Familial Cancer

, Volume 10, Issue 3, pp 455–461

Gastrointestinal polyps and cancer in Peutz-Jeghers syndrome: clinical aspects

Article

Abstract

The two main problems in the management of the gastrointestinal tract in patients with Peutz-Jeghers syndrome (PJS) are the long term cancer risk and managing polyp related complications, such as intussusception and bleeding. In this article we will focus mainly on the clinical management of these problems. We will highlight some of the controversies regarding gastrointestinal PJS polyps, cancer development and cancer risk. We will review the available literature, particularly focusing on clinical data, to provide insights into these controversies. We describe guidelines for the surveillance and management of gastrointestinal polyps in PJS and review the data behind current recommendations.

Keywords

Surveillance Cancer Peutz-Jeghers syndrome Polyp 

References

  1. 1.
    Connor J (1895) Aesculapian society of London. Lancet 2:1169Google Scholar
  2. 2.
    Bruwer A, Bargen JA, Kierland RR (1954) Surface pigmentation and generalized intestinal polyposis; (Peutz-Jeghers syndrome). Proc Staff Meet Mayo Clin 29:168–171PubMedGoogle Scholar
  3. 3.
    Peutz J (1921) Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied ny peculiar pigmentations of skin and mucous membrane. Nederl maandschr v geneesk 10:134–146Google Scholar
  4. 4.
    Jeghers HMV, Katz K (1949) Generalised intestinal polyposis and melanin spots of the oral mucosa, lips and digits. N Engl J Med 241:993–1005PubMedCrossRefGoogle Scholar
  5. 5.
    Utsunomiya J, Gocho H, Miyanaga T, Hamaguchi E, Kashimure A (1975) Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J 136:71–82PubMedGoogle Scholar
  6. 6.
    Giardiello FM, Trimbath JD (2006) Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 4:408–415PubMedCrossRefGoogle Scholar
  7. 7.
    Boudeau J, Sapkota G, Alessi DR (2003) LKB1, a protein kinase regulating cell proliferation and polarity. FEBS Lett 546:159–165PubMedCrossRefGoogle Scholar
  8. 8.
    Shepherd NA, Bussey HJ, Jass JR (1987) Epithelial misplacement in Peutz-Jeghers polyps. A diagnostic pitfall. Am J Surg Pathol 11:743–749PubMedCrossRefGoogle Scholar
  9. 9.
    McGarrity TJ, Kulin HE, Zaino RJ (2000) Peutz-Jeghers syndrome. Am J Gastroenterol 95:596–604PubMedCrossRefGoogle Scholar
  10. 10.
    Vogel T, Schumacher V, Saleh A, Trojan J, Moslein G (2000) Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe. Int J Colorectal Dis 15:118–123PubMedCrossRefGoogle Scholar
  11. 11.
    Finan MC, Ray MK (1989) Gastrointestinal polyposis syndromes. Dermatol Clin 7:419–434PubMedGoogle Scholar
  12. 12.
    Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD (1987) Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 316:1511–1514PubMedCrossRefGoogle Scholar
  13. 13.
    Spigelman AD, Murday V, Phillips RK (1989) Cancer and the Peutz-Jeghers syndrome. Gut 30:1588–1590PubMedCrossRefGoogle Scholar
  14. 14.
    Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, Ahlquist DA, Podratz KC, Pittelkow M, Hartmann LC (1998) Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 128:896–899PubMedGoogle Scholar
  15. 15.
    Linos DA, Dozois RR, Dahlin DC, Bartholomew LG (1981) Does Peutz-Jeghers syndrome predispose to gastrointestinal malignancy? A later look. Arch Surg 116:1182–1184PubMedGoogle Scholar
  16. 16.
    Schumacher V, Vogel T, Leube B, Driemel C, Goecke T, Moslein G, Royer-Pokora B (2005) STK11 genotyping and cancer risk in Peutz-Jeghers syndrome. J Med Genet 42:428–435PubMedCrossRefGoogle Scholar
  17. 17.
    Choi HS, Park YJ, Youk EG, Yoon KA, Ku JL, Kim NK, Kim SM, Kim YJ, Moon DJ, Min JS, Park CJ, Bae OS, Yang DH, Jun SH, Chung ES, Jung PM, Whang Y, Park JG (2000) Clinical characteristics of Peutz-Jeghers syndrome in Korean polyposis patients. Int J Colorectal Dis 15:35–38PubMedCrossRefGoogle Scholar
  18. 18.
    Hizawa K, Iida M, Matsumoto T, Kohrogi N, Kinoshita H, Yao T, Fujishima M (1993) Cancer in Peutz-Jeghers syndrome. Cancer 72:2777–2781PubMedCrossRefGoogle Scholar
  19. 19.
    Laughlin EH (1991) Benign and malignant neoplasms in a family with Peutz-Jeghers syndrome: study of three generations. South Med J 84:1205–1209PubMedCrossRefGoogle Scholar
  20. 20.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119:1447–1453PubMedCrossRefGoogle Scholar
  21. 21.
    Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Moslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12:3209–3215PubMedCrossRefGoogle Scholar
  22. 22.
    Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, Scott RJ, Trimbath J, Giardiello FM, Gruber SB, Gille JJ, Offerhaus GJ, de Rooij FW, Wilson JH, Spigelman AD, Phillips RK, Houlston RS (2004) Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126:1788–1794PubMedCrossRefGoogle Scholar
  23. 23.
    Bosman FT (1999) Molecular pathology of colorectal cancer. Cytogenet Cell Genet 86:112–117PubMedCrossRefGoogle Scholar
  24. 24.
    Bouraoui S, Azouz H, Kechrid H, Lemaiem F, Mzabi-Regaya S (2008) Peutz-Jeghers’ syndrome with malignant development in a hamartomatous polyp: report of one case and review of the literature. Gastroenterol Clin Biol 32:250–254PubMedCrossRefGoogle Scholar
  25. 25.
    Hizawa K, Iida M, Matsumoto T, Kohrogi N, Yao T, Fujishima M (1993) Neoplastic transformation arising in Peutz-Jeghers polyposis. Dis Colon Rectum 36:953–957PubMedCrossRefGoogle Scholar
  26. 26.
    Latchford A, Neale K, Phillips RKSP, Clark S (2009) Outcomes from GI tract surveillance in Peutz-Jeghers syndrome. Abstract InSiGHTGoogle Scholar
  27. 27.
    Jansen M, de Leng WW, Baas AF, Myoshi H, Mathus-Vliegen L, Taketo MM, Clevers H, Giardiello FM, Offerhaus GJ (2006) Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis. Gut 55:1–5PubMedCrossRefGoogle Scholar
  28. 28.
    Entius MM, Keller JJ, Westerman AM, van Rees BP, van Velthuysen ML, de Goeij AF, Wilson JH, Giardiello FM, Offerhaus GJ (2001) Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. J Clin Pathol 54:126–131PubMedCrossRefGoogle Scholar
  29. 29.
    Miyaki M, Iijima T, Hosono K, Ishii R, Yasuno M, Mori T, Toi M, Hishima T, Shitara N, Tamura K, Utsunomiya J, Kobayashi N, Kuroki T, Iwama T (2000) Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome. Cancer Res 60:6311–6313PubMedGoogle Scholar
  30. 30.
    Beggs AD, Latchford AR, Vasen HFA, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bülow S, Burn J, Capella G, Colas C, Friedl W, Hes FJ, Järvinen H, Mecklin JP, Myrhøi T, Nagengast FM, Parc Y, Phillips RKS, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJW, Wijnen J, Clark SK, Hodgson SV (2010) Peutz-Jeghers Syndrome: a systematic review and recommendations for management. Gut 59:975–986PubMedCrossRefGoogle Scholar
  31. 31.
    Dunlop MG (2002) Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut 51(Suppl 5):V21–V27PubMedCrossRefGoogle Scholar
  32. 32.
    Hinds R, Philp C, Hyer W, Fell JM (2004) Complications of childhood Peutz-Jeghers syndrome: implications for pediatric screening. J Pediatr Gastroenterol Nutr 39:219–220PubMedCrossRefGoogle Scholar
  33. 33.
    Brown G, Fraser C, Schofield G, Taylor S, Bartram C, Phillips R, Saunders B (2006) Video capsule endoscopy in Peutz-Jeghers syndrome: a blinded comparison with barium follow-through for detection of small-bowel polyps. Endoscopy 38:385–390PubMedCrossRefGoogle Scholar
  34. 34.
    Mata A, Llach J, Castells A, Rovira JM, Pellise M, Gines A, Fernandez-Esparrach G, Andreu M, Bordas JM, Pique JM (2005) A prospective trial comparing wireless capsule endoscopy and barium contrast series for small-bowel surveillance in hereditary GI polyposis syndromes. Gastrointest Endosc 61:721–725PubMedCrossRefGoogle Scholar
  35. 35.
    Postgate A, Hyer W, Phillips R, Gupta A, Burling D, Bartram C, Marshall M, Taylor S, Brown G, Schofield G, Bassett P, Spray C, Fitzpatrick A, Latchford A, Fraser C (2009) Feasibility of video capsule endoscopy in the management of children with Peutz-Jeghers syndrome: a blinded comparison with barium enterography for the detection of small bowel polyps. J Pediatr Gastroenterol Nutr 49:417–423PubMedCrossRefGoogle Scholar
  36. 36.
    Kurugoglu S, Aksoy H, Kantarci F, Cetinkaya S, Mihmanli I, Korman U (2003) Radiological work-up in Peutz-Jeghers syndrome. Pediatr Radiol 33:766–771PubMedGoogle Scholar
  37. 37.
    Caspari R, von Falkenhausen M, Krautmacher C, Schild H, Heller J, Sauerbruch T (2004) Comparison of capsule endoscopy and magnetic resonance imaging for the detection of polyps of the small intestine in patients with familial adenomatous polyposis or with Peutz-Jeghers’ syndrome. Endoscopy 36:1054–1059PubMedCrossRefGoogle Scholar
  38. 38.
    Gupta A, Postgate AJ, Burling D, Ilangovan R, Marshall M, Phillips RK, Clark SK, Fraser CH (2010) A prospective study of MR enterography versus capsule endoscopy for the surveillance of adult patients with Peutz-Jeghers syndrome. AJR Am J Roentgenol 195:108–116PubMedCrossRefGoogle Scholar
  39. 39.
    Edwards DP, Khosraviani K, Stafferton R, Phillips RK (2003) Long-term results of polyp clearance by intraoperative enteroscopy in the Peutz-Jeghers syndrome. Dis Colon Rectum 46:48–50PubMedCrossRefGoogle Scholar
  40. 40.
    Oncel M, Remzi FH, Church JM, Connor JT, Fazio VW (2004) Benefits of ‘clean sweep’ in Peutz-Jeghers patients. Colorectal Dis 6:332–335PubMedCrossRefGoogle Scholar
  41. 41.
    Gao H, van Lier MG, Poley JW, Kuipers EJ, van Leerdam ME, Mensink PB (2010) Endoscopic therapy of small-bowel polyps by double-balloon enteroscopy in patients with Peutz-Jeghers syndrome. Gastrointest Endosc 71:768–773PubMedCrossRefGoogle Scholar
  42. 42.
    Kopacova M, Bures J, Ferko A, Tacheci I, Rejchrt S (2010) Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc 24:1904–1910PubMedCrossRefGoogle Scholar
  43. 43.
    Despott E, Phillips RKS, Clark S, Postgate A, Fitzpatrick A, Tripoli E, Konieczko K, Fraser C (2009) Small bowel polypectomy by double balloon enteroscopy—advancing endoscopic therapy for patients with Peutz-Jeghers syndrome. Abstract InSiGHT 2009Google Scholar
  44. 44.
    Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL (2004) Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 18:1533–1538PubMedCrossRefGoogle Scholar
  45. 45.
    Wei C, Amos CI, Zhang N, Wang X, Rashid A, Walker CL, Behringer RR, Frazier ML (2008) Suppression of Peutz-Jeghers polyposis by targeting mammalian target of rapamycin signaling. Clin Cancer Res 14:1167–1171PubMedCrossRefGoogle Scholar
  46. 46.
    McGarrity TJ, Peiffer LP, Amos CI, Frazier ML, Ward MG, Howett MK (2003) Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers syndrome. Am J Gastroenterol 98:671–678PubMedCrossRefGoogle Scholar
  47. 47.
    Udd L, Katajisto P, Rossi DJ, Lepisto A, Lahesmaa AM, Ylikorkala A, Jarvinen HJ, Ristimaki AP, Makela TP (2004) Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. Gastroenterology 127:1030–1037PubMedCrossRefGoogle Scholar
  48. 48.
    Huang X, Wullschleger S, Shpiro N, McGuire VA, Sakamoto K, Woods YL, McBurnie W, Fleming S, Alessi DR (2008) Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J 412:211–221PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of GastroenterologyDerriford HospitalPlymouthUK
  2. 2.Polyposis RegistrySt Mark’s HospitalHarrowUK

Personalised recommendations