Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Radical surgery is the only potential curative procedure. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. Early detection of PDAC is thus considered to be the most effective way to improve survival. In this regard, pancreatic screening has been proposed to improve results by detecting asymptomatic stages of PDAC and its precursors. There is now evidence of benefits of systematic surveillance in high-risk individuals, and the current guidelines emphasize the potential of screening to affect overall survival in individuals with genetic susceptibility syndromes or familial occurrence of PDAC. Here we aim to summarize the current knowledge about screening strategies for PDAC, including the latest epidemiological data, risk factors, associated hereditary syndromes, available screening modalities, benefits, limitations, as well as management implications.

2nd Department of Internal Medicine Gastroenterology and Geriatrics Faculty of Medicine and Dentistry Palacky University and University Hospital Olomouc 1 P Pavlova 185 6 77900 Olomouc Czech Republic

Zobrazit více v PubMed

Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. PubMed DOI

Arnold M., Abnet C.C., Neale R.E., Vignat J., Giovannucci E.L., McGlynn K.A., Bray F. Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology. 2020;159:335–349.e15. doi: 10.1053/j.gastro.2020.02.068. PubMed DOI PMC

Dusek L., Muzik J., Kubasek M., Koptikova J., Zaloudik J., Vyzula R. Epidemiology of Malignant Tumours in the Czech Republic. 2022. [(accessed on 26 February 2022)]. Available online: http://www.svod.cz.

Ústav zdravotnických informací a statistiky České republiky. 2022. [(accessed on 26 February 2022)]. Novotvary 2018 ČR. Available online: https://www.uzis.cz/res/f/008352/novotvary2018.pdf.

Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020;70:7–30. doi: 10.3322/caac.21590. PubMed DOI

Rahib L., Smith B.D., Aizenberg R., Rosenzweig A.B., Fleshman J.M., Matrisian L.M. 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. doi: 10.1158/0008-5472.CAN-14-0155. PubMed DOI

Huang L., Jansen L., Balavarca Y., Molina-Montes E., Babaei M., Van Der Geest L., Lemmens V., Van Eycken L., De Schutter H., Johannesen T.B., et al. Resection of pancreatic cancer in Europe and USA: An international large-scale study highlighting large variations. Gut. 2019;68:130–139. doi: 10.1136/gutjnl-2017-314828. PubMed DOI

Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021;71:7–33. doi: 10.3322/caac.21654. PubMed DOI

National Cancer Institute Cancer Stat Facts: Pancreatic Cancer. [(accessed on 29 August 2021)];2021 Available online: https://seer.cancer.gov/statfacts/html/pancreas.html.

Hernandez Y.G., Lucas A.L. MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions. World J. Gastrointest. Oncol. 2016;8:18–29. doi: 10.4251/wjgo.v8.i1.18. PubMed DOI PMC

Falasca M., Kim M., Casari I. Pancreatic cancer: Current research and future directions. Biochim. Biophys. Acta. 2016;1865:123–132. doi: 10.1016/j.bbcan.2016.01.001. PubMed DOI

Gharibi A., Adamian Y., Kelber J.A. Cellular and molecular aspects of pancreatic cancer. Acta Histochem. 2016;118:305–316. doi: 10.1016/j.acthis.2016.01.009. PubMed DOI PMC

Zhang X., Shi S., Zhang B., Ni Q., Yu X., Xu J. Circulating biomarkers for early diagnosis of pancreatic cancer: Facts and hopes. Am. J. Cancer Res. 2018;8:332–353. PubMed PMC

Ryska M. Karcinom pankreatu–současný efektivní diagnostický a terapeutický postup. Cas. Lek. Ces. 2016;155:38–43. PubMed

Aslanian H.R., Lee J.H., Canto M.I. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review. Gastroenterology. 2020;159:358–362. doi: 10.1053/j.gastro.2020.03.088. PubMed DOI

Owens D.K., Davidson K.W., Krist A.H., Barry M.J., Cabana M., Caughey A.B., Curry S.J., Doubeni C.A., Epling J.W., Kubik M., et al. Screening for pancreatic cancer: US preventive services Task force reaffirmation recommendation statement. JAMA. 2019;322:438–444. doi: 10.1001/jama.2019.10232. PubMed DOI

Goggins M., Overbeek K.A., Brand R., Syngal S., Del Chiaro M., Bartsch D.K., Bassi C., Carrato A., Farrell J., Fishman E.K., et al. Management of patients with increased risk for familial pancreatic cancer: Updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69:7–17. doi: 10.1136/gutjnl-2019-319352. PubMed DOI PMC

Trikudanathan G., Lou E., Maitra A., Majumder S. Early detection of pancreatic cancer: Current state and future opportunities. Curr. Opin. Gastroenterol. 2021;37:532–538. doi: 10.1097/MOG.0000000000000770. PubMed DOI PMC

Syngal S., Brand R.E., Church J.M., Giardiello F.M., Hampel H.L., Burt R.W. American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 2015;110:223–262. doi: 10.1038/ajg.2014.435. PubMed DOI PMC

Henrikson N.B., Bowles E.J.A., Blasi P.R., Morrison C.C., Nguyen M., Pillarisetty V.G., Lin J.S. Screening for pancreatic cancer: Updated evidence report and systematic review for the US preventive services Task force. JAMA. 2019;322:445–454. doi: 10.1001/jama.2019.6190. PubMed DOI

Calderwood A.H., Sawhney M.S., Thosani N.C., Rebbeck T.R., Wani S., Canto M.I., Fishman D.S., Golan T., Hidalgo M., Kwon R.S., et al. American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: Methodology and review of evidence. Gastrointest. Endosc. 2022;95:827–854.e3. doi: 10.1016/j.gie.2021.12.002. PubMed DOI

Burra P., Bretthauer M., Buti Ferret M., Dugic A., Fracasso P., Leja M., Budnik T.M., Michl P., Ricciardiello L., Seufferlein T., et al. Digestive cancer screening across Europe. United Eur. Gastroenterol. J. 2022;10:435–437. doi: 10.1002/ueg2.12230. PubMed DOI PMC

Canto M.I., Harinck F., Hruban R.H., Offerhaus G.J., Poley J.-W., Kamel I., Nio Y., Schulick R.S., Bassi C., Kluijt I., et al. 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. doi: 10.1136/gutjnl-2012-303108. PubMed DOI PMC

Klein A.P., Brune K.A., Petersen G.M., Goggins M., Tersmette A.C., Offerhaus G.J.A., Griffin C., Cameron J.L., Yeo C.J., Kern S., et al. Prospective Risk of Pancreatic Cancer in Familial Pancreatic Cancer Kindreds. Cancer Res. 2004;64:2634–2638. doi: 10.1158/0008-5472.CAN-03-3823. PubMed DOI

Schneider R., Slater E.P., Sina M., Habbe N., Fendrich V., Matthäi E., Langer P., Bartsch D.K. German national case collection for familial pancreatic cancer (FaPaCa): Ten years experience. Fam. Cancer. 2011;10:323–330. doi: 10.1007/s10689-010-9414-x. PubMed DOI

Bosetti C., Lucenteforte E., Silverman D.T., Petersen G., Bracci P.M., Ji B.T., Negri E., Li D., Risch H.A., Olson S.H., et al. Cigarette smoking and pancreatic cancer: An analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4) Ann. Oncol. 2012;23:1880–1888. doi: 10.1093/annonc/mdr541. PubMed DOI PMC

Iodice S., Gandini S., Maisonneuve P., Lowenfels A.B. Tobacco and the risk of pancreatic cancer: A review and meta-analysis. Langenbecks Arch. Surg. 2008;393:535–545. doi: 10.1007/s00423-007-0266-2. PubMed DOI

Lowenfels A.B., Maisonneuve P., Whitcomb D.C. Risk factors for cancer in hereditary pancreatitis. Med. Clin. N. Am. 2000;84:565–573. doi: 10.1016/S0025-7125(05)70240-6. PubMed DOI

Yeo T.P., Hruban R.H., Brody J., Brune K., Fitzgerald S., Yeo C.J. Assessment of “gene-environment” interaction in cases of familial and sporadic pancreatic cancer. J. Gastrointest. Surg. 2009;13:1487–1494. doi: 10.1007/s11605-009-0923-6. PubMed DOI

Malka D., Hammel P., Maire F., Rufat P., Madeira I., Pessione F., Lévy P., Ruszniewski P. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut. 2002;51:849–852. doi: 10.1136/gut.51.6.849. PubMed DOI PMC

Garcea G., Dennison A.R., Steward W.P., Berry D.P. Role of inflammation in pancreatic carcinogenesis and the implications for future therapy. Pancreatology. 2005;5:514–529. doi: 10.1159/000087493. PubMed DOI

Ben Q., Xu M., Ning X., Liu J., Hong S., Huang W., Zhang H., Li Z. Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur. J. Cancer. 2011;47:1928–1937. doi: 10.1016/j.ejca.2011.03.003. PubMed DOI

Tan J., You Y., Guo F., Xu J., Dai H., Bie P. Association of elevated risk of pancreatic cancer in diabetic patients: A systematic review and meta-analysis. Oncol. Lett. 2017;13:1247–1255. doi: 10.3892/ol.2017.5586. PubMed DOI PMC

Giardiello F.M., Welsh S.B., Hamilton S.R., Offerhaus G.J.A., Gittelsohn A.M., Booker S.V., Krush A.J., Yardley J.H., Luk G.D. Increased Risk of Cancer in the Peutz–Jeghers Syndrome. N. Engl. J. Med. 1987;316:1511–1514. doi: 10.1056/NEJM198706113162404. PubMed DOI

Giardiello F.M., Brensinger J.D., Tersmette A.C., Goodman S.N., Petersen G.M., Booker S.V., Cruz–Correa M., Offerhaus J.A. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000;119:1447–1453. doi: 10.1053/gast.2000.20228. PubMed DOI

van Lier M.G., Wagner A., Mathus-Vliegen E.M., Kuipers E.J., Steyerberg E., Et van Leerdam M. High Cancer Risk in Peutz–Jeghers Syndrome: A systematic review and surveillance recommendations. Am. J. Gastroenterol. 2010;105:1258–1264. doi: 10.1038/ajg.2009.725. PubMed DOI

DaVee T., Coronel E., Papafragkakis C., Thaiudom S., Lanke G., Chakinala R.C., González G.M.N., Bhutani M.S., Ross W.A., Weston B.R., et al. Pancreatic cancer screening in high-risk individuals with germline genetic mutations. Gastrointest. Endosc. 2018;87:1443–1450. doi: 10.1016/j.gie.2017.12.019. PubMed DOI

Vasen H.F., Gruis N.A., Frants R.R., van der Velden P.A., Hille E.T., Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden) Int. J. Cancer. 2000;87:809–811. doi: 10.1002/1097-0215(20000915)87:6<809::AID-IJC8>3.0.CO;2-U. PubMed DOI

Goldstein A.M., Fraser M.C., Struewing J.P., Hussussian C.J., Ranade K., Zametkin D.P., Fontaine L.S., Organic S.M., Dracopoli N.C., Clark W.H., et al. Increased Risk of Pancreatic Cancer in Melanoma-Prone Kindreds with p16INK4 Mutations. N. Engl. J. Med. 1995;333:970–974. doi: 10.1056/NEJM199510123331504. PubMed DOI

Yang X., Leslie G., Doroszuk A., Schneider S., Allen J., Decker B., Dunning A.M., Redman J., Scarth J., Plaskocinska I., et al. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J. Clin. Oncol. 2020;38:674–685. doi: 10.1200/JCO.19.01907. PubMed DOI PMC

Kastrinos F., Mukherjee B., Tayob N., Wang F., Sparr J., Raymond V.M., Bandipalliam P., Stoffel E.M., Gruber S.B., Syngal S. Risk of Pancreatic Cancer in Families With Lynch Syndrome. JAMA. 2009;302:1790–1795. doi: 10.1001/jama.2009.1529. PubMed DOI PMC

Hsu F.C., Roberts N.J., Childs E., Porter N., Rabe K.G., Borgida A., Ukaegbu C., Goggins M.G., Hruban R.H., Zogopoulos G., et al. Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene. JAMA Oncol. 2021;7:1664–1668. doi: 10.1001/jamaoncol.2021.3701. PubMed DOI PMC

Dite P., Hermanová M., Trna J., Novotný I., Růžička M., Liberda M., Bártková A. The Role of Chronic Inflammation: Chronic Pancreatitis as a Risk Factor of Pancreatic Cancer. Dig. Dis. 2012;30:277–283. doi: 10.1159/000336991. PubMed DOI

Lowenfels A.B., Maisonneuve P., DiMagno E.P., Elitsur Y., Gates L.K., Jr., Perrault J., Whitcomb D.C., International Hereditary Pancreatitis Study Group Hereditary Pancreatitis and the Risk of Pancreatic Cancer. J. Natl. Cancer Inst. 1997;89:442–446. doi: 10.1093/jnci/89.6.442. PubMed DOI

Rebours V., Boutron-Ruault M.C., Schnee M., Férec C., Maire F., Hammel P., Ruszniewski P., Lévy P. Risk of Pancreatic Adenocarcinoma in Patients with Hereditary Pancreatitis: A National Exhaustive Series. Am. J. Gastroenterol. 2008;103:111–119. doi: 10.1111/j.1572-0241.2007.01597.x. PubMed DOI

Muller N., Sarantitis I., Rouanet M., de Mestier L., Halloran C., Greenhalf W., Férec C., Masson E., Ruszniewski P., Lévy P., et al. Natural history of SPINK1 germline mutation related-pancreatitis. eBioMedicine. 2019;48:581–591. doi: 10.1016/j.ebiom.2019.09.032. PubMed DOI PMC

Klein A.P., Beaty T.H., Bailey-Wilson J.E., Brune K.A., Hruban R.H., Petersen G.M. Evidence for a major gene influencing risk of pancreatic cancer. Genet. Epidemiology. 2002;23:133–149. doi: 10.1002/gepi.1102. PubMed DOI

Permuth-Wey J., Egan K.M. Family history is a significant risk factor for pancreatic cancer: Results from a systematic review and meta-analysis. Fam. Cancer. 2009;8:109–117. doi: 10.1007/s10689-008-9214-8. PubMed DOI

Stoffel E.M., McKernin S.E., Brand R., Canto M., Goggins M., Moravek C., Nagarajan A., Petersen G.M., Simeone D.M., Yurgelun M., et al. Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. J. Clin. Oncol. 2019;37:153–164. doi: 10.1200/JCO.18.01489. PubMed DOI

National Comprehensive Cancer Network NCCN Guidelines-Pancreatic Adenocarcinoma. 2021. [(accessed on 29 August 2021)]. Available online: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455.

Lowery M.A., Wong W., Jordan E.J., Wong W., Lee J.W., Kemel Y., Vijai J., Mandelker D., Zehir A., Capanu M., et al. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. J. Natl. Cancer Inst. 2018;110:1067–1074. doi: 10.1093/jnci/djy024. PubMed DOI PMC

Grant R.C., Selander I., Connor A.A., Selvarajah S., Borgida A., Briollais L., Petersen G.M., Lerner-Ellis J., Holter S., Gallinger S. Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients With Pancreatic Cancer. Gastroenterology. 2015;148:556–564. doi: 10.1053/j.gastro.2014.11.042. PubMed DOI PMC

Salo-Mullen E.E., O'Reilly E.M., Kelsen D.P., Ashraf A.M., Lowery M.A., Yu K.h., Reidy D.L., Epstein A.S., Lincoln A., Saldia A., et al. Identification of germline genetic mutations in patients with pancreatic cancer. Cancer. 2015;121:4382–4388. doi: 10.1002/cncr.29664. PubMed DOI PMC

Yurgelun M.B., Chittenden A.B., Morales-Oyarvide V., Rubinson D.A., Dunne R.F., Kozak M.M., Qian Z.R., Welch M.W., Brais L.K., Da Silva A., et al. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genet. Med. 2019;21:213–223. doi: 10.1038/s41436-018-0009-5. PubMed DOI PMC

Brand R., Borazanci E., Speare V., Dudley B., Karloski E., Peters M.L.B., Stobie L., Bahary N., Zeh H., Zureikat A., et al. Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma. Cancer. 2018;124:3520–3527. doi: 10.1002/cncr.31628. PubMed DOI

Dudley B., Karloski E., Monzon F.A., Singhi A.D., Lincoln S.E., Bahary N., Brand R.E. Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy. Cancer. 2018;124:1691–1700. doi: 10.1002/cncr.31242. PubMed DOI

Shindo K., Yu J., Suenaga M., Fesharakizadeh S., Cho C., Macgregor-Das A., Siddiqui A., Witmer P.D., Tamura K., Song T.J., et al. Deleterious Germline Mutations in Patients with Apparently Sporadic Pancreatic Adenocarcinoma. J. Clin. Oncol. 2017;35:3382–3390. doi: 10.1200/JCO.2017.72.3502. PubMed DOI PMC

Zemanek T., Melichar B., Lovecek M., Soucek P., Mohelnikova-Duchonova B. Biomarkers and pathways of chemoresistance and chemosensitivity for personalized treatment of pancreatic adenocarcinoma. Pharmacogenomics. 2019;20:113–127. doi: 10.2217/pgs-2018-0073. PubMed DOI

Canto M.I., Hruban R.H., Fishman E.K., Kamel I.R., Schulick R., Zhang Z., Topazian M., Takahashi N., Fletcher J., Petersen G., et al. Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals. Gastroenterology. 2012;142:796–804. doi: 10.1053/j.gastro.2012.01.005. PubMed DOI PMC

Joergensen M.T., Gerdes A.-M., Sorensen J., de Muckadell O.S., Mortensen M.B. Is screening for pancreatic cancer in high-risk groups cost-effective?–Experience from a Danish national screening program. Pancreatology. 2016;16:584–592. doi: 10.1016/j.pan.2016.03.013. PubMed DOI

Poley J.W., Kluijt I., Gouma D.J., Harinck F., Wagner A., Aalfs C., van Eijck C.H.J., Cats A., Kuipers E.J., 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. doi: 10.1038/ajg.2009.276. PubMed DOI

Canto M.I., Goggins M., Yeo C.J., Griffin C., Axilbund J.E., Brune K., Ali S.Z., Jagannath S., Petersen G.M., Fishman E.K., et al. Screening for pancreatic neoplasia in high-risk individuals: An EUS-based approach. Clin. Gastroenterol. Hepatol. 2004;2:606–621. doi: 10.1016/S1542-3565(04)00244-7. PubMed DOI

Canto M.I., Goggins M., Hruban R.H., Petersen G.M., Giardiello F.M., Yeo C., Fishman E.K., Brune K., Axilbund J., Griffin C., et al. Screening for Early Pancreatic Neoplasia in High-Risk Individuals: A Prospective Controlled Study. Clin. Gastroenterol. Hepatol. 2006;4:766–781. doi: 10.1016/j.cgh.2006.02.005. PubMed DOI

Verna E.C., Hwang C., Stevens P.D., Rotterdam H., Stavropoulos S.N., Sy C.D., Prince M.A., Chung W.K., Fine R.L., Chabot J.A., et al. Pancreatic Cancer Screening in a Prospective Cohort of High-Risk Patients: A Comprehensive Strategy of Imaging and Genetics. Clin. Cancer Res. 2010;16:5028–5037. doi: 10.1158/1078-0432.CCR-09-3209. PubMed DOI

Harinck F., Konings I.C., Kluijt I., Poley J.W., Van Hooft J.E., Van Dullemen H.M., Nio C.Y., Krak N.C., Hermans J.J., Aalfs C.M., et al. Dutch Research Group on Pancreatic Cancer Surveillance in High-Risk Individuals. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut. 2016;65:1505–1513. doi: 10.1136/gutjnl-2014-308008. PubMed DOI

Gangi A., Malafa M., Klapman J. Endoscopic Ultrasound-Based Pancreatic Cancer Screening of High-Risk Individuals: A Prospective Observational Trial. Pancreas. 2018;47:586–591. doi: 10.1097/MPA.0000000000001038. PubMed DOI

Del Chiaro M., Verbeke C.S., Kartalis N., Mucelli R.P., Gustafsson P., Hansson J., Haas S.L., Segersvärd R., Andren-Sandberg Löhr M. Short-term Results of a Magnetic Resonance Imaging–Based Swedish Screening Program for Individuals at Risk for Pancreatic Cancer. JAMA Surg. 2015;150:512–518. doi: 10.1001/jamasurg.2014.3852. PubMed DOI

Al-Sukhni W., Borgida A., Rothenmund H., Holter S., Semotiuk K., Grant R., Wilson S., Moore M., Narod S., Jhaveri K., et al. Screening for Pancreatic Cancer in a High-Risk Cohort: An Eight-Year Experience. J. Gastrointest. Surg. 2012;16:771–783. doi: 10.1007/s11605-011-1781-6. PubMed DOI

Barnes C.A., Krzywda E., Lahiff S., McDowell D., Christians K.K., Knechtges P., Tolat P., Hohenwalter M., Dua K., Khan A.H., et al. Development of a high risk pancreatic screening clinic using 3.0 T MRI. Fam. Cancer. 2018;17:101–111. doi: 10.1007/s10689-017-0057-z. PubMed DOI

Overbeek K.A., Levink I.J.M., Koopmann B.D.M., Harinck F., Konings I.C.A.W., Ausems M.G.E.M., Wagner A., Fockens P., van Eijck C.H., Koerkamp B.G., et al. Long-term yield of pancreatic cancer surveillance in high-risk individuals. Gut. 2022;71:1152–1160. doi: 10.1136/gutjnl-2020-323611. PubMed DOI PMC

Canto M.I., Almario J.A., Schulick R.D., Yeo C.J., Klein A., Blackford A., Shin E.J., Sanyal A., Yenokyan G., Lennon A.M., et al. Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology. 2018;155:740–751.e2. doi: 10.1053/j.gastro.2018.05.035. PubMed DOI PMC

Psar R., Urban O., Cerna M., Rohan T., Hill M. Improvement of the Diagnosis of Isoattenuating Pancreatic Carcinomas by Defining Their Characteristics on Contrast Enhanced Computed Tomography and Endosonography with Fine-Needle Aspiration (EUS-FNA) Diagnostics. 2021;11:776. doi: 10.3390/diagnostics11050776. PubMed DOI PMC

Săftoiu A., Vilmann P. Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer. J. Clin. Ultrasound. 2009;37:1–17. doi: 10.1002/jcu.20534. PubMed DOI

Klapman J.B., Chang K.J., Lee J.G., Nguyen P. Negative Predictive Value of Endoscopic Ultrasound in a Large Series of Patients with a Clinical Suspicion of Pancreatic Cancer. Am. J. Gastroenterol. 2005;100:2658–2661. doi: 10.1111/j.1572-0241.2005.00315.x. PubMed DOI

Danai L.V., Babic A., Rosenthal M.H., Dennstedt E.A., Muir A., Lien E.C., Mayers J.R., Tai K., Lau A.N., Jones-Sali P., et al. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature. 2018;558:600–604. doi: 10.1038/s41586-018-0235-7. PubMed DOI PMC

Sah R.P., Sharma A., Nagpal S., Patlolla S.H., Sharma A., Kandlakunta H., Anani V., Angom R.S., Kamboj A.K., Ahmed N., et al. Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma. Gastroenterology. 2019;156:1742–1752. doi: 10.1053/j.gastro.2019.01.039. PubMed DOI PMC

Hanada K., Minami T., Shimizu A., Fukuhara M., Yano S., Sasaki K., Koda M., Sugiyama K., Yonehara S., Yanagisawa A. Roles of ERCP in the Early Diagnosis of Pancreatic Cancer. Diagnostics. 2019;9:30. doi: 10.3390/diagnostics9010030. PubMed DOI PMC

Kanno Y., Koshita S., Ogawa T., Kusunose H., Masu K., Sakai T., Yonamine K., Kawakami Y., Fujii Y., Miyamoto K., et al. Predictive Value of Localized Stenosis of the Main Pancreatic Duct for Early Detection of Pancreatic Cancer. Clin. Endosc. 2019;52:588–597. doi: 10.5946/ce.2019.018. PubMed DOI PMC

Wu J., Matthaei H., Maitra A., Dal Molin M., Wood L.D., Eshleman J.R., Goggins M., Canto M.I., Schulick R.D., Edil B.H., et al. Recurrent GNAS Mutations Define an Unexpected Pathway for Pancreatic Cyst Development. Sci. Transl. Med. 2011;3:92ra66. doi: 10.1126/scitranslmed.3002543. PubMed DOI PMC

Kanda M., Knight S., Topazian M., Syngal S., Farrell J., Lee J., Kamel I., Lennon A.M., Borges M., Young A., et al. Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. Gut. 2013;62:1024–1033. doi: 10.1136/gutjnl-2012-302823. PubMed DOI PMC

Kanda M., Sadakari Y., Borges M., Topazian M., Farrell J., Syngal S., Lee J., Kamel I., Lennon A.M., 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;11:719–730.e5. doi: 10.1016/j.cgh.2012.11.016. PubMed DOI PMC

Mizrahi J.D., Surana R., Valle J.W., Shroff R.T. Pancreatic cancer. Lancet. 2020;395:2008–2020. doi: 10.1016/S0140-6736(20)30974-0. PubMed DOI

Ballehaninna U.K., Chamberlain R.S. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J. Gastrointest. Oncol. 2012;3:105–119. doi: 10.3978/j.issn.2078-6891.2011.021. PubMed DOI PMC

Kaur S., Baine M.J., Jain M., Sasson A.R., Batra S.K. Early diagnosis of pancreatic cancer: Challenges and new developments. Biomarkers Med. 2012;6:597–612. doi: 10.2217/bmm.12.69. PubMed DOI PMC

Locker G.Y., Hamilton S., Harris J., Jessup J.M., Kemeny N., Macdonald J.S., Somerfield M.R., Hayes D.F., Bast R.C., Jr. ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. J. Clin. Oncol. 2006;24:5313–5327. doi: 10.1200/JCO.2006.08.2644. PubMed DOI

Kunovsky L., Tesarikova P., Kala Z., Kroupa R., Kysela P., Dolina J., Trna J. The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer. Can. J. Gastroenterol. Hepatol. 2018;2018:5389820. doi: 10.1155/2018/5389820. PubMed DOI PMC

Kim J.-E., Lee K.T., Lee J.K., Paik S.W., Rhee J.C., Choi K.W. 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. doi: 10.1111/j.1440-1746.2004.03219.x. PubMed DOI

Eid M., Karousi P., Kunovský L., Tuček S., Brančíková D., Kala Z., Slabý O., Mayer J., Kontos C.K., Trna J. The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma. Biomedicines. 2021;9:1468. doi: 10.3390/biomedicines9101468. PubMed DOI PMC

Zubarik R., Gordon S.R., Lidofsky S.D., Anderson S.R., Pipas J.M., Badger G., Ganguly E., Vecchio J. Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: A feasibility study. Gastrointest. Endosc. 2011;74:87–95. doi: 10.1016/j.gie.2011.03.1235. PubMed DOI

Kau S.Y., Shyr Y.M., Su C.H., Wu C.-W., Lui W.-Y. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J. Am. Coll. Surg. 1999;188:415–420. doi: 10.1016/S1072-7515(98)00326-3. PubMed DOI

Goonetilleke K.S., Siriwardena A.K. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur. J. Surg. Oncol. 2007;33:266–270. doi: 10.1016/j.ejso.2006.10.004. PubMed DOI

Mann D.V., Edwards R., Ho S., Lau W.Y., Glazer G. Elevated tumour marker CA19-9: Clinical interpretation and influence of obstructive jaundice. Eur. J. Surg. Oncol. 2000;26:474–479. doi: 10.1053/ejso.1999.0925. PubMed DOI

Lang J., Kunovsky L., Kala Z., Trna J. Risk factors of pancreatic cancer and their possible uses in diagnostics. Neoplasma. 2021;68:227–239. doi: 10.4149/neo_2020_200706N699. PubMed DOI

Goggins M. Molecular Markers of Early Pancreatic Cancer. J. Clin. Oncol. 2005;23:4524–4531. doi: 10.1200/JCO.2005.19.711. PubMed DOI

Fahrmann J.F., Schmidt C.M., Mao X., Irajizad E., Loftus M., Zhang J., Patel N., Vykoukal J., Dennison J.B., Long J.P., et al. Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection. Gastroenterology. 2021;160:1373–1383.e6. doi: 10.1053/j.gastro.2020.11.052. PubMed DOI PMC

Rawat M., Kadian K., Gupta Y., Kumar A., Chain P.S., Kovbasnjuk O., Parasher G. MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential. Genes. 2019;10:752. doi: 10.3390/genes10100752. PubMed DOI PMC

Johansen J.S., Calatayud D., Albieri V., Schultz N.A., Dehlendorff C., Werner J., Jensen B.V., Pfeiffer P., Bojesen S.E., Giese N., et al. The potential diagnostic value of serum microRNA signature in patients with pancreatic cancer. Int. J. Cancer. 2016;139:2312–2324. doi: 10.1002/ijc.30291. PubMed DOI

Liu J., Gao J., Du Y., Li Z., Ren Y., Gu J., Wang X., Gong Y., Wang W., Kong X. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int. J. Cancer. 2012;131:683–691. doi: 10.1002/ijc.26422. PubMed DOI

Schultz N.A., Dehlendorff C., Jensen B.V., Bjerregaard J.K., Nielsen K.R., Bojesen S.E., Calatayud D., Nielsen S.E., Yilmaz M., Holländer N.H., et al. MicroRNA Biomarkers in Whole Blood for Detection of Pancreatic Cancer. JAMA. 2014;311:392–404. doi: 10.1001/jama.2013.284664. PubMed DOI

Cohen J.D., Li L., Wang Y., Thoburn C., Afsari B., Danilova L., Douville C., Javed A.A., Wong F., Mattox A., et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359:926–930. doi: 10.1126/science.aar3247. PubMed DOI PMC

Brand R.E., Persson J., Bratlie S.O., Chung D.C., Katona B.W., Carrato A., Castillo M., Earl J., Kokkola A., Lucas A.L., et al. Detection of Early-Stage Pancreatic Ductal Adenocarcinoma From Blood Samples: Results of a Multiplex Biomarker Signature Validation Study. Clin. Transl. Gastroenterol. 2022;13:e00468. doi: 10.14309/ctg.0000000000000468. PubMed DOI PMC

Hart P.A., Bellin M.D., Andersen D.K., Bradley D., Cruz-Monserrate Z., Forsmark C.E., Goodarzi M.O., Habtezion A., Korc M., Kudva Y.C., et al. Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol. Hepatol. 2016;1:226–237. doi: 10.1016/S2468-1253(16)30106-6. PubMed DOI PMC

Sharma A., Smyrk T.C., Levy M.J., Topazian M.A., Chari S.T. Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. Gastroenterology. 2018;155:490–500. doi: 10.1053/j.gastro.2018.04.025. PubMed DOI PMC

Frič P., Šedo A., Škrha J. Časná detekce sporadického karcinomu pankreatu. Čas Lék Čes. 2016;155:44–47. PubMed

Wolrab D., Jirásko R., Cífková E., Höring M., Mei D., Chocholoušková M., Peterka O., Idkowiak J., Hrnčiarová T., Kuchař L., et al. Lipidomic profiling of human serum enables detection of pancreatic cancer. Nat. Commun. 2022;13:124. doi: 10.1038/s41467-021-27765-9. PubMed DOI PMC

Vasen H., Ibrahim I., Ponce C.G., Slater E.P., Matthäi E., Carrato A., Earl J., Robbers K., van Mil A.M., Potjer T., et al. Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers. J. Clin. Oncol. 2016;34:2010–2019. doi: 10.1200/JCO.2015.64.0730. PubMed DOI

Roberts N.J., Norris A.L., Petersen G.M., Bondy M.L., Brand R., Gallinger S., Kurtz R.C., Olson S.H., Rustgi A.K., Schwartz A.G., et al. Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer. Cancer Discov. 2016;6:166–175. doi: 10.1158/2159-8290.CD-15-0402. PubMed DOI PMC

Bartsch D.K., Dietzel K., Bargello M., Matthaei E., Kloeppel G., Esposito I., Heverhagen J., Gress T.M., Slater E.P., Langer P. Multiple small “imaging” branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: Indicator for concomitant high grade pancreatic intraepithelial neoplasia? Fam. Cancer. 2013;12:89–96. doi: 10.1007/s10689-012-9582-y. PubMed DOI

Brune K., Abe T., Canto M., O'Malley L., Klein A.P., Maitra A., Adsay N.V., Fishman E.K., Cameron J.L., Yeo C.J., 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. PubMed PMC

Konings I.C., Sidharta G.N., Harinck F., Aalfs C.M., Poley J.-W., Kieffer J.M., Kuenen M.A., Smets E.M.A., Wagner A., Van Hooft J.E., et al. Repeated participation in pancreatic cancer surveillance by high-risk individuals imposes low psychological burden. Psycho-Oncology. 2016;25:971–978. doi: 10.1002/pon.4047. PubMed DOI

Cazacu I.M., Luzuriaga Chavez A.A., Saftoiu A., Bhutani M.S. Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals: A systematic review. Endosc. Ultrasound. 2019;8:17–24. doi: 10.4103/eus.eus_25_18. PubMed DOI PMC

Lewis Z.K., Frost C.J., Venne V.L. Pancreatic Cancer Surveillance Among High-Risk Populations: Knowledge and Intent. J. Genet. Couns. 2009;18:229–238. doi: 10.1007/s10897-008-9205-9. PubMed DOI

Harinck F., Nagtegaal T., Kluijt I., Aalfs C., Smets E., Poley J.-W., Wagner A., van Hooft J., Fockens P., Bruno M., et al. Feasibility of a pancreatic cancer surveillance program from a psychological point of view. Genet. Med. 2011;13:1015–1024. doi: 10.1097/GIM.0b013e31822934f5. PubMed DOI

Konings I.C., Harinck F., Kuenen M.A., Sidharta G.N., Kieffer J.M., Aalfs C.M., Poley J.-W., Smets E.M., Wagner A., van Rens A., et al. Dutch research group on pancreatic cancer surveillance in high-risk individuals. Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance. Fam. Cancer. 2017;16:143–151. doi: 10.1007/s10689-016-9930-4. PubMed DOI PMC

Paiella S., Salvia R., De Pastena M., Pollini T., Casetti L., Landoni L., Esposito A., Marchegiani G., Malleo G., De Marchi G., et al. Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results. Pancreatology. 2018;18:420–428. doi: 10.1016/j.pan.2018.04.002. PubMed DOI

Corral J.E., Das A., Bruno M.J., Wallace M.B. Cost-effectiveness of Pancreatic Cancer Surveillance in High-Risk Individuals: An Economic Analysis. Pancreas. 2019;48:526–536. doi: 10.1097/MPA.0000000000001268. PubMed DOI

Kowada A. Cost-effectiveness of Abdominal Ultrasound Versus Magnetic Resonance Imaging for Pancreatic Cancer Screening in Familial High-Risk Individuals in Japan. Pancreas. 2020;49:1052–1056. doi: 10.1097/MPA.0000000000001614. PubMed DOI

Vasen H.F., Wasser M., van Mil A., Tollenaar R.A., Konstantinovski M., Gruis N., Bergman W., Hes F.J., Hommes D.W., Offerhaus G.J.A., et al. Magnetic Resonance Imaging Surveillance Detects Early-Stage Pancreatic Cancer in Carriers of a p16-Leiden Mutation. Gastroenterology. 2011;140:850–856. doi: 10.1053/j.gastro.2010.11.048. PubMed DOI

Yu J., Sadakari Y., Shindo K., Suenaga M., Brant A., Almario J.A.N., 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. doi: 10.1136/gutjnl-2015-311166. PubMed DOI PMC

Suenaga M., Yu J., Shindo K., Tamura K., Almario J.A., Zaykoski C., Witmer P.D., Fesharakizadeh S., Borges M., Lennon A.-M., et al. Pancreatic Juice Mutation Concentrations Can Help Predict the Grade of Dysplasia in Patients Undergoing Pancreatic Surveillance. Clin. Cancer Res. 2018;24:2963–2974. doi: 10.1158/1078-0432.CCR-17-2463. PubMed DOI PMC

Pea A., Yu J., Marchionni L., Noe M., Luchini C., Pulvirenti A., de Wilde R.F., Brosens L.A., Rezaee N., Javed A., et al. Genetic Analysis of Small Well-differentiated Pancreatic Neuroendocrine Tumors Identifies Subgroups with Differing Risks of Liver Metastases. Ann. Surg. 2020;271:566–573. doi: 10.1097/SLA.0000000000003022. PubMed DOI PMC

Falconi M., Eriksson B., Kaltsas G., Bartsch D.K., Capdevila J., Caplin M., Kos-Kudla B., Kwekkeboom D., Rindi G., Klöppel G., et al. ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. Neuroendocrinology. 2016;103:153–171. doi: 10.1159/000443171. PubMed DOI PMC

Matthaei H., Hong S.-M., Molin M.D., Wolfgang C., Schulick R., Maitra A., Hruban R. Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. Ann. Surg. Oncol. 2011;18:3493–3499. doi: 10.1245/s10434-011-1745-9. PubMed DOI PMC

Basturk O., Hong S.-M., Wood L.D., Adsay V., Albores-Saavedra J., Biankin A., Brosens L.A., Fukushima N., Goggins M., Hruban R.H., 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. doi: 10.1097/PAS.0000000000000533. PubMed DOI PMC

Canto M.I., Kerdsirichairat T., Yeo C.J., Hruban R.H., Shin E.J., Almario J.A., Blackford A., Ford M., Klein A.P., Javed A.A., et al. Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. J. Gastrointest. Surg. 2020;24:1101–1110. doi: 10.1007/s11605-019-04230-z. PubMed DOI PMC

Diabetes Mellitus in Pancreatic Cancer: A Distinct Approach to Older Subjects with New-Onset Diabetes Mellitus