Gastroenterology
Volume 137, Issue 5 , Pages 1661-1668.e2 , November 2009

Lanreotide Reduces the Volume of Polycystic Liver: A Randomized, Double-Blind, Placebo-Controlled Trial

  • Loes van Keimpema

      Affiliations

    • Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • ,
  • Frederik Nevens

      Affiliations

    • Department of Hepatology, University Hospital Leuven, Leuven
  • ,
  • Ragna Vanslembrouck

      Affiliations

    • Department of Radiology, University Hospital Leuven, Leuven, Belgium
  • ,
  • Martijn G.H. van Oijen

      Affiliations

    • Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • ,
  • Aswin L. Hoffmann

      Affiliations

    • Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen
  • ,
  • Helena M. Dekker

      Affiliations

    • Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  • ,
  • Robert A. de Man

      Affiliations

    • Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands
  • ,
  • Joost P.H. Drenth

      Affiliations

    • Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • Corresponding Author InformationReprint requests Address requests for reprints to: Joost P. H. Drenth, MD, PhD, Professor of Molecular Gastroenterology and Hepatology, Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, P. O. Box 9101, code 455, 6500 HB Nijmegen, The Netherlands. fax: (31) 24 354 0103

Received 19 April 2009 ,Accepted 10 July 2009.

References 

  1. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369:1287–1301
  2. Bae KT, Zhu F, Chapman AB, et al. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol. 2006;1:64–69
  3. Fick GM, Gabow PA. Natural history of autosomal dominant polycystic kidney disease. Annu Rev Med. 1994;45:23–29
  4. Everson GT, Taylor MR, Doctor RB. Polycystic disease of the liver. Hepatology. 2004;40:774–782
  5. Davila S, Furu L, Gharavi AG, et al. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet. 2004;36:575–577
  6. Drenth JP, te Morsche RH, Smink R, et al. Germ-line mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet. 2003;33:345–347
  7. Gabow PA, Johnson AM, Kaehny WD, et al. Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. Hepatology. 1990;11:1033–1037
  8. Grantham JJ, Torres VE, Chapman AB, et al. Volume progression in polycystic kidney disease. N Engl J Med. 2006;354:2122–2130
  9. Everson GT, Scherzinger A, Berger-Leff N, et al. Polycystic liver disease: quantitation of parenchymal and cyst volumes from computed tomography images and clinical correlates of hepatic cysts. Hepatology. 1988;8:1627–1634
  10. Hoevenaren IA, Wester R, Schrier RW, et al. Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease. Liver Int. 2008;28:264–270
  11. Qian Q, Li A, King BF, et al. Clinical profile of autosomal dominant polycystic liver disease. Hepatology. 2003;37:164–171
  12. Arnold HL, Harrison SA. New advances in evaluation and management of patients with polycystic liver disease. Am J Gastroenterol. 2005;100:2569–2582
  13. van Keimpema L, de Koning DB, Strijk SP, et al. Aspiration-sclerotherapy results in effective control of liver volume in patients with liver cysts. Dig Dis Sci. 2008;53:2251–2257
  14. van Keimpema L, Ruurda JP, Ernst MF, et al. Laparoscopic fenestration of liver cysts in polycystic liver disease results in a median volume reduction of 12.5%. J Gastrointest Surg. 2008;12:477–482
  15. Lazaridis KN, Strazzabosco M, Larusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology. 2004;127:1565–1577
  16. Everson GT, Emmett M, Brown WR, et al. Functional similarities of hepatic cystic and biliary epithelium: studies of fluid constituents and in vivo secretion in response to secretin. Hepatology. 1990;11:557–565
  17. Gong AY, Tietz PS, Muff MA, et al. Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes. Am J Physiol Cell Physiol. 2003;284:C1205–C1214
  18. Banales JM, Masyuk TV, Bogert PS, et al. Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease. Am J Pathol. 2008;173:1637–1646
  19. Banales JM, Masyuk TV, Gradilone SA, et al. The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). Hepatology. 2009;49:160–174
  20. Alvaro D, Gigliozzi A, Attili AF. Regulation and deregulation of cholangiocyte proliferation. J Hepatol. 2000;33:333–340
  21. Masyuk TV, Masyuk AI, Torres VE, et al. Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology. 2007;132:1104–1116
  22. van Keimpema L, de Man RA, Drenth JP. Somatostatin analogues reduce liver volume in polycystic liver disease. Gut. 2008;57:1338–1339
  23. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet. 2001;357:1191–1194
  24. Bovenschen HJ, Janssen MJ, van Oijen MG, et al. Evaluation of a gastrointestinal symptoms questionnaire. Dig Dis Sci. 2006;51:1509–1515
  25. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36) (I. Conceptual framework and item selection). Med Care. 1992;30:473–483
  26. Barbanoj M, Antonijoan R, Morte A, et al. Pharmacokinetics of the somatostatin analog lanreotide in patients with severe chronic renal insufficiency. Clin Pharmacol Ther. 1999;66:485–491
  27. Ruggenenti P, Remuzzi A, Ondei P, et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int. 2005;68:206–216
  28. Belibi FA, Reif G, Wallace DP, et al. Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int. 2004;66:964–973
  29. Astruc B, Marbach P, Bouterfa H, et al. Long-acting octreotide and prolonged-release lanreotide formulations have different pharmacokinetic profiles. J Clin Pharmacol. 2005;45:836–844
  30. Lamberts SW, van der Lely AJ, de Herder WW, et al. Octreotide. N Engl J Med. 1996;334:246–254
  31. Ben-Shlomo A, Melmed S. Somatostatin agonists for treatment of acromegaly. Mol Cell Endocrinol. 2008;286:192–198
  32. Croxtall JD, Scott LJ. Lanreotide autogel: a review of its use in the management of acromegaly. Drugs. 2008;68:711–723
  33. Debono M, Hon LQ, Bax N, et al. Gluteal nodules in patients with metastatic midgut carcinoid disease treated with depot somatostatin analogs. J Clin Endocrinol Metab. 2008;93:1860–1864
  34. Fiamingo P, Tedeschi U, Veroux M, et al. Laparoscopic treatment of simple hepatic cysts and polycystic liver disease. Surg Endosc. 2003;17:623–626
  35. Gigot JF, Jadoul P, Que F, et al. Adult polycystic liver disease: is fenestration the most adequate operation for long-term management?. Ann Surg. 1997;225:286–294
  36. Konstadoulakis MM, Gomatos IP, Albanopoulos K, et al. Laparoscopic fenestration for the treatment of patients with severe adult polycystic liver disease. Am J Surg. 2005;189:71–75
  37. Robinson TN, Stiegmann GV, Everson GT. Laparoscopic palliation of polycystic liver disease. Surg Endosc. 2005;19:130–132

 To view this article's video abstract, go to the AGA's YouTube Channel.

 Conflicts of interest The authors disclose the following: Robert A. de Man: consulting and lecture fees and grant support from Gilead Sciences, consulting fees and grant support from Bristol–Myers Squibb, consulting fees from Novartis, and lecture fees from UCB. Joost P. H. Drenth: grant/research support from Roche. The remaining authors disclose no conflicts.

 Funding Supported by Ipsen, Boulogne Billancourt, France, and a ZON-MW VIDI research grant (J.P.H.D.).

PII: S0016-5085(09)01377-8

doi: 10.1053/j.gastro.2009.07.052

Gastroenterology
Volume 137, Issue 5 , Pages 1661-1668.e2 , November 2009