Global Prevalence of Pancreatic Cystic Lesions in the General Population on Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Understanding the burden of pancreatic cystic lesions (PCLs) in the general population is important for clinicians and policymakers. In this systematic review, we sought to estimate the global prevalence of PCLs using magnetic resonance imaging (MRI) and to investigate factors that contribute to its variation. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central, from database inception through February 2023. We included full-text articles that reported the prevalence of PCLs using MRI in the general population. A proportional meta-analysis was performed, and the prevalence of PCLs was pooled using a random-effects model. RESULTS: Fifteen studies with 65,607 subjects were identified. The pooled prevalence of PCLs was 16% (95% confidence interval [CI], 13%-18%; I2 = 99%), most of which were under 10 mm. Age-specific prevalence of PCLs increased from 9% (95% CI, 7%-12%) at 50 to 59 years, to 18% (95% CI, 14%-22%) at 60 to 69 years, 26% (95% CI, 20%-33%) at 70 to 79 years, and 38% at 80 years and above (95% CI, 25%-52%). There was no difference in prevalence between sexes. Subgroup analysis showed higher PCL prevalence when imaging findings were confirmed by independent radiologist(s) (25%; 95% CI, 16%-33%) than when chart review alone was used (5%; 95% CI, 4%-7%; P < .01). There was no independent association of PCL prevalence with geographic location (Europe, North America, or Asia), MRI indication (screening vs evaluation of non-pancreatic pathology), enrollment period, sample size, magnet strength (1.5 vs 3 tesla), and MRI sequence (magnetic resonance cholangiopancreatography vs no magnetic resonance cholangiopancreatography). CONCLUSION: In this systematic review, the global prevalence of PCLs using a highly sensitive noninvasive imaging modality ranged between 13% and 18%.

Tracking incidentally discovered pancreatic cysts smaller than 30 mm: Natural course and predictors of malignancy.

BACKGROUND AND AIMS: The aim of this study was to assess the natural course and predictors of malignancy in incidentally detected small pancreatic cysts (PCs). METHOD: We retrospectively included patients with PCs smaller than 30 mm followed up with the same cross-sectional imaging modality at least 12 months apart between January 2010 and December 2019 in three academic institutions. Cyst growth, pancreatic cancer incidence, and associated factors associated with pancreatic cancer were analyzed. RESULTS: A total of 1109 patients were followed up for a median of 34 months (range, 12‒118 months). Cyst growth and rapid cyst growth (≥ 5 mm/2 years) during follow-up were observed in 20.7% and 8.3%, respectively, both with higher rates for 15‒30 mm sized PCs. Eight patients were diagnosed with pancreatic cancer. The standardized incidence ratio for pancreatic cancer in small PCs was calculated as 5.2 [95% Confidence interval (CI): 1.3‒20.5].  The development of pancreatic cancer was associated with rapid growth [hazard ratio (HR): 8.1, 95% CI: 1.5‒43.4, p = 0.015] and newly developed worrisome features (HR: 11.7, 95% CI: 1.7‒79.6, p = 0.012) in competing risk analysis. CONCLUSIONS: One-fifth of small incidentally detected PCs increased in size. Rapid growth and newly developed worrisome features were predictors of malignancy.

Relationship Between Pancreatic Cysts and Cysts in Other Organs in Patients Undergoing Medical Checkup.

OBJECTIVE: We investigated the association between pancreatic cysts and cystic diseases of other organs using abdominal ultrasonography in patients undergoing medical checkup. METHODS: Between April 2021 and March 2022, 4496 patients had a comprehensive medical checkup at our hospital, which included abdominal ultrasonography. RESULTS: Among 4496 patients, 172 (3.8%), 1592 (35.4%), and 1425 (31.7%) had pancreatic, liver, and renal cysts, respectively. Multivariate analysis revealed that the significant factors were female sex and the presence of renal cysts. CONCLUSION: Pancreatic cysts were more common in females. Renal cysts are relatively commonly detected on abdominal ultrasonography. If renal cysts are detected, comorbidities with pancreatic cysts should be considered.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm.

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model.

BACKGROUND & AIMS: Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. METHODS: A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration). RESULTS: Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. CONCLUSIONS: Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.

A Novel Scoring System to Improve the Detection Efficiency of Pancreatic Cystic Lesions in the General Population.

Objective Pancreatic cystic lesions (PCLs) are known risk factors for pancreatic cancer. Therefore, this study explored the predictors identifying PCLs in a general population and developed a scoring system to help more efficiently diagnose these entities during medical checkups. Methods We reviewed 9,369 examinees of abdominal ultrasound (AUS) during medical checkups between January 2013 and November 2019. Predictors of PCLs were identified using a multivariate logistic regression analysis, and we constructed a scoring system based on these predictors. Results PCLs were detected in 118 (1.3%). Age 50-59 years old [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.18-5.35], 60-69 years old (OR 3.91, 95% CI 1.86-8.26), and ≥70 years old (OR 10.5, 95% CI 5.03-21.7) as well as abdominal pain (OR 1.85, 95% CI 1.14-3.00), alcohol consumption (OR 1.72, 95% CI 1.03-2.89), a family history of pancreatic cancer (OR 2.41, 95% CI 1.09-5.34), and pre-diabetes or diabetes (OR 1.78, 95% CI 1.05-3.00) were predictors of PCLs. The following scores were assigned according to regression coefficients: age (50-59 years old, 1 point; 60-69 years old, 1.5 points; ≥70 years old, 2.5 points); abdominal pain, 1 point, alcohol consumption, 1 point; a family history of pancreatic cancer, 1 point; and pre-diabetes, 1 point. The PCL detection rate increased with the total score: 0.2% for total score 0 point, 5.4% for ≥4.0 points. The area under the curve of the scoring system was 0.75 (95% CI 0.70-0.79). Conclusion Our scoring system allows the risk of PCLs to be determined and may help more efficiently diagnose these entities.

Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.

Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data.

BACKGROUND: Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data. METHODS: Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. RESULTS: The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018. CONCLUSIONS: The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

Diabetes mellitus and the risk of progression or malignancy of pancreatic cystic neoplasms in patients undergoing surveillance: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Patients with pancreatic cystic neoplasms (PCN) generally undergo surveillance by cross-sectional imaging or endoscopic-ultrasound due to their pre-malignant potential. Appearance of certain cyst characteristics during surveillance is associated with aggressive behavior or presence of malignancy. Patient characteristics associated with progression or induction of malignancy in PCN is unclear from current studies. We performed this meta-analysis to determine the patient characteristics associated with progression or malignancy in patients with PCN who undergo surveillance. METHODS: We performed a systematic research of several electronic databases for all the studies on surveillance of PCN which reported demographic data of patients who had progression or malignancy and controls. We calculated Risk ratio (RR) or Hazard ratio (HR) with 95% confidence interval (CI) for each variable. Mantel- Haenszel method or Inverse-variance model was used to pool data of progression or malignant transformation into fixed or random effect model meta-analysis. RESULTS: 11observational studies, 4 assessing risk factors for malignancy (3955 patients) and 7 evaluating risk factors for progression of PCN (3144 patients) were included in the meta-analysis. Diabetes mellitus was associated with higher risk for malignant transformation as well as progression of PCN (RR = 1.54, CI 1.23, 1.92). Advanced age was associated with higher risk of progression. Male gender had higher risk for malignant transformation but not progression of PCN. CONCLUSION: Diabetes is associated with an increased risk of both malignancy and progression of PCN in patients who undergo surveillance. Advanced age is also associated with higher risk of progression of PCN.

Analysis of Comorbidity for Patients with Pancreatic Cysts in Medical Checkup Screening.

OBJECTIVES: We investigated whether there is a difference in the frequency of comorbidity between patients with pancreatic cysts and those without pancreatic cysts by abdominal ultrasonography in patients undergoing medical checkup screening. METHODS: The subjects were 6,627 patients who underwent abdominal ultrasonography at Tokai University Hachioji Hospital's Health Screening Center between April 2019 and March 2020. RESULTS: Of the total 6,627 patients, 158 (2.4%) were pointed out to have pancreatic cysts. Multivariate analysis revealed that the related factors were female sex, age 60 years or older, diabetes, lung cancer, and uterine/ovarian cancer. CONCLUSION: Unlike pancreatic cancer, pancreatic cysts are more common in women. In addition, it is known that pancreatic cysts have a high complication rate of cancers of other organs; lung cancer and uterine/ovarian cancer were identified as high-risk factors in this study.

Pancreatic Incidentalomas on CT Colonography: Ignore, Follow up or Investigate?

Background: Increasing use of cross-sectional abdominal imaging such as CT colonography (CTC), has resulted in increased identification of incidental pancreatic cystic lesions. Such incidental findings are a cause for anxiety amongst patients and clinicians and can result in increased cost to healthcare delivery resultant from referral to subsequent investigations. Our study explored the prevalence of incidental cystic pancreatic lesions on CTC at a tertiary pancreatic centre, and their management. Methods: A detailed review of CTC reports and patient case notes between 2010-2016 was undertaken. Patients from both screening (National Bowel Cancer Screening) and non-screening cohorts were included in our study. Results: 136 of 4666 patients who underwent CTC had an incidental finding of a pancreatic lesion (2.9%) and 117 confirmed cystic pancreatic lesions (2.5%). Radiological diagnosis of intraductal papillary mucinous neoplasm (IPMN) was available in the CTC report for 71 patients. Twelve patients (0.2%) were found to have pancreatic ductal adenocarcinoma (PDAC) incidentally at CTC, 2 resectable and 10 unresectable with the diagnosis confirmed on biopsy. Follow-up surveillance imaging recommendations were made for 39.3% of patients within one year of the diagnosis of a cystic pancreatic lesion on CTC. One patient with pancreatic duct dilatation of 7mm was lost in follow-up and was found to develop PDAC at 21 months. Conclusions: Pancreatic lesions are increasingly found incidentally on CTC. All patients with pancreatic cystic tumour should be referred to pancreatic multidisciplinary team for discussion to determine management pathway.

Incidence and Risk Factors for New-Onset Diabetes Mellitus After Surgical Resection of Pancreatic Cystic Lesions: A MarketScan Study.

OBJECTIVES: There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs. METHODS: We utilized the IBM MarketScan Database (2012-2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs. Patients with any other pancreatic disease were excluded. We performed Kaplan-Meier analysis and multivariable Cox proportional hazards regression to define the incidence and risk factors of postoperative NODM. RESULTS: Among 311 patients, the overall risk (95% confidence interval) of NODM was 9.1% (6.3-12.9%), 15.1% (11.3-20.2%), and 20.2% (15.3-26.4%) at 6, 12 and 24 months, respectively. Multivariable analysis (adjusted hazard ratio; 95% confidence interval) revealed that older age (1.97; 1.04-3.72; 55-64 vs 18-54 years), obesity (2.63; 1.35-5.12), hypertension (1.79; 1.01-3.17), and cardiovascular disease (2.54; 1.02-6.28) were independent predictors of NODM. Rates of NODM were similar after distal pancreatectomy versus pancreaticoduodenectomy. CONCLUSIONS: Within 2 years, 1 in 5 patients without any other pancreatic disease will develop NODM after partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counseling and intensive postoperative monitoring, education, and treatment for diabetes mellitus.

Incidence of pancreatic cancer during long-term follow-up in patients with incidental pancreatic cysts smaller than 2 cm.

PURPOSE: To assess the long-term malignancy risk of incidental small pancreatic cysts. MATERIALS AND METHODS: In this HIPAA-compliant, IRB-approved, retrospective, multi-institutional study, the long-term incidence of pancreatic cancer was compared between patients with and without small pancreatic cysts. Patients with incidental pancreatic cysts ≥ 0.5 and < 2.0 cm in maximal diameter, detected on MRI performed between 1999 and 2011, represented the "small pancreatic cyst" group. Patients that underwent MRI between 2005 and 2011 and had no reported pancreatic cysts represented the comparison "no cyst" group. RESULTS: The "small pancreatic cyst" group included 267 patients, ages 63.4 ± 11.8 years, 166/267 (62%) women with a mean follow-up of 8.6 ± 4.3 years, median 9.2 years; the "no cyst" group included 1,459 patients, ages 64.6 ± 12 years, 794/1,459 (54%) women with a mean follow-up of 7.0 ± 4.2 years, median 7.8 (p values 0.12, 0.02, < 0.001, respectively). Two/267 (0.7%) patients developed pancreatic cancer at a separate location from the known cyst in the "small pancreatic cyst" group, with a cancer rate of 0.9 (95% CI 0.1-3.1) cases per 1,000 patient-years. In the "no cyst" cohort, 18/1,459 (1.2%) patients developed pancreatic cancer, with a cancer rate of 1.8 (95% CI 1.2-3.1) cases per 1,000 patient-years (p = 0.6). The all-cause mortality was similar in both groups: 57/267 (21%) vs. 384/1,459 (26%) (p = 0.09). CONCLUSION: The long-term risk of pancreatic malignancy in asymptomatic patients with incidental pancreatic cysts less than 2 cm is 0.9 cases per 1,000 patient-years of follow-up, similar to those without pancreatic cysts. These very few pancreatic cancers developed at a separate location from the known cyst. KEY POINTS: • After a median of 9.2 years of follow-up, the risk of pancreatic malignancy in patients with an asymptomatic small pancreatic cyst was 0.9 cases per 1,000 patient-years of follow-up, similar to those without pancreatic cysts. • Very few pancreatic cancer cases developed in the location separate from the known pancreatic cyst.

Pancreas Cancer Incidence and Pancreas Cancer-Associated Mortality Are Low in National Cohort of 7211 Pancreas Cyst Patients.

BACKGROUND AND AIMS: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. METHODS: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. RESULTS: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). CONCLUSIONS: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

Current trends in the management of pancreatic cystic neoplasms in Korea: a national survey.

BACKGROUND/AIMS: The study aimed to investigate the current practice patterns in the management of pancreatic cystic neoplasms in Korea. METHODS: An electronic survey was systematically distributed by email to members of the Korean Pancreatobiliary Association from December 2019 to February 2020. RESULTS: In total, 115 (110 gastroenterologists, five surgeons) completed the survey, 72.2% of whom worked in a tertiary/academic medical center. Most (65.2%) followed the 2012/2017 International Association of Pancreatology guidelines for the management of pancreatic cystic neoplasms. A gadolinium-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography was the most common first-line diagnostic modality (42.1%), but a contrast-enhanced computed tomography scan was preferred as a subsequent surveillance tool (58.3%). Seventy-four percent of respondents routinely performed endoscopic ultrasound-guided fine needle aspiration for pancreatic cystic neoplasms with suspicious mural nodules. Endoscopic ultrasound-guided fine needle aspiration cytology (94.8%) and cystic fluid carcinoembryonic antigen (95.7%) were used for cystic fluid analysis. Most (94%) typically recommended surgery in patients with high-risk stigmata, but 18.3% also considered proceeding with surgery in patients with worrisome features. Most (96.5%) would continue surveillance of pancreatic cystic neoplasms for more than 5 years. CONCLUSION: According to this survey, there was variability in the management of pancreatic cystic neoplasms among the respondents. These results suggest that the development of evidence-based guidelines for pancreatic cystic neoplasms that fit the Korean practice is needed to create an optimal approach to the management of pancreatic cystic neoplasms.

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance.

BACKGROUND & AIMS: The Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among "low-risk" mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes. METHODS: A single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis. RESULTS: 502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group. CONCLUSION: Through real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.

Prevalence, Incidence, and Risk of Progression of Asymptomatic Pancreatic Cysts in Large Sample Real-world Data.

OBJECTIVES: Using large-sample, real-world administrative claims data, we evaluated the prevalence of putatively asymptomatic pancreatic cysts, the historical growth in their incident diagnosis, and their risk of malignant progression. METHODS: Data were sourced from IBM MarketScan administrative claims databases of more than 200 million patients. Period prevalence was assessed using 700,000 individuals without conditions that predispose to pancreatic cyst. The standardized cumulative incidence was compared with the cross-sectional abdominal imaging rate from 2010-2017. The risk of progression to pancreatic cancer for 14,279 newly diagnosed patients with a cyst was estimated using Kaplan-Meier analysis. RESULTS: Standardized prevalence increased exponentially with age and was 1.84% (95% confidence interval, 1.80%-1.87%) for patients older than 45. Standardized incidence nearly doubled from 2010-2017 (6.3 to 11.4 per 10,000), whereas the imaging rate changed from only 8.0% to 9.4%. The cumulative risk of pancreatic cancer at 7 years was 3.0% (95% confidence interval, 2.4%-3.5%), increasing linearly (R2 = 0.991) with an annual progression risk of 0.47%. CONCLUSIONS: Using large-sample data, we show a significant burden of asymptomatic pancreatic cysts, with an annual risk of progression to cancer of 0.47% for 7 years. Rapid growth in cyst diagnosis over the last decade far outpaced increases in the imaging rate.

High-Risk Characteristics Associated with Advanced Pancreatic Cystic Lesions: Results from a Retrospective Surgical Cohort.

BACKGROUND AND AIM: The management of pancreatic cystic lesions (PCLs) remains controversial. We performed a retrospective study to determine characteristics associated with advanced PCLs (A-PCLs) and whether these characteristics vary in different pathological types of PCLs. The additional diagnostic value of endoscopic ultrasound (EUS) was also evaluated. METHODS: Patients who underwent surgical resection for an identified PCLs by imaging modalities were included. A logistic regression model was developed to identify significant characteristics for A-PCLs. EUS data was assessed separately. RESULTS: Three hundred and fifty-three patients were included, and 125 patients (35.4%) were A-PCLs. The presence of main pancreatic duct (MPD) diameter ≥ 10 mm (odds ratio [OR], 11.7; 95% confidence interval [CI], 1.53-89.2; P = 0.018), mural nodules ≥ 5 mm (OR, 11.67; 95% CI, 2.3-59.05; P = 0.003), solid components within cysts (OR, 30.87; 95% CI, 7.23-131.7; P < 0.0001) and high serum CA19-9 levels (OR, 1.006; 95% CI, 1.001-1.011; P = 0.02) were independently associated with the presence of A-PCLs. The presence of septa was independently associated with the presence of non-A-PCLs (OR, 0.147; 95% CI, 0.04-0.6; P = 0.008). Males who had a history of tobacco abuse (P < 0.0001) and had a greatly dilated MPD (P < 0.0001) were more common in advanced intraductal papillary mucinous neoplasms (IPMC) patients. Solid pseudopapillary neoplasm (SPT) often occurred in young women (P < 0.0001), mostly asymptomatically (P < 0.0001) and with lower serum CA19-9 levels (P < 0.0001). In the 124 patients who underwent EUS-guided fine-needle aspiration (EUS-FNA), five additional characteristics (4 mural nodules and 1 MPD involvement) were identified by EUS imaging and 17 patients were identified with abnormal cytological results (13 atypical cells and 4 suspicious for malignancy cells) by EUS-FNA. CONCLUSION: On the basis of a retrospective study with large sample size, the presence of MPD ≥ 10 mm, mural nodules, solid components, and high serum CA19-9 levels were independently associated with the presence of A-PCLs. The high-risk characteristics may vary across different types of A-PCLs. EUS and EUS-FNA could provide additional diagnostic information for PCLs.

Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis.

BACKGROUND: Discontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated. METHODS: We performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS). RESULTS: Of 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12-23) vs. 12 (9-17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4-6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively. CONCLUSIONS: Incidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients' overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.

Comparing the clinical impact of pancreatic cyst surveillance programs: A trial of the ECOG-ACRIN cancer research group (EA2185).

BACKGROUND: The optimal surveillance strategy for pancreatic cysts, which occur in up to 20% of the adult population, is ill defined. The risk of malignant degeneration of these cysts is low, however the morbidity and mortality associated with pancreatic cancer are high. Two clinical surveillance guidelines are in regular use. Both the Fukuoka and American Gastroenterological Association (AGA) guidelines rely on radiographic and endoscopic imaging. They differ primarily in their recommended frequencies of interval surveillance imaging. While evidence driven clinical guidelines should promote higher quality care, competing guidelines on the same topic may provide discordant recommendations and potential reduction in the quality and/or value of care. OBJECTIVES: The primary objective is to compare the clinical effectiveness of the two surveillance guidelines to identify patients most likely to benefit from pancreatic resection. Secondary objectives include comparison of resource utilization, patient reported outcomes, incidental findings are other clinical outcomes. METHODS: 4606 asymptomatic patients with newly identified pancreatic cysts ≥1 cm in diameter will be randomized 1:1 to high intensity (Fukuoka) or low intensity (AGA) surveillance. All participants will be followed prospectively for 5 years. CONCLUSION: Differing guidelines confuse providers, patients and policymakers. This large, prospective, randomized trial will compare the clinical effectiveness and resource allocation requirements of two guidelines addressing a common clinical entity. CLINICALTRIALS. GOV IDENTIFIER: NCT04239573.