Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021.

BACKGROUND: Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. OBJECTIVE: We aimed to assess the global, regional and national burden of gastrointestinal cancers. DESIGNS: Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). RESULTS: In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. CONCLUSIONS: Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

Racial, Ethnic, and Geographic Disparities in Digestive Diseases Mortality in the United States, 2000-2019.

BACKGROUND AND AIMS: The global burden of digestive diseases mortality has been increasing over the last 3 decades. However, little is known about disparities in digestive diseases-specific mortality in the United States. This study aimed to examine racial, ethnic, and state- and county-level disparities in digestive diseases mortality rate in the United States between 2000 and 2019. METHODS: We used the Institute of Health Metrics and Evaluation Global Health Data Exchange to gather digestive diseases age-standardized mortality rates for 5 racial and ethnic groups (White, Black, Latino, American Indian/Alaska Native [AI/AN], and Asian/Pacific Islander [API]) by sex, state, and county between 2000 and 2019. We used joinpoint regression analysis to evaluate the overall temporal trends by demography. RESULTS: The overall cause-specific mortality rate decreased from 36.0 to 34.5 deaths per 100,000 population across all groups (2000-2019). In 2019, AI/AN individuals had the highest mortality rate (86.2), followed by White (35.5), Latino and Black (both at 33.6), and API (15.6) individuals. Significant increases occurred across some of the racial and ethnic groups, with an increased average annual percentage change for 2000-2019 among AI/AN (0.87%; 95% confidence interval, 0.77%-0.97%) and White individuals (0.12%; 95% confidence interval, 0.02%-0.22%) particularly among females, while Latino, Black, and API individuals showed reduced average annual percentage change for 2000-2019. AI/AN constitutes the main race affected in the top 10 counties. Substantial state-level variation emerged, with the highest mortality rates in 2019 seen in West Virginia. CONCLUSIONS: Despite an overall decrease in digestive diseases mortality, significant disparities persist across racial and ethnic groups. AI/AN and White individuals experienced increased mortality rates, particularly among females. Targeted interventions and further research are needed to address these disparities and improve digestive health equity.

Temporal Trends in Body Composition and Metabolic Markers Prior to Diagnosis of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Changes in body composition and metabolic factors may serve as biomarkers for the early detection of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to capture the longitudinal changes in body composition and metabolic factors before diagnosis of PDAC. METHODS: We performed a retrospective cohort study in which all patients (≥18 years) diagnosed with PDAC from 2002 to 2021 were identified. We collected all abdominal computed tomography scans and 10 different blood-based biomarkers up to 36 months before diagnosis. We applied a fully automated abdominal segmentation algorithm previously developed by our group for 3-dimensional quantification of body composition on computed tomography scans. Longitudinal trends of body composition and blood-based biomarkers before PDAC diagnosis were estimated using linear mixed models, compared across different time windows, and visualized using spline regression. RESULTS: We included 1690 patients in body composition analysis, of whom 516 (30.5%) had ≥2 prediagnostic computed tomography scans. For analysis of longitudinal trends of blood-based biomarkers, 3332 individuals were included. As an early manifestation of PDAC, we observed a significant decrease in visceral and subcutaneous adipose tissue (ß = -1.94 [95% confidence interval (CI), -2.39 to -1.48] and ß = -2.59 [95% CI, -3.17 to -2.02]) in area (cm2)/height (m2) per 6 months closer to diagnosis, accompanied by a decrease in serum lipids (eg, low-density lipoprotein [ß = -2.83; 95% CI, -3.31 to -2.34], total cholesterol [ß = -2.69; 95% CI, -3.18 to -2.20], and triglycerides [ß = -1.86; 95% CI, -2.61 to -1.11]), and an increase in blood glucose levels. Loss of muscle tissue and bone volume was predominantly observed in the last 6 months before diagnosis. CONCLUSIONS: This study identified significant alterations in a variety of soft tissue and metabolic markers that occur in the development of PDAC. Early recognition of these metabolic changes may provide an opportunity for early detection.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis.

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

Can optical evaluation distinguish between t1a and t1b esophageal adenocarcinoma: an international expert inter-observer agreement study.

INTRODUCTION: While piecemeal endoscopic mucosal resection (EMR) for T1a oesophageal adenocarcinoma is acceptable, enbloc-R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We sought to ascertain whether expert Barrett's endoscopists were able to make this distinction based on optical evaluation. METHODS: Sixty sets of endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a and T1b disease (n=20 for each) were compiled from consecutive patients at a single institution. Each set contained four images, and were standardized to include an overview, a close-up in high-definition white light, a near-focus magnification image, and a narrow-band image. Experts were invited to predict histology for each set. RESULTS: 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for >20 years, with a median annual case volume for Barrett's EMR of 50 (IQR 18-75), and Barrett's ESD of 25 (IQR 10-45). Oesophageal adenocarcinoma (T1a/b) could be distinguished from HGD, with a pooled sensitivity of 89.1% (95% CI:84.7-93.4. When predicting T-stage for T1b adenocarcinoma cases, pooled sensitivity was 43.8% (95% CI:29.9-57.7). Fleiss' kappa was 0.421 (95% CI:0.399-0.442, P<0.001), indicating fair-to-moderate agreement. CONCLUSIONS: Expert Barrett's endoscopists can reliably differentiate T1a/T1b oesophageal adenocarcinoma from HGD. Although there is fair-to-moderate agreement for T-staging, T1b disease cannot be reliably distinguished from T1a disease. This may have implications on clinical decision making and selection of endoscopic treatment methods.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global Burden of Disease Study 2019.

BACKGROUND AND AIM: In recent years, there has been a growing incidence of gastrointestinal cancer in young individuals. Despite its significant morbidity and mortality, research on upper gastrointestinal (UGI) cancer in young populations has been relatively limited. Therefore, studies on the epidemiological changes of this cancer are needed. METHODS: Using data from the Global Burden of Disease Study 2019, we examined the incidence, death, and disability-adjusted life years (DALYs) from UGI cancers in the young, namely, early-onset esophageal cancer (EOEC) and early-onset gastric cancer (EOGC). These results were stratified by sex, geographical region, country, and sociodemographic index. RESULTS: There was a total of 185 140 cases, 120 289 deaths, and 5.70 million DALYs attributable to early-onset UGI cancers globally. From 2010 to 2019, the global incidence, death, and DALYs rates of early-onset UGI cancers decreased. In contrast, the incidence rates increased in both EOEC (+1.15%) and EOGC (+0.21%) in the Eastern Mediterranean region. CONCLUSIONS: Over the past decade, the burden of UGI cancer in the young has decreased. However, it has increased in the Eastern Mediterranean region. Further research to elucidate the attributable risk factors in this population is warranted.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia.

BACKGROUND & AIMS: Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS: Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS: A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS: AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS: gov, Number: NCT03954548.

Neoplasia Diagnosis After Multi-target Stool DNA Is Enhanced Among Lowest Baseline Detectors.

BACKGROUND AND AIMS: Variation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics. METHODS: We retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams. RESULTS: During the study period (2014-17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28-39%) and serrated lesion detection rate was 13% (8-15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36-56%) and serrated lesion diagnosis increased to 31% (17-42%) (both p < 0.0001). Median withdrawal time increased from 10 (7-13) to 12 (10-17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092). CONCLUSIONS: Knowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy. Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.

Artificial intelligence and colonoscopy experience: lessons from two randomised trials.

BACKGROUND AND AIMS: Artificial intelligence has been shown to increase adenoma detection rate (ADR) as the main surrogate outcome parameter of colonoscopy quality. To which extent this effect may be related to physician experience is not known. We performed a randomised trial with colonoscopists in their qualification period (AID-2) and compared these data with a previously published randomised trial in expert endoscopists (AID-1). METHODS: In this prospective, randomised controlled non-inferiority trial (AID-2), 10 non-expert endoscopists (<2000 colonoscopies) performed screening/surveillance/diagnostic colonoscopies in consecutive 40-80 year-old subjects using high-definition colonoscopy with or without a real-time deep-learning computer-aided detection (CADe) (GI Genius, Medtronic). The primary outcome was ADR in both groups with histology of resected lesions as reference. In a post-hoc analysis, data from this randomised controlled trial (RCT) were compared with data from the previous AID-1 RCT involving six experienced endoscopists in an otherwise similar setting. RESULTS: In 660 patients (62.3±10 years; men/women: 330/330) with equal distribution of study parameters, overall ADR was higher in the CADe than in the control group (53.3% vs 44.5%; relative risk (RR): 1.22; 95% CI: 1.04 to 1.40; p<0.01 for non-inferiority and p=0.02 for superiority). Similar increases were seen in adenoma numbers per colonoscopy and in small and distal lesions. No differences were observed with regards to detection of non-neoplastic lesions. When pooling these data with those from the AID-1 study, use of CADe (RR 1.29; 95% CI: 1.16 to 1.42) and colonoscopy indication, but not the level of examiner experience (RR 1.02; 95% CI: 0.89 to 1.16) were associated with ADR differences in a multivariate analysis. CONCLUSIONS: In less experienced examiners, CADe assistance during colonoscopy increased ADR and a number of related polyp parameters as compared with the control group. Experience appears to play a minor role as determining factor for ADR. TRIAL REGISTRATION NUMBER: NCT:04260321.

Educational intervention to improve quality of care in Barrett's esophagus: the AQUIRE randomized controlled trial.

BACKGROUND AND AIMS: Despite quality measures in upper endoscopy (EGD) for Barrett's esophagus (BE), considerable variability remains in practice among gastroenterologists. This randomized controlled trial evaluated the role of structured intensive training on the quality of EGD in BE. METHODS: In this multicenter study, 8 sites (from the GI Quality Consortium) were cluster randomized (1:1) to receive AQUIRE (A Quality Improvement program in cancer care during Endoscopy) training (intervention) or continue local standard practices (control). The primary outcome was compliance with the Seattle biopsy protocol. Secondary outcomes were change in knowledge of BE detection and sampling assessed by questionnaire and dysplasia detection rate (DDR) before and after completion of the 6-month study period. RESULTS: The intervention sites (n = 4) had 31 gastroenterologists and the control sites (n = 4) had 34. There was a significant improvement in the compliance rates with the Seattle biopsy protocol from baseline to the end of the study in the intervention sites (64.8%-73.2%, P = .002) but not in the control sites (69.5%-69.4%, P = .953). The accurate response rate on the questionnaire at the intervention sites increased from 73% at baseline to 88% after AQUIRE training (difference, 14.8%; standard deviation, 18.7; P = .008). DDR did not change significantly from baseline to 6 months in either the control or intervention groups (P = .06). CONCLUSIONS: This study confirms the capacity of a structured educational intervention to improve utilization of a standard biopsy protocol and knowledge of standards of care in BE but without significant change in DDR.

Simple risk score to predict the likelihood of a positive EUS in idiopathic acute pancreatitis.

BACKGROUND AND AIMS: We sought to derive a risk score, DORM65, of known variables to predict the likelihood of a positive EUS in patients with idiopathic acute pancreatitis (IAP). METHODS: A retrospective cohort study of 180 patients with IAP was performed across 3 tertiary care centers between January 2018 and December 2021. Multivariate logistic regression modeling was performed to predict a positive EUS. Accuracy of the models was assessed by the area under the receiver-operating characteristic curve (AUROCC). RESULTS: The diagnostic yield of EUS was 58.9% (95% confidence interval [CI], 51.7-66.1). The DORM65 scores of 5 predictors present before EUS with the best discrimination were a delayed EUS (defined as ≥82 days from the last episode of AP), obesity, not having had a repeated transabdominal US, male sex, and age ≥65 years at the time of EUS. For those at the lowest risk score group, the positive EUS rate was 13.0% compared with 100% in those at the highest risk group (relative risk, 7.67; P < .001). A score of 3 or more had a positive predictive value of 86.0% with a sensitivity of 34.9% and specificity of 91.9%. The model had a high predictive accuracy (AUROCC, .774; 95% CI, .707-.841). Adding 3 additional predictors (no cholecystectomy, no MRCP, and a single episode of AP) did not increase the accuracy significantly (AUROCC, .805; 95% CI, .742-.867). CONCLUSIONS: DORM65 is easily calculated and accurately predicts a positive EUS in patients with IAP. Further validation is needed.

Artificial intelligence for the assessment of bowel preparation.

BACKGROUND AND AIMS: A reliable assessment of bowel preparation is important to ensure high-quality colonoscopy. Current bowel preparation scoring systems are limited by interobserver variability. This study aimed to demonstrate objective assessment of bowel preparation adequacy using an artificial intelligence (AI)/convolutional neural network (CNN) algorithm developed from colonoscopy videos. METHODS: Two CNNs were developed using a training set of 73,304 images from 200 colonoscopies. First, a binary CNN was developed and trained to distinguish video frames that were appropriate versus inappropriate for scoring with the Boston Bowel Preparation Scale (BBPS). A second multiclass CNN was developed and trained on 26,950 appropriate frames that were expertly annotated with BBPS segment scores (0-3). We validated the algorithm using 252 10-second video clips that were assigned BBPS segment scores by 2 experts. The algorithm provided mean BBPS scores based on the algorithm (AI-BBPS) by calculating mean BBPS based on each frame's scoring. We maximized the algorithm's performance by choosing a dichotomized AI-BBPS score that closely matched dichotomized BBPS scores (ie, adequate vs inadequate). We tested the mean BBPS score based on the algorithm AI-BBPS against human rating using 30 independent 10-second video clips (test set 1) and 10 full withdrawal colonoscopy videos (test set 2). RESULTS: In the validation set, the algorithm demonstrated an area under the curve of .918 and accuracy of 85.3% for detection of inadequate bowel cleanliness. In test set 1, sensitivity for inadequate bowel preparation was 100% and agreement between raters and AI was 76.7% to 83.3%. In test set 2, sensitivity for inadequate bowel preparation for each segment was 100% and agreement between raters and AI was 68.9% to 89.7%. Agreement between raters alone versus raters and AI were similar (κ = .694 and .649, respectively). CONCLUSIONS: The algorithm assessment of bowel cleanliness as measured with the BBPS showed good performance and agreement with experts including full withdrawal colonoscopies.

Comparing the number and relevance of false activations between 2 artificial intelligence computer-aided detection systems: the NOISE study.

BACKGROUND AND AIMS: Artificial intelligence has been shown to be effective in polyp detection, and multiple computer-aided detection (CADe) systems have been developed. False-positive (FP) activation emerged as a possible way to benchmark CADe performance in clinical practice. The aim of this study was to validate a previously developed classification of FPs comparing the performances of different brands of approved CADe systems. METHODS: We compared 2 different consecutive video libraries (40 video per arm) collected at Humanitas Research Hospital with 2 different CADe system brands (CADe A and CADe B). For each video, the number of CADe false activations, cause, and time spent by the endoscopist to examine the area erroneously highlighted were reported. The FP activations were classified according to the previously developed classification of FPs (the NOISE classification) according to their cause and relevance. RESULTS: In CADe A 1021 FP activations were registered across the 40 videos (25.5 ± 12.2 FPs per colonoscopy), whereas in CADe B 1028 were identified (25.7 ± 13.2 FPs per colonoscopy; P = .53). Among them, 22.9 ± 9.9 (89.8% in CADe A) and 22.1 ± 10.0 (86.0% in CADe B) were because of artifacts from the bowel wall. Conversely, 2.6 ± 1.9 (10.2% in CADe A) and 3.5 ± 2.1 (14% in CADe B) were caused by bowel content (P = .45). Within CADe A each false activation required .2 ± .9 seconds, with 1.6 ± 1.0 FPs (6.3%) requiring additional time for endoscopic assessment. Comparable results were reported within CADe B with .2 ± .8 seconds spent per false activation and 1.8 ± 1.2 FPs per colonoscopy requiring additional inspection. CONCLUSIONS: The use of a standardized nomenclature provided comparable results with either of the 2 recently approved CADe systems. (Clinical trial registration number: NCT04399590.).

Barrett's Epithelial Thickness, Assessed by Volumetric Laser Endomicroscopy, Is Associated With Response to Radiofrequency Ablation.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is the most common treatment for flat Barrett's esophagus (BE), but reasons for varying outcomes are poorly understood. A recently developed contrast-enhancement algorithm allows reliable measurement of Barrett's epithelial thickness (BET) from volumetric laser endomicroscopy (VLE) images and correlation with response to RFA. Using this algorithm, we investigated whether patients with thicker Barrett's mucosa are less likely to respond to RFA. In the future, this algorithm may guide choice of RFA dosing or endoscopic resection. METHODS: We performed a retrospective analysis on all patients with BE who received a baseline VLE scan between May 2015 and October 2016, followed by RFA and 1 follow-up exam, from 14 institutions participating in the United States VLE registry. We measured BET on equidistant locations by estimating the distance between the esophageal surface and the superficial edge of the deepest lamina propria. The primary outcome variable was the percentage reduction in Prague length; secondary outcome variables were complete remission of intestinal metaplasia (CRIM) and presence of strictures after 12 months. RESULTS: Images from 61 patients were included in our final analysis. Mean BET per patient ranged from 224 µm to 705 µm. A 100 µm thicker mean BET per patient resulted in a 12% lower response to treatment, measured by a reduction of Prague length (P = .03), after adjustment for confounders. We found an association between mean BET and CRIM, but not with stricture formation. CONCLUSIONS: Based on measurements on contrast-enhanced VLE images, we found that BET correlates with response to RFA. For clinical implementation, larger studies with a standardized follow-up and development of computer-aided image analysis systems are needed.

Systemic anticoagulation is associated with decreased mortality and morbidity in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is a procoagulant state, and markers of coagulopathy are associated with AP severity. We aimed to explore the association of systemic anticoagulation therapy before AP onset with the inpatient outcomes of patients with acute pancreatitis. METHODS: This case-control, retrospective study used data from the Nationwide Inpatient Sample (Jan 2014-Dec 2016). We used medical coding data to identify patients with a principal diagnosis of AP who were receiving systemic anticoagulation therapy. Patients with anticoagulation were matched to those without it on the propensity for having anticoagulation. The propensity for having anticoagulation was estimated using a logistic regression model, matching for age, gender, race, median household income for patients' zip code, Charlson comorbidity score, region of hospital, location of hospital (urban/rural), teaching status of hospital, if admission day was on a weekend, pancreatic cancer class, obesity, tobacco usage. Secondary outcomes were inpatient outcomes and hospital expenditures. RESULTS: A total of 190,474 patients admitted for acute pancreatitis were identified, out of which 7827 patients were on anticoagulation. After propensity matching, 5776 matched pairs were successfully identified. Patients with AP on anticoagulation tended to have lower risk for ICU admission, acute kidney injury, organ failure or inpatient mortality. However, the group with anticoagulation had longer hospital length of stay and higher hospital costs. CONCLUSIONS: Anticoagulation therapy may have a pivotal role in the pathogenesis and progression of AP. These data suggest a potential therapeutic role for anticoagulants in AP. Further studies are needed to better understand these observations.

Pancreatic steatosis on computed tomography is an early imaging feature of pre-diagnostic pancreatic cancer: A preliminary study in overweight patients.

BACKGROUND: The prevalence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, driven by factors such as aging and an increasing prevalence of obesity and diabetes mellitus. To improve the poor survival rate of PDAC, early detection is vital. Recently, pancreatic steatosis has gained novel interest as a risk factor for PDAC. This study aimed to investigate if pancreatic steatosis on computed tomography (CT) is an early imaging feature in patients with pre-diagnostic PDAC. METHODS: A retrospective case-control study was performed. Patients diagnosed with PDAC (2010-2016) were reviewed for abdominal non-contrast CT-imaging 1 month-3 years prior to their diagnosis. Cases were matched 1:4 with controls based on age, gender and imaging date. Unenhanced CT-images were evaluated for pancreatic steatosis (pancreas-to-spleen ratio in Hounsfield Units <0.70) by a blinded radiologist and results were compared between cases and controls. RESULTS: In total, 32 cases and 117 controls were included in the study with a comparable BMI (29.6 and 29.2 respectively, p = 0.723). Pancreatic steatosis was present in 71.9% of cases compared to 45.3% of controls (Odds ratio (OR) 3.09(1.32-7.24), p = 0.009). Adjusted for BMI and diabetes mellitus, pancreatic steatosis on CT remained a significant independent risk factor for PDAC (Adjusted OR 2.70(1.14-6.58), p = 0.037). CONCLUSION: Pancreatic steatosis measured on CT is independently associated with PDAC up to three years before the clinical diagnosis in overweight patients. If these data are confirmed, this novel imaging feature may be used to identify high-risk individuals and to stratify the risk of PDAC in individuals that already undergo PDAC screening.

Impact of topical budesonide on prevention of esophageal stricture after mucosal resection.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are treatment modalities for Barrett's esophagus involving high-grade dysplasia or early cancer. Injectional corticosteroid therapy decreases the risk of procedure-related esophageal stricture (ES) formation. Our aim was to assess the efficacy of topical budesonide on the rate of ES formation after EMR or ESD. METHODS: Patients included prospectively from 3 tertiary endoscopy centers received 3 mg budesonide orally twice a day for 8 weeks after esophageal EMR or ESD of 50% or more of the esophageal circumference between January 1, 2014 and June 30, 2018. These patients were matched (1:3 ratio) retrospectively with a consecutive patient cohort who underwent EMR or ESD of 50% or more of the esophageal circumference without concomitant corticosteroid therapy. The primary endpoint was the presence of ES at the 12-week follow-up. RESULTS: Twenty-five patients (budesonide) were matched with 75 patients (no budesonide). Most underwent EMR for Barrett's esophagus with biopsy-proven high-grade dysplasia or suspected T1a cancer. Although most baseline characteristics did not differ significantly, patients in the budesonide cohort tended to have a higher proportion of circumferential EMR. The proportion of patients with ES was not significantly lower in the budesonide cohort (16% vs 28%). On logistic regression analysis, budesonide remained associated with a lower incidence of ES (P = .023); however, when controlling for baseline characteristics with a propensity score weighted logistic regression model, there was no significant effect on ES formation (P = .176). CONCLUSIONS: Topical budesonide might be associated with a reduction of ES after EMR or ESD; however, further studies are needed to verify our results.