git 4th crc 2016

1

Dr. Mohamed AlshekhaniProfessor in Medicine

MBChB-CABM-FRCP-EBGH2016

CRC:

Epidemiology:

• The second most common cause of cancer & cancer-related mortality in men &women.

• The cumulative lifetime risk is 1 /19 in men & 1 / 20 in women. • 50% are diagnosed with stage III & IV cancer, with 5-year survival

rates 65% &10%, respectively. • The incidence has steadily declined over the past 30 years. • Decline due to the use of colorectal cancer screening.• CRC Screening: every adult 50&> with average risk & earlier for

those with hereditary CRC syndromes.• CR Carcinogenesis is through 2 pathways:• 1. Adenoma-carcinoma 85%.• 2. Serrated polyposis pathway 15%.

Epidemiology:

Risk factors:

• Modifiable Factors:• High dietary fat or red meat, low dietary fiber, smoking, excess

alcohol ingestion, T2DM, low PE.• Non-modifiable risk factors:• Male gender, acromegaly, older age ,black ethnicity• Chronic colorectal inflammation from IBD, dependent on the

proximal extent of mucosal involvement; with pancolitis are at highest risk, negligible in patients with proctitis, increased with longer duration of disease, greater severity of inflammation& coexistent primary sclerosing cholangitis. After a decade of disease, the cancer risk increases yearly by 0.5- 1%.

• Ureterosigmoidostomy also increases the risk for colon cancer.

Risk factors:

• A personal history of adenomatous polyps or colorectal cancer increases the risk for metachronous colorectal cancer.

• Nonsyndromic Family History:• Individuals with a first-degree relative have *2-3 increased risk • The risk is increased with a greater number of relatives affected &

an earlier age of cancer onset (< 60 years).

Risk factors:Hereditary CRC Syndromes

• Have the highest risk of colorectal cancer • Require an accurate & comprehensive family history, ;ages & causes

of death of relatives in three generations, any diagnosis of cancer& age of onset, birth defects&other inherited conditions.


• Lynch syndrome: Hereditary (Nonpolyposis) Colon Cancer (HNPCC) • The Amsterdam II criteria :• Three or more relatives with HNPCC-related cancers (CRC or

endometrium, small intestine, ureter, or renal pelvis)• One relative a first-degree relative of the other two• At least two successive generations affected• One cancer diagnosed before age 50 years• Familial adenomatous polyposis excluded• Tumors verified histologically


• Colon cancer occurs in up to 80% of individuals with Lynch syndrome, usually at a mean age of 44 years.

• The colon cancer is often right-sided and has particular pathologic features(tumor-infiltrating lymphocytes, a Crohn-like lymphocytic reaction& mucin or signet cell histology).

• Associated with an increased risk for extracolonic tumors (endometrial [40%-60%], much less commonly ovarian, urothelial, gastric, brain, small bowel, hepatobiliary tract, sebaceous& pancreatic).


• FAP:• Caused by a mutation of (APC) gene• Results in the development of hundreds to thousands of CR

adenomas often in the second decade of life. • Without treatment, CRC typically develops in all patients by the age

of 40 years. • Gastric fundic gland polyposis & duodenal adenomas are also

present in most patients. • Gastric cancer is rare, but duodenal & periampullary cancers are the

second leading cause of cancer death in this group (2.5-30%). • Papillary carcinoma of the thyroid is increasingly recognized.


• Attenuated FAP (AFAP): milder form • Fewer colorectal polyps, generally <100, later age of onset &lower

cumulative lifetime risk. • The colorectal polyps are often right-sided.


• Gardner syndrome :• A phenotypic variant of FAP characterized by colonic polyposis,

benign soft tissue tumors (including sebaceous cysts& lipomas), osteomas, supernumerary teeth, desmoid tumors& congenital hypertrophy of the retinal pigment epithelium.


• Turcot syndrome:• Another variant of FAP ,polyposis with brain tumors, including

cerebellar medulloblastoma, astrocytoma& ependymoma.


• Peutz-Jeghers syndrome (PJS):• Caused by a mutation in threonine kinase (STK11) gene.• Diffuse intestinal hamartomatous polyps (often cause small-bowel

obstruction by 20 years) & mucocutaneous pigmentation most obvious on the lips.

• Diagnostic criteria: two or more of the following: • Two or more small-bowel hamartomas, mucocutaneous

pigmentation, or a family history of PJS. • There is a 90% cumulative lifetime risk for intestinal &

extraintestinal cancer: breast; colon; pancreas; gastric; ovary; lung; small intestine; uterus & cervix; unusual gonadal neoplasms of the ovary&testes.


• Juvenile polyposis syndrome (JPS):• Develop numerous hamartomatous or juvenile polyps, in the colon. • Germline mutations detected in 50% , BMPR1A or SMAD4 gene. • Most develop symptoms by the age of 20 years.


• The clinical criteria for this syndrome consist of :• (1) more than three juvenile polyps of the colon• (2) juvenile polyps throughout the gastrointestinal tract• or (3) one or more juvenile polyps combined with a family history of

juvenile polyposis syndrome. • Juvenile polyposis syndrome usually presents with GIB, diarrhea,

gastric outlet obstruction, or protein-losing enteropathy from massive gastric polyposis.

• There is an increased risk for CRC(39%), GC(25%)& more rarely small-bowel &pancreatic cancer.


• Solitary juvenile polyps are one of the most commonly found colorectal polyps, particularly in children <10 years

• No future health risk once the polyp is removed &follow-up surveillance colonoscopy is not required.

Risk factors: Hereditary CRC Syndromes

• Serrated polyposis syndrome:• Familial polyposis syndrome with multiple, large, proximal

hyperplastic polyps or serrated adenomas without a genetic cause.

Risk factors: Hereditary CRC Syndromes

• Serrated polyposis syndrome: WHO criteria• (1) 5 or more serrated polyps proximal to the sigmoid colon, two or

more of which are 10 mm in diameter or greater• (2) Any number of serrated polyps proximal to the sigmoid colon in

an individual with a 1st-degree relative who has serrated polyposis syndrome

• or (3) >20 serrated polyps throughout the colon. • Associated with an increased risk of CRC but not Extra Intestinal

cancer. • The mean age of CRC diagnosis is 56 years&metachronous CRC

occurs in 7% at 5 years of follow-up. Surveillance is recommended.

Chemoprevention:

• Not indicated for patients at average risk for colorectal neoplasia, • Not routinely recommended for patients at high or very high risk for

colorectal neoplasia.

Diagnosis:

• The diagnosis of CR neoplasia is most often made by colonoscopy performed for gastrointestinal symptoms, screening, or surveillance.

Staging:

• If diagnosed, staging provides a uniform description of the depth of tumor invasion into the colon wall, other structures, lymph nodes & distant organs.

• There are two types of staging for colorectal cancer: • A clinical stage & pathologic stage.

Staging:

• Clinical staging by:• Physical exam• Colonoscopic biopsy• Pretreatment CT chest, abdomen& pelvis& If an indeterminate liver

mass is detected, MRI of the abdomen with & without gadolinium- contrast enhancement is suggested.

• MRI of the pelvis is recommended for patients with rectal cancer.

Staging:

• Pathologic staging after the tumor is removed , by:• Reports the tumor type / differentiation, depth of invasion, lymph

node involvement, distant metastasis, margin status, perineural/angiolymphatic invasion&many other clinically validated factors.

Staging:

Management:

• EMR or ESD for very early detected cancers.• Surgery is the mainstay if early detected.• Paliative stenting or surgery for obstruction.

BO5:1

• 1. As cause of morbidity & mortality in men & women CRC ranks the:

• A. First.• B. Second.• C. Third.• D. Fourth.• E. Fifth.

BO5:2

• 2. Most cases of CRC are:• A. Sporadic.• B. Syndromic Familial.• C. Non syndromic familial.• D. Secondary to IBD.• E. Not preventable.

BO5:3

• 3. CR carcinogenesis is mainly through:• A. One pathway.• B. Two pathways.• C. Three pathways.• D. Four pathways .• E. Five pathways.

BO5:4

• 4. Most of CRC occur through:• A. Adenoma-carcinoma pathway.• B. Serrated pathways.• C. Alternative pathways.• D. All.• E. None.

BO5:5

• 5. The adnemoa-carcinoma sequence in CRC pathogenesis occur over:

• A. 2 years.• B. 4 years.• C. 5 years.• D. 6 years.• E. 10 years.

BO5:6

• 6. The rationale for prevention of CRC by screening is:• A. Slowly developing adenoma-carcinoma sequence.• B. Rapidly developing adenoma-carcinoma sequence.• C. Rapidly developing serrated polyposis syndrome.• D. All of the above.• E. None of the above.

BO5:7

• 7. The following are risk factors for CRC except:• A. Smoking.• B. Alcohol.• C. Acromegaly.• D. T1DM.• E. Ureterosigmoidostomy.

BO5:8

• 8. The largest number of premalignant colonic polyps occurs in:

• A. FAP.• B. AFAP.• C. PJS.• D. Gardener syndrome.• E. Turcot syndrome.

BO5:9

• 9. Oral muco-cutaneous pigmentations associated with colonic polyposis occurs in:

• A. FAP.• B. AFAP.• C. PJS.• D. Gardener syndrome.• E. Turcot syndrome.

BO5:10

• 10. The polyps in PJS are:• A. Hyperplastic.• B. Adenomatous.• C. Vilous.• D. Hamartomatous.• E. Serrated.

BO5:11

• 11. Most CRCs occur in:• A. Anus.• B. Rectum.• C. Splenic flexture.• D. Cecum.• E. Ascending colon.

BO5:12

• 12. Most CRCs are:• A. Left-sided.• B. Right-sided.• C. In middle colon.• D. Equally distributed.• E. Non of the above.

git 4th crc 2016

Health & Medicine