European Surgery

, Volume 41, Issue 6, pp 268–279 | Cite as

Diagnostic workup of patients with pancreatic diseases

  • M. Kraft
  • P. Simon
  • A. Aghdassi
  • C. D. Heidecke
  • G. Sauter
  • J.-P. Kühn
  • F. U. Weiss
  • M. M. Lerch
  • J. Mayerle
Main Topic
  • 64 Downloads

Summary

BACKGROUND: Pancreatic disorders comprise a large number of entities that include congenital malformations, inflammatory disorders such as acute and chronic pancreatitis, neoplasias of epithelial, mesenchymal, and neuroendocrine origin, inherited disorders that are associated with germline mutations and autoimmune pancreatitis. METHODS: The following article will not only review the strength and weaknesses of the most commonly used laboratory tests and imaging modalities such as endoscopic ultrasound, CT scanning, and MRI but also outline the indications for genetic studies and function tests. Rare disorders that often present as a challenging differential diagnosis and genetic predispositions for pancreatitis and pancreatic cancer will also be covered. RESULTS AND CONCLUSIONS: The spectrum of diagnostic tests being used for the clinical work-up of patients with pancreatic disorders and at-risk relatives is accordingly broad. It ranges from simple clinical chemistry to function tests for endocrine and exocrine insufficiency, to imaging techniques and genetic testing.

Keywords

Acute pancreatitis Chronic pancreatitis Pancreatic function tests Genetic testing Pancreatic cancer 

Diagnostik bei Pankreas-Erkrankungen

Zusammenfassung

GRUNDLAGEN: Zu den Erkrankungen der Bauchspeicheldrüse gehören eine große Zahl unterschiedlicher Krankheitsbilder, die von angeborenen Fehlbildungen über entzündliche Erkrankungen wie der akuten und chronischen Pankreatitis, über Neoplasien epithelialen, mesenchymalen und neuroendokrinen Ursprungs, bis zu erblichen Erkrankungen, die mit Keimbahnmutationen einhergehen und bis zur Autoimmunpankreatitis reichen. METHODIK: Im folgenden Artikel werden nicht nur die Stärken und Schwächen der am häufigsten verwendeten Laboruntersuchungen und bildgebenden Verfahren dargestellt, zu denen der endoskopische Ultraschall, die Computertomographie und die Kernspintomographie gehören, sondern auch die Indikationen für genetische Untersuchungen und Funktionstests. Seltene Erkrankungen, die häufig eine Herausforderung für die Differentialdiagnose darstellen und erbliche Prädispositionen für die Pankreatitis und das Pankreaskarzinom werden ebenfalls diskutiert. ERGEBNISSE UND SCHLUSSFOLGERUNGEN: Das Spektrum der diagnostischen Verfahren, die in der Klinik für die Differentialdiagnose bei Patienten mit Pankreaserkrankungen eingesetzt und auch bei deren Verwandten mit hohem Erkrankungsrisiko verwendet werden, ist deshalb außerordentlich breit. Es reicht von einfachen klinisch-chemischen Untersuchungen über Funktionsuntersuchungen für die endokrine und exokrine Pankreasinsuffizienz bis zu bildgebenden Verfahren und Gentests.

Schlüsselwörter

Akute Pankreatitis Chronische Pankreatitis Funktionstests Genetische Testung Pankreaskarzinom 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Comfort MGE, Baggenstoss A. Chronic relasping pancreatitis: a study of 29 cases without associated disease of the biliary or gastrointestinal tract. Gastroenterology 1946;6:239–85Google Scholar
  2. Liu CL, Fan ST, Lo CM, Tso WK, Wong Y, Poon RT, Lam CM, Wong BC, Wong J. Comparison of early endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis: a prospective randomized study. Clin Gastroenterol Hepatol 2005;3:1238–44CrossRefPubMedGoogle Scholar
  3. Blamey SL, Osborne DH, Gilmour WH, O'Neill J, Carter DC, Imrie CW. The early identification of patients with gallstone associated pancreatitis using clinical and biochemical factors only. Ann Surg 1983;198:574–8CrossRefPubMedGoogle Scholar
  4. Ammori BJ, Boreham B, Lewis P, Roberts SA. The biochemical detection of biliary etiology of acute pancreatitis on admission: a revisit in the modern era of biliary imaging. Pancreas 2003;26:e32–5CrossRefPubMedGoogle Scholar
  5. Sugiyama M, Atomi Y. Risk factors for acute biliary pancreatitis. Gastrointest Endosc 2004;60:210–2CrossRefPubMedGoogle Scholar
  6. Thorboll J, Vilmann P, Jacobsen B, Hassan H. Endoscopic ultrasonography in detection of cholelithiasis in patients with biliary pain and negative transabdominal ultrasonography. Scand J Gastroenterol 2004;39:267–9CrossRefPubMedGoogle Scholar
  7. Saraswat VA, Sharma BC, Agarwal DK, Kumar R, Negi TS, Tandon RK. Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain: response to therapy. J Gastroenterol Hepatol 2004;19:1206–11CrossRefPubMedGoogle Scholar
  8. Moon JH, Cho YD, Cha SW, Cheon YK, Ahn HC, Kim YS, Kim YS, Lee JS, Lee MS, Lee HK, Shim CS, Kim BS. The detection of bile duct stones in suspected biliary pancreatitis: comparison of MRCP, ERCP, and intraductal US. Am J Gastroenterol 2005;100:1051–7CrossRefPubMedGoogle Scholar
  9. Balthazar EJ, Freeny PC, vanSonnenberg E. Imaging and intervention in acute pancreatitis. Radiology 1994;193:297–306PubMedGoogle Scholar
  10. Uhl W, Roggo A, Kirschstein T, Anghelacopoulos SE, Gloor B, Muller CA, Malfertheiner P, Buchler MW. Influence of contrast-enhanced computed tomography on course and outcome in patients with acute pancreatitis. Pancreas 2002;24:191–7CrossRefPubMedGoogle Scholar
  11. UK guidelines for the management of acute pancreatitis. Gut 2005;54(Suppl 3):iii1–9Google Scholar
  12. Mortele KJ, Wiesner W, Intriere L, Shankar S, Zou KH, Kalantari BN, Perez A, vanSonnenberg E, Ros PR, Banks PA, Silverman SG. A modified CT severity index for evaluating acute pancreatitis: improved correlation with patient outcome. Am J Roentgenol 2004;183:1261–5Google Scholar
  13. Balthazar EJ. Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology 2002;223:603–13CrossRefPubMedGoogle Scholar
  14. Arvanitakis M, Delhaye M, De Maertelaere V, Bali M, Winant C, Coppens E, Jeanmart J, Zalcman M, Van Gansbeke D, Deviere J, Matos C. Computed tomography and magnetic resonance imaging in the assessment of acute pancreatitis. Gastroenterology 2004;126:715–23CrossRefPubMedGoogle Scholar
  15. Buchler M, Malfertheiner P, Schoetensack C, Uhl W, Scherbaum W, Beger HG. Value of biochemical and imaging procedures for the diagnosis and prognosis of acute pancreatitis – results of a prospective clinical study. Z Gastroenterol 1986;24:100–9PubMedGoogle Scholar
  16. Brown A, Orav J, Banks PA. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas 2000;20:367–72CrossRefPubMedGoogle Scholar
  17. Lankisch PG, Mahlke R, Blum T, Bruns A, Bruns D, Maisonneuve P, Lowenfels AB. Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal. Am J Gastroenterol 2001;96:2081–5CrossRefPubMedGoogle Scholar
  18. Shafiq N, Malhotra S, Bhasin DK, Rana S, Siddhu S, Pandhi P. Estimating the diagnostic accuracy of procalcitonin as a marker of the severity of acute pancreatitis: a meta-analytic approach. Jop 2005;6:231–7PubMedGoogle Scholar
  19. Rau BM, Bothe A, Kron M, Beger HG. Role of early multisystem organ failure as major risk factor for pancreatic infections and death in severe acute pancreatitis. Clin Gastroenterol Hepatol 2006;4:1053–61CrossRefPubMedGoogle Scholar
  20. Jensen AR, Matzen P, Malchow-Moller A, Christoffersen I. Pattern of pain, duct morphology, and pancreatic function in chronic pancreatitis. A comparative study. Scand J Gastroenterol 1984;19:334–8PubMedGoogle Scholar
  21. Ammann RW, Muellhaupt B. The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology 1999;116:1132–40CrossRefPubMedGoogle Scholar
  22. Layer P, Yamamoto H, Kalthoff L, Clain JE, Bakken LJ, DiMagno EP. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology 1994;107:1481–7PubMedGoogle Scholar
  23. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996;14:141–5CrossRefPubMedGoogle Scholar
  24. Simon P, Weiss FU, Sahin-Toth M, Parry M, Nayler O, Lenfers B, Schnekenburger J, Mayerle J, Domschke W, Lerch MM. Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 →Cys) that alters autoactivation and autodegradation of cationic trypsinogen. J Biol Chem 2002;277:5404–10CrossRefPubMedGoogle Scholar
  25. Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2004;2:252–61CrossRefPubMedGoogle Scholar
  26. Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, Landt O, Becker M. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000;25:213–6CrossRefPubMedGoogle Scholar
  27. Weiss FU, Simon P, Witt H, Mayerle J, Hlouschek V, Zimmer KP, Schnekenburger J, Domschke W, Neoptolemos JP, Lerch MM. SPINK1 mutations and phenotypic expression in patients with pancreatitis associated with trypsinogen mutations. J Med Genet 2003;40:e40CrossRefPubMedGoogle Scholar
  28. Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998;339:653–8CrossRefPubMedGoogle Scholar
  29. Sharer N, Schwarz M, Malone G, Howarth A, Painter J, Super M, Braganza J. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 1998;339:645–52CrossRefPubMedGoogle Scholar
  30. Weiss FU, Simon P, Bogdanova N, Mayerle J, Dworniczak B, Horst J, Lerch MM. Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls. Gut 2005;54:1456–60CrossRefPubMedGoogle Scholar
  31. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 1990;19:783–91PubMedGoogle Scholar
  32. Mooren F, Hlouschek V, Finkes T, Turi S, Weber IA, Singh J, Domschke W, Schnekenburger J, Kruger B, Lerch MM. Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction. J Biol Chem 2003;278:9361–9CrossRefPubMedGoogle Scholar
  33. Mooren FC, Turi S, Gunzel D, Schlue WR, Domschke W, Singh J, Lerch MM. Calcium-magnesium interactions in pancreatic acinar cells. Faseb J 2001;15:659–72CrossRefPubMedGoogle Scholar
  34. Popovic M, Goobie S, Morrison J, Ellis L, Ehtesham N, Richards N, Boocock G, Durie PR, Rommens JM. Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene. Eur J Hum Genet 2002;10:250–8CrossRefPubMedGoogle Scholar
  35. Zenker M, Mayerle J, Lerch MM, Tagariello A, Zerres K, Durie PR, Beier M, Hulskamp G, Guzman C, Rehder H, Beemer FA, Hamel B, Vanlieferinghen P, Gershoni-Baruch R, Vieira MW, Dumic M, Auslender R, Gil-da-Silva-Lopes VL, Steinlicht S, Rauh M, Shalev SA, Thiel C, Ekici AB, Winterpacht A, Kwon YT, Varshavsky A, Reis A. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nat Genet 2005;37:1345–50CrossRefPubMedGoogle Scholar
  36. DiMagno EP, Go VL, Summerskill WH. Relations between pancreatic enzyme ouputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973;288:813–5PubMedGoogle Scholar
  37. Chowdhury RS, Forsmark CE. Review article: pancreatic function testing. Aliment Pharmacol Ther 2003;17:733–50CrossRefPubMedGoogle Scholar
  38. Burton P, Evans DG, Harper AA, Howath T, Oleesky S, Scott JE, Varley H. A test of pancreatic function in man based on the analysis of duodenal contents after administration of secretin and pancreozymin. Gut 1960;1:111–24CrossRefPubMedGoogle Scholar
  39. Gregg JA. The intraductal secretin test: an adjunct to ERCP. Gastrointest Endosc 1982;28:199–203CrossRefPubMedGoogle Scholar
  40. Raimondo M, Imoto M, DiMagno EP. Rapid endoscopic secretin stimulation test and discrimination of chronic pancreatitis and pancreatic cancer from disease controls. Clin Gastroenterol Hepatol 2003;1:397–403CrossRefPubMedGoogle Scholar
  41. Stevens T, Conwell DL, Zuccaro G, Van Lente F, Khandwala F, Purich E, Vargo JJ, Fein S, Dumot JA, Trolli P, O'Laughlin C. Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects. Gastrointest Endosc 2004;60:351–5CrossRefPubMedGoogle Scholar
  42. Stevens T, Conwell DL, Zuccaro G Jr, Van Lente F, Purich E, Khandwala F, Fein S. A randomized crossover study of secretin-stimulated endoscopic and dreiling tube pancreatic function test methods in healthy subjects. Am J Gastroenterol 2006;101:351–5CrossRefPubMedGoogle Scholar
  43. Cappeliez O, Delhaye M, Deviere J, Le Moine O, Metens T, Nicaise N, Cremer M, Stryuven J, Matos C. Chronic pancreatitis: evaluation of pancreatic exocrine function with MR pancreatography after secretin stimulation. Radiology 2000;215:358–64PubMedGoogle Scholar
  44. Matos C, Metens T, Deviere J, Nicaise N, Braude P, Van Yperen G, Cremer M, Struyven J. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997;203:435–41PubMedGoogle Scholar
  45. Stein J, Jung M, Sziegoleit A, Zeuzem S, Caspary WF, Lembcke B. Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 1996;42:222–6PubMedGoogle Scholar
  46. Lankisch PG, Schmidt I, Konig H, Lehnick D, Knollmann R, Lohr M, Liebe S. Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency. Gut 1998;42:551–4PubMedCrossRefGoogle Scholar
  47. Loser C, Mollgaard A, Folsch UR. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Gut 1996;39:580–6CrossRefPubMedGoogle Scholar
  48. Lerch MM, Nolte I, Riehl J, Gladziwa U, Mann H, Sieberth HG, Matern S. Diagnostic value of indirect pancreatic function test in serum of anuric patients with chronic renal failure. Scand J Clin Lab Invest 1994;54:247–50CrossRefPubMedGoogle Scholar
  49. Lowenfels AB, Maisonneuve P, Whitcomb DC, Lerch MM, DiMagno EP. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 2001;286:169–70CrossRefPubMedGoogle Scholar
  50. Ellis I, Lerch MM, Whitcomb DC. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology 2001;1:405–15CrossRefPubMedGoogle Scholar
  51. Ferlay J, Bray F, Pisani P, et al. Globocan 2000: Cancer incidence, mortality and prevalence worldwide, Version 1.0. IARC CancerBase No. 5. Lyons: IARC Press; 2001Google Scholar
  52. Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP, Whitcomb DC, Hruban RH, Brentnall TA, Lynch HT, Canto MI. Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 2007;56(10):1460–9CrossRefPubMedGoogle Scholar
  53. Ariyama J, Suyama M, Satoh K, et al. Imaging of small pancreatic ductal adenocarcinoma. Pancreas 1998;16:396–401CrossRefPubMedGoogle Scholar
  54. Egawa S, Takeda K, Fukuyama S, et al. Clinicopathological aspects of small pancreatic cancer. Pancreas 2004;28:235–40CrossRefPubMedGoogle Scholar
  55. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200–10CrossRefPubMedGoogle Scholar
  56. Kim JE, Lee KT, Lee JK, et al. Clinical usefulness of carbohydrate antigen CA 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol 2004;19:182–6CrossRefPubMedGoogle Scholar
  57. Malesci A, Montorsi M, Mariani A, et al. Clinical utility of the serum CA 19-9 test for diagnosing pancreatic carcinoma in symptomatic patients: a prospective study. Pancreas 1992;7:497–502PubMedGoogle Scholar
  58. Brand R. The diagnosis of pancreatic cancer. Cancer J 2001;7:287–97PubMedGoogle Scholar
  59. American society of clinical oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncology 2003;21:2397–406Google Scholar
  60. Axilbund JE, Brune KA, Canto MI, et al. Patient perspective on the value of genetic counseling for familial pancreatic cancer. Hered. Cancer Clin. Pract. 2005;3:115–22PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • M. Kraft
    • 1
  • P. Simon
    • 1
  • A. Aghdassi
    • 1
  • C. D. Heidecke
    • 1
  • G. Sauter
    • 1
  • J.-P. Kühn
    • 1
  • F. U. Weiss
    • 1
  • M. M. Lerch
    • 1
  • J. Mayerle
    • 1
  1. 1.Departments of Medicine A, Surgery and RadiologyErnst-Moritz-Arndt Universität GreifswaldGreifswaldGermany

Personalised recommendations