Skip to main content
SpringerLink
Log in

Lynch Syndrome: Management of the Colon, What Operation?

  • Chapter
  • First Online:
Management of Hereditary Colorectal Cancer

Abstract

Lynch syndrome (LS) is the most common of the hereditary colorectal cancer (CRC) syndromes, accounting for 3–6% of CRC. Individuals with LS also have significantly increased risks for endometrial, ovarian, gastric, and other cancers, including high rates of synchronous and metachronous CRC diagnosed at an earlier age (LS accounts for 8% of CRC diagnosed before the age of 50) because of an accelerated carcinogenetic process, from normal mucosa to adenoma to carcinoma, requiring early (beginning at age 20–25) and more frequent (every 1–2 years) screening/surveillance colonoscopy. The early age of diagnosis combined with the propensity for the development of metachronous CRC and other organ cancers has forced a re-evaluation of surgical dogma regarding segmental resection as the routine, conventional operation performed for CRC presenting in LS patients. Previous systematic reviews of segmental versus extended colectomy in LS patients, while acknowledging limited data, concluded that segmental resection is the standard of care. However, given the increased interest and published literature on the subject, including several studies revealing a statistically significant increase in metachronous CRC in LS patients who underwent segmental versus extended colectomy as the initial operation for CRC (especially in the past decade), there is enough accumulated evidence to now make a rational, informed decision on the best operation for LS patients who develop CRC. Table 9.2 provides striking evidence from 5 continents to support extended or subtotal/total colectomy as the operation of choice for LS patients who develop CRC. The final decision, including length of large bowel remnant left, may be tailored to limit potential postoperative bowel dysfunction such as urgency, frequency, and fecal incontinence. Extended colectomy (subtotal/total abdominal colectomy) has increased support in the literature and is preferred for younger patients, under the age of 60–65 years, with good sphincter function. All patients will still require close endoscopic observation of their residual large bowel remnant and surveillance of other at-risk organs, regardless of the extent of colectomy.

The only other organs to consider for prophylactic resection are the reproductive organs of women, as accurate screening for reproductive organ cancer is questionable and prophylactic surgical removal reliably eliminates the risk of cancer. Therefore, prophylactic removal of the reproductive organs is recommended for women who have completed childbearing or who do not wish to preserve fertility, regardless of age.

Current evidence supports extended colectomy for the young, healthy, and continent patient combined with prophylactic reproductive organ removal for women who have completed or are not considering childbearing. The decision regarding extended or subtotal/total colectomy along with prophylactic reproductive organ removal for women should be discussed and resolved in concert with other surgical specialists (gynecologic oncologists), together with the LS patient who faces the uncertainty and anxiety associated with this lifelong genetic predisposition to CRC and other organ cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Giardello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society task force on colorectal cancer. Dis Colon Rectum. 2014;57:1025–48.

    Article  Google Scholar 

  2. Edelstein DL, Axilbund JE, Baxter M, et al. Rapid development of colorectal neoplasia in patients with Lynch syndrome. Clin Gastroenterol Hepatol. 2011;9:340–3.

    Article  PubMed  Google Scholar 

  3. Jass JR, Stewart SM, Stewart J, et al. Herditary nonpolyposis colorectal cancer- morphologics, genes and mutations. Mutat Res. 1994;310:125–33.

    Article  CAS  PubMed  Google Scholar 

  4. De Jong AE, Morreau H, Van Puijenbroek M, et al. The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology. 2004;126:42–8.

    Article  CAS  PubMed  Google Scholar 

  5. Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378:2081–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jenkins MA, Hayashi S, O’Shea AM, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population based study. Gastroenterology. 2007;133:48–56.

    Article  CAS  PubMed  Google Scholar 

  7. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;115(2):223–62.

    Article  Google Scholar 

  8. Vasen HFA, Blanco I, Aktan-Collan K, Gropie JP, Alonso A, Aretz S, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013;62(6):812–23.

    Article  CAS  PubMed  Google Scholar 

  9. Barrow E, Hill J, Evans DG. Cancer risk in Lynch syndrome. Familial Cancer. 2013;12(2):229–40.

    Article  CAS  PubMed  Google Scholar 

  10. Senter L, Clendenning M, Sotamaa K, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135:419–28.

    Article  CAS  PubMed  Google Scholar 

  11. Bonadona V, Bonaiti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304–10.

    Article  CAS  PubMed  Google Scholar 

  12. https://seer.cancer.gov/statfacts/html/corp.html.

  13. Hendriks YM, Wagner A, Morreau H, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004;127:17–25.

    Article  CAS  PubMed  Google Scholar 

  14. Church JM. Prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer. Ann Med. 1996;28:479–82.

    Article  CAS  PubMed  Google Scholar 

  15. Rodriguez-Bigas MA. Prophylactic colectomy for gene carriers in hereditary nonpolyposis colorectal cancer. Has the time come? Cancer. 1996;78:199–201.

    Article  CAS  PubMed  Google Scholar 

  16. Vasen HF, Wijnen JT, Menko FH, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996;110:1020–7.

    Article  CAS  PubMed  Google Scholar 

  17. Syngal S, Weeks JC, Schrag D, Garber JE, Kuntz KM. Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations. Ann Intern Med. 1998;129:787–96.

    Article  CAS  PubMed  Google Scholar 

  18. de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, Menk FH, Taal BG, Kleibeuker JH, Vasen HF. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum. 2002;45:1588–94.

    Article  Google Scholar 

  19. Natarajan N, Watson P, Silva-Lopez E, Lynch HT. Comparison of extended colectomy and limited resection in patients with Lynch syndrome. Dis Colon Rectum. 2010;53:77–82.

    Article  PubMed  Google Scholar 

  20. Baucom RB, Wise PE. Endoscopic and surgical management of hereditary nonpolyposis colorectal cancer. Clin Colon Rectal Surg. 2012;25:90–6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Heneghan HM, Martin ST, Winter DC. Segmental vs extended colectomy in the management of hereditary nonpolyposis colorectal cancer: a systematic review and meta-analysis. Color Dis. 2014;17:382–9.

    Article  Google Scholar 

  22. Scaife CL, Rodriguez-Bigas MA. Lynch syndrome: implications for the surgeon. Clin Colorectal Cancer. 2003;3(2):92–8.

    Article  PubMed  Google Scholar 

  23. Schmeler KM, Lynch HT, Chen LM, Munsell MF, Soliman PT, Clark MB, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354(3):261–9.

    Article  CAS  PubMed  Google Scholar 

  24. Kwon JS, Sun CC, Peterson SK, White KG, Daniels MS, Boyd-Rogers SG, et al. Cost-effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome. Cancer. 2008;113(2):326–35.

    Article  PubMed  Google Scholar 

  25. Goodfellow PJ, Buttin BM, Herzog TJ, et al. Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci U S A. 2003;100:5908–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wagner A, Hendriks Y, Meijers-Hejboer EJ, et al. Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J Med Genet. 2001;38:318–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dove-Edwin I, Boks D, Goff S, et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer. 2002;94:1708–12.

    Article  PubMed  Google Scholar 

  28. Church J, Simmang C. Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Dis Colon Rectum. 2003;46:1001–12.

    Article  PubMed  Google Scholar 

  29. Watson P, Butzow R, Lynch HT, et al. The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol. 2001;82:223–8.

    Article  CAS  PubMed  Google Scholar 

  30. Mecklin J-P, Jarvinen H. Treatment and follow-up strategies in hereditary nonpolyposis colorectal carcinoma. Dis Colon Rectum. 1993;36:927–9.

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez-Bigas MA, Vasen HFA, Pekka-Mecklin J, Myrhoj T, Rozen P, Bertario L, Jarvinen H, Jass JR, Kunitomo K, Nomizu T, Driscoll DL. Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. Ann Surg. 1997;225:202–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Van Dalen R, Church J, McGannon E, Fay S, Burke C, Clark B. Patterns of surgery in patients belonging to Amsterdam-positive families. Dis Colon Rectum. 2003;46:617–20.

    Article  PubMed  Google Scholar 

  33. Kalady MF, McGannon E, Vogel JD, Manilich E, Fazio VW, Church JM. Risk of colorectal adenoma and carcinoma after colectomy for colorectal cancer in patients meeting Amsterdam criteria. Ann Surg. 2010;252:507–13.

    PubMed  Google Scholar 

  34. Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, Baron JA, Giles GG, Leggett BA, Winship I, Lipton L, Young GP, Young JP, Lodge CJ, Southey MC, Newcomb PA, Le Marchand L, Haile RW, Lindor NM, Gallinger S, Hopper JL, Jenkins MA. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers- the advantage of more extensive colon surgery. Gut. 2011;60:950–7.

    Article  PubMed  Google Scholar 

  35. Stupart DA, Goldberg PA, Baigrie RJ, Algar U, Ramesar R. Surgery for colonic cancer in HNPCC: total vs segmental colectomy. Color Dis. 2011;13:1395–9.

    Article  CAS  Google Scholar 

  36. Cirillo L, Urso EDL, Parrinello G, Pucciarelli S, Moneghini D, Agostini M, Nitti D, Nasciembeni R. High risk of rectal cancer and of metachronous colorectal cancer in probands of families fulfilling the Amsterdam criteria. Ann Surg. 2013;257:900–4.

    Article  PubMed  Google Scholar 

  37. Aronson M, Holter S, Semotiuk K, Winter L, Pollett A, Gallinger S, Cohen Z, Gryfe R. DNA mismatch repair status predicts need for future colorectal surgery for metachronous neoplasms in young individuals undergoing colorectal cancer resection. Dis Colon Rectum. 2015;58:645–52.

    Article  PubMed  Google Scholar 

  38. Renkonen-Sinisalo L, Seppala TT, Jarvinen HJ, Mecklin J-P. Subtotal colectomy for colon cancer reduces the need for subsequent surgery in Lynch Syndrome. Dis Colon Rectum. 2017;60:792–9.

    Google Scholar 

  39. Kim TJ, Kim ER, Hong SN, Kim Y-H, Huh JW, Park YA, Cho YB, Yun SH, Kim HC, Lee WY, Kim K, Kim K, Chang DK. Survival outcome and risk of metachronous colorectal cancer after surgery in Lynch syndrome. Ann Surg Oncol. 2017;24:1085–92.

    Article  PubMed  Google Scholar 

  40. Anele C, Adegbola S, Askari A, Rajendra A, Clark SK, Latchford A, Faiz OD. Risk of metachronous colorectal cancer following colectomy in Lynch syndrome: a systematic review and meta-analysis. Color Dis. 2017;19(6):528–36.

    Article  CAS  Google Scholar 

  41. You YN, Chua HK, Nelson H, Hassan I, Barnes SA, Harrington J. Segmental vs. extended colectomy: measurable differences in morbidity, function, and quality of life. Dis Colon Rectum. 2008;51:1036–43.

    Article  PubMed  Google Scholar 

  42. Haanstra JF, de Vos tot Nederveen Cappel WH, Gopie JP, Vecht J, Vanhoutvin SALW, Cats A, van der Zaag-Loonen HJ, Langers AMJ, Bergmann JHW, van de Meeberg PC, Dekker E, Kleibeuker JH, Vasen HFA, Nagengast FM, van Duijvendijk P. Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy. Dis Colon Rectum. 2012;55:653–9.

    Article  PubMed  Google Scholar 

  43. Lynch AC, Church JM, Lavery IC. Quality of life following partial or total colectomy: relevance to HNPCC. Dis Colon Rectum. 2003;46:A55.

    Google Scholar 

  44. Kalady MF. Expert commentary on the diagnosis and management of Lynch syndrome. Dis Colon Rectum. 2019;62:406–7.

    Article  PubMed  Google Scholar 

  45. Warrier SK, Trainer AH, Lynch AC, Mitchell C, Hiscock R, Sawyer S, Boussioutas A, Heriot AG. Preoperative diagnosis of Lynch syndrome with DNA mismatch repair immunohistochemistry on a diagnostic biopsy. Dis Colon Rectum. 2011;54:1480–7.

    Article  CAS  PubMed  Google Scholar 

  46. de Vos tet Nederveen Cappel WH, Buskens E, van Duijvendijk P, Cats A, Menko FH, Griffioen G, Slors JF, Nagengast FM, Kleibeuker JH, Vasen HFA. Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut. 2003;52:1752–5.

    Article  Google Scholar 

  47. Vasen HF, Moslein G, Alonso A, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 2007;44:353–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lin KM, Shashidharan M, Ternent CA, Thorson AG, Blatchford GJ, Christensen MA, Lanspa SJ, Lemon SJ, Watson P, Lynch HT. Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population. Dis Colon Rectum. 1998;41:428–33.

    Article  CAS  PubMed  Google Scholar 

  49. Moller P, Seppala T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rodland EA, Thamaratnam K, de Vo stet Nederveen Cappel WH, Hill J, Wijnen J, Jenkins M, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer J-P, Pylvanainen K, Genuardi M, Mecklin J-P, Moslein G, Sampson JR, Capella G. Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut. 2017;66:1657–64.

    Article  CAS  PubMed  Google Scholar 

  50. Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, Lynch P, Burke W, Press N. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA. 2006;296:1507–17.

    Article  CAS  PubMed  Google Scholar 

  51. Plaschke J, Engel C, Kruger S, et al. Lower incidence of colorectal cancer and later age of disease onset in 27 families with pathogenic MSH 6 germline mutations compared with families with MLH 1 or MSH 2 mutations. J Clin Oncol. 2004;22:4486–94.

    Article  CAS  PubMed  Google Scholar 

  52. Evans DG, Gaarenstroom KN, Stirling D, et al. Screening for familial ovarian cancer: poor survival of BRCA 1/2 related cancers. J Med Genet. 2009;46:593–7.

    Article  CAS  PubMed  Google Scholar 

  53. Church J. Prevention of metachronous colorectal cancer in patients with Lynch syndrome. Dis Colon Rectum. 2010;53:3–4.

    Article  PubMed  Google Scholar 

  54. Maeda T, Cannom RR, Beart RW Jr, Etzioni DA. Decision model of segmental compared with total abdominal colectomy for colon cancer in hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2010;28:1175–80.

    Article  PubMed  Google Scholar 

  55. Moller P, Seppala TT, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons RH, Jeffries J, Vasen HFA, Burn J, Nakken S, Hovig E, Rodland EA, Tharmaratnam K, deVos tet Nederveen Cappel WH, Hill J, Wijnen JT, Jenkins MA, Green K, Lalloo F, Sunde L, Mints M, Beretario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Valentin MD, Frayling IM, Plazzer J-P, Pylvanainen K, Genuardi M, Mecklin J-P, Moeslein G, Sampson JR, Capella G. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the prospective Lynch syndrome database. Gut. 2018;67:1306–16.

    Article  PubMed  Google Scholar 

Download references

Conflicts of Interest

Ms. Hampel: Ms. Hampel has performed collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc. (included free and discounted genetic testing for research subjects). Ms. Hampel is on the scientific advisory board for InVitae Genetics and Genome Medical. Ms. Hampel has stock in Genome Medical.

Author information

Authors and Affiliations

  1. Colon & Rectal Surgery Section, Banner MD Anderson Cancer Center, Phoenix, AZ, USA

    William C. Cirocco

  2. Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

    Heather Hampel

Authors
  1. William C. Cirocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather Hampel
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Gastrointestinal Surgery, University of North Carolina, Chapel Hill, NC, USA

    Jose G. Guillem

  2. Department of Surgery, Mike O’Callaghan Federal Medical Center, Las Vegas, NV, USA

    Garrett Friedman

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cirocco, W.C., Hampel, H. (2020). Lynch Syndrome: Management of the Colon, What Operation?. In: Guillem, J., Friedman, G. (eds) Management of Hereditary Colorectal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-26234-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-26234-1_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-26233-4

  • Online ISBN: 978-3-030-26234-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation