Citations

Abstract 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.

SummaryIntroductionPost‐colonoscopy colorectal cancers (PCCRCs) have been proposed as a performance metric for colonoscopy quality assurance programs. Previously, there was no standardised terminology or reporting methods. In 2018, the World Endoscopy Organization (WEO) advised standardised definitions and prevalence calculation methodology.AimsTo assess PCCRC burden using WEO standardised methods, to explore causes of heterogeneity, and to review changes in prevalence over timeMethodsWe updated a prior systematic review by searching Ovid MEDLINE and EMBASE databases from 1 January 2013 to 31 January 2021 to identify population‐based studies (or multicentre studies representative of the local population) reporting PCCRC prevalence (PROSPERO [CRD42020183796]). Two authors independently determined study eligibility, assessed quality, and extracted data. We estimated the PCCRC 3‐year prevalence using WEO‐recommended methodologies and investigated between‐study sources of heterogeneity. We examined changes in prevalence over time.ResultsFifteen studies reporting on 25 872 PCCRC cases met eligibility criteria. Pooled PCCRC 3 year prevalence was 8.2% (95% CI = 6.9%‐9.4%, I2 = 98.2%) across four European studies using WEO precise methodology. Proximal PCCRC prevalence was greater than distal (9.7% [95% CI = 7.0%‐12.4%] vs 5.4% [95% CI = 2.9%‐7.8%], I2 = 99.2%). Seven studies reporting PCCRC rates over time showed no consistent trend: four showed a decrease, one an increase and two were unchanged. Between‐study heterogeneity was high.ConclusionsPooled 3‐year PCCRC prevalence was 8.2% (95% CI = 6.9%‐9.4%). Despite WEO standardised methodology to define and calculate PCCRC rates, there was significant heterogeneity among studies. Comparing rates between populations remains challenging and additional studies are needed to better understand the global PCCRC burden to inform quality assurance programs.

Abstract 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.

AbstractThe liver is unique in its remarkable regenerative capacity, which enables the use of liver resection as a treatment for specific liver diseases, including removal of neoplastic liver disease. After resection, the remaining liver tissue (i.e, liver remnant) regenerates to maintain normal hepatic function. In experimental settings as well as patients, removal of up to two-thirds of the liver mass stimulates a rapid and highly coordinated process resulting in the regeneration of the remaining liver. Mechanisms controlling the initiation and termination of regeneration continue to be discovered, and many of the fundamental signaling pathways controlling the proliferation of liver parenchymal cells (i.e., hepatocytes) have been uncovered. Interestingly, while hemostatic complications (i.e., bleeding and thrombosis) are primarily thought of as a complication of surgery itself, strong evidence suggests that components of the hemostatic system are, in fact, powerful drivers of liver regeneration. This review focuses on the clinical and translational evidence supporting a link between the hemostatic system and liver regeneration, and the mechanisms whereby the hemostatic system directs liver regeneration discovered using experimental settings.

Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involvement of gene modifiers that regulate disease progression. As individuals exhibiting mutations in mitochondrial DNA (mtDNA) present cardiac phenotypes, the mitochondrial genome is a promising candidate to harbor gene modifiers of HCM. Herein, we sequenced the mtDNA of isogenic pluripotent stem cell-cardiomyocyte models of HCM focusing on two sarcomeric mutations. This approach was extended to unrelated patient families totaling 52 cell lines. By correlating cellular and clinical phenotypes with mtDNA sequencing, potentially HCM-protective or -aggravator mtDNA variants were identified. These novel mutations were mostly located in the non-coding control region of the mtDNA and did not overlap with those of other mitochondrial diseases. Analysis of unrelated patients highlighted family-specific mtDNA variants, while others were common in particular population haplogroups. Further validation of mtDNA variants as gene modifiers is warranted but limited by the technically challenging methods of editing the mitochondrial genome. Future molecular characterization of these mtDNA variants in the context of HCM may identify novel treatments and facilitate genetic screening in cardiomyopathy patients towards more efficient treatment options.

AbstractLutetium-177-dotatate (177Lu-dotatate), a form of peptide receptor radionuclide therapy, was approved by the U.S. Food and Drug Administration for the treatment of advanced somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (NETs) in 2018 based on the promising results of the NETTER-1 trial for grade 1–2 midgut NETs. Here, we present a patient with a grade 3 pancreatic neuroendocrine tumor and BRCA1 germline mutation who had a significant response to 177Lu-dotatate.

Abstract Background Metformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones. We evaluated the effect of metformin on sex hormones in MA.32, a phase III trial of nondiabetic BC subjects who were randomly assigned to metformin or placebo. Methods We studied the subgroup of postmenopausal hormone receptor-negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after being randomly assigned. Sex hormone-binding globulin, bioavailable testosterone, and estradiol levels were assayed using electrochemiluminescence immunoassay. Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models. Results 312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2-negative BC and had received (neo)adjuvant chemotherapy. Mean age was 58.1 (SD=6.9) vs 57.5 (SD=7.9) years, mean body mass index (BMI) was 27.3 (SD=5.5) vs 28.9 (SD=6.4) kg/m2 for metformin vs placebo, respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (−5.7 vs 0 pmol/L; P < .001) in univariable analysis and after controlling for baseline BMI and BMI change (P < .001). There was no change in sex hormone-binding globulin or bioavailable testosterone. Conclusion Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.