WorldWideScience

Sample records for pancreatic cancer risk

  1. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  2. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  3. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  4. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

  5. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  6. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

    Science.gov (United States)

    Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

    2011-01-01

    Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

  7. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

    Science.gov (United States)

    Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

    2013-03-01

    Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  8. Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Cronin Fenton, Deirdre; Heide-Jørgensen, Uffe

    2018-01-01

    . Pancreatic cancer risk was expressed as hazard ratios (HRs) with 95% CIs, calculated using the Cox proportional hazards model. Cox models were stratified by age, sex, and year of pancreatitis diagnosis and adjusted for alcohol- and smoking-related conditions, and Charlson Comorbidity Index score. Results We...... included 41,669 patients diagnosed with incident acute pancreatitis and 208,340 comparison individuals. Patients with acute pancreatitis had an increased risk of pancreatic cancer compared with the age- and sex-matched general population throughout the follow-up period. The risk decreased over time......Background & Aims Acute pancreatitis may be a risk factor for pancreatic cancer. However, findings from studies on this association are conflicting. We investigated the association between acute pancreatitis and increased risk of pancreatic cancer. Methods We conducted a nationwide, population...

  9. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-09-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

  10. Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

    Science.gov (United States)

    Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

    2017-09-01

    Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

  11. Increased pancreatic cancer risk following radiotherapy for testicular cancer.

    Science.gov (United States)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

    2016-09-27

    Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

  12. Childhood body mass index and risk of adult pancreatic cancer

    DEFF Research Database (Denmark)

    Nogueira, Leticia; Stolzenberg-Solomon, Rachael; Gamborg, Michael

    2017-01-01

    incident pancreatic cancer cases from 1968-2012. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regressions. Results: During 8,207,015 person-years of follow-up, 1,268 pancreatic cancer cases were diagnosed. Childhood BMI z-scores at ages 7-13 years were......Background: Excess weight in adulthood is one of the few modifiable risk factors for pancreatic cancer, and height has associations as well. This leads to question whether body weight and height in childhood are associated with adult pancreatic cancer. Objective: To examine if childhood body mass...... from 7-13 years is positively and linearly associated with adult pancreatic cancer; the higher the BMI, the higher the risk. Excess childhood BMI may be indicative of processes initiated early in life that lead to this cancer. Prevention of childhood adiposity may decrease the burden of pancreatic...

  13. Occupational exposures and risk of pancreatic cancer

    International Nuclear Information System (INIS)

    Santibanez, Miguel; Vioque, Jesus; Alguacil, Juan; Hera, Manuela Garcia de la; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-01-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  14. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Directory of Open Access Journals (Sweden)

    Hannah Arem

    Full Text Available Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN totaling 213 single nucleotide polymorphisms (SNPs, and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L for the most significant SNPs using a subset of cohort cases (n = 713 and controls (n = 878. The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830. Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186, LRP2 (rs4668123, CYP24A1 (rs2762932, GC (rs2282679, and CUBN (rs1810205 genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037, but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  15. Association between allergies and risk of pancreatic cancer.

    Science.gov (United States)

    Cotterchio, Michelle; Lowcock, Elizabeth; Hudson, Thomas J; Greenwood, Celia; Gallinger, Steven

    2014-03-01

    Less than 10% of pancreatic cancer cases survive 5 years, yet its etiology is not well understood. Studies suggest allergies are associated with reduced pancreatic cancer risk. Our study collected additional information on allergies (including skin prick test results and differentiation of allergic/nonallergic asthma), and is the first to assess possible confounding by allergy medications. A population-based case-control study was designed to comprehensively assess the association between allergy and pancreatic cancer risk. Pancreas cancer cases were diagnosed during 2011 to 2012, and identified through the Ontario Cancer Registry (345 cases). Population-based controls were identified using random digit dialing and age/sex frequency matched to cases (1,285 controls). Questionnaires collected lifetime allergy history (type of allergy, age at onset, skin prick testing results), allergy medications, and established pancreas cancer risk factors. Logistic regression was used to estimate odd ratios and test potential confounders, including allergy medications. Hay fever was associated with a significant reduction in pancreatic cancer risk [AOR = 0.68; 95% confidence intervals (CI), 0.52-0.89], and reduction was greatest for those whose skin prick test was positive for hay fever allergens. No particular patterns were observed as regards age at onset and duration of allergy. Positive dust/mold allergy skin prick test and animal allergies were associated with a statistically significant reduced pancreatic cancer risk; AOR = 0.49; 95% CI, 0.31-0.78 and AOR = 0.68; 95% CI, 0.46-0.99, respectively. Asthma was not associated with pancreatic cancer risk. These findings support the growing body of evidence that suggests certain allergies are associated with reduced pancreatic cancer risk. ©2014 AACR.

  16. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2015-10-01

    09/08/15-08/31/19 0.96 cal. mo. NIH/NCI $168,300 A prospective investigation of the oral microbiome and pancreatic cancer 1.To perform a...and BWHS. 2.To evaluate racial differences in the oral microbiome using 165 AA and 165 EA controls (from the SCCS only), and to identify any racial...risk factors for pancreatic cancer (cigarette smoking, obesity, red meat and processed meat consumption, alcohol consumption, type 2 diabetes) and oral

  17. Selected medical conditions and risk of pancreatic cancer.

    Science.gov (United States)

    Olson, Sara H

    2012-01-01

    We review the current evidence for associations of several medical conditions with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy. There are consistent findings of reduced risk associated with presence of self-reported allergies, particularly hay fever but not asthma; data on other allergies are limited and inconclusive. Several studies provide evidence that patients with pancreatic cancer are more likely than comparison groups to report pancreatitis. Those studies that investigated the time between onset of pancreatitis and diagnosis of pancreatic cancer found that risk estimates declined with longer periods of time; however, increased risks were noted for long-term pancreatitis, indicating that this condition is both a risk factor and a sign of early disease. Increased risk was reported in association with cholelithiasis, but the few studies that considered time before diagnosis of cancer did not find increased risk for cholelithiasis diagnosed in the more distant past. There is weak evidence that cholecystectomy 2 or more years before cancer diagnosis is related to risk, but this is based on only a few studies. There is no consistent association between ulcers and risk, while gastrectomy may increase risk. Overall, study of these conditions, particularly those that are rare, presents methodologic challenges. Time between diagnoses is likely to be important but is not considered in most studies. Lack of adequate control in several studies for risk factors such as smoking and heavy alcohol use also makes it difficult to draw firm conclusions about these results. Copyright © 2011 Wiley Periodicals, Inc.

  18. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    Science.gov (United States)

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L.; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N.

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

  19. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

    Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

  20. Helicobacter pylori infection, atrophic gastritis, and pancreatic cancer risk

    Science.gov (United States)

    Liu, Hong; Chen, Yue-Tong; Wang, Rui; Chen, Xin-Zu

    2017-01-01

    Abstract Background: To investigate the associations of Helicobacter pylori (Hp) infection and atrophic gastritis (AG) with pancreatic cancer risk. Methods: A literature search in PubMed was performed up to July 2017. Only prospective cohort and nested case–control studies enrolling cancer-free participants were eligible. Incident pancreatic cancer cases were ascertained during the follow-up. The risks of pancreatic cancer were compared between persons infected and noninfected with Hp, or between those with and without AG status at baseline. Odds ratios (ORs) or hazard ratios were combined. Subgroup and sensitivity analyses were performed, and publication bias was estimated. Results: Three cohort studies and 6 nested case–control studies, including 65,155 observations, were analyzed. The meta-analyses did not confirm the association between pancreatic cancer risk and Hp infection (OR = 1.09, 95% confidence interval [CI] = 0.81–1.47) or AG status (OR = 1.18, 95% CI = 0.80–1.72). However, particular subpopulations potentially had increased risks of pancreatic cancer. Cytotoxin-associated gene A (CagA)-negative strains of Hp might be a causative factor of pancreatic cancer (OR = 1.30, 95% CI = 1.05–1.62), but a sensitivity analysis by leave-one-out method did not fully warrant it (OR = 1.20, 95% CI = 0.93–1.56). In 1 nested case–control study, AG at stomach corpus in Hp-negative subpopulation might have increased risk of pancreatic cancer, but with a poor test power = 0.56. Publication biases were nonsignificant in the present meta-analysis. Conclusion: Based on current prospective epidemiologic studies, the linkage of pancreatic cancer to Hp infection or AG status was not warranted on the whole. Nevertheless, prospective studies only focusing on those specific subpopulations are further required to obtain better power. PMID:28816977

  1. Risk factors for pancreatic cancer and early diagnosis of pancreatic cancer

    International Nuclear Information System (INIS)

    Yamao, Kenji; Mizuno, Nobumasa; Sawaki, Akira; Shimizu, Yasuhiro; Chang, K.J.

    2008-01-01

    This paper describes the strategy for improving the poor prognosis of the pancreatic (P) cancer by its early imaging diagnosis followed by resection, based on recent findings on its high risk group. Epidemiological studies have revealed that patients with diabetes, chronic pancreatitis, intraductal papillary-mucious tumor, P cyst, familial history of P cancer, and hereditary P cancer syndrome are involved in the high risk group of P cancer. Imaging diagnosis with CT and/or endoscopic ultrasonography (EUS) followed by histological confirmation for resection can be a useful approach to improve the prognosis in those high risk, asymptomatic individuals with abnormal levels of P enzyme and tumor marker, and with US findings of P ductal dilation and cyst. The guideline 2006 for P cancer by Japan Pancreas Society shows the algorithm leading to the final diagnosis for the positive high risk group: firstly, CT and/or MRCP (MR cholangiopancreatography (CP)); or, in case of uncertainty, EUS and/or ERCP (E retrograde CP) and/or PET; and finally, cytological, histological diagnosis. The newer approach proposed recently for the group is: multi detector row (MD)-CT and EUS; then cytodiagnosis guided by ERCP and/or with fine needle aspiration by EUS, also a promising early diagnosis. As well, molecular biological approaches are supposedly useful for the future diagnosis. (R.T.)

  2. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer

  3. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974?2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated w...

  4. Dietary Mutagen Exposure and Risk of Pancreatic Cancer

    OpenAIRE

    Li, Donghui; Sue Day, Rena; Bondy, Melissa L.; Sinha, Rashmi; Nguyen, Nga T.; Evans, Douglas B.; Abbruzzese, James L.; Hassan, Manal M.

    2007-01-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases tha...

  5. Dietary mutagen exposure and risk of pancreatic cancer.

    Science.gov (United States)

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  6. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  7. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  8. Prevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Stefan Kuroczycki-Saniutycz

    2017-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  9. The epidemiology of pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B

    2013-06-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. The Epidemiology of Pancreatitis and Pancreatic Cancer

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  11. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Zamora-Ros, Raul; Bueno-de-Mesquita, H. Bas; Wark, Petra A.; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C.; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Quirós, José Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H.; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie Christine; Clavel-Chapelon, Françoise; Cross, Amanda J.; Lu, Yunxia; Riboli, Elio; Duell, Eric J.

    2016-01-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the

  12. Dairy products and pancreatic cancer risk: A pooled analysis of 14 cohort studies

    NARCIS (Netherlands)

    Genkinger, J.M.; Wang, M.; Li, R.; Albanes, D.; Anderson, K.E.; Bernstein, L.; Brandt, P.A. van den; English, D.R.; Freudenheim, J.L.; Fuchs, C.S.; Gapstur, S.M.; Giles, G.G.; Goldbohm, R.A.; Håkansson, N.; Horn-Ross, P.L.; Koushik, A.; Marshal, J.R.; McCullough, M.L.; Miller, A.B.; Robien, K.; Rohan, T.E.; Schairer, C.; Silverman, D.T.; Stolzenberg-Solomon, R.Z.; Virtamo, J.; Willett, W.C.; Wolk, A.; Ziegler, R.G.; Smith-Warner, S.A.

    2014-01-01

    Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy

  13. Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Buckland, Genevieve; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Amiano, Pilar; Wark, Petra A.; Kühn, Tilman; Katzke, Verena; Huerta, José María; Ardanaz, Eva; Quirós, José Ramón; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie Christine; Peeters, Petra H.; Ye, Weimin; Sund, Malin; Boeing, Heiner; Iqbal, Khalid; Ohlsson, Bodil; Sonestedt, Emily; Tjønneland, Anne; Petersen, Kristina EN; Travis, Ruth C.; Skeie, Guri; Agnoli, Claudia; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Sacerdote, Carlotta; Freisling, Heinz; Huybrechts, Inge; Overvad, Kim; Trichopoulou, Antonia; Bamia, Christina; Vasilopoulou, Effie; Wareham, Nick; Khaw, Kay Tee; Cross, Amanda J.; Ward, Heather A.; Riboli, Elio; Duell, Eric J.

    2017-01-01

    Background:The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European

  14. Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study

    Science.gov (United States)

    Moossavi, Shirin; Mohamadnejad, Mehdi; Pourshams, Akram; Poustchi, Hossein; Islami, Farhad; Sharafkhah, Maryam; Mirminachi, Babak; Nasseri-Moghaddam, Siavosh; Semnani, Shahryar; Shakeri, Ramin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Kamangar, Farin; Malekzadeh, Reza

    2018-01-01

    Background We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in Northeast of Iran. Methods A total of 50,045 adults were systematically followed-up (median of 7.4 years) and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models. Results Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared to never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors [HR=3.01; 95% CI 1.25-7.26]. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking [HR=3.56; 95% CI 1.49-8.50]. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk [HR=2.75; 95% CI 1.14-6.64]. Conclusion Our results showed a positive association between opium consumption and pancreatic cancer. Impact This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. PMID:29263189

  15. Increased pancreatic cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

    2016-01-01

    with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

  16. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

    NARCIS (Netherlands)

    Campa, Daniele; Pastore, Manuela; Gentiluomo, Manuel; Talar-Wojnarowska, Renata; Kupcinskas, Juozas; Malecka-Panas, Ewa; Neoptolemos, John P.; Niesen, Willem; Vodicka, Pavel; Delle Fave, Gianfranco; Bueno-de-Mesquita, H. Bas; Gazouli, Maria; Pacetti, Paola; Di Leo, Milena; Ito, Hidemi; Klüter, Harald; Soucek, Pavel; Corbo, Vincenzo; Yamao, Kenji; Hosono, Satoyo; Kaaks, Rudolf; Vashist, Yogesh; Gioffreda, Domenica; Strobel, Oliver; Shimizu, Yasuhiro; Dijk, Frederike; Andriulli, Angelo; Ivanauskas, Audrius; Bugert, Peter; Tavano, Francesca; Vodickova, Ludmila; Zambon, Carlo Federico; Lovecek, Martin; Landi, Stefano; Key, Timothy J.; Boggi, Ugo; Pezzilli, Raffaele; Jamroziak, Krzysztof; Mohelnikova-Duchonova, Beatrice; Mambrini, Andrea; Bambi, Franco; Busch, Olivier; Pazienza, Valerio; Valente, Roberto; Theodoropoulos, George E.; Hackert, Thilo; Capurso, Gabriele; Cavestro, Giulia Martina; Pasquali, Claudio; Basso, Daniela; Sperti, Cosimo; Matsuo, Keitaro; Büchler, Markus; Khaw, Kay-Tee; Izbicki, Jakob; Costello, Eithne; Katzke, Verena; Michalski, Christoph; Stepien, Anna; Rizzato, Cosmeri; Canzian, Federico

    2016-01-01

    The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter

  17. Development and Validation of a Prediction Model to Estimate Individual Risk of Pancreatic Cancer.

    Science.gov (United States)

    Yu, Ami; Woo, Sang Myung; Joo, Jungnam; Yang, Hye-Ryung; Lee, Woo Jin; Park, Sang-Jae; Nam, Byung-Ho

    2016-01-01

    There is no reliable screening tool to identify people with high risk of developing pancreatic cancer even though pancreatic cancer represents the fifth-leading cause of cancer-related death in Korea. The goal of this study was to develop an individualized risk prediction model that can be used to screen for asymptomatic pancreatic cancer in Korean men and women. Gender-specific risk prediction models for pancreatic cancer were developed using the Cox proportional hazards model based on an 8-year follow-up of a cohort study of 1,289,933 men and 557,701 women in Korea who had biennial examinations in 1996-1997. The performance of the models was evaluated with respect to their discrimination and calibration ability based on the C-statistic and Hosmer-Lemeshow type χ2 statistic. A total of 1,634 (0.13%) men and 561 (0.10%) women were newly diagnosed with pancreatic cancer. Age, height, BMI, fasting glucose, urine glucose, smoking, and age at smoking initiation were included in the risk prediction model for men. Height, BMI, fasting glucose, urine glucose, smoking, and drinking habit were included in the risk prediction model for women. Smoking was the most significant risk factor for developing pancreatic cancer in both men and women. The risk prediction model exhibited good discrimination and calibration ability, and in external validation it had excellent prediction ability. Gender-specific risk prediction models for pancreatic cancer were developed and validated for the first time. The prediction models will be a useful tool for detecting high-risk individuals who may benefit from increased surveillance for pancreatic cancer.

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

    NARCIS (Netherlands)

    Konings, Ingrid C. A. W.; Sidharta, Grace N.; Harinck, Femme; Aalfs, Cora M.; Poley, Jan-Werner; Kieffer, Jacobien M.; Kuenen, Marianne A.; Smets, Ellen M. A.; Wagner, Anja; van Hooft, Jeanin E.; van Rens, Anja; Fockens, Paul; Bruno, Marco J.; Bleiker, Eveline M. A.

    2016-01-01

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

  19. The association between dietary zinc intake and risk of pancreatic cancer: a meta-analysis.

    Science.gov (United States)

    Li, Li; Gai, Xuesong

    2017-06-30

    Previous reports have suggested a potential association on dietary zinc intake with the risk of pancreatic cancer. Since the associations between different studies were controversial, we therefore conducted a meta-analysis to reassess the relationship between dietary zinc intake and pancreatic cancer risk. A comprehensive search from the databases of PubMed, Embase, Web of Science, and Medline was performed until January 31, 2017. Relative risk (RR) with 95% confidence intervals (CI) derived by using random effect model was used. Sensitivity analysis and publication bias were conducted. Our meta-analysis was based on seven studies involving 1659 cases, including two prospective cohort studies and five case-control studies. The total RR of pancreatic cancer risk for the highest versus the lowest categories of dietary zinc intake was 0.798 (0.621-0.984), with its significant heterogeneity among studies ( I 2 =58.2%, P =0.026). The average Newcastle-Ottawa scale (NOS) score was 7.29, suggesting a high quality. There was no publication bias in the meta-analysis about dietary zinc intake on the risk of pancreatic cancer. Subgroup analyses showed that dietary zinc intake could reduce the risk of pancreatic cancer in case-control studies and among American populations. In conclusion, we found that highest category of dietary zinc intake can significantly reduce the risk of pancreatic cancer, especially among American populations. © 2017 The Author(s).

  20. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2016-10-01

    information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing...individuals provide extensive data on metabolic phenotypes, such as obesity and diabetes, and banked plasma samples for interrogation . The potential...banked plasma samples for interrogation . The potential impact of understanding the mechanisms underlying early pancreatic cancer growth is

  1. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  2. PANCREATIC CANCER

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  3. Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies.

    Science.gov (United States)

    Dong, Jie; Zou, Jian; Yu, Xiao-Feng

    2011-03-07

    To quantitatively assess the relationship between coffee consumption and incidence of pancreatic cancer in a meta-analysis of cohort studies. We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Studies were included if they reported relative risks (RRs) and corresponding 95% CIs of pancreatic cancer with respect to frequency of coffee intake. We performed random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of pancreatic cancer associated with a 1 cup/d increment in coffee consumption. Fourteen studies met the inclusion criteria, which included 671,080 individuals (1496 cancer events) with an average follow-up of 14.9 years. Compared with individuals who did not drink or seldom drank coffee per day, the pooled RR of pancreatic cancer was 0.82 (95% CI: 0.69-0.95) for regular coffee drinkers, 0.86 (0.76-0.96) for low to moderate coffee drinkers, and 0.68 (0.51-0.84) for high drinkers. In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of pancreatic cancer in men, while this association was not seen in women. These associations were also similar in studies from North America, Europe, and the Asia-Pacific region. Findings from this meta-analysis suggest that there is an inverse relationship between coffee drinking and risk of pancreatic cancer.

  4. Dietary Factors Associated with Pancreatic Cancer Risk in

    Science.gov (United States)

    Abdelrehim, Marwa G; Mahfouz, Eman M; Ewis, Ashraf A; Seedhom, Amany E; Afifi, Hassan M; Shebl, Fatma M

    2018-02-26

    Background: Pancreatic cancer (PC) is a serious and rapidly progressing malignancy. Identifying risk factors including dietary elements is important to develop preventive strategies. This study focused on possible links between diet and PC. Methods: We conducted a case-control study including all PC patients diagnosed at Minia Cancer Center and controls from general population from June 2014 to December 2015. Dietary data were collected directly through personal interviews. Principal component analysis (PCA) was performed to identify dietary groups. The data were analyzed using crude odds ratios (ORs) and multivariable logistic regression with adjusted ORs and 95% confidence intervals (CIs). Results: A total of 75 cases and 149 controls were included in the study. PCA identified six dietary groups, labeled as cereals and grains, vegetables, proteins, dairy products, fruits, and sugars. Bivariate analysis showed that consumption of vegetables, fruits, sugars, and total energy intake were associated with change in PC risk. In multivariable-adjusted models comparing highest versus lowest levels of intake, we observed significant lower odds of PC in association with vegetable intake (OR 0.24; 95% CI, 0.07-0.85, P=0.012) and a higher likelihood with the total energy intake (OR 9.88; 95% CI, 2.56-38.09, Plink between high fruit consumption and reduced odds of PC. Conclusions: The study supports the association between dietary factors and the odds of PC development in Egypt. It was found that higher energy intake is associated with an increase in likelihood of PC, while increased vegetable consumption is associated with a lower odds ratio. Creative Commons Attribution License

  5. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    OpenAIRE

    Ramadani, Naser; Dedushi, Kreshnike; Mu?aj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research s...

  6. Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Calderon R

    2007-08-01

    Full Text Available Abstract Background Diabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28–40 years for whom information on diabetes had been collected at the time they gave birth, in 1964–1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up. Methods We used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring. Results We observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14–35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8–18.0. Conclusion We conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.

  7. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

    NARCIS (Netherlands)

    Canto, Marcia Irene; Harinck, Femme; Hruban, Ralph H.; Offerhaus, George Johan; Poley, Jan-Werner; Kamel, Ihab; Nio, Yung; Schulick, Richard S.; Bassi, Claudio; Kluijt, Irma; Levy, Michael J.; Chak, Amitabh; Fockens, Paul; Goggins, Michael; Bruno, Marco; Arcidiacono, Paolo Giorgio; Bartsch, Detlef; Biermann, Katharina; Brentnall, Terri; Dite, Petr; Donahue, Timothy; Early, Dayna; Farrell, James; Fernandez-del Castillo, Carlos; Frucht, Harold; Fukushima, Noriyoshi; Geurts, Jenny; Hamell, Pascal; Iglesias-Garcia, Julio; Klein, Alison; Kloeppel, Guenter; Lachter, Jesse; Langer, Peter; Lee, Jeffrey; Levy, Michael; Maguchi, Hiroyuki; Margolis, Daniel; Ohtsuka, Takao; Olson, Sara; Petersen, Gloria; Savides, Thomas; Syngal, Sapna; Tamm, Eric; Tanaka, Masao; Vasen, Hans; Wagner, Anja; Wang, Huamin; Williams, David; Yamao, Kenjii

    2013-01-01

    Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. A 49-expert multidisciplinary

  8. Physical activity and risk of pancreatic cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Behrens, Gundula; Jochem, Carmen; Schmid, Daniela; Keimling, Marlen; Ricci, Cristian; Leitzmann, Michael F

    2015-04-01

    Physical activity may prevent pancreatic cancer by regulating body weight and decreasing insulin resistance, DNA damage, and chronic inflammation. Previous meta-analyses found inconsistent evidence for a protective effect of physical activity on pancreatic cancer but those studies did not investigate whether the association between physical activity and pancreatic cancer varies by smoking status, body mass index (BMI), or level of consistency of physical activity over time. To address these issues, we conducted an updated meta-analysis following the PRISMA guidelines among 30 distinct studies with a total of 10,501 pancreatic cancer cases. Random effects meta-analysis of cohort studies revealed a weak, statistically significant reduction in pancreatic cancer risk for high versus low levels of physical activity (relative risk (RR) 0.93, 95 % confidence interval (CI) 0.88-0.98). By comparison, case-control studies yielded a stronger, statistically significant risk reduction (RR 0.78, 95 % CI 0.66-0.94; p-difference by study design = 0.07). When focusing on cohort studies, physical activity summary risk estimates appeared to be more pronounced for consistent physical activity over time (RR 0.86, 95 % CI 0.76-0.97) than for recent past physical activity (RR 0.95, 95 % CI 0.90-1.01) or distant past physical activity (RR 0.95, 95 % CI 0.79-1.15, p-difference by timing in life of physical activity = 0.36). Physical activity summary risk estimates did not differ by smoking status or BMI. In conclusion, physical activity is not strongly associated with pancreatic cancer risk, and the relation is not modified by smoking status or BMI level. While overall findings were weak, we did find some suggestion of potential pancreatic cancer risk reduction with consistent physical activity over time.

  9. Coffee consumption and risk of gastric and pancreatic cancer--a prospective cohort study.

    Science.gov (United States)

    Bidel, Siamak; Hu, Gang; Jousilahti, Pekka; Pukkala, Eero; Hakulinen, Timo; Tuomilehto, Jaakko

    2013-04-01

    Only few prospective studies have examined the association between coffee consumption and risk of gastric and pancreatic cancer. This study is designed to evaluate this relationship among Finns, whose coffee consumption is the highest in the world. A total of 60,041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Coffee consumption and other study parameters were determined at baseline using standardized measurements. Participants were prospectively followed up for onset of gastric and/or pancreatic cancer, emigration, death or until June 30, 2006. During a mean follow-up period of 18 years, 299 cases of gastric cancer and 235 cases of pancreatic cancer were found. There was a nonsignificant inverse association between coffee consumption and risk of gastric cancer among men but not in the women. The multivariate-adjusted hazard ratio of stomach and pancreatic cancer incidence for ≥ 10 cups of coffee per day compared with nondrinkers were 0.75 (95% CI, 0.40-1.41) (P for trend = 0.19) and 0.82 (95% CI, 0.38-1.76) (P for trend = 0.95) for the combined population of men and women, respectively. We did not find a significant association between coffee consumption and the risk of gastric and/or pancreatic cancers. Copyright © 2012 UICC.

  10. ABO blood groups and pancreatic cancer risk and survival: Results from the PANcreatic Disease ReseArch (PANDoRA) consortium

    Czech Academy of Sciences Publication Activity Database

    Rizzato, C.; Campa, D.; Pezzilli, R.; Souček, P.; Greenhalf, W.; Capurso, G.; Talar-Wojnarowska, R.; Heller, A.; Jamroziak, K.; Khaw, K. T.; Key, T.; Bambi, F.; Landi, S.; Mohelníková-Duchoňová, B.; Vodičková, Ludmila; Buechler, M. W.; Bugert, P.; Vodička, Pavel; Neoptolemos, J. P.; Werner, J.; Hoheisel, J. D.; Bauer, A. S.; Giese, N.; Canzian, F.

    2013-01-01

    Roč. 29, č. 4 (2013), s. 1637-1644 ISSN 1021-335X Institutional support: RVO:68378041 Keywords : pancreatic cancer * genetic susceptibility * cancer risk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.191, year: 2013

  11. Nitrate in drinking water and risk of death from pancreatic cancer in Taiwan.

    Science.gov (United States)

    Yang, Chun-Yuh; Tsai, Shang-Shyue; Chiu, Hui-Fen

    2009-01-01

    The relationship between nitrate levels in drinking water and risk of pancreatic cancer development remains inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to pancreatic cancer and nitrate exposure from Taiwan's drinking water. All pancreatic cancer deaths of Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios and confidence limits for pancreatic cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.03 (0.9-1.18) and 1.1 (0.96-1.27), respectively. The results of the present study show that there was no statistically significant association between the levels of nitrate in drinking water and increased risk of death from pancreatic cancer.

  12. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Arem, Hannah; Mayne, Susan T; Sampson, Joshua; Risch, Harvey; Stolzenberg-Solomon, Rachael Z

    2013-09-01

    Epidemiologic and experimental studies suggest that dietary fat intake may affect risk of pancreatic cancer, but published results are inconsistent. We examined risk associations for specific types of dietary fat intakes and related food sources among 111,416 participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used Cox proportional hazards regression to examine associations between fat intake and pancreatic cancer risk. Over a mean 8.4 years of follow-up, 411 pancreatic cancer cases were identified. We observed an inverse association between saturated fat intake and pancreatic cancer risk (hazard ratio [HR], 0.64 comparing extreme quintiles; 95% confidence interval [CI], 0.46-0.88), but the association became weaker and nonsignificant when individuals with fewer than 4 years of follow-up were excluded to avoid possible reverse causation (HR, 0.88; 95% CI, 0.58-1.33). Total fat intake showed a similar pattern of association, whereas intakes of monounsaturated and polyunsaturated fats and fats from animal or plant sources showed no associations with risk. These results do not support the hypothesis of increased pancreatic cancer risk with higher fat consumption overall or by specific fat type or source. Dietary changes owing to undetected disease may explain the observed inverse association with saturated fat. Published by Elsevier Inc.

  13. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO.

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-04-01

    The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients-61.6 % of cases (n=223) with the highest number found at 51-60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61-70 years age group. The F/M ratio is 1:1.6. The "plane" nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. This retrospective research study intends to present the role of the risk factor, that

  14. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Results: Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients–61.6 % of cases (n=223) with the highest number found at 51–60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61–70 years age group. The F/M ratio is 1:1.6. The “plane” nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. Discussion and conclusion: This

  15. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  16. Gallstones, a cholecystectomy, chronic pancreatitis, and the risk of subsequent pancreatic cancer in diabetic patients: a population-based cohort study.

    Science.gov (United States)

    Lai, Hsueh-Chou; Tsai, I-Ju; Chen, Pei-Chun; Muo, Chih-Hsin; Chou, Jen-Wei; Peng, Cheng-Yuan; Lai, Shih-Wei; Sung, Fung-Chang; Lyu, Shu-Yu; Morisky, Donald E

    2013-06-01

    The causal association between diabetes and pancreatic cancer remains unclear in Asian populations. This study examined whether gallstones, a cholecystectomy, chronic pancreatitis and the treatment of antidiabetic agents affect the risk of subsequent pancreatic cancer for patients with diabetes in a Taiwanese population. Using claims data from the universal health insurance program in Taiwan, 449,685 newly diagnosed diabetic cases among insured people from 2000 to 2003 were identified as the case group. The comparison group, matched for gender, age, and the index year of the diabetes cohort, consisted of 325,729 persons without diabetes. Pancreatic cancer incidence was measured in both groups until the end of 2008. Other risk factors associated with this cancer were also measured. The incidence of pancreatic cancer in the diabetic cohort was 2-fold greater than that in the comparison group (1.46 vs. 0.71 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.75 [95 % confidence interval (CI) 1.45-2.10]. The risk slightly increased for diabetic patients with gallstones, cholecystitis, and a cholecystectomy (HR 1.92, 95% CI 1.18-3.11), but greatly increased for those with comorbidity of chronic pancreatitis (HR 22.9, 95% CI 12.6-41.4). Pancreatic cancer risk also increased significantly for those patients who used more insulin for treating diabetes (OR 2.20, 95% CI 1.40-3.45). Our data suggest that the risk of pancreatic cancer is moderately increased in patients with diabetes, especially those using insulin therapy. The risk is greatly increased for diabetic patients with chronic pancreatitis.

  17. Meat and fat intake and pancreatic cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Meat contains numerous carcinogens, such as heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds, which can be derived either from natural food or during the process of food preparation. These carcinogens may increase pancreatic cancer risk. Furthermore, studies in animals

  18. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    Science.gov (United States)

    Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N

    2010-07-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50- or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.

  19. Active and passive smoking and risk of death from pancreatic cancer: findings from the Japan Collaborative Cohort Study.

    Science.gov (United States)

    Lin, Yingsong; Yagyu, Kiyoko; Ueda, Junko; Kurosawa, Michiko; Tamakoshi, Akiko; Kikuchi, Shogo

    2013-01-01

    There is uncertainty in the risk of pancreatic cancer with particular aspects of smoking, such as a dose-response relationship and cumulative amount, in Japanese men and women. Very few studies have addressed the role of passive smoking in pancreatic cancer among Japanese women. We examined the association between active or passive smoking and the risk of death from pancreatic cancer using data from the Japan Collaborative Cohort Study. The cohort participants (46,395 men and 64,190 women) were followed-up for mortality from baseline (1988-1990) through December 31, 2009. Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). During follow-up, we recorded 611 pancreatic cancer deaths. After adjustment for potential confounding factors, current smokers had a significantly increased risk of death from pancreatic cancer compared with non-smokers, with an RR of 1.70 (95% CI: 1.33-2.19). The risk of death from pancreatic cancer significantly increased with increasing numbers of cigarettes smoked per day. Exposure to environmental tobacco smoke (ETS) in public spaces was not associated with risk of death from pancreatic cancer. The RR for women who reported ETS exposure was 1.20 (95% CI: 0.87-1.67). Women exposed to ETS during childhood or adolescence had 1.21-fold increased risk, but the association was statistically insignificant. Cigarette smoking is associated with an approximately 70% increase in the risk of death from pancreatic cancer. Further studies with improved exposure assessment are needed to better quantify the association between passive smoking and pancreatic cancer. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  20. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study.

    NARCIS (Netherlands)

    Naudin, Sabine; Li, Kuanrong; Jaouen, Tristan; Assi, Nada; Kyrø, Cecilie; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Védié, Anne-Laure; Boeing, Heiner; Kaaks, Rudolf; Katzke, Verena; Bamia, Christina; Naska, Androniki; Trichopoulou, Antonia; Berrino, Franco; Tagliabue, Giovanna; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Peeters, Petra H; Bueno-de-Mesquita, Bas; Weiderpass Vainio, Elisabete; Gram, Inger Torhild; Skeie, Guri; Chirlaque, Maria-Dolores; Rodríguez-Barranco, Miguel; Barricarte, Aurelio; Quirós, Jose Ramón; Dorronsoro, Miren; Johansson, Ingegerd; Sund, Malin; Sternby, Hanna; Bradbury, Kathryn E; Wareham, Nick; Riboli, Elio; Gunter, Marc; Brennan, Paul; Duell, Eric J; Ferrari, Pietro

    2018-01-01

    Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In this study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking.

  1. Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Navarrete-Muñoz, Eva M; Wark, Petra A; Romaguera, Dora; Bhoo-Pathy, Nirmala; Michaud, Dominique; Molina-Montes, Esther; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Katzke, Verena A; Kühn, Tilman; Steffen, Annika; Trichopoulou, Antonia; Klinaki, Eleni; Papatesta, Eleni-Maria; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Naccarati, Alessio; Mattiello, Amalia; Peeters, Petra H; Rylander, Charlotta; Parr, Christine L; Skeie, Guri; Weiderpass, Elisabete; Quirós, J Ramón; Duell, Eric J; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Key, Tim; Stepien, Magdalena; Freisling, Heinz; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2016-09-01

    The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk. The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa. Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake. Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and

  2. Contribution of DNA repair xeroderma pigmentosum group D genotypes to pancreatic cancer risk in the Chinese Han population

    Directory of Open Access Journals (Sweden)

    Dong Yan

    2017-12-01

    Full Text Available Abstract This study aimed to determine the association between the polymorphisms and haplotypes in the xeroderma pigmentosum group D (XPD gene and the risk of pancreatic cancer in the Chinese Han population. SNaPshot was used for genotyping six SNP sites of the XPD gene. Comparisons of the correlations between different genotypes in combination with smoking and the susceptibility to pancreatic cancer were performed. Individual pancreatic cancer risk in patients who carry mutant C alleles (AC, CC, and AC+CC at rs13181 increased (p < 0.05. Taking non-smoking individuals who carry the AA genotype as a reference, and non-smoking individuals who carry mutant allele C (AC+CC, the risk of pancreatic cancer increased by 3.343 times in individuals who smoked ≥ 20 cigarettes daily, 3.309 times in individuals who smoked ≥ 14 packs per year, 5.011 times in individuals who smoked ≥ 24 packs per year, and 4.013 times in the individuals who smoked ≥ 37 packs per year (P < 0.05. In addition, haplotype analysis revealed that haplotype AGG, which comprised rs13181, rs3916874 and rs238415, was associated with a 1.401-fold increase in pancreatic cancer risk (p < 0.05. We conclude that the polymorphism of XPD Lys751Gln (rs13181 in combination with smoking contributes to increased risk of pancreatic cancer in the Chinese Han population. Haplotype AGG might be a susceptibility haplotype for pancreatic cancer.

  3. Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

    Science.gov (United States)

    Olson, Sara H; Hsu, Meier; Satagopan, Jaya M; Maisonneuve, Patrick; Silverman, Debra T; Lucenteforte, Ersilia; Anderson, Kristin E; Borgida, Ayelet; Bracci, Paige M; Bueno-de-Mesquita, H Bas; Cotterchio, Michelle; Dai, Qi; Duell, Eric J; Fontham, Elizabeth H; Gallinger, Steven; Holly, Elizabeth A; Ji, Bu-Tian; Kurtz, Robert C; La Vecchia, Carlo; Lowenfels, Albert B; Luckett, Brian; Ludwig, Emmy; Petersen, Gloria M; Polesel, Jerry; Seminara, Daniela; Strayer, Lori; Talamini, Renato

    2013-09-01

    In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

  4. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Takeda, Yutaka; Kitagawa, Toru; Nakamori, Shoji

    2009-01-01

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  5. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

    DEFF Research Database (Denmark)

    Naudin, Sabine; Li, Kuanrong; Jaouen, Tristan

    2018-01-01

    Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In this study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking...... alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake. This article is protected by copyright. All rights reserved....

  6. Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

    Science.gov (United States)

    Jeurnink, Suzanne M; Ros, Martine M; Leenders, Max; van Duijnhoven, Franzel J B; Siersema, Peter D; Jansen, Eugene H J M; van Gils, Carla H; Bakker, Marije F; Overvad, Kim; Roswall, Nina; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Grote, Verena; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Krogh, Vittorio; Vineis, Paolo; Tumino, Rosario; Mattiello, Amalia; Weiderpass, Elisabete; Skeie, Guri; Castaño, José María Huerta; Duell, Eric J; Barricarte, Aurelio; Molina-Montes, Esther; Argüelles, Marcial; Dorronsoro, Mire; Johansen, Dorthe; Lindkvist, Björn; Sund, Malin; Crowe, Francesca L; Khaw, Kay-Tee; Jenab, Mazda; Fedirko, Veronika; Riboli, E; Bueno-de-Mesquita, H B

    2015-03-15

    Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. © 2014 UICC.

  7. Helicobacter pylori infection, atrophic gastritis, and pancreatic cancer risk: A meta-analysis of prospective epidemiologic studies.

    Science.gov (United States)

    Liu, Hong; Chen, Yue-Tong; Wang, Rui; Chen, Xin-Zu

    2017-08-01

    To investigate the associations of Helicobacter pylori (Hp) infection and atrophic gastritis (AG) with pancreatic cancer risk. A literature search in PubMed was performed up to July 2017. Only prospective cohort and nested case-control studies enrolling cancer-free participants were eligible. Incident pancreatic cancer cases were ascertained during the follow-up. The risks of pancreatic cancer were compared between persons infected and noninfected with Hp, or between those with and without AG status at baseline. Odds ratios (ORs) or hazard ratios were combined. Subgroup and sensitivity analyses were performed, and publication bias was estimated. Three cohort studies and 6 nested case-control studies, including 65,155 observations, were analyzed. The meta-analyses did not confirm the association between pancreatic cancer risk and Hp infection (OR = 1.09, 95% confidence interval [CI] = 0.81-1.47) or AG status (OR = 1.18, 95% CI = 0.80-1.72). However, particular subpopulations potentially had increased risks of pancreatic cancer. Cytotoxin-associated gene A (CagA)-negative strains of Hp might be a causative factor of pancreatic cancer (OR = 1.30, 95% CI = 1.05-1.62), but a sensitivity analysis by leave-one-out method did not fully warrant it (OR = 1.20, 95% CI = 0.93-1.56). In 1 nested case-control study, AG at stomach corpus in Hp-negative subpopulation might have increased risk of pancreatic cancer, but with a poor test power = 0.56. Publication biases were nonsignificant in the present meta-analysis. Based on current prospective epidemiologic studies, the linkage of pancreatic cancer to Hp infection or AG status was not warranted on the whole. Nevertheless, prospective studies only focusing on those specific subpopulations are further required to obtain better power.

  8. Green Tea Consumption and Risk of Pancreatic Cancer: A Meta-analysis

    Directory of Open Access Journals (Sweden)

    Jin-Long Zeng

    2014-10-01

    Full Text Available Emerging laboratory and animal studies indicate that green tea inhibits development and progression of pancreatic cancer, but evidence from epidemiologic studies appears inconsistent and inconclusive. A meta-analysis summarizing published case-control and cohort studies was performed to evaluate the association of green tea consumption with risk of pancreatic cancer. Pertinent studies were identified by a search of PubMed and EMBASE up to April 2014. A random-effects model was assigned to compute summary risk estimates. A total of three case-control studies and five prospective studies were included, comprising 2317 incident cases and 288209 subjects. Of them, three studies were from China and the reminders were conducted in Japan. Overall, neither high vs. low green consumption (odds ratio (OR = 0.99, 95% confidence interval [CI] = 0.78–1.25, nor an increase in green tea consumption of two cups/day (OR = 0.95, 95% CI = 0.85–1.06 was associated with risk of pancreatic cancer. The null association persisted when the analysis was stratified by sex or restricted to non-smokers. In the stratification by study location, the summary OR for the studies from China and for those from Japan was 0.77 (95% CI = 0.60–0.99 and 1.21 (95% CI = 0.94–1.54, respectively (P for differences = 0.04. Cumulative epidemiologic evidence suggests that green tea consumption is not associated with pancreatic cancer.

  9. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    Science.gov (United States)

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  10. Pancreatic cancer

    International Nuclear Information System (INIS)

    Diamond, D.; Fisher, B.

    1975-01-01

    Diagnostic and therapeutic advances of the last 30 years have left unchanged the course and prognosis of carcinoma of the exocrine pancreas. The most important reasons for this are the anatomic location and biologic nature of the tumor. An additional factor of importance is the consistently reported 4 to 9 month delay in diagnosis, also unchanged in 30 years. Recent controversy has developed concerning the mainstay of our current surgical treatment surgical treatment, the Whipple pancreaticoduodenectomy and its modifications, and its role as the most efficacious surgical approach to this disease. It is the purpose of this paper to review and summarize the clinical characteristics of carcinoma of the exocrine pancreas and to review and reassess the standard operative approach. Cancer of the head, body, and tail of the pancreas will be considered together because they have many features in common

  11. Hypermutation in pancreatic cancer

    OpenAIRE

    Humphris, Jeremy L.; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J.; Johns, Amber L.; McKay, Skye; Chang, David K.; Miller, David K.; Pajic, Marina; Kassahn, Karin S.; Quinn, Michael C.J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechan...

  12. Molecular biology of pancreatic cancer.

    Science.gov (United States)

    Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

    2011-06-28

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  13. Diabetes, pancreatic cancer, and metformin therapy

    Directory of Open Access Journals (Sweden)

    Jun eGong

    2014-11-01

    Full Text Available Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1, and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.

  14. Ingested nitrate and nitrite, disinfection by-products, and pancreatic cancer risk in postmenopausal women.

    Science.gov (United States)

    Quist, Arbor J L; Inoue-Choi, Maki; Weyer, Peter J; Anderson, Kristin E; Cantor, Kenneth P; Krasner, Stuart; Freeman, Laura E Beane; Ward, Mary H; Jones, Rena R

    2018-01-15

    Nitrate and nitrite are precursors of N-nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by-products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986-2011). We used historical monitoring and treatment data to estimate levels of long-term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one-half the maximum contaminant level (>½ MCL; 5 mg/L nitrate-nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HR p95 vs . Q1  = 1.16, 95% CI: 0.51-2.64). Associations with average TTHM levels were also null (HR Q4 vs . Q1  = 0.70, 95% CI:0.42-1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HR p95 vs . Q1  = 1.66, 95% CI 1.00-2.75;p trend  = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer. 2017 UICC.

  15. Stages of Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  16. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium.

    Science.gov (United States)

    Campa, Daniele; Obazee, Ofure; Pastore, Manuela; Panzuto, Francesco; Liço, Valbona; Greenhalf, William; Katzke, Verena; Tavano, Francesca; Costello, Eithne; Corbo, Vincenzo; Talar-Wojnarowska, Renata; Strobel, Oliver; Zambon, Carlo Federico; Neoptolemos, John P; Zerboni, Giulia; Kaaks, Rudolf; Key, Timothy J; Lombardo, Carlo; Jamroziak, Krzysztof; Gioffreda, Domenica; Hackert, Thilo; Khaw, Kay-Tee; Landi, Stefano; Milanetto, Anna Caterina; Landoni, Luca; Lawlor, Rita T; Bambi, Franco; Pirozzi, Felice; Basso, Daniela; Pasquali, Claudio; Capurso, Gabriele; Canzian, Federico

    2017-08-01

    Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which very little is known about either environmental or genetic risk factors. Only a handful of association studies have been performed so far, suggesting a small number of risk loci. Methods: To replicate the best findings, we have selected 16 SNPs suggested in previous studies to be relevant in PNET etiogenesis. We genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634, rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081, rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and 2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium. Results: After correction for multiple testing, we did not observe any statistically significant association between the SNPs and PNET risk. We also used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict a possible functional role of the SNPs, but we did not observe any clear indication. Conclusions: None of the selected SNPs were convincingly associated with PNET risk in the PANDoRA consortium. Impact: We can exclude a major role of the selected polymorphisms in PNET etiology, and this highlights the need for replication of epidemiologic findings in independent populations, especially in rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349-51. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  19. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  20. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  1. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.

    Science.gov (United States)

    Fan, Xiaozhou; Alekseyenko, Alexander V; Wu, Jing; Peters, Brandilyn A; Jacobs, Eric J; Gapstur, Susan M; Purdue, Mark P; Abnet, Christian C; Stolzenberg-Solomon, Rachael; Miller, George; Ravel, Jacques; Hayes, Richard B; Ahn, Jiyoung

    2018-01-01

    A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans , were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study. This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  2. Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study.

    Science.gov (United States)

    Huang, Jiaqi; Zagai, Ulrika; Hallmans, Göran; Nyrén, Olof; Engstrand, Lars; Stolzenberg-Solomon, Rachael; Duell, Eric J; Overvad, Kim; Katzke, Verena A; Kaaks, Rudolf; Jenab, Mazda; Park, Jin Young; Murillo, Raul; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Bradbury, Kathryn E; Riboli, Elio; Aune, Dagfinn; Tsilidis, Konstantinos K; Capellá, Gabriel; Agudo, Antonio; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Weiderpass, Elisabete; Tjønneland, Anne; Olsen, Anja; Martínez, Begoña; Redondo-Sanchez, Daniel; Chirlaque, Maria-Dolores; Hm Peeters, Petra; Regnér, Sara; Lindkvist, Björn; Naccarati, Alessio; Ardanaz, Eva; Larrañaga, Nerea; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Barré, Amélie; Bueno-de-Mesquita, H B As; Ye, Weimin

    2017-04-15

    The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms. © 2016 UICC.

  3. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  4. Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer

    International Nuclear Information System (INIS)

    Gemici, Cengiz; Sargin, Mehmet; Uygur-Bayramicli, Oya; Mayadagli, Alpaslan; Yaprak, Gokhan; Dabak, Resat; Kocak, Mihriban

    2013-01-01

    Background: Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Materials and methods: Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. Results: At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Conclusions: Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk

  5. Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer.

    Science.gov (United States)

    Gemici, Cengiz; Sargin, Mehmet; Uygur-Bayramicli, Oya; Mayadagli, Alpaslan; Yaprak, Gokhan; Dabak, Resat; Kocak, Mihriban

    2013-05-01

    Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. ABO blood group and risk of pancreatic cancer in a Turkish population in Western Blacksea region.

    Science.gov (United States)

    Engin, Huseyin; Bilir, Cemil; Üstün, Hasan; Gökmen, Ayla

    2012-01-01

    We aimed to investigate the relationship between blood groups and pancreatic cancer in a Turkish population in Western Blacksea region. This is a retrospective study. Zonguldak Karaelmas University outpatient oncology clinic records were screened for the period between 2004 and 2011. The median age of patients were 56 (± 16) and 132 of 633 study population had pancreatic cancer. Pancreatic cancer patients had significantly higher rates of blood group A compared to controls (OR 1.8, 95%CI, p 0.005). Rates of blood group AB was significantly lower than the control group (OR 0.37, 95% CI, p 0.04). The median survival (IR) time in subjects having the blood groups A, B, AB and O were 7.0 (1-28), 7.0 (2-38), 10 (2-36) and 9.0 (2-48) months respectively; the blood group 0 had significantly higher overall survival (OS) compared to the non-0 groups (p 0.04). Pancreatic cancer patients had more common blood group A in our population. Moreover, blood group AB appeared to be a protective factor against pancreatic cancer in our population. Blood group 0 had a significantly longer survival compared to non-0, regardless of prognostic factors.

  7. Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

    Science.gov (United States)

    Molina-Montes, E; Gomez-Rubio, P; Márquez, M; Rava, M; Löhr, M; Michalski, C W; Molero, X; Farré, A; Perea, J; Greenhalf, W; Ilzarbe, L; O'Rorke, M; Tardón, A; Gress, T; Barberà, V M; Crnogorac-Jurcevic, T; Domínguez-Muñoz, E; Muñoz-Bellvís, L; Balsells, J; Costello, E; Huang, J; Iglesias, M; Kleeff, J; Kong, Bo; Mora, J; Murray, L; O'Driscoll, D; Poves, I; Scarpa, A; Ye, W; Hidalgo, M; Sharp, L; Carrato, A; Real, F X; Malats, N

    2018-04-01

    Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

  8. Is screening for pancreatic cancer in high-risk groups cost-effective?

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Gerdes, Anne-Marie; Sørensen, Jan

    2016-01-01

    OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems to......$ per QALY. CONCLUSIONS: With a threshold value of 50,000 US$ per QALY this screening program appears to constitute a cost-effective intervention although screening of HP patients appears to be less cost-effective than FPC patients....... with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no......-screening was assessed by the incremental cost-utility ratio (ICER). RESULTS: By screening the FPC group we identified 2 patients with PDAC who were treated by total pancreatectomy. One patient is still alive, while the other died after 7 months due to cardiac surgery complications. Stratified analysis of patients...

  9. Pancreatic cancer: any prospects for prevention?

    OpenAIRE

    Hart, A.

    1999-01-01

    Primary prevention of pancreatic cancer and public health measures to reduce its incidence are dependent on data from epidemiological studies. Currently, the only definite risk factor is smoking, although a diet rich in fruit and vegetables may be protective. The K-ras mutation may have a role in diagnosis and screening.


Keywords: pancreatic cancer; epidemiology; risk factors; smoking; diet; alcohol

  10. Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus

    DEFF Research Database (Denmark)

    Andersen, E S; Omland, L H; Jepsen, Peter

    2015-01-01

    The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim...

  11. Systemic therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Andrezalova Vochyanova, I.; Salek, T.

    2012-01-01

    Pancreatic cancer is the fourth comment cause of cancer-related death in men. Most patients with pancreatic cancer are diagnosed at advanced, non-resectable stage. Late detection, early metastases, difficult surgical approached, cancer resistant to systemic chemo and radiotherapy - all contribute to its in faust prognosis. Only about 5 % of patients will live 5 years after diagnosis. Gemcitabine - based combination treatments is the standard for advanced pancreatic cancer. The combination of fluorouracil, folinic acid, irinotecan and oxaliplatin led to median survival of 11 months. No standard second-line treatment exists for pancreatic cancer. (author)

  12. Current knowledge on pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Juan eIovanna

    2012-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3-5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes and the deregulation of many signalling pathways. Therefore, the strategies targeting these molecules as well as their downstream signalling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical and therapeutic aspects of pancreatic cancer.

  13. Current Knowledge on Pancreatic Cancer

    International Nuclear Information System (INIS)

    Iovanna, Juan; Mallmann, Maria Cecilia; Gonçalves, Anthony; Turrini, Olivier; Dagorn, Jean-Charles

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  14. Current Knowledge on Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iovanna, Juan [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France); Mallmann, Maria Cecilia [Centre d’Investigation Clinique de Marseille, Marseille (France); Gonçalves, Anthony [Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille (France); Turrini, Olivier [Département de Chirurgie Oncologique, Institut Paoli-Calmettes, Marseille (France); Dagorn, Jean-Charles, E-mail: juan.iovanna@inserm.fr [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France)

    2012-01-31

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  15. COFFEE, TEA AND SUGAR-SWEETENED CARBONATED SOFT DRINK INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF 14 COHORT STUDIES

    Science.gov (United States)

    Genkinger, Jeanine M.; Li, Ruifeng; Spiegelman, Donna; Anderson, Kristin E.; Albanes, Demetrius; Bergkvist, Leif; Bernstein, Leslie; Black, Amanda; van den Brandt, Piet A.; English, Dallas R.; Freudenheim, Jo L.; Fuchs, Charles S.; Giles, Graham G.; Giovannucci, Edward; Goldbohm, R. Alexandra; Horn-Ross, Pamela L.; Jacobs, Eric J.; Koushik, Anita; Männistö, Satu; Marshall, James R.; Miller, Anthony B.; Patel, Alpa V.; Robien, Kim; z, Thomas E.; Schairer, Catherine; Stolzenberg-Solomon, Rachael; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2011-01-01

    BACKGROUND Coffee has been hypothesized to have pro- and anti-carcinogenic properties, while tea may contain anti-carcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, while findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (abbreviated as SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model. RESULTS No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR=1.10, 95% CI=0.81-1.48 comparing ≥900 to 0.05). These associations were consistent across levels of sex, smoking status and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR=1.06, 95% CI=1.02-1.12). CONCLUSION AND IMPACT Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB. PMID:22194529

  16. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    : Death is monitored using data from the Danish Civil Registry. This registry monitors the survival status of the Danish population, and the registration is virtually complete. All data in the database are audited by all participating institutions, with respect to baseline characteristics, key indicators......AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients...... with microscopically verified ductal adenocarcinoma of the pancreas have been registered in the database. As of June 30, 2014, the total number of patients registered was 2,217. All data are cross-referenced with the Danish Pathology Registry and the Danish Patient Registry to ensure the completeness of registrations...

  17. Parity and pancreatic cancer risk: a dose-response meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. METHODS: Relevant published studies of parity and PC were identified using MEDLINE (PubMed and Web of Science databases until November 2013. Two authors (H-BG and LW independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR estimates and 95% confidence intervals (CIs of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. RESULTS: The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%. Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR = 0.81; 95% CI: 0.68-0.98, Type 2 diabetes mellitus (RR = 0.83; 95% CI: 0.75-0.93, and those that included all confounders or important risk factors (RR = 0.85; 95% CI: 0.76-0.96. Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83, P<0.001, I2 = 69.8%, which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: In summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.

  18. Low-fat Dietary Pattern and Pancreatic Cancer Risk in the Women's Health Initiative Dietary Modification Randomized Controlled Trial.

    Science.gov (United States)

    Jiao, Li; Chen, Liang; White, Donna L; Tinker, Lesley; Chlebowski, Rowan T; Van Horn, Linda V; Richardson, Peter; Lane, Dorothy; Sangi-Haghpeykar, Haleh; El-Serag, Hashem B

    2018-01-01

    Observational studies suggest that diet may influence pancreatic cancer risk. We investigated the effect of a low-fat dietary intervention on pancreatic cancer incidence. The Women's Health Initiative Dietary Modification (WHI-DM) trial is a randomized controlled trial conducted in 48 835 postmenopausal women age 50 to 79 years in the United States between 1993 and 1998. Women were randomly assigned to the intervention group (n = 19 541), with the goal of reducing total fat intake and increasing intake of vegetables, fruits, and grains, or to the usual diet comparison group (n = 29 294). The intervention concluded in March 2005. We evaluated the effect of the intervention on pancreatic cancer incidence with the follow-up through 2014 using the log-rank test and multivariable Cox proportional hazards regression model. All statistical tests were two-sided. In intention-to-treat analyses including 46 200 women, 92 vs 165 pancreatic cancer cases were ascertained in the intervention vs the comparison group (P = .23). The multivariable hazard ratio (HR) of pancreatic cancer was 0.86 (95% confidence interval [CI] = 0.67 to 1.11). Risk was statistically significantly reduced among women with baseline body mass indexes (BMIs) of 25 kg/m2 or higher (HR = 0.71, 95% CI = 0.53 to 0.96), but not among women with BMIs of less than 25 kg/m2 (HR = 1.62, 95% CI = 0.97 to 2.71, Pinteraction = .01). A low-fat dietary intervention was associated with reduced pancreatic cancer incidence in women who were overweight or obese in the WHI-DM trial. Caution needs to be taken in interpreting the findings based on subgroup analyses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Diagnostic Management of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

    2011-01-31

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.

  20. Diagnostic Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Dabizzi, Emanuele; Assef, Mauricio Saab; Raimondo, Massimo

    2011-01-01

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used

  1. Current radiotherapeutic approaches to pancreatic cancer

    International Nuclear Information System (INIS)

    Dobelbower, R.R. Jr.

    1981-01-01

    Adenocarcinoma of the pancreas is not a radioresistant neoplasm, as was once believed. The data now suggest that in some instances this cancer may be radiocurable. This fact seems to justify the risk of pancreatic biopsy even in the face of unresectable disease, for it is well known that many benign conditions imitate pancreatic cancer. Clinical benefit from radiation for pancreatic cancer treatment is dose related. Careful delineation of tumor margins, precision treatment planning, and precision dose delivery can minimize damage to adjacent normal tissues. Interstitial implantation and intraoperative electron beam therapy are being studied as methods of accurate dose delivery for pancreatic cancer. Fractionation studies and high LET studies are in embryonic stages. Combined modality regimens may have much to offer in terms of improved palliation and survival for patients with localized adenocarcinoma of the pancreas

  2. Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

    Science.gov (United States)

    Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

    2018-04-01

    Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier

  3. Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Haining; Liu, Ye; Tian, Qing; Yang, Jin; Lu, Ran; Zhan, Siyan; Haukka, Jari; Hong, Tianpei

    2018-04-01

    To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM). For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and ClininalTrials.gov databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of ≥52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate. A total of 33 studies (n = 79 971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55 248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for ≥104 weeks, 84 pancreatic cancer events were identified in 59 919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95). Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for ≥104 weeks. © 2017 John Wiley & Sons Ltd.

  4. Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case–control study in Japan

    International Nuclear Information System (INIS)

    Lin, Yingsong; Kikuchi, Shogo; Ueda, Junko; Yagyu, Kiyoko; Ishii, Hiroshi; Ueno, Makoto; Egawa, Naoto; Nakao, Haruhisa; Mori, Mitsuru; Matsuo, Keitaro

    2013-01-01

    It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. We conducted a hospital-based case–control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk. The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07–2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70–3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07–1.85). There were no significant interactions between TA/AA genotypes and body mass index. Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples

  5. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  6. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  7. Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase (CEL) gene as risk factors in pancreatic cancer.

    Science.gov (United States)

    Dalva, Monica; El Jellas, Khadija; Steine, Solrun J; Johansson, Bente B; Ringdal, Monika; Torsvik, Janniche; Immervoll, Heike; Hoem, Dag; Laemmerhirt, Felix; Simon, Peter; Lerch, Markus M; Johansson, Stefan; Njølstad, Pål R; Weiss, Frank U; Fjeld, Karianne; Molven, Anders

    We have recently described copy number variants (CNVs) of the human carboxyl-ester lipase (CEL) gene, including a recombined deletion allele (CEL-HYB) that is a genetic risk factor for chronic pancreatitis. Associations with pancreatic disease have also been reported for the variable number of tandem repeat (VNTR) region located in CEL exon 11. Here, we examined if CEL CNVs and VNTR length polymorphisms affect the risk for developing pancreatic cancer. CEL CNVs and VNTR were genotyped in a German family with non-alcoholic chronic pancreatitis and pancreatic cancer, in 265 German and 197 Norwegian patients diagnosed with pancreatic adenocarcinoma, and in 882 controls. CNV screening was performed using PCR assays followed by agarose gel electrophoresis whereas VNTR lengths were determined by DNA fragment analysis. The investigated family was CEL-HYB-positive. However, an association of CEL-HYB or a duplication CEL allele with pancreatic cancer was not seen in our two patient cohorts. The frequency of the 23-repeat VNTR allele was borderline significant in Norwegian cases compared to controls (1.2% vs. 0.3%; P = 0.05). For all other VNTR lengths, no statistically significant difference in frequency was observed. Moreover, no association with pancreatic cancer was detected when CEL VNTR lengths were pooled into groups of short, normal or long alleles. We could not demonstrate an association between CEL CNVs and pancreatic cancer. An association is also unlikely for CEL VNTR lengths, although analyses in larger materials are necessary to completely exclude an effect of rare VNTR alleles. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Recent Progress in Pancreatic Cancer

    Science.gov (United States)

    Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

    2013-01-01

    Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

  9. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  10. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... Acute Pancreatitis in Children Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and ...

  11. Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study

    OpenAIRE

    Makhoul, Issam; Yacoub, Abdulraheem; Siegel, Eric

    2016-01-01

    Background: The etiology of pancreatic cancer remains elusive. Several studies have suggested a role for diabetes mellitus, but the magnitude of its contribution remains controversial. Objectives: Utilizing a large administrative database, this retrospective cohort study was designed to investigate the relationship between type 2 diabetes mellitus and pancreatic cancer. Patients and design: Using the Veterans Integrated Services Network 16 database, 322,614 subjects were enrolled in the study...

  12. Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic Cancer: Three Different Lines of Evidence

    Directory of Open Access Journals (Sweden)

    Aleksandra Buha

    2017-01-01

    Full Text Available Although profoundly studied, etiology of pancreatic cancer (PC is still rather scant. Exposure to cadmium (Cd, a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.

  13. Vitamin D and pancreatic cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.

    2008-01-01

    Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultra-violet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D3-1α-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)2 D form. Thus, 25(OH)D concentrations could affect pancreatic fun...

  14. A Cohort Study of Adolescent and Midlife Diet and Pancreatic Cancer Risk in the NIH-AARP Diet and Health Study.

    Science.gov (United States)

    Gordon-Dseagu, Vanessa L Z; Thompson, Frances E; Subar, Amy F; Ruder, Elizabeth H; Thiébaut, Anne C M; Potischman, Nancy; Stolzenberg-Solomon, Rachael

    2017-08-01

    Given the long latency period of pancreatic cancer, exploring the influence of early and midlife exposures will further advance our understanding of the disease. We assessed associations between diet and pancreatic cancer incidence in the National Institutes of Health (NIH)-AARP (formerly American Association of Retired Persons) Diet and Health Study. In 1996, a total of 303,094 participants completed 2 food frequency questionnaires that assessed diet at ages 12-13 years and 10 years previously. We used Cox proportional hazards regression to estimate adjusted hazard ratios and 95% confidence intervals. Through the end of 2006, a total of 1,322 pancreatic cancer cases occurred (average follow up time = 10.1 years). When comparing the highest tertiles with the lowest, carbohydrate intake during adolescence (hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.76, 0.99), but not 10 years before baseline, was inversely associated with pancreatic cancer risk. Total fat intake 10 years before baseline was significantly associated with increased risk (HR = 1.17, 95% CI: 1.02, 1.34), while risk was higher for high fat intake during both adolescence and midlife. Calcium intake 10 years before baseline was associated with reduced risk (HR = 0.87, 95% CI: 0.76, 0.99), as was a change from low intake in adolescence to high intake in midlife (HR = 0.71, 95% CI: 0.54, 0.93). Our study found a number of dietary factors present during adolescence and midlife to be associated with pancreatic cancer. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Incidence of pancreatic cancer in Denmark

    DEFF Research Database (Denmark)

    Weble, Tanja Cruusberg; Bjerregaard, Jon Kroll; Kissmeyer, Peter

    2017-01-01

    BACKGROUND: The aim of this study was to monitor the evolution of the incidence of pancreatic cancer in Denmark over 70 years. We also compared registrations of pancreatic cancer in a nationwide population-based database, the Danish Cancer Registry, and a clinical database, the Danish Pancreatic...... Cancer Database, in 2012-2013. MATERIAL AND METHODS: Registrations of pancreatic cancer from the Danish Cancer Registry over 1943-2012 were used to calculate age-specific incidence rates per 100 000 person years by sex and age in 5-year period, weighted by the Segi World Standard Population for age...... standardization. We used absolute numbers from the Cancer Registry and the Pancreatic Cancer Database, including distribution of topography of cancers registered in 2012-2013, to compare registration in the two data sources. RESULTS: The incidence rates of pancreatic cancer among Danish men increased until 1968...

  16. [Treatments for Pancreatic Cancer with Oligometastasis].

    Science.gov (United States)

    Furuse, Junji

    2017-10-01

    Pancreatic cancer, adenocarcinoma, generally rapidly progresses, and if a metastatic lesion is detected, chemotherapy is applied even in solitary metastasis. However, surgical resection for solitary metastasis have been reported to achieve long survival in some pancreatic cancer patients. In a prospective study of surgery for hepatic and lymph node oligometastasis of pancreatic cancer, long survival of 5 years or more was reported around 10%. Furthermore, longer survival and fewer rerecurrence were achieved with surgery in lung metastasis than in liver metastasis and loco-regional recurrence. Although there has been no establishment of concept or no consensus of treatment strategy for oligometastasis in pancreatic cancer, some patients with pancreatic cancer have long disease-free survival by surgery for oligometastasis. A population of pancreatic cancer patients who have benefits of surgery for oligometastasis should be identified, and it is necessary to establish treatments for oligometastasis as standard treatments in pancreatic cancer.

  17. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  18. Chronic alcohol drinking: Liver and pancreatic cancer?

    Science.gov (United States)

    Zakhari, Samir

    2015-09-01

    Cancer is a multifactorial disease that results from complex interactions of numerous risk factors - genetic and environmental - over time, eventually leading to the diseased phenotypes. Thus, while epidemiological studies can point to risk factors, they cannot determine cause and effect relationships, and are unable to give biological and clinical insights into carcinogenesis. The link between any risk factor and carcinogenesis needs to be validated in experimental models. This is particularly true in epidemiological studies on alcohol consumption and its consequences. While there is no doubt that heavy alcohol consumption has devastating health effects, the inconsistencies in alcohol-related epidemiological studies and cancer suffer from possible sources of the variability in outcomes, ranging from inaccuracy of self-report of consumption to the problem of correlating cancer that started decades earlier to current or recent alcohol consumption. To further study the interactions between alcohol and cancer, the use of "Molecular Pathological Epidemiology" (MPE) advocated by Ogino et al. for dissecting the interplay between etiological factors, cellular and molecular characteristics, and disease progression in cancer is appropriate. MPE does not consider cancer as a single entity, rather it integrates analyses of epidemiological studies with the macroenvironment and molecular and microenvironment. This approach allows investigating the relationships between potential etiological agents and cancer based on molecular signatures. More research is needed to fully elucidate the link between heavy alcohol consumption and pancreatic cancer, and to further investigate the roles of acetaldehyde and FAEEs in pancreatic carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Endoscopic Palliation for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Mihir Bakhru

    2011-04-01

    Full Text Available Pancreatic cancer is devastating due to its poor prognosis. Patients require a multidisciplinary approach to guide available options, mostly palliative because of advanced disease at presentation. Palliation including relief of biliary obstruction, gastric outlet obstruction, and cancer-related pain has become the focus in patients whose cancer is determined to be unresectable. Endoscopic stenting for biliary obstruction is an option for drainage to avoid the complications including jaundice, pruritus, infection, liver dysfunction and eventually failure. Enteral stents can relieve gastric obstruction and allow patients to resume oral intake. Pain is difficult to treat in cancer patients and endoscopic procedures such as pancreatic stenting and celiac plexus neurolysis can provide relief. The objective of endoscopic palliation is to primarily address symptoms as well improve quality of life.

  20. New insights into pancreatic cancer biology.

    Science.gov (United States)

    Hidalgo, M

    2012-09-01

    Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

  1. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  2. Pancreatic cancer stromal biology and therapy

    Science.gov (United States)

    Xie, Dacheng; Xie, Keping

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

  3. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Pastore, M.; Gentiluomo, M.; Talar-Wojnarowska, R.; Kupcinskas, J.; Malecka-Panas, E.; Neoptolemos, J. P.; Niesen, W.; Vodička, Pavel; Delle Fave, G.; Bueno-de-Mesquita, H. B.; Gazouli, M.; Pacetti, P.; Di Leo, M.; Ito, H.; Klüter, H.; Souček, P.; Corbo, V.; Yamao, K.; Hosono, S.; Kaaks, R.; Vashist, Y.; Gioffreda, D.; Strobel, O.; Shimizu, Y.; Dijk, F.; Andriulli, A.; Ivanauskas, A.; Bugert, P.; Tavano, F.; Vodičková, L.; Zambon, C.F.; Lovecek, M.; Landi, S.; Key, T. J.; Boggi, U.; Pezzilli, R.; Jamroziak, K.; Mohelníková-Duchoňová, B.; Mambrini, A.; Bambi, F.; Busch, O.; Pazienza, V.; Valente, R.; Theodoropoulos, G.E.; Hackert, T.; Capurso, G.; Cavestro, G.M.; Pasquali, C.; Basso, D.; Sperti, C.; Matsuo, K.; Büchler, M.; Khaw, K. T.; Izbicki, J.; Costello, E.; Katzke, V.; Michalski, Ch.; Stepien, A.; Rizzato, C.; Canzian, F.

    2016-01-01

    Roč. 7, č. 35 (2016), s. 57011-57020 ISSN 1949-2553 R&D Projects: GA ČR GAP301/12/1734 Institutional support: RVO:68378041 Keywords : pancreatic cancer * CDKN2A * single nucleotide polymorphisms Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.168, year: 2016

  4. A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Chuang, Shu-Chun; Stolzenberg-Solomon, Rachael; Ueland, Per Magne; Vollset, Stein Emil; Midttun, Oivind; Olsen, Anja; Tjonneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Morois, Sophie; Clavel-Chapelon, Francoise; Teucher, Birgit; Kaaks, Rudolf; Weikert, Cornelia; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Naska, Androniki; Jenab, Mazda; Slimani, Nadia; Romieu, Isabelle; Michaud, Dominique S.; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Skeie, Guri; Duell, Eric J.; Rodriguez, Laudina; Molina-Montes, Esther; Maria Huerta, Jose; Larranaga, Nerea; Barricarte Gurrea, Aurelio; Johansen, Dorthe; Manjer, Jonas; Ye, Weimin; Sund, Malin; Peeters, Petra H. M.; Jeurnink, Suzanne; Wareham, Nicholas; Khaw, Kay-Tee; Crowe, Francesca; Riboli, Elio; Bueno-de-Mesquita, Bas; Vineis, Paolo

    Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin

  5. Hedgehog signaling and therapeutics in pancreatic cancer.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

  6. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... for BRCA2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ... and PALB2 gene mutations. We advise that people speak with a trained cancer genetics counselor before undergoing genetic ...

  7. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W. Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch

  8. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  9. Ultrasonographic diagnosis of pancreatic and peripancreatic cancer

    International Nuclear Information System (INIS)

    Park, Churl Min; Kim, Ho Kyun; Yoon, Yup; Lee, Sun Wha; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Seventeen cases of cancers in and adjacent to the pancreas were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducer. The result were as follows: 1. In a total of 17 cases, 7 cases were pancreatic cancers and the rests were 3 cases of ampulla of Vaster cancer, 3 cases of distal CBD cancers, and 4 cases of metastatic cancers, respectively. 2. Pancreatic cancers were located mainly in head portion, and metastatic cancers were noted in head, tail, and retropancreatic areas. 3. The sizes of all distal CBD cancer were less than 1.8 cm, usually smaller than other tumors, and the size of metastatic cancers were variable (1-6 cm). 4. The shape, margin, contour and echogenicity of the tumors were variable. 5. Pancreatic duct showed marked dilatation in one of pancreatic cancer, and mild dilatation in one of ampulla of Vater cancer. 6. The caliber of extrahepatic duct were moderately or markedly dilated in nearly all cases except 2 cases of pancreatic body cancer. 7. The pancreatic margin is partially obliterated in pancreatic and ampulla of Vater cancers but not in distal CBD cancer. 8. Gallbladder enlargement is secondary change due to the obstruction of extrahepatic bile duct. 9. Effects on the vessels are due to not only direct mass effect but direct invasion resulting in obliteration. The most commonly involved vessels are spleno-portal junction, splenic vein and portal vein. In case of pancreatic cancer in uncinate process, the superior mesenteric vessels are displaced anteriorly. 10. Surrounding metastatic lesions were suspected in pancreatic and ampulla of Vater cancer, but not seen in distal CBD cancer. 11. Ascites were seen in only two cases of metastasis

  10. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  11. Biomarkers and Targeted Therapy in Pancreatic Cancer.

    Science.gov (United States)

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  12. Diagnosis and treatment of pancreatic cancer. Oncology overview

    International Nuclear Information System (INIS)

    1982-09-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiological diagnosis of pancreatic cancer; Biopsy and cytology in the diagnosis of pancreatic cancer; Pathology and morphology of pancreatic cancer; Staging and prognosis of pancreatic cancer; Biological and immunological markers in the diagnosis of pancreatic cancer; Surgical treatment of pancreatic cancer; Drug therapy of pancreatic cancer; Radiation therapy of pancreatic cancer; Selected studies on the epidemiology of pancreatic cancer; Clinical correlates and syndromes associated with pancreatic neoplasia

  13. Apoptosis: Targets in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Kalthoff Holger

    2003-01-01

    Full Text Available Abstract Pancreatic adenocarcinoma is characterized by poor prognosis, because of late diagnosis and lack of response to chemo- and/or radiation therapies. Resistance to apoptosis mainly causes this insensitivity to conventional therapies. Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Certain genetic disturbances of apoptotic signaling pathways have been found in carcinomas leading to tumor development and progression. In the past few years, the knowledge about the complex pathways of apoptosis has strongly increased and new therapeutic approaches based on this knowledge are being developed. This review will focus on the role of apoptotic proteins contributing to pancreatic cancer development and progression and will demonstrate possible targets to influence this deadly disease.

  14. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  15. Immunotherapy for pancreatic cancer: present and future.

    Science.gov (United States)

    Aroldi, Francesca; Zaniboni, Alberto

    2017-06-01

    Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer. Thus, therapies acting on innate or adaptive immunity are being investigated. Here, we review the literature, report the most interesting results and hypothesize future treatment directions.

  16. Preoperative biliary drainage for pancreatic cancer

    NARCIS (Netherlands)

    van Heek, N. T.; Busch, O. R.; van Gulik, T. M.; Gouma, D. J.

    2014-01-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile

  17. Epidermal Growth Factor Receptor in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  18. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

    Science.gov (United States)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

    2016-05-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. Based on a retrospective analysis of patients admitted to Dutch hospitals, a first

  19. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  20. A diagnostic pitfall: pancreatic tuberculosis, not pancreatic cancer

    International Nuclear Information System (INIS)

    Samuel, D.O.; Mukhtar, A.A.M.; Philip, I.O.

    2013-01-01

    Abdominal tuberculosis (TB) is one of the most common forms of extra-pulmonary tuberculosis and is responsible for considerable morbidity and mortality globally. Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum, liver, spleen and the pancreatobiliary system. The occurrence of abdominal TB is independent of pulmonary disease in most patients, with a reported incidence of co-existing pulmonary disease varying from 6 to 38% worldwide. We report a case of pancreatic tuberculosis also involving the vertebrae, which was initially treated as a case of pancreatic cancer. (author)

  1. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Background & Aims: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. Methods: We performed a cross-sectional study of 669 patients with a first episode of acute

  2. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ali, U.A.; Issa, Y.; Hagenaars, J.C.; Bakker, O.J.; Goor, H. van; Nieuwenhuijs, V.B.; Bollen, T.L.; Ramshorst, B. van; Witteman, B.J.; Brink, M.A.; Schaapherder, A.F.; Dejong, C.H.; Spanier, B.W.; Heisterkamp, J.; Harst, E. van der; Eijck, C.H. van; Besselink, M.G.; Gooszen, H.G.; Santvoort, H.C. van; Boermeester, M.A.

    2016-01-01

    BACKGROUND & AIMS: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. METHODS: We performed a cross-sectional study of 669 patients with a first episode of acute

  3. Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study.

    Science.gov (United States)

    Chen, Xin-Zu; Schöttker, Ben; Castro, Felipe Andres; Chen, Hongda; Zhang, Yan; Holleczek, Bernd; Brenner, Hermann

    2016-03-29

    To assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort. Serum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50-75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry. During an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73-1.56) or pancreatic cancer (HR = 1.32; 0.73-2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6-137.6). This large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.

  4. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  5. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

    2008-01-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  6. External beam radiotherapy for unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kagami, Yoshikazu; Nishio, Masamichi; Narimatsu, Naoto; Ogawa, Hajime; Betsuyaku, Takashi; Hirata, Kouji; Ikeda, Shigeyuki (Sapporo National Hospital (Japan). Hokkaido Cancer Center)

    1992-04-01

    Between 1980 to 1989, 24 patients with unresectable pancreatic cancer (10 with localized tumor alone and 14 with distant metastases) have been treated with external beam radiation at Sapporo National Hospital, Hokkaido Cancer Center. Response rate of pancreatic tumor treated with external beam radiation was 33.3% (7/21) with no complete response. Median survival time of the patients with localized tumor was 10 months and that of the patients with distant metastases was 3 months. Relief of pain occurred in 92.9% (12/13) of patients having pain due to pancreatic tumor and in 75% (3/4) of patients having pain due to bone metastases. Major complication was gastric ulcer which developed in 5 patients of 21 patients given stomach irradiation. We concluded that unresectable pancreatic cancer would be frequently indicated for radiotherapy. (author).

  7. Targeting Apoptosis Signaling in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Fulda, Simone

    2011-01-01

    The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery

  8. Targeting Apoptosis Signaling in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fulda, Simone [Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Komturstr. 3a, 60528 Frankfurt (Germany)

    2011-01-11

    The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery.

  9. Plasma cotinine levels and pancreatic cancer in the EPIC cohort study

    NARCIS (Netherlands)

    Leenders, M.; Chuang, S.C.; Dahm, C.C.; Overvad, K.; Ueland, P.M.; Midttun, O.; Vollset, S.E.; Tjonneland, A.; Halkjaer, J.; Jenab, M.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Kaaks, R.; Canzian, F.; Boeing, H.; Weikert, C.; Trichopoulou, A.; Bamia, C.; Naska, A.; Palli, D.; Pala, V.; Mattiello, A.; Tumino, R.; Sacerdote, C.; Duijnhoven, F.J.B. van; Peeters, P.H.M.; Gils, C.H. van; Lund, E.; Rodriguez, L.; Duell, E.J.; Perez, M.J.; Molina-Montes, E.; Castano, J.M.; Barricarte, A.; Larrañaga, N.; Johansen, D.; Lindkvist, B.; Sund, M.; Ye, W.; Khaw, K.T.; Wareham, N.J.; Michaud, D.S.; Riboli, E.; Xun, W.W.; Allen, N.E.; Crowe, F.L.; Bueno-De-Mesquita, H.B.; Vineis, P.

    2012-01-01

    Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective

  10. Pancreatic cancer: Incidence, clinical profile, and frequency of ...

    African Journals Online (AJOL)

    Hana T. Al-Majed

    2012-08-09

    Aug 9, 2012 ... Diabetes has been postulated to be both a risk factor and a consequence of pancreatic cancer, ... (A.A.. El-Basmi),. Shihab@yahoo.com. (S.H. Al-Mohannadi) ..... A recent meta-analysis reported that obese people may have a ...

  11. Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer.

    Science.gov (United States)

    Underhill, Meghan; Hong, Fangxin; Lawrence, Janette; Blonquist, Traci; Syngal, Sapna

    2018-03-23

    Describe relationships between self-reported personal demographics or familial characteristics and psychosocial outcomes (Patient Reported Outcome Measurement Information System Global Health, Impact of Event Scale-Revised [pancreatic cancer risk-related distress], cancer risk perception, and cancer worry) in participants with inherited or familial pancreatic cancer risk. A multisite cross sectional survey of adults with elevated pancreatic cancer risk based on family history. All variables were summarized with descriptive statistics. To assess univariate associations, t test and chi-square/Fisher's exact test were used, and backward model selection was used in multivariable analysis. Respondents (N = 132) reported moderate to high frequency of cancer worry and 59.3% perceived a 50% or more perceived lifetime risk for pancreatic cancer, which far exceeds objective risk estimates. Cancer worry was associated with female gender (P = .03) and pancreatic cancer risk specific distress (P = .05). Higher-risk perception was associated with having a high school education or less (P = .001), higher distress (P = .02), and cancer worry (P = .008) and family cancer death experience (P = .02). Higher distress was associated with experience as a caregiver to a seriously ill family member in the past 5 years (P = .006). Individuals with inherited or familial pancreatic cancer risk experience cancer worry, distress, and have increased risk perception, particularly in the period following caring for a loved one with cancer. Routine evaluation of distress in this setting, as well as the development of supportive care resources, will help support patients living with risk for pancreatic cancer. Copyright © 2018 John Wiley & Sons, Ltd.

  12. Out-FOXing Pancreatic Cancer | Center for Cancer Research

    Science.gov (United States)

    Pancreatic cancer is one of the most lethal cancer types worldwide with increasing incidence and mortality rates in the United States. Consequently, it is projected to become the second leading cause of cancer death by 2020. Poor patient outcomes are due to a combination of diagnosis at an advanced stage and a lack of effective treatments. However, a better understanding of the molecular pathways at work in pancreatic cancers may lead to the identification of novel therapeutic targets.

  13. Obesity adversely affects survival in pancreatic cancer patients.

    Science.gov (United States)

    McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A; Kim, George P; Halfdanarson, Thorvardur R; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R

    2010-11-01

    Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self-reported diabetes and fasting blood glucose in the survival model. BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], PFasting blood glucose and diabetes did not affect the results. Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Copyright © 2010 American Cancer Society.

  14. Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report.

    Science.gov (United States)

    Hine, R Jean; Srivastava, Sudhir; Milner, John A; Ross, Sharon A

    2003-11-01

    Adenocarcinoma of the pancreas is one of most catastrophic and least understood of cancers. Evidence from clinical studies indicates that the development of pancreas cancer progresses over many years before symptoms appear. Most people with pancreatic cancer die within six months of diagnosis. The lack of early disease markers, the paucity of direct subject/patient interview data and limited availability of high quality biological samples have slowed progress toward identifying environmental and genetic disease risk factors. Much remains to be learned about the development of pancreatic cancer and about potential interventions for disease prevention. Epidemiological and mechanistic studies examining risk factors for pancreatic cancer supply little consistent or strong evidence to provide a cohesive prevention strategy for this cancer, but offer clues for future research concerning the prevention and early detection of this devastating disease. This Executive Summary provides background discussion on pancreatic cancer and summaries of each of the topics discussed at the workshop, including 1) Molecular aspects, 2) Dietary and other risk factors for pancreatic cancer, 3) The metabolic hypothesis for pancreatic cancer, 4) Preclinical studies on pancreatic cancer, 5) Methylation, 6) Oxidative stress and 7) Biomarker Profiling. This document also contains a compilation of recommendations for future research, concluding remarks, a list of speakers and participants attending the workshop, and a selection of key references to aid future research into nutritional links to mechanisms underlying pancreas cancer. The recommendations section suggests gaps in current knowledge and articulates future directions for this area of investigation.

  15. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms.

    Science.gov (United States)

    Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max

    2014-10-01

    serum pancreatic enzymes may be useful markers in stratification of pancreatic cancer risk in patients with IPMN. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  17. Engineered T cells for pancreatic cancer treatment

    Science.gov (United States)

    Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

    2011-01-01

    Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

  18. Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

    Science.gov (United States)

    Shakeri, Ramin; Kamangar, Farin; Mohamadnejad, Mehdi; Tabrizi, Reza; Zamani, Farhad; Mohamadkhani, Ashraf; Nikfam, Sepideh; Nikmanesh, Arash; Sotoudeh, Masoud; Sotoudehmanesh, Rasoul; Shahbazkhani, Bijan; Ostovaneh, Mohammad Reza; Islami, Farhad; Poustchi, Hossein; Boffetta, Paolo; Malekzadeh, Reza; Pourshams, Akram

    2016-07-01

    Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population. Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39). In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.

  19. Assessment value of quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jiang-Xia Lei

    2016-10-01

    Full Text Available Objective: To analyze the assessment value of the quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer. Methods: A total of 58 patients with space-occupying pancreatic lesions were divided into 20 patients with pancreatic cancer and 38 patients with benign pancreatic lesions after pancreatic CT perfusion. Patients with pancreatic cancer received palliative surgery, and the cancer tissue and para-carcinoma tissue specimens were collected during operation. The differences in pancreatic CT perfusion scanning parameter values and serum tumor marker levels were compared between patients with pancreatic cancer and patients with benign pancreatic lesions, mRNA expression levels of malignant molecules in pancreatic cancer tissue and para-carcinoma tissue were further determined, and the correlation between pancreatic CT perfusion scanning parameter values and malignant degree of pancreatic cancer was analyzed. Results: CT perfusion scanning BF, BV and Per values of patients with pancreatic cancer were lower than those of patients with benign pancreatic lesions; serum CA19-9, CEA, CA125 and CA242 levels were higher than those of patients with benign pancreatic lesions (P<0.05; mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue samples were higher than those in paracarcinoma tissue samples, and mRNA expression levels of P53 and Bax were lower than those in para-carcinoma tissue samples (P<0.05; CT perfusion scanning parameters BF, BV and Per values of patients with pancreatic cancer were negatively correlated with CA19-9, CEA, CA125 and CA242 levels in serum as well as mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue, and positively correlated with mRNA expression levels of P53 and Bax in pancreatic cancer tissue (P<0.05. Conclusions: Pancreatic CT perfusion scanning is a reliable way to judge the malignant degree of pancreatic cancer and plays a

  20. The pathobiological impact of cigarette smoke on pancreatic cancer development (review).

    Science.gov (United States)

    Wittel, Uwe A; Momi, Navneet; Seifert, Gabriel; Wiech, Thorsten; Hopt, Ulrich T; Batra, Surinder K

    2012-07-01

    Despite extensive efforts, pancreatic cancer remains incurable. Most risk factors, such as genetic disposition, metabolic diseases or chronic pancreatitis cannot be influenced. By contrast, cigarette smoking, an important risk factor for pancreatic cancer, can be controlled. Despite the epidemiological evidence of the detrimental effects of cigarette smoking with regard to pancreatic cancer development and its unique property of being influenceable, our understanding of cigarette smoke-induced pancreatic carcinogenesis is limited. Current data on cigarette smoke-induced pancreatic carcinogenesis indicate multifactorial events that are triggered by nicotine, which is the major pharmacologically active constituent of tobacco smoke. In addition to nicotine, a vast number of carcinogens have the potential to reach the pancreatic gland, where they are metabolized, in some instances to even more toxic compounds. These metabolic events are not restricted to pancreatic ductal cells. Several studies show that acinar cells are also greatly affected. Furthermore, pancreatic cancer progenitor cells do not only derive from the ductal epithelial lineage, but also from acinar cells. This sheds new light on cigarette smoke-induced acinar cell damage. On this background, our objective is to outline a multifactorial model of tobacco smoke-induced pancreatic carcinogenesis.

  1. Current status and progress of pancreatic cancer in China.

    Science.gov (United States)

    Lin, Quan-Jun; Yang, Feng; Jin, Chen; Fu, De-Liang

    2015-07-14

    Cancer is currently one of the most important public health problems in the world. Pancreatic cancer is a fatal disease with poor prognosis. As in most other countries, the health burden of pancreatic cancer in China is increasing, with annual mortality rates almost equal to incidence rates. The increasing trend of pancreatic cancer incidence is more significant in the rural areas than in the urban areas. Annual diagnoses and deaths of pancreatic cancer in China are now beyond the number of cases in the United States. GLOBOCAN 2012 estimates that cases in China account for 19.45% (65727/337872) of all newly diagnosed pancreatic cancer and 19.27% (63662/330391) of all deaths from pancreatic cancer worldwide. The population's growing socioeconomic status contributes to the rapid increase of China's proportional contribution to global rates. Here, we present an overview of control programs for pancreatic cancer in China focusing on prevention, early diagnosis and treatment. In addition, we describe key epidemiological, demographic, and socioeconomic differences between China and developed countries. Facts including no nationwide screening program for pancreatic cancer, delay in early detection resulting in a late stage at presentation, lack of awareness of pancreatic cancer in the Chinese population, and low investment compared with other cancer types by government have led to backwardness in China's pancreatic cancer diagnosis and treatment. Finally, we suggest measures to improve health outcomes of pancreatic cancer patients in China.

  2. Variation in the γ-glutamyltransferase 1 gene and risk of chronic pancreatitis.

    Science.gov (United States)

    Brand, Harrison; Diergaarde, Brenda; O'Connell, Michael R; Whitcomb, David C; Brand, Randall E

    2013-07-01

    Individuals with chronic pancreatitis are at increased risk for pancreatic cancer. We hypothesized that genetic variation in the γ-glutamyltransferase 1 (GGT1) gene, which was recently reported associated with pancreatic cancer risk in a genome-wide association study, is also associated with risk of chronic pancreatitis. Associations between common polymorphisms in GGT1 and chronic pancreatitis were evaluated using data and samples from the North American Pancreatitis Study 2. Patients (n = 496) and control subjects (n = 465) were genotyped for 4 single-nucleotide polymorphisms: rs4820599, rs2017869, rs8135987, and rs5751901. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) for chronic pancreatitis risk were calculated using multiple logistic regression models. Interactions with cigarette smoking and alcohol use were explored. Single-nucleotide polymorphisms rs8135987 and rs4820599 were both statistically significantly associated with risk of chronic pancreatitis; compared with common allele homozygotes, individuals with at least 1 minor allele were at increased risk (rs8135987: OR, 1.36; 95% CI, 1.03-1.80 [P(trend) = 0.01]; rs4820599: OR, 1.39; 95% CI, 1.04-1.84 [P(trend) = 0.0]; adjusted for age, sex, race, smoking status, and alcohol use). No significant interactions with cigarette smoking and alcohol use were observed. Our results suggest that common variation in the GGT1 gene may also affect risk of chronic pancreatitis.

  3. Molecular biology of pancreatic cancer: how useful is it in clinical practice?

    Science.gov (United States)

    Sakorafas, George H; Smyrniotis, Vasileios

    2012-07-10

    During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the

  4. Pancreatic cancer and depression: myth and truth

    Directory of Open Access Journals (Sweden)

    Schmid Roland M

    2010-10-01

    Full Text Available Abstract Background Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression. However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se? Discussion Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy. Summary A review of the literature on this issue should reveal which are the facts and what is myth.

  5. The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

    Science.gov (United States)

    Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

    2018-04-01

    An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

  6. The advanced glycation end-product Nϵ -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes-associated risk and its prevention.

    Science.gov (United States)

    Menini, Stefano; Iacobini, Carla; de Latouliere, Luisa; Manni, Isabella; Ionta, Vittoria; Blasetti Fantauzzi, Claudia; Pesce, Carlo; Cappello, Paola; Novelli, Francesco; Piaggio, Giulia; Pugliese, Giuseppe

    2018-03-13

    Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE N ϵ -carboxymethyllysine (CML) in human pancreatic ductal adenocarcinoma (PDA) cell lines and in a mouse model of Kras-driven PaC interbred with a bioluminescent model of proliferation. Tumour growth was monitored in vivo by bioluminescence imaging and confirmed by histology. CML promoted PDA cell growth and RAGE expression, in a concentration-dependent and time-dependent manner, and activated downstream tumourigenic signalling pathways. These effects were counteracted by RAGE antagonist peptide (RAP). Exogenous AGE administration to PaC-prone mice induced RAGE upregulation in pancreatic intraepithelial neoplasias (PanINs) and markedly accelerated progression to invasive PaC. At 11 weeks of age (6 weeks of CML treatment), PaC was observed in eight of 11 (72.7%) CML-treated versus one of 11 (9.1%) vehicle-treated [control (Ctr)] mice. RAP delayed PanIN development in Ctr mice but failed to prevent PaC promotion in CML-treated mice, probably because of competition with soluble RAGE for binding to AGEs and/or compensatory upregulation of the RAGE homologue CD166/ activated leukocyte cell adhesion molecule, which also favoured tumour spread. These findings indicate that AGEs modulate the development and progression of PaC through receptor-mediated mechanisms, and might be responsible for the additional risk conferred by diabetes and other

  7. Whole genomes redefine the mutational landscape of pancreatic cancer

    OpenAIRE

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (...

  8. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  9. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-01-01

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti

  10. Therapeutic management of locally unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Lombard-Bohas, C.; Saurin, J.C.; Mornex, F.

    1997-01-01

    Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10 % of patients can undergo surgery with an overall 5-year survival rate of less than 2 %. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used. (author)

  11. Common variables in European pancreatic cancer registries

    DEFF Research Database (Denmark)

    De Leede, E. M.; Sibinga Mulder, B. G.; Bastiaannet, E.

    2016-01-01

    Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer...... registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between...

  12. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  13. Pancreatic cancer surgery: past, present, and future.

    Science.gov (United States)

    Griffin, James F; Poruk, Katherine E; Wolfgang, Christopher L

    2015-08-01

    The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

  14. Indicative findings of pancreatic cancer in prediagnostic CT

    International Nuclear Information System (INIS)

    Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok; Kim, Myeong-Jin

    2009-01-01

    We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

  15. Analysis of related risk factors for pancreatic fistula after pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Qi-Song Yu

    2016-08-01

    Full Text Available Objective: To explore the related risk factors for pancreatic fistula after pancreaticoduodenectomy to provide a theoretical evidence for effectively preventing the occurrence of pancreatic fistula. Methods: A total of 100 patients who were admitted in our hospital from January, 2012 to January, 2015 and had performed pancreaticoduodenectomy were included in the study. The related risk factors for developing pancreatic fistula were collected for single factor and Logistic multi-factor analysis. Results: Among the included patients, 16 had pancreatic fistula, and the total occurrence rate was 16% (16/100. The single-factor analysis showed that the upper abdominal operation history, preoperative bilirubin, pancreatic texture, pancreatic duct diameter, intraoperative amount of bleeding, postoperative hemoglobin, and application of somatostatin after operation were the risk factors for developing pancreatic fistula (P<0.05. The multi-factor analysis showed that the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin were the dependent risk factors for developing pancreatic fistula (OR=4.162, 6.104, 5.613, 4.034, P<0.05. Conclusions: The occurrence of pancreatic fistula after pancreaticoduodenectomy is closely associated with the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin; therefore, effective measures should be taken to reduce the occurrence of pancreatic fistula according to the patients’ own conditions.

  16. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  17. Ultrasound-enhanced nanotherapy of pancreatic cancer

    Science.gov (United States)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

    2010-03-01

    The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

  18. Contemporary Management of Localized Resectable Pancreatic Cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ma, Wen Wee; Mahipal, Amit

    2018-01-20

    Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15-20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

  19. Vaginal metastasis of pancreatic cancer | Benhayoune | Pan African ...

    African Journals Online (AJOL)

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of ...

  20. The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Javier Martinez-Useros

    2016-01-01

    Full Text Available Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

  1. FDA Approves Irinotecan Liposome to Treat Pancreatic Cancer

    Science.gov (United States)

    Patients with metastatic pancreatic cancer that has progressed after receiving gemcitabine-based chemotherapy now have a new treatment option: irinotecan liposome in combination with fluorouracil and leucovorin.

  2. Early Detection of Sporadic Pancreatic Cancer

    Science.gov (United States)

    Chari, Suresh T.; Kelly, Kimberly; Hollingsworth, Michael A.; Thayer, Sarah P.; Ahlquist, David A.; Andersen, Dana K.; Batra, Surinder K.; Brentnall, Teresa A.; Canto, Marcia; Cleeter, Deborah F.; Firpo, Matthew A.; Gambhir, Sanjiv Sam; Go, Vay Liang W.; Hines, O. Joe; Kenner, Barbara J.; Klimstra, David S.; Lerch, Markus M.; Levy, Michael J.; Maitra, Anirban; Mulvihill, Sean J.; Petersen, Gloria M.; Rhim, Andrew D.; Simeone, Diane M.; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I.; Wong, David

    2015-01-01

    Abstract Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC. PMID:25931254

  3. Exosomes Derived From Pancreatic Stellate Cells: MicroRNA Signature and Effects on Pancreatic Cancer Cells.

    Science.gov (United States)

    Takikawa, Tetsuya; Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Kogure, Takayuki; Shimosegawa, Tooru

    2017-01-01

    Pancreatic stellate cells (PSCs) interact with pancreatic cancer cells in the tumor microenvironment. Cell constituents including microRNAs may be exported from cells within membranous nanovesicles termed exosomes. Exosomes might play a pivotal role in intercellular communication. This study aimed to clarify the microRNA signature of PSC-derived exosomes and their effects on pancreatic cancer cells. Exosomes were prepared from the conditioned medium of immortalized human PSCs. MicroRNAs were prepared from the exosomes and their source PSCs, and the microRNA expression profiles were compared by microarray. The effects of PSC-derived exosomes on proliferation, migration, and the mRNA expression profiles were examined in pancreatic cancer cells. Pancreatic stellate cell-derived exosomes contained a variety of microRNAs including miR-21-5p. Several microRNAs such as miR-451a were enriched in exosomes compared to their source PSCs. Pancreatic stellate cell-derived exosomes stimulated the proliferation, migration and expression of mRNAs for chemokine (C - X - C motif) ligands 1 and 2 in pancreatic cancer cells. The stimulation of proliferation, migration, and chemokine gene expression by the conditioned medium of PSCs was suppressed by GW4869, an exosome inhibitor. We clarified the microRNA expression profile in PSC-derived exosomes. Pancreatic stellate cell-derived exosomes might play a role in the interactions between PSCs and pancreatic cancer cells.

  4. Morphometrical differences between resectable and non-resectable pancreatic cancer: a fractal analysis.

    Science.gov (United States)

    Vasilescu, Catalin; Giza, Dana Elena; Petrisor, Petre; Dobrescu, Radu; Popescu, Irinel; Herlea, Vlad

    2012-01-01

    Pancreatic cancer is a highly aggressive cancer with a rising incidence and poor prognosis despite active surgical treatment. Candidates for surgical resection should be carefully selected. In order to avoid unnecessary laparotomy it is useful to identify reliable factors that may predict resectability. Nuclear morphometry and fractal dimension of pancreatic nuclear features could provide important preoperative information in assessing pancreas resectability. Sixty-one patients diagnosed with pancreatic cancer were enrolled in this retrospective study between 2003 and 2005. Patients were divided into two groups: one resectable cancer group and one with non-resectable pancreatic cancer. Morphometric parameters measured were: nuclear area, length of minor axis and length of major axis. Nuclear shape and chromatin distribution of the pancreatic tumor cells were both estimated using fractal dimension. Morphometric measurements have shown significant differences between the nuclear area of the resectable group and the non-resectable group (61.9 ± 19.8µm vs. 42.2 ± 15.6µm). Fractal dimension of the nuclear outlines and chromatin distribution was found to have a higher value in the non-resectable group (p<0.05). Objective measurements should be performed to improve risk assessment and therapeutic decisions in pancreatic cancer. Nuclear morphometry of the pancreatic nuclear features can provide important pre-operative information in resectability assessment. The fractal dimension of the nuclear shape and chromatin distribution may be considered a new promising adjunctive tool for conventional pathological analysis.

  5. Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

    Science.gov (United States)

    Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

    2012-01-01

    BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

  6. Methylation of the SPARC gene promoter and its clinical implication in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Lv Shunli

    2010-03-01

    Full Text Available Abstract Background The secreted protein acidic and rich in cysteine (SPARC plays a pivotal role in regulating cell-matrix interactions and tumor angiogenesis, proliferation, and migration. Detection of SPARC gene methylation may be useful as a tumorigenesis marker for early detection of pancreatic cancer. Methods Methylation of the SPARC gene transcriptional regulation region (TRR was detected using bisulfite-specific (BSP PCR-based sequencing analysis in 40 cases of pancreatic cancer and the adjacent normal tissues, 6 chronic pancreatitis tissues, and 6 normal pancreatic tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed. Results Analysis of SPARC gene TRR methylation showed two hypermethylation wave peak regions: CpG Region 1 (CpG site 1-7 and CpG Region 2 (CpG site 8-12. Pancreatic tissues have shown methylation in both regions with gradual increases from normal, chronic pancreatitis, and adjacent normal tissues to cancerous tissues. However, Methylation of CpG Region 2 was more sensitive than CpG Region 1 in pancreatic tumorigenesis. Furthermore, the methylation level of CpG Region 2 was associated with increased tumor size and exposure to the risk factors (tobacco smoke and alcohol consumption for developing pancreatic cancer. Conclusion Methylation of the SPARC gene, specifically CpG Region 2, may be an early event during pancreatic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of pancreatic cancer.

  7. Chronic pancreatitis: review and update of etiology, risk factors, and management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Angela Pham

    2018-05-01

    Full Text Available Chronic pancreatitis is a syndrome involving inflammation, fibrosis, and loss of acinar and islet cells which can manifest in unrelenting abdominal pain, malnutrition, and exocrine and endocrine insufficiency. The Toxic-Metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis, Obstructive (TIGAR-O classification system categorizes known causes and factors that contribute to chronic pancreatitis. Although determining disease etiology provides a framework for focused and specific treatments, chronic pancreatitis remains a challenging condition to treat owing to the often refractory, centrally mediated pain and the lack of consensus regarding when endoscopic therapy and surgery are indicated. Further complications incurred include both exocrine and endocrine pancreatic insufficiency, pseudocyst formation, bile duct obstruction, and pancreatic cancer. Medical treatment of chronic pancreatitis involves controlling pain, addressing malnutrition via the treatment of vitamin and mineral deficiencies and recognizing the risk of osteoporosis, and administering appropriate pancreatic enzyme supplementation and diabetic agents. Cornerstones in treatment include the recognition of pancreatic exocrine insufficiency and administration of pancreatic enzyme replacement therapy, support to cease smoking and alcohol consumption, consultation with a dietitian, and a systematic follow-up to assure optimal treatment effect.

  8. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  9. Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    J. Iglesias García

    2009-09-01

    Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

  10. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

  11. Management of pancreatic cancer in the elderly.

    Science.gov (United States)

    Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

    2016-01-14

    Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

  12. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Nakao, Akimasa

    2010-01-01

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated

  13. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Akimasa [Department of Surgery II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2010-11-24

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated.

  14. Role of chymotrypsin C in development and progression of pancreatitis and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Zejie

    2016-11-01

    Full Text Available Chymotrypsin C (CTRC is a trypsinogen synthesized by pancreatic acinar cells and secreted by pancreatic duct cells and belongs to the family of serine chymotrypsin. The main function of CTRC is to regulate the balance between activation and degradation of trypsin and maintain the structural and functional integrity of the pancreas. CTRC gene mutations can cause abnormal activation of trypsinogen and abnormal degradation of trypsin and then lead to the development of pancreatitis. The downregulation or absence of CTRC expression may be associated with the development and metastasis of pancreatic cancer. This article introduces the structure and biological function of CTRC and its mechanism of action in the development and progression of pancreatitis and pancreatic cancer.

  15. Legumain is activated in macrophages during pancreatitis

    NARCIS (Netherlands)

    Edgington-Mitchell, L.E.; Wartmann, T.; Fleming, A.K.; Gocheva, V.; Linden, W.A. van der; Withana, N.P.; Verdoes, M.; Aurelio, L.; Edgington-Mitchell, D.; Lieu, T.; Parker, B.S.; Graham, B.; Reinheckel, T.; Furness, J.B.; Joyce, J.A.; Storz, P.; Halangk, W.; Bogyo, M.; Bunnett, N.W.

    2016-01-01

    Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked

  16. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

    Directory of Open Access Journals (Sweden)

    Manju D. Chandrasegaram

    2013-01-01

    Full Text Available Background. Autoimmune pancreatitis (AIP often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS- guided fine-needle aspiration (FNA of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP.

  17. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  18. Emphasis on neoadjuvant therapy for “resectable” pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Chang

    2015-05-01

    Full Text Available The treatment concept for pancreatic cancer is being transferred from “surgery first” to MDT model. The postoperative adjuvant treatment of pancreatic cancer can significantly improve the prognosis of patients and has become the standardized diagnostic and treatment practice; the value and significance of neoadjuvant therapy remains unclear. Limited clinical studies of “borderline resectable” pancreatic cancer have shown that neoadjuvant therapy can improve the R0 resection rate and improve the prognosis of patients, and it is recommended for clinical application. But the significance of neoadjuvant therapy in “resectable” pancreatic cancer is still controversial. There is a lack of consensus on indications, cycles, and regimens. It is necessary to carry out a series of prospective control studies to objectively evaluate the value of neoadjuvant therapy in improving the prognosis of “resectable” pancreatic cancer.

  19. Mortality, Cancer, and Comorbidities Associated With Chronic Pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich Christian; Benfield, Thomas; Hyldstrup, Lars

    2014-01-01

    BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP). METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated...... cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic...... pulmonary disease (HR, 1.9; 95% CI, 1.8-2.1), ulcer disease (HR, 3.6; 95% CI, 3.3-3.9), diabetes (HR, 5.2; 95% CI, 5.0-5.6), and chronic renal disease (HR, 1.7; 95% CI, 1.5-1.9) occurred more frequently among patients with CP, but myocardial infarction did not (HR, 0.9; 95% CI, 0.8-1.0). CONCLUSIONS: Based...

  20. Comparison of Pancreas Juice Proteins from Cancer Versus Pancreatitis Using Quantitative Proteomic Analysis

    Science.gov (United States)

    Chen, Ru; Pan, Sheng; Cooke, Kelly; Moyes, Kara White; Bronner, Mary P.; Goodlett, David R.; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Objectives Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. Methods In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. Results In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer. PMID:17198186

  1. Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit

    NARCIS (Netherlands)

    van Rijssen, L. Bengt; Koerkamp, Bas G.; Zwart, Maurice J.; Bonsing, Bert A.; Bosscha, Koop; van Dam, Ronald M.; van Eijck, Casper H.; Gerhards, Michael F.; van der Harst, Erwin; de Hingh, Ignace H.; de Jong, Koert P.; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J.; Molenaar, I. Quintus; Patijn, Gijs A.; Rupert, Coen G.; van Santvoort, Hjalmar C.; Scheepers, Joris J.; van der Schelling, George P.; Busch, Olivier R.; Besselink, Marc G.; Bollen, Thomas L.; Bruno, Marco J.; van Tienhoven, Geert-Jan; Norduyn, Arnold; Berry, David P.; Tingstedt, Bobby; Tseng, Jennifer F.; Wolfgang, Christopher L.

    2017-01-01

    Background: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Methods: Performance indicators and case-mix factors were identified by a PubMed search for randomized

  2. Pancreatic cancer clinical trials and accrual in the United States.

    Science.gov (United States)

    Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

    2013-09-20

    Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

  3. Kidney Cancer Risk Questionnaire

    Science.gov (United States)

    ... NCI Cancer Information A to Z Treatment Roles Cancer Types Bladder Brain/Spine Breast Cervical Colorectal Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic ...

  4. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  5. [Non surgical treatment of pancreatic cancers].

    Science.gov (United States)

    Bleiberg, H; Gerard, B; Hendlisz, A; Jagodzinski, R

    1997-09-01

    Pancreatic cancer is a disease difficult to treat. Diagnosis is late, cancer remaining clinically unapparent even if locally advanced or metastatic. Few patients can be submitted to curative surgery. Even if resection is possible, 5-year survival varies from 0% to 18% according to series. Some data suggest that chemotherapy with or without radiotherapy could influence disease free survival but a benefit on overall survival has not been demonstrated. For locally advanced disease, the results of a trial published in 1968, showed that a combination of radiotherapy and 5-Fluorouracil (5FU) improved median survival as compared to radiotherapy alone (5.5 versus 10 months). Since then, no progress has been achieved. At the present time, survival of patients with metastatic pancreatic cancer cannot be improved. Very recently, a new agent, gemcitabine, has been compared to 5FU. Criteria for activity were based on clinical improvement analgesia consumption, performance status and weight gain. Twenty-four percent of the patients treated with gemcitabine had a clinical benefit as compared to 5% for those treated with 5FU. Other studies comparing chemotherapy to best supportive care show a significant decrease of depression and anxiety as well as an improvement in quality of life for patients being treated.

  6. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  7. CT findings of the mucin producing pancreatic cancer

    International Nuclear Information System (INIS)

    Ri, Kyoushichi; Hashimoto, Toushi; Munechika, Hirotsugu

    1992-01-01

    Mucin-producing pancreatic cancers (MPPC), which include mucinous adenocarcinoma, papillary adenocarcinoma and cystadenocarcinoma, are radiographically characterized by diffuse or localized dilatation of the main pancreatic duct due to excessive mucin production. Therefore, MPPC are occasionally difficult to distinguish from chronic pancreatitis on CT unless the primary pancreatic lesion is visualized. We compared five cases of MPPC with five cases of chronic pancreatitis with marked duct dilatation to determine differences in CT images between the two diseases. There was no significant difference between the two diseases in the nature of duct dilatation (size, extent, contour) or parenchymal changes (atrophy, enlargement, calcification, cystic lesion). However, dilatation of the intramural duct was characteristically observed in MPPC but not in chronic pancreatitis. Papillary masses in the pancreatic duct, when observed, were another finding specific to MPPC. (author)

  8. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    Science.gov (United States)

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  9. Laboratory diagnosis of pancreatitis and cancer of the pancreas

    International Nuclear Information System (INIS)

    Degtyareva, I.I.; Gajsenko, A.V.; Putseva, N.M.

    1989-01-01

    The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsine, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages 3-4) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrinous insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas

  10. Multimodal treatment for unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori

    1998-01-01

    In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

  11. Multimodal treatment for unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Katayama, Kanji; Iida, Atsushi; Fujita, Takashi; Kobayashi, Taizo; Shinmoto, Syuichi; Hirose, Kazuo; Yamaguchi, Akio; Yoshida, Masanori [Fukui Medical School, Matsuoka (Japan)

    1998-07-01

    In order to improve in prognosis and quality of life (QOL), the multimodal treatment for unresectable pancreatic cancers were performed. Bypass surgery was carried out for unresectable pancreatic cancer with intraoperative irradiation (IOR). After surgery, patients were treated with the combination of CDDP (25 mg) and MMC (4 mg) administration, intravenously continuous injection of 5-FU (250 mg for 24 hours), external radiation by the high voltage X-ray (1.5 Gy per irradiation, 4 times a week, and during hyperthermia 3 Gy per irradiation) and hyperthermia using the Thermotron RF-8 warmer. Six out of 13 patients received hyperthermia at over 40degC, were obtained PR, and their survival periods were 22, 21, 19, 18, 11 and 8 months and they could return to work. For all patients with pain, the symptom was abolished or reduced. The survival periods in cases of the multimodal treatment were longer than those of only bypass-surgery or of the resective cases with the curability C. The multimodal treatment combined with radiation, hyperthermia and surgery is more useful for the removal of pain and the improvement of QOL, and also expected the improvement of the prognosis than pancreatectomy. And hyperthermia has an important role on the effect of this treatment. (K.H.)

  12. Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic retrograde cholangiopancreatography.

    Directory of Open Access Journals (Sweden)

    Yuki Ishikawa-Kakiya

    Full Text Available Advanced techniques have been developed to overcome difficult cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP. Pancreatic duct guidewire placement method (PGW is performed in difficult cannulation cases; it is possible that it places patients at risk of post-ERCP pancreatitis (PEP. The mechanism of PEP is still unclear, but pancreatic duct pressure and injury of pancreatic duct are known causes of PEP. Therefore, we hypothesized a relationship between pancreatic duct diameter and PEP and predicted that PGW would increase the risk of PEP in patients with non-dilated pancreatic ducts. This study aimed to investigate whether PGW increased the risk of PEP in patients with pancreatic duct diameter ≤ 3 mm.We analyzed 332 patients with pancreatic duct ≤ 3 mm who performed first time ERCP session. The primary endpoint was the rate of adverse event of PEP. We evaluated the risk of PEP in patients who had undergone PGW compared to those who had not, using the inverse probability of treatment weighting (IPTW analysis.PGW was found to be an independent risk factor for PEP by univariate analysis (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.12-5.38; p = 0.03 after IPTW in patients with pancreatic duct diameter ≤ 3 mm. Adjusted for all covariates, PGW remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33-7.33; p = 0.01.Our results indicate that PGW in patients with pancreatic duct diameter ≤ 3 mm increases the risk of PEP.

  13. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

  14. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  15. Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics.

    Science.gov (United States)

    Yoo, Joseph; Kistler, C Andrew; Yan, Linda; Dargan, Andrew; Siddiqui, Ali A

    2016-12-01

    Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer.

  16. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  17. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  18. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

    2011-01-01

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

  19. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  20. Icotinib plus gemcitabine for metastatic pancreatic cancer: a case report.

    Science.gov (United States)

    Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

    2015-03-21

    A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative.

  1. Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course.

    Science.gov (United States)

    Maruyama, Masahiro; Arakura, Norikazu; Ozaki, Yayoi; Watanabe, Takayuki; Ito, Tetsuya; Yoneda, Suguru; Maruyama, Masafumi; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Kawa, Shigeyuki

    2012-05-01

    Autoimmune pancreatitis (AIP) has the potential to progress to a chronic state that forms pancreatic stones. The aim of this study was to clarify the risk factors underlying pancreatic stone formation in AIP. Sixty-nine patients with AIP who had been followed for at least 3 years were enrolled for evaluation of clinical and laboratory factors as well as computed tomography and endoscopic retrograde cholangiopancreatography findings. During the course of this study, increased or de novo stone formation was seen in 28 patients, who were defined as the stone-forming group. No stones were observed in 32 patients, who were defined as the non-stone-forming group. Nine patients who had stones at diagnosis but showed no change during the course of this study were excluded from our cohort. Univariate analysis revealed no significant differences in clinical or laboratory factors associated with AIP-specific inflammation between the two groups. However, pancreatic head swelling (P = 0.006) and narrowing of both Wirsung's and Santorini's ducts in the pancreatic head region (P = 0.010) were significantly more frequent in the stone-forming group. Furthermore, multivariate analysis identified Wirsung and Santorini duct narrowing at diagnosis as a significant independent risk factor for pancreatic stone formation (OR 4.4, P = 0.019). A primary risk factor for pancreatic stone formation in AIP was narrowing of both Wirsung's and Santorini's ducts, which most presumably led to pancreatic juice stasis and stone development.

  2. Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

    Science.gov (United States)

    van Rijssen, L Bengt; Koerkamp, Bas G; Zwart, Maurice J; Bonsing, Bert A; Bosscha, Koop; van Dam, Ronald M; van Eijck, Casper H; Gerhards, Michael F; van der Harst, Erwin; de Hingh, Ignace H; de Jong, Koert P; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J; Molenaar, I Quintus; Patijn, Gijs A; Rupert, Coen G; van Santvoort, Hjalmar C; Scheepers, Joris J; van der Schelling, George P; Busch, Olivier R; Besselink, Marc G

    2017-10-01

    Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  3. The study on risk factor of metabolic diseases in pancreatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

    2016-03-15

    The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease.

  4. The study on risk factor of metabolic diseases in pancreatic steatosis

    International Nuclear Information System (INIS)

    Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun

    2016-01-01

    The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease

  5. The relationship between the use of statins and mortality, severity, and pancreatic cancer in Danish patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich C; Watanabe, Tomohiro; Bendtsen, Flemming

    2018-01-01

    OBJECTIVES: Chronic pancreatitis (CP) is associated with a shortened life expectancy. Statins have anti-inflammatory properties and we aimed to evaluate the association between the use of statins and the risk of death, progression of CP, and pancreatic cancer in patients with CP. PATIENTS...... AND METHODS: We carried out a nested case-cohort study and included patients with CP. We used claims of proton pump inhibitors as an active comparator. Patients with cirrhosis or cancer were excluded. We evaluated the exposure on the basis of pharmacy claims of statins. We used propensity score matching...... with a statins : nonstatins ratio of 1 : 1. RESULTS: A total of 4807 patients were eligible for propensity score matching; 33% were women and the mean (SD) age at cohort entry was 56 (10) years. During follow-up, a total of 2073 (43%) patients had died and the risk of death was significantly lower among patients...

  6. Preoperative biliary drainage for pancreatic cancer.

    Science.gov (United States)

    Van Heek, N T; Busch, O R; Van Gulik, T M; Gouma, D J

    2014-04-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery. Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important.

  7. Results of intraoperative radiotherapy for pancreatic cancers

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Shinozaki, Jun; Noda, Masanobu

    1991-01-01

    Reported are the results and observations of the authors who, from July 1986 through December 1989, have used electron beam intraoperative radiotherapy (IORT) on 20 patients with locally advanced pancreatic cancers, said number including 3 patients given a resection. In 14 of the 17 unresected patients, a chief symptom was pain, and 8 patients were given a celiac plexus block at the same time. The results and observations are given below. Life-threatening complications occurred in two patients, i.e., an insufficient pancreatojejunostomy, and a perforative peritonitis. In 12 of 13 evaluable patients, pain control was achieved for a mean period of 5 months, indicating that an IORT with celiac plexus block may be useful for palliation. In the resected patients, the mean survival time was 6 months, whereas in the unresected patients, the mean survival time was 7 months. The common cause of death in the unresected patients was a metastatic dissemination. Finally, in 3 of the 5 unresected patients, marked effects such as massive fibrosis were seen in the pancreatic tumor on autopsy. (author)

  8. MicroRNA-gene signaling pathways in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Alexandra Drakaki

    2013-10-01

    Full Text Available Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.

  9. Genetic Risk for Alcoholic Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Flair José Carrilho

    2011-06-01

    Full Text Available In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.

  10. Pancreatic Cancer: Multicenter Prospective Data Collection and Analysis by the Hungarian Pancreatic Study Group.

    Science.gov (United States)

    Lakatos, Gábor; Balázs, Anita; Kui, Balázs; Gódi, Szilárd; Szücs, Ákos; Szentesi, Andrea; Szentkereszty, Zsolt; Szmola, Richárd; Kelemen, Dezső; Papp, Róbert; Vincze, Áron; Czimmer, József; Pár, Gabriella; Bajor, Judit; Szabó, Imre; Izbéki, Ferenc; Halász, Adrienn; Leindler, László; Farkas, Gyula; Takács, Tamás; Czakó, László; Szepes, Zoltán; Hegyi, Péter; Kahán, Zsuzsanna

    2016-06-01

    Pancreatic cancer is a devastating disease with poor prognosis. There is very limited information available regarding the epidemiology and treatment strategies of pancreatic cancer in Central Europe. The purpose of the study was to prospectively collect and analyze data of pancreatic cancer in the Hungarian population. The Hungarian Pancreatic Study Group (HPSG) organized prospective, uniform data collection. Altogether 354 patients were enrolled from 14 Hungarian centers. Chronic pancreatitis was present in 3.7% of the cases, while 33.7% of the patients had diabetes. Family history for pancreatic cancer was positive in 4.8%. The most frequent presenting symptoms included pain (63.8%), weight loss (63%) and jaundice (52.5%). The reported frequency of smoking and alcohol consumption was lower than expected (28.5% and 27.4%, respectively). The majority of patients (75.6%) were diagnosed with advanced disease. Most patients (83.6%) had a primary tumor located in the pancreatic head. The histological diagnosis was ductal adenocarcinoma in 90.7% of the cases, while neuroendocrine tumor was present in 5.3%. Biliary stent implantation was performed in 166 patients, 59.2% of them received metal stents. Primary tumor resection was performed in 60 (16.9%) patients. Enteral or biliary bypass was done in 35 and 49 patients, respectively. In a multivariate Cox-regression model, smoking status and presence of gemcitabine-based chemotherapy were identified as independent predictors for overall survival. We report the first data from a large cohort of Hungarian pancreatic cancer patients. We identified smoking status and chemotherapy as independent predictors in this cohort.

  11. Surgical management of malignant bowel obstruction in recurrent pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Hyung Sun Kim

    2017-01-01

    Discussion and conclusion: Palliative surgery improves quality of life in recurrent pancreatic cancer patients and can continue patient’s palliative management. In selected patients, palliative surgery may effective management for progress of survival and quality of life.

  12. Influence of radiation and non-radiation factors on pancreatic cancer incidence among Mayak PA workers

    Energy Technology Data Exchange (ETDEWEB)

    Zhuntova, G.V.; Tokarskaya, Z.B.; Belyaeva, Z.D. [Southern Ural Biophysics Institute (SUBI), Ozyorsk (Russian Federation); Syrchikov, V.A.; Grigoryeva, E.S. [Mayak Production Association (Mayak PA), Ozyorsk (Russian Federation)

    2006-07-01

    The finding of this nested case-control study suggests that high levels of 239 Pu incorporation (239 Pu body burden > 3.7), alcohol abuse and smoking were associated with increasing the risk of pancreatic cancer among Mayak PA workers chronically exposed to ionizing radiation. The contribution of non radiation factors (alcohol abuse and smoking) to pancreatic tumor incidence is greater (AR=51%) than 239 Pu incorporation kBq; AR = 7%). No significant effect of external gamma rays ({<=} 6.8 Gy), prior exposure to chemical agents, or chronic digestive diseases was found on the incidence of pancreatic tumor. Evaluation of the absorbed alpha-radiation pancreatic dose will permit to make more exact the 239 Pu risk estimation in the further extended study.

  13. Influence of radiation and non-radiation factors on pancreatic cancer incidence among Mayak PA workers

    International Nuclear Information System (INIS)

    Zhuntova, G.V.; Tokarskaya, Z.B.; Belyaeva, Z.D.; Syrchikov, V.A.; Grigoryeva, E.S.

    2006-01-01

    The finding of this nested case-control study suggests that high levels of 239 Pu incorporation (239 Pu body burden > 3.7), alcohol abuse and smoking were associated with increasing the risk of pancreatic cancer among Mayak PA workers chronically exposed to ionizing radiation. The contribution of non radiation factors (alcohol abuse and smoking) to pancreatic tumor incidence is greater (AR=51%) than 239 Pu incorporation kBq; AR = 7%). No significant effect of external gamma rays (≤ 6.8 Gy), prior exposure to chemical agents, or chronic digestive diseases was found on the incidence of pancreatic tumor. Evaluation of the absorbed alpha-radiation pancreatic dose will permit to make more exact the 239 Pu risk estimation in the further extended study

  14. Surgery for oligometastasis of pancreatic cancer.

    Science.gov (United States)

    Lu, Fengchun; Poruk, Katherine E; Weiss, Matthew J

    2015-08-01

    The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

  15. Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Dongping Wei

    2015-02-01

    Full Text Available In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1, an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.

  16. Accuracy of computed tomography in determining pancreatic cancer tumor size

    International Nuclear Information System (INIS)

    Aoki, Kazunori; Okada, Shuichi; Moriyama, Noriyuki

    1994-01-01

    We compared tumor sizes determined by computed tomography (CT) with those of the resected specimens in 26 patients with pancreatic cancer in order to clarify whether or not the size of a pancreatic tumor can be accurately determined by CT. From the precontrast, postcontrast and arterial dominant phases of dynamic CT, the arterial dominant phase was found to yield the highest correlation between CT measured tumor size and that of the resected specimens (p<0.01). The correlation coefficient was, however, not high (r=0.67). CT alone may therefore be insufficient to determine tumor size in pancreatic cancer accurately. (author)

  17. Multislice CT for preoperative diagnosis of pancreatic cancer

    International Nuclear Information System (INIS)

    Horiguchi, Akihiko; Ishihara, Shin; Ito, Masahiro

    2007-01-01

    We investigated the ability of multislice (MS) CT to visualize and diagnose the progression of pancreatic cancer. With regard to local progression, good diagnosis was possible for detecting the invasion of the intrapancreatic bile duct, duodenum, portal vein, arteries and other organs, and liver metastasis. Sensitivity was high but specificity was not good for detecting the invasion of the anterior and posterior pancreatic tissue. This is thought to be because of the positive diagnosis with pancreatitis that accompanies cancer. Pancreatic plexus invasion was also thought to be a cause of the lipid elevation of the nerve plexus and decreased sensitivity accompanying pancreatitis. Identification of cancer invasion and tumor periphery changes based on concomitant pancreatitis also depends on the amount of fibrous stroma, but this will require further investigation. Factors other than the size of lymph node metastases also need to be investigated. MS-CT can provide detailed volume data in a short time and making it an essential test in diagnosing the stage of pancreatic cancer. (author)

  18. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  19. Screening Technologies for Target Identification in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Michl, Patrick; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte

    2010-01-01

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments

  20. Patients with chronic pancreatitis are at increased risk for osteoporosis.

    LENUS (Irish Health Repository)

    Duggan, SN

    2012-10-01

    Patients with chronic pancreatitis may be at an increased risk of low bone density because of malabsorption of vitamin D and calcium, poor diet, pain, alcoholism, and smoking. We investigated the rates of osteoporosis in patients with chronic pancreatitis compared to matched controls.

  1. Design of a nanoplatform for treating pancreatic cancer

    Science.gov (United States)

    Manawadu, Harshi Chathurangi

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. Asymptomatic early cancer stages and late diagnosis leads to very low survival rates of pancreatic cancers, compared to other cancers. Treatment options for advanced pancreatic cancer are limited to chemotherapy and/or radiation therapy, as surgical removal of the cancerous tissue becomes impossible at later stages. Therefore, there's a critical need for innovative and improved chemotherapeutic treatment of (late) pancreatic cancers. It is mandatory for successful treatment strategies to overcome the drug resistance associated with pancreatic cancers. Nanotechnology based drug formulations have been providing promising alternatives in cancer treatment due to their selective targeting and accumulation in tumor vasculature, which can be used for efficient delivery of chemotherapeutic agents to tumors and metastases. The research of my thesis is following the principle approach to high therapeutic efficacy that has been first described by Dr. Helmut Ringsdorf in 1975. However, I have extended the use of the Ringsdorf model from polymeric to nanoparticle-based drug carriers by exploring an iron / iron oxide nanoparticle based drug delivery system. A series of drug delivery systems have been synthesized by varying the total numbers and the ratio of the tumor homing peptide sequence CGKRK and the chemotherapeutic drug doxorubicin at the surfaces of Fe/Fe3O 4-nanoparticles. The cytotoxicity of these nanoformulations was tested against murine pancreatic cancer cell lines (Pan02) to assess their therapeutic capabilities for effective treatments of pancreatic cancers. Healthy mouse fibroblast cells (STO) were also tested for comparison, because an effective chemotherapeutic drug has to be selective towards cancer cells. Optimal Experimental Design methodology was applied to identify the nanoformulation with the highest therapeutic activity. A statistical analysis method known as response

  2. Combining PubMed knowledge and EHR data to develop a weighted bayesian network for pancreatic cancer prediction.

    Science.gov (United States)

    Zhao, Di; Weng, Chunhua

    2011-10-01

    In this paper, we propose a novel method that combines PubMed knowledge and Electronic Health Records to develop a weighted Bayesian Network Inference (BNI) model for pancreatic cancer prediction. We selected 20 common risk factors associated with pancreatic cancer and used PubMed knowledge to weigh the risk factors. A keyword-based algorithm was developed to extract and classify PubMed abstracts into three categories that represented positive, negative, or neutral associations between each risk factor and pancreatic cancer. Then we designed a weighted BNI model by adding the normalized weights into a conventional BNI model. We used this model to extract the EHR values for patients with or without pancreatic cancer, which then enabled us to calculate the prior probabilities for the 20 risk factors in the BNI. The software iDiagnosis was designed to use this weighted BNI model for predicting pancreatic cancer. In an evaluation using a case-control dataset, the weighted BNI model significantly outperformed the conventional BNI and two other classifiers (k-Nearest Neighbor and Support Vector Machine). We conclude that the weighted BNI using PubMed knowledge and EHR data shows remarkable accuracy improvement over existing representative methods for pancreatic cancer prediction. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Prospective assessment of the influence of pancreatic cancer resection on exocrine pancreatic function.

    Science.gov (United States)

    Sikkens, E C M; Cahen, D L; de Wit, J; Looman, C W N; van Eijck, C; Bruno, M J

    2014-01-01

    Exocrine insufficiency frequently develops in patients with pancreatic cancer owing to tumour ingrowth and pancreatic duct obstruction. Surgery might restore this function by removing the primary disease and restoring duct patency, but it may also have the opposite effect, as a result of resection of functional parenchyma and anatomical changes. This study evaluated the course of pancreatic function, before and after pancreatic resection. This prospective cohort study included patients with tumours in the pancreatic region requiring pancreatic resection in a tertiary referral centre between March 2010 and August 2012. Starting before surgery, exocrine function was determined monthly by measuring faecal elastase 1 levels (normal value over 0.200 µg per g faeces). Endocrine function, steatorrhoea-related symptoms and bodyweight were also evaluated before and after surgery. Subjects were followed from diagnosis until 6 months after surgery, or until death. Twenty-nine patients were included, 12 with pancreatic cancer, 14 with ampullary carcinoma and three with bile duct carcinoma (median tumour size 2.6 cm). Twenty-six patients underwent pancreaticoduodenectomy and three distal pancreatectomy. Thirteen patients had exocrine insufficiency at preoperative diagnosis. After a median follow-up of 6 months, this had increased to 24 patients. Diabetes was present in seven patients at diagnosis, and developed in one additional patient within 1 month after surgery. Most patients with tumours in the pancreatic region requiring pancreatic resection either had exocrine insufficiency at diagnosis or became exocrine-insufficient soon after surgical resection. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  4. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

    2015-07-17

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

  5. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    International Nuclear Information System (INIS)

    Chang, Aeson; Kim-Fuchs, Corina; Le, Caroline P.; Hollande, Frédéric; Sloan, Erica K.

    2015-01-01

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer

  6. Obesity and Cancer Risk

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... hormone therapy and for tumors that express hormone receptors . Obesity is also a risk factor for breast ...

  7. Personalized RNA Medicine for Pancreatic Cancer.

    Science.gov (United States)

    Gilles, Maud-Emmanuelle; Hao, Liangliang; Huang, Ling; Rupaimoole, Rajesha; Lopez-Casas, Pedro P; Pulver, Emilia; Jeong, Jong Cheol; Muthuswamy, Senthil K; Hidalgo, Manuel; Bhatia, Sangeeta N; Slack, Frank J

    2018-04-01

    Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21, was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy. Clin Cancer Res; 24(7); 1734-47. ©2018 AACR . ©2018 American Association for Cancer Research.

  8. Ultraviolet B Irradiance and Vitamin D Status are Inversely Associated With Incidence Rates of Pancreatic Cancer Worldwide

    Science.gov (United States)

    2010-01-01

    Inst. 2005;97:1458Y1465. 9. Larsson SC, Hakanson N, Permert J, et al. Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer...and higher breast cancer risk in 107 countries. Breast J. 2008;14:255Y260. 50. Mishal AA. Effects of different dress styles on vitamin D levels in

  9. Pancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study.

    Science.gov (United States)

    Aschebrook-Kilfoy, Briseis; Cross, Amanda J; Stolzenberg-Solomon, Rachael Z; Schatzkin, Arthur; Hollenbeck, Albert R; Sinha, Rashmi; Ward, Mary H

    2011-08-01

    Nitrate and nitrite are precursors of N-nitroso compounds, which induce tumors of the pancreas in animals. The authors evaluated the relation of dietary nitrate and nitrite to pancreatic cancer risk in the NIH-AARP Diet and Health Study. Nitrate and nitrite intakes were assessed at baseline using a 124-item food frequency questionnaire. During approximately 10 years of follow-up between 1995 and 2006, 1,728 incident pancreatic cancer cases were identified. There was no association between total nitrate or nitrite intake and pancreatic cancer in men or women. However, men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio = 1.18, 95% confidence interval: 0.95, 1.47; P-trend = 0.11). The authors observed a stronger increase in risk among men for nitrate/nitrite intake from processed meat at ages 12-13 years (highest quintile vs. lowest: hazard ratio = 1.32, 95% confidence interval: 0.99, 1.76; P-trend = 0.11), though the relation did not achieve statistical significance. The authors found no associations between adult or adolescent nitrate or nitrite intake from processed meats and pancreatic cancer among women. These results provide modest evidence that processed meat sources of dietary nitrate and nitrite may be associated with pancreatic cancer among men and provide no support for the hypothesis in women.

  10. Factors that affect risk for pancreatic disease in the general population: a systematic review and meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Alsamarrai, Ammar; Das, Stephanie L M; Windsor, John A; Petrov, Maxim S

    2014-10-01

    Pancreatic diseases place significant burdens on health care systems worldwide. However, there is lack of agreement about which factors increase or reduce risk for pancreatic disease. We reviewed high-quality studies of factors that affect risk for pancreatic diseases in the general population. We searched 3 databases (Medline, Embase, and Scopus) for prospective cohort studies of modifiable risk and/or protective factors for acute pancreatitis, chronic pancreatitis, and pancreatic cancer in adult populations. Factors that were investigated in 2 or more studies were assessed by meta-analysis if the required data were available. Subgroup analyses were performed when appropriate. Outcome measures were relative risk (RR) and 95% confidence interval (CI). Our analysis included 51 population-based studies with more than 3 million individuals and nearly 11,000 patients with pancreatic diseases. A total of 31 different factors were investigated. Current tobacco use was the single most important risk factor for pancreatic diseases (RR, 1.87; 95% CI, 1.54-2.27), followed by obesity (RR, 1.48; 95% CI, 1.15-1.92) and heavy use of alcohol (RR, 1.37; 95% CI, 1.19-1.58). Tobacco and heavy use of alcohol had bigger effects on risk of acute pancreatitis and chronic pancreatitis than pancreatic cancer. Vegetable consumption (RR, 0.71; 95% CI, 0.57-0.88) and fruit consumption (RR, 0.73; 95% CI, 0.60-0.90) provided the greatest degree of protection against pancreatic diseases on the basis of meta-analyses. Vegetable consumption had stronger association with protection against acute pancreatitis and fruit consumption with protection against pancreatic cancer. On the basis of systematic review and meta-analysis, current tobacco use, obesity, and heavy use of alcohol are associated with significant increases in risk for pancreatic diseases. Vegetables and fruit consumption are associated with reduced risk for pancreatic diseases. Prevention strategies for acute pancreatitis, chronic

  11. Concurrent chemoradiation for unresectable pancreatic cancer

    International Nuclear Information System (INIS)

    Kim, Yong Bae; Seong, Jin Sil; Song, Si Young; Park, Seung Woo; Suh, Chang Ok

    2002-01-01

    To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. The patients, who were diagnosed by imaging modalities or by explo-laparotomy were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine 1,000 mg/m 2 or Paclitaxel 50 mg/m 2 weekly and oral 5-FU daily. The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months. Survival was analyzed using the Kaplan-Meier method. Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 60 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to; disease progression for 6 (50%), poor performance status for 4 (33.3%), intercurrent disease for 1 (8.3%), and refusal for 1 (8.3%). Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was 59%. The survival rates were 46.7% and 17.0% at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients (19%), while grade III or IV non-hematologic toxicity was shown in 5 patients (12%). Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient

  12. Cardiorespiratory fitness and muscle strength in pancreatic cancer patients.

    Science.gov (United States)

    Clauss, Dorothea; Tjaden, Christine; Hackert, Thilo; Schneider, Lutz; Ulrich, Cornelia M; Wiskemann, Joachim; Steindorf, Karen

    2017-09-01

    Cancer patients frequently experience reduced physical fitness due to the disease itself as well as treatment-related side effects. However, studies on physical fitness in pancreatic cancer patients are missing. Therefore, we assessed cardiorespiratory fitness and muscle strength of pancreatic cancer patients. We included 65 pancreatic cancer patients, mostly after surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was used to evaluate isometric muscle strength. Physical fitness values were compared to reference values of a healthy population. Associations between sociodemographic and clinical variables with patients' physical fitness were analyzed using multiple regression models. Cardiorespiratory fitness (VO 2 peak, 20.5 ± 6.9 ml/min/kg) was significantly lower (-24%) compared to healthy reference values. In the 6MWT pancreatic cancer patients nearly reached predicted values (555 vs. 562 m). Maximal voluntary isometric contraction (MVIC) of the upper (-4.3%) and lower extremities (-13.8%) were significantly lower compared to reference values. Overall differences were larger in men than those in women. Participating in regular exercise in the year before diagnosis was associated with greater VO 2 peak (p fitness with regard to both cardiorespiratory function and isometric muscle strength, already in the early treatment phase (median 95 days after surgical resection). Our findings underline the need to investigate exercise training in pancreatic cancer patients to counteract the loss of physical fitness.

  13. [Surgery for pancreatic cancer: Evidence-based surgical strategies].

    Science.gov (United States)

    Sánchez Cabús, Santiago; Fernández-Cruz, Laureano

    2015-01-01

    Pancreatic cancer surgery represents a challenge for surgeons due to its technical complexity, the potential complications that may appear, and ultimately because of its poor survival. The aim of this article is to summarize the scientific evidence regarding the surgical treatment of pancreatic cancer in order to help surgeons in the decision making process in the management of these patients .Here we will review such fundamental issues as the need for a biopsy before surgery, the type of pancreatic anastomosis leading to better results, and the need for placement of drains after pancreatic surgery will be discussed. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Incidence, risk factors and clinical course of pancreatic fluid collections in acute pancreatitis.

    Science.gov (United States)

    Cui, Mei Lan; Kim, Kook Hyun; Kim, Ho Gak; Han, Jimin; Kim, Hyunsoo; Cho, Kwang Bum; Jung, Min Kyu; Cho, Chang Min; Kim, Tae Nyeun

    2014-05-01

    Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems. Acute fluid collections and pseudocyst formation are the most frequent complications of acute pancreatitis. The aims of this study were to evaluate the incidence, risk factors, and clinical course of pancreatic fluid collections and pseudocyst formation following acute pancreatitis. A prospective multicenter study was conducted in five participating centers with 302 patients diagnosed with acute pancreatitis from January 2011 to July 2012. The incidence of pancreatic fluid collections and pseudocyst was 42.7 and 6.3 %, respectively. Patients with fluid collections were significantly younger, compared to those without fluid collections (51.5 ± 15.9 vs. 60.4 ± 16.5 years, P = 0.000). The proportion of alcoholic etiology (54.3 %) in patients with fluid collections was significantly higher compared to other etiologies (P = 0.000). C-reactive protein (CRP) (48 h) was significantly higher in patients with fluid collections, compared to patients without fluid collections (39.2 ± 77.4 vs. 15.1 ± 36.2 mg/dL, P = 0.016). LDH (48 h) was significantly higher in patients with pseudocyst formation, compared to patients with complete resolution (1,317.6 ± 706.4 vs. 478.7 ± 190.5 IU/L, P = 0.000). Pancreatic fluid collections showed spontaneous resolution in 69.8 % (90/129) and 84.2 % of the pseudocysts disappeared or decreased in size during follow up. Age, CRP (48 h), and alcohol etiology are risk factors for pancreatic fluid collections. LDH (48 h) appears to be a risk factor for pseudocyst formation. Most pseudocysts showed a decrease in size or spontaneous resolution with conservative management.

  15. Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.

    Directory of Open Access Journals (Sweden)

    Shanmiao Gou

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.

  16. Low Concentrations of Metformin Selectively Inhibit CD133+ Cell Proliferation in Pancreatic Cancer and Have Anticancer Action

    Science.gov (United States)

    Li, Xiangsheng; Shi, Pengfei; Liu, Tao; Wang, Chunyou

    2013-01-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133+ but not CD24+CD44+ESA+ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133+ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease. PMID:23667692

  17. Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells.

    Science.gov (United States)

    Chen, Wenxue; Ayala-Orozco, Ciceron; Biswal, Nrusingh C; Perez-Torres, Carlos; Bartels, Marc; Bardhan, Rizia; Stinnet, Gary; Liu, Xian-De; Ji, Baoan; Deorukhkar, Amit; Brown, Lisa V; Guha, Sushovan; Pautler, Robia G; Krishnan, Sunil; Halas, Naomi J; Joshi, Amit

    2014-01-01

    We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy.

  18. Computer-aided diagnosis of pancreatic and lung cancer

    Directory of Open Access Journals (Sweden)

    B. Luis Lancho Tofé

    2008-12-01

    Full Text Available When we talk about cancer diagnosis the most important thing is early diagnosis to prevent cancer cells from spreading. We may also consider the high cost of diagnostic tests. Our approach seeks to address both problems. It uses a software based on Bayesian networks that simulates the causeeffect relationships and gets the chance of suffering a pancreatic cancer or lung cancer. This software would support doctors and save a lot of time and resources.

  19. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias; Brunner, Thomas B.; Niyazi, Maximilian

    2016-01-01

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [de

  20. Risk Factors for Migration, Fracture, and Dislocation of Pancreatic Stents

    Directory of Open Access Journals (Sweden)

    Yoshiaki Kawaguchi

    2015-01-01

    Full Text Available Aim. To analyze the risk factors for pancreatic stent migration, dislocation, and fracture in chronic pancreatitis patients with pancreatic strictures. Materials and Methods. Endoscopic stent placements (total 386 times were performed in 99 chronic pancreatitis patients with pancreatic duct stenosis at our institution between April 2006 and June 2014. We retrospectively examined the frequency of stent migration, dislocation, and fracture and analyzed the patient factors and stent factors. We also investigated the retrieval methods for migrated and fractured stents and their success rates. Results. The frequencies of stent migration, dislocation, and fracture were 1.5% (5/396, 0.8% (3/396, and 1.2% (4/396, respectively. No significant differences in the rates of migration, dislocation, or fracture were noted on the patient factors (etiology, cases undergoing endoscopic pancreatic sphincterotomy, location of pancreatic duct stenosis, existence of pancreatic stone, and approach from the main or minor papilla and stent factors (duration of stent placement, numbers of stent placements, stent shape, diameter, and length. Stent retrieval was successful in all cases of migration. In cases of fractured stents, retrieval was successful in 2 of 4 cases. Conclusion. Stent migration, fracture, and dislocation are relatively rare, but possible complications. A good understanding of retrieval techniques is necessary.

  1. Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer.

    Science.gov (United States)

    Altieri, Barbara; Grant, William B; Della Casa, Silvia; Orio, Francesco; Pontecorvi, Alfredo; Colao, Annamaria; Sarno, Gerardo; Muscogiuri, Giovanna

    2017-11-02

    Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

  2. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  3. Laparoscopic versus open distal pancreatectomy for pancreatic cancer

    NARCIS (Netherlands)

    Riviere, D.M.; Gurusamy, K.S.; Kooby, D.A.; Vollmer, C.M.; Besselink, M.G.; Davidson, B.R.; Laarhoven, C.J.H.M. van

    2016-01-01

    BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In

  4. Laparoscopic versus open distal pancreatectomy for pancreatic cancer

    NARCIS (Netherlands)

    Riviere, Deniece; Gurusamy, Kurinchi Selvan; Kooby, David A.; Vollmer, Charles M.; Besselink, Marc G. H.; Davidson, Brian R.; van Laarhoven, Cornelis J. H. M.

    2016-01-01

    Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on

  5. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery

  6. Survivin as a radioresistance factor in pancreatic cancer

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Moriai, Ryosuke; Yajima, Tomomi; Yagihashi, Atsuhito; Yamada, Mikako; Kobayashi, Daisuke; Watanabe, Naoki

    2000-01-01

    We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy. (author)

  7. Rare case of pancreatic cancer with leptomeningeal carcinomatosis

    Science.gov (United States)

    Yoo, In Kyung; Lee, Hong Sik; Kim, Chang Duk; Chun, Hoon Jai; Jeen, Yoon Tae; Keum, Bora; Kim, Eun Sun; Choi, Hyuk Soon; Lee, Jae Min; Kim, Seung Han; Nam, Seung Joo; Hyun, Jong Jin

    2015-01-01

    Leptomeningeal carcinomatosis occurs very rarely in patients with pancreatic cancer. Leptomeningeal carcinomatosis is characterized by multifocal seeding of the leptomeninges by malignant cells that originate from a solid tumor. To the best of our knowledge, brain metastasis from pancreatic cancer is extremely rare. Leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of cases of solid tumors. The clinical manifestation usually involves neurological symptoms, including dizziness, headache, vomiting, nausea, and hemiparesis, symptoms similar to those of meningitis or brain tumors. Diagnostic methods for leptomeningeal carcinomatosis include brain magnetic resonance imaging and cerebrospinal fluid examination. Here, we describe a case of leptomeningeal carcinomatosis in which the primary tumor was later determined to be pancreatic cancer. Brain magnetic resonance imaging findings showed mild enhancement of the leptomeninges, and cerebrospinal fluid cytology was negative at first. However, after repeated spinal taps, atypical cells were observed on cerebrospinal fluid analysis and levels of tumor markers such as carbohydrate antigen 19-9 in cerebrospinal fluid were elevated. Abdominal computed tomography, performed to determine the presence of extracerebral tumors, revealed pancreatic cancer. Pancreatic cancer was confirmed histopathologically on examination of an endoscopic ultrasound-guided fine needle aspiration specimen. PMID:25624740

  8. File list: ALL.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.05.AllAg.Pancreatic_cancer_cells mm9 All antigens Pancreas Pancreatic cancer... cells SRX174586,SRX174585,SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  9. File list: Oth.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.20.AllAg.Pancreatic_cancer_cells mm9 TFs and others Pancreas Pancreatic cancer... cells SRX174585,SRX174586 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  10. File list: His.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.20.AllAg.Pancreatic_cancer_cells mm9 Histone Pancreas Pancreatic cancer cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  11. File list: His.Pan.10.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.10.AllAg.Pancreatic_cancer_cells mm9 Histone Pancreas Pancreatic cancer cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Pan.10.AllAg.Pancreatic_cancer_cells.bed ...

  12. File list: Pol.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.50.AllAg.Pancreatic_cancer_cells mm9 RNA polymerase Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  13. File list: Oth.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.05.AllAg.Pancreatic_cancer_cells mm9 TFs and others Pancreas Pancreatic cancer... cells SRX174586,SRX174585 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  14. File list: ALL.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.50.AllAg.Pancreatic_cancer_cells mm9 All antigens Pancreas Pancreatic cancer... cells SRX174585,SRX174586,SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  15. File list: Unc.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Pan.50.AllAg.Pancreatic_cancer_cells mm9 Unclassified Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  16. File list: His.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.50.AllAg.Pancreatic_cancer_cells mm9 Histone Pancreas Pancreatic cancer cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  17. File list: DNS.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Pan.20.AllAg.Pancreatic_cancer_cells mm9 DNase-seq Pancreas Pancreatic cancer c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  18. CT of the pancreatic body and tail in cancer of the head

    International Nuclear Information System (INIS)

    Ono, Minoru; Muranaka, Tooru; Nishitani, Hiromu; Onitsuka, Hideo; Kawanami, Takashi; Matsuura, Keiichi

    1983-01-01

    In comparison with chronic pancreatitis (27 cases), CT images of secondary changes in the pancreatic body and tail in cancer of the pancreatic head were studied in 17 cases. In cancer cases, the pancreatic duct was dilated in a rosary or linear form, and a fairly large portion of the duct was visualized in continuation in one slice. The parenchyma was uniformly atrophic. Chronic pancreatitis demonstrated various CT images. In the localized-mass-forming type, the pancreatic body and tail showed findings similar to those of cancer in some cases, but unevenness of the pancreatic parenchyma and flexion, tortuosity and discontinuity of the pancreatic duct were observed only in chronic pancreatitis. As well as improvement in CT images, the spatial relationship between the pancreatic duct and parenchyma should be studied in more detail. (Chiba, N.)

  19. The WSB1 gene is involved in pancreatic cancer progression.

    Directory of Open Access Journals (Sweden)

    Cendrine Archange

    Full Text Available BACKGROUND: Pancreatic cancer cells generate metastases because they can survive the stress imposed by the new environment of the host tissue. To mimic this process, pancreatic cancer cells which are not stressed in standard culture conditions are injected into nude mice. Because they develop xenografts, they should have developed adequate stress response. Characterizing that response might provide new strategies to interfere with pancreatic cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the human pancreatic cancer cell lines Panc-1, Mia-PaCa2, Capan-1, Capan-2 and BxPC3, we used Affymetrix DNA microarrays to compare the expressions of 22.000 genes in vitro and in the corresponding xenografts. We identified 228 genes overexpressed in xenografts and characterized the implication of one of them, WSB1, in the control of apoptosis and cell proliferation. WSB1 generates 3 alternatively spliced transcripts encoding distinct protein isoforms. In xenografts and in human pancreatic tumors, global expression of WSB1 mRNA is modestly increased whereas isoform 3 is strongly overexpressed and isoforms 1 and 2 are down-regulated. Treating Mia-PaCa2 cells with stress-inducing agents induced similar changes. Whereas retrovirus-forced expression of WSB1 isoforms 1 and 2 promoted cell growth and sensitized the cells to gemcitabine- and doxorubicin-induced apoptosis, WSB1 isoform 3 expression reduced cell proliferation and enhanced resistance to apoptosis, showing that stress-induced modulation of WSB1 alternative splicing increases resistance to apoptosis of pancreatic cancer cells. CONCLUSIONS/SIGNIFICANCE: Data on WSB1 regulation support the hypothesis that activation of stress-response mechanisms helps cancer cells establishing metastases and suggest relevance to cancer development of other genes overexpressed in xenografts.

  20. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.

    Science.gov (United States)

    Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K; Smyrk, Thomas C; Lau, Julie S; Bhattacharya, Santanu; Truty, Mark; Petersen, Gloria M; Kaufman, Randal J; Chari, Suresh T; Mukhopadhyay, Debabrata

    2015-04-01

    Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into

  1. Discussion of difficult problems of early diagnosis of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    GUO Xiaozhong

    2014-08-01

    Full Text Available Pancreatic cancer is a common malignant neoplasm of the pancreas with an extremely high mortality. Currently, the early diagnosis of pancreatic cancer is still not ideal. Attention should be paid to some clinical warning symptoms, such as unexplained abdominal and back pain, jaundice, and unexpected diabetes. Additionally, the combined use of CA19-9, CEA, and other tumor markers, the attention to biochemical indicators, the detection of mutation in KAI1 or p53 gene, and the exploration of the value of miRNA in clinical diagnosis are of great significance. On the other hand, ultrasound, CT, MRCP, ERCP, PET-CT, and other imaging methods, as well as effective collection of cytology specimens, should be performed. Thus, there is hope for the early diagnosis of pancreatic cancer.

  2. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Samm, Nicole; Werner, Kristin; Rückert, Felix; Saeger, Hans Detlev; Grützmann, Robert; Pilarsky, Christian

    2010-01-01

    Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-x L and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer

  3. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Hans Detlev Saeger

    2010-12-01

    Full Text Available Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

  4. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  5. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  6. Pancreatic cancer seeding of percutaneous needle tract

    Directory of Open Access Journals (Sweden)

    Qiao Zhou, MD

    2017-03-01

    Full Text Available A 65-year old African-American female presents with biliary ductal dilatation due to an obstructive pancreatic head mass. Percutaneous transhepatic cholangiogram performed and biliary drainage catheter placement for decompression of the biliary system. The patient had a Whipple procedure performed several months later. On follow up CT imaging, there was interval development and enlargement of a subcutaneous lesion by the right oblique muscles. Biopsy of this lesion revealed pancreatic adenocarcinoma from percutaneous seeding of the transhepatic needle tract.

  7. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  8. Fluorodeoxyglucose positron emission tomography in pancreatic cancer: an unsolved problem

    International Nuclear Information System (INIS)

    Kato, Takashi; Fukatsu, Hiroshi; Ito, Kengo; Tadokoro, Masanori; Ota, Toyohiro; Ikeda, Mitsuru; Isomura, Takayuki; Ito, Shigeki; Nishino, Masanari; Ishigaki, Takeo

    1995-01-01

    The aim of this study was to examine the significance and problems of 2-[fluorine-18]-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in diagnosing pancreatic cancer and mass-forming pancreatitis (MFP). PET, X-ray computed tomography (CT) and magnetic resonance (MR) imaging were performed in 15 patients with pancreatic cancer and nine patients with MFP. The areas of the PET scan were determined according to the markers drawn on the patients at CT or MR imaging. Regions of interests (ROIs) were placed by reference to the CT or MR images corresponding to the PET images. Tissue metabolism was evaluated by the differential absorption ratio (DAR) at 50 min after intravenous injection of FDG [DAR = tissue tracer concentration/(injected dose/body weight). The DAR value differed significantly in pancreatic cancer (mean±SD, 4.64±1.94) and MFP (mean±SD, 2.84±2.22) (P<0.05). In one false-negative case (mucinous adenocarcinoma), the tumour contained a small number of malignant cells. In one false-positive case, lymphocytes accumulated densely in the mass in the pancreatic head. Further studies are necessary to investigate the histopathological characteristics (especially the cellularity) and other factors affecting the FDG DAR on PET images. (orig.)

  9. Post-ERCP acute pancreatitis and its risk factors.

    Science.gov (United States)

    Iorgulescu, A; Sandu, I; Turcu, F; Iordache, N

    2013-03-15

    Endoscopic retrograde cholangiopancreatography (ERCP) is a complex endoscopic technique that evolved from a diagnostic to a mainly therapeutic procedure. This was due to the identification of post-procedural complications that can follow both simple ERCP and that associated with the instrumentation of the biliary and pancreatic ductals. The identification of post ERCP complications in a proportion of 5 to 10% of cases, with a mortality rate of 0.33%, imposed their analysis and study of risk factors involved in their occurrence. The significance of post ERCP complications reveals the necessity of their avoidance by adopting additional measures if risk factors are identified. We have retrospectively analyzed 900 cases that underwent ERCP in the Surgery Department of "Sf. Ioan" Clinical Hospital in a period of 17 years. The complications of the procedure were studied. Among them, a special attention was given to post-ERCP acute pancreatitis (pERCP-AP), the most common complication that occurred in the study group. We also tried to find out and highlight the risk factors for this complication. ERCP is a relatively safe invasive procedure, yet it has complications (8% of cases), some of them potentially fatal (mortality 0.43%). The most common complications after ERCP are acute pancreatitis (3.7%), papillary bleeding (1.04%), retroperitoneal duodenal perforation (0.69%) and biliary septic complications like acute cholecystitis and cholangitis (1.21%). Acute pancreatitis is by far the most common complication. Risk factors for its occurrence are difficult sphincterotomy with precut use, failure of CBD desobstruction, pancreatic sphincterotomy, repeated injection of contrast in the pancreatic ductal system, dysfunction of the sphincter of Oddi and the absence of changes of chronic pancreatitis. When risk factors are identified, the patients' selection must be very strict and diagnostic ERCP should be avoided in favor of non-invasive diagnostic methods (MRI

  10. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  11. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

    2010-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  12. Intraoperative radiotherapy in pancreatic cancer: A systematic review

    International Nuclear Information System (INIS)

    Ruano-Ravina, Alberto; Almazan Ortega, Raquel; Guedea, Ferrran

    2008-01-01

    Background and purpose: Intraoperative radiotherapy (IORT) has been considered for treatment of pancreas cancer since local recurrence rates are very high. This study assesses the efficacy and safety of IORT in pancreatic cancer. Materials and methods: We conducted a systematic review of scientific literature from January 1995 to February 2007, including Medline, Embase, ISI Web of Science and HTA (Health Technology Assessment). By applying a series of inclusion criteria, two independent reviewers selected those studies in which a minimum of 30 patients received IORT and which furnished survival results based on a minimum 3-month follow-up. Results: Fourteen papers were included, one was an IORT assessment report, 5 were cohort studies, and the remaining 8 were case series studies, 2 of which belonged to the same series. In general, these studies showed that IORT could slightly increase survival among patients with pancreatic cancer in localized stages. However, the results were not conclusively in favor of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There were no published studies that assessed quality of life. Conclusions: There is no clear evidence to indicate that IORT is more effective than other therapies in treating pancreatic cancer in locally advanced and metastatic stages

  13. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  14. Pancreatic cancer in patients with chronic calcifying pancreatitis: Computed tomography findings – a retrospective analysis of 48 patients

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, Amir, E-mail: amir.med87@gmail.com [Department of Radiology, Brabois Adults Hospital, Nancy (France); Ayav, Ahmet [Department of HPB Surgery, University Hospital of Nancy (France); Belle, Arthur [Department of Hepatogastroenterologie, Brabois Adults Hospital, Nancy (France); Orry, Xavier [Department of Radiology, Brabois Adults Hospital, Nancy (France); Chevaux, Jean-Baptiste [Department of Hepatogastroenterologie, Brabois Adults Hospital, Unité Inserm U954, Nancy (France); Laurent, Valerie [Department of Radiology, Brabois Adults Hospital, Nancy (France); Laboratory IADI, INSERM u947 (France)

    2017-01-15

    Objective: Chronic calcifying pancreatitis (CCP) is a risk factor for pancreatic cancer (PC). Symptoms of PC are non-specific in patients with CCP, and diagnostic imaging can be difficult. Some studies have shown that diagnosis may take several months, leading to delays in treatment (Lin et al., 2015; Lennon et al., 2014) . The aim of this study was to describe the radiological signs of PC in patients with CCP. Methods: This retrospective, single-center study was conducted between January 2004 and December 2014. Patients with CCP who were being monitored for PC were included. Each patient diagnosed with PC was matched with two CCP controls who did not develop PC. Results: We studied 48 patients with CCP (30 men (62%) and 18 women (38%), mean age 69.4 years). Sixteen patients (with 18 tumor sites) who developed PC (1.52%) were compared with 32 controls who did not develop PC. A hypodense mass was observed in all of the patients with PC, predominantly in the pancreatic head (61.2%). No such masses were observed in the controls (p < 0.001). The average mass size was 36.3 mm, and the masses were observed to push aside the calcifications in all patients (p < 0.001). Calcifications were very abundant (>10) in 33.3% of the patients with PC and in 71.9% of the controls (p = 0.0076). The main pancreatic duct (MPD) was dilated in all of the patients with PC (average diameter 8.6 mm; homogeneous in 83.3%) and in only 46.9% of the controls (average 7.4 mm; homogeneous in 37.5%) (p > 0.05). Dilation of the intrahepatic bile ducts and common bile duct was observed in 15 (94.4%) of the patients with PC and in none of the controls (p < 0.0001). The average alcohol consumption was 1 g/day (0–5 g/day) in the PC group and 4.6 g/day (0–20 g/day) in the control group. In addition, the average smoking history was 14.25 pack-years (0–40 PY) in the PC group and 27.70 PY (0–60 PY) in the control group. Conclusion: The presence of a pancreatic mass in a patient with CCP is

  15. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

    NARCIS (Netherlands)

    Klein, Alison P.; Wolpin, Brian M.; Risch, Harvey A.; Stolzenberg-Solomon, Rachael Z.; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J.; Hoskins, Jason W.; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A.; Babic, Ana; Bamlet, William R.; Beane-Freeman, Laura; Berndt, Sonja I.; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M.; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G.; Chung, Charles C.; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J.; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J. Michael; Gazouli, Maria; Giles, Graham G.; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E.; Goodman, Phyllis J.; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J.; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A.; Hoover, Robert; Hung, Rayjean J.; Jacobs, Eric J.; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A.; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H.; Kupcinskas, Juozas; Kurtz, Robert J.; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T.; Lee, I.-Min; Lemarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E.; Neoptolemos, John P.; Oberg, Ann L.; Olson, Sara H.; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V.; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X.; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D.; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P.; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D.; Tobias, Geoffrey S.; van den Eeden, Stephen K.; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M.; Amundadottir, Laufey T.

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  16. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

    NARCIS (Netherlands)

    Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Chen, Fei; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Albanes, Demetrius; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  17. Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease

    Science.gov (United States)

    Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

    2016-01-01

    Abstract The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19–1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19–1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31–1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04–1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02–1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31–1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16–1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72–1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56–1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06–1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is

  18. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  19. Gastric, pancreatic, and colorectal carcinogenesis following remote peptic ulcer surgery. Review of the literature with the emphasis on risk assessment and underlying mechanism

    NARCIS (Netherlands)

    Offerhaus, G. J.; Tersmette, A. C.; Tersmette, K. W.; Tytgat, G. N.; Hoedemaeker, P. J.; Vandenbroucke, J. P.

    1988-01-01

    Based upon literature data, a 2-fold risk for gastric and colorectal cancer and a 2- to 5-fold risk for pancreatic cancer are predicted after remote peptic ulcer surgery. The association between previous ulcer surgery and subsequent gastric cancer appears firm; the linkage between colorectal and

  20. Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

    Science.gov (United States)

    Gąsiorowska, Anita; Talar-Wojnarowska, Renata; Kaczka, Aleksandra; Borkowska, Anna; Czupryniak, Leszek; Małecka-Panas, Ewa

    2013-01-01

    Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  1. Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT

    International Nuclear Information System (INIS)

    Amin, Z.; Theis, B.; Russell, R.C.G.; House, C.; Novelli, M.; Lees, W.R.

    2006-01-01

    Aims: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. Materials and methods: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. Results: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. Conclusion: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features

  2. Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Z.; Theis, B.; Russell, R.C.G.; House, C.; Novelli, M.; Lees, W.R

    2006-12-15

    Aims: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. Materials and methods: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. Results: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. Conclusion: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features.

  3. Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Alireza Tavassoli

    2013-08-01

    Full Text Available Introduction : Severepain is a major problem in patients with unresectable pancreatic cancer. The goal of this study is to evaluate the effects of Thoracoscopic Splanchnicectomy (TS on pain control in these patients suffering from unresectable pancreatic cancer. Methods:Between years 2000 to 2011, 20 patients suffering from unresectable pancreatic cancer underwent TS due to severe pain. They were studied in terms of age, sex, location of pancreas tumor, history of previous surgery, response to treatments for pain control (assessed with VAS scoring system and complications of surgery. Results:M/F = 14/6 with a mean age of 63 years. The most common tumour site was at the pancreas head (in 8 patients. The most cause of unresectability was local expansion to critical adjacent elements (in 10 patients. Surgery was performed successfully in all patients. Post-operative complication included only pleural effusion on the left side which was cured by proper treatment. There were no post-op mortalities.  15 patients had acceptable levels of pain at the end of a six month follow-up period. ConclusionTS provides good pain control, little side effects and minimal invasiveness, the technique is recommended for pain control in patients with unresectable pancreatic cancer.

  4. Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model. Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay ...

  5. Electroacupuncture treatment for pancreatic cancer pain: a randomized controlled trial.

    Science.gov (United States)

    Chen, Hao; Liu, Tang-Yi; Kuai, Le; Zhu, Ji; Wu, Cai-Jun; Liu, Lu-Ming

    2013-01-01

    Pancreatic cancer is often accompanied by severe abdominal or back pain. It's the first study to evaluate the analgesic effect of electroacupuncture on pancreatic cancer pain. A randomized controlled trial compared electroacupuncture with control acupuncture using the placebo needle. Sixty patients with pancreatic cancer pain were randomly assigned to the electroacupuncture group (n = 30) and the placebo control group (n = 30). Patients were treated on Jiaji (Ex-B2) points T8-T12 bilaterally for 30 min once a day for 3 days. Pain intensity was assessed with numerical rated scales (NRS) before the treatment (Baseline), after 3 treatments, and 2 days follow-up. Baseline characteristics were similar in the two groups. After 3 treatment, pain intensity on NRS decreased compared with Baseline (-1.67, 95% confidence interval [CI] -1.46 to -1.87) in the electroacupuncture group; there was little change (-0.13, 95% CI 0.08 to -0.35) in control group; the difference between two groups was statistically significant (P electroacupuncture group compared with the control group (P Electroacupuncture was an effective treatment for relieving pancreatic cancer pain. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Stolzenberg-Solomon, R.; Pacetti, P.; Vodička, Pavel; Cleary, S.P.; Capurso, G.; Bueno-de-Mesquita, H. B.; Werner, J.; Gazouli, M.; Butterbach, K.; Ivanauskas, A.; Giese, N.; Petersen, G. M.; Fogar, P.; Wang, Z.; Bassi, C.; Ryska, M.; Theodoropoulos, G.E.; Kooperberg, Ch.; Li, D.; Greenhalf, W.; Pasquali, C.; Hackert, T.; Fuchs, Ch.S.; Mohelníková-Duchoňová, B.; Sperti, C.; Funel, N.; Dieffenbach, A.K.; Wareham, N.J.; Buring, J.; Holcátová, I.; Costello, E.; Zambon, C.F.; Kupcinskas, J.; Risch, H.A.; Kraft, P.; Bracci, P.M.; Pezzilli, R.; Olson, S.H.; Sesso, H. D.; Hartge, P.; Strobel, O.; Malecka-Panas, E.; Visvanathan, K.; Arslan, A. A.; Pedrazzoli, S.; Souček, P.; Gioffreda, D.; Key, T.J.; Talar-Wojnarowska, R.; Scarpa, A.; Mambrini, A.; Jacobs, E.J.; Jamroziak, K.; Klein, A.; Tavano, F.; Bambi, F.; Landi, S.; Austin, M. A.; Vodičková, Ludmila; Brenner, H.; Chanock, S. J.; Fave, G.D.; Piepoli, A.; Cantore, M.; Zheng, W.; Wolpin, B.M.; Amundadottir, L. T.; Canzian, F.

    2015-01-01

    Roč. 137, č. 9 (2015), s. 2175-2183 ISSN 0020-7136 R&D Projects: GA ČR GAP301/12/1734 Institutional support: RVO:68378041 Keywords : pancreatic cancer * polymorphisms * telomerase * susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.531, year: 2015

  7. Knowledge discovery for pancreatic cancer using inductive logic programming.

    Science.gov (United States)

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

  8. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  9. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  10. Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: A retrospective study

    Directory of Open Access Journals (Sweden)

    Fujii Shoichi

    2008-10-01

    Full Text Available Abstract Background Postoperative pancreas fistula (POPF is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy. Methods Fifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT between the anterior abdominal skin and the back skin (U-APD and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD and the distance of a horizontal plane at a right angle to CAD (CATD were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD was calculated. Results POPF occurred in 7 patients (14.0% and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25 and a high CA depth ratio (≥0.370 independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively. Conclusion Surgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.

  11. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

    2011-01-01

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

  12. Radiotherapy Technical Considerations in the Management of Locally Advanced Pancreatic Cancer: American-French Consensus Recommendations

    International Nuclear Information System (INIS)

    Huguet, Florence; Goodman, Karyn A.; Azria, David; Racadot, Severine; Abrams, Ross A.

    2012-01-01

    Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose

  13. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations.

    Science.gov (United States)

    Huguet, Florence; Goodman, Karyn A; Azria, David; Racadot, Severine; Abrams, Ross A

    2012-08-01

    Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity

  14. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  15. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

    Science.gov (United States)

    Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

    2018-03-16

    Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  16. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice

    Directory of Open Access Journals (Sweden)

    Kayla A. Quirin

    2018-03-01

    Full Text Available Recombinant adeno-associated virus (rAAV-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9 expressing GFP in a self-complementary (sc AAV vector under an EF1α promoter (scAAV.GFP following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg. Intraductal delivery of 1 × 1011 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 1011 vg. In a KrasG12D-driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  17. Study of inter-fractional variations and adaptive radiotherapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Yang Chengliang; Wang Jianhua; Li Dingjie; Mao Ronghu; Li, X. Allen

    2012-01-01

    Objective: To quantitatively characterize the inter-fractional anatomy variations and advantages of dosimetry for the adaptive radiotherapy in pancreatic cancer. Methods: A total of 226 daily CT images acquired from 10 patients with pancreatic cancer treated with image-guided radiotherapy were analyzed retrospectively. Targets and organs at risk (OARs) were delineated by the atlas-based automatic segmentation and modified by the skilled physician. Various parameters,including the center of mass (COM) distance, the maximal overlap ratio (MOR) and the Dice coefficient (DC), were used to quantify the inter-fractional organ displacement and deformation. The adaptive radiation therapy (ART) was applied to handle the daily GT images. The dose distributions parameters from the ART plan were compared with those from the repositioning plan. Results: The inter-fractional anatomy variations of pancreas head were obvious in the pancreatic cancer irradiation. The mean COM distance, MOR and DC of pancreas head after the bony or soft tissue alignment and registration was (7.8 ± 1.3)mm, (87.2 ± 8.4)% and (77.2 ±7.9)% respectively. Compared with the repositioning plan, the ART plan had better target coverage and OARs sparing. For example, the mean V 100 of PTV was improved from (93.32 ± 2.89) % for repositioning plan to (96.03 ± 1.42)% for ART plan with t =2.79, P =0.008 and the mean V 50.4 for duodenum was reduced from (43.4 ± 12.71)% for the repositioning plan to (15.6 ± 6.25)% for the ART plan with t =3.52, P=0.000. Conclusions: The ART can effectively account for the obvious inter-fractional anatomy variations in pancreatic cancer irradiation and be used to escalate the radiotherapy dose for the pancreatic cancer, which will lead to a promising higher local control rate. (authors)

  18. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  19. CHOLECYSTOKININ RECEPTOR ANTAGONIST HALTS PROGRESSION OF PANCREATIC CANCER PRECURSOR LESIONS AND FIBROSIS IN MICE

    Science.gov (United States)

    Smith, Jill P.; Cooper, Timothy K.; McGovern, Christopher O.; Gilius, Evan L.; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A.; Gutkind, J. Silvio; Matters, Gail L.

    2014-01-01

    Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved with the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK-receptor antagonist (proglumide, 0.1mg/ml). Pancreas from mice were removed and examined histologically for number and grade of PanINs after 1, 2 or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed and progression to advanced lesions arrested in mice treated with proglumide compared to controls (p=0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared to vehicle (pitalic>0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. Use of CCK-receptor antagonists may have a role in cancer prophylaxis in high risk subjects, and may reduce fibrosis in the microenvironment. PMID:25058882

  20. Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.

    Science.gov (United States)

    Guo, Songchuan; Contratto, Merly; Miller, George; Leichman, Lawrence; Wu, Jennifer

    2017-06-10

    Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

  1. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  2. Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with diabetes: a case-control study.

    Science.gov (United States)

    Murakami, Mariko; Nagai, Yoshio; Tenjin, Ayumi; Tanaka, Yasushi

    2018-04-11

    Pancreatic cancer is a highly lethal malignancy. CA19-9 is a well-known marker for diagnosis of pancreatic cancer, but the serum CA19-9 level is reported to be elevated in patients with poorly controlled diabetes. This study evaluated the sensitivity, specificity, and cut-off value of serum CA19-9 for detection of pancreatic cancer in patients with diabetes. A case-control study of 236 patients was performed. The case group was selected from diabetic patients with pancreatic cancer, while one control was selected for each case from among diabetic patients without pancreatic cancer during the same period. The case group (n = 118) and the control group (n = 118) were matched for age, sex, and pancreatic cancer risk factors. Receiver operating characteristic (ROC) curves were plotted to determine the serum CA19-9 level that predicted pancreatic cancer. Then the sensitivity and specificity of CA19-9 were calculated for the threshold value. There were no significant differences of age, sex, BMI, smoking, alcohol intake, and HbA1c between the case and control groups. According to ROC analysis, a serum CA19-9 level of 75 U/mL had the maximum sensitivity and specificity for separating diabetic patients with or without pancreatic cancer. Using this cut-off value, the sensitivity and specificity of CA19-9 for pancreatic cancer was 69.5% and 98.2%, respectively, while the area under the ROC curve was 0.875 [95%CI: 0.826-0.924]. We propose that a serum CA19-9 level of 75 U/mL should be used as the cut-off value when screening patients with diabetes for pancreatic cancer.

  3. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Science.gov (United States)

    Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  4. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  5. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis.

    Science.gov (United States)

    Karagianni, Vasiliki Th; Papalois, Apostolos E; Triantafillidis, John K

    2012-12-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance of the nutritional and functional status and the prevention or attenuation of cachexia. Oral nutrition could reduce complications while restoring quality of life. Enteral nutrition in the post-operative period could also reduce infective complications. The evidence for immune-enhanced feed in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported by the available clinical data. Nutritional support during the post-operative period on a cyclical basis is preferred because it is associated with low incidence of gastric stasis. Postoperative total parenteral nutrition is indicated only to those patients who are unable to be fed orally or enterally. Thus nutritional deficiency is a relatively widesoread and constant finding suggesting that we must optimise the nutritional status both before and after surgery.

  6. Laparoscopic versus open distal pancreatectomy for pancreatic cancer.

    Science.gov (United States)

    Riviere, Deniece; Gurusamy, Kurinchi Selvan; Kooby, David A; Vollmer, Charles M; Besselink, Marc G H; Davidson, Brian R; van Laarhoven, Cornelis J H M

    2016-04-04

    Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance. To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both. We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non-randomised studies. We also searched the reference lists of included trials to identify additional studies. We considered for inclusion in the review RCTs and non-randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status.. Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed-effect and random-effects models with RevMan 5 on the basis of intention-to-treat analysis when possible. We found no RCTs on this topic. We included in this review 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182

  7. Genetic cancer risk assessment in practice

    International Nuclear Information System (INIS)

    Gruber, S.

    2004-01-01

    The advent of genetic testing has made a dramatic impact on the management of individuals with inherited susceptibility to cancer and their relatives. Genetic counsel ing, with or without testing, is warranted when clues to familial cancer are recognized. Today, genetic testing for classic cancer genetic syndromes is now the standard of care, and has been complemented by genetic testing for other situations commonly encountered in clinical practice. Genetic testing for colorectal cancer, breast cancer, kidney cancer, thyroid cancer, melanoma, and pancreatic cancer raise important issues about the parameters for testing. Genetic cancer risk assessment can lead to measurable reductions in morbidity and mortality through strategies that rely on surveillance, chemo prevention, and risk-reducing surgery

  8. Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1 production through the MAP kinase pathway

    International Nuclear Information System (INIS)

    Yoshida, Seiya; Yokota, Tokuyasu; Ujiki, Michael; Ding Xianzhong; Pelham, Carolyn; Adrian, Thomas E.; Talamonti, Mark S.; Bell, Richard H.; Denham, Woody

    2004-01-01

    Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be responsible for production of this extracellular matrix. When activated, PSCs have a myofibroblast phenotype and produce not only components of the extracellular matrix including collagen, fibronectin, and laminin, but also matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma, we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1 production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen-activated protein (MAP) kinase pathway, and TIMP-1 gene induction were determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation and TIMP-1 through the MAP kinase (ERK 1/2) pathway

  9. Value of computed tomography as a screening examination of pancreatic cancer

    International Nuclear Information System (INIS)

    Honda, Hiroshi; Watanabe, Katsushi; Nishikawa, Kiyoshi

    1983-01-01

    The abdominal CT films of 50 patients were reviewed by ten radiologists to evaluate the role of CT examination in the screening of pancreatic cancer. The 50 patients consisted of 10 with pancreatic cancer, 8 with other pancreatic abnormalities, and 32 with normal pancreas. Ten radiologists were divided into two groups according to their experience in evaluating CT examinations, an experienced group and an unexperienced group, respectively. In the detectability of pancreatic abnormality, the experienced group showed a sensitivity of 72.2% and a specificity of 86.2%. The unexperienced group showed a sensitivity of 70.9% and a specificity of 72.0%. In the detectability of pancreatic cancer, the experienced group showed a sensitivity of 62.0% and a specificity of 83.4%. The unexperienced group showed a sensitivity of 66.0% and a specificity of 81.8%. In the localization of the pancreatic cancer, there was no difference between the two groups. Pancreatic abnormality can be detected with high accuracy, but diagnosis of the nature of pancreatic cancer is difficult. Experience in evaluating CT examinations elevates the detectability of pancreatic abnormality but does not elevate the detectability of pancreatic cancer. These results suggest the difficulty in diagnosis of pancreatic cancer. (author)

  10. Complex role for the immune system in initiation and progression of pancreatic cancer.

    Science.gov (United States)

    Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

    2014-08-28

    The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

  11. Fast neutron irradiation for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-01-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials

  12. Fast neutron irradiation for locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.P. (Georgetown Univ. Medical Center, Washington, DC); Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-11-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

  13. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2014-01-01

    Full Text Available Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered.

  14. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...

  15. Imaging pancreatic cancer using bioconjugated InP quantum dots.

    Science.gov (United States)

    Yong, Ken-Tye; Ding, Hong; Roy, Indrajit; Law, Wing-Cheung; Bergey, Earl J; Maitra, Anirban; Prasad, Paras N

    2009-03-24

    In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

  16. Current options for palliative treatment in patients with pancreatic cancer.

    Science.gov (United States)

    Ridwelski, K; Meyer, F

    2001-01-01

    Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression. Copyright 2001 S. Karger AG, Basel

  17. Pancreatic Cysts

    Science.gov (United States)

    ... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

  18. Quantification of CT images for the classification of high- and low-risk pancreatic cysts

    Science.gov (United States)

    Gazit, Lior; Chakraborty, Jayasree; Attiyeh, Marc; Langdon-Embry, Liana; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

    2017-03-01

    Pancreatic cancer is the most lethal cancer with an overall 5-year survival rate of 7%1 due to the late stage at diagnosis and the ineffectiveness of current therapeutic strategies. Given the poor prognosis, early detection at a pre-cancerous stage is the best tool for preventing this disease. Intraductal papillary mucinous neoplasms (IPMN), cystic tumors of the pancreas, represent the only radiographically identifiable precursor lesion of pancreatic cancer and are known to evolve stepwise from low-to-high-grade dysplasia before progressing into an invasive carcinoma. Observation is usually recommended for low-risk (low- and intermediate-grade dysplasia) patients, while high-risk (high-grade dysplasia and invasive carcinoma) patients undergo resection; hence, patient selection is critically important in the management of pancreatic cysts.2 Radiologists use standard criteria such as main pancreatic duct size, cyst size, or presence of a solid enhancing component in the cyst to optimally select patients for surgery.3 However, these findings are subject to a radiologist's interpretation and have been shown to be inconsistent with regards to the presence of a mural nodule or solid component.4 We propose objective classification of risk groups based on quantitative imaging features extracted from CT scans. We apply new features that represent the solid component (i.e. areas of high intensity) within the cyst and extract standard texture features. An adaptive boost classifier5 achieves the best performance with area under receiver operating characteristic curve (AUC) of 0.73 and accuracy of 77.3% for texture features. The random forest classifier achieves the best performance with AUC of 0.71 and accuracy of 70.8% with the solid component features.

  19. Dynamic MR imaging of pancreatic cancer

    International Nuclear Information System (INIS)

    Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo

    1994-01-01

    Dynamic MRI was performed on 21 patients with pancreatic duct cell carcinoma. Turbo-FLASH or FLASH3D was performed immediately following rapid bolus injection of gadopentetate dimeglumine, and these FLASH images and conventional spin echo images were evaluated about detectability of the lesion. All images were classified into three groups of detectability of the lesion ; good, fair, and poor. On T 1 weighted image, 23% of cases were 'good' and 48% were evaluated as 'fair'. On the other hand, on dynamic MRI, 62% of cases were 'good' and 33% of cases were evaluated as 'fair'. Both T 2 weighted image and enhanced T 1 weighted image were not useful for depiction of the lesion. Direct comparison between T 1 weighted image and dynamic MRI was also done. In 55% of cases, dynamic MRI was superior to T 1 weighted image and in 40% of cases, dynamic MRI was equal to T 1 weighted image. Thus, dynamic MRI was superior to conventional spin echo images for detection of duct cell carcinoma. In 17 patients of duct cell carcinoma who underwent FLASH3D, contrast/noise ratio (CNR) was calculated before and after injection of gadopentetate dimeglumine. The absolute value of CNR became significantly larger by injection of contrast material. In nine resectable pancreatic carcinomas, two cases of INF α and two cases of medullary type were well depicted. It was concluded that dynamic MRI was useful for evaluation of pancreatic carcinoma. (author)

  20. Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth

    International Nuclear Information System (INIS)

    Ohkura, Yu; Sasaki, Kazunari; Matsuda, Masamichi; Hashimoto, Masaji; Fujii, Takeshi; Watanabe, Goro

    2015-01-01

    Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think

  1. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  2. Whole genomes redefine the mutational landscape of pancreatic cancer.

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K; Kassahn, Karin S; Bailey, Peter; Johns, Amber L; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C J; Robertson, Alan J; Fadlullah, Muhammad Z H; Bruxner, Tim J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Lee, Hong C; Jones, Marc D; Nagrial, Adnan M; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Steinmann, Angela M; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Pettitt, Jessica A; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; Graham, Janet S; Niclou, Simone P; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A; Gill, Anthony J; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Pearson, John V; Biankin, Andrew V; Grimmond, Sean M

    2015-02-26

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

  3. Whole genomes redefine the mutational landscape of pancreatic cancer

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

  4. Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells.

    Science.gov (United States)

    Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Takikawa, Tetsuya; Nabeshima, Tatsuhide; Shimosegawa, Tooru

    2018-01-01

    Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Incidence, risk factors, and treatment of pancreatic leakage after pancreaticoduodenectomy: drainage versus resection of the pancreatic remnant

    NARCIS (Netherlands)

    van Berge Henegouwen, M. I.; de Wit, L. T.; van Gulik, T. M.; Obertop, H.; Gouma, D. J.

    1997-01-01

    BACKGROUND: Pancreatic leakage is a major cause of morbidity and mortality after pancreaticoduodenectomy, with incidences varying between 6-24% and a mortality rate up to 40%. Treatment is an issue of controversy. In this study we analyzed risk factors for pancreatic leakage and the results of early

  6. Nutrition Following Pancreatic Surgery

    Science.gov (United States)

    ... BACK Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Nutrition Following Pancreatic Surgery Home Facing Pancreatic Cancer Living with Pancreatic Cancer Diet and Nutrition Nutrition Following Pancreatic Surgery Ver esta página en ...

  7. Free-breathing conformal irradiation of pancreatic cancer.

    Science.gov (United States)

    Solla, Ignazio; Zucca, Sergio; Possanzini, Marco; Piras, Sara; Pusceddu, Claudio; Porru, Sergio; Meleddu, Gianfranco; Farace, Paolo

    2013-07-08

    The purpose of this study was to assess treatment margins in free-breathing irradiation of pancreatic cancer after bone alignment, and evaluate their impact on conformal radiotherapy. Fifteen patients with adenocarcinoma of the head of the pancreas underwent implantation of single fiducial marker. Intrafraction uncertainties were assessed on simulation four-dimensional computed tomography (4D CT) by calculating maximal intrafraction fiducial excursion (MIFE). In the first ten patients, after bony alignment, the position of the fiducial was identified on weekly acquired megavolt cone-beam CT (MV-CBCT). The interfraction residual uncertainties were estimated by measuring the fiducial displacements with respect to the position in the first session. Patient mean (pM) and patient standard deviation (pSD) of fiducial displacement, mean (μM) and standard deviation (μSD) of pM, and root-mean-square of pSD (σ(res)) were calculated. In the other five patients, MIFE was added to the residual component to obtain personalized margin. In these patients, conformal kidney sparing (CONKISS) irradiation was planned prescribing 54/45 Gy to PTV1/PTV2. The organ-at-risk limits were set according to current NCCN recommendation. No morbidity related to the fiducial marker implantation was recorded. In the first ten patients, along right-left, anterior-posterior, and inferior-superior directions, MIFE was variable (mean ± std = 0.24 ± 0.13 cm, 0.31 ± 0.14 cm, 0.83 ± 0.35 cm, respectively) and was at most 0.51, 0.53, and 1.56 cm, respectively. Along the same directions, μM were 0.09, -0.05, -0.05 cm, μSD were 0.30, 0.17, 0.33 cm, and σ(res) were 0.35, 0.26, and 0.30 cm, respectively. MIFE was not correlated with pM and pSD. In the five additional patients, it was possible to satisfy recommended dose limits, with the exception of slightly higher doses to small bowel. After bony alignment, the margins for target expansion can be obtained by adding personalized MIFE to the residual

  8. Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

    Science.gov (United States)

    Colvin, Emily K.; Susanto, Johana M.; Kench, James G.; Ong, Vivienna N.; Mawson, Amanda; Pinese, Mark; Chang, David K.; Rooman, Ilse; O'Toole, Sandra A.; Segara, Davendra; Musgrove, Elizabeth A.; Sutherland, Robert L.; Apte, Minoti V.; Scarlett, Christopher J.; Biankin, Andrew V.

    2011-01-01

    Background Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. PMID:22220202

  9. Retinoid signaling in pancreatic cancer, injury and regeneration.

    Directory of Open Access Journals (Sweden)

    Emily K Colvin

    Full Text Available BACKGROUND: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC. These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1, a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A. However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.

  10. Intervention on toll-like receptors in pancreatic cancer.

    Science.gov (United States)

    Vaz, Juan; Andersson, Roland

    2014-05-21

    Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with pronounced morbidity and a high mortality rate. Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate. Experimental stimulation of the immune system in murine PDA models has revealed some promising results. Toll-like receptors (TLRs) are pillars of the immune system that have been linked to several forms of malignancy, including lung, breast and colon cancer. In humans, TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines, whereas they are not expressed in the normal pancreas. In the present review, we explore the current knowledge concerning the role of different TLRs associated to PDA. Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment, there are only five TLRs suggested as possible therapeutic targets. Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.g. future adjuvant therapies. The elucidation of the role of TLR3 in PDA is only in its initial phase. The inhibition/blockage of TLR4-related pathways has shown some promising effects, but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents. Finally, TLR7 antagonists seem to be potential candidates for therapy. Independent of their potential in immunotherapies, all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.

  11. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.

    Science.gov (United States)

    Kamerkar, Sushrut; LeBleu, Valerie S; Sugimoto, Hikaru; Yang, Sujuan; Ruivo, Carolina F; Melo, Sonia A; Lee, J Jack; Kalluri, Raghu

    2017-06-22

    The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras G12D , a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.

  12. Pan-European survey on the implementation of minimally invasive pancreatic surgery with emphasis on cancer

    NARCIS (Netherlands)

    de Rooij, Thijs; Besselink, Marc G.; Shamali, Awad; Butturini, Giovanni; Busch, Olivier R.; Edwin, Bjørn; Troisi, Roberto; Fernández-Cruz, Laureano; Dagher, Ibrahim; Bassi, Claudio; Abu Hilal, Mohammad

    2016-01-01

    Minimally invasive (MI) pancreatic surgery appears to be gaining popularity, but its implementation throughout Europe and the opinions regarding its use in pancreatic cancer patients are unknown. A 30-question survey was sent between June and December 2014 to pancreatic surgeons of the European

  13. Recent Advances in Pancreatic Cancer Surgery of Relevance to the Practicing Pathologist

    NARCIS (Netherlands)

    van Rijssen, Lennart B.; Rombouts, Steffi J. E.; Walma, Marieke S.; Vogel, Jantien A.; Tol, Johanna A.; Molenaar, Isaac Q.; van Eijck, Casper H. J.; Verheij, Joanne; van de Vijver, Marc J.; Busch, Olivier R. C.; Besselink, Marc G. H.

    2016-01-01

    Recent advances in pancreatic surgery have the potential to improve outcomes for patients with pancreatic cancer. We address 3 new, trending topics in pancreatic surgery that are of relevance to the pathologist. First, increasing awareness of the prognostic impact of intraoperatively detected

  14. Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

    Science.gov (United States)

    Sho, Masayuki; Murakami, Yoshiaki; Kawai, Manabu; Motoi, Fuyuhiko; Satoi, Sohei; Matsumoto, Ippei; Honda, Goro; Uemura, Kenichiro; Yanagimoto, Hiroaki; Kurata, Masanao; Akahori, Takahiro; Kinoshita, Shoichi; Nagai, Minako; Nishiwada, Satoshi; Fukumoto, Takumi; Unno, Michiaki; Yamaue, Hiroki; Nakajima, Yoshiyuki

    2016-03-01

    The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older. A retrospective multicenter analysis of 1401 patients who had undergone pancreatic resection for pancreatic cancer was performed. The patients aged ≥ 80 years (n = 99) were compared with a control group <80 years of age (n = 1302). There were no significant differences in the postoperative complications and mortality between the two groups. However, the prognosis of octogenarians was poorer than that of younger patients for both resectable and borderline resectable tumors. Importantly, there were few long-term survivors in the elderly group, especially among those with borderline resectable pancreatic cancer. A multivariate analysis of the prognostic factors in the very elderly patients indicated that the completion of adjuvant chemotherapy was the only significant factor. In addition, preoperative albumin level was the only independent risk factor for a failure to complete adjuvant chemotherapy. This study demonstrates that the postoperative prognosis in octogenarian patients was not good as that in younger patients possibly due to less frequent completion of adjuvant chemotherapy. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  15. Pancreatic cancer screening employing noncontrast magnetic resonance imaging combined with ultrasonography

    International Nuclear Information System (INIS)

    Kuroki-Suzuki, Seiko; Nagashima, Chieko; Machida, Minoru; Muramatsu, Yukio; Moriyama, Noriyuki; Kuroki, Yoshifumi; Nasu, Katsuhiro

    2011-01-01

    We have conducted an initial evaluation on the potential of combining noncontrast magnetic resonance imaging (MRI) and ultrasonography (US) to screen for pancreatic cancer. An independent ethics committee approved this study. A total of 2511 patients who underwent US were enrolled. Among them, noncontrast MRI was performed in patients in whom the entire pancreas was difficult to depict or in those with US-suspected pancreatic lesions. In total, using 1.5-T MRI, T1- and T2-weighted imaging, magnetic resonance cholangiopancreatography, and diffusion-weighted imaging, we acquired a variety of images. The efficacy of US and MRI in screening for pancreatic lesions, including pancreatic cancer, was evaluated. Of 2511 patients, 184 underwent MRI, and the pancreas was demonstrated in all of them. Among the 2511, five pancreatic cancers were detected by MRI combined with US (detection rate 0.20%). Of the five pancreatic cancers, three were detected by US (detection rate 0.12%) and two by MRI. Four of the five pancreatic cancers were resectable. By combining noncontrast MRI with US, pancreatic cancer can be detected with high accuracy. Other pancreatic lesions that require follow-up, including intraductal papillary mucinous neoplasms, can also be detected. Thus, pancreatic cancer screening with a combination of US and MRI is suggested. (author)

  16. Statins and the risk of acute pancreatitis: A population-based case-control study

    DEFF Research Database (Denmark)

    Thisted, Henriette; Jacobsen, Jacob; Munk, Estrid Muff

    2006-01-01

    BACKGROUND: Case reports have suggested that statins may cause acute pancreatitis. AIM: To examine if statins are associated with risk of acute pancreatitis. METHODS: We identified 2576 first-time admitted cases of acute pancreatitis from hospital discharge registers in three Danish counties, and......: Our findings speak against a strong causative effect of statins on the risk of acute pancreatitis, and may even indicate a mild protective effect....

  17. Paratesticular adenocarcinoma. Unusual presentation of metastasis of pancreatic cancer

    International Nuclear Information System (INIS)

    Ocvirk, J.; Seruga, B.

    2007-01-01

    Metastatic paratesticular adenocarcinoma from the pancreatic cancer is very rare. To our knowledge, there are less than 20 cases published in the literature. We experienced a case of paratesticular adenocarcinoma from the primary pancreatic cancer. A 42-year-old man was presented with locoregionally advanced carcinoma of the tail of the pancreas with intraoperatively found liver metastases and with a tumour in the right hemi-scrotum. Ultrasound of the scrotum revealed a paratesticular tumour. A fine needle aspiration biopsy (FNAB) confirmed a poorly differentiated adenocarcinoma and it was in concordance with the diagnosis of the primary tumour. The patient started treatment with chemotherapy with gemcitabine. Unfortunately, he progressed one month later and the treatment was discontinued. Outcome in the adenocarcinoma of the pancreas is dismal. The only possible treatment option for metastatic disease is systemic therapy but the results are disappointing, as in the present case. (author)

  18. Role of radiation therapy in patients with resectable pancreatic cancer.

    Science.gov (United States)

    Palta, Manisha; Willett, Christopher; Czito, Brian

    2011-07-01

    The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

  19. Development of the PANVAC-VF vaccine for pancreatic cancer.

    Science.gov (United States)

    Petrulio, Christian A; Kaufman, Howard L

    2006-02-01

    PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

  20. Hybrid kappa\\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.

    Science.gov (United States)

    Hao, Mingju; Li, Wenli; Yi, Lang; Yu, Songlin; Fan, Gaowei; Lu, Tian; Yang, Xin; Wang, Guojing; Zhang, Dong; Ding, Jiansheng; Zhang, Kuo; Zhang, Rui; Lin, Guigao; Han, Yanxi; Wang, Lunan; Li, Jinming

    2016-06-08

    The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.

  1. Chronic Pancreatitis.

    Science.gov (United States)

    Stram, Michelle; Liu, Shu; Singhi, Aatur D

    2016-12-01

    Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers.

    Science.gov (United States)

    Jin, H; Wu, Y; Tan, X

    2017-08-01

    Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.

  3. Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    2017-01-01

    Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

  4. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

    2013-01-01

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

  5. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  6. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

    2014-01-01

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  7. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  8. Genetic testing for hereditary melanoma and pancreatic cancer: a longitudinal study of psychological outcome.

    Science.gov (United States)

    Aspinwall, Lisa G; Taber, Jennifer M; Leaf, Samantha L; Kohlmann, Wendy; Leachman, Sancy A

    2013-02-01

    CDKN2A/p16 mutations confer 76% lifetime risk of melanoma and up to 17% lifetime risk of pancreatic cancer. Our objective was to determine the short- and long-term impact of CDKN2A/p16 genetic counseling and test reporting on psychological distress, cancer worry, and perceived costs and benefits of testing. Prospective changes in anxiety, depression, and cancer worry following CDKN2A/p16 counseling and test reporting were evaluated at multiple assessments over 2 years among 60 adult members of melanoma-prone families; 37 participants completed the 2-year follow-up. Quantitative and qualitative assessments of the costs and benefits of testing were carried out. Outcomes were evaluated among unaffected noncarriers (n = 27), unaffected carriers (n = 15), and affected carriers (n = 18). Reported anxiety and depression were low. For carriers and noncarriers, anxiety decreased significantly throughout the 2-year period, whereas depression and melanoma worry showed short-term decreases. Worry about pancreatic cancer was low and decreased significantly. In all groups, test-related distress and uncertainty were low, regret was absent, and positive experiences were high. All participants (>93% at each assessment) reported at least one perceived benefit of genetic testing; only 15.9% listed any negative aspect. Carriers reported increased knowledge about melanoma risk and prevention (78.3%) and increased prevention and screening behaviors for self and family (65.2%). Noncarriers reported increased knowledge (95.2%) and emotional benefits (71.4%). Among US participants familiar with their hereditary melanoma risk through prior epidemiological research participation, CDKN2A/p16 genetic testing provides multiple perceived benefits to both carriers and noncarriers without inducing distress in general or worry about melanoma or pancreatic cancer. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Cachexia and pancreatic cancer: Are there treatment options?

    Science.gov (United States)

    Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

    2014-01-01

    Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods. PMID:25071331

  10. Pancreatic Cancer: What the Oncologist Can Offer for Palliation

    Directory of Open Access Journals (Sweden)

    Malcolm J Moore

    2002-01-01

    Full Text Available Because pancreatic cancer has a poor survival rate and only 20% of patients present with potentially resectable disease, a key goal of therapy is to provide palliation. The poor medical condition of many patients interferes with their ability to tolerate traditional chemotherapy. Recently, however, a nucleoside analogue, gemcitabine, has been developed. This drug is more effective than 5-fluorouracil (5-FU, can be used in patients who fail to respond to 5-FU and has only modest toxicity. Combination therapies including gemcitabine and other agents are being tested. Local radiotherapy seems to provide pain relief, but gastrointestinal toxicity is significant. The effect of combined modality therapy (5-FU with radiotherapy on survival is unclear, and it does not prevent local disease progression. Some novel biological agents, including angiogenesis inhibitors, matrix metalloproteinase inhibitors, antisense compounds, inhibitors of cell signalling such as epidermal growth factor and vascular endothelial growth factor, and inhibitors of oncogene activation, are undergoing phase II and III trials in patients with pancreatic cancer. Among the most promising are farnesyl protein transferase inhibitors, which modulate K-ras function. Such an approach is promising for the treatment of pancreatic cancer because this tumour frequently exhibits mutation of the ras gene.

  11. Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis

    Science.gov (United States)

    Berglund, Lars; Brunzell, John D.; Goldberg, Anne C.; Goldberg, Ira J.; Stalenhoef, Anton

    2013-01-01

    While there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research. PMID:24840268

  12. ABO blood group and risk of cancer

    DEFF Research Database (Denmark)

    Vasan, Senthil K; Hwang, Jinseub; Rostgaard, Klaus

    2016-01-01

    groups and site-specific cancer risk in a large cohort of healthy blood donors from Sweden and Denmark. RESULTS: A total of 1.6 million donors were followed over 27 million person-years (20 million in Sweden and 7 million in Denmark). We observed 119,584 cancer cases. Blood groups A, AB and B were......INTRODUCTION: The associations between ABO blood group and cancer risk have been studied repeatedly, but results have been variable. Consistent associations have only been reported for pancreatic and gastric cancers. MATERIALS AND METHODS: We estimated associations between different ABO blood...... associated either with increased or decreased risk of cancer at 13 anatomical sites (p≤0.05), compared to blood group O. Consistent with assessment using a false discovery rate approach, significant associations with ABO blood group were observed for cancer of the pancreas, breast, and upper gastrointestinal...

  13. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

    The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

  14. Prognostic significance of new onset ascites in patients with pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Luzardo German

    2006-03-01

    Full Text Available Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm. All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

  15. Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Caravatta Luciana

    2012-06-01

    Full Text Available Abstract Background Radiotherapy (RT is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI in the preoperative and definitive treatment of pancreatic cancer. Methods The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. Results We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. Conclusions The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

  16. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

    Directory of Open Access Journals (Sweden)

    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  17. Dosimetric impact of gastrointestinal air column in radiation treatment of pancreatic cancer.

    Science.gov (United States)

    Estabrook, Neil C; Corn, Jonathan B; Ewing, Marvene M; Cardenes, Higinia R; Das, Indra J

    2018-02-01

    Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum.

  18. Endogenous glutamine decrease is associated with pancreatic cancer progression.

    Science.gov (United States)

    Roux, Cecilia; Riganti, Chiara; Borgogno, Sammy Ferri; Curto, Roberta; Curcio, Claudia; Catanzaro, Valeria; Digilio, Giuseppe; Padovan, Sergio; Puccinelli, Maria Paola; Isabello, Monica; Aime, Silvio; Cappello, Paola; Novelli, Francesco

    2017-11-10

    Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both in vitro and in vivo . The higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.

  19. Management of advanced pancreatic cancer in daily clinical practice.

    Science.gov (United States)

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  20. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  1. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes.

    Science.gov (United States)

    Rouanet, Marie; Lebrin, Marine; Gross, Fabian; Bournet, Barbara; Cordelier, Pierre; Buscail, Louis

    2017-06-08

    A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes). The latest developments in pancreatic carcinoma gene therapy are described including gene-based tumor cell sensitization to chemotherapy, vaccination and adoptive immunotherapy (chimeric antigen receptor T-cells strategy). Nowadays, there is a specific development of oncolytic virus therapies including oncolytic adenoviruses, herpes virus, parvovirus or reovirus. A summary of all published and on-going phase-1 trials is given. Most of them associate gene therapy and chemotherapy or radiochemotherapy. The first results are encouraging for most of the trials but remain to be confirmed in phase 2 trials.

  2. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance.

    Science.gov (United States)

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-30

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.

  3. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research.

    Science.gov (United States)

    Husain, Sohail Z; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y; Schwarzenberg, Sarah J; Usatin, Danielle; Uc, Aliye

    2016-04-01

    Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies, and their rationale. We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: hyperlipidemia, hypercalcemia, chronic renal failure, smoking exposure, alcohol, and medications. Areas of additional research were identified. Hypertriglyceridemia of 1000 mg/dL or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end-stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and bystander status may be implicated. Other pancreatitis risk factors must be sought in all cases. The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children.

  4. Toxic-Metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management and Future Research

    Science.gov (United States)

    Husain, Sohail Z.; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D.; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Usatin, Danielle; Uc, Aliye

    2016-01-01

    Objectives Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies and their rationale. Methods We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: (a) hyperlipidemia, (b) hypercalcemia, (c) chronic renal failure, (d) smoking exposure, (e) alcohol, and (f) medications. Areas of additional research were identified. Results Hypertriglyceridemia of 1000 mg/dl or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and by-stander status may be implicated. Other pancreatitis risk factors must be sought in all cases. Conclusions The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/ removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children. PMID:26594832

  5. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.

    Science.gov (United States)

    Sada, Masafumi; Ohuchida, Kenoki; Horioka, Kohei; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi

    2016-03-28

    Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Functional annotation of rare gene aberration drivers of pancreatic cancer | Office of Cancer Genomics

    Science.gov (United States)

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC).

  7. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells

    OpenAIRE

    Wang, Baochun; Li, Yixiong; Tan, Fengbo; Xiao, Zhanxiang

    2016-01-01

    Pancreatic cancer ranks No.1 in mortality rate worldwide. This study aims to identify the novel anti-pancreatic cancer drugs. Human pancreatic carcinoma cell lines were purchased from ATCC. CPE-based screening assay was used to examine the cell viability. Patient derived tumor xenografts in SCID mice was established. The Caspase-3 and 7 activities were measured using the Caspase Glo 3/7 Assay kit. Soft agar colony formation assay was used to evaluate the colony formation. Wound healing assay ...

  8. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    OpenAIRE

    George H Sakorafas; Vasileios Smyrniotis

    2012-01-01

    Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

  9. Expression and significance of Axin2 in pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    ZHANG Tao

    2016-05-01

    Full Text Available ObjectiveTo investigate the expression of Axin2 in pancreatic cancer cells, and to observe the influence of Axin2 on the proliferation, invasion, and migration of human pancreatic cancer cells (PANC-1. MethodsQuantitative real-time PCR was used to measure the expression of Axin2 in pancreatic cancer cell lines with different invasive abilities (PANC-1, Mia PaCa-2, and BxPC-3 and immortalized normal pancreatic cells (H6C7. PANC-1 cells with low expression were transfected with over-expressed Axin2 plasmid by transient transfection. MTT assay, Transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration of cells transfected with over-expressed Axin2. One-way analysis of variance was used for comparison between multiple groups, and SNK-q test was used for comparison between any two groups. ResultsThe relative expression levels of Axin2 in PANC-1, BxPC-3, Mia PaCa-2, and H6C7 cells were 0.13±0.01, 0.42±0.05, 0.24±0.011, and 1.00±0.00, respectively, and PANC-1 cells had the lowest expression level of Axin2, with significant differences compared with the other cells (all P<0.05. When PANC-1 cells were transfected with over-expressed Axin2 plasmid, the cells in the over-expression group had a significant increase in the expression level of Axin2 compared with those in the blank group and the negative control group (both P<0.05. Compared with those in the non-transfection group and the blank group, PANC-1 cells in the over-expression group showed significant reductions in the proliferation, invasion, and migration abilities. ConclusionThe expression of Axin2 is down-regulated in pancreatic cancer cell lines and decreases with the increasing invasion ability, suggesting the role of tumor suppressor gene. High expression of Axin2 can reduce the proliferation, invasion, and migration abilities of PANC-1 cells.

  10. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  11. File list: NoD.Pan.10.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Pan.10.AllAg.Pancreatic_cancer_cells mm9 No description Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Pan.10.AllAg.Pancreatic_cancer_cells.bed ...

  12. File list: InP.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.05.AllAg.Pancreatic_cancer_cells mm9 Input control Pancreas Pancreatic cancer... cells SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  13. Incidence and clinical findings of benign, inflammatory disease in patients resected for presumed pancreatic head cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Reeders, J. W.; Bosma, A.; Moojen, T. M.; Smits, N. J.; Allema, J. H.; Rauws, E. A.; Offerhaus, G. J.; Obertop, H.; Gouma, D. J.

    1997-01-01

    BACKGROUND: The differentiation between cancer and benign disease in the pancreatic head is difficult. The aim of this study was to examine common features in a group of patients that had undergone pancreatoduodenectomy for a benign, inflammatory lesion misdiagnosed as pancreatic head cancer.

  14. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  15. Which patients with resectable pancreatic cancer truly benefit from oncological resection: is it destiny or biology?

    Science.gov (United States)

    Zheng, Lei; Wolfgang, Christopher L

    2015-01-01

    Pancreatic cancer has a dismal prognosis. A technically perfect surgical operation may still not provide a survival advantage for patients with technically resectable pancreatic cancer. Appropriate selection of patients for surgical resections is an imminent issue. Recent studies have provided an important clue on what serum biomarkers may be used to select out the patients who would unlikely benefit from the surgical resection.

  16. Development of a high risk pancreatic screening clinic using 3.0 T MRI.

    Science.gov (United States)

    Barnes, Chad A; Krzywda, Elizabeth; Lahiff, Shannon; McDowell, Dena; Christians, Kathleen K; Knechtges, Paul; Tolat, Parag; Hohenwalter, Mark; Dua, Kulwinder; Khan, Abdul H; Evans, Douglas B; Geurts, Jennifer; Tsai, Susan

    2018-01-01

    Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.

  17. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  18. Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

    International Nuclear Information System (INIS)

    Damaraju, Vijaya L; Bouffard, David Y; Wong, Clarence KW; Clarke, Marilyn L; Mackey, John R; Leblond, Lorraine; Cass, Carol E; Grey, Mike; Gourdeau, Henriette

    2007-01-01

    Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug

  19. Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis

    Science.gov (United States)

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer. PMID:24809702

  20. MicroRNA functional network in pancreatic cancer: From biology to ...

    Indian Academy of Sciences (India)

    [Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. ... growth factor type I receptor; INSR, insulin receptor; IPA, Ingenuity Pathway Analysis; IPMN, ..... Prostate cancer signalling.

  1. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

    Science.gov (United States)

    Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  3. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  4. Inaugural Meeting of North American Pancreatic Cancer Organizations: Advancing Collaboration and Communication.

    Science.gov (United States)

    Kenner, Barbara J; Fleshman, Julie M; Goldberg, Ann E; Rothschild, Laura J

    2015-11-01

    A meeting of North American Pancreatic Cancer Organizations planned by Kenner Family Research Fund and Pancreatic Cancer Action Network was held on July 15-16, 2015, in New York City. The meeting was attended by 32 individuals from 20 nonprofit groups from the United States and Canada. The objectives of this inaugural convening were to share mission goals and initiatives, engage as leaders, cultivate potential partnerships, and increase participation in World Pancreatic Cancer Day. The program was designed to provide opportunities for informal conversations, as well as facilitated discussions to meet the stated objectives. At the conclusion of the meeting, the group agreed that enhancing collaboration and communication will result in a more unified approach within the field and will benefit individuals diagnosed with pancreatic cancer. As a first step, the group will actively collaborate to participate in World Pancreatic Cancer Day, which is planned for November 13, 2015, and seeks to raise the level of visibility about the disease globally.

  5. Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

    Science.gov (United States)

    Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

    2015-01-01

    In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

  6. Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscop

    Directory of Open Access Journals (Sweden)

    Marcela Kopáčová

    2016-09-01

    Full Text Available Double balloon enteroscopy (DBE was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%. Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase. Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

  7. Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy.

    Science.gov (United States)

    Kopáčová, Marcela; Bureš, Jan; Rejchrt, Stanislav; Vávrová, Jaroslava; Bártová, Jolana; Soukup, Tomáš; Tomš, Jan; Tachecí, Ilja

    Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

  8. The Impact of Risk Factors of Chronic Pancreatitis on Secretin Pancreatic Function Testing: Results of a 20-Year Study.

    Science.gov (United States)

    Kothari, Darshan; Ketwaroo, Gyanprakash; Freedman, Steven D; Sheth, Sunil G

    2017-08-01

    The aim of this study was to determine the effect of established risk factors on the outcome of secretin pancreatic function testing (sPFT) in patients undergoing work-up for suspected chronic pancreatitis. We completed a retrospective review of patients who underwent sPFT for suspected chronic pancreatitis over 20 years. We compared peak bicarbonate concentrations between groups and completed univariate and multivariate analyses to determine associations between risk factors and positive sPFT results (peak bicarbonate pancreatitis (RAP) and with local complications from acute pancreatitis (AP) (P ≤ 0.05). The bicarbonate concentration in patients with and without other risk factors such as tobacco use, alcohol use, and family history of pancreatitis was not significantly different. Female sex, a history of AP, and a history of RAP were associated with positive sPFT results on univariate analysis (P ≤ 0.05). On multivariate analysis, sex and RAP remained significant. Our study demonstrates that female sex, history of AP and RAP, and AP with local complications are associated with positive sPFT results or lower peak bicarbonate concentration. However, other risk factors do not impact the results of sPFT.

  9. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

    2013-01-01

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

  10. Characterization and Management of Interfractional Anatomic Changes for Pancreatic Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu Feng; Erickson, Beth; Peng Cheng [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2012-07-01

    Purpose: To quantitatively characterize interfractional anatomic variations in pancreatic cancer radiotherapy (RT) and to study dosimetric advantages for using an online adaptive replanning scheme to account for these variations. Methods and Materials: Targets and organs at risk (OAR) were delineated by autosegmentation based on daily computed tomography (CT) images acquired using a respiration-gated in-room CT during daily image-guided RT (IGRT) for 10 pancreatic cancer patients. Various parameters, including the maximum overlap ratio (MOR) between the volumes based on planning and daily CTs for a structure, while the overlapping volumes were maximized, were used to quantify the interfractional organ deformation with the intrafractional variations largely excluded. An online adaptive RT (ART) was applied to these daily CTs. To evaluate the dosimetric benefits of ART, the dose distributions from the online ART were compared to those from the repositioning in the current standard IGRT practice. Results: The interfractional anatomic variations, particularly the organ deformation, are significant during pancreas irradiation. For the patients studied, the average MORs of all daily CTs were 80.2%, 61.7%, and 72.2% for pancreatic head, duodenum, and stomach, respectively. The online ART leads to improved dosimetric plan with better target coverage and/or OAR sparing than IGRT repositioning. For the patients studied, the mean V{sub 50.4Gy} (volume covered by 50.4 Gy) for the duodenum was reduced from 43.4% for IGRT to 15.6% for the online ART scheme. Conclusions: The online adaptive RT scheme can effectively account for the significant interfractional anatomic variations observed in pancreas irradiation. The dosimetric advantages with the online ART may enable safe dose escalation in radiation therapy for pancreatic cancer.

  11. Characterization and Management of Interfractional Anatomic Changes for Pancreatic Cancer Radiotherapy

    International Nuclear Information System (INIS)

    Liu Feng; Erickson, Beth; Peng Cheng; Li, X. Allen

    2012-01-01

    Purpose: To quantitatively characterize interfractional anatomic variations in pancreatic cancer radiotherapy (RT) and to study dosimetric advantages for using an online adaptive replanning scheme to account for these variations. Methods and Materials: Targets and organs at risk (OAR) were delineated by autosegmentation based on daily computed tomography (CT) images acquired using a respiration-gated in-room CT during daily image-guided RT (IGRT) for 10 pancreatic cancer patients. Various parameters, including the maximum overlap ratio (MOR) between the volumes based on planning and daily CTs for a structure, while the overlapping volumes were maximized, were used to quantify the interfractional organ deformation with the intrafractional variations largely excluded. An online adaptive RT (ART) was applied to these daily CTs. To evaluate the dosimetric benefits of ART, the dose distributions from the online ART were compared to those from the repositioning in the current standard IGRT practice. Results: The interfractional anatomic variations, particularly the organ deformation, are significant during pancreas irradiation. For the patients studied, the average MORs of all daily CTs were 80.2%, 61.7%, and 72.2% for pancreatic head, duodenum, and stomach, respectively. The online ART leads to improved dosimetric plan with better target coverage and/or OAR sparing than IGRT repositioning. For the patients studied, the mean V 50.4Gy (volume covered by 50.4 Gy) for the duodenum was reduced from 43.4% for IGRT to 15.6% for the online ART scheme. Conclusions: The online adaptive RT scheme can effectively account for the significant interfractional anatomic variations observed in pancreas irradiation. The dosimetric advantages with the online ART may enable safe dose escalation in radiation therapy for pancreatic cancer.

  12. Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis.

    Science.gov (United States)

    Zhao, Zhen-Hua; Hu, Liang-Hao; Ren, Hong-Bo; Zhao, An-Jing; Qian, Yang-Yang; Sun, Xiao-Tian; Su, Song; Zhu, Shu-Guang; Yu, Jin; Zou, Wen-Bin; Guo, Xiao-Rong; Wang, Lei; Li, Zhao-Shen; Liao, Zhuan

    2017-09-01

    Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ 2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis. In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor. Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  13. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  14. Oxidative Stress: A New Target for Pancreatic Cancer Prognosis and Treatment

    Directory of Open Access Journals (Sweden)

    Javier Martinez-Useros

    2017-03-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal types of tumors, and its incidence is rising worldwide. Survival can be improved when tumors are detected at an early stage; however, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. Several risk factors are associated to this disease. Chronic pancreatitis, diabetes, and some infectious disease are the most relevant risk factors. Incidence of PDAC has increased in the last decades. It is hypothesized it could be due to other acquired risk habits, like smoking, high alcohol intake, and obesity. Indeed, adipose tissue is a dynamic endocrine organ that secretes different pro-inflammatory cytokines, enzymes, and other factors that activate oxidative stress. Reactive oxygen species caused by oxidative stress, damage DNA, proteins, and lipids, and produce several toxic and high mutagenic metabolites that could modify tumor behavior, turning it into a malignant phenotype. Anti-oxidant compounds, like vitamins, are considered protective factors against cancer. Here, we review the literature on oxidative stress, the molecular pathways that activate or counteract oxidative stress, and potential treatment strategies that target reactive oxygen species suitable for this kind of cancer.

  15. Risk factors for and management of graft pancreatitis.

    Science.gov (United States)

    Nadalin, Silvio; Girotti, Paolo; Königsrainer, Alfred

    2013-02-01

    Systematic and detailed analysis of risk factors, pathophysiology, clinical manifestation, diagnosis and management of graft pancreatitis in its different forms, that is acute and chronic graft pancreatitis (A-GP and C-GP), and A-GP being further distinguished into: physiological (P-AGP), early (E-AGP) and late AP (L-AGP). Graft pancreatitis is the second most-frequent complication following pancreas transplantation. P-AGP is an unavoidable entity related to ischemic reperfusion injury. It is usually clinically silent. It is a timely and prognostically self-limited process. E-AGP occurs within 3 months after pancreas transplantation (PTx) in 35% of cases and is associated with high rates of graft loss (78-91%). Clinical signs are pain, systemic inflammatory response (SIRS) and haematuria. Therapy can be medical, interventional and surgical. L-AGP occurs 3 months following PTx in 14-25% of cases and represents an uncommon cause of graft loss. Typical clinical signs are pain, abdominal tenderness and fever. Typical laboratory signs are hyperamylasaemia, hyperglycaemia and hypercreatininaemia. Therapy is usually conservative. C-GP is difficult to be distinguished from chronic rejection and is associated to graft loss in 4-10% of cases. Recurrent A-GPs and infections are the main risk factors. Specific symptoms are chronic abdominal malaise, constipation and recurrence of DM. Isolated hyperglycaemia is typical of C-GP. The therapy is usually conservative. This systematic analysis of different manifestations of graft pancreatitis provides the basis for a clinical approach to tackling this complex entity.

  16. The Replication Stress Response in Pancreatic Cancer

    Science.gov (United States)

    2014-12-01

    both causes cell death. We hypothesize that novel RSR genes maintain genome integrity and that deregulation of RSR genes and their cancer barrier...Microscopy, Jena, Germany ) microscope with Axiovision Rei 4.8 software (Zeiss, Jena. Germany ) using the x 63 oil objective. Foci quantitation was

  17. A Study on the Dietary Intake and the Nutritional Status among the Pancreatic Cancer Surgical Patients.

    Science.gov (United States)

    Kang, Jimin; Park, Joon Seong; Yoon, Dong Sup; Kim, Woo Jeong; Chung, Hae-Yun; Lee, Song Mi; Chang, Namsoo

    2016-10-01

    The adequate dietary intake is important to maintain the nutritional status of the patients after pancreatic cancer surgery. This prospective study was designed to investigate the dietary intake and the nutritional status of the patients who had pancreatic cancer surgery. Thirty-one patients (15 men, 16 women) were enrolled and measured body weight, body mass index (BMI), nutritional risk index (NRI), and Malnutrition Universal Screening Tool (MUST). Actual oral intake with nutritional impact symptoms recorded on the clinical research foam at every meal and medical information were collected from electronic medical charts. The rates of malnutrition at admission were 45.1% (14/31) and 28.9% (9/31) by NRI and MUST method, respectively, but those were increased to 87% (27/31) and 86.6% (26/31) after operation on discharge. The median values of daily intake of energy, carbohydrates, fat, and protein were 588.1 kcal, 96.0 g, 11.8 g, and 27.0 g, respectively. Most patients (n = 20, 64.5%) experienced two or more symptoms such as anorexia, abdominal bloating and early satiety. There were negative correlations between C-reactive protein (CRP) levels and the intake of total energy, protein, fat, and zinc. The rates of malnutrition were increased sharply after surgery and the dietary intake also influenced the inflammatory indicators. The results suggested that need of considering special therapeutic diets for the patients who received pancreatic surgery.

  18. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut

    2011-01-01

    Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually

  19. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut, E-mail: friess@chir.med.tu-muenchen.de [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, D-81675 Munich (Germany)

    2011-02-14

    Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

  20. Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results

    International Nuclear Information System (INIS)

    Coquard, Regis; Ayzac, Louis; Gilly, Francois-Noeel; Romestaing, Pascale; Ardiet, Jean-Michel; Sondaz, Chrystel; Sotton, Marie-Pierre; Sentenac, Irenee; Braillon, Georges; Gerard, Jean-Pierre

    1997-01-01

    Background and purpose: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. Materials and methods: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. Results: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early post-operative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. Conclusion: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma

  1. The RON receptor tyrosine kinase in pancreatic cancer pathogenesis and its potential implications for future targeted therapies.

    Science.gov (United States)

    Kang, Chang Moo; Babicky, Michele L; Lowy, Andrew M

    2014-03-01

    Pancreatic cancer remains a devastating disease with a mortality rate that has not changed substantially in decades. Novel therapies are therefore desperately needed. The RON receptor tyrosine kinase has been identified as an important mediator of KRAS oncogene addiction and is overexpressed in the majority of pancreatic cancers. Preclinical studies show that inhibition of RON function decreases pancreatic cancer cell migration, invasion, and survival and can sensitize pancreatic cancer cells to chemotherapy. This article reviews the current state of knowledge regarding RON biology and pancreatic cancer and discusses its potential as a therapeutic target.

  2. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...

  3. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

    Science.gov (United States)

    Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T

    2018-02-08

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10 -8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10 -14 ), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10 -10 ), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10 -8 ), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10 -8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

  4. Serum Immunoglobulin G4 in Discriminating Autoimmune Pancreatitis From Pancreatic Cancer: A Diagnostic Meta-analysis.

    Science.gov (United States)

    Dai, Cong; Cao, Qin; Jiang, Min; Sun, Ming-Jun

    2018-03-01

    Differentiation between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) is a clinical challenge. Emerging published data on the accuracy of serum immunoglobulin G4 (IgG4) for the differential diagnosis between AIP and PC are inconsistent. The objective of our study was to perform a meta-analysis evaluating the clinical utility of serum IgG4 in the differential diagnosis between AIP and PC. We performed a systematic literature search of multiple electronic databases. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. Random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy. Eleven studies comprising 523 AIP patients and 771 PC patients were included in the meta-analysis. The summary estimates for serum IgG4 in distinguishing AIP from PC were as follows: diagnostic odds ratio, 57.30 (95% confidence interval [CI], 23.17-141.67); sensitivity, 0.72 (95% CI, 0.68-0.76); specificity, 0.93 (95% CI, 0.91-0.94). The area under the curve of serum IgG4 in distinguishing AIP from PC was 0.9200. Our meta-analysis found that serum IgG4 has high specificity and relatively low sensitivity in the differential diagnosis between AIP and PC. Therefore, serum IgG4 is useful in distinguishing AIP from PC.

  5. Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

    Science.gov (United States)

    2015-10-01

    The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

  6. Stem cell-based approach in diabetes and pancreatic cancer management

    Directory of Open Access Journals (Sweden)

    Yi-Zhou Jiang

    2017-01-01

    Full Text Available Stem cell-mediated therapy is a promising strategy for treating pancreatic diseases such as Type-1 diabetes (T1D and pancreatic cancers. Although islet transplantation has been reported to be an effective diabetes therapy, its worldwide application is extremely limited due to the shortage of donor islets and immune rejection problems. Stem cell-based approach for islet neogenesis in vivo could provide a promising alternative source of islets for treating diabetes. On the other hand, targeting the cancer stem cells could be very effective for the treatment of pancreatic cancers. In this review, we focused on the present progress in the field of adult pancreatic stem cells, stem cell-mediated strategies for treating T1D, and pancreatic cancer stem cells, while discussing of the possible challenges involved in them.

  7. A missing link between RON expression and oncological outcomes in resected left-sided pancreatic cancer.

    Science.gov (United States)

    Han, Dai Hoon; Kang, Chang Moo; Lee, Sung Whan; Hwang, Ho Kyoung; Lee, Woo Jung

    2017-10-01

    Alteration and activation of recepteur d'origine nantais (RON) expression is known to be associated with cancer progression and decreased survival in various types of human cancer, including pancreatic cancer. Therefore, in the present study, RON expression levels were determined in resected left-sided pancreatic cancer to evaluate the potential oncological role of RON in the clinical setting of distal pancreatic cancer. From January 2005 to December 2011, a total of 57 patients underwent radical distal pancreatectomy for left-sided pancreatic cancer. Ductal adenocarcinoma was confirmed in all patients. Among these patients, 17 patients who received preoperative neoadjuvant treatment and 7 patients without available paraffin-embedded tissue blocks were excluded from the present study. RON expression in a the pancreatic cancer cell lines ASPC-1, BxPC-3, MiaPaCa-3 and Panc-1, as well as in resected left-sided pancreatic cancer specimens was determined by Western blot analysis. RON and vascular endothelial growth factor (VEGF) overexpression in resected left-sided pancreatic cancer was also evaluated by immunohistochemistry using pre-diluted anti-RON and anti-VEGF antibodies. An association was identified between the oncological outcome and RON overexpression. Increased levels of RON expression were observed in two pancreatic cancer cell lines, AsPC-1 and BxPC-3. RON overexpression was detected in specimens from 15/33 patients (45.5%) using immunohistochemistry. No significant association was identified between RON overexpression and VEGF overexpression (25.5 vs. 87.9%; P=0.667). No significant differences in disease-free survival or disease-specific survival associated with RON overexpression were identified. Although the results of previous studies have suggested that RON is a potential target for the treatment of pancreatic cancer, in the present study no association between RON overexpression and any adverse oncological effect was identified.

  8. Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

    Science.gov (United States)

    Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

    2018-01-01

    Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

  9. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    International Nuclear Information System (INIS)

    Rizwani, Wasia; Allen, Amanda E.; Trevino, Jose G.

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer

  10. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Rizwani, Wasia [Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007 (India); Allen, Amanda E.; Trevino, Jose G., E-mail: Jose.Trevino@surgery.ufl.edu [Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610 (United States)

    2015-09-03

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  11. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Directory of Open Access Journals (Sweden)

    Wasia Rizwani

    2015-09-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF, the sole ligand for c-MET (mesenchymal-epithelial transition, an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  12. Risks of Skin Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of skin cancer. Skin cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about skin cancer: Skin Cancer Prevention Skin Cancer Treatment Melanoma Treatment Genetics ...

  13. Coffee consumption and risk of fatal cancers.

    Science.gov (United States)

    Snowdon, D A; Phillips, R L

    1984-01-01

    In 1960, the coffee consumption habits and other lifestyle characteristics of 23,912 white Seventh-day Adventists were assessed by questionnaire. Between 1960 and 1980, deaths due to cancer were identified. There were positive associations between coffee consumption and fatal colon and bladder cancer. The group consuming two or more cups of coffee per day had an estimated relative risk (RR) of 1.7 for fatal colon cancer and 2.0 for fatal bladder cancer, compared to the group that consumed less than one cup per day (RR = 1.0). These positive associations were apparently not confounded by age, sex, cigarette smoking, or meat consumption habits. In this study, there were no significant or suggestive associations between coffee consumption and fatal pancreatic, breast, and ovarian cancer, or a combined group of all other cancer sites. PMID:6742274

  14. Solitary pancreatic metastasis from breast cancer: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Márcio Apodaca-Rueda

    2017-11-01

    Full Text Available ABSTRACT CONTEXT: Pancreatic metastases from primary malignant tumors at other sites are rare, constituting about 2% of the neoplasms that affect the pancreas. Pancreatic metastasis from breast cancer is extremely rare and difficult to diagnose, because its clinical and radiological presentation is similar to that of a primary pancreatic tumor. CASE REPORT: A 64-year-old female developed a lesion in the pancreatic tail 24 months after neoadjuvant therapy, surgery and adjuvant radiation therapy for right-side breast cancer (ductal carcinoma. She underwent distal pancreatectomy with splenectomy and left adrenalectomy, and presented an uneventful outcome. The immunohistochemical analysis on the surgical specimen suggested that the lesion originated from the breast. CONCLUSION: In cases of pancreatic lesions detected in patients with a previous history of breast neoplasm, the possibility of pancreatic metastasis should be carefully considered.

  15. Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer.

    Science.gov (United States)

    Koliopanos, Alexander; Kleeff, Jörg; Xiao, Yi; Safe, Stephen; Zimmermann, Arthur; Büchler, Markus W; Friess, Helmut

    2002-09-05

    The arylhydrocarbon receptor (AhR) was initially identified as a member of the adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we sought to determine the functional significance of the AhR pathway in pancreatic carcinogenesis. AhR expression was analysed by Northern blotting. The exact site of AhR expression was analysed by in situ hybridization and immunohistochemistry. The effects of TCDD and four selective AhR agonists on pancreatic cancer cell lines were investigated by growth assays, apoptosis assays, and induction of the cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14 out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis tissues, and faint expression in all normal pancreata. In pancreatic cancer tissues, AhR mRNA and protein expression were localized in the cytoplasm of pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic cancer cell growth in a dose-dependent manner, and decreased anchorage-independent cell growth. DAPI staining did not reveal nuclear fragmentation and CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR agonists induced the expression of the cyclin-dependent kinase inhibitor p21. In conclusion, the relatively non-toxic AhR agonists caused growth inhibition in pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In addition, almost all human pancreatic cancer tissues expressed this receptor at high levels, suggesting that these or related compounds may play a role in the therapy of pancreatic cancer in the future.

  16. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    Directory of Open Access Journals (Sweden)

    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  17. EMMPRIN as a novel target for pancreatic cancer therapy

    Science.gov (United States)

    Kim, Hyunki; Zhai, Guihua; Liu, Zhiyong; Samuel, Sharon; Shah, Nemil; Helman, Emily E.; Knowles, Joseph A.; Stockard, Cecil R.; Fineberg, Naomi S.; Grizzle, William E.; Zhou, Tong; Zinn, Kurt R.; Rosenthal, Eben L.

    2013-01-01

    The objective of this study was to evaluate extracelluar matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic-cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, while MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, while the other groups served as the control. In residual tumor model, tumor growth of anti-EMMPRIN treated group was successfully arrested for 21 days (15±4 mm3), significantly lower than that of EMMPRIN knockdown group (80±15 mm3; p=0.001) or control group (240±41 mm3; pEMMPRIN therapy lowered tumor-volume increase about 40% compared with control regardless of dose amount. Ki67-expressed cell densities of group 5 was 939±150 mm−2, significantly lower than that of group 4 (1709±145 mm−2; p=0.006). Microvessel density of group 5 (30±6 mm−2) was also significantly lower than that of group 4 (53±5 mm−2; p=0.014), while the microvessel size of group 5 (191±22 μm2) was significantly larger than that of group 4 (113±26 μm2; p=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer, and support its clinical translation. PMID:21730821

  18. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  19. Platinum-Based Therapy in Adenosquamous Pancreatic Cancer: Experience at Two Institutions

    OpenAIRE

    Andre Luiz De Souza; Muhammad Wasif Saif

    2014-01-01

    Adenosquamous carcinoma of the pancreas is a rare type of pancreatic cancer. Although its molecular biology profile hasbeen shown to be similar to pancreatic ductal adenocarcinoma tumors, it has different prognostic features. There is noconsensus or guidelines to treat this tumor differently from pancreatic adenocarcinoma, but therapies based on gemcitabineand platinum chemotherapeutics such as cisplatin and oxaliplatin have been used based on results of a few case reports. Wediscuss the Abst...

  20. Progress in cancer genetics: lessons from pancreatic cancer

    NARCIS (Netherlands)

    Goggins, M.; Kern, S. E.; Offerhaus, J. A.; Hruban, R. H.

    1999-01-01

    In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. The literature was reviewed concerning the genetic alterations that

  1. Results of diagnosis of pancreatic cancer by computed tomography (CT)

    International Nuclear Information System (INIS)

    Kimura, Kazue; Okuaki, Koji; Ito, Masami; Katakura, Toshihiko; Suzuki, Kenji

    1981-01-01

    Results of examination of pancreatic diseases, especially pancreatic cancer, conducted by CT during the past 3 years are summarized. The EMI CT Type 5000 or 5005 were used. During the 3 years from September 1976 to August 1979, a total of 1961 patients were examined by CT, and the upper abdomen was examined in 772 of these patients. In 97 patients, positive findings were obtained in the CT image of the pancreas. In 52 of these patients, the findings were confirmed operatively or by autopsy. Though cancer of the pancreas was diagnosed by CT in 30 patients, it was confirmed in 20 by surgical operation and in 1 by autopsy. Of the 9 misdiagnosed cases, 4 were cases of infiltration of the pancreas by carcinoma of the stomach or bile duct, and the other 5 were one case each of lipoma of the abdominal wall, normal pancreas, hyperplasia of Langerhans's islets of the pancreas tail, abscess between the pancreas and the posterior wall of the stomach, and choledocholithiasis. A case diagnosed by CT as cholelithiasis was a carcinoma measuring 5 x 5 x 6 cm located on the head of the pancreas, complicated by choledocholithiasis. The 22 patients with carcinoma of the pancreas were 9 with lesions less than 3.5 x 3.0 x 3.0 cm in size who could be radically operated, 6 who underwent exploratory laparotomy or autopsy, and 7 in whom operation was impossible. False negative and false positive CT results are also discussed. (author)

  2. Intraarterial Ultrasound in Pancreatic Cancer: Feasibility Study and Preliminary Results

    International Nuclear Information System (INIS)

    Larena-Avellaneda, Axel; Timm, Stephan; Kickuth, Ralph; Kenn, Werner; Steger, Ulrich; Jurowich, Christian; Germer, Christoph-Thomas

    2010-01-01

    Despite technological advances in computed tomography (CT) and magnetic resonance imaging, the involvement of the celiac or mesenteric artery in pancreatic cancer remains uncertain in many cases. Infiltration of these vessels is important in making decisions about therapy choices but often can only be definitively determined through laparotomy. Local (intraarterial) ultrasound may increase diagnostic accuracy. Using the Volcano intravascular ultrasound (IVUS) system, we applied a transfemoral method to scan the celiac and mesenteric arteries directly intraarterial. This technique was used in five patients with suspected pancreatic cancer. Technical success was achieved in all cases. In one case, a short dissection of the mesenteric artery occurred but could be managed interventionally. In tumors that did not contact with the vessels, IVUS was unable to display the tissue pathology. Our main interest was the infiltration of the arteries. In one case, infiltration was certain in the CT scan but uncertain in two patients. In the latter two cases, IVUS correctly predicted infiltration in one and freedom from tumor in the other case. In our preliminary study, IVUS correctly predicted arterial infiltration in all cases. IVUS did not provide new information when the tumor was far away from the vessel. Compared with IVUS in the portal vein, the information about the artery is more detailed, and the vessel approach is easier. These results encouraged us to design a prospective study to evaluate the sensitivity and specificity of this method.

  3. Surgical palliation of unresectable pancreatic head cancer in elderly patients

    Science.gov (United States)

    Hwang, Sang Il; Kim, Hyung Ook; Son, Byung Ho; Yoo, Chang Hak; Kim, Hungdai; Shin, Jun Ho

    2009-01-01

    AIM: To determine if surgical biliary bypass would provide improved quality of residual life and safe palliation in elderly patients with unresectable pancreatic head cancer. METHODS: Nineteen patients, 65 years of age or older, were managed with surgical biliary bypass (Group A). These patients were compared with 19 patients under 65 years of age who were managed with surgical biliary bypass (Group B). In addition, the results for group A were compared with those obtained from 17 patients, 65 years of age or older (Group C), who received percutaneous transhepatic biliary drainage to evaluate the quality of residual life. RESULTS: Five patients (26.0%) in Group A had complications, including one intraabdominal abscess, one pulmonary atelectasis, and three wound infections. One death (5.3%) occurred on postoperative day 3. With respect to morbidity, mortality, and postoperative hospitalization, no statistically significant difference was noted between Groups A and B. The number of readmissions and the rate of recurrent jaundice were lower in Group A than in Group C, to a statistically significant degree (P = 0.019, P = 0.029, respectively). The median hospital-free survival period and the median overall survival were also significantly longer in Group A (P = 0.001 and P < 0.001, respectively). CONCLUSION: Surgical palliation does not increase the morbidity or mortality rates, but it does increase the survival rate and improve the quality of life in elderly patients with unresectable pancreatic head cancer. PMID:19248198

  4. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  5. Pancreatic Tail Cancer with Sole Manifestation of Left Flank Pain: A Very Rare Presentation

    Directory of Open Access Journals (Sweden)

    Hsing-Lin Lin

    2008-06-01

    Full Text Available Pancreatic cancer is sometimes called a “silent disease” because it often causes no symptoms in the early stage. The symptoms can be quite vague and various depending on the location of cancer in the pancreas. The anatomic site distribution is 78% in the head of the pancreas, 11% in the body, and 11% in the tail. Pancreatic cancer is rarely detected in the early stage, and it is very uncommon to diagnose pancreatic tail cancer during an emergency department visit. The manifestation of pancreatic tail cancer as left flank pain is very rare and has seldom been identified in the literature. We present a case of pancreatic tail cancer with the sole manifestation of dull left flank pain. Having negative findings on an ultrasound study initially, this female patient was misdiagnosed as having possible acute gastritis, urolithiasis or muscle strain after she received gastroendoscopy and colonofiberscopy. Her symptoms persisted for several months and she visited our emergency department due to an acute exacerbation of a persistent dull pain in the left flank area. Radiographic evaluation with computed tomography was performed, and pancreatic tail tumor with multiple metastases was found unexpectedly. We review the literature and discuss this rare presentation of pancreatic tail cancer.

  6. Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells.

    Science.gov (United States)

    Wang, Baochun; Li, Yixiong; Tan, Fengbo; Xiao, Zhanxiang

    2016-01-01

    Pancreatic cancer ranks No.1 in mortality rate worldwide. This study aims to identify the novel anti-pancreatic cancer drugs. Human pancreatic carcinoma cell lines were purchased from ATCC. CPE-based screening assay was used to examine the cell viability. Patient derived tumor xenografts in SCID mice was established. The Caspase-3 and 7 activities were measured using the Caspase Glo 3/7 Assay kit. Soft agar colony formation assay was used to evaluate the colony formation. Wound healing assay was employed to determine the cell migration. We screened a Chinese herbal product library and found three "hits" that kill cancer cells at nanomolar to micromolar concentrations. One of these compounds, rocaglamide, was found to be potent inhibitors of a wide spectrum of pancreatic cancer cell lines. Furthermore, Rocaglamide reduced the tumor size in a patient-derived pancreatic cancer xenograft mouse model without noticeable toxicity in vivo. Rocaglamide also inhibits pancreatic cancer cell migration and invasion. In conclusion, these data support that Rocaglamide may be a promising anti-pancreatic cancer drug.

  7. Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation

    Directory of Open Access Journals (Sweden)

    Philip Sutera

    2018-03-01

    Full Text Available IntroductionPancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT.Materials and methodsPatients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS, local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan–Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models.ResultsWe identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4 Gy in 28 fractions. SBRT was delivered to a median dose of 24.5 Gy in 1–3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4 months (inter-quartile range, 14.9–32.7 months, the median OS from diagnosis for the entire cohort was 26.6 months (95% CI: 20.3–29.8 with 2-year OS of 53.0%. Median survival from SBRT was 9.7 months (95% CI, 5.5–13.8. The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2

  8. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

    OpenAIRE

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-01

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resis...

  9. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

    2011-01-01

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  10. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    International Nuclear Information System (INIS)

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-01-01

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy

  12. Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1

    Directory of Open Access Journals (Sweden)

    Ryoji Takada

    2014-06-01

    Full Text Available 2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as