Ingrid C. Konings

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

Objective Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. Design Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. Results Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. Conclusions EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.

Repeated participation in pancreatic cancer surveillance by high-risk individuals imposes low psychological burden.

When assessing the feasibility of surveillance for pancreatic cancer (PC), it is important to address its psychological burden. The aim of this ongoing study is to evaluate the psychological burden of annual pancreatic surveillance for individuals at high risk to develop PC.

Prevalence and Progression of Pancreatic Cystic Precursor Lesions Differ Between Groups at High Risk of Developing Pancreatic Cancer

Objectives The aim of this study was to compare the prevalence of cystic pancreatic lesions and their natural behavior in 2 distinct high-risk groups for developing pancreatic ductal adenocarcinoma (PDAC): (1) carriers of a mutation that predisposes to PDAC and (2) individuals without a known gene mutation but with a family history of PDAC (familial pancreatic cancer [FPC]). Methods Pancreatic surveillance by annual magnetic resonance imaging and endoscopic ultrasound was performed in individuals with an estimated lifetime risk of developing PDAC of 10% or greater. Progression of a lesion was defined as growth 4 mm or greater or the development of worrisome features. Results We included 186 individuals: 98 mutation carriers and 88 FPC individuals (mean follow-up, 51 months). Individuals with FPC were significantly more likely than mutation carriers to have a pancreatic cyst 10 mm or greater (16% vs 5%, P = 0.045). Pancreatic cysts detected in mutation carriers, however, were significantly more likely to progress than those in FPC individuals (16% vs 2%, P = 0.050). Conclusions This study provides evidence that the prevalence and growth characteristics of pancreatic cysts differ between distinct high-risk groups: individuals with FPC have a higher prevalence of pancreatic cysts 10 mm or greater, whereas cysts in mutation carriers are more likely to progress. These observations may help to develop more optimally tailored surveillance strategies in specific high-risk populations.

Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer

Background and study aims  During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up. Patients and methods  Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed. Results  A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86 % (2012) and 81 % (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83 %. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β = – 1.6, P  = 0.005). Conclusions  This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.

Tu1905 Exploring the Relevance and Effect Size of Factors Associated With the Outcome of Pancreatic Cancer Screening in High-Risk Individuals

Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.