A blood-based metabolomic signature predictive of risk for pancreatic cancer.

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of >13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies.

High Persistence of Novel Polyfluoroalkyl Betaines in Aerobic Soils.

Some contemporary aqueous film-forming foams (AFFFs) contain n:3 and n:1:2 fluorotelomer betaines (FTBs), which are often detected at sites impacted by AFFFs. As new chemical replacements, little is known about their environmental fate. For the first time, we investigated the biotransformation potential of 5:3 and 5:1:2 FTBs and a commercial AFFF that mainly contains n:3 and n:1:2 FTBs (n = 5, 7, 9, 11, and 13). Although some polyfluoroalkyl compounds are precursors to perfluoroalkyl acids, 5:3 and 5:1:2 FTBs exhibited high persistence, with no significant changes even after 120 days of incubation. While the degradation of 5:3 FTB into suspected products such as fluorotelomer acids or perfluoroalkyl carboxylic acids (PFCAs) could not be conclusively confirmed, we did identify a potential biotransformation product, 5:3 fluorotelomer methylamine. Similarly, 5:1:2 FTB did not break down or produce short-chain hydrogen-substituted polyfluoroalkyl acids (n:2 H-FTCA), hydrogen-substituted PFCA (2H-PFCA), or any other products. Incubating the AFFF in four soils with differing properties and microbial communities resulted in 0.023-0.25 mol % PFCAs by day 120. Most of the products are believed to be derived from n:2 fluorotelomers, minor components of the AFFF. Therefore, the findings of the study cannot be fully explained by the current understanding of structure-biodegradability relationships.

ACG Clinical Guideline: Diagnosis and Management of Gastrointestinal Subepithelial Lesions.

Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

PURPOSE: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

State-of-the-Art Update of Pancreatic Cysts.

Andrew Canakis.

Updates in diagnosis and management of pancreatic cysts.

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.

COVID-19 related pancreatic cancer surveillance disruptions amongst high-risk individuals.

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.

Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection.

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.

Evaluation of endoscopic ultrasound fine-needle aspiration versus fine-needle biopsy and impact of rapid on-site evaluation for pancreatic masses.

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 ±â€Š1.62 versus 3.04 ±â€Š1.88; P  = 0.11) and (3.08 ±â€Š1.63 versus 3.35 ±â€Š2.02; P  = 0.137)]. FNA + ROSE was superior to FNA alone regarding sensitivity and accuracy [91.96 % versus 70.83 %; P  < 0.001) and (91.80 % versus 80.28 %; P  = 0.020)]. Sensitivity of FNB + ROSE and FNB alone were superior to FNA alone [(92.17 % versus 70.83 %; P  < 0.001) and (87.44 % versus 70.83 %; P  < 0.001)]. There was no difference in sensitivity though improved accuracy between FNA + ROSE versus FNB alone [(91.96 % versus 87.44 %; P  = 0.193) and (91.80 % versus 80.72 %; P  = 0.006)]. FNB + ROSE was more accurate than FNA + ROSE (93.13 % versus 91.80 % ; P  = 0.001). Multivariate analysis showed ROSE was a significant predictor of accuracy [OR 2.60 (95 % CI, 1.41-4.79)]. One adverse event occurred after FNB resulting in patient death. 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.

EUS-guided fine-needle biopsy sampling versus FNA in the diagnosis of subepithelial lesions: a large multicenter study.

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 < .001). Overall, sensitivity and accuracy were superior for FNB sampling versus FNA (79.41% vs 51.92% [P = .001] and 88.03% vs 77.19% [P = .030], respectively). On subgroup analysis, sensitivity and accuracy of FNB sampling alone was superior to FNA + ROSE (79.03% vs 46.67% [P = .001] and 87.25% vs 68.00% [P = .024], respectively). There was no significant difference in diagnostic yield of FNB sampling alone versus FNB sampling + ROSE (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.

Endoscopic Ultrasound Fine-Needle Aspiration versus Fine-Needle Biopsy for Lymph Node Diagnosis: A Large Multicenter Comparative Analysis.

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.

Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing.

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 cyst fluid (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 = 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.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

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.).

Sorption, Aerobic Biodegradation, and Oxidation Potential of PFOS Alternatives Chlorinated Polyfluoroalkyl Ether Sulfonic Acids.

Global phase out of perfluorooctanesulfonic acid (PFOS) has led to increasing production of alternatives such as the chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) for which little is known on their environmental fate. In this study, sorption by soils, aerobic soil biodegradation, and oxidation potential of 6:2 Cl-PFESA (9-chlorohexadecafluoro-3-oxanonane-1-sulfonate) and 8:2 Cl-PFESA (9-chlorooctadecafluoro-3-oxanonane-1-sulfonate) were evaluated. 6:2 Cl-PFESA sorption was quantified for aqueous and acetone/water solutions, whereas 8:2 PFESA could only be accurately measured in acetone/water solutions. The log-linear cosolvency model was applied and validated to estimate sorption of 8:2 Cl-PFESA. Only soil organic carbon (OC, 0.76-4.30%) was highly and positively correlated to sorption of the Cl-PFESAs ( R2 > 0.96). The resulting log Koc values (OC-normalized sorption coefficients) are 4.01 ± 0.09 ( n = 6) and 5.54 ± 0.05 ( n = 4) L kg-1 for 6:2 Cl-PFESA and 8:2 Cl-PFESA, respectively. Aerobic biodegradation in a loam soil at 24 ± 0.5 °C showed negligible degradation of both Cl-PFESAs. Cl-PFESAs also remained unchanged in an unbuffered heat (50 °C)-activated 42 mM persulfate oxidation treatment. Therefore, Cl-PFESAs are equally recalcitrant as PFOS in addition to being more sorptive, thus with a higher bioaccumulation potential for a similar alkyl chain length.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

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.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis.

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.

A multi-institutional consensus on how to perform endoscopic ultrasound-guided peri-pancreatic fluid collection drainage and endoscopic necrosectomy.

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard of care for the creation of an endoscopic cystenterostomy in patients with pancreatic walled-off necrosis (WON); 95.5% (21/22) recommended large diameter (d=15 mm) LAMS for drainage in patients with WON; 54.5% (12/22) would not dilate LAMS after placement into the WOPN; 86.4% (19/22) would not perform endoscopic necrosectomy during the same procedure as the creation of the cystenterostomy; 45.5% (10/22) recommend that agents, such as diluted hydrogen peroxide, should be used to lavage the peri-pancreatic fluid collection (PFC) cavity in patients with WON; and 45.5% (10/22) considered a naso-cystic or other tube to be necessary for lavage of WON after initial drainage. The mean optimal interval recommended for endoscopic necrosectomy procedures after EUS-guided drainage was 6.23 days. The mean optimal interval recommended for repeat imaging in patients undergoing endoscopic necrosectomy was 12.32 days. The mean time recommended for LAMS removal was 4.59 weeks. This is the first worldwide survey on the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need to establish a best practice consensus.