1. A Prof Of Colorectal Surgery
Colorectal polyposis
Prof/ Walid ELshazly
A Prof Of Colorectal Surgery

2. Colorectal polyps
Visible protrusion above the surface of the surrounding normal large bowel mucosa

3. Classification of colorectal polyps
Histological classification
Polyp type
Malignant potential
Non-neoplastic
Hyperplastic No
Hamartomatous
(juvenile, Peutz-Jeghers)
Lymphoid
Inflammatory
Neoplastic (adenoma)
Tubular adenoma
(0-25% villous tissue)
Yes
Tubulovillous adenoma
(25-75% villous tissue)
Villous adenoma
(75-100% villous tissue)

4. Hyperplastic polyps Majority of non-neoplastic polyps
Prevalence rates of 20-34% (autopsy and screening colonoscopy studies)
Predominantly located in the distal colon and rectum
Generally small (<0.5cm) in size

5. Classification of colorectal polyps
Histological classification
Polyp type
Malignant potential
Non-neoplastic
Hyperplastic No
Hamartomatous
(juvenile, Peutz-Jeghers)
Lymphoid
Inflammatory
Neoplastic (adenoma)
Tubular adenoma
(0-25% villous tissue)
Yes
Tubulovillous adenoma
(25-75% villous tissue)
Villous adenoma
(75-100% villous tissue)

6. Hamartomatous polyposis syndromes
Juvenile polyps
Peutz-Jeghers polyps
Cronkhite-Canada syndrome

7. Juvenile polyposis Presence of 10 juvenile polyps in the GI tract
Incidence: 1 in 100,000 persons
Autosomal dominant
Mutation of SMAD4 gene on chromosome 18

8. Juvenile polyposis
Developmental malformations affecting the glands and lamina propria
Commonly occur in children under 5 years old in the rectum.
In adult called retention polyp.

9. Juvenile polyposis Colon cancer risk 50%
Risk of gastric, duodenal, and pancreatic cancers

10. Peutz-Jeghers syndrome
Incidence: 1 in 200,000 persons
Autosomal dominant
Mutations of the STK11 gene on chromosome 19
Characterized by perioral pigmentations and hamartomatous polyps throughout the GI tract
GI and non-GI cancers are common
Site of polyps
Frequency
Stomach
38%
Small bowel
78%
Colon
42%
Rectum
28%

11. Peutz-Jeghers syndrome

12. Cancer risk in P-J syndrome
GI cancers
Cancer risks
Colon
39%
Pancreatic
36%
Stomach
29%
Small bowel
13%
Esophagus
0.5%
Non-GI cancers
Breast
54%
Ovarian
21%
Uterine 9%
Sex cord tumour with annular tubules (SCTAT)
20% become malignant
Sertoli cell tumour
10-20% become malignant
Lung
15%

13. Cronkhite-Canada syndrome
Gastrointestinal hamartomatous polyposis that lead to
Diarrhea,
Weight loss and
Abdominal pain
Extra-intestinal manifestations
Alopecia,
Cutaneous hyperpigmentation,
Onycho-dystrophy

14. Cronkhite-Canada syndrome
Five-year mortality rates as high as 55 percent have been reported with most deaths due to
gastrointestinal bleeding,
sepsis, and
congestive heart failure.
Treatment has included nutritional support, corticosteroids, acid suppression, and antibiotics

15. Classification of colorectal polyps
Histological classification
Polyp type
Malignant potential
Non-neoplastic
Hyperplastic No
Hamartomatous
(juvenile, Peutz-Jeghers)
Lymphoid
Inflammatory
Neoplastic (adenoma)
Tubular adenoma
(0-25% villous tissue)
Yes
Tubulovillous adenoma
(25-75% villous tissue)
Villous adenoma
(75-100% villous tissue)

16. Lymphoid polyps
Mucosal nodularity in representing lymphoid hyperplasia

17. Classification of colorectal polyps
Histological classification
Polyp type
Malignant potential
Non-neoplastic
Hyperplastic No
Hamartomatous
(juvenile, Peutz-Jeghers)
Lymphoid
Inflammatory
Neoplastic (adenoma)
Tubular adenoma
(0-25% villous tissue)
Yes
Tubulovillous adenoma
(25-75% villous tissue)
Villous adenoma
(75-100% villous tissue)

18. Inflammatory polyps/ pseudopolyps
These lesions develop as by-products of the ulcers that penetrate into the submucosa, leaving islands of adjacent regenerative mucosa.
Although most common in ulcerative colitis, inflammatory polyps may also be seen in Crohn's disease, ischemia, and other ulcerative conditions of the colon.

19. Inflammatory polyps/ pseudopolyps

20. Classification of colorectal polyps
Histological classification
Polyp type
Malignant potential
Non-neoplastic
Hyperplastic No
Hamartomatous
(juvenile, Peutz-Jeghers)
Lymphoid
Inflammatory
Neoplastic (adenoma)
Tubular adenoma
(0-25% villous tissue)
Yes
Tubulovillous adenoma
(25-75% villous tissue)
Villous adenoma
(75-100% villous tissue)

21. Adenomas – facts and figures
70% of all colorectal polyps
Increase with age (33% of population by 50yr, and in 50% by 70yr)
70% located in the left colon
70% are solitary (30% synchronous)
70% are small (<1cm in size)
7% have severe dysplasia, 3-5% have invasive cancer

22. Adenoma-carcinoma sequence
CRC
10 years
Regardless of aetiology, most CRC arise from adenomas

23. Factors determining risk of malignant transformation within adenomas
High risk
Low risk
Large size ( >1.5cm)
Small size ( <1cm)
Sessile or flat
Pedunculated
Severe dysplasia
Mild dysplasia
Villous architecture
Tubular architecture
Polyposis syndrome (multiple polyps)
Single polyp

24. Percent of adenomas containing invasive cancer by size and histology

25. Malignant colorectal polyp
Polyp that contains invasive cancer
Malignant cells that have invaded through the mucularis mucosa into the submucosa mm

26. Familial adenomatous polyposis (FAP)
1% of all CRC
Present in about 1 in 8000 births
Autosomal dominant with near 100% penetrance

27. FAP
>100 adenomas
Patients develop adenomas by the mean age of 16 years, and CRC by 39 years
Adenomas form early, but it takes years to develop CRC from adenomas
Disease of abnormal tumour initiation

28. Molecular genetics of FAP
Caused by mutations of APC gene (tumour suppressor gene) on chromosome 5q21
Encodes for a protein, which functions in cell adhesion and signal transduction
Mutations will result in truncated protein and affect cell growth

29. APC as gatekeeper gene adenoma-carcinoma sequence
Loeb 1991

30. Mechanisms of Carcinogenesis in FAP

31. Genotype vs. phenotype Affected part of gene Clinical Presentation
Extracolonic manifestations
Cell adhesion and structural molecules

32. Extracolonic manifestations
Congenital hypertrophy of retinal pigmented epithelium (CHRPE)
Osteomas, desmoid tumours, epidermoid cysts (Gardner’s syndrome)
CNS malignancies including medulloblastoma and glioblastoma (Turcot’s syndrome)
Duodenal, hepatobiliary-pancreatic, thyroid tumours
CHRPE

33. Gardner’s syndrome Desmoid Chest fibroma Mandibular osteoma
Skull osteoma

34. Attenuated FAP (AFAP) Variant of FAP <100 adenomas
Late age-of-onset (adenomas at 44; CRC at 56)
Proximal distribution of adenomas
*Colonoscopy for surveillance
*Infrequent involvement of the rectum supports the role of total colectomy and IRA

35. Cancer risks in FAP Cancer Cancer risks Colon Near 100%
Duodenal or periampullary
5-10%
Pancreatic
About 2%
Thyroid
Gastric
About 0.5%
CNS, usually cerebellar medulloblastoma (Turcot's syndrome)
<1%
Hepatoblastoma
1.6% of children <5 years of age

36. Protein truncation test
Diagnosis of FAP
Endoscopy
Genetic tests
Mutation
Protein truncation test
DNA sequencing

37. Screening of FAP Genetic screening of family members for APC mutations
Annual flexible sigmoidoscopy beginning at age until age 40, then every 3-5 years
*If polyposis is present, colectomy should be considered
Upper GIT Endoscopy every 1-3 years is also recommended to evaluate for upper GI adenomas

38. Hereditary nonpolyposis colorectal cancer (HNPCC)
Dr. A. S. Warthin and the first HNPCC pedigree, ‘the family G’ 1895
Dr. Henry Lynch first described the term ‘cancer family syndrome’ in 1966 (later renamed as Lynch syndrome and HNPCC)

39. HNPCC 2-5% of all CRC Autosomal dominant 70-80% penetrance
It takes only 3-5 years to develop CRC from adenomas
Accelerated progression

40. HNPCC: Lynch syndromes
Lynch syndrome I
Lynch syndrome II
Early onset of CRC (40-45 years)
Features of Lynch Syndrome I + extracolonic malignancies
Predominantly proximal to the splenic flexure (60-70%)
*Gastric, small bowel, hepatobiliary, endometrial, ovarian, ureteral and renal tumours
Increase frequency of synchronous and metachronous lesions (33%)

41. HNPCC related extracolonic tumors
Endometrial cancer is the most common extracolonic malignancy

42. Diagnosis: Amsterdam criteria 1
Due to lack of phenotypic markers like polyps
Diagnosis is based on family history of CRC only
One member less than 50 years of age
Two involved generations
Three family members affected, one of whom is a first-degree relative of the other two

43. Diagnosis: Amsterdam criteria 2
Same as Amsterdam 1 but includes all HNPCC related tumors

44. Molecular genetics of HNPCC
HNPCC is caused by mutations of
DNA mismatch repair (MMR) genes
Survey DNA for replication errors

45. Molecular genetics of HNPCC
Mutations of these MMR genes will result in replication errors during DNA synthesis (microsatellite instability) leading to acceleration of genetic mutations
HNPCC patients develop adenomas at the same rate as the general population
Once these adenomas develop, however, defective DNA repair ensues and mismatches accumulates
Thus, it takes only 3-5 years to develop CRC from adenomas

46. Molecular genetics of HNPCC

47. Screening of HNPCC Colonoscopy every 2 years starting at ages 20-25 or
5 years younger than the earliest diagnosis of CRC
whichever is earlier until 40yr , and then annually
Flexible sigmoidoscopy is not acceptable, due to the proximal location of tumours
Transvaginal US and endometrial aspiration annually starting at ages years are also recommended

48. Management of colorectal polyps Factors Affecting
Location: colon or rectum
Number: solitary or multiple
Morphology: pedunculated or sessile
Histology: benign or malignant

49. Management of colorectal polyps Excision
Pedunculated
Colonoscopic polypectomy usually possible (Snaring)

50. Management of colorectal polyps Excision
Sessile
Colonoscopic polypectomy if possible
(larger polyps may require piecemeal removal)
5-8 snaring excision
> 8 removal of affected segment segmental colectomy
Endoscopic removable not possible  operative removal
Colon: colectomy

51. Management of colorectal polyps Excision
Sessile
Colon: colectomy
Rectum: staged with EUS or MRI
Benign / Early malignant (T1No) : Transanal local excision or TEMS (may need further radical surgery)
Other malignant : radical excision (APR /anterior resection)

52. Management of colorectal polyps Definitive Mx (histology)
Benign
Surveillance
colonoscopy
Malignant
Depends on histological characteristics
Radical Surgery

53. Surveillance after polypectomy Benign polyps
Characteristics of polyps
Next FU colonoscopy
small rectal hyperplasic polyps (=average risk)
10 years
one or two small (<1cm) tubular adenomas
5-10 years
3 to 10 adenomas, or adenoma ≥ 1cm, or villous features, or high-grade dysplasia
3 years
>10 adenomas
<3 years
sessile adenomas removed piecemeal
2-6 months
Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society (2006)

54. Malignant Polyp Factors determining need of radical surgery
Histology
Poorly differentiated
Margin <2mm
Stalk invasion
Lymphovascular invasion
Increase risk of recurrence and LN 2o

55. Timing of surgery in FAP
Clinical presentation
Timing of surgery
Asymptomatic patient with modest number of small adenomas
Able to wait for a few years for surgery, as long as colonoscopic surveillance is performed yearly
Symptomatic patient with large number of adenomas
Early surgery
Suspicious of CRC
Very early/urgent surgery

56. Standard surgical treatment
Restorative proctocolectomy with ileal pouch-anal anastomosis
Suitable for most patients with FAP

57. TPC IPIAA

58. IPIAA

59. Total colectomy Ileorectal anastmosis

60. Other surgical options
Total colectomy with ileorectal anastomosis (IRA)
Proctocolectomy with ileostomy
low rectal cancers
poor sphincters
Desmoid tumors
Attenuated FAP

61. Medical treatment of FAP?
Sulindac (NSAID) and celecoxib (COX-2 inhibitor) shown to control and reduce the number of colorectal adenomas in FAP
Not definitive treatment
Temporizing treatment (eg when surgery needs to be delayed)
May control pouch and rectal polyposis after initial prophylactic surgery

62. Surgical treatment of HNPCC
Total colectomy with ileorectal anastomosis
Restorative proctocolectomy with ileal pouch-anal anastomosis
Segmental colectomy not recommended because of high rate of metachronous CRC
TAHBSO for endometrial cancer

63. Thank you