Colorectal Cancer (CRC)

One of the most common cancers in the world

US: 4th most common cancer (after lung,

prostate, and breast
cancers)
2nd most common cause of cancer
death (after lung cancer)

2001: 130,000 new cases of CRC

56,500 deaths
caused by CRC
 Anatomic Location of CRC
Cecum 14 %
Ascending colon
10 %
Transverse colon
12 %
Descending colon 7
%
Sigmoid colon 25 %
Rectosigmoid junct.9
%
Rectum 23 %
Symptoms associated with CRC
Colon cancers result from a series of pathologic changes that
transform normal epithelium into invasive carcinoma. Specific
genetic events, shown by vertical arrows, accompany this
multistep process.
 WHO Classification of CRC
Adenocarcinoma in situ / severe dysplasia
Adenocarcinoma
Mucinous (colloid) adenocarcinoma (>50%
mucinous)
Signet ring cell carcinoma (>50% signet ring
cells)
Squamous cell (epidermoid) carcinoma
Adenosquamous carcinoma
Small-cell (oat cell) carcinoma
Medullary carcinoma
Undifferentiated Carcinoma
 Risk factors for CRC

Age
Adenomas, Polyps
Sedentary lifestyle, Diet, Obesity
Family History of CRC
Inflammatory Bowel Disease (IBD)
Hereditary Syndromes (familial
adenomatous polyposis (FAP))
 Development of CRC
Result of interplay between environmental and
genetic factors

Central environmental factors:

Diet and lifestyle

35% of all cancers are attributable to diet

50%-75% of CRC in the US may be preventable

through dietary modifications
 Dietary factors implicated in
colorectal carcinogenesis
consumption of red
meat

animal and saturated

Increased risk fat

refined carbohydrates

alcohol
 Dietary factors implicated in
colorectal carcinogenesis
dietary fiber

vegetables

fruits
Decreased risk
antioxidant vitamins

calcium

folate (B Vitamin)
Specimen containing an invasive colorectal carcinoma and
two adenomatous polyps.
Multiple adenomatous polyps of the cecum are seen here in a
case of familial polyposis.
Familial polyposis in which mucosal surface of the colon is a
carpet of small adenomatous polyps. Even though they are small ,
there is a 100% risk over time for development of
adenocarcinoma, for which total colectomy is recommended
Adenocarcinoma of the rectosigmoid region . Heaped up margin
of tumor at each side with a central area of ulceration. Normal
mucosa at the right. The tumor encircles the colon and infiltrates
into the wall. Staging is based upon the degree of invasion into
Adenocarcinoma of the cecum demonstrates an exophytic growth
pattern.
The barium enema instills the radiopaque barium sulfate into the colon,
producing a contrast with the wall of the colon that highlights any masses
present. In this case, the classic "apple core” lesion is present, representing an
encircling adenocarcinoma that constricts the lumen.
 Staging of CRC
TNM system

Primary tumor (T)

Regional lymph nodes (N)

Distant metastasis (M)

*Note: Tis includes cancer cells confined within the glandular basement membrane
(intraepithelial) or lamina propria (intramucosal) with no extension through the
muscularis mucosae into the submucosa.

**Note: Direct invasion in T4 includes invasion of other segments of the colorectum

by way of the serosa; for example, invasion of the sigmoid colon by a carcinoma
of the cecum.
 Dukes staging system

A Mucosa 80%
B Into or through M. propria
50%
C1 Into M. propria, + LN !
40%
C2 Through M. propria, + LN!
12%
D distant metastatic spread <5%
 Sites of metastasis

Via blood Via lymphatics Per continuitatem

Liver
Abdominal wall
Lung
Lymph nodes Nerves
Brain
Vessels
Bone
 Therapy

Surgical resection the only curative

treatment

Likelihood of cure is greater when disease

is detected at an early stage

Early detection and screening is of pivotal

importance
Surgery is the mainstay of treatment of RC
After surgical resection, local failure is common
Local recurrence after conventional surgery:
15%-45% (average of 28%)

Radiotherapy significantly reduces the number

of local recurrences in rectal cancers, its use in
colon cancer is not routine due to the sensitivity
of the bowels to radiation.
 Radiotherapy in the management
of Rectal Cancer
In at least 28 randomised trials the value of
either preoperative or postoperative RT has
been tested

Preoperative RT (30+Gy): 57% relative

reduction of local failure
Postoperative RT (35+Gy): 33% relative
reduction

Colorectal Cancer Collaborative Group. Lancet

2001;358:1291
Gamma C. JAMA 2000;284:1008
 Adjuvant Therapy of Rectal
Cancer
1990 US NIH Consensus Conference

Postoperative chemoradiotherapy =
standard of care for RC Stage II,III

The consensus statement was based

upon the results of three randomised trials
 ESMO Recommendations
Resectable cases
Surgical procedure: TME
Preoperative RT: recommended
Postoperative chemoradiotherapy: T3,4 or
N+

Non-resectable cases: local recurrences

Preoperative RT with or without CT
 Predicting risk of recurrence in
Rectal Carcinoma
Surgery-related Tumor-related
-Low anterior resection -Anatomic location
-Excision of the -Histologic type
mesorectum -Tumor grade
-Extend of -Pathologic stage
lymphadenectomy -radial resection
-postoperative margin
anastomotic -neural, venous,
leakage lymphatic invasion
-Tumor perforation
Incidence of local failure in RC
T1-2,No,Mo <10%
T3,No,Mo 15-35%
T1,N1,Mo 15-35%
T3-4,N1-2,Mo 45-65%
 Total Mesorectal Excision
(TME)
Local recurrence rates after surgical
resection of RC have decreased from
about 30% to < 10%

1. Radio(chemo)therapy
2. Importance of circumferential margin
(TME)
 Screening

What is screening?

A public health service in which members of a

defined population are examined to identify
those individuals who would benefit from
treatment

To benefit:
to reduce the risk of a disease or its
complications
 Types of Screening

Fecal occult blood test (FOBT)

Chemical test for blood in a stool sample.
Annual screening by FOBT reduces
colorectal cancer deaths by 33%

Flexible sigmoidoscopy can detect about

65%–75% of polyps and 40%–65% of
colorectal cancers.
Rectum and sigmoid colon are visually
inspected
 Current Screening Guidelines

Regular screening for all adults aged 50

years or older is recommended

FOBT every year

Flexible sigmoidoscopy every 5 years

Total colon examination by colonoscopy every

10 years or by barium enema every 5–10
years
NORMAL COLONIC MUCOSA
Concept of differentiation is demonstrated by this small
adenomatous polyp of the colon. Note the difference in staining
quality between the epithelial cells of the adenoma at the top and
the normal glandular epithelium of the colonic mucosa below.
At high magnification,normalal epithelium at the left contrasts with the
atypical epithelium of the adenomatous polyp at the right. Nuclei are
darker and more irregularly sized and closer together in the
adenomatous polyp than in the normal mucosa.
Poorly differentiated neoplasm, it is difficult to tell the cell of origin.
It is probably a carcinoma because of the polygonal nature of the
cells. Note that nucleoli are numerous and large in this neoplasm.
CK staining reaction for carcinomas helps to distinguish carcinoma from
sarcomas and lymphomas. Immunoperoxidase staining is helpful to determine
the cell type of a neoplasm when the degree of differentiation, or morphology
alone, does not allow an exact classification.
Changes resulting in colon cancer
 Molecular Biology & Pathology

CRCs arise from a series of histopathological and molecular

changes that transform normal epithelial cells

Intermediate step is the adenomatous polyp

Adenoma-Carcinoma-Sequence (Vogelstein & Kinzler)

Polyps occur universally in FAP, but FAP accounts for only

1% of CRCs

Adenomatous Polyps in general population:

33% at age 50
70% at age 70
 Summary
CRC is a leading cause of death

Early stages are detectable

Screening can prevent CRC

 REFERENCES
Katie Couric: http://
www.nccra.com/about/videos.htm
http://
en.wikipedia.org/wiki/File:Colon_cancer.jpg
http://
ehumanbiofield.wikispaces.com/colon+cancer