Idiopathic Pancreatitis and Cystic Fibrosis

For citation: Gubergritz N.B., Monogarova N.E., Belyaeva N.V., Fomenko P.G., Burka A.A., Zeinalova A.A. Idiopathic Pancreatitis and Cystic Fibrosis. Doctor.Ru. 2019; 8(163): 18–27. (in Russian) DOI: 10.31550/1727-2378-2019-163-8-18-27
23 august 2019

Objective: to describe the current information on idiopathic pacreatitis (IP) and cystic fibrosis (CF).

Key Points. The article contains information about IP, and the diagnostic algorithm to find out the root cause of the disease is described. The aetiology, nosotropic mechanisms of CF occurrence, known CFTR gene mutations affecting the course of the disease, as well as the principles of enzyme replacement therapy for patients with CF are discussed. The data from evidence-based medicine are presented which confirm the efficiency and safety of pancreatin-containing enzyme drugs for the management of exocrine pancreatic insufficiency.

Conclusion. The heavy growth of the medical science brings about new information on the causes and initiation of genetic disorders, and gives new knowledge on possible therapeutic and gene management, improving the quality and length of life of patients, including patients with CF.

Contribution: Gubergritz, N.B. — article idea and reviewing; Monogarova, N.E. — description of extrapulmonary cystic fibrosis manifestations; Belyaeva, N.V. — analysis of causes of idiopathic pancreatitis; Fomenko, P.G. — literary review and article compilation; Burka, A.A. — analysis of gene mutations causing cystic fibrosis; Zeinalova, A.A. — description of pulmonary cystic fibrosis manifestations.

Conflict of interes: The authors declare that they do not have any conflict of interests.

N.B. Gubergritz — M. Gorky Donetsk National Medical University; 27 Privokzalnaya Str., Liman, Donetsk Region, Ukraine 84404. ORCID: http://orcid.org/0000-0003-3655-9554. E-mail: profnbg@ukr.net

N.E. Monogarova — M. Gorky Donetsk National Medical University; 16 Ilyich Avenue, Donetsk, Ukraine 83003. E-mail: fakultetskaya-terapia@dnmu.ru

N.V. Belyaeva — M. Gorky Donetsk National Medical University; 27 Privokzalnaya Str., Liman, Donetsk Region, Ukraine 84404. E-mail: 771984@gmail.com

P.G. Fomenko — M. Gorky Donetsk National Medical University; 16 Ilyich Avenue, Donetsk, Ukraine 83003. E-mail: fomenko_pg@mail.ru

A.A. Burka — Municipal Children’s Hospital No. 38 of the Moscow Department of Health; 2 10-letiya Oktyabrya Str., Moscow, Russian Federation 117036. E-mail: burka@dr.com

A.A. Zeinalova — M. Gorky Donetsk National Medical University; 16 Ilyich Avenue, Donetsk, Ukraine 83003. E-mail: fakultetskaya-terapia@dnmu.ru

23 August 22:28
  1. Lee J.K., Enns R. Review of idiopathic pancreatitis. World J. Gastroenterol. 2007; 13(47): 6296–313. DOI: 10.3748/wjg.v13.i47.6296
  2. Coyle W.J., Pineau B.C., Tarnasky P., Knapple W.L., Aabakken L., Hoffman B.J. et al. Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddi manometry and endoscopic ultrasound. Endoscopy. 2002; 34(8): 617–23. DOI: 10.1055/s-2002-33245
  3. Thomson H.J. Acute pancreatitis in north and north-east Scotland. J. R. Coll. Surg. Edinb. 1985; 30(2): 104–11.
  4. Ammann R.W. Alcohol- and non-alcohol induced pancreatitis: clinical aspects. NY: McGraw-Hill; 1992: 253–72.
  5. Thorsgaard Pedersen N., Nyboe Andersen B., Pedersen G., Worning H. Chronic pancreatitis in Copenhagen. A retrospective study of 64 consecutive patients. Scand. J. Gastroenterol. 1982; 17(7): 925–31. DOI: 10.3109/00365528209181116
  6. Hayakawa T., Kondo T., Shibata T., Sugimoto Y., Kitagawa M. Chronic alcoholism and evolution of pain in chronic pancreatitis. Dig. Dis. Sci. 1989; 34(1): 33–8. DOI: 10.1007/bf01536151
  7. Robles-Díaz G., Vargas F., Uscanga L., Fernández-del Castillo C. Chronic pancreatitis in Mexico City. Pancreas. 1990; 5(4): 479–83. DOI: 10.1097/00006676-199007000-00017
  8. Etemad B., Whitcomb D.C. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001; 120(3): 682–707. DOI: 10.1053/gast.2001.22586
  9. Layer P., Yamamoto H., Kalthoff L., Clain J.E., Bakken L.J., DiMagno E.P. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology. 1994; 107(5): 1481–7. DOI: 10.1016/0016-5085(94)90553-3
  10. Keller J., Layer P. Idiopathic chronic pancreatitis. Best Pract. Res. Clin. Gastroenterol. 2008; 22(1): 105–13. DOI: 10.1016/j.bpg.2007.10.006
  11. Ardengh J.C., Malheiros C.A., Rahal F., Pereira V., Ganc A.J. Microlithiasis of the gallbladder: role of endoscopic ultrasonography in patients with idiopathic acute pancreatitis. Rev. Assoc. Med. Bras. 2010; 56(1): 27–31. DOI: 10.1590/s0104-42302010000100011
  12. Hewison M. Vitamin D and immune function: an overview. Proc. Nutrit. Soc. 2012; 71(1): 50–61. DOI: 10.1017/S0029665111001650
  13. Kaw M., Brodmerkel G.J. Jr. ERCP, biliary crystal analysis and sphincter of Oddi manometry in idiopathic recurrent pancreatitis. Gastrointest. Endosc. 2002; 55(2): 157–62. DOI: 10.1067/mge.2002.118944
  14. Blanco G., Gesuale С., Varanese М., Monteleone G., Paoluzi O. Idiopathic acute pancreatitis: a review on etiology and diagnostic work-up. Clin. J. Gastroenterol. 2019. URL: https://doi.org/10.1007/s12328-019-00987-7 (дата обращения — 15.09.2019).
  15. Carrier Testing for Cystic Fibrosis. Cystic Fibrosis Foundation. 2019. URL:: https://www.cff.org/What-is-CF/Testing/Carrier-Testing-for-Cystic-Fibrosis (дата обращения — 15.09.2019).
  16. Cystic Fibrosis Foundation. Patient registry highlights. 2019. URL: https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2017-Cystic-Fibrosis-Foundation-Patient-Registry-Highlights.pdf (дата обращения — 15.09.2019).
  17. Madácsy T., Pallagi P., Maleth J. Cystic fibrosis of the pancreas: the role of CFTR channel in the regulation of intracellular Ca2+ signaling and mitochondrial function in the exocrine pancreas. Front. Physiol. 2018; 9: 1585. DOI: 10.3389/fphys.2018.01585
  18. ROO MO “Pomoshch' bol'nym mukovistsidozom”. URL: https://cfmo.ru/ (data obrashcheniya — 15.09.2019). (in Russian)
  19. Cystic Fibrosis Foundation. CFTR structure and regulation. 2019. URL: http://www.cftr.info/about-cf/genetics-and-cell-biology-of-cftr/cftr-structure-and-regulation/ (дата обращения — 15.09.2019).
  20. Linsdell P. Functional architecture of the CFTR chloride channel. Mol. Membr. Biol. 2014; 31(1): 1–16. DOI: 10.3109/09687688.2013.868055
  21. Quon B.S., Rowe S.M. New and emerging targeted therapies for cystic fibrosis. BMJ. 2016; 352: i859. DOI: 10.1136/bmj.i859
  22. Veit G., Avramescu R.G., Chiang A.N., Houck S.A., Cai Z., Peters K.W. et al. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol. Biol. Cell. 2016; 27(3): 424–33. DOI: 10.1091/mbc.E14-04-0935
  23. Pranke I., Golec A., Hinzpeter A., Edelman A., Sermet-Gaudelus I. Emerging therapeutic approaches for cystic fibrosis. From gene editing to personalized medicine. Front. Pharmacol. 2019; 10: 121. DOI: 10.3389/fphar.2019.00121
  24. Gibson-Corley K.N., Meyerholz D.K., Engelhardt J.F. Pancreatic pathophysiology in cystic fibrosis. J. Pathol. 2016; 238(2): 311–20. DOI: 10.1002/path.4634
  25. Kopelman H., Corey M., Gaskin K., Durie P., Weizman Z., Forstner G. Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas. Gastroenterology. 1988; 95(2): 349–55. DOI: 10.1016/0016-5085(88)90490-8
  26. Kopelman H., Durie P., Gaskin K., Weizman Z., Forstner G. Pancreatic fluid secretion and protein hyperconcentration in cystic fibrosis. N. Engl. J. Med. 1985; 312(6): 329–34. DOI: 10.1056/NEJM198502073120601
  27. Wilschanski M., Novak I. The cystic fibrosis of exocrine pancreas. Cold Spring Harb. Perspect. Med. 2013; 3(5): a009746. DOI: 10.1101/cshperspect.a009746
  28. Meyerholz D.K., Stoltz D.A., Pezzulo A.A., Welsh M.J. Pathology of gastrointestinal organs in a porcine model of cystic fibrosis. Am. J. Pathol. 2010; 176(3): 1377–89. DOI: 10.2353/ajpath.2010.090849
  29. Olivier A.K., Gibson-Corley K.N., Meyerholz D.K. Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology. Am. J. Physiol. Gastrointest. Liv. Physiol. 2015; 308(6): G459–71. DOI: 10.1152/ajpgi.00146.2014
  30. Tucker J.A., Spock A., Spicer S.S., Shelburne J.D., Bradford W. Inspissation of pancreatic zymogen material in cystic fibrosis. Ultrastruct. Pathol. 2003; 27(5): 323–35.
  31. Augarten A., Ben Tov A., Madgar I., Barak A., Akons H., Laufer J. et al. The changing face of the exocrine pancreas in cystic fibrosis: the correlation between pancreatic status, pancreatitis and cystic fibrosis genotype. Eur. J. Gastroenterol. Hepatol. 2008; 20(3): 164–8. DOI: 10.1097/MEG.0b013e3282f36d04
  32. Hegyi P., Rakonczay Z. Jr. The role of pancreatic ducts in the pathogenesis of acute pancreatitis. Pancreatology. 2015; (4 suppl.): S13–7. DOI: 10.1016/j.pan.2015.03.010
  33. DiMagno M.J., Lee S.H., Hao Y., Zhou S.Y., McKenna B.J., Owyang C. A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice. Gastroenterology. 2005; 129(2): 665–81. DOI: 10.1016/j.gastro.2005.05.059
  34. DiMagno M.J., Lee S.H., Owyang C., Zhou S.Y. Inhibition of acinar apoptosis occurs during acute pancreatitis in the human homologue DeltaF508 cystic fibrosis mouse. Am. J. Physiol. Gastrointest. Liver Physiol. 2010; 299(2): G400–12. DOI: 10.1152/ajpgi.00061.2010
  35. Ko S.B., Azuma S., Yoshikawa T., Yamamoto A., Kyokane K., Ko M.S. et al. Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. Front. Physiol. 2012; 3: 415. DOI: 10.3389/fphys.2012.00415
  36. Barrio R. Management of endocrine disease: cystic fibrosis-related diabetes: novel pathogenic insights opening new therapeutic avenues. Eur. J. Endocrinol. 2015; 172(4): R131–41. DOI: 10.1530/EJE-14-0644
  37. Moran A., Dunitz J., Nathan B., Saeed A., Holme B., Thomas W. Cystic fibrosis-related diabetes: current trends in prevalence, incidence, and mortality. Diabetes Care. 2009; 32(9): 1626–31. DOI: 10.2337/dc09-0586
  38. Ode K.L., Moran A. New insights into cystic fibrosis-related diabetes in children. Lancet Diabetes Endocrinol. 2013; 1(1): 52–8. DOI: 10.1016/S2213-8587(13)70015-9
  39. Lanng S., Thorsteinsson B., Erichsen G., Nerup J., Koch C. Glucose tolerance in cystic fibrosis. Arch. Dis. Child. 1991; 66(5): 612–16. DOI: 10.1136/adc.66.5.612
  40. Lavie M., Fisher D., Vilozni D., Forschmidt R., Sarouk I., Kanety H. et al. Glucose intolerance in cystic fibrosis as a determinant of pulmonary function and clinical status. Diabetes Res. Clin. Pract. 2015; 110(3): 276–84. DOI: 10.1016/j.diabres.2015.10.007
  41. Nathan B.M., Laguna T., Moran A. Recent trends in cystic fibrosis-related diabetes. Curr. Opin. Endocrinol. Diabetes Obes. 2010; 17(4): 335–41. DOI: 10.1097/MED.0b013e32833a780d
  42. Chamnan P., Shine B.S., Haworth C.S., Bilton D., Adler A.I. Diabetes as a determinant of mortality in cystic fibrosis. Diabetes Care. 2010; 33(2): 311–16. DOI: 10.2337/dc09-1215
  43. Milla C.E., Warwick W.J., Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am. J. Respir. Crit. Care Med. 2000; 162(3 Pt1): 891–5. DOI: 10.1164/ajrccm.162.3.9904075
  44. Moran A., Hardin D., Rodman D., Allen H.F., Beall R.J., Borowitz D. et al. Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res. Clin. Pract. 1999; 45(1): 61–73. DOI: 10.1016/s0168-8227(99)00058-3
  45. Galli F., Battistoni A., Gambari R., Pompella A., Bragonzi A., Pilolli F. et al. Oxidative stress and antioxidant therapy in cystic fibrosis. Biochim. Biophys. Acta. 2012; 1822(5): 690–713. DOI: 10.1016/j.bbadis.2011.12.012
  46. Stecenko A.A., Moran A. Update on cystic fibrosis-related diabetes. Curr. Opin. Pulm. Med. 2010; 16(6): 611–15. DOI: 10.1097/MCP.0b013e32833e8700
  47. Arif S., Moore F., Marks K., Bouckenooghe T., Dayan C.M., Planas R. et al. Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated β-cell death. Diabetes. 2011; 60(8): 2112–19. DOI: 10.2337/db10-1643
  48. Yaochite J.N., Caliari-Oliveira C., Davanso M.R., Carlos D., Malmegrim K.C., Cardoso C.R. et al. Dynamic changes of the Th17/Tc17 and regulatory T cell populations interfere in the experimental autoimmune diabetes pathogenesis. Immunobiology. 2013; 218(3): 338–52. DOI: 10.1016/j.imbio.2012.05.010
  49. Guo J.H., Chen H., Ruan Y.C., Zhang X.L., Zhang X.H., Fok K.L. et al. Glucose-induced electrical activities and insulin secretion in pancreatic islet beta-cells are modulated by CFTR. Nat. Commun. 2014; 5: 4420. DOI: 10.1038/ncomms5420
  50. Mansour G. Cystic fibrosis. Hospital Medicine. URL: https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/cystic-fibrosis-3/ (дата обращения — 15.09.2019).
  51. Castellani C., Duff А., Bell S., Heijerman H., Munck A., Ratjen F. et al. ECFS best practice guidelines: the 2018 revision. J. Cyst. Fibros. 2018; 17(2): 153–78. DOI: 10.1016/j.jcf.2018.02.006
  52. Borowitz D., Stevens C., Brettman L.R., Campion M., Wilschanski M., Thompson H. et al. Liprotamase long-term safety and support of nutritional status in pancreatic-insufficient cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 2012; 54(2): 248–57. DOI: 10.1097/MPG.0b013e31823315d1
  53. Graff G.R., Maguiness K., McNamara J., Morton R., Boyd D., Beckmann K. et al. Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study. Clin. Ther. 2010; 32(1): 89–103. DOI: 10.1016/j.clinthera.2010.01.012
  54. Trapnell B.C., Maguiness K., Graff G.R., Boyd D., Beckmann K., Caras S. Efficacy and safety of Creon 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis. J. Cyst. Fibros. 2009; 8(6): 370–7. DOI: 10.1016/j.jcf.2009.08.008
  55. Stern R.C., Eisenberg J.D., Wagener J.S., Ahrens R., Rock M., doPico G. et al. A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency. Am. J. Gastroenterol. 2000; 95(8): 1932–8. DOI: 10.1111/j.1572-0241.2000.02244.x
  56. Trapnell B.C., Strausbaugh S.D., Woo M.S., Tong S.Y., Silber S.A., Mulberg A.E. et al. Efficacy and safety of PANCREAZE® for treatment of exocrine pancreatic insufficiency due to cystic fibrosis. J. Cyst. Fibros. 2011; 10(5): 350–6. DOI: 10.1016/j.jcf.2011.04.005
  57. Layer P., Kashirskaya N., Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J. Gastroenterol. 2019; 25(20): 2430–41. DOI: 10.3748/wjg.v25.i20.2430
  58. Somaraju U.R., Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst. Rev. 2016; 11: CD008227. DOI: 10.1002/14651858.CD008227.pub3

Похожие статьи


1 October 10:52
A New Issue of Doctor.Ru Internal Medicine, Vol. 21, No. 6 (2022), Published

Find original articles and reviews covering various aspects of сardiology, gastroenterology, internal medicine and the interview with Professor Alexey Nikolaevich Kalyagin

7 July 17:16
A New Issue of Doctor.Ru Neurology Psychiatry, Vol. 21, No. 4 (2022), Published

Find original articles and reviews covering various aspects of neurology, psychiatry and the interview with Professor Alexander Vitalievich Amelin

12 May 11:25
A New Issue of Doctor.Ru Pediatrics, Vol. 21 No. 3 (2022), Published

See the original papers, reviews and clinical cases in headings Pulmonology, Rheumatology, Endocrinology, Neurology, Cross-disciplinary approach and Interview with with an Honoured Scientist of the Sakha (Yakutia) Republic Professor Maria Vasilievna Khandy

4 May 10:02
A New Issue of Doctor.Ru Internal Medicine, Vol. 21, No. 2 (2022), Published

Find original articles and reviews covering various aspects of gastroenterology, internal medicine, rheumatology, endocrinology, special section of postgraduate training and the interview with Professor Dmitry Alexeevich Sychev

18 March 00:00
A New Issue of Doctor.Ru Gynecology, Vol. 21 No. 1 (2022), Published

Find original articles and reviews covering various aspects of obstetrics, perinatology and gynecology, and the interview with Feldberg Dov, MD

All news