Colon and rectal cancer

Epidemiology• The 3. cancer type in incidence and mortality in Western

Europe and North America

Epidemiology• The 2. cancer type in

incidence men and 3. in women in Romania

Anatomy• Large

bowel=colon+rectum• Colon=cecum,

ascendending c., transverse c., descending c., sigmoid c.

AnatomyAnatomic anal canal: 2 -3 cm (stratified scuamos cell

epithelium)Rectum: from 2-3 from the anus until 15 cm from the

anus (cylindrical epithelium)

Risk factors I. Genetic risk factors (75% of colon cancers are sporadic but 25% are

familial)1. Polyposis syndromes-familial (autosomal dominant) and non-

familial• The familial polyposis syndromes can be further subdivided

depending on whether the polyps are adenomas or hamartomas. • Adenomatous polyposis syndromes include the familial

adenomatous polyposis, Gardner syndrome and Turcot syndrome.• Hamartomatous familial polyposis syndromes include Peutz-

Jeghers syndrome, juvenile polyposis syndrome, Cowden disease and Ruvalcaba-Myhre-Smith syndrome.

2. Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)

3. BRCA1/2 mutations

Risk factorsII. Racial background• African Americans have the highest colorectal cancer

incidence and mortality rates of all racial groups in the United States. The reason for this is not yet understood.

• Jews of European descent (Ashkenazi Jews) have one of the highest colorectal cancer risks of any ethnic group in the world. Several gene mutations leading to an increased risk of colorectal cancer have been found. The most common of these DNA changes, called the I1307K APC mutation, is present in about 6% of American Jews.

Risk factors III. Premalignant conditionsInflammatory bowel disease (ulcerative colitis and Crohn's disease)IV. Lifestyle (environmental factors)1. Diet - high in red meats (beef, lamb, or liver) or processed meats (hot

dogs and some luncheon meats)- low in vegetables and fruits - whether fibers play a role in prevention is still debated2. Physical inactivity and obesity3. Smoking (causes probably as much as 30% of colon cancers !)4. Heavy alcohol use-partially may be due to the fact that heavy

alcohol users tend to have lower levels of folic acid. Still, alcohol use should be limited to no more than 2 drinks a day for men and 1 drink a day for women.

Risk factors 5. Type II diabetes

Controversial factors:1. Night shift work - working a night shift at least 3 nights a

month for at least 15 years may increase the risk of colorectal cancer in women; this might be due to changes in levels of melatonin.

2. Previous radiotherapy for other cancers (prostate, cervical cancer)

Histology, pathology• Colon, rectum: adenocarcinoma (98%)• Anal canal: scuamos carcinoma (risk factor: HPV)

• 2/3 of cancer found in the left (terminal) colon• 1/3 on the right

• Synchronous: 4%• Associated polyposis: 25%

Signs and symptoms

• Ascending colon: the stool here is softer=> tumors can grow large before causing obstruction

Most frequent symptoms:- abdominal pain (74%)- asthenia (29%)- occult bleeding causing anemia (27%)- palpable abdominal mass (23%)

Signs and symptoms

• Descending colon:Most frequent symptoms:- abdominal pain (72%)- hematochezia (53%)- constipation (42%) obstruction- decrease in the stool diameter (“pencil stool”)

Signs and symptoms• Sygmoid colon:Most frequent symptoms:- hematochezia (85%)- constipation (46%)- tenesmus (feeling the need to empty the bowels,

along with pain, cramping, and straining) (30%)- Diarrhea ! (30%)- Abdominal pain (26%)- decrease in the stool diameter (“pencil stool”)

Diagnosis• COMPLETE colonoscopy (if possible)• Biopsy• Rigid proctoscopy for rectal tumors in order to

measure the exact distance from the anal verge• Chest radiography• Abdominal + pelvic CT• Transrectal US or MRI with endorectal coil for T an

d N stage • CEA (carcinoembryonic antigen)

Staging-rectal cancer

Treatment• Colon cancer: right or left hemicolectomy / transversectomy /

sigmoidectomy PLUS lymph node resection• Rectal cancer: rectal resection with total mesorectal excision

(TME) along with lymphadenectomy

Treatment• Rectal excision types:1. Anterior rectal resection2. Abdominoperineal resection (rectal amputation) plus

colostomy

Earlier: tumors closer than 5 cm to the anus => amputationToday: with modern surgical techniques (staplers): 2-4 cm

margin is achievable

Radiotherapy• Can precede or follow rectal surgery• In both cases improves local control• BUT: Concomitant chemoradiation should always precede rectal surgery!!!

(stages T2-T4)• Benefits of neoadjuvant chemoradiation versus adjuvant:-tumor regression and thus improvement in resectability-a higher rate of sphincter preservation-lower rate of side effects• Followed by additional adjuvant chemotherapy after surgery.

• For colon cancer: RT only adjuvant in resected cancers invading through the wall of the colon (T4)

Chemotherapy

• Neoadjuvant• Adjuvant• OR: in unresectable disease: to increase

survival

Curable M1!

• Up to 4 liver or pulmonary metastases can be resected and along with chemotherapy assure a disease control rate of 25%

Biologic treatments

• Cetuximab=chimeric (mouse/human) monoclonal antibody, an epidermal growth factor receptor (EGFR) inhibitor

Screening

• Based on solid evidence, screening for colorectal cancer (CRC) reduces CRC mortality, (but there is little evidence that it reduces all-cause mortality, possibly because of an observed increase in other causes of death). The patient and clinician can choose or combine different screening methods such as fecal occult blood testing and endoscopic procedures.

American Cancer Society (2008)-medium risk subjects

• For high risk subjects: colonoscopy (gold standard), earlier and more frequent

Questions • Enumerate the 4 groups of risk factors for colorectal

cancer and give some examples from every group.• What is the typical presentation for colon cancer in

the ascending/descending/sigmoid colon?• What is the therapeutic sequence for T2-T4 rectal

cancer?• How are liver metastases treated in colon cancer if

the primary disease is resectable?• When should screening be started for colorectal

cancer and what screening tests can be used?