1. Adenomatous polyposis syndromes (APS) The Familial Adenomatous Polyposis (FAP)
1.1. Consider FAP, AFP, or MAP ...
1.1.1. When colonoscopy shows what ?
1.1.1.1. Think
1.1.1.1.1. Personal history of >10 cumulative colorectal adenomas,
1.1.1.2. > 100 to 1000's of adenomas
1.1.1.2.1. Classic familial adenomatous polyposis (FAP)
1.1.1.3. 10-99 adenomas
1.1.1.3.1. AFAP
1.1.1.3.2. MUTYH-associated polyposis (MAP)
1.1.2. Family Hx
1.1.2.1. a family history of FAP, APC
1.2. Personal history of FAP-type extracolonic manifestations
1.2.1. List
1.2.1.1. duodenal/ampullary adenomas,
1.2.1.2. desmoid tumors
1.2.1.3. papillary thyroid cancer,
1.2.1.3.1. Skin and bones (epidermal cysts, osteomas)
1.2.2. congenital hypertrophy of the retinal pigment epithelium,
1.3. Surveillance and Managment
1.3.1. when do you start/ how often ?
1.3.1.1. Colon
1.3.1.1.1. q1-2 y colon exam start at age 10-12
1.3.1.2. Stomach - Duodenum
1.3.1.2.1. Page 3 10. Screening for gastric and proximal small bowel tumors should be done using upper endoscopy including duodenoscopy starting at age 25–30 years. Surveillance should be repeated every 0.5–4 years depending on Spigelman stage of duodenal polyposis: 0=4 years; I=2–3 years, II=1–3 years, III=6–12 months, and IV=surgical evaluation. Examination of the stomach should include random sampling of fundic gland polyps. Low-grade dysplasia is common in fundic gland polyps, and surgery should be reserved for high-grade dysplasia or cancer (strong recommendation, very low quality of evidence).
1.3.2. Management
1.3.2.1. If surgery is delayed longer than a year after polyps emerge, annual colonoscopy should be used for surveillance
1.4. Basics
1.4.1. CRC is inevitable in FAP unless colectomy is completed. Some stats:
1.4.1.1. 25% incidence of colon cancer in newly diagnosed FAP
1.4.1.2. by 50 years, it increased to 93%.
1.4.1.3. 41% synchronous
1.4.1.4. 84% were at or distal to the splenic flexure
1.4.1.5. In AFAP, the emergence of adenomas and cancer is delayed 10 to 20 years compared with typical FAP.
1.4.2. FAP AFAP, MAP are germline mutations that acclerate carcinogenesis
1.5. When/how to test
1.5.1. example
1.5.1.1. relatives of an individual with a KNOWN pathogenic mutation are tested for the presence or absence of that particular mutation.
1.5.1.1.1. what is the implication of a negative test?
1.5.2. example
1.5.2.1. Personal history of >10 cumulative colorectal adenomas, but no other phenotypic manifestations
1.5.2.1.1. I don' t do this. Literature?
1.5.3. what is the test
1.5.3.1. Genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analysis.
2. Raf Rizk, MD 01/07/2016
3. Fundamentals
3.1. (prep quality, reached cecum)
3.1.1. , the colon should be cleared of stool and debris to allow for visualization of lesions 5 mm or greater.
3.2. Red flag for polyp characteristics ?
3.2.1. Advanced adenoma size >= 10 mm, villous histology or HGD
4. 2015 AGA Guideline on the Diagnosis and Management of Lynch Syndrome.
4.1. Hamartomatous Polyposis Syndromes (HPS)
4.1.1. Peutz–Jeghers syndrome (PJS)
4.1.1.1. Consider PJS when ...
4.1.1.1.1. diagnosis: any one of the following:
4.1.1.1.2. 1:8000 and 1:200,000 births.
4.1.1.2. Surveillance
4.1.2. Cowden Syndrome, also known
4.1.2.1. as Bannayan Riley Ruvalcaba Syndrome (BRRS) and PTEN-Hamartoma Tumor Syndrome
4.1.3. JPS is a hamartomatous polyposis syndrome
4.1.3.1. ~40-90% lifetime risk for developing any cancer by age 70
4.1.3.1.1. ●Stomach – 29 percent
4.1.3.1.2. ●Small bowel – 13 percent
4.1.3.1.3. ●Colorectal – 39 percent
4.1.3.1.4. ●Pancreas – 11 to 36 percent
4.1.3.1.5. 80% of of malignancy in PJS is extra-intestinal
4.1.3.2. Consider JPS when ...
4.1.3.2.1. More than five juvenile polyps in the colorectum or/and
4.1.3.2.2. Multiple juvenile polyps throughout the GI-tract or/and
4.1.3.2.3. Any number of juvenile polyps with a family history of juvenile polyposis
4.1.3.3. Benign condition
4.2. Lynch syndrome (LS)
4.2.1. Evidence for accelerated colorectal adenoma–carcinoma progression in MUTYH-associated polyposis?
4.2.2. Consider LS when ...
4.2.2.1. CRC tumors show evidence of MMR deficiency
4.2.2.2. Personal Hx (patient's cumulative polyp hx or cancer hx) is positive for ...
4.2.2.3. Family hx is positive for ...
4.2.2.3.1. Amsterdam criteria I
4.2.2.3.2. Amsterdam criteria II
4.2.2.3.3. Revised Bethesda guidelines
4.2.2.3.4. CRC risk assessment tool
4.2.2.3.5. Computational models
4.2.3. When/how to test
4.2.3.1. "All newly diagnosed CRCs should be evaluated for mismatch repair (MMR) deficiency."
4.2.3.1.1. What tests?
4.2.3.1.2. Why?
4.2.4. Surveillance
4.2.4.1. List
4.2.4.1.1. Extra-colonic cancers
4.2.4.1.2. Colon or rectal cancer