Higher Incidence Of Pancreatic Cancer Research Articles

Prediabetes increases the risk of pancreatic cancer: A meta-analysis of longitudinal observational studies.

Glycemic disorder is closely related to the risk of pancreatic cancer, but previous studies focused on the influence of diabetes. The aim of this meta-analysis was to investigate the influence of prediabetes, an intermediate state between normoglycemia and diabetes, on the risk of pancreatic cancer. Relevant longitudinal observational studies were identified through a search of Medline, Embase, and Web of Science databases. To minimize the influence of between-study heterogeneity, a randomized-effects model was used to pool the results. Nine cohort studies including 26,444,624 subjects were available for the meta-analysis. Among them, 2,052,986 (7.8%) had prediabetes at baseline, and the participants were followed for a mean duration of 5.9 years. It was found that, compared to people with normoglycemia, those with prediabetes had a higher incidence of pancreatic cancer (risk ratio [RR]: 1.42, 95% confidence interval: 1.36 to 1.49, p<0.001) with no statistical heterogeneity (I2 = 0%). Sensitivity analysis performed by excluding one dataset at a time did not significantly change the results (RR: 1.38 to 1.45, p all <0.05). Subgroup analyses indicated that the association between prediabetes and increased risk of pancreatic cancer was not significantly impacted by study characteristics such as study design, location, age, and sex of participants, definition of prediabetes, duration of follow-up, or adjustment for alcohol intake (p for subgroup difference all >0.05). Prediabetes may be associated with an increased risk of pancreatic cancer compared to normoglycemia.

Explainable multi-omics deep clustering model reveals an important role of DNA methylation in pancreatic ductal adenocarcinoma

Patients with pancreatic ductal adenocarcinoma (PDAC) have the lowest survival rate among all cancer patients in Europe. Since western societies have the highest incidence of pancreatic cancer, it has been projected that PDAC will soon become the second leading cause of cancer-related deaths. The main challenge of PDAC treatment is that patients with similar somatic genotypes exhibit a wide range of disease phenotypes. Artificial Intelligence (AI) is currently transforming the field of healthcare and represents a promising technology for integrating various datasets and optimizing evidence-based decision making. However, the interpretability of most AI models is limited and it is challenging to understand how and why a decision is made. In this study, we developed a deep clustering model for PDAC patient stratification using integrated methylation and gene expression data. We placed a specific emphasis on model explainability, with the aim to understand the hidden patterns learned by the model. The results showed two subgroups of PDAC patients with different prognoses and biological factors. The multi-omics profile analysis revealed the important role of DNA methylation. We also showed how the model was able to learn underlying patterns using both single modalities and their combinations. We hope that this study will help to promote more explainable AI in real-world clinical applications, where the knowledge of decision factors is crucial. The code of this project is publicly available in GitHub (https://github.com/albertolzs/edc_mo_pdac).

Detection of Pancreatic Cancer and Nutritional Support in Chronic Pancreatitis

Chronic pancreatitis (CP) is a significant risk factor for pancreatic cancer and there had been a great deal of interest in surveillance and detection of pancreatic cancer. According to presence of genetic mutation, CP can be classified into hereditary CP and sporadic CP. CP with PRSS1 gene mutation showed a high incidence of pancreatic cancer justifying screening and surveillance for those older than 40 years. But CP with other mutations and sporadic CP have relatively low incidence of pancreatic cancer and surveillance is not recommended. While computed tomography or magnetic resonance imaging is widely used for screening, endoscopic ultrasound is not recommended because of parenchymal inflammation, fibrosis, and calcification associated with CP. However, when a patient with CP has multiple risk factors for pancreatic cancer, risk of pancreatic cancer increases significantly. Patients with CP have increased risk of pancreatic cancer at five years after diagnosis; individualized screening and surveillance based on symptoms and specific circumstances should be considered. Patients with CP have a high risk of malnutrition and malnutrition is quite common. Clinicians should assess nutritional status and implement nutritional support. Nutritional support must include both macronutrients and micronutrients. Given the high risk of osteoporosis and osteopathy in CP, clinicians should consider early diagnosis, prevention, and treatment. Consultation with nutritional support team is highly recommended.

Effective abdominal ultrasonographic detection of pancreatic cystic lesions using artificial intelligence‐assisted noise reduction

AbstractIntroductionPatients with intraductal papillary mucinous neoplasms (IPMNs) exhibit a high incidence of pancreatic cancer. An IPMN presents as a pancreatic cystic lesion (PCL). Artificial intelligence (AI) can be used to enhance ultrasonographic images. We retrospectively evaluated the utility of AI‐assisted ultrasonography in terms of PCL detection.MethodsIn total, 969 patients who underwent artificial narrow intelligence‐assisted transabdominal ultrasound examinations (AI group) were compared with 943 patients who underwent non‐AI‐assisted examinations (control group). The morphological changes and the frequencies of newly detected PCLs were compared between the groups.ResultsThe PCL detection rate was significantly higher in the AI group than in the control group (1.25 ± 0.36 and 0.21 ± 0.15%, respectively; p = .008). AI‐assisted ultrasound evaluation was independently associated with enhanced PCL detection (odds ratio: 5.83, 95% confidence interval: 1.29–26.29, p = .02). PCLs smaller than 8 mm and all PCLs in the pancreatic tail were detected in the AI group.PCL morphological changes were more common in the AI group than in the control group (63.6 ± 14.5 and 16.7 ± 15.2%, respectively; p = .04).ConclusionAI‐assisted transabdominal ultrasonography enhances the PCL detection rate. The use of AI is likely to increase the IPMN detection rate.

Abstract C107: Use of spatial transcriptomics to identify molecular features associated with African American heritage in pancreatic cancer

Abstract Pancreatic cancer is the third leading cause of cancer-related deaths in the US, with a 5-year survival rate of 12%. Black or African American patients (BAA) have a 20% higher incidence of pancreatic cancer, and recent studies suggest that there are biological factors that may influence this disparity, in addition to complex socioeconomic factors. Pancreatic tumors are highly enriched with stroma and exhibit significant inter- and intra-patient morphological and molecular heterogeneity. To improve the care for all patients, we need to better understand the disease mechanisms by comprehensively mapping different spatial locations within individual patients’ tumors and determining whether there are common patterns of pathogenesis across diverse patient populations. In this study, we utilized the 10X Visium spatial transcriptomics platform on eight treatment-naïve primary pancreatic tumors. We tested multiple published bioinformatic packages, including SpatialDE, SPARK-X, Spatial PCA, and Cottrazm, and optimized a multi-sample integrated analysis pipeline that allows us to automatically segment tumor lesions, infer major cell types in regions of interest on tissues, detect spatially variant genes, and assess associations between tissue morphological phenotypes and transcriptomic features. Importantly, our study cohort includes four White patients and four BAA patients. Through the comparison of spatial transcriptomes between White and BAA patients, we identified several genes displaying differential expression in tumor lesions of distinct racial groups, including Trefoil Factor 1 (TFF1) and CYP3A5. These genes present potential candidates for further investigation to elucidate the biological mechanisms underlying racial disparities in pancreatic cancer. Citation Format: Yuesong Wu, Aoqi Xie, Ian Loveless, Madison George, Kendyll Gartrelle, Julie Clark, Daniel Salas-Escabillas, Rupen Shah, David Kwon, Ralph Francescone, Débora B. Vendramini Costa, Howard Crawford, Brian Theisen, Yuehua Cui, Ling Huang, Nina G. Steele. Use of spatial transcriptomics to identify molecular features associated with African American heritage in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C107.

Molecular profiling of African American patients with pancreatic cancer.

e16242 Background: Pancreatic cancer (PC) is a highly fatal disease, and multiple studies have shown that African Americans (AA) have a higher incidence of PC compared with Whites and have a higher risk of PC-related mortality. Differences in known risk factors for PC including cigarette smoking, obesity, diabetes and family history have been demonstrated to not fully account for the racial disparity in incidence. Furthermore, differing mortality rates by race are not entirely attributable to variables such as access to care and disparate management. Whether there are molecular and biologic differences in PC that could explain these disparities is a question that has important scientific and clinical consequences. Unfortunately, most large studies of genomic alterations in PC include very few AA patients (pts). This study tries to characterize molecular alterations seen in AA pts with PC. Methods: The electronic medical record was queried for all self-identified Black or AA pts who were diagnosed with PC and had molecular profiling from November 2015 to November 2021. Patient demographics, clinical characteristics and molecular genomics were analyzed. The primary outcome was percent of patients with specific KRAS mutations. The secondary outcome was differences in KRAS mutations by gender. Results: We identified 50 AA pts with PC who underwent molecular profiling, 19 of whom (38%) were female. As expected, most (66%) were advanced stage at diagnosis. 32 pts (64%) had tissue-based molecular profiling with 18 (36%) having blood-based testing. A KRAS mutation was identified in 38 pts (76%). 15 (30%), 12 (24%), and 11 (22%) had G12V, G12D, and G12R mutations in KRAS, respectively. Men were more likely to have a G12D mutation (35.5% vs 5.3%, P = 0.018), and women were more likely to have a G12V mutation (47.4% vs 19.4%, P = 0.036). There was no significant difference in overall survival between men and women. 30 pts (60%) had additional mutations other than KRAS. 6 pts (12%) did not have a KRAS mutation detected despite the presence of other alterations. 4 pts had no mutations detected on molecular next generation sequencing, 3 of which had blood-based testing. Conclusions: In our review of genomic mutations of AA pts with PC, KRAS G12V mutations were most common. Only 24% of our studied population had KRAS G12D mutations. The frequency of specific KRAS mutations differs from what has been described in the literature among predominantly White pts with PC, where almost half of pts have a G12D mutation and 28% and 17% harbor G12V and G12R mutations, respectively. Two major limitations of this study are the small sample size which limits definitive comparisons between races, and the imperfect sensitivity of molecular profiling. KRAS is thought to be present in &gt; 90% of PC, but the mutation was only identified in 76% of our pts. Further studies should be conducted to determine whether different molecular characteristics could account for racial disparities in PC mortality.

Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China

A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited. To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China. This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from China from the ChinaMAP database. Data were updated and analyzed in July 2021. Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups. A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P < .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort. In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.

Race, sex, age, and geographic disparities in pancreatic cancer incidence.

520 Background: Pancreatic cancer has a poor prognosis and a 5-year survival rate of 10%. A population-risk level analysis of pancreatic cancer will identify epidemiologic risk factors including geographic, racial, ethnic, and sex inequities which could lead to improved prevention strategies. Methods: Incidence data for invasive pancreatic cancer from 2009 through 2018 was obtained from the Surveillance, Epidemiology, and End Results Research (SEER) Plus Limited-Field database (SEER 21) that covers about 37% of the US population. Age-adjusted incidence rates (AAIR) and trends were estimated by race, sex, age categories (ten-year age groups starting from age 30), and county-level rural-urban classification developed by the United States Department of Agriculture (USDA). Trends over the period are described using the annual percent change (APC) calculated using weighted least squares method. Results: Overall pancreatic cancer incidence (per 100,000 population) for all ages during 2009-2018 was 13.0. Rates were highest among Black (15.4), followed by non-Hispanic white (13.2) and Hispanic (11.6) groups in both men and women. Males carries a higher rate of incidence (14.8) than females (11.6) in pancreatic cancer although both sexes experienced a 0.6% increase in incidence yearly. Incidence of pancreatic cancer increased with age across all ethnicities in men and women. The highest rate of incidence was found in ages 80 and above (99.5) and the lowest in age group 30-39 (1.0). Pancreatic cancer rates increased by 0.6% yearly and increased in every racial/ethnic group for both males and females, except Black males (0.0) and American Indian/Alaska Native females (-0.2). Although incidence in urban counties (13.1, n = 321) and rural counties (12.8, n = 411) was comparable, rural countries observed a faster increase in rates between 2009 and 2018 (p &lt; 0.05). Conclusions: Incidence of pancreatic cancer has increased from 2009 to 2018 across all ethnicities and in both men and women. Minorities, males, and individuals living in rural counties are disproportionately affected by pancreatic cancer. Additionally, older individuals have a higher incidence of pancreatic cancer, suggesting an increased risk in this patient population. This data will inform strategies to identify high-risk populations and implement preventative care, screening, and surveillance.[Table: see text]

Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records

BackgroundPancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics.MethodsWe conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models.ResultsWe observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer.ConclusionsSeveral factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

ID: 3525792 FACTORS INFLUENCING THE DETECTION OF PANCREATIC CANCER NOT SEEN ON CROSS-SECTIONAL IMAGING WITH ENDOSCOPIC ULTRASOUND IN PATIENTS PRESENTING WITH CHRONIC OR ACUTE IDIOPATHIC PANCREATITIS

Pancreatic cancer continues to have a high mortality rate as compared to other malignancies. Poor prognosis is attributed to the lack of validated screening tests, often leading to a late stage diagnosis. Patients with an existing diagnosis of acute idiopathic pancreatitis (AIP) or chronic pancreatitis (CP) have a higher incidence of pancreatic cancer. Cross-sectional imaging studies have limited sensitivity to diagnose smaller sized tumors in the setting of concurrent pancreatic inflammation. Endoscopic ultrasound (EUS) has been shown to be more sensitive for smaller tumors; however, there is limited data on when pancreatic cancer screening should be considered in patients with AIP or CP when cross-sectional imaging is negative.

Prospective randomized controlled trial of omental roll-up technique on pancreatojejunostomy anastomosis for reducing perioperative complication in patients undergoing pancreatoduodenectomy.

BackgroundWrapping pancreatojejunal anastomosis with omentum to prevent postoperative pancreatic fistula (POPF) has only been reported in non‐randomized, controlled trials. Therefore, this study aimed to conduct a randomized, controlled trial to compare outcomes between omental roll‐up and non‐omental roll‐up in pancreatojejunal anastomosis.MethodsThis single‐center, randomized, two‐arm trail (Clinical Trials Register: NCT03083938) was conducted between February 2017 and February 2019. We studied 34 patients in the omental roll‐up group and 34 patients in the non‐omental roll‐up group. The primary endpoint was the incidence of clinically relevant POPF. Thirty‐day mortality and morbidity were recorded.ResultsPatients’ demographic data were not significantly different between the two groups, except for histological diagnosis, with a significantly higher incidence of pancreatic cancer in the omental roll‐up group (n = 15, 44.1%) than in the non‐omental roll‐up group (n = 9, 26.4%) (P = 0.042). There was one death in the non‐omental roll‐up group due to myocardial infarction. The incidence of POPF was not different between the omental roll‐up group (n = 5, 14.7%) and non‐omental roll‐up group (n = 7, 20.6%) (P = 0.525). No differences were found in postoperative hemorrhage after pancreatectomy, delayed gastric emptying, and chyle leakage between the groups.ConclusionThis study shows that omental roll‐up does not decrease the incidence of POPF after pancreatoduodenectomy.

PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer.

BACKGROUNDPancreatic cancer is one of the deadliest cancers, with low long-term survival rates. Despite recent advances in treatment, it is important to identify and screen high-risk individuals for cancer prevention. Familial pancreatic cancer (FPC) accounts for 4%–10% of pancreatic cancers. Several germline mutations are related to an increased risk and might offer screening and therapy options. In this study, we aimed to identity of a susceptibility gene in a family with FPC.METHODSWhole exome sequencing and PCR confirmation was performed on the surgical specimen and peripheral blood of an index patient and her sister in a family with high incidence of pancreatic cancer, to identify somatic and germline mutations associated with familial pancreatic cancer. Compartment-specific gene expression data and immunohistochemistry were also queried.RESULTSThe identical germline mutation of the PALLD gene (NM_001166108.1:c.G154A:p.D52N) was detected in the index patient with pancreatic cancer and the tumor tissue of her sister. Whole genome sequencing showed similar somatic mutation patterns between the 2 sisters. Apart from the PALLD mutation, commonly mutated genes that characterize pancreatic ductal adenocarcinoma were found in both tumor samples. However, the 2 patients harbored different somatic KRAS mutations (G12D and G12V). Healthy siblings did not have the PALLD mutation, indicating a disease-specific impact. Compartment-specific gene expression data and IHC showed expression in cancer-associated fibroblasts (CAFs).CONCLUSIONWe identified a germline mutation of the palladin (PALLD) gene in 2 siblings in Europe, affected by familial pancreatic cancer, with a significant overexpression in CAFs, suggesting that stromal palladin could play a role in the development, maintenance, and/or progression of pancreatic cancer.FUNDINGDFG SFB 1321

A Prospective Analysis of Intake of Red and Processed Meat in Relation to Pancreatic Cancer among African American Women.

African Americans have the highest incidence of pancreatic cancer of any racial/ethnic group in the United States. There is evidence that consumption of red or processed meat and foods containing saturated fats may increase the risk of pancreatic cancer, but there is limited evidence in African Americans. Utilizing the Black Women's Health Study (1995-2018), we prospectively investigated the associations of red and processed meat and saturated fats with incidence of pancreatic adenocarcinoma (n = 168). A food frequency questionnaire was completed by 52,706 participants in 1995 and 2001. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. We observed interactions with age (P interaction = 0.01). Thus, results were stratified at age 50 (<50, ≥50). Based on 148 cases among women aged ≥50 years, total red meat intake was associated with a 65% increased pancreatic cancer risk (HRQ4 vs. Q1 = 1.65; 95% CI, 0.98-2.78; P trend = 0.05), primarily due to unprocessed red meat. There was also a nonsignificant association between total saturated fat and pancreatic cancer (HRQ4 vs. Q1 = 1.85; 95% CI, 0.92-3.72; P trend = 0.08). Red meat and saturated fat intakes were not associated with pancreatic cancer risk in younger women, and there was no association with processed meat in either age group. Red meat-specifically, unprocessed red meat-and saturated fat intakes were associated with an increased risk of pancreatic cancer in African-American women aged 50 and older, but not among younger women. The accumulating evidence-including now in African-American women-suggests that diet, a modifiable factor, plays a role in the etiology of pancreatic cancer, suggesting opportunities for prevention.

Epidemiology of the Incidence and Mortality of Pancreas Cancer and its Relationship with the Human Development Index (HDI) in the World: An Ecological Study in 2018.

Pancreatic cancer is one of the leading causes of mortality in developed countries and a lethal malignant neoplasm worldwide. This study aims to evaluate the epidemiology of pancreatic cancer incidence and mortality and its relationship with HDI. This is a descriptive cross-sectional study that is based on cancer incidence data and cancer mortality rates derived from the GLOBOCAN in 2018. The incidence and mortality rates of Pancreas as well as Pancreas cancer distribution maps were derived for world countries. The data analysis was conducted using a correlation test, and regression tests were used to evaluate the correlation of the incidence and mortality of Pancreas with HDI. The statistical analysis was carried out by Stata-14, and a significance level of 0.05 was considered. The highest incidence of pancreatic cancer was reported in Asia with 214499 (46.7%) cases and the lowest incidence was related to Oceania with 4529 cases (0.99%). The results showed a positive and significant correlation between incidence (r = 0.764, P <0.0001) and mortality (r = 0.771, P <0.0001) of pancreatic cancer and the HDI index. The results of ANOVA revealed that the highest mean incidence was related to the very high HDI (P <0.0001) and the highest mortality was connected to the very high human development (P <0.0001). The results exhibited that incidence was positively and significantly correlated with GNI (r = 0.497, P <0.0001), MYS (r = 0.746, P <0.0001), LEB (r = 0.676, <0.0001) and EYS (r = 0.738, P <0.0001). Also, a significant positive correlation was found between mortality and GNI (r = 0.507, P <0.0001), MYS (r = 0.745, P <0.0001), LEB (r = 0.679, <0.0001), and EYS (r = 0.748, P <0.0001). Given the higher incidence and mortality of pancreatic cancer in countries with HDI, it is necessary to pay a greater attention to risk factors and appropriate planning to reduce these factors and minimize the impact and mortality rate of this disease.

Abstract C071: Racial/ethnic disparities in weight, weight change in adulthood, and pancreatic cancer incidence: The Multiethnic Cohort

Abstract Purpose: Japanese Americans, Native Hawaiians and African Americans have a higher incidence of pancreatic cancer compared to non-Hispanic whites that cannot be explained by the rates of obesity or absolute body weight. While absolute body weight in adulthood is positively associated with pancreatic cancer risk, the effect of weight change throughout adulthood, particularly among a racially diverse population, is not well documented for this high-risk group. Methods: This population-based prospective cohort study included 155,308 participants enrolled in the Multiethnic Cohort from 1993-1996 (median follow-up = 20.2 years). We identified 1,328 participants diagnosed with incident primary invasive pancreatic cancer from the linked cohort data with the Hawaii and California SEER registries. Participants diagnosed with other cancers were excluded from the cohort analysis. Body weight at 21 years old and at baseline enrollment (age 45 or older) were assessed using a self-administered questionnaire at cohort entry. Multivariable Cox proportional hazards regression models were used to determine the association between weight change from age 21 to cohort entry and pancreatic cancer risk adjusting for known risk factors such as smoking status, physical activity, alcohol intake, family history of pancreatic cancer and other sociodemographic characteristics. Results: The mean age at cohort entry was 59.3 years (SD 8.9) and the largest proportion of the cohort were Japanese American (30.1%), White (25.0%), and Latino (21.8%), respectively. The mean weight change from age 21 to baseline age was 28 pounds (SD 26.7). We observed that increased risk of pancreatic cancer was associated with weight at age 21 (HR 1.06; 95% CI 1.03-1.09, per 10-pound increase; p-trend&amp;lt;0.001) and weight at baseline (1.03; 1.00-1.05, per 10-pound increase; p-tend=0.03). Weight gain through adulthood (per pound increase per year) was associated with 11% increased risk of pancreatic cancer (1.11; 1.03-1.20) after adjusting for known lifestyle and behavioral risk factors. There was a significant interaction (p=0.03) between weight gain per year in adulthood and race/ethnicity, where Japanese Americans and Latinos experienced a 36% (1.36; 95% CI 1.14-1.64; p-trend&amp;lt;0.001) and 33% (1.33; 95% CI 1.11-1.59; p-trend=0.02) increased risk of pancreatic cancer per pound gained per year, respectively. Conclusion: Our findings indicate that weight gain in adulthood has a significant and independent impact on pancreatic cancer risk and specifically among racial/ethnic minorities. This study underscores the importance of maintaining a stable weight through adulthood, regardless of weight at age 21, in order to lower the risk of pancreatic cancer. Citation Format: Albert J Farias, Daniel O Stram, Songren Wang, Stephen J Pandol, Kristine R Monroe, V. Wendy Setiawan. Racial/ethnic disparities in weight, weight change in adulthood, and pancreatic cancer incidence: The Multiethnic Cohort [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C071.

Association between chronic pancreatitis and pancreatic cancer: A 10-year retrospective study of endoscopically treated and surgical patients.

Pancreatic cancer (PC) has a poor prognosis. Chronic pancreatitis (CP) associates with high morbidity and mortality, and serves as a risk factor for PC. Our study aimed to assess the association between endoscopically treated CP patients and PC, and to establish the rate of CP among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed 458 CP patients undergoing endoscopic treatment (ET) between 2000 and 2010 and 349 PDAC patients undergoing pancreatic resection between 2000 and 2014 at the Helsinki University Hospital. The likelihood of diagnosing PC was highest within 2 years of a CP diagnosis: 21 of 30 PC diagnoses occurred during this time. After 2 years follow-up: 9 of 30 PC diagnoses occurred 2-12 years from CP diagnosis. Two patients were diagnosed with CP before PDAC. Multivariate analysis showed two prognostic factors indicative of PC development: biliary stricture (HR 9.21; 95% CI 3.76-22.08) and a higher age (per 5-year increases) at CP onset (HR 1.55; 95% CI 1.30-1.85). Among 458 CP patients, the median overall survival without PC was 14.7 years (95% CI 12.0-17.3), falling to 1.6 years (95% CI 1.2-2.0) with PC. The high incidence of PC among CP patients at the beginning of follow-up likely reflected an initially missed PC diagnoses. In long-term follow-up, an increasing PC incidence might reflect the PC-predisposing impact of CP. Thus, we recommend careful follow-up for patients presenting with a recently diagnosed CP and risk factors for PC.

Identification of Individuals at Increased Risk for Pancreatic Cancer in a Community-Based Cohort of Patients With Suspected Chronic Pancreatitis.

OBJECTIVES:We lack reliable methods for identifying patients with chronic pancreatitis (CP) at increased risk for pancreatic cancer. We aimed to identify radiographic parameters associated with pancreatic cancer in this population.METHODS:We conducted a retrospective cohort study of patients with suspected CP within an integrated healthcare system in Southern California in 2006–2015. Patients were identified by a diagnostic code and confirmed by imaging findings (parenchymal calcification, ductal stones, glandular atrophy, pseudocyst, main duct dilatation, duct irregularity, abnormal side branch, or stricture) defined by the natural language processing of radiographic reports. We used Cox regression to determine the relationship of smoking, alcohol use, acute pancreatitis, diabetes, body mass index, and imaging features with the risk of incident pancreatic cancer at least 1 year after abnormal pancreas imaging.RESULTS:We identified 1,766 patients with a diagnostic code and an imaging feature for CP with a median follow-up of 4.5 years. There were 46 incident pancreatic cancer cases. Factors that predicted incident pancreatic cancer after 1-year of follow-up included obesity (hazard ratio 2.7, 95% confidence interval: 1.2–6.1) and duct dilatation (hazard ratio 10.5, 95% confidence limit: 4.0–27). Five-year incidence of pancreatic cancer in this population with duct dilatation was 6.3%.DISCUSSION:High incidence of pancreatic cancer in suspected patients with CP with pancreatic duct dilatation warrants regular surveillance for pancreatic cancer.

Oral Health in Relation to Pancreatic Cancer Risk in African American Women.

Incidence of pancreatic cancer is higher in African Americans than in U.S. whites. We hypothesized that poor oral health, disproportionately common in African Americans and associated with increased risk of pancreatic cancer in several studies of predominantly white populations, may play a role in this disparity. We examined the relation of self-reported measures of oral health (periodontal disease and adult tooth loss) in relation to pancreatic cancer incidence in the prospective Black Women's Health Study (BWHS). Cox proportional hazard analyses were used to calculate HRs of pancreatic cancer for women with periodontal disease, tooth loss, or both, relative to women who reported neither. Multivariable models adjusted for age, cigarette smoking, body mass index (BMI), type 2 diabetes, and alcohol consumption. Participants aged 33 to 81 were followed for an average of 9.85 years from 2007 through 2016, with occurrence of 78 incidence cases of pancreatic cancer. Multivariable HRs for pancreatic cancer incidence were 1.77 [95% confidence interval (CI) 0.57-5.49] for periodontal disease with no tooth loss, 2.05 (95% CI, 1.08-3.88) for tooth loss without report of periodontal disease, and 1.58 (95% CI, 0.70-3.57) for both tooth loss and periodontal disease. The HR for loss of at least five teeth, regardless of whether periodontal disease was reported, was 2.20 (95% CI, 1.11-4.33). The poor oral health experienced by many African Americans may contribute to their higher incidence of pancreatic cancer. Future research will assess associations between the oral microbiome and pancreatic cancer risk in this population.

Cancer-Associated Hypercoagulation Increases the Risk of Early Recurrent Stroke in Patients with Active Cancer

Background: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. Methods: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. Results: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher ­D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42–30.7, p = 0.015). Conclusions: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.