Utilization and Outcomes of Multigene Panel Testing in Patients With Pancreatic Ductal Adenocarcinoma.

PURPOSE: Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in patients with PDAC. METHODS: This retrospective, multisite study included patients with PDAC diagnosed between May 2018 and August 2020 at Mayo Clinic Arizona, Florida, and Minnesota. Discussion, uptake, and outcomes of GT were compared before (May 1, 2018-May 1, 2019) and after (August 1, 2019-August 1, 2020) the guideline update, accounting for a transition period. RESULTS: The study identified 533 patients with PDAC, with 321 (60.2%) preguideline and 212 (39.8%) postguideline. Patient characteristics did not differ between the preguideline and postguideline periods. GT was discussed in 34.3% (110 of 321) of preguideline and 39.6% (84 of 212) of postguideline patients (odds ratio [OR], 1.26 [95% CI, 0.88 to 1.80]) and subsequently performed in 80.9% (89 of 110) of preguideline and 75.0% (63 of 84) of postguideline patients (OR, 1.10 [95% CI, 0.75 to 1.61]). Of 152 tested patients, 26 (17.1%) had a pathogenic variant (PV), of whom 17 (11.2%; 17 of 152) were PDAC-associated. Over the entire study period, GT was more likely in younger patients (65 v 70 years; P < .001), those seen by a medical oncologist (82.9% v 69.0%; P < .001), and those surviving more than 12 months from diagnosis (70.4% v 43.4%; P < .001). Demographics and personal/family cancer history were comparable between patients with and without a PDAC PV. CONCLUSION: GT remains underutilized despite National Comprehensive Cancer Network guideline recommendations. Given the poor prognosis of PDAC and potential implications of GT, efforts to increase utilization are needed to provide surveillance and support to both patients with PDAC and at-risk family members.

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.

The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors: A Perspective From Global Burden of Disease Study 2019.

OBJECTIVES: Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking. MATERIALS AND METHODS: Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period. RESULTS: In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC -0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%). CONCLUSIONS: The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.

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.

The association between menopausal hormone therapy and gastroesophageal reflux disease: a systematic review and meta-analysis.

IMPORTANCE AND OBJECTIVE: Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women. EVIDENCE REVIEW: We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI. FINDINGS: The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity. CONCLUSIONS AND RELEVANCE: There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications.

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.

Identification of individuals at high-risk for pancreatic cancer using a digital patient-input tool combining family cancer history screening and new-onset diabetes.

Capturing family history might be a valuable tool for identification of individuals at increased risk of pancreatic cancer, which would allow enrollment into pancreatic surveillance programs. In addition, weight loss and concurrent new-onset diabetes may be utilized as an early marker for pancreatic cancer. This study evaluates the yield of combining family history and the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model to identify individuals who could benefit from pancreatic surveillance. A novel questionnaire and digital input tool was created that combined questions on family cancer history and criteria of the ENDPAC model. Individuals meeting ENDPAC criteria were enrolled directly in the high-risk pancreatic clinic. Individuals who met the criteria for a significant family history of cancer were offered referral to a genetic counselor. The questionnaire was completed by 453 patients. Of those, 25.8% (117/453) had significant familial risk factors. Eighteen individuals (15.4%) completed genetic testing previously, of whom five had a pathogenic variant. Thirty-four (29.9%) out of 117 individuals with a strong family history - flagged by the questionnaire - underwent genetic testing. Four (11.8%) of these patients harbored a pathogenic variant. Additionally, through cascade family testing, two siblings were found to carry pathogenic variants. Four (0.9%) of the 453 patients matched ENDPAC criteria. Two were diagnosed with pancreatic cancer and the others were enrolled in the surveillance program. In conclusion, identification of high-risk individuals for pancreatic cancer can be achieved by combining family history screening and the ENDPAC model to facilitate referral to genetic counseling and high-risk clinics.

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.

Post-EMR for colorectal polyps, thermal ablation of defects reduces adenoma recurrence: A meta-analysis.

Background and study aims Adenoma recurrence is one of the key limitations of endoscopic mucosal resection (EMR), which occurs in 15 % to 30 % of cases during first surveillance colonoscopy. The main hypothesis behind adenoma recurrence is leftover micro-adenomas at the margins of post-EMR defects. In this systematic review and meta-analysis, we evaluated the efficacy of snare tip soft coagulation (STSC) at the margins of mucosal defects to reduce adenoma recurrence and bleeding complications. Methods Electronic databases such as PubMed and the Cochrane library were used for systematic literature search. Studies with polyps only resected by piecemeal EMR and active treatment: with STSC, comparator: non-STSC were included. A random effects model was used to calculate the summary of risk ratio and 95 % confidence intervals. The main outcome of the study was to compare the effect of STSC versus non-STSC with respect to adenoma recurrence at first surveillance colonoscopy after thermal ablation of post-EMR defects. Results Five studies were included in the systematic review and meta-analysis. The total number patients who completed first surveillance colonoscopy (SC1) in the STSC group was 534 and in the non-STSC group was 514. The pooled adenoma recurrence rate was 6 % (37 of 534 cases) in the STSC arm and 22 % (115 of 514 cases) in the non-STSC arm, (odds ratio [OR] 0.26, 95 % confidence interval [CI], 0.16-0.41, P  = 0.001). The pooled delayed post-EMR bleeding rate 19 % (67 of 343) in the STSC arm and 22 % (78 of 341) in the non-STSC arm (OR 0.82, 95 %CI, 0.57-1.18). Conclusions Thermal ablation of post-EMR defects significantly reduces adenoma recurrence at first surveillance colonoscopy.

Prevalence, features, and explanations of missed and misinterpreted pancreatic cancer on imaging: a matched case-control study.

PURPOSE: To characterize the prevalence of missed pancreatic masses and pancreatic ductal adenocarcinoma (PDAC)-related findings on CT and MRI between pre-diagnostic patients and healthy individuals. MATERIALS AND METHODS: Patients diagnosed with PDAC (2010-2016) were retrospectively reviewed for abdominal CT- or MRI-examinations 1 month-3 years prior to their diagnosis, and subsequently matched to controls in a 1:4 ratio. Two blinded radiologists scored each imaging exam on the presence of a pancreatic mass and secondary features of PDAC. Additionally, original radiology reports were graded based on the revised RADPEER criteria. RESULTS: The cohort of 595 PDAC patients contained 60 patients with a pre-diagnostic CT and 27 with an MRI. A pancreatic mass was suspected in hindsight on CT in 51.7% and 50% of cases and in 1.3% and 0.9% of controls by reviewer 1 (p < .001) and reviewer 2 (p < .001), respectively. On MRI, a mass was suspected in 70.4% and 55.6% of cases and 2.9% and 0% of the controls by reviewer 1 (p < .001) and reviewer 2 (p < .001), respectively. Pancreatic duct dilation, duct interruption, focal atrophy, and features of acute pancreatitis is strongly associated with PDAC (p < .001). In cases, a RADPEER-score of 2 or 3 was assigned to 56.3% of the CT-reports and 71.4% of MRI-reports. CONCLUSION: Radiological features as pancreatic duct dilation and interruption, and focal atrophy are common first signs of PDAC and are often missed or unrecognized. Further investigation with dedicated pancreas imaging is warranted in patients with PDAC-related radiological findings.

Hereditary pancreatic cancer.

Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.

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.

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.

Pooled diagnostic parameters of artificial intelligence in EUS image analysis of the pancreas: A descriptive quantitative review.

EUS is an important diagnostic tool in pancreatic lesions. Performance of single-center and/or single study artificial intelligence (AI) in the analysis of EUS-images of pancreatic lesions has been reported. The aim of this study was to quantitatively study the pooled rates of diagnostic performance of AI in EUS image analysis of pancreas using rigorous systematic review and meta-analysis methodology. Multiple databases were searched (from inception to December 2020) and studies that reported on the performance of AI in EUS analysis of pancreatic adenocarcinoma were selected. The random-effects model was used to calculate the pooled rates. In cases where multiple 2 × 2 contingency tables were provided for different thresholds, we assumed the data tables as independent from each other. Heterogeneity was assessed by I2% and 95% prediction intervals. Eleven studies were analyzed. The pooled overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 86% (95% confidence interval [82.8-88.6]), 90.4% (88.1-92.3), 84% (79.3-87.8), 90.2% (87.4-92.3) and 89.8% (86-92.7), respectively. On subgroup analysis, the corresponding pooled parameters in studies that used neural networks were 85.5% (80-89.8), 91.8% (87.8-94.6), 84.6% (73-91.7), 87.4% (82-91.3), and 91.4% (83.7-95.6)], respectively. Based on our meta-analysis, AI seems to perform well in the EUS-image analysis of pancreatic lesions.

Diagnostic performance of volumetric laser endomicroscopy for Barrett's esophagus dysplasia amongst gastroenterology trainees.

BACKGROUND: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett's esophagus (BE) surveillance. VLE image interpretation is challenged by subtle grayscale image variation across a large amount of data. Training in VLE interpretation is not standardized. This study aims to determine if VLE training can be incorporated into a gastroenterology (GI) fellowship curriculum with the use of a self-directed module. METHODS: A standardized, self-directed training module (30 min) was created explaining the background and established VLE criteria for the diagnosis of BE dysplasia. A VLE image dataset was generated from a multicenter VLE database of targeted biopsies. GI trainees were asked to grade each image for the presence or absence of the following criteria (I) increased surface optical frequency domain imaging (OFDI) signal intensity and (II) atypical glands and provide a final diagnosis (dysplastic vs. non-dysplastic). Diagnostic performance was calculated and results compared to VLE expert interpretation using histology as the gold-standard. RESULTS: The dataset included 50 VLE images (10 high-grade dysplasia, 40 non-dysplastic BE). VLE images were reviewed in a randomized and blinded fashion by 5 GI trainees with no prior VLE experience and 5 experienced VLE users. Sensitivity, specificity and accuracy of GI trainees was 83.3% (95% CI: 71.5-91.7%), 59.0% (95% CI: 51.6-66.0%), and 64.8% (95% CI: 58.5-70.7%) compared to 80.0% (95% CI: 67.7-89.2%), 79.5% (95% CI: 73.0-85.0%), and 79.6% (95% CI: 74.1-84.4%) for VLE experts respectively. The difference in specificity and accuracy between the two groups were statistically significant with P<0.001. CONCLUSIONS: A brief training session on VLE is inadequate to reach competency in interpretation of VLE by GI trainees. Additional experience is required to accurately interpret VLE images.

International external validation of a stratification tool to identify branch-duct intraductal papillary mucinous neoplasms at lowest risk of progression.

BACKGROUND: Identifying branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) at lowest risk of progression may allow for a reduced intensity of surveillance. OBJECTIVE: We aimed to externally validate the previously developed Dutch-American Risk stratification Tool (DART-1; https://rtools.mayo.edu/DART/), which identifies cysts at low risk of developing worrisome features (WFs) or high-risk stigmata (HRS). METHODS: Three prospective cohorts of individuals under surveillance for BD-IPMNs were combined, independent from the original development cohort. We assessed the performance (discrimination and calibration) of DART-1, a multivariable Cox-proportional logistic regression model with five predictors for the development of WFs or HRS. RESULTS: Of 832 individuals (mean age 77 years, SD 11.5) under surveillance for a median of 40 months (IQR 44), 163 (20%) developed WFs or HRS. DART-1's discriminative ability (C-statistic 0.68) was similar to that in the development cohort (0.64-0.72) and showed moderate calibration. DART-1 adequately estimated the risk for patients in the middle risk quintile, and slightly underestimated it in the lowest quintiles. Their range of predicted versus observed 3-year risk was 0%-0% versus 0%-3.7% for Q1; 0.3%-0.4% versus 3%-11% for Q2; and 2.6%-3% versus 2.4%-9.8% for Q3. The development of WFs or HRS was associated with pancreatic cancer (p < 0.001). Vice versa, in absence of WFs or HRS, the risk of malignancy was low (0.3%). CONCLUSIONS: The performance of DART-1 to predict the development of WFs or HRS in BD-IPMN was validated in an external international cohort, with a discriminative ability equal as in the development cohort. Risk estimations were most accurate for patients with BD-IPMNs in the middle risk quintile and slightly underestimated in the lowest quintiles.