Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

Andrew McGuigan, Paul Kelly, Richard C Turkington, Claire Jones, Helen G Coleman, R Stephen McCain, Andrew McGuigan, Paul Kelly, Richard C Turkington, Claire Jones, Helen G Coleman, R Stephen McCain

Abstract

This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.

Keywords: Pancreatic adenocarcinoma; Pancreatic cancer; Pancreatic cancer risk factors; Pancreatic cancer treatment.

Conflict of interest statement

Conflict-of-interest statement: All the authors of this manuscript confirm there is no conflict of interest.

Figures

Figure 1
Figure 1
Diagram of incidence of pancreatic cancer in both sexes throughout the world Adapted from Globocan[1] 2018.
Figure 2
Figure 2
Pathogenesis. A: Normal duct; B: Low grade pancreatic intraepithelial neoplasia (PanIN); C: High grade PanIN.

References

    1. International Agency for Research on Cancer, World Health Organization. Global Cancer Observatory 2018; Available from: URL:
    1. Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol. 2016;22:9694–9705.
    1. Wong MCS, Jiang JY, Liang M, Fang Y, Yeung MS, Sung JJY. Global temporal patterns of pancreatic cancer and association with socioeconomic development. Sci Rep. 2017;7:3165.
    1. Saad AM, Turk T, Al-Husseini MJ, Abdel-Rahman O. Trends in pancreatic adenocarcinoma incidence and mortality in the United States in the last four decades; a SEER-based study. BMC Cancer. 2018;18:688.
    1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7–30.
    1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–2921.
    1. IARC. Globocan 2012; Available from: URL: .
    1. McMenamin ÚC, McCain S, Kunzmann AT. Do smoking and alcohol behaviours influence GI cancer survival? Best Pract Res Clin Gastroenterol. 2017;31:569–577.
    1. Midha S, Chawla S, Garg PK. Modifiable and non-modifiable risk factors for pancreatic cancer: A review. Cancer Lett. 2016;381:269–277.
    1. Wood HE, Gupta S, Kang JY, Quinn MJ, Maxwell JD, Mudan S, Majeed A. Pancreatic cancer in England and Wales 1975-2000: patterns and trends in incidence, survival and mortality. Aliment Pharmacol Ther. 2006;23:1205–1214.
    1. Wahi MM, Shah N, Schrock CE, Rosemurgy AS 2nd, Goldin SB. Reproductive factors and risk of pancreatic cancer in women: a review of the literature. Ann Epidemiol. 2009;19:103–111.
    1. Silverman DT, Hoover RN, Brown LM, Swanson GM, Schiffman M, Greenberg RS, Hayes RB, Lillemoe KD, Schoenberg JB, Schwartz AG, et al. Why do Black Americans have a higher risk of pancreatic cancer than White Americans? Epidemiology. 2003;14:45–54.
    1. Arnold LD, Patel AV, Yan Y, Jacobs EJ, Thun MJ, Calle EE, Colditz GA. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity? Cancer Epidemiol Biomarkers Prev. 2009;18:2397–2405.
    1. Pernick NL, Sarkar FH, Philip PA, Arlauskas P, Shields AF, Vaitkevicius VK, Dugan MC, Adsay NV. Clinicopathologic analysis of pancreatic adenocarcinoma in African Americans and Caucasians. Pancreas. 2003;26:28–32.
    1. Wolpin BM, Chan AT, Hartge P, Chanock SJ, Kraft P, Hunter DJ, Giovannucci EL, Fuchs CS. ABO blood group and the risk of pancreatic cancer. J Natl Cancer Inst. 2009;101:424–431.
    1. Wolpin BM, Kraft P, Gross M, Helzlsouer K, Bueno-de-Mesquita HB, Steplowski E, Stolzenberg-Solomon RZ, Arslan AA, Jacobs EJ, Lacroix A, et al. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium. Cancer Res. 2010;70:1015–1023.
    1. Memba R, Duggan SN, Ni Chonchubhair HM, Griffin OM, Bashir Y, O’Connor DB, Murphy A, McMahon J, Volcov Y, Ryan BM, et al. The potential role of gut microbiota in pancreatic disease: A systematic review. Pancreatology. 2017;17:867–874.
    1. Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4) Ann Oncol. 2012;23:1880–1888.
    1. Iodice S, Gandini S, Maisonneuve P, Lowenfels AB. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg. 2008;393:535–545.
    1. Lynch SM, Vrieling A, Lubin JH, Kraft P, Mendelsohn JB, Hartge P, Canzian F, Steplowski E, Arslan AA, Gross M, et al. Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol. 2009;170:403–413.
    1. Rohrmann S, Linseisen J, Vrieling A, Boffetta P, Stolzenberg-Solomon RZ, Lowenfels AB, Jensen MK, Overvad K, Olsen A, Tjonneland A, et al. Ethanol intake and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cancer Causes Control. 2009;20:785–794.
    1. Lin Y, Tamakoshi A, Kawamura T, Inaba Y, Kikuchi S, Motohashi Y, Kurosawa M, Ohno Y. Risk of pancreatic cancer in relation to alcohol drinking, coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk. Int J Cancer. 2002;99:742–746.
    1. Genkinger JM, Spiegelman D, Anderson KE, Bergkvist L, Bernstein L, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, et al. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol Biomarkers Prev. 2009;18:765–776.
    1. Wang YT, Gou YW, Jin WW, Xiao M, Fang HY. Association between alcohol intake and the risk of pancreatic cancer: a dose-response meta-analysis of cohort studies. BMC Cancer. 2016;16:212.
    1. 2015. WCRFI. Pancreatic cancer statistics | World Cancer Research Fund International. Available from: URL: .
    1. Guo Y, Liu W, Wu J. Helicobacter pylori infection and pancreatic cancer risk: A meta-analysis. J Cancer Res Ther. 2016;12:C229–C232.
    1. Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg. 2010;44:293–311.
    1. Becker AE, Hernandez YG, Frucht H, Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol. 2014;20:11182–11198.
    1. Permuth-Wey J, Egan KM. Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis. Fam Cancer. 2009;8:109–117.
    1. Chen F, Roberts NJ, Klein AP. Inherited pancreatic cancer. Chin Clin Oncol. 2017;6:58.
    1. Del Chiaro M, Segersvärd R, Lohr M, Verbeke C. Early detection and prevention of pancreatic cancer: is it really possible today? World J Gastroenterol. 2014;20:12118–12131.
    1. Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer. 2007;96:507–509.
    1. Huxley R, Ansary-Moghaddam A, Berrington de González A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076–2083.
    1. Grote VA, Rohrmann S, Nieters A, Dossus L, Tjønneland A, Halkjær J, Overvad K, Fagherazzi G, Boutron-Ruault MC, Morois S, et al. Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Diabetologia. 2011;54:3037–3046.
    1. Cummings KM, Dresler CM, Field JK, Fox J, Gritz ER, Hanna NH, Ikeda N, Jassem J, Mulshine JL, Peters MJ, et al. E-cigarettes and cancer patients. J Thorac Oncol. 2014;9:438–441.
    1. Samokhvalov AV, Rehm J, Roerecke M. Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses. EBioMedicine. 2015;2:1996–2002.
    1. Machicado JD, Rebours V, Yadav D. Epidemiology of chronic pancreatitis. Pancreapedia. 2016:1–15.
    1. Raimondi S, Lowenfels AB, Morselli-Labate AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 2010;24:349–358.
    1. El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, Giordano TP. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of US veterans. Hepatology. 2009;49:116–123.
    1. Walker MM, Talley NJ. Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract--beyond the era of Helicobacter pylori. Aliment Pharmacol Ther. 2014;39:767–779.
    1. Luo J, Xiao L, Wu C, Zheng Y, Zhao N. The incidence and survival rate of population-based pancreatic cancer patients: Shanghai Cancer Registry 2004-2009. PLoS One. 2013;8:e76052.
    1. 2017. Society TAC. Key Statistics for Pancreatic Cancer. Available from: URL: .
    1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378:607–620.
    1. Cancer Research UK. 2017. Survival Pancreatic cancer. Cancer Research UK. Available from: .
    1. Of U, Per C, Of U, Per D, Survival Y, Prevalence Y. 2013. Pancreas Cancer.
    1. Feldmann G, Beaty R, Hruban RH, Maitra A. Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg. 2007;14:224–232.
    1. Jun SY, Hong SM. Nonductal Pancreatic Cancers. Surg Pathol Clin. 2016;9:581–593.
    1. Luchini C, Capelli P, Scarpa A. Pancreatic Ductal Adenocarcinoma and Its Variants. Surg Pathol Clin. 2016;9:547–560.
    1. Reid MD, Saka B, Balci S, Goldblum AS, Adsay NV. Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications. Am J Clin Pathol. 2014;141:168–180.
    1. Verbeke C. Morphological heterogeneity in ductal adenocarcinoma of the pancreas - Does it matter? Pancreatology. 2016;16:295–301.
    1. Hong SM, Park JY, Hruban RH, Goggins M. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med. 2011;135:716–727.
    1. Bosman FT, Carneiro F, Hruban RH TN. WHO Classification of Tumours of the Digestive System WHO Classification of Tumours of the Digestive System IARC Publications Website - WHO Classification of Tumours of the Digestive System. 2018;2:7–8.
    1. Mohammed S, Van Buren G 2nd, Fisher WE. Pancreatic cancer: advances in treatment. World J Gastroenterol. 2014;20:9354–9360.
    1. Esposito I, Konukiewitz B, Schlitter AM, Klöppel G. Pathology of pancreatic ductal adenocarcinoma: facts, challenges and future developments. World J Gastroenterol. 2014;20:13833–13841.
    1. Brune K, Abe T, Canto M, O’Malley L, Klein AP, Maitra A, Volkan Adsay N, Fishman EK, Cameron JL, Yeo CJ, et al. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol. 2006;30:1067–1076.
    1. Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett ES, Goodman SN, Kern SE, Klimstra DS, Klöppel G, Longnecker DS, et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol. 2001;25:579–586.
    1. Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, et al. A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas. Am J Surg Pathol. 2015;39:1730–1741.
    1. Peters MLB, Eckel A, Mueller PP, Tramontano AC, Weaver DT, Lietz A, Hur C, Kong CY, Pandharipande PV. Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model. Pancreatology. 2018
    1. Lensing RJ, Bipat S. Incidences of Pancreatic Malignancy and Mortality in Patients With Untreated Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Surveillance: A Systematic Review. Pancreas. 2017;46:1098–1110.
    1. Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S; International Association of Pancreatology. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.
    1. Crippa S, Salvia R, Warshaw AL, Domínguez I, Bassi C, Falconi M, Thayer SP, Zamboni G, Lauwers GY, Mino-Kenudson M, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg. 2008;247:571–579.
    1. European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut. 2018;67:789–804.
    1. Tanaka M, Fernández-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17:738–753.
    1. Hruban RH, Maitra A, Goggins M. Update on pancreatic intraepithelial neoplasia. Int J Clin Exp Pathol. 2008;1:306–316.
    1. Löhr M, Klöppel G, Maisonneuve P, Lowenfels AB, Lüttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. Neoplasia. 2005;7:17–23.
    1. Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47–52.
    1. Corbishley TP, Iqbal MJ, Wilkinson ML, Williams R. Androgen receptor in human normal and malignant pancreatic tissue and cell lines. Cancer. 1986;57:1992–1995.
    1. Kanda T, Jiang X, Yokosuka O. Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers. World J Gastroenterol. 2014;20:9229–9236.
    1. Konduri S, Schwarz MA, Cafasso D, Schwarz RE. Androgen receptor blockade in experimental combination therapy of pancreatic cancer. J Surg Res. 2007;142:378–386.
    1. Georgiadou D, Sergentanis TN, Sakellariou S, Vlachodimitropoulos D, Psaltopoulou T, Lazaris AC, Gounaris A, Zografos GC. Prognostic role of sex steroid receptors in pancreatic adenocarcinoma. Pathol Res Pract. 2016;212:38–43.
    1. Garrido-Laguna I, Hidalgo M. Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol. 2015;12:319–334.
    1. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M; International Cancer of Pancreas Screening (CAPS) Consortium. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62:339–347.
    1. Unger K, Mehta KY, Kaur P, Wang Y, Menon SS, Jain SK, Moonjelly RA, Suman S, Datta K, Singh R, et al. Metabolomics based predictive classifier for early detection of pancreatic ductal adenocarcinoma. Oncotarget. 2018;9:23078–23090.
    1. Poley JW, Kluijt I, Gouma DJ, Harinck F, Wagner A, Aalfs C, van Eijck CH, Cats A, Kuipers EJ, Nio Y, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol. 2009;104:2175–2181.
    1. Yu J, Sadakari Y, Shindo K, Suenaga M, Brant A, Almario JAN, Borges M, Barkley T, Fesharakizadeh S, Ford M, et al. Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms. Gut. 2017;66:1677–1687.
    1. Zamboni G, Hirabayashi K, Castelli P, Lennon AM. Precancerous lesions of the pancreas. Best Pract Res Clin Gastroenterol. 2013;27:299–322.
    1. Lu C, Xu CF, Wan XY, Zhu HT, Yu CH, Li YM. Screening for pancreatic cancer in familial high-risk individuals: A systematic review. World J Gastroenterol. 2015;21:8678–8686.
    1. Mills K, Birt L, Emery JD, Hall N, Banks J, Johnson M, Lancaster J, Hamilton W, Rubin GP, Walter FM. Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study. BMJ Open. 2017;7:e015682.
    1. Keane MG, Horsfall L, Rait G, Pereira SP. A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer. BMJ Open. 2014;4:e005720.
    1. Xu J, Cao Z, Liu W, You L, Zhou L, Wang C, Lou W, Sun B, Miao Y, Liu X, et al. Plasma miRNAs Effectively Distinguish Patients With Pancreatic Cancer From Controls: A Multicenter Study. Ann Surg. 2016;263:1173–1179.
    1. Kim JE, Lee KT, Lee JK, Paik SW, Rhee JC, Choi KW. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004;19:182–186.
    1. Fahrmann JF, Bantis LE, Capello M, Scelo G, Dennison JB, Patel N, Murage E, Vykoukal J, Kundnani DL, Foretova L, et al. A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer. J Natl Cancer Inst. 2018
    1. Mayerle J, Kalthoff H, Reszka R, Kamlage B, Peter E, Schniewind B, González Maldonado S, Pilarsky C, Heidecke CD, Schatz P, et al. Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis. Gut. 2018;67:128–137.
    1. Riva F, Dronov OI, Khomenko DI, Huguet F, Louvet C, Mariani P, Stern MH, Lantz O, Proudhon C, Pierga JY, et al. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. Mol Oncol. 2016;10:481–493.
    1. Princivalle A, Monasta L, Butturini G, Bassi C, Perbellini L. Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air. BMC Cancer. 2018;18:529.
    1. Kanda M, Sadakari Y, Borges M, Topazian M, Farrell J, Syngal S, Lee J, Kamel I, Lennon AM, Knight S, et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol. 2013;11:719–30.e5.
    1. Zhou B, Xu JW, Cheng YG, Gao JY, Hu SY, Wang L, Zhan HX. Early detection of pancreatic cancer: Where are we now and where are we going? Int J Cancer. 2017;141:231–241.
    1. Demir IE, Jäger C, Schlitter AM, Konukiewitz B, Stecher L, Schorn S, Tieftrunk E, Scheufele F, Calavrezos L, Schirren R, et al. R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer. Ann Surg. 2017
    1. Kim KS, Kwon J, Kim K, Chie EK. Impact of Resection Margin Distance on Survival of Pancreatic Cancer: A Systematic Review and Meta-Analysis. Cancer Res Treat. 2017;49:824–833.
    1. Blamey SL, Fearon KC, Gilmour WH, Osborne DH, Carter DC. Prediction of risk in biliary surgery. Br J Surg. 1983;70:535–538.
    1. Wang Q, Gurusamy KS, Lin H, Xie X, Wang C. Preoperative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2008:CD005444.
    1. van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, Gerritsen JJ, Greve JW, Gerhards MF, de Hingh IH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:129–137.
    1. Hua J, He Z, Qian D, Meng H, Zhou B, Song Z. Duct-to-Mucosa Versus Invagination Pancreaticojejunostomy Following Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis. J Gastrointest Surg. 2015;19:1900–1909.
    1. Cheng Y, Briarava M, Lai M, Wang X, Tu B, Cheng N, Gong J, Yuan Y, Pilati P, Mocellin S. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy. Cochrane Database Syst Rev. 2017;9:CD012257.
    1. Venkat R, Edil BH, Schulick RD, Lidor AO, Makary MA, Wolfgang CL. Laparoscopic distal pancreatectomy is associated with significantly less overall morbidity compared to the open technique: a systematic review and meta-analysis. Ann Surg. 2012;255:1048–1059.
    1. Pericleous S, Middleton N, McKay SC, Bowers KA, Hutchins RR. Systematic review and meta-analysis of case-matched studies comparing open and laparoscopic distal pancreatectomy: is it a safe procedure? Pancreas. 2012;41:993–1000.
    1. Zhang J, Wu WM, You L, Zhao YP. Robotic versus open pancreatectomy: a systematic review and meta-analysis. Ann Surg Oncol. 2013;20:1774–1780.
    1. Buchs NC, Chilcott M, Poletti PA, Buhler LH, Morel P. Vascular invasion in pancreatic cancer: Imaging modalities, preoperative diagnosis and surgical management. World J Gastroenterol. 2010;16:818–831.
    1. Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J. Arterial resection during pancreatectomy for pancreatic cancer. Ann Surg. 2011;254:882–93.
    1. Yu XZ, Li J, Fu DL, Di Y, Yang F, Hao SJ, Jin C. Benefit from synchronous portal-superior mesenteric vein resection during pancreaticoduodenectomy for cancer: a meta-analysis. Eur J Surg Oncol. 2014;40:371–378.
    1. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–1481.
    1. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–1081.
    1. Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389:1011–1024.
    1. Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, et al. A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. J Clin Oncol. 2018;36:LBA4001–LBA4001.
    1. Ghosn M, Kourie HR, El Rassy E, Haddad FG, Hanna C, El Karak F, Nasr D. Where does chemotherapy stands in the treatment of ampullary carcinoma? A review of literature. World J Gastrointest Oncol. 2016;8:745–750.
    1. Altorki N, Harrison S. What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer? Ann Cardiothorac Surg. 2017;6:167–174.
    1. Labori KJ, Lassen K, Hoem D, Grønbech JE, Søreide JA, Mortensen K, Smaaland R, Sorbye H, Verbeke C, Dueland S. Neoadjuvant chemotherapy versus surgery first for resectable pancreatic cancer (Norwegian Pancreatic Cancer Trial - 1 (NorPACT-1)) - study protocol for a national multicentre randomized controlled trial. BMC Surg. 2017;17:94.
    1. Zhan HX, Xu JW, Wu D, Wu ZY, Wang L, Hu SY, Zhang GY. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med. 2017;6:1201–1219.
    1. Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol. 2014;20:10740–10751.
    1. Versteijne E, Vogel JA, Besselink MG, Busch ORC, Wilmink JW, Daams JG, van Eijck CHJ, Groot Koerkamp B, Rasch CRN, van Tienhoven G; Dutch Pancreatic Cancer Group. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105:946–958.
    1. Van Tienhoven G, Versteijne E, Suker M, Groothuis KBC, Busch OR, Bonsing BA, de Hingh IHJT, Festen S, Patijn GA, de Vos-Geelen J, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial. J Clin Oncol. 2018;36:LBA4002–LBA4002.
    1. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825.
    1. Mahaseth H, Brutcher E, Kauh J, Hawk N, Kim S, Chen Z, Kooby DA, Maithel SK, Landry J, El-Rayes BF. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas. 2013;42:1311–1315.
    1. Chu QD, Sun G, Pope M, Luraguiz N, Curiel DT, Kim R, Li BD, Mathis JM. Virotherapy using a novel chimeric oncolytic adenovirus prolongs survival in a human pancreatic cancer xenograft model. Surgery. 2012;152:441–448.
    1. Yamamoto Y, Hiraoka N, Goto N, Rin Y, Miura K, Narumi K, Uchida H, Tagawa M, Aoki K. A targeting ligand enhances infectivity and cytotoxicity of an oncolytic adenovirus in human pancreatic cancer tissues. J Control Release. 2014;192:284–293.
    1. Rouanet M, Lebrin M, Gross F, Bournet B, Cordelier P, Buscail L. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes. Int J Mol Sci. 2017:18.

Source: PubMed

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