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A Society of Environmental Toxicology and Chemistry (SETAC) Focused Topic Meeting (FTM) on the environmental management of per- and polyfluoroalkyl substances (PFAS) convened during August 2019 in Durham, North Carolina (USA). Experts from around the globe were brought together to critically evaluate new and emerging information on PFAS including chemistry, fate, transport, exposure, and toxicity. After plenary presentations, breakout groups were established and tasked to identify and adjudicate via panel discussions overarching conclusions and relevant data gaps. The present review is one in a series and summarizes outcomes of presentations and breakout discussions related to (1) primary sources and pathways in the environment, (2) sorption and transport in porous media, (3) precursor transformation, (4) practical approaches to the assessment of source zones, (5) standard and novel analytical methods with implications for environmental forensics and site management, and (6) classification and grouping from multiple perspectives. Outcomes illustrate that PFAS classification will continue to be a challenge, and additional pressing needs include increased availability of analytical standards and methods for assessment of PFAS and fate and transport, including precursor transformation. Although the state of the science is sufficient to support a degree of site-specific and flexible risk management, effective source prioritization tools, predictive fate and transport models, and improved and standardized analytical methods are needed to guide broader policies and best management practices. Environ Toxicol Chem 2021;40:3234-3260. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

BACKGROUND: COVID-19 pandemic-related disruptions to EUS-based pancreatic cancer surveillance in high-risk individuals remain uncertain. METHODS: Analysis of enrolled participants in the CAPS5 Study, a prospective multicenter study of pancreatic cancer surveillance in high-risk individuals. RESULTS: Amongst 693 enrolled high-risk individuals under active surveillance, 108 (16%) had an EUS scheduled during the COVID-19 pandemic-related shutdown (median length of 78 days) in the spring of 2020, with 97% of these procedures being canceled. Of these canceled surveillance EUSs, 83% were rescheduled in a median of 4.1 months, however 17% were not rescheduled after 6 months follow-up. Prior history of cancer was associated with increased likelihood of rescheduling. To date no pancreatic cancer has been diagnosed among those whose surveillance was delayed. CONCLUSIONS: COVID-19 delayed pancreatic cancer surveillance with no adverse outcomes in efficiently rescheduled individuals. However, 1 in 6 high-risk individuals had not rescheduled surveillance, indicating the need for vigilance to ensure timely surveillance rescheduling.

Objective While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. Methods An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool. Results The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. Conclusions The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.

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.

Background/aims Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is preferred for sampling of lymph nodes (LNs) adjacent to the gastrointestinal wall; however, fine-needle biopsy (FNB) may provide improved diagnostic outcomes. This study aimed to evaluate the comparative efficacy and safety of FNA versus FNB for LN sampling. Methods This was a multicenter retrospective study of prospectively collected data to evaluate outcomes of EUS-FNA and EUS-FNB for LN sampling. Characteristics analyzed included sensitivity, specificity, accuracy, the number of needle passes, diagnostic adequacy of rapid on-site evaluation (ROSE), cell-block analysis, and adverse events. Results A total of 209 patients underwent EUS-guided LN sampling. The mean lesion size was 16.22±8.03 mm, with similar sensitivity and accuracy between FNA and FNB ([67.21% vs. 75.00%, respectively, p=0.216] and [78.80% vs. 83.17%, respectively, p=0.423]). The specificity of FNB was better than that of FNA (100.00% vs. 93.62%, p=0.01). The number of passes required for diagnosis was not different. Abdominal and peri-hepatic LN location demonstrated FNB to have a higher sensitivity (81.08% vs. 64.71%, p=0.031 and 80.95% vs. 58.33%, p=0.023) and accuracy (88.14% vs. 75.29%, p=0.053 and 88.89% vs. 70.49%, p=0.038), respectively. ROSE was a significant predictor for accuracy (odds ratio, 5.16; 95% confidence interval, 1.15-23.08; p=0.032). No adverse events were reported in either cohort. Conclusion Both EUS-FNA and EUS-FNB are safe for the diagnosis of LNs. EUS-FNB is preferred for abdominal LN sampling. EUS-FNA+ ROSE was similar to EUS-FNB alone, showing better diagnosis for EUS-FNB than traditional FNA. While ROSE remained a significant predictor for accuracy, due to its poor availability in most centers, its use may be limited to cases with previous inconclusive diagnoses.

Background and study aims Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is traditionally considered a first-line strategy for diagnosing pancreatic lesions; however, given less than ideal accuracy rates, fine-needle biopsy (FNB) has been recently developed to yield histological tissue. The aim of this study was to compare diagnostic yield and safety between EUS-FNA and EUS-FNB in sampling of pancreatic masses. Patients and methods This was a multicenter retrospective study to evaluate efficacy and safety of EUS-FNA and EUS-FNB for pancreatic lesions. Baseline characteristics including sensitivity, specificity, and accuracy, were evaluated. Rapid on-site evaluation (ROSE) diagnostic adequacy, cell-block accuracy, and adverse events were analyzed. Subgroup analyses comparing FNA versus FNB route of tissue acquisition and comparison between methods with or without ROSE were performed. Multivariable logistic regression was also performed. Results A total of 574 patients (n = 194 FNA, n = 380 FNB) were included. Overall sensitivity, specificity, and accuracy of FNB versus FNA were similar [(89.09 % versus 85.62 %; P = 0.229), (98.04 % versus 96.88 %; P = 0.387), and 90.29 % versus 87.50 %; P = 0.307)]. Number of passes for ROSE adequacy and cell-block accuracy were comparable for FNA versus FNB [(3.06 ± 1.62 versus 3.04 ± 1.88; P = 0.11) and (3.08 ± 1.63 versus 3.35 ± 2.02; P = 0.137)]. FNA + ROSE was superior to FNA alone regarding sensitivity and accuracy [91.96 % versus 70.83 %; P Conclusion EUS-FNB allowed for more consistent cell-block evaluation as compared to EUS-FNA. EUS-FNA + ROSE was found to have a similar sensitivity to EUS-FNB alone suggesting a reduced need for ROSE as part of the standard algorithm of pancreatic sampling. While FNB alone produced similar diagnostic findings to EUS-FNA + ROSE, FNB + ROSE still was noted to increase diagnostic yield. This finding may favor a unique role for FNB + ROSE, suggesting it may be useful in cases when previous EUS-guided sampling may have been indeterminate.

Andrew Canakis.

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cystfluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86–0.99), 0.71 (0.57–0.85), and 0.72(0.60–0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve 5 0.86 (95% confidence interval: 0.77–0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.

Purpose of Review Per- and polyfluoroalkyl substances (PFAS) are a family of > 4700 recalcitrant compounds, many of which are ubiquitous in the environment. This review aims to (1) identify PFAS sources and fate processes relevant to agricultural systems and (2) expand on plant uptake mechanisms and plant responses to PFAS. Recent Findings The number of PFAS being quantified in studies involving soil, water, and plants is increasing. Transformation of precursors that tend to stay in the rhizosphere can lead to long-term PFAS reservoir to plants. Some PFAS are readily taken up, particularly the shorter-chain PFAS, and can evoke metabolic responses and phytotoxic effects at high concentrations. PFAS translocation from roots to shoots occurs through both active and passive transport mechanisms. Both PFAS uptake and effects vary between and within species. Summary As new PFAS emerge, it will be necessary to continue expanding the list of PFAS quantified in land-applied media and assessing their accumulation potential in plants. While controlled laboratory or greenhouse studies have merit, comprehensive field studies are needed to provide clarity on PFAS fate and their relative risk in agricultural systems. Field studies should include identifying site-specific PFAS sources, quantifying a broader suite of PFAS and identifying potential precursors, evaluating plant uptake of replacement PFAS, reporting of soil properties and climatic conditions, and assessing risk of impacts to source and irrigation waters. This information can be utilized to inform future studies towards evaluating and mitigating risks to our food chain associated with PFAS in agricultural systems.

Background & Aims There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. Methods CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined. Results In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection. Conclusion CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

Chronic pancreatitis (CP) is a progressive inflammatory disease, which leads to loss of pancreatic function and other disease-related morbidities. A group of academic physicians and scientists developed comprehensive guidance statements regarding the management of CP that include its epidemiology, diagnosis, medical treatment, surgical treatment, and screening. The statements were developed through literature review, deliberation, and consensus opinion. These statements were ultimately used to develop a conceptual framework for the multidisciplinary management of chronic pancreatitis referred to as an academic pancreas center of excellence (APCOE).

There are very few available data on the novel SharkCore™ needles for EUS-FNB.Comparison of the performance of the SharkCore™ needles with the standard EUS-FNA needles for the diagnosis of solid upper GI masses.Single-center, retrospective cohort study in an academic tertiary referral hospital. Patients were matched 1:1 for the site of the lesion and the presence or absence of rapid on-site evaluation (ROSE).A total of 102 patients were included. There was no statistically significant difference in the mean number of passes (3.3 ± 1.3 versus 3.4 ± 1.5; p = .89). Similar results were observed at the subgroup with ROSE (4.3 ± 1.3 versus 3.7 ± 1.5; p = .26). More histological specimens were obtained with the SharkCore™ needles compared to standard needles (59 versus 5%; p .001). Diagnostic test characteristics were not significantly different (sensitivity: 91.5 versus 85.7; specificity: 100 versus 100%; accuracy: 92.2 versus 85.4% for SharkCore™ versus standard needles, p .05 in all cases). At multivariable analysis, there was no statistically significant difference in the mean number of passes in all patients (p = .23) and in the ROSE subgroup (p = .66). However, the SharkCore™ needle obtained significantly more histological material than the standard needle (odds ratio 66; 95% confidence interval: 11.8, 375.8, p .001). There was no significant difference in complication rates (p = .5).Retrospective study, single-center.The SharkCore needles were similar to standard FNA needles in terms of the number of passes to reach diagnosis, but obtained significantly more histological specimen.

OBJECTIVES Diagnosing chronic pancreatitis remains challenging. Endoscopic ultrasound (EUS) is utilized to evaluate pancreatic disease. Abnormal pancreas function test is considered the "nonhistologic" criterion standard for chronic pancreatitis. We derived a prediction model for abnormal endoscopic pancreatic function test (ePFT) by enriching EUS findings with patient demographic and pancreatitis behavioral risk characteristics. METHODS Demographics, behavioral risk characteristics, EUS findings, and peak bicarbonate results were collected from patients evaluated for pancreatic disease. Abnormal ePFT was defined as peak bicarbonate of less than 75 mEq/L. We fit a logistic regression model and converted it to a risk score system. The risk score was validated using 1000 bootstrap simulations. RESULTS A total of 176 patients were included; 61% were female with median age of 48 years (interquartile range, 38-57 years). Abnormal ePFT rate was 39.2% (69/176). Four variables formulated the risk score: alcohol or smoking status, number of parenchymal abnormalities, number of ductal abnormalities, and calcifications. Abnormal ePFT occurred in 10.7% with scores 4 or less versus 92.0% scoring 20 or greater. The model C-statistic was 0.78 (95% confidence interval, 0.71-0.85). CONCLUSIONS Number of EUS pancreatic duct and parenchymal abnormalities, presence of calcification, and smoking/alcohol status were predictive of abnormal ePFT. This simple model has good discrimination for ePFT results.

Endoscopic retrograde cholangiopancreatography (ERCP) has become the mainstay of therapy for pancreatobiliary diseases. While ERCP is safe and highly effective in the general population, the procedure remains challenging or impossible in patients with surgically altered anatomy (SAA). Endoscopic ultrasound (EUS) allows transmural access to the bile or pancreatic duct (PD) prior to ductal drainage using ERCP-based techniques. Also known as endosonography-guided cholangiopancreatography (ESCP), the procedure provides multiple advantages over overtube-assisted enteroscopy ERCP or percutaneous or surgical approaches. However, the procedure should only be performed by endoscopists experienced in both EUS and ERCP and with the proper tools. In this review, various EUS-guided diagnostic and therapeutic drainage techniques in patients with SAA are examined. Detailed step-by-step procedural descriptions, technical tips, feasibility, and safety data are also discussed.

Interprofessional education (IPE) is promoted as a necessary precursor to the implementation of the collaborative practices in patient care thought to improve teamwork and communication among health care providers, patients, their families, and communities. Yet barriers to IPE persist, due largely to a lack of understanding on the part of health care team members about the norms and practices of health professions outside their own. A by-product of social interactions within groups and networks, social capital is a collective asset that contributes to the development of trust, innovation, and coordination of efforts toward mutual goals. Duke AHEAD (Academy for Health Professions Education and Academic Development), an interprofessional educator academy, is examined through the lens of social capital theory as a viable means of breaking down barriers to IPE, thereby improving patient care.

Background and Aims Minimum EUS and ERCP volumes that should be offered per trainee in “high quality” advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an “average” advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. Methods American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. Results Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. Conclusion The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.)

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

Intensification of concentrated animal feeding operations combined with the use of tile drains in agricultural fields has resulted in land-applied manure being a significant source of hormones to the environment. Currently, no model exists to simulate hormone fluxes from tile drains under field conditions. Therefore, we developed the Hormone Export and Recovery Dynamics (HERD) model, which incorporates hydro-climatic, biogeochemical, and anthropogenic drivers that affect hormone fate and transport. We validated HERD using known input (rainfall; lagoon effluent irrigation) and response data (tile drain flow; 17β-estradiol and estrone fluxes) from the 2009 growing season, 18 years after land-application activities began at a tile-drained field in Indiana. We used HERD to better understand the: (1) decision-making process underlying effluent irrigation activities; (2) contribution of macropore flow to estrogen transport; (3) potential for long-term applications to result in the development of legacy estrogen sources within the soil profile; and (4) potential recovery trajectory of estrogen transport following the cessation of animal waste applications. HERD adequately predicted irrigation events based on lagoon storage limits. Simple threshold exceedance logic for macropore flow activation accounted for ∼87% of the observed estrogen loads. Application history was found to be important, as not accounting for 18 years of application led to a severe underestimation of the observed estrogen loads; however, accounting for application history led to a much closer match between modeled and observed fluxes. Simulated trajectories after cessation of applications indicated that estrogens may continue to leach for several decades, which has important implications for mitigating hormone concentrations in receiving water bodies.

Research projects in translational science are increasingly complex and require interdisciplinary collaborations. In the context of training translational researchers, this suggests that multiple mentors may be needed in different content areas. This study explored mentoring structure as it relates to perceived mentoring effectiveness and other characteristics of master's-level trainees in clinical-translational research training programs. A cross-sectional online survey of recent graduates of clinical research master's program was conducted. Of 73 surveys distributed, 56.2% (n = 41) complete responses were analyzed. Trainees were overwhelmingly positive about participation in their master's programs and the impact it had on their professional development. Overall the majority (≥75%) of trainees perceived they had effective mentoring in terms of developing skills needed for conducting clinical-translational research. Fewer trainees perceived effective mentoring in career development and work-life balance. In all 15 areas of mentoring effectiveness assessed, higher rates of perceived mentor effectiveness was seen among trainees with ≥2 mentors compared to those with solo mentoring (SM). In addition, trainees with ≥2 mentors perceived having effective mentoring in more mentoring aspects (median: 14.0; IQR: 12.0-15.0) than trainees with SM (median: 10.5; IQR: 8.0-14.5). Results from this survey suggest having ≥2 mentors may be beneficial in fulfilling trainee expectations for mentoring in clinical-translational training.

Background and Aims Although conventional EUS-guided FNA (EUS-FNA) has previously been considered first-line for sampling subepithelial lesions (SELs), variable accuracy has resulted in increased use of fine-needle biopsy (FNB) sampling to improve diagnostic yield. The primary aim of this study was to compare FNA versus FNB sampling for the diagnosis of SELs. Methods This was a multicenter, retrospective study to evaluate the outcomes of EUS-FNA and EUS-guided FNB sampling (EUS-FNB) of SELs over a 3-year period. Demographics, lesion characteristics, sensitivity, specificity, accuracy, number of needle passes, diagnostic adequacy of rapid on-site evaluation (ROSE), cell block accuracy, and adverse events were analyzed. Subgroup analyses were performed comparing FNA versus FNB sampling by location and diagnostic yield with or without ROSE. Multivariable logistic regression was also performed. Results Two hundred twenty-nine patients with SELs (115 FNA and 114 FNB sampling) underwent EUS-guided sampling. Mean patient age was 60.86 ± 12.84 years. Most lesions were gastric in location (75.55%) and from the fourth layer (71.18%). Cell block for FNB sampling required fewer passes to achieve conclusive diagnosis (2.94 ± 1.09 vs 3.55 ± 1.55; P = .003). The number of passes was not different for ROSE adequacy (P = .167). Immunohistochemistry was more able to be successfully performed in more FNB sampling samples (69.30% vs 40.00%; P .05). Multivariate analysis showed no predictors associated with accuracy. One minor adverse event was reported in the FNA group. Conclusions EUS-FNB was superior to EUS-FNA in the diagnosis of SELs. EUS-FNB was also superior to EUS-FNA alone and EUS-FNA + ROSE. These results suggest EUS-FNB should be considered a first-line modality and may suggest a reduced role for ROSE in the diagnosis of SELs. However, a large randomized controlled trial is required to confirm our findings.

Background and Aims Teaching endoscopy is a key objective of gastroenterology (GI) fellowship programs but the best approach is not known. We sought to characterize which teaching competencies experts considered most critical for endoscopy education. Methods We developed and refined 18 endoscopy teaching competencies based on literature review, personal experience, and interviews with experts. We invited GI fellowship program directors and endoscopy education experts to participate in a Delphi process to rate each proposed competency as essential, important but not essential, or not important using a 70% agreement threshold for consensus. Thirty-four GI fellowship program directors and 2 experts in endoscopy education participated (n = 36). Results Most survey participants were male (61.8%), associate professors (55.9%), and had performed at least a quarter of procedures with fellows (80.6%). Survey response rates were 94% (34 of 36) for round 1 and 91% (31 of 34) for round 2 (overall 31 of 36; 86.1%). After 2 rounds we achieved the predefined consensus level for most competencies. Fourteen of 18 competencies (77.8%) reached consensus after round 2: 10 (55.6%) were deemed essential and 4 (22.2%) were deemed important but not essential. Essential competencies included the following: discusses patient history and plans for procedure with trainee (100%), assumes control of procedure when trainee is unable to progress or if patient safety concerns arise (100%), maintains attention throughout the case (96.8%), and discusses the next steps in management for the patient (96.8%). Conclusions In a national Delphi survey of endoscopy education experts, we identified 10 essential endoscopy teaching competencies. These can be used to frame faculty development and standardize GI fellowship programs to promote high-quality endoscopy education.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic EUS. The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

Background: Writing for publication is an integral skill for both sharing research findings and career advancement, yet many faculty lack expertise, support, and time to author scholarly publications. Health professions educators identified writing as an area in which a new educators’ academy could offer support.Case Presentation: To address this need, a writing task force was formed consisting of a librarian, a School of Medicine faculty member, and a School of Nursing faculty member. The task force launched two initiatives to motivate and support faculty writing and publication over two academic years. In the first year, a structured interprofessional “boot camp” consisting of a sequenced, modularized approach to manuscript completion was offered. In the second year, community building, in-person writing sessions, and incentives were added to the structured tasks. In year one, twenty participants enlisted in the boot camp, nine of whom completed a manuscript for submission by the end of the program. Qualitative feedback indicated potential improvements, which were put in place in the second program. In year two, twenty-eight participants enrolled, and eleven submitted thirteen manuscripts for publication by the end of the program.Conclusions: Structured tasks, frequent deadlines, and professional editorial assistance were highly valued by participants. Time remains a barrier for faculty seeking to complete manuscripts. As experts in many facets of the publication process, librarians are well positioned to partner with others to facilitate faculty and staff development in writing.

Objectives Management of asymptomatic pancreatic cysts is challenging. Guidelines by the American Gastroenterological Association (AGA) and International Association of Pancreatology (Fukuoka) seek to identify high-risk patients. We assessed performance of these guidelines in selecting patients for endoscopic ultrasound (EUS) and/or surgery. Methods PART I – We retrospectively studied 143 asymptomatic cysts with magnetic resonance imaging (MRI) followed by EUS. Appropriate selection for EUS was defined as: malignant cytology or surgical pathology, or development of concerning features on MRI as defined by the guidelines. PART II – We retrospectively studied 152 resected cysts to assess the performance of guidelines in selecting cysts for surgery using malignant histology as the outcome. Results PART I – Of 143 EUS, 43 (30.1 %) were male with median age 65.0 years (interquartile range [IQR] 58.0 – 73.0). AGA guideline demonstrated lower sensitivity (17.6 % versus 35.3 %, P = 0.03), higher specificity (94.5 % versus 66.1 %, p Conclusions For referral to EUS, the AGA guideline was highly specific compared to Fukuoka; both suffered from poor sensitivity, although the Fukuoka guideline was relatively more sensitive than AGA. For referral to surgery, both guidelines have modest sensitivity and specificity and miss a similar percentage of malignant lesions.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN).METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence.RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one.CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Examination of small bowel has been challenging due its anatomy, length, and tortuosity. The advent of newer enteroscopic devices such as double-balloon enteroscopy (DBE), single-balloon enteroscopy (SBE), spiral enteroscopy (SE), and through-the-scope balloon-assisted enteroscopy has dramatically changed the approach in management of small intestinal diseases. While wireless video capsule endoscopy revolutionized diagnostic capabilities in the small bowel, only after the introduction of enteroscopic devices did the therapeutic approach transform with the ability to biopsy and perform various interventions. Although all the available modalities (DBE, SBE, and SE) are comparable, and each has its own advantages, selection of a specific enteroscope depends on the availability and the endoscopist’s experience with these devices.

Background & Aims Endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. Methods Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. Results We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%–84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%–94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC ( P Conclusions We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Pancreatic cysts challenge clinicians due to their increased incidental identification on radiology imaging, the limitations of currently available diagnostic tools, and potential for malignancy. Following initial identification of an incidental pancreatic cyst, a dedicated pancreatic protocol abdominal CT scan or MRI pancreas with MRCP should be performed. Surgical resection is recommended for all surgical candidates with MD-IPMN, mixed or combined type IPMN, mucinous cystic neoplasm, and solid pseudopapillary neoplasm. Serous cystadenoma may be followed with serial imaging unless the patient develops symptoms, the cyst is larger than 4 cm or rapidly growing, or diagnostic uncertainty remains despite thorough evaluation. Surveillance is also recommended for BD-IPMN without the following features concerning malignancy: obstructive jaundice with a cyst in the head of the pancreas; solid component; nodule; main pancreatic duct ≥10 mm; or cytology suspected or positive for malignancy. BD-IPMN ≥3 cm without concerning features may also be followed carefully, although surgical resection should be considered in surgically fit patients. EUS-FNA for cyst wall cytology, CEA, amylase, and occasionally k-ras mutation are also likely aids in the diagnosis of pancreatic cysts beyond radiologic imaging. This author typically recommends EUS-FNA to further evaluate cysts larger than 1 cm without definitive indication for resection. EUS is also appropriate in patients with solid component, nodule, or size ≥3 cm to aid in decision making, especially in older patients who may be less suitable surgical candidates. A multidisciplinary approach with a team of dedicated gastrointestinal radiologists, pancreatic surgeons, gastrointestinal pathologists, and gastroenterologists is essential for managing patients with pancreatic cysts.

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Background & Aims It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. Methods We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. Results By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). Conclusions In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416 .

This is one of a series of documents prepared by the ASGE Training Committee. This curriculum document contains recommendations for training, intended for use by endoscopy training directors, endoscopists involved in teaching endoscopy, and trainees in endoscopy. It was developed as an overview of techniques currently favored for the performance and training of small-bowel endoscopy and to serve as a guide to published references, videotapes, and other resources available to the trainer. By providing information to endoscopy trainers about the common practices used by experts in performing the technical aspects of the procedure, the ASGE hopes to improve the teaching and performance of small-bowel endoscopy.

Objective This study aimed to determine if the improved pain response to endoscopic retrograde cholangiopancreatogrphy (ERCP) and pancreatic stent placement (EPS) predicts pain response in patients with chronic pancreatitis after modified lateral pancreaticojejunostomy (LPJ). Methods A multi-institutional, retrospective review of patients who underwent successful EPS before LPJ between 2001 and 2010 was performed. The primary outcome was narcotic independence (NI) within 2 months after ERCP or LPJ. Results A total of 31 narcotic-dependent patients with chronic pancreatitis underwent successful EPS before LPJ. Ten (32%) achieved post-LPJ NI (median follow-up, 8.5 months; interquartile range [IQR], 2-38 months). Eight (80%) of 10 patients with NI post-ERCP achieved NI post-LPJ. Two (10%) without NI post-ERCP achieved NI post-LPJ. Narcotic independence post-EPS was associated strongly with NI post-LPJ with an odds ratio of 38 (P = 0.0025) and predicted post-LPJ NI with a sensitivity, specificity, positive predictive value, and negative predictive value of 80%, 90.5%, 80%, and 90.5%, respectively. Conclusions Narcotic independence after EPS is associated with NI after LPJ. Failure to achieve NI post-ERCP predicts failure to achieve NI post-LPJ. These results support the need for larger studies to confirm the predictive value of pancreatic duct stenting for better selection of chronic pancreatitis patients who will benefit from LPJ.

Confocal laser endomicroscopy for real-time diagnosis during endoscopic procedures has now been in the mainstream clinical arena for a decade. Indeterminate biliary strictures and pancreatic cysts remain 2 difficult diagnostic challenges for the gastroenterologist, and the role this technology will play in the approach to these problems is still evolving. There is now a body of literature to guide the endoscopist in the use of this imaging tool, including how it may be useful in excluding biliary malignancy, and how miniaturization has allowed for endoscopic ultrasound-guided application of the probe within cysts. Interobserver variability remains a weakness of the system. Tips for use of this tool and interpretation of the imaging data it provides are discussed.

Item does not contain fulltext BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.

Endoscopic therapy is the primary modality for hemostasis of both upper and lower gastrointestinal (GI) bleeding. Some technical differences exist, however, with regard to the application of hemostasis in the lower GI tract relative to the upper gut. A working knowledge of the techniques and hemostatic devices available for the treatment of particular bleeding lesions in the lower GI tract is necessary for the safe and effective use of these modalities. Herein, the specifics of endoscopic techniques for hemostasis of lower GI bleeding will be highlighted, in addition to the role of the interventional radiologist and surgeon when colonoscopic management fails or is not feasible.

Chronic abdominal pain is often associated with chronic pancreatitis and pancreatic malignancy, and it is a major cause of patient morbidity and healthcare cost. Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) and celiac plexus neurolysis (CPN) are viable options for treatment of chronic abdominal pain in these clinical situations and have advantages over analgesic medications and/or percutaneous CPB/CPN. Technique for EUS-guided CPB/CPN varies from center to center, but all facilitate delivery of medication to the area of the celiac plexus in a safe, controlled manner via a transgastric anterior approach. Published reports demonstrate that EUS-guided CPN for pancreatic cancer pain is beneficial in selected patients and is at least as effective as percutaneous CPN. Comparatively, studies have shown that for chronic pancreatitis pain, CPB provides a lower degree of analgesia and a shorter duration of effect, whether by EUS or percutaneous approach. Serious complications from EUS-guided CPB/CPN are rare. Recently, direct targeting of the celiac plexus ganglia for block or neurolysis has been investigated and may provide greater analgesic effect than traditional CPB/CPN. Other areas of research include variations in injection technique and use of brachytherapy.