1. Colon and rectal cancer

2. Epidemiology
The 3. cancer type in incidence and mortality in Western Europe and North America

3. Epidemiology
The 2. cancer type in incidence men and 3. in women in Romania

4. Anatomy Large bowel=colon+rectum
Colon=cecum, ascendending c., transverse c., descending c., sigmoid c.

5. Anatomy
Anatomic anal canal: 2 -3 cm (stratified scuamos cell epithelium)
Rectum: from 2-3 from the anus until 15 cm from the anus (cylindrical epithelium)

6. 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

7. Risk factors II. 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.

8. Risk factors III. Premalignant conditions
Inflammatory bowel disease (ulcerative colitis and Crohn's disease)
IV. Lifestyle (environmental factors)
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 debated
Physical inactivity and obesity
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.

9. Risk factors 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)

10. 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%

11. 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%)

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

13. 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”)

14. 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)

15. Staging-rectal cancer

16. 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

17. Treatment Rectal excision types: Anterior rectal resection
Abdominoperineal resection (rectal amputation) plus colostomy
Earlier: tumors closer than 5 cm to the anus => amputation
Today: with modern surgical techniques (staplers): 2-4 cm margin is achievable

18. 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)

25. Chemotherapy Neoadjuvant Adjuvant
OR: in unresectable disease: to increase survival

26. Curable M1!
Up to 4 liver or pulmonary metastases can be resected and along with chemotherapy assure a disease control rate of 25%

27. Biologic treatments
Cetuximab=chimeric (mouse/human) monoclonal antibody, an epidermal growth factor receptor (EGFR) inhibitor

28. 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.

29. American Cancer Society (2008)-medium risk subjects
For high risk subjects: colonoscopy (gold standard), earlier and more frequent

30. 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?