Sabiston polyp

Question 1

The molecular events in CRC

Answer 1

include early APC (adenomatous polyposis coli) gene mutations, subsequent activating mutations in the oncogene KRAS, as well as mutations resulting in inactivation of the tumor suppressor gene TP53

Question 2

CpG Island Methylator Phenotype

Answer 2

• involves a mutation of the BRAF gene resulting in inhibition of normal colon cell apoptosis.
• development of hyperplastic or sessile serrated adenomas or polyps > prone to epigenetic silencing of genes within “CpG islands”
• The hMLH1 gene (one of the DNA repair genes involved in Lynch syndrome) is one of the best characterized genes that undergoes this type of epigenetic silencing by CpG hypermethylation.
• result in a microsatellite instable-high (MSI-H) cancer if there is further gene mutation or methylation.
• most cancers arising from sessile serrated adenomas will have a MSI-H phenotype and are often located in the right colon.

Question 3

Microsatellite Instability Mutator Pathway

Answer 3

• These genes include mutL homologue 1 (MLH1), MLH3, mutS homologue 2 (MSH2), MSH3, MSH6, or PMS1 homologue 2 (PMS2)
• These associated cancers will be MSI-H
• often characterized by location in the proximal colon, large local tumor, typical absence of metastatic disease, and poor tumor differentiation.
• When this occurs in patients with sporadic cancer, they are often elderly; when this occurs in the hereditary form (i.e., Lynch syndrome), patients are often younger (<50 years old)
• Testing for the presence of a BRAF mutation will aid in differentiating sporadic (BRAF mutation present) from inherited forms

Question 4

Epithelial-Mesenchymal Transition

Answer 4

• Epithelial-mesenchymal transition is the process whereby cells lose their epithelial functional and morphologic functional features and gain a “mesenchymal” phenotype.
• Through this process, locally growing cancer cells gain the ability to invade through the bowel wall and spread to regional lymph nodes.
• Once cancer cells reach a metastatic site, they must reverse this process and undergo mesenchymal-to-epithelial transition.

Question 5

Polyp

Answer 5

endoscopic appearance into pedunculated (with a stalk) sessile (flat)

histologic appearance
(adenomas, hamartomas, inflammatory, serrated, etc.).

Question 6

Nonneoplastic Polyps

Answer 6

• Hyperplastic polyps :
  > small sessile lesions, usually less than 5 mm, consisting of elongated colonic crypts with a papillary configuration of epithelial cells without atypia.
  > They are common colonic polyps, frequently grossly indistinguishable from small adenomas.
• Inflammatory polyps (pseudopolyps) are found in regions of healing inflammation.
  > may be large, mimicking a neoplasm.
  > found in diseased colons otherwise at risk for cancer (e.g., in IBD)
• Hamartomas
  > uncommon polyps found in the GI tract
  > sporadic or related to a genetic syndrome such as Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, and PTEN hamartoma syndrome.
• No malignant potential.
• Removal is indicated for obstructive symptoms or bleeding.

Question 7

Serrated Polyps

Answer 7

three types:
> hyperplastic polyps (which are not considered precancerous)

> sessile serrated polyps

> traditional serrated adenomas.

• Sessile serrated polyps and traditional serrated adenomas are combinations of adenomatous and hyperplastic polyps, sharing features of both types including colonic crypts with a saw-tooth serrated configuration and nuclear atypia :

increased risk of CRC
follows the serrated neoplasia pathway in contrast to the classic adenoma–carcinoma pathway seen in adenomatous polyps. These polyps should be removed, and patients should be followed with serial endoscopy.

Question 8

Neoplastic Polyps

Answer 8

• All adenomas have a malignant potential.

> Tubular adenomas
Villous adenomas
Tubulovillous adenomas

The most common type are tubular adenomas,
frequently pedunculated.

• Villous adenomas are commonly sessile.
  The risk of malignancy increases dependent on the size (large), gross shape (sessile), histologic type (villous), and grade of dysplasia.

Patients with an advanced adenoma defined as
- size at least 1 cm
- high-grade dysplasia
- tubulovillous or villous histology are at a significantly increased risk of developing CRC.

Question 9

Polyp Excision

Answer 9

forceps and snares.

Pedunculated polyps >
removed using cold or hot snare polypectomy.

Sessile polyps > elevated from the underlying muscularis by injection of saline and then excised using an assortment of techniques.

Sessile polyps with a central depression that do not elevate adequately with saline injection (nonlifting sign) are at increased risk for perforation with endoscopic removal and at higher risk of harboring neoplasia and are commonly referred for surgical removal by segmental colectomy.

Large polyps that cannot be removed endoscopically are also referred for surgery.

Larger polyps can also be removed endoscopically using techniques such as endoscopic mucosal resection and endoscopic submucosal resection.

Question 10

Malignant Polyps

Answer 10

Malignant polyps are those in which histologic examination following removal of a polyp reveals a focus of carcinoma that has invaded through the muscularis mucosa.

The question that arises is whether complete endoscopic removal of these polyps is sufficient.

Carcinomas that do not pass the muscularis mucosa are considered “carcinoma in situ” and do not carry metastatic risk. However, those that invade the muscularis mucosa harbor a significant risk of local recurrence and lymph node metastasis.

Question 11

High Risk Polyp

Answer 11

• Malignant polyps are commonly referred for completion colectomy in cases of
• pedunculated Haggitt level 4
• sessile Kikuchi level Sm2 and Sm3
• histologic poor differentiation
• lymphovascular invasion
• incomplete removal or close resection margins

Question 12

Recommendations for repeat colonoscopy following endoscopic removal of polyps

Answer 12

see

Question 13

Familial Adenomatous Polyposis

Answer 13

• germline mutation in the APC tumor suppressor gene which is responsible for regulation of β-catenin and located on chromosome 5q21

Question 14

fewer than 100 adenomas

Answer 14

are considered to have attenuated FAP (AFAP)

Question 15

A variety of benign and malignant extracolonic manifestations have been described in FAP.

Answer 15

• gastroduodenal adenomas and carcinoma
• desmoids
• osteomas
• epidermoid cysts
• papillary thyroid carcinoma
• small bowel polyps and carcinoma
• congenital hyperplasia of the retinal pigment epithelium (CHRPE)
• dental anomalies

Question 16

Inherited colorectal cancer syndromes

Answer 16

see

Question 17

the second most common cause of death in FAP patients

Answer 17

Duodenal adenomas occur in 30% to 70% of patients with FAP, and there is a predilection for the ampullary and periampullary regions.

The lifetime risk for duodenal cancer is 4% to 10%, constituting the second most common cause of death in FAP patients

Question 18

desmoid tumors

Answer 18

• About half of FAP-associated desmoid tumors arise intraabdominally in the bowel mesentery and 40% develop in the abdominal wall.
• Surgery of intraabdominal desmoid tumors, in general, is not recommended
• NSAIDs and antiestrogens showed similar outcomes to surgery. Combination chemotherapy, including doxorubicin, seems to be the best option for progressively growing intraabdominal desmoids.

Question 19

CHRPE

Answer 19

CHRPE is a benign lesion

characterized as well-delineated grayish-black or brown oval spots seen in 60% to 85% of FAP patients on fundoscopic scan.

Normally, this does not require intervention but can be used to help make a diagnosis

Question 20

Gardner syndrome and Turcot syndrome

Answer 20

Gardner syndrome
(FAP with epidermal inclusion cysts, osteomas, desmoid tumors)

Turcot syndrome
(FAP associated with malignant tumors of the central nervous system)

Question 21

Indications for genetic counseling

Answer 21

family history of FAP
personal history of more than 10 adenomas
personal history of adenomas
and an extracolonic manifestation of FAP.

For individuals suspected of AFAP, gene testing is recommended if 20 or more cumulative colorectal adenomas are found

Question 22

Screening

Answer 22

Colorectal screening
> begins at age 12 , initiated with flexible proctosigmoidoscopy. If polyps are seen >colonoscopy is warranted.

If no polyps are identified on the initial flexible proctosigmoidoscopy > repeated every 1 to 2 years until the age of 35 and every 3 to 5 years thereafter

Question 23

Patients at risk for AFAP should receive endoscopic screening with colonoscopy at

Answer 23

ages 12, 15, 18, and 21 years, and then every 2 years

About one-third of patients with AFAP can be managed long-term endoscopically by polypectomy

Question 24

For the upper GI tract, screening

Answer 24

screening begins at 20 to 25 years of age.

Screening intervals are based on the Spigelman staging system.

Question 25

Annual thyroid screening

Answer 25

Annual thyroid screening by ultrasound should be recommended to FAP patients

Question 26

Proctocolectomy and IPAA

Answer 26

> reduce the risk of rectal cancer especially with rectal mucosectomy and hand-sewn anastomosis. > associated with higher morbidity than IRA > results in more frequent bowel movements > risk of nerve injury that can lead to sexual or urologic dysfunction. > Pelvic dissection can cause infertility due to adhesions

Question 27

Timing of surgery in patients with familial polyposis

Answer 27

see

Question 28

Indications for IPAA.

Answer 28

- Patients with rectal cancer - a large polyp burden (>20 synchronous adenomas, adenoma with high-grade dysplasia, large (>30 mm) adenomas) - severe familial phenotype (>1000 synchronous adenomas)

Question 29

stapled anastomosis Vs Handsewn

Answer 29

The benefits of a stapled anastomosis ( Keep anal Transition Zone ) > better function (less risk of incontinence) > fewer complications > easier to survey > anal transitional zone adenomas may possibly be treated endoscopically or transanally. The benefit of a handsewn IPAA ( Removes It ) > reduced incidence of anal transitional zone adenomas, > worse bowel function. This procedure can be performed with or without a diverting ileostomy

Question 30

A temporary diverting ileostomy Benefits

Answer 30

- mitigate the effects of anastomotic leakage - prevent pelvic sepsis , fistulization, and thus compromised pouch function. - prevent the need for relaparotomy.

Question 31

Subtotal colectomy and IRA

Answer 31

- Good functional outcomes - long-term follow-up of the retained rectum. - risk of metachronous rectal cancer 30%. > recommended for patients with : - few rectal polyps - AFAP, - family history of a mild phenotype - young women with desire to become pregnant after recommendations of genetic counseling. IRA should not be performed in : - patients with a severely diseased rectum (adenomas >3 cm diameter, adenomas with severe dysplasia, cancer, sphincter dysfunction, or a rectum containing more than 20 rectal adenomas) or in the presence of colon cancer

Question 32

Proctocolectomy with end ileostomy

Answer 32

- very low rectal cancer, when sphincter preservation is not possible - in cases of malignant transformation after IPAA - or ileal pouch failure - or in cases in which there is poor sphincter function.

Question 33

Post Surgery

Answer 33

- chemoprevention after surgery because proctocolectomy with IPAA or a colectomy with IRA can retain “at-risk” rectal mucosa, and the duodenal mucosa remains “at risk” in all these patients. - Chemoprevention (i.e., taking medications that slow polyp growth such as sulindac or celecoxib) should not replace routine endoscopic surveillance. - Regular follow-up is mandatory after any procedure. - Standard care includes perianal digital and flexible endoscopic examination at yearly intervals.

Question 34

MUTYH-Associated Polyposis

Answer 34

- MUTYH gene, located on chromosome 1. - CRC risk is increased twenty-eight fold for individuals with biallelic MUTYH mutations

Question 35

indications for MUTYH gene testing:

Answer 35

- patients with 10 to 100 polyps - siblings of patients with biallelic MUTYH gene mutation, - patients with early-onset CRC (<44–55 years) - or children of monoallelic or biallelic MUTYH gene mutation carriers

Question 36

MAP Tx and Screen

Answer 36

- colonoscopy every 1 to 2 years - Subtotal colectomy with IRA is recommended if endoscopic management fails or if CRC develops. - Patients with rectal cancer in MAP should be considered for proctocolectomy and IPAA. - Esophagogastroduodenoscopy with a side-viewing gastroscope to more accurately examine the ampulla should be performed to evaluate for duodenal adenomatous neoplasia. - This screening should start at the age of 30 and be repeated every 3 to 5 years if the exam is normal

Question 37

Peutz-Jeghers Syndrome

Answer 37

- 39% lifetime risk of CRC - 90% lifetime risk of cancer, including colorectal (most common) - 90% of PJS patients will develop hamartomatous polyps, most commonly in the small bowel, followed by the colon, stomach, and rectum - mutation of the STK11/LKB1 gene located on chromosome 19p

Question 38

Polyps differ histologically from juvenile polyps

Answer 38

Polyps differ histologically from juvenile polyps in that they arise due to an overgrowth of the muscularis mucosa rather than the lamina propria.

Question 39

PJS is a clinical diagnosis based on any one of the following World Health Organization criteria:

Answer 39

(1) three or more histologically confirmed Peutz-Jeghers polyps (2) any number of PJ polyps with a family history of PJS (3) characteristic, prominent, mucocutaneous pigmentation with a family history of PJS (4) any number of Peutz-Jeghers polyps and characteristic prominent, mucocutaneous pigmentation

Question 40

Screening

Answer 40

- at 8 to 10 years of age with an evaluation of the small bowel. - repeat evaluation at the age of 18 and then at 2- to 3-year intervals. - Males > annual testicular physical examination starting at age 10 years - females > annual pelvic examination and Papanicolaou stain starting at age 18 to 20 years - Women > breast physical examinations every 6 months and yearly mammogram and breast MRI starting at age 25 years. - Colonoscopy and upper endoscopy should start in the late teens and be repeated every 2 to 3 years for both genders. - Pancreatic cancer screening involves endoscopic ultrasound or magnetic resonance cholangiopancreatography along with serum CA19-9 every 1 to 2 years starting at age 25 to 30 years.

Question 41

Tx

Answer 41

- Polypectomy - Asymptomatic gastric or colonic polyps larger than 1 cm should be removed endoscopically. - Small bowel polyps larger than 1 to 1.5 cm or those that are have grown rapidly should be removed to decrease future complications such as bleeding and intussusception. - Surgery is most commonly reserved for symptoms, the most common being obstruction (caused by intussusception) and bleeding in the small bowel.

Question 42

What to add in Surgery

Answer 42

push enteroscopy or combined laparoscopy/laparotomy with endoscopy in the operating room as these small bowel polyps may not be visualized by other means

Question 43

Juvenile Polyposis Syndrome

Answer 43

- hamartomatous intestinal polyps - clinically diagnosed : > five or more juvenile polyps in the colorectum > multiple juvenile polyps throughout the GI tract > any number or juvenile polyps with a family history > or juvenile polyposis.

Question 44

Genes ?

Answer 44

Two genes, SMAD4 (chromosome 18q) and BMPR1A (chromosome 10q)

Question 45

Screening

Answer 45

- Screening by colonoscopy should begin between the ages of 12 to 15 years. - If there are no polyps, colonoscopy should be repeated in 2 to 3 years. - When polyps are present and removed, colonoscopy should be done annually

Question 46

Surgical indications

Answer 46

- presence of high-grade dysplasia or cancer - polyp burden cannot be effectively managed endoscopically. Prophylactic colectomy may be considered for patients with poor surveillance compliance or in patients with family history of CRC.