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Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience

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Abstract

Background

Desmoids are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP), 70% being intra-abdominal desmoids (IAD). Since the morbidity and mortality due to desmoids is almost entirely attributable to IAD, we aimed to identify specifically risk factors predicting IAD development in FAP.

Methods

We undertook a retrospective review of our institutional database. Multivariate analysis was performed, and hazard ratios (HR) calculated for variables including female gender, 3′ APC mutation, surgical intervention for FAP (colectomy with ileo-rectal anastomosis or restorative proctocolectomy), age at surgery and family history (FH) of desmoids.

Results

Of the 558 patients analysed, 49 (9%) developed IAD; 22 (4%) diagnosed intra-operatively and 27 (5%) developing over a median post-operative period of 34 (7–120) months. 75% of IAD had developed before age 40. A 3′ APC mutation (HR 5.2, 95% CI 2.1–13.3, P = 0.001), positive FH (HR 2.5, 95% CI 1.4–4.6, P = 0.003) and female gender (HR 1.9, 95% CI 1.0–3.5, P = 0.04) were found to be predictive of IAD development. No significant difference in IAD risk was detected between the type of surgical intervention (P = 0.37) or age at surgery (P = 0.29).

Conclusions

Our analysis confirms 3′ APC mutation to be the most significant risk factor for IAD development. The independent association between positive FH and IAD risk suggests the existence of modifier genes, independent of the APC genotype–phenotype correlation. Few of these risk factors can be meaningfully modified. Delaying prophylactic surgery may be appropriate in female patients with a 3′ APC mutation and attenuated polyposis.

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References

  1. Kinzler KW, Nilbert MC, Su LK et al (1991) Identification of FAP locus genes from chromosome 5q21. Science 253:661–664

    Article  CAS  PubMed  Google Scholar 

  2. Bussey HJ (1987) Historical developments in familial polyposis coli. Semin Surg Oncol 3:67–70

    Article  CAS  PubMed  Google Scholar 

  3. Vasen HF, Moslein G, Alonso A et al (2008) Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 57:704–713

    Article  CAS  PubMed  Google Scholar 

  4. Aziz O, Athanasiou T, Fazio VW et al (2006) Meta-analysis of observational studies of ileorectal versus ileal pouch-anal anastamosis for familial adenomatous polyposis. Br J Surg 93:407–417

    Article  CAS  PubMed  Google Scholar 

  5. Heiskanen I, Luostarinen T, Jarvinen HJ (2000) Impact of screening examinations on survival in familial adenomatous polyposis. Scand J Gastroenterol 35:1284–1287

    Article  CAS  PubMed  Google Scholar 

  6. Bülow S, Bülow C, Nielsen TF et al (1995) Centralized registration, prophylactic examination, and treatment results in improved prognosis in familial adenomatous polyposis. Results from the Danish polyposis register. Scand J Gastroenterol 30:989–993

    Article  PubMed  Google Scholar 

  7. Sturt NJ, Clark SK (2006) Current ideas in desmoid tumours. Fam Cancer 5:275–285

    Article  PubMed  Google Scholar 

  8. Lofti AM, Dozois RR, Gordon H et al (1989) Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment. Int J Colorectal Dis 4:30–36

    Article  Google Scholar 

  9. Bertario L, Russo A, Sala P et al (2001) Genotype and phenotype factors as determinants of desmoid tumours in patients with familial adenomatous polyposis. Int J Cancer 95:102–107

    Article  CAS  PubMed  Google Scholar 

  10. Heinimann K, Mullhaupt B, Weber W et al (1998) Phenotypic differences in familial adenomatous polyposis based on APC germline mutation status. Gut 43:675–679

    Article  CAS  PubMed  Google Scholar 

  11. Bertario L, Presciuttini S, Sala P et al (1994) Causes of death and postsurgical survival in familial adenomatous polyposis: results from the Italian registry of familial polyposis writing committee. Semin Surg Oncol 10:225–234

    Article  CAS  PubMed  Google Scholar 

  12. Arvanitis ML, Jagelman DG, Fazio VW et al (1990) Mortality in patients with familial adenomatous polyposis. Dis Colon Rectum 33:639–642

    Article  CAS  PubMed  Google Scholar 

  13. Clark SK, Neale KF, Landgrebe JC et al (1999) Desmoid tumours complicating familial adenomatous polyposis. Br J Surg 86:1185–1189

    Article  CAS  PubMed  Google Scholar 

  14. Church JM (1995) Desmoid tumours in patients with familial adenomatous polyposis. Semin Colon Rectal Surg 6:29–32

    Google Scholar 

  15. Janinis J, Patriki M, Vini L et al (2003) The pharmacological treatment of aggressive fibromatosis: a systematic review. Ann Oncol 14:181–190

    Article  CAS  PubMed  Google Scholar 

  16. Sturt NJH, Gallagher MC, Bassett P et al (2004) Evidence for genetic predisposition to desmoid tumours in familial adenomatous polyposis independent of the germline APC mutation. Gut 53:1832–1836

    Article  CAS  PubMed  Google Scholar 

  17. Heiskanen I, Jarvinen HJ (1996) Occurrence of desmoid tumours in familial adenomatous polyposis and results of treatment. Int J Colorect Dis 11:157–162

    Article  CAS  Google Scholar 

  18. Lefevre JH, Parc Y, Kerneis S et al (2008) Risk factors for development of desmoid tumours in familial adenomatous polyposis. Br J Surg 95:1136–1139

    Article  CAS  PubMed  Google Scholar 

  19. Nieuwenhuis MH, Dees J, Wijnen J et al (2008) Desmoid tumours in a Dutch cohort of patients with familial adenomatous polyposis. Clin Gastro Hep 6:215–219

    Article  Google Scholar 

  20. Caspari R, Olschwang S, Friedl W et al (1995) Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Human Mol Genet 4:337–340

    Article  CAS  Google Scholar 

  21. Durno C, Monga N, Bapat B et al (2007) Does early colectomy increase desmoid risk in familial adenomatous polyposis? Clin Gastro Hep 5:1190–1194

    Article  Google Scholar 

  22. Friedl W, Caspari R, Sengteller M et al (2001) Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. Gut 48:515–521

    Article  CAS  PubMed  Google Scholar 

  23. Hartley JE, Church JM, Gupta S et al (2004) Significance of incidental desmoids identified during surgery for familial adenomatous polyposis. Dis Colon Rectum 47:334–340

    Article  CAS  PubMed  Google Scholar 

  24. Bus PJ, Verspaget HW, van Krieken HJM et al (1999) Treatment of mesenteric desmoids with the anti-oestrogenic Toremifene: case histories and an overview of the literature. Eur J Gastroenterol Hepatol 11:1179–1183

    Article  CAS  PubMed  Google Scholar 

  25. Hansmann A, Adolph C, Vogel T et al (2004) High dose tamoxifen and sulindac as first-line treatment for desmoid tumours. Cancer 100:612–620

    Article  CAS  PubMed  Google Scholar 

  26. Hartley JE, Church JM, Gupta S et al (2004) Significance of incidental desmoids identified during surgery for familial adenomatous polyposis. Dis Colon Rectum 47:334–340

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge Cancer Research UK for funding the St. Mark’s Hospital Polyposis Registry database and thank Muditha Samarasinghe, Jo Rawlings, Tina Isherwood and Pam Nye for maintaining the data.

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Authors and Affiliations

  1. Polyposis Registry, St. Mark’s Hospital and Imperial College, Northwick Park, Watford Road, Harrow, London, HA1 3UJ, UK

    A. Sinha, K. F. Neale, R. K. S. Phillips & S. K. Clark

  2. Royal Marsden Hospital and Imperial College, London, UK

    P. P. Tekkis

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  1. A. Sinha
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  2. P. P. Tekkis
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  3. K. F. Neale
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  4. R. K. S. Phillips
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  5. S. K. Clark
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Correspondence to S. K. Clark.

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Sinha, A., Tekkis, P.P., Neale, K.F. et al. Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience. Tech Coloproctol 14, 141–146 (2010). https://doi.org/10.1007/s10151-010-0573-4

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  • DOI: https://doi.org/10.1007/s10151-010-0573-4

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