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.

Efficacy and safety of long-term indwelling plastic stents after resolution of pancreatic fluid collections with endoscopic transmural drainage: a systematic review and meta-analysis.

BACKGROUND: Pancreatic fluid collections (PFCs) may recur after resolution with endoscopic transmural drainage (ETD) and standard stent removal (SSR). Herein, we compared the efficacy and safety of leaving long-term indwelling plastic stents (LTIS) vs. standard stent removal after PFC resolution with ETD. METHODS: We performed a systematic review of MEDLINE, EMBASE, CINAHL, Scopus, and Cochrane databases from inception to September 2022. Full-text articles comparing long-term (> 6 months) outcomes of LTIS and SSR were eligible, as well as single-arm studies with ≥ 10 patients with LTIS. Two independent reviewers selected studies, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale. Measured outcomes included the following: (A) PFC recurrence; (B) interventions for PFC recurrence; (C) technical success; and (D) adverse events (AEs). Meta-analysis was carried out using random-effects models. RESULTS: We included 16 studies, encompassing 1285 patients. Compared to SSR after PFC resolution with ETD, LTIS was associated with significantly lower risk of PFC recurrence (3% vs. 23%; OR 0.22 [95%CI 0.09-0.52]; I2 = 45%) and need for interventions (2% vs. 14%; OR 0.35 [95%CI 0.16-0.78]; I2 = 0%). The superiority of LTIS on reducing PFC recurrence was found with walled-off necrosis, with or without disconnected pancreatic duct, and with placement of ≥ 2 LTIS. When using LTIS, the pooled proportion of AEs was 8% (95%CI 4-11%) and technical success was 93% (95%CI 86-99%). CONCLUSIONS: Our results show that LTIS after PFC resolution with ETD is feasible, safe, and superior to SSR in reducing the risk of PFC recurrence and need for interventions.

Comparison of lumen apposing metal stents versus endoscopic balloon dilation for the management of benign colorectal anastomotic strictures.

BACKGROUND AND AIMS: Limited data exist evaluating lumen apposing metal stents (LAMS) with endoscopic balloon dilation (EBD) for the treatment of benign colorectal anastomotic strictures (BCAS). This study compares outcomes of both interventions. METHODS: Patients with left-sided BCAS treated with LAMS vs. EBD were identified retrospectively. The primary outcome was a composite of crossover to another intervention to achieve clinical success or recurrence requiring reintervention. RESULTS: Twenty-nine patients (11 LAMS; 18 EBD) were identified, with longer follow-up in the EBD group (734 vs. 142 days, p=0.003). No significant differences were found in the composite outcome, technical success, clinical success, or components of composite outcome. With LAMS, there was a nonsignificant trend toward fewer procedures (2.4 vs. 3.3, p=0.06) and adverse events (0 vs. 16.7%, p=0.26). CONCLUSIONS: LAMS appears to be as effective as EBD for the treatment of BCAS but may require fewer procedures and may be safer than EBD.

Accessibility to ERCP-performing hospitals among patients with pancreatic cancer living in SEER regions.

BACKGROUND AND AIMS: The two most common interventions used to treat painless jaundice from pancreatic cancer are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD). Our study aimed to characterize the geographic distribution of ERCP-performing hospitals among patients with pancreatic cancer in the United States and the association between geographic accessibility to ERCP-performing hospitals and biliary interventions patients receive. METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database for pancreatic cancer from 2005 to 2013. Multilevel models were used to examine the association between accessibility to ERCP hospitals within a 30- and 45-min drive from the patient's residential ZIP Code and the receipt of ERCP treatment. A two-step floating catchment area model was used to calculate the measure of accessibility based on the distribution across SEER regions. RESULTS: 7464 and 782 patients underwent ERCP and PTBD, respectively, over the study period. There were 808 hospitals in which 8246 patients diagnosed with pancreatic cancer in SEER regions from 2005 to 2013 received a procedure. Patients with high accessibility within both 30- and 45-min drive to an ERCP-performing hospital were more likely to receive an ERCP (30-min adjusted odds ratio [aOR]: 1.53, 95% confidence interval [CI]: 1.17-2.01; 45-min aOR: 1.31, 95% CI: 1.01-1.70). Furthermore, in the adjusted model, Black patients (vs. White) and patients with stage IV disease were less likely to receive ERCP than PTBD. CONCLUSIONS: Patients with pancreatic cancer and high accessibility to an ERCP-performing hospital were more likely to receive ERCP. Disparities in the receipt of ERCP persisted for Black patients regardless of their access to ERCP-performing hospitals.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

KRT17High/CXCL8+ tumor cells display both classical and basal features and regulate myeloid infiltration in the pancreatic cancer microenvironment.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single cell RNA sequencing has uncovered the co-existence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. EXPERIMENTAL DESIGN: We performed subtyping on a single cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy. RESULTS: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17High/CXCL8+ cells in patient tumors correlated with intra-tumoral myeloid abundance, and, interestingly, high pro-tumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17High/CXCL8+cells and induced myeloid cell migration in an CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis. CONCLUSIONS: Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence.

This document from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used in the review of the evidence used to inform the final guidance outlined in the accompanying Summary and Recommendations document regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. This guideline used the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, the ASGE suggests surgical evaluation over endosic approaches.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based summary and recommendations regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. It is accompanied by the document subtitled "Methodology and Review of Evidence," which provides a detailed account of the methodology used for the evidence review. This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well- or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, we suggest surgical evaluation over endoscopic approaches.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the role of fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic workup of these patients, we suggest the use of fluoroscopic-guided biopsy sampling in addition to brush cytology over brush cytology alone, especially for hilar strictures. We suggest the use of cholangioscopic and EUS-guided biopsy sampling especially for patients who undergo nondiagnostic sampling, cholangioscopic biopsy sampling for nondistal strictures and EUS-guided biopsy sampling distal strictures or those with suspected spread to surrounding lymph nodes and other structures.

American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: methodology and review of evidence.

Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.

American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: methodology and review of evidence

Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.

American Society for Gastrointestinal Endoscopy guideline on the role of ergonomics for prevention of endoscopy-related injury: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach to strategies to prevent endoscopy-related injury (ERI) in GI endoscopists. It is accompanied by the article subtitled "Methodology and Review of Evidence," which provides a detailed account of the methodology used for the evidence review. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline estimates the rates, sites, and predictors of ERI. Additionally, it addresses the role of ergonomics training, microbreaks and macrobreaks, monitor and table positions, antifatigue mats, and use of ancillary devices in decreasing the risk of ERI. We recommend formal ergonomics education and neutral posture during the performance of endoscopy, achieved through adjustable monitor and optimal procedure table position, to reduce the risk of ERI. We suggest taking microbreaks and scheduled macrobreaks and using antifatigue mats during procedures to prevent ERI. We suggest the use of ancillary devices in those with risk factors predisposing them to ERI.

Flexible fiber cholangioscope for detection of near-infrared fluorescence.

Video 1Flexible fiber cholangioscope for detection of near-infrared fluorescence.

American Society for Gastrointestinal Endoscopy guideline on management of post-liver transplant biliary strictures: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for strategies to manage biliary strictures in liver transplant recipients. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses the role of ERCP versus percutaneous transhepatic biliary drainage and covered self-expandable metal stents (cSEMSs) versus multiple plastic stents for therapy of post-transplant strictures, use of MRCP for diagnosing post-transplant biliary strictures, and administration of antibiotics versus no antibiotics during ERCP. In patients with post-transplant biliary strictures, we suggest ERCP as the initial intervention and cSEMSs as the preferred stent for extrahepatic strictures. In patients with unclear diagnoses or intermediate probability of a stricture, we suggest MRCP as the diagnostic modality. We suggest that antibiotics should be administered during ERCP when biliary drainage cannot be ensured.

American Society for Gastrointestinal Endoscopy guideline on management of post-liver transplant biliary strictures: methodology and review of evidence.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for strategies to manage biliary strictures in liver transplant recipients. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses the role of ERCP versus percutaneous transhepatic biliary drainage and covered self-expandable metal stents (cSEMSs) versus multiple plastic stents for therapy of strictures, use of MRCP for diagnosing post-transplant biliary strictures, and administration of antibiotics versus no antibiotics during ERCP. In patients with post-transplant biliary strictures, we suggest ERCP as the initial intervention and cSEMSs as the preferred stent. In patients with unclear diagnosis or intermediate probability of a stricture, we suggest MRCP as the diagnostic modality. We suggest that antibiotics should be administered during ERCP when biliary drainage cannot be assured.

Pronounced squamous cell contamination in biliary tract cytology: A diagnostic pitfall.

Squamous cells are rarely found in biliary tract cytology specimens, and when present are typically scant in quantity. Over an 8-year time period, two cases at our institution reporting abundant squamous cells were identified. Both patients underwent endoscopic retrograde cholangiopancreatography with bile duct brushings and removal of a migrated biliary stent. The migrated stents were retrieved using rat toothed forceps and required removal of the endoscope through the esophagus with the stent exposed to esophageal and oral mucosa outside of the endoscope. Cytologic examination of the accompanying biliary stent material accordingly revealed abundant benign squamous cells. However, bile duct brushings showed benign ductal epithelial cells without squamous cells. Prior and subsequent cytology and bile duct surgical pathology specimens did not show squamous metaplasia. Migrated biliary stents that require endoscopic withdrawal increase the risk of contaminating samples with squamous cells. Recognition of this unique scenario is important, as the differential diagnosis includes squamous metaplasia and squamous neoplasia.