Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Prophylactic Perioperative Antibiotics in Open Pancreaticoduodenectomy: When Less Is More and When It Is Not. A National Surgical Quality Improvement Program Propensity-Matched Analysis.

INTRODUCTION: We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present. METHODS: The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes. RESULTS: Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P < 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates. CONCLUSIONS: G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.

The Role of Endoscopic Ultrasonography in the Diagnosis and Staging of Pancreatic Cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death and the second gastrointestinal cancer-related death in the United States. Early detection and accurate diagnosis and staging of pancreatic cancer are paramount in guiding treatment plans, as surgical resection can provide the only potential cure for this disease. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. The 5-year survival after surgical resection is ~10% in node-positive disease compared to ~30% in node-negative disease. The advancement of imaging studies and the multidisciplinary approach involving radiologists, gastroenterologists, advanced endoscopists, medical, radiation, and surgical oncologists have a major impact on the management of pancreatic cancer. Endoscopic ultrasonography is essential in the diagnosis by obtaining tissue (FNA or FNB) and in the loco-regional staging of the disease. The advancement in EUS techniques has made this modality a critical adjunct in the management process of pancreatic cancer. In this review article, we provide an overall description of the role of endoscopic ultrasonography in the diagnosis and staging of pancreatic cancer.

Endoscopic cryotherapy: Indications, techniques, and outcomes involving the gastrointestinal tract.

Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett's esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.

Malignant colon polyps: predicting lymph node metastasis following endoscopic excision.

AIM: The risk of lymph node metastasis (LNM) of malignant colon polyps (MCPs) is partly estimated by histologic features of the sampled polyp. However, the routinely available histologic data is limited to tumor grade and status of lymphovascular invasion (LVI). METHODS: The NCDB for colon cancer 2004-2018 was utilized. Patients with pT1Nx adenocarcinoma arising in a polyp and undergoing partial colectomy with ≥ 12 retrieved nodes were selected. NCDB 2004-2017 was used as a training cohort to develop two scoring systems based on a multivariable regression for predictors of LNM including clinical characteristics, grade, and LVI: a nomogram scoring system (NSS) and a simplified scoring system (SSS). These models were internally validated using NCDB 2018 to calculate precision metrics for each model. RESULTS: Six thousand sixty-nine patients were selected in the training cohort. 64.5% of MCPs were in the sigmoid, and LNM rate was 11.2%. Multivariable regression identified younger age, females, hindgut location, higher grade, and LVI as significant predictors of LNM. LNM risk was 1.2% when all unfavorable predictors were absent and exceeded 10% when NSS > 70 or SSS ≥ 3. In the 2018 validation cohort, 723 patients were scored per NSS and SSS, and the negative predictive value for both was 96%. CONCLUSION: Estimating LNM risk in MCPs by applying clinical characteristics along with limited histologic data can help inform decision-making when considering formal oncologic resection. The NSS and SSS demonstrated comparable predictability of LNM among pT1Nx MCPs. The models require external validation and may be strengthened by incorporating additional endoscopic and pathologic characteristics.

Choice of sedation in endoscopic retrograde cholangiopancreatography: is monitored anesthesia care as safe as general anesthesia? A systematic review and meta-analysis.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) are the 2 most common methods of sedation used for endoscopic retrograde cholangiopancreatography (ERCP). We performed a systematic review and meta-analysis to compare the overall safety between MAC vs. GA in ERCP. METHODS: We conducted a comprehensive search of electronic databases to identify studies reporting the use of MAC or GA as a choice of sedation for ERCP. The primary outcome was to compare the overall rate of sedation-related adverse events in MAC vs. GA groups. The secondary endpoint was to investigate the total duration of the procedure, recovery time, ERCP cannulation rates, and conversion rate of MAC to GA. The meta-analysis was performed using a Der Simonian and Laird random-effects model. RESULTS: A total of 21 studies reporting on 11,592 patients were included. The overall sedation-related side-effects were similar in the GA (12.76%, 95% confidence interval [CI] 5.80-21.73; I2=95%) and MAC (12.08%, 95%CI 5.38-20.89; I2=99%) groups (P=0.956). Hypoxia, arrhythmias, hypotension, aspiration and other sedation-related side-effects were similar between the 2 groups. The mean duration of the procedure was longer in the MAC group, but the mean recovery time was shorter. Significant heterogeneity was noted in our meta-analysis. CONCLUSIONS: In our meta-analysis, the overall sedation-related side-effects were similar between the MAC and GA groups. MAC could be used as a safer alternative to GA when performing ERCP. However, large multicenter randomized control trials are needed to further validate our findings.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Impact of margin status on outcomes after endoscopic resection of well-differentiated duodenal neuroendocrine tumors.

BACKGROUND AND AIMS: Duodenal neuroendocrine tumors (DNETs) are known to have low metastatic potential and follow an indolent course. Although DNETs <1 cm in size are amenable to endoscopic resection, little is known about the long-term outcomes and recurrence rates of this approach. METHODS: Sixty-three patients with DNETs from 3 centers were retrospectively studied from 2003 to 2018. We analyzed their resection modality (EMR, snare polypectomy, or forceps polypectomy), margin status, risk factors for recurrence, recurrence rate, and endoscopic surveillance patterns. RESULTS: Of the 63 patients who underwent endoscopic resection, 13 (20.6%) had recurrence. The presence of R1 margins was found to be a statistically significant risk factor for recurrence (P = .048). Mean surveillance time for all DNETs was 2.8 ± 2.6 years. Ninety-two percent of recurrences were detected within 3 years of resection. CONCLUSIONS: Our data suggest that the main predictor of recurrence in low-grade DNETs <1.0 cm is the presence of positive tumor margins at the initial endoscopic resection. More frequent, earlier surveillance after resection than that currently recommended by European Neuroendocrine Tumor Society guidelines may be warranted to promptly capture DNET recurrences. Additionally, no recurrences occurred in our cohort after 4 years of surveillance.

Narrative review of the role of gastroenterologist in the diagnosis, treatment and palliation in gastric and gastroesophageal cancer.

Esophageal cancer (EC) and gastric cancer (GC) carry a high mortality rate. Unfortunately, a majority of patients are asymptomatic and at the time of diagnosis, the disease may invariably be in its advanced stages with limited curative options. Thus, it is imperative to recognize certain risk factors including gastroesophageal reflux disease (GERD), male gender, pre-existing Barrett's esophagus, smoking history, obesity, Helicobacter pylori infection, atrophic gastritis among others for both EC and GC, intervene on time with screening and surveillance modalities if indicated and optimize treatment plans. With advances in endoscopic techniques, early neoplastic lesions are increasingly managed by gastroenterologists, offering an alternative to surgery. The gold standard for diagnosis of EC and GC is high definition endoscopy with adequate targeted biopsies. Endoscopic ultrasound (EUS) is a key in the staging of early cancers dictating the pathway for treatment options. We also play a key role in palliation cases with the aim to reduce the symptoms like nausea, vomiting and even when possible, restore oral intake and improve nutrition in both advanced GC and EC. This review article discusses the risk factors, diagnostic and endoscopic treatment modalities of early EC and GC and palliation of advanced cancer where gastroenterologists play a key role.

A narrative review of Barrett's esophagus in 2020, molecular and clinical update.

Barrett's esophagus (BE) is a condition resulting from an acquired metaplastic epithelial change in the esophagus in response to gastroesophageal reflux. BE is the only known precursor lesion to esophageal adenocarcinoma, and can progress from non-dysplastic BE (NDBE) to low grade dysplasia (LGD) and high grade dysplasia (HGD), and ultimately invasive carcinoma. Although the risk of developing esophageal adenocarcinoma (EAC) in NBDE is less than 0.5% per year, there has been a rising incidence of EAC in Western countries, which continue to drive efforts to optimize screening and surveillance methods. The current gold standard for diagnosis is esophagogastroduodenoscopy (EGD), and there has been significant interest in alternative, minimally invasive methods for screening which would be more readily accessible in the primary care setting. Surveillance endoscopy in 3-5 years is recommended for NDBE given the low progression to EAC. The mainstay of treatment for LGD and HGD is endoscopic eradication therapy (EET). Visible lesions are treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Radiofrequency ablation (RFA) is considered first line therapy for flat dysplastic BE and cryotherapy has shown promising results as an alternate form of treatment for of dysplasia. The molecular progression of BE to EAC is a complex process involving multiple pathways involving genetic and epigenetic modifications. Genomic studies have further led to the understanding of the complex molecular landscape that occurs early and late in the disease process. Promising biomarker panels have been investigated to help with the diagnosis of BE as well as aid in the risk stratification of BE during surveillance. In addition, clinical prediction models have been developed to categorize BE patients in low, intermediate, and high risk for progression to HGD and EAC. Further clinical and translational research is needed to help refine markers and techniques in diagnosis, screening, and surveillance.

Imaging of Pancreatic Tumors.

Imaging plays a key role in the diagnosis and staging of pancreatic tumors. Imaging modalities utilized for the evaluation of pancreatic tumors include: transabdominal and endoscopic ultrasound, computed tomography, and magnetic resonance imaging. Each of these modalities has different strengths and weaknesses which must be considered in the setting of evaluating a pancreatic tumor. Imaging can determine if a pancreatic tumor is cystic or solid and help develop a differential diagnosis based on the lesion's imaging features. If a malignant pancreatic tumor is diagnosed, imaging can assist with initial staging by determining the size and local extent of the tumor as well as evaluating for nodal and metastatic disease. Here we review the different imaging modalities utilized to evaluate pancreatic masses, describe the key imaging features of the most significant entities in the differential diagnosis, and describe the diagnostic imaging approach.

Comparison of imaging modalities for measuring the diameter of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic cysts detected by imaging. Cyst size is one of many features evaluated on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS) to help guide IPMN management. Our objective was to determine which imaging modality best predicts pathological cyst size. METHODS: We analyzed records for 57 IPMN cases surgically treated at Moffitt Cancer Center from 2008 to 2016 for whom pre-operative CT, MRI, and EUS IPMN cyst size and post-operative pathological cyst size values were available. Long axis cyst diameter measurements were compared to each other and corresponding pathological cyst measurements using within-subjects ANOVA, Bland-Altman analysis, and linear regression. Consensus measurements were also performed on CT and MRI images. RESULTS: Cyst size measured via CT and MRI overestimated pathological size by 0.33 cm and 0.27 cm, respectively, whereas EUS underestimated pathological size by 0.05 cm and had the narrowest 95% limit of agreement (LOA). Among pathologically-confirmed cysts <3 cm, MRI overestimated pathological size by 0.30 cm (P = 0.049) and had the widest LOA, followed by EUS and CT. Among cysts ≥3 cm, EUS underestimated pathological size by 0.35 cm (P = 0.059) and MRI and CT overestimated pathological size by 0.23 cm and 0.51 cm, respectively. CONCLUSIONS: In this small retrospective study, EUS cyst size measurements correlated best with pathologic specimens compared to CT and MRI, especially for cysts < 3 cm. Larger prospective studies are needed to determine which imaging modalities are best to risk-stratify IPMNs and guide surgical versus. Non-surgical management.

An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advanced pancreatic cancer (OncoPaC-1): Technical details and study protocol.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed. Currently, there is no brachytherapy device approved for pancreatic cancer treatment. Hereby, we present the protocol of a prospective, multicenter, interventional, open-label, single-arm pilot study (OncoPac-1, Clinicaltrial.gov-NCT03076216) aiming to determine the safety and efficacy of Phosphorus-32 when implanted directly into pancreatic tumors using EUS guidance, for patients with unresectable LAPC undergoing chemotherapy (gemcitabine ± nab-paclitaxel).

CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett's Esophagus.

BACKGROUND: CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs. AIMS: This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett's esophagus (BE). METHODS: This study received IRB approval (17,284). Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years. Initial and follow-up staining results were evaluated for age/sex. RESULTS: Differences between development of goblet cell IM in CDX-2-negative and CDX-2-positive groups were evaluated. A Kaplan-Meier curve showed that, out of the 134 patients initially positive for CDX-2, 25 (18.7%) had developed goblet cell IM after 2 years and 106 (79.1%) after 3 years. Conversely, of the 47 patients initially negative for CDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model). CONCLUSION: In cases that are initially AB negative and CDX-2 positive, CDX-2 was demonstrated to have a potential prognostic utility for early detection of progression to BE. CDX-2 expression is significantly predictive for risk of goblet cell IM development 40 to 45 months after initial biopsy.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

Endoscopic Ultrasound Placement of Preloaded Fiducial Markers Shortens Procedure Time Compared to Back-Loaded Markers.

BACKGROUND & AIMS: Fiducial markers are inert radiopaque gold or carbon markers implanted in or near pancreatic tumor to demarcate areas for image-guided radiation therapy. Endoscopic ultrasound (EUS) pre-loaded fiducial needles (PLNs) have been developed to circumvent technical issues associated with traditional back-loaded fiducials (BLNs). We performed a randomized controlled trial to compare procedure times in patients with pancreatic adenocarcinoma undergoing EUS-guided placement of BLNs vs PLNs. METHODS: In a prospective study, 44 patients with pancreatic adenocarcinoma referred for fiducial marker placement at 2 tertiary care centers were assigned to groups that received PLNs (n = 22) or BLNs (n = 22); each group had the same proportion of patients with tumors of different locations (head or neck vs body or tail).The procedure was standardized among all endoscopists and placement of a minimum of 3 markers inside the tumor was defined as technical success. The times for procedure and fiducial placement were recorded, total number of fiducial markers used documented, and grade of procedure difficulty ranked by passing the needle or deploying the fiducials. Other recorded variables included tumor characteristics, fluoroscopy use, and the number of fiducials clearly seen by EUS and fluoroscopy. The primary aim was to compare the duration of EUS-guided fiducial insertion of BLNs vs PLNs. RESULTS: The median placement time was significantly shorter in the PLN group (9 min) than the BLN group (16 min) (P < .001). However, the 44% reduction in time did not reach pre-specified levels (≥60%). Similar results were found after stratifying by tumor location. Deployment of BLNs was easier than deployment of PLNs (P = .03). There was no significant difference between groups in technical success, number of fiducials placed, EUS or fluoroscopic visualization, or adverse events. During simulation computed tomography and image-guided radiation therapy, there was no difference between groups in visualization of fiducials, migration rate, or accuracy of placement. CONCLUSIONS: In a randomized controlled trial of 44 patients with pancreatic adenocarcinoma, we found EUS-guided placement of PLNs to require less time and produce similar results compared with BLNs. Further refinements in PLN delivery system are needed to increase the ease of deployment. Clinicaltrials.gov no: NCT02332863.

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.).

Characteristics and Clinical Outcomes of Individuals at High Risk for Pancreatic Cancer: A Descriptive Analysis from a Comprehensive Cancer Center.

Pancreatic cancer (PC), a leading cause of cancer-related deaths in the United States, is typically diagnosed at an advanced stage. To improve survival, there is an unmet need to detect pre-malignant lesions and early invasive disease. Prime populations to study for early detection efforts include cohorts of high risk individuals (HRI): those with increased risk to develop pre-malignant pancreatic cysts and PC because of a familial or hereditary predisposition to the disease and those in the general population of sporadic cases who are incidentally found to harbor a pre-malignant pancreatic cyst. The objective of this study was to describe the characteristics and clinical outcomes of cohorts of HRI identified at Moffitt Cancer Center. We set out to determine the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected. Of a total of 329 HRI, roughly one-third were found to have pancreatic lesions, most of which constituted pre-malignant cysts known as intraductal papillary mucinous neoplasms. Individuals with the highest genetic risk for PC were found to have smaller cysts at a much earlier age than sporadic cases with incidental findings; however, many individuals at high genetic risk did not have abdominal imaging reports on file. We also identified a subset of HRI at moderate genetic risk for PC that were found to have cystic and solid pancreatic lesions as part of a diagnostic work-up rather than a screening protocol. These findings suggest the pancreatic research community should consider expanding criteria for who should be offered screening. We also emphasize the importance of continuity of care between cancer genetics and gastrointestinal oncology clinics so that HRI are made aware of the opportunities related to genetic counseling, genetic testing, and screening.

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.