Surveillance of Individuals at High Risk for Developing Pancreatic Cancer

__Abstract__ We still face great difficulties to treat and cure patients with pancreatic ductal adenocarcinoma (henceforth referred to as pancreatic cancer). The survival is dismal even in those who undergo intended curative surgery in case of a localized tumor. Despite the relatively low incidence of 9-12 per 100.000 per year in Western populations (approximate lifetime-risk 1.0%), pancreatic cancer is ranked among the to

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

International cancer of the pancreas screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screeni

Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance

It is important to adequately and timely identify individuals with cancer worries amongst participants in a pancreatic ductal adenocarcinoma (PDAC) surveillance program, because they could benefit from psychosocial support to decrease distress. Therefore, the aim of this study was to assess both psychosocial and clinical factors associated with cancer worries. High-risk individuals participating in PDAC-surveillance were invited to annually complete a cancer worry scale (CWS) questionnaire which was sent after counseling by the clinical geneticist (T0), after intake for participation in PDAC-surveillance (T1), and then annually after every MRI and endoscopic ultrasonography (EUS) (T2 and furth

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaff

Identifying key factors for the effectiveness of pancreatic cancer screening

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: −57% for “Progressive-only” vs −41% for “Indolent Included”). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.</p

Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance

Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. We included 144 PJS patients (49% male) from 61 families (5640 person years follow-up). Seven (5%) patients developed PC at a median age of 54 years. Four patients (3%) were diagnosed with distal bile duct (n=2) or ampullary cancer (n=2) at a median age of 55 years. The cumulative risk for PC was 26% (95% CI 4% to 47%) at age 70 years and relative risk was 76 (95% CI 36 to 160; p <0.001). The cumulative risk for pancreatico-biliary cancer was 32% (95% CI 11% to 52%) at age 70 years, with a relative risk of 96 (95% CI 53 to 174; p <0.001). PJS patients have a highly increased risk for pancreatico-biliary cancer. Therefore, patients are eligible for surveillance within well defined research programmes to establish the benefit of such surveillanc

Pancreatic cancer risk in Peutz-Jeghers syndrome patients: A large cohort study and implications for surveillance

Background Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. Methods PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. Results We included 144 PJS patients (49% ma