New Cases Of Pancreatic Cancer Research Articles

Simulating the healthcare workforce impact and capacity for pancreatic cancer care in Victoria: a model-based analysis

BackgroundThe incidence of pancreatic cancer is rising. With improvements in knowledge for screening and early detection, earlier detection of pancreatic cancer will continue to be more common. To support workforce planning, our aim is to perform a model-based analysis that simulates the potential impact on the healthcare workforce, assuming an earlier diagnosis of pancreatic cancer.MethodsWe developed a simulation model to estimate the demand (i.e. new cases of pancreatic cancer) and supply (i.e. the healthcare workforce including general surgeons, medical oncologists, radiation oncologists, pain medicine physicians, and palliative care physicians) between 2023 and 2027 in Victoria, Australia. The model compares the current scenario to one in which pancreatic cancer is diagnosed at an earlier stage. The incidence of pancreatic cancer in Victoria, five-year survival rates, and Victoria’s population size were obtained from Victorian Cancer Registry, Cancer Council NSW, and Australian Bureau of Statistics respectively. The healthcare workforce data were sourced from the Australian Government Department of Health and Aged Care’s Health Workforce Data. The model was constructed at the remoteness level. We analysed the new cases and the number of healthcare workforce by profession together to assess the impact on the healthcare workforce.ResultsIn the status quo, over the next five years, there will be 198 to 220 stages I-II, 297 to 330 stage III, and 495 to 550 stage IV pancreatic cancer cases diagnosed annually, respectively. Assuming 20–70% of the shift towards pancreatic cancer’s earlier diagnosis (shifting from stage IV to stages I-II pancreatic cancer within one year), the stages I-II cases could increase to 351 to 390 or 598 to 665 per year. The shift to early diagnosis led to substantial survival gains, translating into an additional 284 or 795 out of 5246 patients with pancreatic cancer remaining alive up to year 5 post-diagnosis. Workforce supply decreases significantly by the remoteness levels, and remote areas face a shortage of key medical professionals registered in delivering pancreatic cancer care, suggesting travel necessities by patients or clinicians.ConclusionImproving the early detection and diagnosis of pancreatic cancer is expected to bring significant survival benefits, although there are workforce distribution imbalances in Victoria that may affect the ability to achieve the anticipated survival gain.

Regionalization of pancreatic surgery in California: Benefits for preventing postoperative deaths and reducing healthcare costs

IntroductionPancreatic cancer (PC) surgery has been associated with improved outcomes and value when performed at high-volume centers (HVC; ≥20 surgeries annually) compared to low-volume centers (LVC). Some have used these differences to suggest that regionalization of PC surgery would optimize patient outcomes and expenditures. MethodsA Markov model was created to evaluate 30-day mortality, 30-day complications, and 30-day costs. The differences in these outcome measures between the current and future states were measured to assess the population-level benefits of regionalization. A sensitivity analysis was performed to evaluate the impact of variations of input variables in the model. ResultsAmong 5958 new cases of pancreatic cancer in California in 2021, a total of 2443 cases (41 %) would be resectable; among patients with resectable PC, a total of 977 (40 %) patients would undergo surgery. In aggregate, HVC and LVC 30-day postoperative complications occurred in 364 patients, 30-day mortality in 35 patients, and healthcare costs expended managing complications were $6,120,660. In the predictive model of complete regionalization to only HVC in California, an estimated 29 fewer complications, 17 fewer deaths, and a cost savings of $487,635 per year would occur. Conclusions and relevancePancreatic cancer (PC) surgery has been associated with improved outcomes and value when performed at high-volume centers (HVC; ≥20 surgeries annually) compared to low-volume centers (LVC). Complete regionalization of pancreatic cancer surgery predicted benefits in mortality, complications and cost, though implementing this strategy at a population-level may require investment of resources and redesigning care delivery models.

Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis.

The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results. This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis. During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure. In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Abstract A076: Pancreatic cancer survival disparities in Florida using a statewide database

Abstract Introduction Pancreatic cancer (PC) portends a poor prognosis, is the current third-leading cause of cancer deaths in the United States, and is still rising. The state of Florida has the second-highest rate of new cases of PC within the United States with an incidence of 460/100,000. It is also a disease with significant disparities. African Americans with PC have a 50–90% increased incidence, lower rates of surgery, and worse overall mortality in comparison to other racial groups. With increased knowledge of these disparities in recent years, we sought out to identify whether these differences were present in the state of Florida by examining differences in pancreatic cancer survival outcomes between race, age, and income. Materials and Methods Patients with pancreatic adenocarcinoma diagnosed from January 1st, 2017 to October 31st, 2020 were identified through the statewide clinical research and network database called OneFlorida Clinical Consortium (OneFlorida) by using the ICD10 diagnosis code for pancreatic cancer. Patients with a diagnosis of neuroendocrine carcinoma were excluded. Patients were followed for at least one year unless a death occurred. Summary statistics were reported for demographic variables. The demographic variable for income was stratified by low being < $53,000 and high being ≥ $53,000. Kaplan-Meier analysis with log-rank test was performed to compare the difference in overall survival time among groups. Cox proportional hazards models were also fitted to test the between-group differences and compute the 95% confidence intervals of hazard ratio, while adjusting for informative covariate(s) when necessary. Results A total of 2,739 unique patients were available for analysis. The distribution of the sample was 68.7% White, 23.4% Black, and 7.9% Other. The median age was 67 years (27–89). There were 49.8% women and 50.2% men. The median income was $52,915 ($23,704–$124,821). Significant differences in overall survival were detected (p-values < 0.001) between age, income, and racial groups, but not between sex. Patients that were Black, >67 years old, and had low-income had a significantly less survival time than their corresponding contrasts independently. The mean survival (in days) for low income vs. high income was 779.5 vs. 945.9 (p<.0001). The differences remained significant in stratified analyses by cancer stage. In stage II PC, the mean survival (in days) for White vs. Black populations was 1134.9 days vs 472.2 days, and in stage IV PC the survival comparison was 770.2 days vs. 787.5 days between the same groups. Discussion Significant race, age and income disparities in survival exist in the state of Florida. These disparities are present even when stage is accounted for. Knowledge of health disparities statistics are not sufficient, and a targeted multi-stakeholder approach needs to be developed to improve survival outcomes of our patients. Limitations to this study include the racial demographic of “other” not having further description due to limited data availability through the clinical research network. Citation Format: Guettchina Telisnor, Alexander S. Lim, Zhongyue Zhang, XiangYang Lou, Ibrahim Nassour, Sherise C. Rogers. Pancreatic cancer survival disparities in Florida using a statewide database [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A076.

Abstract A048: Impact of COVID-19 on pancreatic cancer outcomes in Florida

Abstract Introduction: Pancreatic cancer (PC) is currently the third-leading cause of cancer deaths in the United States. African Americans with PC have an increased incidence and worse survival outcome when compared to other racial groups. During the COVID-19 pandemic, there is evidence that hospital resources were allocated to treating immediate life-threatening conditions. Some of the daily highest case numbers were reported in the state of Florida with several peaks throughout 2020 and 2021. Additionally, the state of Florida has the second-highest rate of new cases of PC within the United States with an incidence of 4860/100,000. Our specific aim is to define the impact of COVID-19 between race, age, income, and gender on the survival time of newly diagnosed patients with pancreatic cancer in Florida. Materials and Methods: Patients with pancreatic adenocarcinoma diagnosed from January 1st, 2017 to October 31st, 2020 were identified through the statewide clinical research and network database called OneFlorida Clinical Consortium by using the ICD10 diagnosis code for pancreatic cancer. Patients were then placed into 3 cohorts based on date of pancreatic cancer diagnosis: pre-pandemic (01/01/2017- 09/30/2019), transition (10/01/2019-02/28/2020), and pandemic (03/1/2020-10/31/2020). Patients with a diagnosis of neuroendocrine carcinoma were excluded. Patients were followed for at least one year unless a death occurred. Summary statistics were reported for demographic variables (age, sex, income, gender). Kaplan-Meier analysis with log-rank test was performed to compare the difference in overall survival time among groups. Results: This retrospective study had a total of 934 unique patients available for analysis. Of the 934 patients, 81.3% were in the pre-pandemic cohort (n= 759), 8.2% transition cohort (n=77), and 10.5% pandemic cohort (n=98). There was a decrease in the rate of diagnosis from the pre-pandemic (23 per month) to pandemic cohort (12.2 per month). The demographic distribution of the sample was 23.4% Black, 68.7% White and 7.9% Other. The median age was 67 years (27–89). There were 49.8% women and 50.2% men. The median income was $52,915 ($23,704–$124,821). The differences in overall survival time were not significant for age and gender across the 3 cohorts. Income <$53,000 had significantly lower survival time across the 3 cohorts. African Americans had significantly lower survival time for pre-pandemic and transition cohort (p< .005), but Caucasians had the lowest survival time for the pandemic cohort (p <.005). When stratified for stage, the mean survival (in months) for White vs. Black populations was 37.8 vs. 26.1 for stage I, 37.6 vs. 27.3 for stage II, 28.5 vs.18.77 for stage III, and 20.7 vs. 21.7 for stage IV. Discussion: This study demonstrated a decrease in diagnosis & survival rate during the COVID-19 pandemic in Florida. Dissemination of resources should target these disparities in income and race. Citation Format: Guettchina Telisnor, Alexander S. Lim, Zhongyue Zhang, XiangYang Lou, Ibrahim Nassour, Bo Han, Edward Agyare, Sherise C. Rogers. Impact of COVID-19 on pancreatic cancer outcomes in Florida [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A048.

Pancreatic tumor with lung tumor: a case report

According to the global cancer observatory (GLOBOCAN), there were 16,485 new cases of pancreatic cancer in Southeast Asia in 2020, with men (9458 cases) having the highest incidence compare to woman (8320 cases). The death rate from 16,485 cases was 16,167 cases (98%). A person's chance of developing pancreatic cancer in addition to other cancers is between 1% to 20%. In this study, we reported a case of pancreatic tumor with lung tumor. A 68 years old woman presented with right quadrant abdominal pain since 1 month ago. The pain occurs randomly, but mostly occur during night. The pain didn’t occur after eat fatty food and during exercise. The pain didn’t relieve by rest. The patient also experienced nausea and vomit. The vomit consist of food and blood. She complains black colored stools and dark yellow urine. She also lost weight from 62 kg to 47 kg. There was history of gastric bleeding in 4 month ago. She was passive smoker. We then did several tests such as complete blood count, blood chemistry, serology, chest x-ray and abdominal CT-scan. The test showed pancreatic tumor with suggestive primary lung tumor. Patient with multiple primary tumor are an extremely rare type of cancer, which need comprehensive approach to both diagnosis and treatment of these numerous primary tumors.

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease which confers to patients a poor prognosis at short term. PDAC is the fourth leading cause of death among cancers in the Western world. The rate of new cases of pancreatic cancer (incidence) is 10 per 100,000 but present a 5-year survival of less than 10%, highlighting the poor prognosis of this pathology. Furthermore, 90% of advanced PDAC tumor present KRAS mutations impacting in several oncogenic signaling pathways, many of them associated with cell proliferation and tumor progression. Different combinations of chemotherapeutic agents have been tested over the years without an improvement of significance in its treatment. PDAC remains as one the more challenging biomedical topics thus far. The lack of a proper early diagnosis, the notable mortality statistics and the poor outcome with the available therapies urge the entire scientific community to find novel approaches against PDAC with real improvements in patients’ survival and life quality. Natural compounds have played an important role in the process of discovery and development of new drugs. Among them, terpenoids, such as sesquiterpene lactones, stand out due to their biological activities and pharmacological potential as antitumor agents. In this review, we will describe the sesquiterpene lactones with in vitro and in vivo activity against pancreatic tumor cells. We will also discuss the mechanism of action of the compounds as well as the signaling pathways associated with their activity.

Recommendations for a More Organized and Effective Approach to the Early Detection of Pancreatic Cancer From the PRECEDE (Pancreatic Cancer Early Detection) Consortium

Recommendations for a More Organized and Effective Approach to the Early Detection of Pancreatic Cancer From the PRECEDE (Pancreatic Cancer Early Detection) Consortium

Neoadjuvant Therapy (NAT) in Localized Pancreatic Cancer: Should We Do It and What Should We Do?

In 2019, approximately 56,770 new cases of pancreatic cancer were diagnosed in the United States, resulting in an estimated 45,750 deaths. Pancreatic cancer is one of the leading causes of cancer-related death, with a five-year survival rate of 9%.

Italian registry of families at risk of pancreatic cancer: AISP Familial Pancreatic Cancer Study Group

Pancreatic cancer is one of the main causes of cancer-related death worldwide, with a survival rate around 9%. In Italy 13,500 new cases of pancreatic cancer occurred in 2019. It is estimated that at least 5% have a hereditary background. Surveillance is advisable for healthy individuals with specific genetic syndromes with or without family history of pancreatic cancer or members of families with multiple cases of pancreatic cancer, irrespective of genetic syndromes. In 2010 the Italian Association for the Study of the Pancreas (AISP) defined criteria to include individuals in such surveillance programs with the first-round results published in 2019. In order to include other categories at high-risk and increase the diagnostic yield of surveillance, these criteria have recently been modified. The present position paper presents the updated criteria of the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) with their diagnostic yield calculation. Also, AISP priority projects concerning: (a) increasing awareness of citizens and primary care physicians through a dedicated App; (b) increasing access to germline testing to personalize surveillance; (c) measuring psychological impact of surveillance; (d) investigating the role of risk-modifiers and (e) evaluating the cost-effectiveness and ability to save lives of the program are briefly presented.

Association of Glycated Hemoglobin Levels With Risk of Pancreatic Cancer

New-onset diabetes after the age of 50 years is a potential indicator of pancreatic cancer. Understanding the associations between hyperglycemia, diabetes, and pancreatic cancer, including pancreatic ductal adenocarcinoma, is key to developing an approach to early detection. To assess the association of elevation in glycated hemoglobin (HbA1c) with the risk of pancreatic cancer. This cohort study was conducted using data collected from an integrated health care system in California. A total of 851 402 patients aged 50 to 84 years who had HbA1c measurements taken between 2010 and 2014 were identified as the base cohort, with 12 contemporaneous cohorts created based on varying HbA1c thresholds (ie, 6.1%, 6.3%, 6.5%, and 6.7%) and prior diabetes status. Data analysis was conducted from August 2018 to September 2019. New cases of pancreatic cancer identified through cancer registry and California death files during a 3-year period. Three-year risk, incidence rate, sensitivity, number of patients needed to screen to detect 1 case, timing, and stage at diagnosis were determined. Among 851 402 patients in the base cohort, 447 502 (52.5%) were women, 255 441 (30.0%) were Hispanic participants, 383 685 (45.1%) were non-Hispanic white participants, 100 477 (11.8%) were Asian participants, and 88 969 (10.4%) were non-Hispanic black participants, with a median (interquartile range) age of 62 (56-69) years and a median (interquartile range) HbA1c level of 6.0% (5.7%-6.6%). The incidence rate of pancreatic cancer was 0.45 (95% CI, 0.43-0.49) per 1000 person-years. After excluding prior diabetes as well as confirmation of new-onset hyperglycemia based on an HbA1c level of 6.5%, a total of 20 012 patients remained, with 74 of 1041 pancreatic ductal adenocarcinoma cases (7.1%) from the base cohort included. The rate of pancreatic cancer was 0.72 (95% CI, 0.32-1.42) per 1000 person-years among Asian patients, 0.83 (95% CI, 0.35-1.71) per 1000 person-years among non-Hispanic black patients, 0.84 (95% CI, 0.48-1.37) per 1000 person-years among Hispanic patients, and 2.37 (95% CI, 1.75-3.14) per 1000 person-years among non-Hispanic white patients. Overall, 42 of 74 cancers (56.8%) were diagnosed within 1 year of the index laboratory test. Among 1041 total cases, 708 (68.0%) had staging information available, of whom 465 (65.7%) had stage III or IV disease at diagnosis. In the base cohort, the number needed to undergo evaluation to identify a single case of pancreatic ductal adenocarcinoma was 818 (95% CI, 770-869), with estimates ranging from 206 (95% CI, 160-264) to 600 (95% CI, 540-666) in the subcohorts. The findings of this study suggest that screening patients for pancreatic cancer based solely on elevation in HbA1c level is unlikely to represent an effective strategy. Future efforts to identify a high-risk population based on changes in glycemic parameters should account for racial/ethnic differences.

The global burden of pancreatic cancer.

IntroductionWe provide here an overview on current worldwide epidemiology of pancreatic malignancies, obtained from Global Health Data Exchange (GHDx) and World Health Organization (WHO) repositories.Material and methodsElectronic searches for collecting information on pancreatic cancer epidemiology were performed in official repositories of GHDx and WHO, and retrieved data were then analyzed.ResultsOverall, 447 665 new cases of pancreatic cancer were recorded around the world in 2017 (58.6 per million), with global prevalence of 49.8 per million and 441 083 deaths (57.7 per million). Incidence, prevalence and mortality increased by 55%, 63% and 53% during the last 25 years. Pancreatic cancer accounts for 1.8% of all cancers, causing 3.9% of all cancer disability- adjusted life years (DALYs) and 4.6% of all cancer deaths. No sex differences can be observed for incidence, prevalence and mortality, whilst DALYs are marginally higher in men. Incidence, prevalence and mortality follow a similar age-related trend, with gradual escalation after 30 years of age, reaching the highest burden after 80 years of age. The DALYs peak between 55 and 74 years, and then decline. The epidemiologic burden is positively associated with socio-demographic status. The largest burden of pancreatic cancers is observed in the East and Asia Pacific region, whilst the lowest is found in the Middle East and North Africa. Pancreatic cancer deaths are expected to increase by ~1.97-fold by the year 2060.ConclusionsAlthough pancreatic cancer remains relatively infrequent, its clinical, societal and economic burden is noteworthy. Future projections suggest that its burden may double during the next 40 years.

The disease burden of pancreatic cancer in China in 1990 and 2017

Objective: To analyze the disease burden of pancreatic cancer in China in 1990 and 2017. Methods: Province-specific data in China from the Global Burden of Disease Study (GBD) 2017 were used to describe the change of death status, disease burden of pancreatic cancer in Chinese population by specific province and age groups, including incidence, mortality, disability-adjusted life years (DALY), years of life lost (YLL) due to premature mortality and years lived with disability (YLD) in 1990 and 2017. Meanwhile the incidence, mortality, DALY rate, YLL rate, YLD rate were standardized by the GBD global standard population in 2017. Results: In 2017, the new cases of pancreatic cancer, incidence and age-standardized incidence accounted for 83.6 thousand, 5.92/100 000 and 4.37/100 000 in China, with an increase of 230.94%, 180.45% and 49.88% compared with 1990, respectively. The total number of deaths, mortality and age-standardized mortality appeared as 85.1 thousand, 6.02/100 000, 4.48/100 000, with an increase of 236.08%, 184.80% and 47.51% respectively. The incidence and mortality of pancreatic cancer increased with age and accelerated from the age of 55 to 59 both in 1990 and 2017. The highest incidence and mortality showed in 85-89 years old in 2017 and in 90-94 years old in 1990. The standardized DALY rate of pancreatic cancer increased from 71.00/100 000 in 1990 to 94.32/100 000 in 2017, increased by 32.84%. The standardized YLL rate increased from 70.39/100 000 to 93.42/100 000, increased by 32.72%. The standardized YLD rate increased from 0.62/100 000 to 0.90/100 000, increased by 45.80%. In terms of age distribution, DALY rate, YLL rate and YLD rate of pancreatic cancer basically showed an increasing trend with age in 1990 and 2017. In 2017, Jiangsu (7.61/100 000), Shanghai (7.52/100 000) and Liaoning (6.84/100 000) ranked the top three provinces in terms of standardized mortality. Compared with 1990, Henan (104.28%), Sichuan (94.02%) and Hebei (90.39%) saw the fastest increase in standardized mortality. Conclusions: The incidence, mortality and disease burden of pancreatic cancer in China increased significantly from 1990 to 2017. Prevention and control measures should be strengthened to reduce the disease burden of pancreatic cancer.

The Distributional Characteristic and Growing Trend of Pancreatic Cancer in China.

Pancreatic cancer is a malignant tumor with difficulty in diagnosis and treatment and was the sixth leading cause of cancer death among both men and women in China. The 5-year relative survivals of pancreatic cancer were only 7.2% in China and the lowest level in all cancers. The proportion of estimated new cases of pancreatic cancer in China was comparatively high in East China, Northeast, North China, and Northwest and relatively low in Central China, Southwest, and South China, showing obvious regional characteristics. It implies that the incidence and mortality in the eastern region are significantly higher than those in the western region, which is consistent with the result that the incidence and mortality increased from low to middle to high urbanization areas in China, and the prevalence of diabetes increased from underdeveloped to intermediately developed to developed region.

Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors.

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.

Abstract 1390: Honokiol, a bioactive component from Magnolia plant, promotes DNA demethylation and reactivates silenced tumor suppressors in pancreatic cancer cells through TET-dependent mechanism

Abstract Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. American Cancer Society estimated that in 2017, approximately 53,670 new cases of pancreatic cancer will be diagnosed and 43,090 deaths will occur. In addition to genetic changes, epigenetic alterations are commonly associated with cancers including pancreatic cancer. Studies have shown that DNA hypermethylation contributes to tumor growth by inactivating tumor suppressors. DNA methyltransferases (DNMTs) regulate DNA methylation, but mechanisms underlying DNA demethylation have not fully elucidated and have enormous translational potential. Ten-eleven translocations (TETs) have been shown to convert 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and eventually reactivates tumor suppressors. Bioactive components from plants have shown their efficacy as potential chemopreventive and therapeutic agents. Here, we investigated the effect of honokiol on DNA methylation using in vitro cell culture model. We first checked the expression levels of global DNA methylation in pancreatic cancer cell lines (PANC-1, AsPC-1) and compared with normal human pancreas duct epithelial cells. Our data revealed that the levels of global DNA methylation were higher in pancreatic cancer cell lines. Treatment of AsPC-1 and PANC-1 cells with honokiol for five days resulted in significant decrease in global DNA methylation levels (60-80%, p<0.001) compared to non-honokiol treated cells. To detect the comparative levels of 5-mC/5-hmC in AsPC-1 and PANC-1 cells immunofluorescence staining was used. Honokiol treatment increases 5-hmC levels in pancreatic cancer cells compared to non-honokiol-treated cells. The number of 5-hmC positive cells were significantly higher in honokiol-treated AsPC-1 (12-61%; p<0.01-0.001) and PANC-1 (42-77%; p<0.001) cells in a dose-dependent manner compared to non-honokiol treated control group as verified by flow cytometry. Honokiol treatment also significantly increases the levels of TET activity and protein expression in cancer cell lines. We also found that concomitant treatment of cancer cells with cycloheximide (proteins synthesis blocking agent) prevented honokiol-induced TET expression and formation of 5-hmC and therefore suggest that honokiol promotes 5-hmC formation (i.e., demethylation) through TET activation. Ascorbate, an inducer of TETs, also promotes 5-hmC formation in pancreatic cancer cells. Additionally, honokiol treatment reactivates tumor suppressor genes/proteins levels, such as p16INK4a and RASSF1A in cancer cells. Together, this study provides evidence that honokiol acts as a DNA demethylating agent and is able to reactivate an epigenetically silenced tumor suppressors and thus inhibits the growth of pancreatic cancer cells. Citation Format: Ram Prasad, Santosh Katiyar. Honokiol, a bioactive component from Magnolia plant, promotes DNA demethylation and reactivates silenced tumor suppressors in pancreatic cancer cells through TET-dependent mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1390.

Disparities in incidence and mortality of pancreatic cancer in the world

Background: Pancreatic cancer (PC) is as the twelfth most frequent cancer and the seventh most important cause of mortality by reason of cancer in the world. Being informed about the incidence and mortality of this cancer and the potential role of development is useful in health policy. The aim of this research is investigating disparities in the incidence and mortality of PC in the world countries in the year 2012.
 Methods: This study was an ecologic study in the World for assessing the correlation between Human Development Index (HDI) and its details (Gross national income (GNI) per capita, average years of schooling and life expectancy at birth) with age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of PC.
 Results: In total, 337872 new cases of PC occurred in 2012 around the world , that 178116 and 159711 cases take happen in men and women respectively, also at the same year 330391 deaths of PC occurred ,that 173,827 and 156564 cases were in men and women. In assessment the relationship between HDI and ASIR and ASMR of PC there is significant positive correlation equal to 0.767 (p <0.001) between HDI and ASIR of PC, and a significant positive correlation equal to 0.776 (p <0.001) between HDI and ASMR of PC.
 Conclusion: The incidence and mortality of PC has a significant positive correlation with the Human Development Index.

Totally laparoscopic pancreaticoduodenectomy. First case reported in México

Abstract Background Approximately 48,960 people in the USA will be diagnosed with pancreatic cancer in 2015 and 40,560 will die for this reason; in Mexico, the new cases of pancreatic cancer in 2012 were 4274, with 4133 deaths; survival rate at 5 years goes from 1% to 15%. Less than 20% of cases were considered resectable at the time of diagnosis. The Whipple procedure is currently the only curative treatment option for periampullary cancers since the first communication by Whipple in 1935, and up until now is a common procedure in several reference centres around the world. In 1994, Gagner reported the first totally laparoscopic pancreaticoduodenectomy. Some groups have currently demonstrated the safety and efficacy of this technique. Objective To report our initial experience with totally laparoscopic pancreaticoduodenectomy in the Hospital General de Mexico. Clinical case The case concerns a 58 year-old women with jaundice and loss of weight of 3 months onset. Her biopsy reported adenocarcinoma of Vater's ampulla, and as it was considered resectable, she underwent a laparoscopic pancreaticoduodenectomy. Conclusions This procedure must be performed in centres with experience in open pancreatic surgery and training in advanced laparoscopic surgery. The main advantages are lower blood loss and shorter hospital stay.

Evolution of novel therapeutic options for pancreatic cancer.

Pancreatic cancer is the most devastating of all cancers with an extremely poor prognosis. In US alone, over 50 000 new cases of pancreatic cancer are reported annually, and about the same number succumb to it, making pancreatic cancer the third most common cause of cancer deaths. Most patients with pancreatic cancer present with advanced disease, which cannot be resected surgically, and for these patients chemotherapy is the only option. Even patients who undergo resection require adjuvant therapy to decrease the risk of recurrence. Since the 1950s, a variety of different agents, like antimetabolites, nucleoside analogs, and DNA intercalating compounds, have been used against pancreatic cancer, alone or in combination, with little improvement in the survival statistics. The current article reviews the evolution of chemotherapy for pancreatic cancer, and discusses some novel therapeutic options that are emerging in recent times, with special emphasis on Minnelide, a novel HSP70 inhibitor, which is currently in clinical trials. Approaches towards developing therapies for pancreatic cancer have evolved tremendously over the past decade. Research has shown that apart from the inherent drug resistance, drug delivery to pancreatic cancer has also posed a major challenge. The extensive desmoplastic stroma of pancreatic cancer is believed to create inordinately high interstitial fluid pressures leading to vascular collapse and substantial barrier to perfusion of chemotherapeutics, thus creating an additional layer of protection for pancreatic cancer. Recent research thus is focused not only on understanding the biology and developing strategies to target cancer cells, but also is targeted towards the depletion of stroma in order to ensure better delivery of chemotherapeutic compounds to the tumor. The current article describes the novel therapies that are constantly being evaluated to address and overcome the challenges that make pancreatic cancer a difficult disease to treat.

Abstract 5236: Bitter melon juice causes strong efficacy towards pancreatic cancer stem cells by modulating the hedgehog signaling pathway

Abstract According to ACS estimates for year 2015, ∼48,960 new cases of pancreatic cancer (PanC) would be diagnosed with 40,560 associated deaths in the US alone. The median life of PanC patients post diagnosis is <6 months and overall 5 year survival is 3-5%. Thus, there is an urgent need for newer strategies to improve the disease outcome in these patients. Recently, considerable efforts have been directed towards natural dietary/non-dietary agents for both prevention/intervention of PanC. One such dietary agent, bitter melon (Momordica charantia) from Cucurbitaceae family, is now being extensively evaluated for its efficacy against various malignancies including PanC. Recently, we have shown significant growth inhibitory effects of bitter melon juice (BMJ) against a panel of PanC cells including Mia PaCa-2 xenograft tumors. Our studies also showed BMJ activity against both gemcitabine (frontline chemotherapeutic in PanC patients) sensitive as well as resistant PanC cell lines. Since the presence of cancer stem cells (CSC) is now recognized as the main cause for initiation, promotion and drug-resistance as well as relapse of most of the cancers, including PanC, there is a possibility that BMJ was affecting the CSC population in the PanC cells. Accordingly, the present study was aimed to determine whether BMJ has the potential to target CSC in PanC. We isolated CSC enriched (CD44+CD24+EpCAMhigh) cell population from the PanC cell lines, MiaPaCa2, PANC1 and AsPC1 and subjected them as well as the unsorted cells to sphere cluster formation assays in the presence or absence (single vs. multiple time treatment) of BMJ (0.25-2% v/v). The% of floating spheroids generated in the sphere cluster assays after 1-2 weeks were determined. The results indicated a dose-dependent effect of BMJ on both number and size (volume) of spheres, with 2% BMJ showing a significant reduction in both number and size of generated spheres in all PanC cell lines; single treatment of BMJ was found to be equally effective as multiple dosing regimens. Since formation of spheroids under specific in vitro conditions is a measure of stemness, our results show that BMJ has the potential to target the self-renewal of CSCs in PanC cell lines. Subsequent studies employing real time RT-PCR and immunofluorescence showed BMJ effect to be mediated in part by a significant down regulation in the expression of CSC marker CD44, CD133, and hedgehog (Hh)-pathway members in PanC cell lines. Further studies found that BMJ also decreases the protein levels of Hh-pathway members SHH and SMO in MiaPaCa2 xenograft tumors. Together, these are significant findings as they clearly show that BMJ interferes with the kinetics of CSC pool expansion via targeting various regulatory signals associated with the survival and multiplication of CSC pool leading to effective anti-cancer efficacy against PanC cells and their resistant phenotypes. Citation Format: Rajesh Agarwal, Deepanshi Dhar, Chapla Agarwal, Gagan Deep. Bitter melon juice causes strong efficacy towards pancreatic cancer stem cells by modulating the hedgehog signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5236.