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More than 75% of cancer-related deaths occur from cancers for which we do not screen. New screening liquid biopsies may help fill these clinical gaps, although evidence of benefit still needs to be assessed. Which lessons can we learn from previous efforts to guide those of the future? Screening trials for ovarian, prostate, pancreatic, and esophageal cancers are revisited to assess the evidence, which has been limited by small effect sizes, short duration of early-stage disease relative to screening frequency, study design, and confounding factors. Randomized controlled trials (RCT) to show mortality reduction have required millions of screening-years, two-decade durations, and been susceptible to external confounding. Future RCTs with late-stage incidence as a surrogate endpoint could substantially reduce these challenges, and clinical studies demonstrating safety and effectiveness of screening in high-risk populations may enable extrapolation to broader average-risk populations. Multicancer early detection tests provide an opportunity to advance these practical study designs. Conditional approvals based on RCTs with surrogate endpoints, contingent upon real world evidence generation and continuation of trials to definitive endpoints, may lower practical barriers to innovation in cancer screening and enable greater progress. [ABSTRACT FROM AUTHOR]

Systems to address follow-up testing of clinically positive surveillance colonoscopy results are lacking. The impact of an ambulatory safety net (ASN) intervention on rates of colonoscopy completion was assessed. The ASN team identified patients using an electronic registry, conducted patient outreach, coordinated care, and tracked colonoscopy completion. In all, 701 patients were captured in the ASN program: 58.1% (407/701) had possible barriers to follow-up colonoscopy completion, with rates of 80.1% (236/294) if no barrier, and 40.9% (287/701) overall. Colonoscopy completion likelihood increased with prior polypectomy (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.3), and decreased with White race (OR, 0.5; 95% CI, 0.3-0.9), increased inpatient visits (OR, 0.6; 95% CI, 0.4-0.9), more outreach attempts (OR, 0.6; 95% CI, 0.5-0.7), and fair/poor/inadequate preparation (OR, 0.4; 95% CI, 0.2-0.7) in logistic regression models. An ASN model for quality improvement promotes colonoscopy completion rates and identifies patient barriers. [ABSTRACT FROM AUTHOR]

Objective: Determination of appropriate endoscopy sedation strategy is an important preprocedural consideration. To address manual workflow gaps that lead to sedation-type order errors at our institution, we designed and implemented a clinical decision support system (CDSS) to review orders for patients undergoing outpatient endoscopy.Materials and Methods: The CDSS was developed and implemented by an expert panel using an agile approach. The CDSS queried patient-specific historical endoscopy records and applied expert consensus-derived logic and natural language processing to identify possible sedation order errors for human review. A retrospective analysis was conducted to evaluate impact, comparing 4-month pre-pilot and 12-month pilot periods.Results: 22 755 endoscopy cases were included (pre-pilot 6434 cases, pilot 16 321 cases). The CDSS decreased the sedation-type order error rate on day of endoscopy (pre-pilot 0.39%, pilot 0.037%, Odds Ratio = 0.094, P-value < 1e-8). There was no difference in background prevalence of erroneous orders (pre-pilot 0.39%, pilot 0.34%, P = .54).Discussion: At our institution, low prevalence and high volume of cases prevented routine manual review to verify sedation order appropriateness. Using a cohort-enrichment strategy, a CDSS was able to reduce number of chart reviews needed per sedation-order error from 296.7 to 3.5, allowing for integration into the existing workflow to intercept rare but important ordering errors.Conclusion: A workflow-integrated CDSS with expert consensus-derived logic rules and natural language processing significantly reduced endoscopy sedation-type order errors on day of endoscopy at our institution. [ABSTRACT FROM AUTHOR]

Tissue metaplasia is uncommon in adults because established cis -element programs resist rewiring. In Barrett's esophagus, the distal esophageal mucosa acquires a predominantly intestinal character, with notable gastric features, and is predisposed to developing invasive cancers. We sought to understand the chromatin underpinnings of Barrett's metaplasia and why it commonly displays simultaneous gastric and intestinal properties. We profiled cis -regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing. Mutations in Barrett's esophagus were examined in relation to tissue-specific enhancer landscapes using a random forest machine-learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett's biopsy specimens using the assay for transposase-accessible chromatin. We used 1- and 2-color immunohistochemistry to examine protein expression of tissue-restricted genes. Barrett's esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis -elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett's metaplasia coexpress gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins; CLDN18; and a novel gastric marker, ANXA10, showed extensive tissue and subclonal heterogeneity of dual stomach-intestinal cell states. These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett's esophagus. Pervasive intragland variation argues against stem-cell governance of this phenotype. [Display omitted] [ABSTRACT FROM AUTHOR]

Submucosal elevation, the process of instilling material in the submucosal space for separation of the surface mucosa and deeper muscularis layer, is a significant aspect of the endoscopic mucosal resection of large lesions performed to facilitate lesion removal and maximize safety. Submucosal injection, when applied, has historically been performed with normal saline, though this is limited by its rapid dissipation; solutions ideally need to be easily injectable, biocompatible, and provide a long‐lasting submucosal cushion with a desirable height. Here, reported is a new set of materials, endoscopically injectable shear‐thinning hydrogels, meeting these requirements because of their biocompatible components and ability to form a solid hydrogel upon injection. These findings are supported by evaluation in a large animal model and ultimately demonstrate the potential of these shear‐thinning hydrogels to serve as efficient submucosal injection fluids for cushion development. Given these unique characteristics, their broad application in mucosal resection techniques is anticipated. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed., Design: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites., Results: Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92)., Conclusion: A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC., Competing Interests: Competing interests: ABu has received consulting fees from Exelixis and Geistlich Pharma. KM declares research funding from Celgene and Trovagene. AJA has consulted for Oncorus, Inc., Arrakis Therapeutics, and Merck & Co., Inc, and has research funding from Mirati Therapeutics, Syros, Deerfield, Inc., and Novo Ventures that is unrelated to this work. AM is listed as an inventor on a patent that has been licensed by Johns Hopkins University to Thrive Earlier Detection and serves as a consultant for Tezcat Biosciences. BG, RS and YD have filed patents on cfDNA analysis technology, and received research funding from GRAIL. BMW declares research funding from Celgene, Eli Lilly Novartis and Revolution Medicines, and consulting for Celgene, GRAIL, Ipsen and Mirati., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Imaging and endoscopy play several important roles in the diagnosis and management of pancreatic ductal adenocarcinoma (PDAC). Computed tomography (CT) and endoscopic ultrasound play complimentary roles in the initial diagnosis and pathologic confirmation of PDAC. Endoscopy can also be used to manage biliary obstruction and gastrointestinal complications. MRI and fluorodeoxyglucose-PET-CT are typically used as problem-solving tools for complex cases. Neoadjuvant chemotherapy and surgery are often selected based on imaging findings related to vascular involvement by tumors and invasion of adjacent structures. Posttreatment surveillance imaging is used to monitor for complications, local recurrence, and systemic metastasis., Competing Interests: Disclosure M. Rosenthal receives research funding from the National Institutes of Health (U01 CA320272, U10 CA180821, and U01 CA200468), Stand Up to Cancer, Lustgarten Foundation, and the Hale Family Center for Pancreatic Cancer at Dana-Farber Cancer Institute., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures: ALC is an employee of Medtronic. ALC is on the YouTube Health Advisory Board. Otherwise, the authors have no relevant potential conflicts of interest to disclose.

Background and study aims  While argon plasma coagulation (APC) is the first-line treatment for gastric antral vascular ectasia (GAVE), endoscopic band ligation (EBL) has shown promising results. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness of EBL for the treatment of GAVE. Methods  Individualized search strategies were developed in accordance with PRISMA and MOOSE guidelines through September 1, 2020. Measured outcomes included endoscopic success (defined as GAVE eradication/improvement), change in hemoglobin, transfusion dependency, number of treatment sessions, adverse events, rebleeding, and bleeding-associated mortality. Outcomes were compared among studies evaluating EBL versus APC. Results  Eleven studies (n = 393; 59.39 % female; mean age 58.65 ± 8.85 years) were included. Endoscopic success was achieved in 87.84 % [(95 % CI, 80.25 to 92.78); I 2  = 11.96 %] with a mean number of 2.50 ± 0.49 treatment sessions and average of 12.40 ± 3.82 bands applied. For 8 studies comparing EBL (n = 143) versus APC (n = 174), there was no difference in baseline patient characteristics. However, endoscopic success was significantly higher for EBL [OR 6.04 (95 % CI 1.97 to 18.56; P  = 0.002], requiring fewer treatment sessions (2.56 ± 0.81 versus 3.78 ± 1.17; P  < 0.001). EBL was also associated with a greater increase in post-procedure hemoglobin [mean difference 0.35 (95 % CI 0.07 to 0.62; P  = 0.0140], greater reduction in transfusions required [mean difference -1.46 (95 % CI -2.80 to -0.12; P  = 0.033], and fewer rebleeding events [OR 0.11 (95 % CI, 0.04 to 0.36); P  < 0.001]. There was no difference in adverse events or bleeding-associated mortality ( P  > 0.050). Conclusions  EBL appears to be safe and effective for treatment of GAVE, with improved outcomes when compared to APC., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC. Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096-111. ©2018 AACR. See related commentary by Collisson, p. 1062 This article is highlighted in the In This Issue feature, p. 1047 ., (©2018 American Association for Cancer Research.)

Background and Aim: To improve diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in solid pancreatic lesions, on-site cytology review has been recommended. Because this is not widely available throughout the world, the aim of this study was to compare the diagnostic yield of EUS-FNA performed with rapid on-site evaluation (ROSE) versus 7 FNA passes without ROSE in pancreatic masses., Methods: In this multicenter randomized noninferiority trial, patients were randomized to ROSE versus 7 passes into a solid pancreatic mass. On the basis of the absolute difference in diagnostic yield with 7 passes versus cytopathologist-guidance, the noninferiority margin for the difference in diagnostic yield was defined as -15%. Definite diagnosis was defined to include positive for malignancy, neoplastic cells present, and negative for malignancy., Results: A total of 142 patients were randomized with 73 in the cytopathologist arm and 69 in the 7 passes arm. Diagnostic yield for definite diagnosis was 78.3% with 7 passes and 78.1% with cytopathology guidance. With an absolute difference 0.2%, 95% CI -14.4 to 14.6, performing 7 passes was noninferior to cytopathologist-guided EUS-FNA. There was no significant difference in complications or time to perform FNA. A median of 5 passes were performed with ROSE. The median charge with onsite cytopathology was significantly greater than performing 7 passes [$1058 (958, 1445) versus $375 (275, 460), p<0.001]., Conclusions: The diagnostic yield for performing 7 passes during EUS-FNA into solid pancreatic masses is noninferior with lower charge compared to cytopathologist-guidance. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Imaging and endoscopy both play important and complementary roles in the initial diagnosis, staging, monitoring, and symptomatic management of pancreatic cancer. This article provides an overview of the uses of each of the diagnostic modalities, common imaging findings, alternative considerations, and areas of ongoing work in diagnostic imaging. This article also provides details of the uses of endoscopy for diagnosis, staging, and intervention throughout the course of a patient's care. These modalities each play important roles in the complex multidisciplinary care of patients with pancreatic cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: Mixed tumors of the pancreas are exceedingly rare., Case Report: We herein report on a 54-year-old female who presented with an enlarging cystic lesion in the head of the pancreas. Right upper quadrant ultrasound and multidetector-row CT scan showed a well-defined unilocular cystic tumor located in the head of the pancreas and surrounded, in part, by a hypervascular solid mass., Conclusion: Although mixed exocrine/endocrine pancreatic tumors have been described previously, to the best of our knowledge, this is the first case of a pancreatic mixed intraductal papillary mucinous neoplasm/endocrine tumor with illustration of its ultrasound and CT features. Moreover, the importance of preoperative analysis of imaging features in the assessment of pancreatic neoplasms is discussed.