lower expectation of dysplasia than Is/IIc/III and mixed lesions. The agreement for border prediction was .5 for junior and .3 for senior endoscopists. CONCLUSIONS: This study demonstrates very low IOA for Paris and modified Paris classifications and low accuracy and IOA for lesion histopathology prediction. Revisions of these classifications are required to create a clinically useful risk stratification tool and enable eventual application of augmented intelligence tools.

Existing Bowel Preparation Quality Scales Are Reliable in the Setting of Centralized Endoscopy Reading.

BACKGROUND: Development of bowel preparation products has been based upon colon cleansing rating by a local endoscopist. It is unclear how bowel preparation scales perform when centrally evaluated. AIMS: To evaluate the reliability of bowel preparation quality scales when assessed by central readers. METHODS: Four central readers evaluated 52 videos in triplicate, 2 weeks apart, during the entire endoscopic procedure (insertion/withdrawal of the colonoscope) and exclusively on colonoscope withdrawal using the Boston Bowel Preparation Scale (BBPS), Chicago Bowel Preparation scale, Harefield Cleansing Scale, Ottawa Bowel Preparation Quality Scale (OBPQS), Aronchick score, a visual analogue scale, and additional items proposed in a modified Research and Development/University of California Los Angeles appropriateness process. Reliability was assessed with intraclass correlation coefficients. RESULTS: Intraclass correlation coefficients (95% confidence interval) for inter-rater reliability of the quality scales ranged from 0.51 to 0.65 (consistent with moderate to substantial inter-rater reliability) during the entire procedure. Corresponding intraclass correlation coefficients for intra-rater reliability ranged from 0.69 to 0.77 (consistent with substantial intra-rater reliability). Reliability was highest in the right colon and lowest in the left colon. No differences were observed in reliability when assessed for the procedure overall (insertion/withdrawal) relative to assessment on withdrawal alone. CONCLUSION: All five bowel preparation quality scales had moderate to substantial inter-rater reliability. Panelists considered the Aronchick score too simplistic for clinical trials and recognized that assessment of residual fluid in the Ottawa Bowel Preparation Quality Scale was not amenable to central assessment.

An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

BACKGROUND: Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures. AIMS: To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process. METHODS: Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale. RESULTS: Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed. CONCLUSIONS: We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

Benefits and challenges in implementation of artificial intelligence in colonoscopy: World Endoscopy Organization position statement.

The number of artificial intelligence (AI) tools for colonoscopy on the market is increasing with supporting clinical evidence. Nevertheless, their implementation is not going smoothly for a variety of reasons, including lack of data on clinical benefits and cost-effectiveness, lack of trustworthy guidelines, uncertain indications, and cost for implementation. To address this issue and better guide practitioners, the World Endoscopy Organization (WEO) has provided its perspective about the status of AI in colonoscopy as the position statement. WEO Position Statement: Statement 1.1: Computer-aided detection (CADe) for colorectal polyps is likely to improve colonoscopy effectiveness by reducing adenoma miss rates and thus increase adenoma detection; Statement 1.2: In the short term, use of CADe is likely to increase health-care costs by detecting more adenomas; Statement 1.3: In the long term, the increased cost by CADe could be balanced by savings in costs related to cancer treatment (surgery, chemotherapy, palliative care) due to CADe-related cancer prevention; Statement 1.4: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADe to support its use in clinical practice; Statement 2.1: Computer-aided diagnosis (CADx) for diminutive polyps (≤5 mm), when it has sufficient accuracy, is expected to reduce health-care costs by reducing polypectomies, pathological examinations, or both; Statement 2.2: Health-care delivery systems and authorities should evaluate the cost-effectiveness of CADx to support its use in clinical practice; Statement 3: We recommend that a broad range of high-quality cost-effectiveness research should be undertaken to understand whether AI implementation benefits populations and societies in different health-care systems.

Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.

OBJECTIVE: Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk. DESIGN: In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk. RESULTS: Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up. CONCLUSION: Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.

A Pilot Study on Automatic Three-Dimensional Quantification of Barrett's Esophagus for Risk Stratification and Therapy Monitoring.

BACKGROUND & AIMS: Barrett's epithelium measurement using widely accepted Prague C&M classification is highly operator dependent. We propose a novel methodology for measuring this risk score automatically. The method also enables quantification of the area of Barrett's epithelium (BEA) and islands, which was not possible before. Furthermore, it allows 3-dimensional (3D) reconstruction of the esophageal surface, enabling interactive 3D visualization. We aimed to assess the accuracy of the proposed artificial intelligence system on both phantom and endoscopic patient data. METHODS: Using advanced deep learning, a depth estimator network is used to predict endoscope camera distance from the gastric folds. By segmenting BEA and gastroesophageal junction and projecting them to the estimated mm distances, we measure C&M scores including the BEA. The derived endoscopy artificial intelligence system was tested on a purpose-built 3D printed esophagus phantom with varying BEAs and on 194 high-definition videos from 131 patients with C&M values scored by expert endoscopists. RESULTS: Endoscopic phantom video data demonstrated a 97.2% accuracy with a marginal ± 0.9 mm average deviation for C&M and island measurements, while for BEA we achieved 98.4% accuracy with only ±0.4 cm2 average deviation compared with ground-truth. On patient data, the C&M measurements provided by our system concurred with expert scores with marginal overall relative error (mean difference) of 8% (3.6 mm) and 7% (2.8 mm) for C and M scores, respectively. CONCLUSIONS: The proposed methodology automatically extracts Prague C&M scores with high accuracy. Quantification and 3D reconstruction of the entire Barrett's area provides new opportunities for risk stratification and assessment of therapy response.

Bone Morphogenetic Protein Pathway Antagonism by Grem1 Regulates Epithelial Cell Fate in Intestinal Regeneration.

BACKGROUND & AIMS: In homeostasis, intestinal cell fate is controlled by balanced gradients of morphogen signaling. The bone morphogenetic protein (BMP) pathway has a physiological, prodifferentiation role, predominantly inferred through previous experimental pathway inactivation. Intestinal regeneration is underpinned by dedifferentiation and cell plasticity, but the signaling pathways that regulate this adaptive reprogramming are not well understood. We assessed the BMP signaling landscape and investigated the impact and therapeutic potential of pathway manipulation in homeostasis and regeneration. METHODS: A novel mouse model was generated to assess the effect of the autocrine Bmp4 ligand on individual secretory cell fate. We spatiotemporally mapped BMP signaling in mouse and human regenerating intestine. Transgenic models were used to explore the functional impact of pathway manipulation on stem cell fate and intestinal regeneration. RESULTS: In homeostasis, ligand exposure reduced proliferation, expedited terminal differentiation, abrogated secretory cell survival, and prevented dedifferentiation. After ulceration, physiological attenuation of BMP signaling arose through upregulation of the secreted antagonist Grem1 from topographically distinct populations of fibroblasts. Concomitant expression supported functional compensation after Grem1 deletion from tissue-resident cells. BMP pathway manipulation showed that antagonist-mediated BMP attenuation was obligatory but functionally submaximal, because regeneration was impaired or enhanced by epithelial overexpression of Bmp4 or Grem1, respectively. Mechanistically, Bmp4 abrogated regenerative stem cell reprogramming despite a convergent impact of YAP/TAZ on cell fate in remodeled wounds. CONCLUSIONS: BMP signaling prevents epithelial dedifferentiation, and pathway attenuation through stromal Grem1 upregulation was required for adaptive reprogramming in intestinal regeneration. This intercompartmental antagonism was functionally submaximal, raising the possibility of therapeutic pathway manipulation in inflammatory bowel disease.

Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care.

BACKGROUND: Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. METHODS: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. RESULTS: One hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 µg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. CONCLUSIONS: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

Dye-based chromoendoscopy for the detection of colorectal neoplasia: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Dye-based chromoendoscopy (DBC) could be effective in increasing the adenoma detection rate (ADR) in patients undergoing colonoscopy, but the technique is time-consuming and its uptake is limited. We aimed to assess the effect of DBC on ADR based on available randomized controlled trials (RCTs). METHODS: Four databases were searched up to April 2022 for RCTs comparing DBC with conventional colonoscopy (CC) in terms of ADR, advanced ADR, and sessile serrated adenoma detection rate as well as the mean adenomas per patient and non-neoplastic lesions. Relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes were calculated using random-effect models. The I2 test was used for quantifying heterogeneity. Risk of bias was evaluated with the Cochrane tool. RESULTS: Overall, 10 RCTs (5334 patients) were included. Indication for colonoscopy was screening or surveillance (3 studies) and mixed (7 studies). Pooled ADR was higher in the DBC group versus the CC group (95% CI, 48.1% [41.4%-54.8%] vs 39.3% [33.5%-46.4%]; RR, 1.20 [1.11-1.29]), with low heterogeneity (I2 = 29%). This effect was consistent for advanced ADR (RR, 1.21 [1.03-1.42]; I2 = .0%), sessile serrated adenomas (6.1% vs 3.5%; RR, 1.68 [1.15-2.47]; I2 = 9.8%), and mean adenomas per patient (MD, .24 [.17-.31]) overall and in the right-sided colon (MD, .28 [.14-.43]). A subgroup analysis considering only trials using high-definition white-light endoscopy reduced the heterogeneity while still showing a significant increase in adenoma detection with DBC: 51.6% (95% confidence interval [CI], 47.1%-56.1%) and 59.1% (95% CI, 54.7-63.3%), RR = 1.14 (95% CI, 1.06-1.23), P = .0004, I2 = .0%, P = .50. CONCLUSIONS: Meta-analysis of RCTs showed that DBC increases key quality parameters in colonoscopy, supporting its use in everyday clinical practice.

Performance measures for colonoscopy in inflammatory bowel disease patients: European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.

The European Society of Gastrointestinal Endoscopy (ESGE) presents a short list of performance measures for colonoscopy in inflammatory bowel disease (IBD) patients. Current performance measures for colonoscopy mainly focus on detecting (pre)malignant lesions. However, these performance measures are not relevant for all colonoscopy indications in IBD patients. Therefore, our aim was to provide endoscopy services across Europe and other interested countries with a tool for quality monitoring and improvement in IBD colonoscopy. Eight key performance measures and one minor performance measure were recommended for measurement and evaluation in daily endoscopy practice.

Definition of competence standards for optical diagnosis of diminutive colorectal polyps: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

BACKGROUND : The European Society of Gastrointestinal Endoscopy (ESGE) has developed a core curriculum for high quality optical diagnosis training for practice across Europe. The development of easy-to-measure competence standards for optical diagnosis can optimize clinical decision-making in endoscopy. This manuscript represents an official Position Statement of the ESGE aiming to define simple, safe, and easy-to-measure competence standards for endoscopists and artificial intelligence systems performing optical diagnosis of diminutive colorectal polyps (1 - 5 mm). METHODS : A panel of European experts in optical diagnosis participated in a modified Delphi process to reach consensus on Simple Optical Diagnosis Accuracy (SODA) competence standards for implementation of the optical diagnosis strategy for diminutive colorectal polyps. In order to assess the clinical benefits and harms of implementing optical diagnosis with different competence standards, a systematic literature search was performed. This was complemented with the results from a recently performed simulation study that provides guidance for setting alternative competence standards for optical diagnosis. Proposed competence standards were based on literature search and simulation study results. Competence standards were accepted if at least 80 % agreement was reached after a maximum of three voting rounds. RECOMMENDATION 1: In order to implement the leave-in-situ strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 90 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm in the rectosigmoid. Histopathology is used as the gold standard.Level of agreement 95 %. RECOMMENDATION 2: In order to implement the resect-and-discard strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 80 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm. Histopathology is used as the gold standard.Level of agreement 100 %. CONCLUSION : The developed SODA competence standards define diagnostic performance thresholds in relation to clinical consequences, for training and for use when auditing the optical diagnosis of diminutive colorectal polyps.

Germline variant testing in serrated polyposis syndrome.

BACKGROUND AND AIM: Serrated polyposis syndrome (SPS) is now known to be the commonest polyposis syndrome. Previous analyses for germline variants have shown no consistent positive findings. To exclude other polyposis syndromes, 2019 British Society of Gastroenterology (BSG) guidelines advise gene panel testing if the patient is under 50 years, there are multiple affected individuals within a family, or there is dysplasia within any of the polyps. METHODS: A database of SPS patients was established at the Oxford University Hospitals NHS Foundation Trust. Patients were referred for genetic assessment based on personal and family history and patient preference. The majority were tested for a hereditary colorectal cancer panel including MUTYH, APC, PTEN, SMAD4, BMPR1A, STK11, NTLH1, POLD1, POLE, GREM1 (40-kb duplication), PMS2, and Lynch syndrome mismatch repair genes. RESULTS: One hundred and seventy-three patients were diagnosed with SPS based on World Health Organization 2019 criteria between February 2010 and December 2020. The mean age of diagnosis was 54.2 ± 16.8 years. Seventy-three patients underwent genetic testing and 15/73 (20.5%) were found to have germline variants, of which 7/73 (9.6%) had a pathogenic variant (MUTYH n = 2, SMAD4 n = 1, CHEK2 n = 2, POLD1 n = 1, and RNF43 n = 1). Only 60% (9/15) of these patients would have been recommended for gene panel testing according to current BSG guidelines. CONCLUSIONS: A total of 20.5% of SPS patients tested were affected by heterozygous germline variants, including previously unreported associations with CHEK2 and POLD1. This led to a change in management in seven patients (9.6%). Current recommendations may miss SPS associated with germline variants, which is more common than previously anticipated.

Oncological outcome after local treatment for early stage rectal cancer.

BACKGROUND: Treatment of early rectal cancer is evolving towards organ-preserving therapy which includes endoscopic resection and transanal approaches. We aimed to explore the role of local treatments such as endoscopic polypectomy (Endoscopic Mucosal Resection (EMR) or Endoscopic submucosal dissection (ESD)) and transanal endoscopic microsurgery/ transanal minimal invasive surgery (TEM/TAMIS) in patients who had early rectal cancer. We considered these outcomes alongside conventional major surgery using total mesorectal excision (TME) for early stage disease. METHODS: All patients identified at MDT with early stage rectal cancer at our institution between 2010 and 2019 were included. Long-term outcomes in terms of local recurrence, survival and procedure-specific morbidity were analysed. RESULTS: In total, 536 patients with rectal cancer were identified, of which 112 were included based on their pre-operative identification at the MDT on the basis that they had node-negative early rectal cancer. Among these, 30 patients (27%) had the lesion excised by flexible endoscopic polypectomy techniques (EMR/ESD), 67 (60%) underwent TEM/TAMIS and 15 (13%) had major surgery. There were no differences in patient demographics between the three groups except for TEM/TAMIS patients being more likely to be referred from another hospital (p < 0.001) and they were less active (WHO performance status p = 0.04). There were no significant differences in overall survival rates and cancer-specific survival between the three treatment groups. The 5-year overall survival rate for endoscopic polypectomy, TEM/TAMIS or major resection was 96% versus 90% and 88%, respectively (p = 0.89). The 5- year cancer-specific survival rate was 96%, versus 96% and 100%, respectively (p = 0.74). CONCLUSION: Endoscopic polypectomy by EMR/ESD is an appropriate local treatment for early stage rectal cancer in selected patients. It is possible to achieve good oncological outcomes with a polypectomy similar to TEM/TAMIS and major surgery; however, a multidisciplinary approach is necessary enabling close surveillance and the use of adjuvant radiotherapy.

Establishing key research questions for the implementation of artificial intelligence in colonoscopy: a modified Delphi method.

BACKGROUND : Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. METHODS : An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers, from nine countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. RESULTS : The top 10 ranked questions were categorized into five themes. Theme 1: clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterization, determining the optimal end points for evaluation of AI, and demonstrating impact on interval cancer rates. Theme 2: technological developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false-positive rates, and minimizing latency. Theme 3: clinical adoption/integration (1 question), concerning the effective combination of detection and characterization into one workflow. Theme 4: data access/annotation (1 question), concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: regulatory approval (1 question), related to making regulatory approval processes more efficient. CONCLUSIONS : This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy.

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist.

BACKGROUND: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. SUMMARY: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.

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).

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.

Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification.

OBJECTIVE: Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (Adenomatous polyposis coli, ß-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (RNF43, RSPO-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. DESIGN: We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups. RESULTS: Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of RSPO may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (AXIN2, NKD1) occurring even in CIMP-negative LD cancers. AXIN2 mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93). CONCLUSIONS: Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential AXIN2 expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.