European Radiology

, Volume 27, Issue 12, pp 4941–4950 | Cite as

Development of pancreatic cancer is predictable well in advance using contrast-enhanced CT: a case–cohort study

  • Wataru GonoiEmail author
  • Takana Yamakawa Hayashi
  • Hidemi Okuma
  • Masaaki Akahane
  • Yousuke Nakai
  • Suguru Mizuno
  • Ryosuke Tateishi
  • Hiroyuki Isayama
  • Kazuhiko Koike
  • Kuni Ohtomo



To investigate the radiological findings prognostic for the development of pancreatic adenocarcinoma in a cohort of patients with hepatocellular carcinoma, using multiphasic computed tomography (CT).


A case–cohort study performed in a single university hospital. A database of patients who received hepatocellular carcinoma (HCC) treatment and trimonthly follow-up with four-phase dynamic CT was used (n = 1848). The cohort group was randomly extracted from the database (n = 103). The case group comprised nine patients from the database who developed pancreatic adenocarcinoma. The radiological findings were assessed during follow-up (average, 32 months).


The incidence of pancreatic mass, inhomogeneous parenchyma, loss of fatty marbling and main pancreatic duct dilatation gradually increased from 4 to 13 months before the diagnosis of pancreatic adenocarcinoma. There was a significantly higher incidence of pancreatic mass, inhomogeneous parenchyma and loss of fatty marbling on CT at baseline (average, 34 months before diagnosis) in the case group compared with the cohort group (P values < 0.01) and those findings at baseline were revealed as prognostic factors for pancreatic carcinogenesis, respectively (log-rank test, P values < 0.001).


Several radiological findings observed on multiphasic CT can assist in predicting pancreatic carcinogenesis well in advance.

Key points

Pancreatic findings in multiphasic CT help predict development of pancreatic adenocarcinoma.

Key findings are mass, inhomogeneous parenchyma and loss of fatty marbling.

Those findings were observed 34 months before confirmed diagnosis of adenocarcinoma.

Those findings were prognostic factors for pancreatic carcinogenesis.


Adenocarcinoma Pancreas Prognosis Radiology Screening 

Abbreviations and acronyms


computed tomography


hepatocellular carcinoma


main pancreatic duct


Compliance with ethical standards


The scientific guarantor of this publication is Kuni Ohtomo (University of Tokyo).

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.


The authors state that this work has not received any funding.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Ethical approval

Institutional review board approval was obtained.

Informed consent

Written informed consent was waived by the institutional review board.


• retrospective

• case–cohort study

• performed at one institution


  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29CrossRefPubMedGoogle Scholar
  2. 2.
    Takayama S (2015) Cancer statistics in Japan '14. Foundation for Promotion of Cancer Research, Tsukiji, Japan. Accessed 3 Jul 2015
  3. 3.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRefPubMedGoogle Scholar
  4. 4.
    Bilimoria KY, Bentrem DJ, Ko CY et al (2007) Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer 110:738–744CrossRefPubMedGoogle Scholar
  5. 5.
    Sachs T, Pratt WB, Callery MP, Vollmer CM Jr (2009) The incidental asymptomatic pancreatic lesion: nuisance or threat? J Gastrointest Surg 13:405–415CrossRefPubMedGoogle Scholar
  6. 6.
    Paspulati RM (2005) Multidetector CT of the pancreas. Radiol Clin North Am 43:999-1020, viiiGoogle Scholar
  7. 7.
    Verslype C, Van Cutsem E, Dicato M et al (2007) The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006. Ann Oncol 18(Suppl 7):vii1–vii10PubMedGoogle Scholar
  8. 8.
    Somers I, Bipat S (2017) Contrast-enhanced CT in determining resectability in patients with pancreatic carcinoma: a meta-analysis of the positive predictive values of CT. Eur Radiol. doi: 10.1007/s00330-016-4708-5 PubMedPubMedCentralGoogle Scholar
  9. 9.
    Pelaez-Luna M, Takahashi N, Fletcher JG, Chari ST (2007) Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis. Am J Gastroenterol 102:2157–2163CrossRefPubMedGoogle Scholar
  10. 10.
    Gangi S, Fletcher JG, Nathan MA et al (2004) Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis. AJR Am J Roentgenol 182:897–903CrossRefPubMedGoogle Scholar
  11. 11.
    Yoon SH, Lee JM, Cho JY et al (2011) Small (</= 20 mm) pancreatic adenocarcinomas: analysis of enhancement patterns and secondary signs with multiphasic multidetector CT. Radiology 259:442–452CrossRefPubMedGoogle Scholar
  12. 12.
    Ahn SS, Kim MJ, Choi JY, Hong HS, Chung YE, Lim JS (2009) Indicative findings of pancreatic cancer in prediagnostic CT. Eur Radiol 19:2448–2455CrossRefPubMedGoogle Scholar
  13. 13.
    Shiina S, Tateishi R, Arano T et al (2012) Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 107:569–577, quiz 578 CrossRefPubMedGoogle Scholar
  14. 14.
    Kanda Y (2013) Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 48:452–458CrossRefPubMedGoogle Scholar
  15. 15.
    Ishikawa O, Ohigashi H, Imaoka S et al (1999) Minute carcinoma of the pancreas measuring 1 cm or less in diameter–collective review of Japanese case reports. Hepatogastroenterology 46:8–15PubMedGoogle Scholar
  16. 16.
    Goodman M, Willmann JK, Jeffrey RB (2012) Incidentally discovered solid pancreatic masses: imaging and clinical observations. Abdom Imaging 37:91–97CrossRefPubMedGoogle Scholar
  17. 17.
    Tamada T, Ito K, Kanomata N et al (2016) Pancreatic adenocarcinomas without secondary signs on multiphasic multidetector CT: association with clinical and histopathologic features. Eur Radiol 26:646–655CrossRefPubMedGoogle Scholar
  18. 18.
    Fitzgerald TL, Smith AJ, Ryan M et al (2003) Surgical treatment of incidentally identified pancreatic masses. Can J Surg 46:413–418PubMedPubMedCentralGoogle Scholar
  19. 19.
    Loizou L, Albiin N, Leidner B et al (2016) Multidetector CT of pancreatic ductal adenocarcinoma: effect of tube voltage and iodine load on tumour conspicuity and image quality. Eur Radiol 26:4021–4029CrossRefPubMedGoogle Scholar
  20. 20.
    Harinck F, Konings IC, Kluijt I et al (2015) A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut. doi: 10.1136/gutjnl-2014-308008 PubMedGoogle Scholar
  21. 21.
    Lu C, Xu CF, Wan XY, Zhu HT, Yu CH, Li YM (2015) Screening for pancreatic cancer in familial high-risk individuals: a systematic review. World J Gastroenterol 21:8678–8686CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lu DS, Vedantham S, Krasny RM, Kadell B, Berger WL, Reber HA (1996) Two-phase helical CT for pancreatic tumors: pancreatic versus hepatic phase enhancement of tumor, pancreas, and vascular structures. Radiology 199:697–701CrossRefPubMedGoogle Scholar
  23. 23.
    Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA (2012) The pancreas cancer microenvironment. Clin Cancer Res 18:4266–4276CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Tada M, Kawabe T, Arizumi M et al (2006) Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients. Clin Gastroenterol Hepatol 4:1265–1270CrossRefPubMedGoogle Scholar
  25. 25.
    Ryan DP, Hong TS, Bardeesy N (2014) Pancreatic adenocarcinoma. N Engl J Med 371:1039–1049CrossRefPubMedGoogle Scholar
  26. 26.
    Berthelemy P, Bouisson M, Escourrou J, Vaysse N, Rumeau JL, Pradayrol L (1995) Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer. Ann Intern Med 123:188–191CrossRefPubMedGoogle Scholar
  27. 27.
    Hruban RH, Wilentz RE, Kern SE (2000) Genetic progression in the pancreatic ducts. Am J Pathol 156:1821–1825CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH (1998) Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol 22:163–169CrossRefPubMedGoogle Scholar
  29. 29.
    Konstantinidis IT, Warshaw AL, Allen JN et al (2013) Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a "true" R0 resection? Ann Surg 257:731–736CrossRefPubMedGoogle Scholar
  30. 30.
    Matsumoto S, Mori H, Miyake H et al (1995) Uneven fatty replacement of the pancreas: evaluation with CT. Radiology 194:453–458CrossRefPubMedGoogle Scholar
  31. 31.
    Heuck A, Maubach PA, Reiser M et al (1987) Age-related morphology of the normal pancreas on computed tomography. Gastrointest Radiol 12:18–22CrossRefPubMedGoogle Scholar
  32. 32.
    Gonoi W, Akahane M, Akai H et al (2011) Retroportal main pancreatic duct with circumportal pancreas: radiographic visualization. Clin Imaging 35:442–446CrossRefPubMedGoogle Scholar
  33. 33.
    Seo N, Byun JH, Kim JH et al (2015) Validation of the 2012 international consensus guidelines using computed tomography and magnetic resonance imaging: branch duct and main duct intraductal papillary mucinous neoplasms of the pancreas. Ann Surg. doi: 10.1097/SLA.0000000000001217 Google Scholar
  34. 34.
    Gonoi W, Akai H, Hagiwara K et al (2011) Pancreas divisum as a predisposing factor for chronic and recurrent idiopathic pancreatitis: initial in vivo survey. Gut 60:1103–1108CrossRefPubMedGoogle Scholar
  35. 35.
    Gonoi W, Akai H, Hagiwara K et al (2012) Meandering main pancreatic duct as a relevant factor to the onset of idiopathic recurrent acute pancreatitis. PLoS One 7, e37652CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Gonoi W, Akai H, Hagiwara K et al (2013) Santorinicele without pancreas divisum pathophysiology: initial clinical and radiographic investigations. BMC Gastroenterol 13:62CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  • Wataru Gonoi
    • 1
    Email author
  • Takana Yamakawa Hayashi
    • 1
  • Hidemi Okuma
    • 1
  • Masaaki Akahane
    • 1
    • 2
  • Yousuke Nakai
    • 3
  • Suguru Mizuno
    • 3
  • Ryosuke Tateishi
    • 3
  • Hiroyuki Isayama
    • 3
  • Kazuhiko Koike
    • 3
  • Kuni Ohtomo
    • 1
  1. 1.Department of Radiology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of RadiologyNTT Medical Centre TokyoTokyoJapan
  3. 3.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan

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