1 / 50

Polyposis Syndromes of the Colon Current Management, Controversies and Future Direction

Polyposis Syndromes of the Colon Current Management, Controversies and Future Direction. Eric J. Dozois, MD Division of Colon & Rectal Surgery Mayo Clinic Rochester, Minnesota. Polyposis Schema. Inherited Polyposis Syndromes. Adenomatous Syndrome : Familial adenomatous polyposis

Download Presentation

Polyposis Syndromes of the Colon Current Management, Controversies and Future Direction

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Polyposis Syndromes of the ColonCurrent Management, Controversies and Future Direction Eric J. Dozois, MD Division of Colon & Rectal Surgery Mayo Clinic Rochester, Minnesota

  2. Polyposis Schema

  3. Inherited Polyposis Syndromes • Adenomatous Syndrome: • Familial adenomatous polyposis • mutY human homologue (MYH) • Hamartomatous Syndromes: • Peutz-Jeghers • Juvenile • Cowden’s • Ruvalcaba-Myhre-Smith

  4. Non-Inherited Polyposis Syndromes • Cronkhite-Canada Syndrome • Hyperplastic Polyposis • Lipomatous Polyposis • Nodular Lymphoid Hyperplasia • Inflammatory Polyposis • Lymphomatous Polyposis

  5. Polyposis Syndromes • Adenomas and hamartomas • Low incidence, Autosomal dominant • Colorectal Malignancies • Extra-colonic malignancies • Controversies in management • Need for Genetic Counseling

  6. Inherited Polyposis Syndromes • Elucidation of underlying gene mutations • Understanding of cell biology and molecular mechanisms associated with cancer pathogenesis • Allows refined categorization, phenotype and cancer risk

  7. Hamartomatous Syndromes

  8. Overgrowth of lamina propria, submucosa & muscular tissue

  9. Hamartomatous Syndromes CS PJS JP Incidence 1:200,000 1:120,000 1:100,000 Gene PTEN STK11 BMPR1A/SMAD4 Risk of CRC 10% Elevated 50% Extracolonic CA Yes Yes Yes

  10. Juvenile Polyposis • Sporadic Juvenile polyps (2% Peds) • Hamartomas throughout GI tract • Rectal bleeding, anemia, intussusception • Capsule endoscopy is emerging tool for dx • *CRC risk 9% - 68%, mean age 34yrs • Extracolonic - Stomach, duodenal, • Genetic etiology in 50% remains elusive *Howe et al. Ann Surg Oncol 1998;5:751

  11. JP – Surgical Management • Colectomy with IRA or IPAA: - Symptomatic bleeding - > 20 polyps - Dysplasia • Endoscopic Polypectomy: - < 20 polyps

  12. Peutz-Jeghers Sydrome • 50-100 Hamartomas: - sb colon rectum stomach • Mucocutaneous melanin pigmentation

  13. Peutz-Jeghers Syndrome • Hamartoma-adenoma-carcinoma sequence* • Intestinal & Extraintestinal cancers* • Ovarian sex-chord tumors, breast, pancreatic • Surgery – complications, malignancy *Wang et al. J Pathol 1999:188:9

  14. PJS - Clinical Presentation • Abdominal cramping • Intussusception • Anemia

  15. PJS - Management • Intussusception & Occult bleeding • Multiple laparotomies • Enteroscopy during laparotomy:* • Polyp clearance to reduce recurrent laparotomies • 4 of 25 patients required surgery in 14yrs *Phillips et al. Dis Colon Rectum 2003;46:48

  16. Cowden Syndrome • Hamartomas of GI, skin, mucus membranes • Hallmark – facial trichilemmomas (wart-like) • GI CA risk – approx. 10% • Extra GI CA – *breast, *thyroid, GYN, retina • Surveillance and prevention of associated malignancies • Surgery for complications

  17. Ruvalcaba-Myhre-Smith Syndrome • Described in 1980* • Gastrointestinal hamartomas • Macrocephaly, mental retardation, lipid storage myopathies, thyroiditis • Hyperpigmentation of penile skin • Alterations in PTEN gene • No CRC or extra-colonic cancer risk Ruvalcaba et al. Clin Genetics 1985;18:413

  18. Adenomatous Syndromes

  19. MYH-Associated Polyposis(mutY human homologue) • Base excision repair gene • Autosomal-recessive – family history • May account for the 7% - 8% of FAP phenotypes in whom no APC germ-line mutation has been identified* • Absence of strong multigenerational family history of polyposis • Difficult to distinguish from FAP, AFAP *Al-Tassen et al. Nat Genet 2002;30:227

  20. MYH-Associated Polyposis(mutY human homologue) • Present between ages 45 – 60 yrs • Average number of adenomas = 16 (100s) • Carriers of bi-allelic and mono-allelic MYH mutations have a significantly increased risk of CRC* *Croitoru et al. J Natl Cancer Inst 2004;96:1631

  21. Familial Adenomatous Polyposis • First reported in literature in 1841 • Autosomal dominant, APC mutation • 825 different germ-line mutations • Hundreds to thousands of polyps • 100% risk of colon cancer • Multiple extra-colonic manifestations

  22. Genotype-Phenotype Correlation

  23. Familial Adenomatous Polyposis • Prophylactic Surgery • Timing of Surgery • Type of Surgery • Choice of Procedure • Choice of Technique

  24. FAP – Type of Surgery • Colectomy with ileorectostomy • Proctocolectomy with IPAA • Anoproctocolectomy, ileostomy • Open or laparoscopic

  25. FAP – Choice of Procedure • Cancer Prophylaxis • Technical feasibility • Complications • Functional Outcome - QOL

  26. Management Controversy Ileal Pouch-Anal Anastomosis vs. Ileo-Rectostomy

  27. Quality of Life after IPAA & IRAFamilial Polyposis • Time: 1981 - 1998 • IPAA (152 pts), IRA (32 pts) • No Difference in: • Early and late complications • Functional Results Hassan et al. Dis Colon Rectum 2005;48:2032

  28. Comparison of SF-36 Physical and Mental Health Summary Scores p = 0.4 Physical Health Mental Health*

  29. Functional Outcome after IRA Institution N Mean # BMs Continence QOL (24 hrs) Day/Night Cleveland 51 4 82/NA 93 Mayo 21 4 83/89 NA St. Marks 62 3 72/NA NA St. Antoine 23 3 98/96 NA Toronto 60 6 90/87 80

  30. Functional Outcome after IPAA Institution N Mean # BMs Continence QOL (24 hrs) Day/Night Cleveland 62 5 75/74 95 Mayo 187 4 84/80 98 St. Marks 37 5 60/NA NA St. Antoine 171 4 98/96 NA Toronto 50 6 75/51 93

  31. Rectal Cancer Rates After IRA Study No. Pts F/U Rectal CA Rate (yrs) (%) Bulow 659 11 7 Bertario 200 7 24 De Cosse 294 25 13 Sarre 133 20 12 Jarvinen 100 20 25 Iwama 320 20 37

  32. FAP - Rectal Cancer • Independent Risk Factors:* • Age at colectomy (>40 yrs) • Length of time after IRA (12%/20yrs) • Number of polyps (> 1000) • Length of distal remnant (ileal-sigmoid) • Presence of colorectal malignancy • Genotype *Bjork et al. Dis Colon Rectum 2000;43:1719

  33. FAP - Poor Results From IRA • Limited surgical options • Treatment and follow-up not routinely performed in specialized centers • Poor understanding of genotype-phenoptype correlation • Inadequate surveillance programs • Focus on “ease” of operation and functional outcome

  34. Rectal Cancer Rates After IRAFunction of Available Surgical Options Timeline No. Pts F/U Cancer Rate (yrs) (%) Pre-pouch era 62 15 13 (1950-1982) Pouch era 135 5 0 (1983-1990) Church et al. DCR 2003;46:1175-1181

  35. Genotype–Phenotype Correlation • Cancer Risk & Severity of Polyposis1: • > 1000 polyps = high risk • < 1000 polyps = 50% less risk • Severity of Polyposis - APC Mutation2: • Codon 1309 - leads to severe disease • Codons 3,4 – attenuated FAP 1Debinski et al. Gastro 1996;110:1028 2Church. Semin Colon Rectum Surg 1998;9:49

  36. Molecular Genetic Tests as a Guide to Surgical Management of Familial Adenomatous PolyposisVasen et al. Lancet 1996;348:433-35 “Might information on the location of the mutation be useful in determining the most appropriate surgical treatment?”

  37. Molecular genetic tests as guide to surgical management of FAP • APC mutation beyond codon 1275 Rectal CA Risk after IRA Risk of Rectal Excision Vasen et al. Lancet 1996;348:433-35

  38. Genotype and Phenotype Factors for Rectal Cancer After IRA • 1955 – 1997 • 371 patients had IRA • Median follow-up 81 mos. • Multivariate analysis: • Sex, Age • No. rectal polyps, Colon CA • APC mutation Bertario et al. Ann Surg 2000;231:538

  39. Results – Risk of Rectal CA • 10 years 7.7% • 15 years 13.1% • 20 years 23.0% Bertario et al. Ann Surg 2000;231:538

  40. Results – Risk of Rectal CA • Univariate Analysis: • Colon cancer at initial operation • More than 30 polyps in the rectum • Mutation between codon1250 – 1464 • Multivariate Analysis: • Colon CA • Codons 1250 - 1464 9-Fold Increase Risk of Rectal Cancer Bertario et al. Ann Surg 2000;231:538

  41. Arguments No Longer ValidIRA over IPAA • Functional results significantly better • Quality of life significantly better • Surgical complications are higher • Surveillance prevents cancer • Cancer can be cured if occurs • Can always do IPAA if CA develops

  42. Ileal Pouch Neoplasia • Lifetime risk of neoplasia unknown • Adenomas form in 35% - 57% • Risk of developing adenomas: 5yrs (7%) 10yrs (35%) 15yrs (75%) • 13 Cancers reported: • Mucosectomy in 8 pts • CRC, multiple polyps Parc et al. Ann Surg 2001;233:360 Groves et al. Dis Colon Rectum 2005;48:816

  43. FAP – Indication for IPAA • Age at time of surgery > 40yrs • > 1000 colonic polyps • > 20 Rectal Polyps • CRC at time of surgery • APC mutation - codon1250-1450 • Unreliable surveillance

  44. FAP – IRA Acceptable? • Less than 1000 polyps in colon • Less than 20 polyps in the rectum • Attenuated FAP • APC mutation before 1250 or after 1450

  45. ConclusionsPolyposis Syndromes of the Colon • Represent a wide spectrum of rare diseases with predisposition for both CRC and extra-colonic disease • A clear understanding of the differences between them ensures accurate diagnosis and proper management • Advances in molecular genetics will continue to provide even more insight to guide treatment

More Related