Prevalence of autoimmune pancreatitis in pancreatic resection for suspected malignancy: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer. METHODS: A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles. RESULTS: Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients). CONCLUSION: Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.

The role of aspirin in the prevention of pancreatic cancer: A nested case-control study in the UK Biobank.

BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort. METHODS: A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk. RESULTS: Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68-0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84-1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42-0.85] P = 0.004) compared to non-use. DISCUSSION: Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM.

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven. Objective: To compare the survival of patients with surveillance-detected PDAC with US national data. Design, Setting, and Participants: This comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023. Exposures: Endoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment. Main Outcomes and Measures: Stage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted. Results: A total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P < .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P < .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P < .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]). Conclusions and Relevance: These findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

Association between chronic pancreatitis and pancreatic cancer at a central hospital in KwaZulu-Natal, South Africa.

BACKGROUND: The frequency of histological chronic pancreatitis (CP) evidence in the resident pancreas of resected periampullary cancers (PACs) has never been studied in Africa. This study aims to describe the spectrum of pathology and outcomes of pancreatic surgeries and address this deficit from a South African central hospital cohort. METHODS: A retrospective audit of patients undergoing pancreatic surgery at Inkosi Albert Luthuli Central Hospital (IALCH) between 2003 and 2023 was conducted. The patient demographics, human immunodeficiency virus (HIV) status, histological subtypes, type and extent of surgery, and 30-day and overall mortality were captured from medical records. The presence of CP in the resident pancreas of patients resected for pancreatic and PAC was obtained from the pathology reports. RESULTS: Of the cohort, 72% were Africans, presenting at an earlier average age than other races. Surgery was performed on 126 (107 for cancer, 19 for CP) patients. Of these, 77 were pancreaticoduodenectomy (PD), of which 34 were for pancreatic ductal adenocarcinoma (PDAC). The prevalence of CP in the resident pancreas was 29.9%, and 55.9% in PDAC. Age was the only factor significantly associated with 30-day mortality, as well as long-term survival amongst patients with pancreatic and PAC. The overall median survival for patients with PAC was seven months; 11 patients are alive. CONCLUSION: In a predominantly African cohort undergoing pancreatic surgery, PDAC presents at a younger age. The high perioperative mortality and low overall survival (OS) in the setting of high CP prevalence in the resident pancreas requires further investigation of its role in the aetiopathogenesis and prognosis in PDAC.

Twenty-five years of surveillance for familial and hereditary pancreatic ductal adenocarcinoma: Historical perspectives and introduction to the special issue.

In the 1990s, as prevention became a central strategy in the battle against cancer and the molecular genetics revolution uncovered the genetic basis of numerous hereditary cancer syndromes, there were no options available for patients at increased risk of developing pancreatic cancer. When surveillance efforts for those at familial and hereditary risk of pancreatic cancer emerged in the late 1990s, it was uncertain if early detection was achievable.In this introduction to the special issue, we offer an overview of the history of surveillance for pancreatic cancer, including the first reports of familial pancreatic cancer in the medical literature, the initial results of surveillance in the United States and the initiation of surveillance programs for hereditary pancreatic cancer in the Netherlands.This special issue features a collection of 18 articles written by prominent experts in the field, focusing specifically on refining surveillance methodologies with the primary objective of improving care of high-risk individuals. Several reviews in this collection highlight improved survival rates associated with pancreas surveillance, underlying the potential of early detection and improved management in the continuing fight against pancreatic cancer.

The impact of the California state lockdown during the COVID-19 pandemic on management of patients with pancreatic ductal adenocarcinoma.

BACKGROUND AND OBJECTIVES: The SARS-COVID-19 pandemic significantly limited healthcare access. We sought to evaluate whether California's lockdown in March 2020 affected staging and time to treatment of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that patients diagnosed after the lockdown would have longer time to treatment and higher stage at presentation. METHODS: We retrospectively identified and categorized 1294 patients presenting to five University of California healthcare systems with a new diagnosis of PDAC into "pre-lockdown" and "post-lockdown" groups based on timing of pathologic diagnosis. RESULTS: In the 12 months pre-lockdown, 835 patients were diagnosed with PDAC, and 459 patients in the 6 months post-lockdown. Demographics, staging, and treatment type were similar between eras. There was a decreased male:female ratio post- versus pre-lockdown (0.97 vs. 1.25; p = 0.03). Time from symptom onset to first treatment was significantly increased among females post-lockdown (p = 0.001). However, overall time from diagnosis to first treatment was shorter in the post-lockdown era (median 23 vs. 26 days, p < 0.001). CONCLUSIONS: The COVID-19 lockdown did not significantly delay initial presentation, diagnosis, or treatment of newly diagnosed PDAC patients. Time from diagnosis to first treatment was shorter post-lockdown. Reduced healthcare utilization for minor complaints and increased telehealth utilization may have contributed.

The Population-Level Prevalence of Exocrine Pancreas Insufficiency and the Subsequent Risk of Pancreatic Cancer.

OBJECTIVES: The aim of this study was to study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk, and pancreatic enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching (PSM) of patients with EPI versus patients without an EPI diagnosis. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years. After PSM, PDAC risk among patients with EPI was twice as high compared with patients without EPI (aHR, 1.97; 95% CI, 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (adjusted odds ratio, 4.25; 95% CI, 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT. No difference was observed in PDAC risk between patients with EPI on PERT and those not on PERT (aHR, 1.10; 95% CI, 0.95-1.26; P = 0.17). CONCLUSIONS: Despite a low prevalence, patients with EPI may have a higher risk of PDAC, and majority with EPI were not on PERT. PERT did not impact incident PDAC risk after an EPI diagnosis.

Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis.

OBJECTIVE: Cost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies. DESIGN: Retrospective analysis of 926 presumed BD-IPMNs lacking worrisome features (WFs)/high-risk stigmata (HRS) under surveillance. Charlson Comorbidity Index (CACI) defined the severity of comorbidities. IPMN relevant changes included development of WF/HRS, pancreatectomy or death for IPMN or pancreatic cancer. Pancreatic malignancy-unrelated death was recorded. Cumulative incidence of IPMN relevant changes were estimated using the competing risk approach. RESULTS: 5-year cumulative incidence of relevant changes was 17.83% and 1.6% developed pancreatic malignancy. 5-year cumulative incidences for IPMN relevant changes were 13.73%, 19.93% and 25.04% in low-risk, intermediate-risk and high-risk groups, respectively. Age ≥75 (HR: 4.15) and CACI >3 (HR: 3.61) were independent predictors of pancreatic malignancy-unrelated death. 5-year cumulative incidence for death for other causes was 15.93% for age ≥75+CACI >3 group and 1.49% for age <75+CACI ≤3. 5-year cumulative incidence of IPMN relevant changes were 13.94% in patients with age <75+CACI ≤3 compared with 29.60% in those with age ≥75+CACI >3. In this group 5-year rate of malignancy-free patients was 95.56% with a 5-year survival of 79.51%. CONCLUSION: Although it is not uncommon the occurrence of changes considered by current guidelines as relevant during surveillance of low risk BD-IPMNs, malignancy rate is low and survival is significantly affected by competing patients' age and comorbidities. IPMN surveillance strategy should be tailored based on these features and modulated over time.

The impact of the COVID-19 pandemic on patients with pancreatic cancer.

BACKGROUND: It remains unclear today whether the poor prognosis of pancreatic ductal adenocarcinoma (PDAC) was further worsened by the COVID-19 pandemic and whether this may affect providers and patients, today. Hence, this study aimed to investigate the effect of COVID-19 on care delivery and outcomes of patients with PDAC in the United States. METHODS: The National Cancer Database was queried for PDAC, between 2017 and 2020. Changes in the number of diagnoses and treatment patterns were compared annually for the entire cohort. Changes in surgical outcomes and median time from diagnosis to treatment were compared and analyzed. Chi-square, Mann-Whitney U, and Kruskal-Wallis tests were performed. RESULTS: Of 127,613 patients with PDAC, PDAC diagnoses from 2017 (30,573) to 2019 (33,465) increased but decreased in 2020 (31,218). The number of patients receiving surgery or radiotherapy was stable between 2017 to 2019 (21.75% ± 0.05% and 13.9% ± 0.3%, respectively) but decreased in 2020 (20.7% and 12.4% respectively). Although patients received chemotherapy with increasing frequently from 2016 (60.7%) to 2019 (63.5%), this trend stopped in 2020 (63%). Of 27,490 patients undergoing surgery, the mean time from diagnosis to surgery increased from 2017 (34 days) to 2019 (56 days), with an increase in delay in 2020 (81 days). Moreover, patients who were tested for COVID-19, had a longer median time from diagnosis to surgery even if tested negative (COVID+, 140 days; COVID-, 112 days; P < .001). CONCLUSION: Although the oncologic quality of PDAC surgery remained the same during the pandemic, not only did the pandemic lead to an underdiagnosis of PDAC and care delays, but even the suspicion of COVID-19 in patients with a negative test adversely affected their care.

Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

Comparative effectiveness of chemotherapy in different histological types of pancreatic cancer: a PSM-based study using the SEER database.

This study aimed to compare the effectiveness of chemotherapy in different histological types of pancreatic cancer using data collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who were diagnosed with pancreatic cancer between 2004 and 2015 were selected from the SEER database. Propensity score matching (PSM) was employed to minimize the selection bias. The Kaplan-Meier survival curves and the log-rank test were utilized to compare the overall survival (OS) and cancer-specific survival (CSS) among different groups. Of the 7,653 pancreatic cancer patients, both OS and CSS were higher in the chemotherapy group than those in the non-chemotherapy group (p < 0.001). After PSM, 2381 pairs were generated. The Kaplan-Meier survival curved indicated that both OS and CSS for pancreatic ductal adenocarcinoma (PDAC), pancreatic adenosquamous carcinoma (PASC), and pancreatic mucin-producing adenocarcinoma (PMPAC) (p < 0.001) in the chemotherapy group were superior to those in the non-chemotherapy group, while there was no significant difference in pancreatic mucinous adenocarcinoma (PMAC) (p = 0.2586). Compared with PASC and PMPAC, PDAC exhibited longer OS and CSS. The results of statistical analysis showed that PASC tumors were mainly poorly differentiated, and the majority of patients with PMPAC had distant metastasis. Chemotherapy could prolong pancreatic cancer patients' survival, especially for patients with advanced disease. PMPAC patients had a higher rate of metastasis, accompanying with the worse survival.

Medicaid Expansion Increases Access for Rural and Impoverished Patients with Pancreatic Ductal Adenocarcinoma in Southern States.

INTRODUCTION: Medicaid expansion (ME) impacted patients when assessed at a national level. However, of the 32 states in which Medicaid expansion occurred, only 3 were Southern states. Whether results apply to Southern states that share similar geopolitical perspectives remains elusive. We aimed to assess the impact of ME on pancreatic ductal adenocarcinoma (PDAC) treatment in eight Southern states in the USA. PATIENTS AND METHODS: We identified uninsured or Medicaid patients (age 40-64 years) diagnosed with PDAC between 2011 and 2018 in Southern states from the North American Association of Central Cancer Registries-Cancer in North America (NAACCR-CiNA) research dataset. Medicaid-expanded states (MES; Louisiana, Kentucky, and Arkansas) were compared with non-MES (NMES; Tennessee, Alabama, Mississippi, Texas, and Oklahoma) using multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: Among 3036 patients, MES significantly increased odds of Medicaid insurance by 36%, and increased proportions of insured Black patients by 3.7%, rural patients by 3.8%, and impoverished patients by 18.4%. After adjusting for age, race, rural-urban status, poverty status, and summary stage, the odds of receiving radiation therapy decreased by 26% for each year of expansion in expanded states (P = 0.01). Last, ME did not result in a significant difference between MES and NMES in diagnosing early stage disease (P = 0.98) nor in receipt of chemotherapy or surgery (P = 0.23 and P = 0.63, respectively). CONCLUSIONS: ME in Southern states increased insurance access to traditionally underserved groups. Interestingly, ME decreased the odds of receiving radiation therapy yearly and had no significant impact on receipt of chemotherapy or surgery.

Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study.

Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.

Metabolic Syndrome Accelerates the Age-Related Increase of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

OBJECTIVES: Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. METHODS: A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. RESULTS: Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28-3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14-6.72; P = 0.003). CONCLUSIONS: The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.

The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants.

BACKGROUND: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance. METHODS: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC. RESULTS: A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance. CONCLUSIONS: Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage.

Risk perception and surveillance uptake in individuals at increased risk for pancreatic ductal adenocarcinoma.

BACKGROUND: Surveillance for pancreatic ductal adenocarcinoma (PDAC) is recommended for high-risk individuals with genetic variants in PDAC-associated genes and/or family history. Surveillance uptake and adherence may depend on the perception of PDAC risk and cancer worry. We aimed to determine PDAC risk perception in at-risk individuals and assess factors associated with PDAC surveillance uptake. METHODS: At-risk individuals identified from a prospective academic registry were sent a survey electronically. PDAC risk perception, cancer worry and surveillance uptake were surveyed. Factors associated with increased risk perception and surveillance were assessed. Five-year PDAC risk was calculated using the PancPRO risk assessment model, and correlation with subjective risk assessment was assessed. RESULTS: The overall survey response rate was 34% (279/816). The median perceived PDAC risk was twofold (IQR 1-4) above respondents' estimates of general population risk. Factors significantly associated with higher perceived PDAC risk included non-Hispanic white race, post-graduate education level, PDAC-affected first-degree relative, genetic variants and lack of personal cancer history. Cancer worry had a very weak correlation across PDAC risk estimates (r=0.16). No correlation between perceived PDAC risk and 5-year calculated PDAC risk was found. Older age, having a first-degree relative with PDAC, meeting with a medical provider about PDAC cancer risk and awareness of surveillance modalities were significant predictors of undergoing PDAC surveillance. CONCLUSIONS: Individuals at risk for PDAC do not report risk perception that correlates with calculated risk. This presents an opportunity for counselling of at-risk patients to individualise management and improve surveillance uptake for eligible individuals.

Risk Factors for Progression in Patients Undergoing Surveillance for Pancreatic Cysts.

OBJECTIVE: To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. BACKGROUND: Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. METHODS: We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. RESULTS: The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR=1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR=1.89; 95% CI: 1.34-2.66) were associated with progression. CONCLUSIONS: Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies.

Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk.

BACKGROUND AND AIMS: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. METHODS: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. RESULTS: A total of 457 HRIs were followed for 48 (range 2-172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%-64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). CONCLUSIONS: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

Risk factors for early-onset pancreatic ductal adenocarcinoma: A systematic literature review.

BACKGROUND: Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in population exposures and lifestyles. PATIENTS AND METHODS: We conducted a PRISMA-standard systematic literature review to identify non-heritable risk factors for early-onset pancreatic ductal adenocarcinoma (PDAC) (PROSPERO number: CRD42022299397). Systematic searches of MEDLINE and Embase bibliographic databases were performed (January 2022), and publications were screened against predetermined eligibility criteria; data were extracted using standardised data fields. The STROBE checklist was used to assess the completeness of reporting as a proxy for publication quality. Data were categorised by risk factor and analysed descriptively. RESULTS: In total, 24 publications were included. All publications reported observational study data; thresholds for age group comparisons ranged between 40 and 65 years. Lifestyle factors investigated included smoking, alcohol consumption, obesity, physical inactivity, meat intake, socioeconomic status and geographical residence. Clinical factors investigated included pancreatitis, diabetes/insulin resistance, prior cancer and cancer stage at diagnosis, hepatitis B infection, metabolic syndrome and long-term proton pump inhibitor exposure. Publication STROBE scores were 6-21 (maximum, 22). Eight studies reported results adjusted for confounders. Potential non-heritable risk factors for early-onset PDAC that warrant further investigation included smoking, alcohol consumption, pancreatitis and hepatitis B infection. CONCLUSION: Evidence for non-heritable risk factors for early-onset PDAC is heterogeneous, but four factors were identified that might aid the identification of at-risk individuals who may benefit from screening and risk reduction strategies.

Surveillance Outcome and Genetic Findings in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRIs) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs. METHODS: A total of 239 HRIs from 202 families were tested genetically and underwent prospective pancreatic surveillance for 6 years. RESULTS: The cohort was divided into 3 groups: familial pancreatic cancer (FPC; 70 individuals, 54 families), familial non-FPC (81 individuals, 73 families), and hereditary pancreatic cancer (PC) (88 individuals, 75 families). PGVs were detected in 37.6% of all families, including 11.1% of FPC families and 9.6% of familial non-FPC families. The hereditary PC group had earlier onset of PDAC compared with the other 2 groups. BRCA2 PGV carriers showed earlier onset of PDAC and pancreatic cysts. Of the 239 HRIs, PDAC was detected in 11 individuals (4.6%), with 73% diagnosed at an early stage; 4 (1.67%) had pancreatic neuroendocrine tumor; 6 (2.5%) had main-duct intraductal papillary neoplasm (IPMN); and 41 (17.15%) had side-branch IPMN. Seventeen individuals were referred to surgery, and 12 were alive at the end of the study. DISCUSSION: The percentage of PDAC was similar in the 3 groups studied. The hereditary PC group, and particularly BRCA2 PGV carriers, had an earlier age of PDAC onset. PGVs were detected in a significant percentage of HRIs with PC. Surveillance seems effective for detection of early-stage PDAC and precursor lesions.