Colon cancer

Colon cancer

1. COLORECTAL
CANCER
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2. Learning Objectives
By the end of the session, you should
be able to:
1.Epidemiology
2.Risk factors
3.Screening & prevention
4.Stages of the disease
5.Sign and symptoms
6.Treatment protocols
7.Side effects/complications
8.Prognosis
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3. Definition
Malignant growth of tumor that beginsfrom the inner
wall of the colon or rectum.
Can also involve the anal canal.
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4. EPIDEMIOLOGY
The 3rd most common malignancy worldwide ( ≥ 1.2
million new cases annually).
The incidence is greatest among males(37.4 per
100,000 vs. 29.9 per 100,000)
3
rd
leading cause of cancer-related deaths in US.
Highest incidence rates in economically developed
countries
Invasive CA of rectumoccurs less frequently (<1/3
cases)
In Palestine: (W.B)
The 2
nd
most common cancer being diagnoses
Cancer 2
nd
leading cause of death (M +F )
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5. Age & Colorectal CA
Relationship:
An individual’s risk of developing cancer of the
colon or rectum increaseswith advancing age.
The likelihood of cancer diagnosis ↑after 40
years of age and rising progressively after age 50.
The median age at diagnosis is 69 years.
< 20% of patients are less than 50 years of age at
the time of diagnosis.
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6. SURVIVAL :
5-year survival rate:
Disease Stage 5-Year
survival
Early stages (localized/stage I, II) of colon 91 %
Early stages rectal cancer. 88%
Regional disease/Stage III:
Colon & rectal cancer after the tumor has spread
regionally to adjacent LNs or tissues
70%
Metastatic disease ≤ 12%
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7. Pathophysiology
The formation of colorectal CA is a multistep process.
Begins with an abnormal growth of tissue known as a
polyp(precursors to the disease) originating from the
innermost wall of the colon.
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8. The process of
transformationfrom polyp
to malignant disease
takes years.
Once transformation
occurs, cancer begins to
spread through the wall
of colon/rectum.
It can eventually invade
blood, L.Ns, or other
organs directly.
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A stalked colon
polyp

9. 95% are adenocarcinoma (glandular tissue).
The disease can be preventedby removal of precancerous
tissue.
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10. Aetiology
Aetiology is complex, involving:
Patient-specific factors
Environmental factor
Genetic factors
Genetic mutations associated with colorectal cancer:
APC mutation/loss (Tumour suppressor gene).
P53 mutation
COX-2 overexpression(growth factor signalling
pathways)
K-RAS mutation 35%, BRAF mutation 5% (oncogenes)
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11. Risk Factors
Increase age: Age >50 (90% of patients)
Male sex
Family history.
Personal history:
(history of colon polyps; multiple adenomas or size
≥10 mm)
IBD (Ulcerative colitis, Crohn’sdisease):
↑5-to 10-fold
Risk ↑with increasing extent of bowel involvement &
disease duration.
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12. Risk Factors
Environmental factors/Lifestyle:
Physical inactivity & obesity
Diet:
fatty food
Red meats
processed meats
(hot dogs and some luncheon meats)
low fibers
Alcohol (excessive)
SMOKING:
Rectal > colon
Dose relationship (pack/year)
Duration
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13. Particularly smoking in early life.
As compared to never-smokers, the risks of
colorectal cancer and mortalityin smokers were
18% and 25% higher, respectively.
Early tobacco use influence risk of cancer
recurrenceand mortality among colon cancer
survivors.
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14. Risk Factors
Genetic/Hereditary colon CA Syndromes:
The 2 most common forms of hereditary colon
cancer are:
1.Familial adenomatous polyposis (FAP):
Risk ↑ 100%
AD
Mutations of the adenomatous polyposis coli (APC)
gene
0.2% to 1% of all colorectal cancers.
Diagnosed by late teens or early 20s.
Total colostomy is recommended when detected.
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15. 2.Hereditary non-polyposis colon cancer (HNPCC)/
LynchSyndrome.
AD
2% to 4%
MMR (mismatch repair) genes mutation in DNA.
Diagnosed later in life as compared to FAP
Tend to be located primarily in the right-sided (proximal
colon)
Other factor can increase risk of colon cancer:
DM (Type 2)
in 15 studies (hyperinsulinemia& ↑ levels of free insulin-
likegrowth factor-1 (IGF-1), promote tumor cell
proliferation
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16. Factors may ↓colorectal CA risk:
Fiber (Fruit & Vegetables)
Physical activity
Regular consumption of milk/Calcium & Vitamin D
(May have antiproliferative effects )
Hormone replacement therapy (HRT). Persist over
10 y
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17. NSAID (Celecoxib) and Aspirin Use:
Regular use (2 x wk), over 10-15 year.
 Inhibition of COX-2 & free radical formation.
COX-2 overexpression is seen in pre-cancerous &
cancerous lesions in the colon
COX-2 overexpression is associated with:
Decreased colon CA cell apoptosis
Increased production of angiogenesis-promoting
factors.
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18. Signs & Symptoms
1.Subtle & nonspecific (generalised symptoms)
2.Asymptomatic (early stage).
3.**Persistent/sudden change in bowel habits:
(*Prolong constipation
*or diarrhea.
*pencil thin stool)
4.Bleeding from rectum or blood
In stool.
5.Vague Cramping or abdominal pain/discomfort,
bloating , N, V 2ndry obstruction, perforation,
bleeding.
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19. Signs and symptoms
6.Weakness and tiredness
(advanced stage).
7.Iron-deficiency anemia.
8.Unintentional weight loss
9.Increased liver enzymes
(sign of liver metastasis) (AST/ALT)
10.Hepatomegaly and jaundice
in advanced disease.
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20. Symptoms 20

21. Anatomy
The large intestine consists of the cecum; the ascending,
transverse, descending, and sigmoid colon; and the rectum
Ascending colon (22% of colorectal carcinomas)
Transverse colon (11% of colorectal carcinomas)
Descending colon (6% of colorectal carcinomas)
Sigmoid colon (55% of colorectal carcinomas)
4 major tissue layers, from the lumen outward, form the large
intestine:
The mucosa
Submucosa
Muscularis propria
Serosa
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22. 22

23. 23

24. DIAGNOSIS
Signs and symptoms
Entire Large bowel evaluation:
Colonoscopy
Double-Contrast Barium Enema
CTColonography(detect adenomas at least 6 mm).
Flexible sigmoidoscopy (FSIG) : examine lower half of
the bowel to the splenic flexure, capable to detect
50%-60% of CA.
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25. DIAGNOSIS
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26. Biopsy
(during colonoscopy)
Ultrasound: Determines
depth of tumor penetration,
assessing L.Ns
CT scan: same as ultrasound + useful in assessing for
metastasis
Blood tests: bldcount, PT, PTT, Liver function test.
CEA(carcinoembryonicantigen)Tumourmarker
Non-sensitive, non specific in early stage
Usually elevated in metastatic or recurrent colon CA
Normal 0-3 ng/mL
Monitor the recurrence.
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27. SCREENING
Often same as diagnosis
Colonoscopy: gold standard for colorectal
screening
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28. SCREENING
A.Colonoscopy/ Barium enema/ CT scan
(alternative for individuals who don’t wish to
undergo /not suitable for colonoscopy.)
B.CEA level
C.Fecalscreening test:
1.Fecal occult blood testing (FOBT)
Many early-stage tumors do not bleed.
High false -verate
Sensitivity 33-75%
Increased sensitivity & specificity when used in
combination with test 2
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29. 2.Fecal immunochemical test (FIT)
Can be used to replace FOBT
Sensitivity 60-85%
Specificity > 97%
No drug or food interactions
Uses ABs to detect globin protein Hg in stool
D.Digital Rectal Exam (DRE):
Can detect anorectal
palpable mass
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30. Screening guidelines for early detection of colorectal
CA with the goal of cancer prevention:
Risk Screening recommendation
Average risk
(R.F ≥ 50 ys)
both M/F
Annual DRE and FOBT/FIT and one of the following:
–Sigmoidoscopy every 5 years
–CT colonographyevery 5 years
–Colonoscopy every 10 years
–Barium enema every 5 years
Family History Begin screening at age of 35-40 years or 10 years younger from
first-degree relative colorectal cancer diagnosis
IBD Begin screening at 8–15 years after diagnosis
FAP Begin screening at 10-12 years
HNPCC Begin screening at age of 20–25 years or 10 years younger
from 1st-degree relative colorectal CA diagnosis
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31. Staging:
TNM Staging System
T –(tumor size), based on DEPTH (penetration)invasion
into mucosa
T1 –Tumourinvades the submucosa
T2 –Invades the muscularispropria
T3 –Invade through the muscularispropriainto
subserosa
T4 –Tumors invading or adhering other local
organs/structures/segments/ surface of visceral
peritoneum
N –lymph node involvement
N1 –1-3 +veL.N
N2 –≥4 or more +veL.N
M –distant metastasis
M0 –no other organs involved
M1 –distant metastases are present
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32. 32

33. Simplified Staging System
Stage
Stage I Tumors that either invade into or through the
submucosawith NO(+) LN
Stage IITumors that invade through the muscularispropria or
into local organs with NO(+) LN
Stage IIIAny T withnodal involvement (+) LN
Stage IVTumor with nodal involvement and with distant
metastasis (usually liver, followed by lungs, then
bones)
25% of patients present with stage IV
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34. 34

35. Treatment
I.Surgery
II.Radiation
III.chemotherapy
IV.Targeted molecular therapies.
Treat Depend on the location & extent of disease.
Prognosis depend on extent of tumour
penetration/LNs involvement, Metastases.
Goals:
Curative therapy for localized CA
Palliative therapy for metastatic CA.
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36. Treatment
Surgery in CA of the colon or rectum (stage, I, II, III):
Complete surgicalresection of the primary tumor
mass with regional lymphadenectomy
At least a 5 cm margin of tumor-free bowel &
regional lymphadenectomy
Selected patients with resectablemetastases,
surgical resection may be an option.
Rectal CA total excision of the mesorectum
(TME), the surrounding tissue containing perirectal
fat and draining LNs.
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37. Treatment
If the distal margin clear of tumor is at least 1 cm,
sphincter-preserving surgerymay be possible for
patients with CAs in the middle and lower portion of
the rectum.
If not Candidate for sphincter-preserving surgery 
Abdomino-perinealresection (APR) = remove distal
sigmoid, recto-segmoid, rectum, anus.
Colostomy (after colectomy) has become an
accepted procedure for colon and rectal cancer.
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38. 38

39. Rectal CA is more difficultto resect with wide margins.
Local recurrence of rectal CA is more common
compared to colon CA
If lies closer to the anal sphincter, so the risk of
localized treatment failure & recurrence at the initial
site of disease is increased
Radiation (XRT) is usually reserved for rectal cancer
AdjuvantXRT + chemo. are standard for stage II/III
rectal CA
Neo-Adjuvanttherapy before rectal surgery to:
Shrink the tumour & make it resectable, prevent local
recurrence in rectal CA.
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40. In metastasis disease, radiotherapy will reduce the
symptoms
Stage I colon or rectal cancer are cured by surgical
resection alone, adjuvant therapy is not indicated.
Adjuvant chemotherapy in –veL.N (stage II) colon
cancer is controversial
Adjuvant chemotherapy should be considered for
stage II disease with pts. at higher risk for relapse :
(inadequate LN sampling, bowel obstruction/ perforation of the
bowel at presentation, poorly differentiated tumors, perineural
invasion, andT
4lesions (stage IIB/IIC).
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41. Adjuvant chemotherapy isstandard therapy
for patients with stage III colon cancer
(decreases risk of cancer recurrence & death)
Combined neo-adjuvant therapy + radiation
therapy (chemoradiation) and surgery for
patients with stage II or III rectal cancer is
considered standard of care to decrease risk
of local and distant disease recurrence.
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42. Stage Management
Stage I Surgery
Stage IIColon: Surgery (observation +/-chemo.)
Rectal:Surgery + XRT + chemo.
Stage IIIColon: Surgery + Chemotherapy
Rectal:Surgery + XRT + chemo.
Stage IV +/-surgery (selected pt.)+ chemo. + MoAB,
Palliative care
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