Introduction

The prognosis for pancreatic cancer is poor, it is an aggressive cancer and comes with few or unspecific symptoms. Diagnosis at an early stage is vital for survival and chance for curative treatment. Surveillance programs for high-risk individuals, so called, “individuals at risk” are therefore of utter importance. However, there is limited data on the psychological burden within participants of these programs.

Aims & Methods

The aim was to investigate the psychological burden for participants in a pancreatic cancer surveillance program. Additionally, this study aimed to explore whether psychological burden was related to the individual’s risk-level for pancreatic cancer.

Results

In total, 278 patients answered the questionnaire. Results indicated high cancer worry among respondents with high scores on CWS (mean=16.45). A majority of 69.3% had scores indicating high cancer worry (cut-off >= 14). Anxiety was not equally high among respondents (mean STAI-T = 35.13; STAI-S=35.9). Female gender and younger age were significantly correlated with higher cancer worry and anxiety (Chi2-tests and linear regression analysis). Outcomes in coping and perceived health were similar to normative populations.

Conclusion

Cancer worry is particularly high within participants, among these women and younger individuals have more cancer worry and anxiety. No correlation was found between risk-level and psychological burden.

Disclosure

no

Introduction

Pancreatic cancer surveillance in high-risk individuals has demonstrated improved survival outcomes resulting from diagnosis of early-stage PDAC and increased surgical resection rates. However, pancreatic surgery is associated with significant postoperative morbidity. This study compared short-term surgical outcomes in patients with a germline CDKN2A pathogenic variant (PV) under pancreatic cancer surveillance with symptomatic patients undergoing surgical resection for PDAC.

Aims & Methods

This was a single-center cohort study of prospectively collected data from the pancreatic cancer surveillance program and Dutch Pancreatic Cancer Audit (DPCA) of the Leiden University Medical Center (LUMC), a high-volume center for pancreatic cancer surgery. We included all patients with a CDKN2A PV under pancreatic cancer surveillance who underwent surgical resection for a suspected PDAC at the LUMC between 2000 and 2022 (i.e. pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy). Short-term surgical outcomes were compared to a control group of symptomatic patients with sporadic PDAC undergoing surgical resection at the same center between 2013 and 2021 using logistic regression analysis. The primary endpoint was major complications (Clavien-Dindo ≥ III) within 30 days after surgery. Secondary endpoints included all pancreatic surgery-specific complications, in-hospital mortality, reinterventions, length of hospital stay, and readmission within 30 days.

Results

In total, 32 patients in the surveillance group underwent surgical resection for suspected PDAC. Histopathology revealed benign lesions in 8 patients (25%) and malignancy in 24 patients (75%), including 23 PDAC and 1 ampullary carcinoma. A total of 247 patients in the control group with sporadic PDAC underwent surgical resection. In the surveillance group, patients were younger (59 [SD ±9] years vs. 67 [SD ±9] years, respectively) and had lower American Society of Anesthesiologists (ASA) scores than the sporadic PDAC group (ASA ≥ III, 0% vs. 30%; Table 1). In addition, tumors diagnosed under surveillance were smaller (15 mm [IQR 6-30] vs. 28 mm [IQR 20-35]) and more often located in the pancreatic body or tail compared with sporadic PDACs (53% vs. 17%). Consequently, distal pancreatectomy was performed more frequently in the surveillance group than in the sporadic PDAC group (50% vs. 14%). After surgical resection, no difference in major complications was found between the surveillance group and the sporadic PDAC group (25% vs. 20%, P=0.50). However, the surveillance group developed more postoperative pancreatic fistulas than the sporadic PDAC group (22% vs. 6%, P<0.01). Mortality, reinterventions, length of hospital stay, and readmission within 30 days did not differ between groups.

Table 1. Patient, tumor, and treatment characteristics

Conclusion

Major complications did not differ between the surveillance and sporadic PDAC groups, despite differences in patient and tumor characteristics including age, ASA score, tumor size, and location. However, patients in the surveillance group had a higher risk of developing postoperative pancreatic fistula.

Introduction

Several studies suggest that new-onset diabetes mellitus (NOD) may be an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the international CAncer of the Pancreas Screening (CAPS) Consortium recommends glucose and HbA1c monitoring in high-risk individuals (HRIs) for PDAC. However, evidence that such monitoring improves the detection of PDAC is lacking.

Aims & Methods

The aim of this study was to investigate NOD, glucose and HbA1c values in relation to the development of PDAC in a screening program for HRIs. Analysis was performed on individuals participating in the Familial Pancreatic Cancer (FPC) surveillance study, in which HRIs with a hereditary predisposition for PDAC are followed yearly by MRI and/or EUS and blood sampling. Individuals who underwent fasting glucose and/or HbA1c monitoring at least once were included.

Results

In October 2021, the FPC cohort consisted of 463 HRIs, of which 404 had undergone at least one glucose or HbA1c measurement. Of these, 9 individuals developed PDAC and 4 non-PDAC individuals were diagnosed with NOD. Glucose levels ranged between 3.4-10.7 mmol/L (mean 5.4 ± 0.7), and HbA1c levels between 25-68 mmol/mol (mean 37.3 ± 3.6). The percentage of cases with at least one elevated value was comparable between the PDAC and non-PDAC group for glucose (33% and 27%, p=0.707) and HbA1c (22% and 14%, p=0.623).

Conclusion

In this large HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.

Introduction

New-onset diabetes (NOD) is associated with the development of pancreatic ductal adenocarcinoma (PDAC) and is suggested as potential biomarker to detect PDAC at an earlier stage. International guidelines recommend routine glucose measurements in pancreatic surveillance of high-risk individuals (HRIs), however, little is known about its added value in addition to imaging. Therefore, this study evaluates the added value of longitudinal glucose measurements as a diagnostic biomarker for PDAC in high-risk surveillance cohorts.

Aims & Methods

HRIs with a CDKN2A germline pathogenic variant participating in pancreatic cancer surveillance who had ≥ 1 fasting blood glucose (FBG) and/or HbA1c measurements were included in this study. Pancreatic surveillance consists of annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), and blood sampling including blood glucose measurements. Individuals with diabetes mellitus at baseline, less than 3 years of follow-up and all follow-up after pancreatectomy were excluded from the study. Data was collected on demographics, FBG- and HbA1c measurements, MRI- and EUS examinations, and pathology reports. NOD was defined as two consecutive FBG values of ≥ 7 mmol/L or one HbA1c value of ≥ 48 mmol/mol. Univariate multivariable logistic regression was performed to assess the relationship between NOD and PDAC, with adjustment for sex, age and smoking history. To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic (ROC) curve and area under the curve (AUC) were computed.

Results

In total, 220 HRIs were included in the analysis. Median age was 61 (IQR 53-71) years, 62.7% of participants were female, and the mean BMI was 26.2 (4.12 SD). More than half (54.1%) of the studied cohort had a positive smoking history and the median amount of glucose measurements per person was 7 (IQR 5-12). During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (OR 1.21; 95% CI, 0.39-3.78). A statistically significant association was exclusively observed between age and development of PDAC (OR 1.05; 95% CI, 1.01-1.1). Furthermore, NOD did not differentiate between HRIs with- and without PDAC (AUC 0.54; 95% CI, 0.46-0.61).

Conclusion

This study demonstrated no added value for longitudinal glucose monitoring in HRI participating in an imaging-based pancreatic cancer surveillance program.

Introduction

Pancreatic cancer is estimated to be the second leading cause of cancer-related deaths in Europe by 2030 and remains a significant challenge with limited risk factors. Pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMN), and mucinous cystic neoplasia (MCN) are three common precursor lesions for this disease. The risk of pancreatic cancer in first-degree relatives (FDRs) of individuals with precursors however remains unknown.

Aims & Methods

This study aims to analyze the absolute incidence and relative risk of pancreatic cancer by family history of precursors using a population-based cohort study in Sweden. We included all patients who had been pathologically diagnosed with precursor lesions of pancreatic cancer between 1965 and 2016 in Sweden and up to 5 matched reference individuals from the general population based on birth year, sex, calendar year, and residency. We identified all their FDRs (parents, full siblings, and offspring) using the Swedish multigeneration registry. All FDRs were followed up through national registries from birth or year 1959 when cancer registry was launched, until the date of pancreatic cancer diagnosis, death, migration, or end of follow-up (January 1^st, 2020). The absolute cancer incidence rate was computed as the number of observed cases divided by person-years and relative risk was calculated as multivariable-adjusted hazard ratio (HR) using Cox proportional hazards regression.

Results

A total of 27,862 FDRs were included in the analyses, among which 4647 were FDRs of 1036 precursor patients and 23,157 were FDRs of 5067 matched reference individuals. During the follow-up, 149 FDRs developed pancreatic cancer, with an incidence rate of 10 (95% CI 8-12) per 100,000 person-years for FDRs of reference individuals, and 21 (16-28) for FDRs of precursor individuals. Compared to FDRs of reference individuals, FDRs of precursor had a 2.24 (1.58-3.18) times higher risk of developing pancreatic cancer during their lifetime. When stratified by subtype of precursors, similar HRs were found for PanIN (2.37 [1.52-3.70]) and IPMN (2.31 [1.29-4.11]), but not for MCN (1.84 [0.89-3.78]). Individuals whose parents had been diagnosed with precursors had 4.94 (2.10-11.62) times higher risk for pancreatic cancer than those without. To facilitate clinical application, we also assessed the association of pancreatic cancer risk after known diagnosis of precursors in FDRs. Compared to reference counterparts, an HR of 4.46 (2.37-8.38) was found for those with known precursors in FDRs.

Conclusion

A family history of precursor lesions of pancreatic cancer can be an indicative risk factor for pancreatic cancer and risk estimates varies by precursor subtypes and type of FDRs with precursors. Precursor lesions in FDR should be considered as a positive phenotype in individuals at risk.

Disclosure

Dr. Wolpin reported receiving grants from AstraZeneca, Celgene, Bristol Myers Squibb, Eli Lilly, Novartis, and Revolution Medicines and receiving personal fees from BioLineRx, Mirati, Ipsen, GRAIL, Celgene, Bristol Myers Squibb, and Third Rock Ventures. Dr. Ludvigsson has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from the Janssen corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national healthcare registers in China. Dr Vujasinovic and Dr Löhr have received lecture fees from Abbott and Viatris. Dr Vujasinovic and Dr Löhr have also received financial support for writing a scientific book from Viatris. All other authors declare that they have no conflicts of interest and nothing to declare.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

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