Prevalence of H. pylori and gastric intestinal metaplasia in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer (GC), however the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of GC risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of GC in this population. 100 unselected BRCA1/2 carriers undergoing endoscopic ultrasound from 3/2022-3/2023 underwent concomitant upper endoscopy with non-targeted gastric antrum and body biopsies. The study population (70% women; mean age: 60.1) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no GCs were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to the general population, however identification of H. pylori or GIM may help inform future GC risk management strategies in BRCA1/2 carriers.

Rise in First-Time ERCP For Benign Indications >1 Year After Cholecystectomy Is Associated With Worse Outcomes.

BACKGROUND & AIMS: Greater availability of less invasive biliary imaging to rule out choledocholithiasis should reduce the need for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients who have a remote history of cholecystectomy. The primary aims were to determine the incidence, characteristics, and outcomes of individuals who undergo first-time ERCP >1 year after cholecystectomy (late-ERCP). METHODS: Data from a commercial insurance claim database (Optum Clinformatics) identified 583,712 adults who underwent cholecystectomy, 4274 of whom underwent late-ERCP, defined as first-time ERCP for nonmalignant indications >1 year after cholecystectomy. Outcomes were exposure and temporal trends in late-ERCP, biliary imaging utilization, and post-ERCP outcomes. Multivariable logistic regression was used to examine patient characteristics associated with undergoing late-ERCP. RESULTS: Despite a temporal increase in the use of noninvasive biliary imaging (35.9% in 2004 to 65.6% in 2021; P < .001), the rate of late-ERCP increased 8-fold (0.5-4.2/1000 person-years from 2005 to 2021; P < .001). Although only 44% of patients who underwent late-ERCP had gallstone removal, there were high rates of post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%). Factors associated with late-ERCP included concomitant disorder of gut-brain interaction (odds ratio [OR], 6.48; 95% confidence interval [CI], 5.88-6.91) and metabolic dysfunction steatotic liver disease (OR, 3.27; 95% CI, 2.79-3.55) along with use of anxiolytic (OR, 3.45; 95% CI, 3.19-3.58), antispasmodic (OR, 1.60; 95% CI, 1.53-1.72), and chronic opioids (OR, 6.24; 95% CI, 5.79-6.52). CONCLUSIONS: The rate of late-ERCP postcholecystectomy is increasing significantly, particularly in patients with comorbidities associated with disorder of gut-brain interaction and mimickers of choledocholithiasis. Late-ERCPs are associated with disproportionately higher rates of adverse events, including initiation of chronic opioid use.

The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis.

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is associated with a higher risk of noncardia intestinal gastric adenocarcinoma (GA). The aim of this study was to estimate lifetime benefits, complications, and cost-effectiveness of GIM surveillance using esophagogastroduodenoscopy (EGD). METHODS: We developed a semi-Markov microsimulation model of patients with incidentally detected GIM, to compare the effectiveness of EGD surveillance with no surveillance at 10-year, 5-year, 3-year, 2-year, and 1-year intervals. We modeled a simulated cohort of 1,000,000 US individuals aged 50 with incidental GIM. Outcome measures were lifetime GA incidence, mortality, number of EGDs, complications, undiscounted life-years gained, and incremental cost-effectiveness ratio with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). RESULTS: In the absence of surveillance, the model simulated 32.0 lifetime GA cases and 23.0 lifetime GA deaths per 1000 individuals with GIM, respectively. Among surveilled individuals, simulated lifetime GA incidence (per 1000) decreased with shorter surveillance intervals (10-year to 1-year, 11.2-6.1) as did GA mortality (7.4-3.6). Compared with no surveillance, all modeled surveillance intervals yielded greater life expectancy (87-190 undiscounted life-years gained per 1000); 5-year surveillance provided the greatest number of life-years gained per EGD performed and was the cost-effective strategy ($40,706/QALY). In individuals with risk factors of family history of GA or anatomically extensive, incomplete-type GIM intensified 3-year surveillance was cost-effective (incremental cost-effectiveness ratio $28,156/QALY and $87,020/QALY, respectively). CONCLUSIONS: Using microsimulation modeling, surveillance of incidentally detected GIM every 5 years is associated with reduced GA incidence/mortality and is cost-effective from a health care sector perspective. Real-world studies evaluating the impact of GIM surveillance on GA incidence and mortality in the United States are needed.

Outcomes of the IMMray PanCan-d Test in High-Risk Individuals Undergoing Pancreatic Surveillance: Pragmatic Data and Lessons Learned.

PURPOSE: An effective blood-based test for pancreatic cancer (PC) screening has remained elusive. The IMMray PanCan-d is the first commercially available blood-based test specifically designed for early detection of PC; however, outcomes from its use in clinical practice have not been reported. METHODS: We performed a blinded spike-in study of 100 individuals who had an IMMray PanCan-d test, including 94 high-risk individuals (HRIs) undergoing PC surveillance and six individuals with known PC. Specimens were processed blindly following the commercial laboratory's standardized operating procedure. Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Cohort characteristics included a median age of 63 (IQR, 55-70) years, 57% female, 96% non-Hispanic White, 57% with a pathogenic variant in a PC risk gene (BRCA2 most commonly-18%), and 83% with a family history of PC. Among IMMray PanCan-d results from 94 HRIs undergoing PC surveillance, there was one positive (1%), seven borderlines (7%), 73 negatives (78%), and 13 tests not performed because of low CA19-9 expression (14%). No PC was diagnosed among these HRIs; however, there were two sub-cm pancreatic neuroendocrine tumors, seven clinically diagnosed side branch intraductal papillary mucinous neoplasms ≥1 cm, and a sub-cm solid mass with indeterminate cytology requiring close follow-up; all these individuals had negative IMMray PanCan-d tests. Of the six spiked-in PCs, four (67%) yielded a positive and two (33%) yielded a negative. With an estimated disease prevalence of 2%, the PPV and NPV are 52% and 99%, respectively, if borderline results are considered negative and 12% and 99%, respectively, if borderline tests are considered positive. CONCLUSION: In clinical practice, IMMray PanCan-d has a robust NPV; however, PPV is dramatically influenced by whether borderline results are characterized as a positive or negative result.

Cost-effectiveness of endoscopic, surgical and pharmacological obesity therapies: a microsimulation and threshold analyses.

OBJECTIVE: Weight loss interventions to treat obesity include sleeve gastrectomy (SG), lifestyle intervention (LI), endoscopic sleeve gastroplasty (ESG) and semaglutide. We aimed to identify which treatments are cost-effective and identify requirements for semaglutide to be cost-effective. DESIGN: We developed a semi-Markov microsimulation model to compare the effectiveness of SG, ESG, semaglutide and LI for weight loss in 40 years old with class I/II/III obesity. Extensive one-way sensitivity and threshold analysis were performed to vary cost of treatment strategies and semaglutide adherence rate. Outcome measures were incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay threshold of US$100 000/quality-adjusted life-year (QALY). RESULTS: When strategies were compared with each other, ESG was cost-effective in class I obesity (US$4105/QALY). SG was cost-effective in class II obesity (US$5883/QALY) and class III obesity (US$7821/QALY). In class I/II/III, obesity, SG and ESG were cost-effective compared with LI. However, semaglutide was not cost-effective compared with LI for class I/II/III obesity (ICER US$508 414/QALY, US$420 483/QALY and US$350 637/QALY). For semaglutide to be cost-effective compared with LI, it would have to cost less than US$7462 (class III), US$5847 (class II) or US$5149 (class I) annually. For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US$1879 (class III), US$1204 (class II) or US$297 (class I) annually. CONCLUSIONS: Cost-effective strategies were: ESG for class I obesity and SG for class II/III obesity. Semaglutide may be cost-effective with substantial cost reduction. Given potentially higher utilisation rates with pharmacotherapy, semaglutide may provide the largest reduction in obesity-related mortality.

An Evaluation of Critical Factors for the Cost-Effectiveness of Real-Time Computer-Aided Detection: Sensitivity and Threshold Analyses Using a Microsimulation Model.

BACKGROUND & AIMS: The use of computer-aided detection (CAD) increases the adenoma detection rates (ADRs) during colorectal cancer (CRC) screening/surveillance. This study aimed to evaluate the requirements for CAD to be cost-effective and the impact of CAD on adenoma detection by endoscopists with different ADRs. METHODS: We developed a semi-Markov microsimulation model to compare the effectiveness of traditional colonoscopy (mean ADR, 26%) to colonoscopy with CAD (mean ADR, 37%). CAD was modeled as having a $75 per-procedure cost. Extensive 1-way sensitivity and threshold analysis were performed to vary cost and ADR of CAD. Multiple scenarios evaluated the potential effect of CAD on endoscopists' ADRs. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay threshold of $100,000/quality-adjusted life year. RESULTS: When modeling CAD improved ADR for all endoscopists, the CAD cohort had 79 and 34 fewer lifetime CRC cases and deaths, respectively, per 10,000 persons. This scenario was dominant with a cost savings of $143 and incremental effectiveness of 0.01 quality-adjusted life years. Threshold analysis demonstrated that CAD would be cost-effective up to an additional cost of $579 per colonoscopy, or if it increases ADR from 26% to at least 30%. CAD reduced CRC incidence and mortality when limited to improving ADRs for low-ADR endoscopists (ADR <25%), with 67 fewer CRC cases and 28 CRC deaths per 10,000 persons compared with traditional colonoscopy. CONCLUSIONS: As CAD is implemented clinically, it needs to improve mean ADR from 26% to at least 30% or cost less than $579 per colonoscopy to be cost-effective when compared with traditional colonoscopy. Further studies are needed to understand the impact of CAD when used in community practice.

Association of Statin Usage and the Development of Diabetes Mellitus after Acute Pancreatitis.

BACKGROUND: Patients with acute pancreatitis (AP) have at least a 2-fold higher risk for developing postpancreatitis diabetes mellitus (PPDM). No therapies have prevented PPDM. Statins were demonstrated to possibly lower the incidence and severity of AP but have not been studied to prevent PPDM. METHODS: Data from a commercial insurance claim database (Optum Clinformatics) were used to assess the impact of statins on patients without pre-existing DM admitted for a first episode of AP in 118,479 patients. Regular statin usage was defined as filled statin prescriptions for at least 80% of the year prior to AP. The primary outcome was defined as PPDM. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional hazards regression modeling, we estimated the risk of PPDM, accounting for competing events. RESULTS: With a median of 3.5 years of follow-up, the 5-year cumulative incidence of PPDM was 7.5% (95% confidence interval [CI], 6.9% to 8.0%) among regular statin users and 12.7% (95% CI, 12.4% to 12.9%) among nonusers. Regular statin users had a 42% lower risk of developing PPDM compared with nonusers (hazard ratio, 0.58; 95% CI, 0.52 to 0.65; P < .001). Irregular statin users had a 15% lower risk of PPDM (hazard ratio, 0.85; 95% CI, 0.81 to 0.89; P < .001). Similar benefits were seen with low, moderate, and high statin doses. CONCLUSIONS: In a large database-based study, statin usage reduced the risk of developing DM after acute pancreatitis. Further prospective studies with long-term follow-up are needed to study the impact of statins on acute pancreatitis and prevention of PPDM.

A Prospective Cohort Study Evaluating PAN-PROMISE, a Patient-reported Outcome Measure to Detect Post-ERCP Morbidity.

BACKGROUND & AIMS: The Cotton Consensus (CC) criteria for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) may not capture post-ERCP morbidity. PAN-PROMISE, a patient-reported outcome measure (PROM), was developed to quantify acute pancreatitis-related morbidity. This study aims to determine the value of PAN-PROMISE in independently defining ERCP-related morbidity. METHODS: We conducted a prospective cohort study of patients undergoing ERCP at 2 academic centers from September 2021 to August 2022. We administered PAN-PROMISE and assessed quality of life and work productivity at baseline, 48 to 72 hours, 7 days, and 30 days following ERCP. PEP was defined by a 3-physician committee using the CC criteria. We defined high morbidity following ERCP (elevated PROM) by an increase of PAN-PROMISE score of >7 at 7 days post-procedure. The McNemar test assessed discordance between PEP and elevated-PROM. RESULTS: A total of 679 patients were enrolled. Choledocholithiasis (30%) and malignant biliary obstruction (29%) were the main indications for ERCP. Thirty-two patients (4.7%) developed PEP. One hundred forty-seven patients (21.6%) had an elevated PROM, whereas only 20 of them (13.4%) had PEP by the CC criteria (P < .001 for discordance). An elevated PROM strongly correlated with lower physical quality of life and increased direct and indirect health care costs ($80 and $25 per point increase in PAN-PROMISE, respectively). Patients with pancreatic cancer (odds ratio, 4.52; 95% confidence interval, 1.68-10.74) and primary sclerosing cholangitis (odds ratio, 1.79; 95% confidence interval, 1.29-2.45) had the highest odds of elevated PROM. CONCLUSIONS: A substantial number of patients experience significant morbidity after ERCP despite not developing PEP or other adverse events. Future studies are needed to characterize better the reasons behind this increase in symptoms and potential interventions to reduce the symptom burden post-ERCP. CLINICALTRIALS: gov number, NCT05310409.

Fully Covered Self-expanding Stents are Cost-effective at Remediating Biliary Strictures in Patients With Chronic Pancreatitis.

Benign biliary strictures (BBS) develop in up to 10% to 30% of patients with chronic pancreatitis (CP).1 Endoscopic endoprosthetics via endoscopic retrograde cholangiopancreatography (ERCP) has become the standard of care for remediating these strictures. Seventy percent to eighty percent of these strictures resolve with sequential or concurrent placement of multiple plastic stents (MPS).1,2 More recently, placement of fully covered self-expanding metal stents (FCSEMS) have been shown to have similar outcomes as MPS.3-6 FCSEMS provide a larger radial diameter and require fewer procedures, but may have drawbacks, including a higher risk of migration, cholecystitis, delamination, and tissue ingrowth. A recent study demonstrated that FCSEMS with a 12-month indwell had similar outcomes to MPS with fewer ERCP needed.7 However, the cost-effectiveness of either strategy for managing BBS has not been assessed previously nor has the impact of additional reimbursement to cover the cost of FCSEMS on the cost-effectiveness of FCSEMS utilization.

Assessment of the Psychosocial Impact of Pancreatic Cancer Surveillance in High-Risk Individuals.

OBJECTIVES: Pancreatic cancer (PC) surveillance of high-risk individuals (HRIs) downstages PC and improves survival. However, it remains less clear whether PC surveillance has a positive psychosocial impact on HRIs. Herein, we aimed to define the attitudes and beliefs of HRIs undergoing PC surveillance, and the immediate and sustained psychosocial impact of PC surveillance in HRIs. METHODS: 100 HRIs undergoing PC surveillance by endoscopic ultrasound (EUS) completed three surveys addressing different components of the psychosocial impact of PC surveillance. Logistic regression analyses were performed to identify predictive factors relating to these components. RESULTS: Most HRIs reported increased perceived benefits of PC surveillance, self-efficacy, and perceived severity of PC. HRIs reported few negative emotions prior to surveillance and frequent positive emotions after surveillance. Compared to prior to surveillance, there was a 53.5% decrease in the level of distress reported by HRIs after surveillance, which was sustained for 4-6 weeks post-surveillance. Family history of PC and lower self-reported mental health were identified as predictors for increased perceived susceptibility to PC (p < 0.01) and greater change in distress pre- to post-surveillance (p < 0.01), respectively. CONCLUSIONS: Our findings suggest that PC surveillance can lead to sustained psychosocial benefits in HRIs.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Effect of Patient-Directed Messaging on Colorectal Cancer Screening: A Randomized Clinical Trial.

Importance: Colorectal cancer (CRC) screening is underused in the US. Tailored message interventions have shown benefit for increasing screening uptake of mammography and Papanicolaou testing, but their role in CRC screening is less clear. Objective: To evaluate the effectiveness of a tailored message telephone intervention prior to scheduling of a screening or surveillance colonoscopy and its effect on CRC screening completion rates. Design, Setting, and Participants: This randomized clinical trial was conducted from July 2017 through August 2018 at the University of Pennsylvania Health System (UPHS), an urban academic medical center. Participants were asymptomatic patients aged 50 to 75 years who were eligible for CRC screening or surveillance, had been referred for colonoscopy, and did not have a scheduled colonoscopy appointment. Data analysis was conducted from January to September 2019. Interventions: Patients underwent block randomization in a 1:1:1 ratio to 1 of 3 study arms. Participants in the usual care group were contacted via a mailed letter and instructed to call to schedule a colonoscopy. In the generic message group, participants were contacted by telephone, completed an assessment, and received a uniform, nontailored message encouraging colonoscopy scheduling. Participants in the tailored message group were contacted by telephone, completed an assessment, and received a tailored message encouraging colonoscopy scheduling based on their identified assessment cohort. Main Outcomes and Measures: The primary outcome was colonoscopy completion rate within 120 days of enrollment. The secondary outcome was colonoscopy scheduling rate appointment within 120 days of enrollment. Results: A total of 600 participants (median [IQR] age, 56 [51-63] years; 373 women [62.2%]) were enrolled, including 200 participants randomized to usual care, 200 participants randomized to the generic message, and 200 participants randomized to the tailored message. The total sample included 12 Asian participants (2.0%), 324 Black participants (54.0%), and 227 White participants (37.8%), and 9 participants (1.5%) were of Latino or Hispanic ethnicity. Colonoscopy completion was significantly higher for both the tailored message group (69 participants [34.5%]) and the generic message group (64 participants [32.0%]) compared with the usual care group (37 participants [18.5%]) (P < .001 and P = .002, respectively). Scheduling rates were also significantly higher in both groups, with 106 participants (53.0%) in the tailored message group and 105 participants (52.5%) in the generic message group scheduling appointments, compared with 54 participants (27.0%) in the usual care arm (P < .001 for both). Conclusions and Relevance: In this randomized clinical trial among individuals whose CRC screening was not up to date, both a tailored message intervention and a generic message intervention were significantly more effective at increasing colonoscopy scheduling and completion rates compared with usual care. These findings suggest that individualized health communications can increase individual motivation to obtain CRC screening. Trial Registration: ClinicalTrials.gov Identifier: NCT03310892.

A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States.

BACKGROUND & AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. METHODS: We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). RESULTS: Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). CONCLUSIONS: Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.

A Multimodal Interdisciplinary QI Intervention Is Associated with Reduction in After Hours Inpatient Endoscopy Cases.

BACKGROUND AND AIMS: Increasing demand for inpatient endoscopic services results in performing more non-emergent endoscopic cases after-hours, which poses risks to patient safety and negatively impacts patient and provider satisfaction. This study sought to quantify the existing state using quality improvement (QI) methodology, design targeted interventions, and determine their effectiveness. METHODS: We conducted an existing state evaluation through a process map, time-series study, and caseload analysis from 7/2017-12/2018. Using end-of-workday (EOW) as a proxy for patient/provider dissatisfaction and risk for patient safety events, we performed a prospective evaluation of a staged interdisciplinary multimodal intervention aimed to decrease the proportion of days with EOW after 7PM, decrease the proportion of cases begun after 5PM, and decrease EOW variability. The post-intervention period was 6/2019-2/2020. RESULTS: Based on existing state analyses, we implemented a series of targeted interventions: (1) provider workflow tips, (2) expedited transport for select patients, (3) pathway to reschedule appropriate cases to outpatient endoscopy, and (4) increased staffing for high caseload days through resource pooling. The proportion of days with EOW after 7PM decreased from 42.4% to 29.3% (caseload-adjusted odds ratio of 0.39, p< 0.001). Despite increased caseload, cases begun after 5PM decreased from 17.5% to 14.2% (OR 0.75, p = 0.009). EOW SD decreased from 2:20 hours to 1:36 hours. CONCLUSIONS: The multimodal intervention reduced days with EOW after 7PM and the proportion of cases begun after 5PM, despite increased caseload. This study shows how applying research methods to implement QI interventions successfully decreases late inpatient endoscopic cases.

EUS-based Pancreatic Cancer Surveillance in BRCA1/BRCA2/PALB2/ATM Carriers Without a Family History of Pancreatic Cancer.

Carriers of a pathogenic/likely pathogenic (P/LP) BRCA1/BRCA2/ATM/PALB2 variant are at increased risk of pancreatic ductal adenocarcinoma (PDAC), yet current guidelines recommend surveillance only for those with a family history of PDAC. We aimed to investigate outcomes of endoscopic ultrasound (EUS)-based PDAC surveillance in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC. We performed a retrospective analysis of all P/LP BRCA1/BRCA2/ATM/PALB2 carriers who underwent EUS at a tertiary care center. Of 194 P/LP BRCA1/BRCA2/ATM/PALB2 carriers who underwent EUS, 64 (33%) had no family history of PDAC and had at least 1 EUS for PDAC surveillance. These individuals underwent 143 total EUSs, were predominantly female (72%), and BRCA2 carriers (73%), with the majority having a personal history of cancer other than PDAC (67%). The median age at time of first EUS was 62 years [interquartile range (IQR), 53-67 years] and a median of 2 EUSs (IQR 1-3) were performed per patient, with a median of 3 years (IQR 2-4.5 years) between the first and last EUS for those with more than 1 EUS. Pancreatic abnormalities were detected in 44%, including cysts in 27%, and incidental luminal abnormalities in 41%. Eight percent developed a new pancreatic mass or cyst during surveillance, 2 individuals developed PDAC, and no serious complications resulted from surveillance. After discussion of the risks, limitations, and potential benefits, PDAC surveillance can be considered in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC; however, the effectiveness of PDAC surveillance in this population requires further study. PREVENTION RELEVANCE: BRCA1/BRCA2/ATM/PALB2 carriers have increased pancreatic ductal adenocarcinoma (PDAC) risk, yet are typically not eligible for PDAC surveillance in the absence of PDAC family history. Herein we describe outcomes of PDAC surveillance in BRCA1/BRCA2/ATM/PALB2 carriers without a family history of PDAC, showing that PDAC surveillance can be considered in this high-risk group.

Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion that EUS is superior. Demonstration of the cost-effectiveness of screening is important to implement screening in high-risk groups. METHODS: Results from centers with EUS-predominant screening were pooled to evaluate efficacy of index EUS in screening. A decision analysis model simulated the outcome of high-risk patients who undergo screening and evaluated the parameters that would make screening cost-effective at a US $100,000 per quality-adjusted life-year willingness to pay. RESULTS: One-time index EUS has a sensitivity of 71.25% and specificity of 99.82% to detection to detect high-risk lesions. Screening with index EUS was cost-effective, particularly at lifetime pancreatic cancer probabilities of greater than 10.8%, or at lower probabilities if life expectancy after resection of a lesion that was at least 16 years, and if missed, lesion rates on index EUS are 5% or less. CONCLUSIONS: Pancreatic cancer screening can be cost-effective through index EUS, particularly for those individuals at high-lifetime risk of cancer.