CRC: EPIDEMIOLOGY
Slides last updated: March 2015
Colorectal cancer incidence and mortality1
CRC caused 694,000
deaths in 2012, 8.5% of
the total. Central and
Eastern Europe had the
highest mortality rates
30
Mortality (% of all cancer types)
Colorectal cancer (CRC)
is the third most common
cancer in men and second
most common in women
worldwide, with 1.4
million new cases in 2012
Lung
25
Stomach
20
15
Liver
10
Colorectal
5
0
Both
sexes
Men
Women
Female
breast
1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.
GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet].
Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on
17/02/2015.
Rates of CRC incidence and mortality differ worldwide1
Australia/New Zealand
Western Europe
46% of new CRC cases and
52% of deaths by CRC occur in
developing countries
Southern Europe
Northern Europe
More developed regions
Central and Eastern Europe
Northern America
Micronesia
Eastern Asia
Highest CRC rates are found in
Australia/New Zealand
CRC is the 2nd most common
cancer in both men and women
in this region
World
Caribbean
South America
Western Asia
South-Eastern Asia
Less developed regions
Southern Africa
Polynesia
Melanesia
Lowest CRC rates are found in
Western Africa
CRC is the 3rd most common
cancer in men and 4th most
common in women this region
Central America
Incidence
Northern Africa
Mortality
Eastern Africa
South-Central Asia
Middle Africa
Male
Female
Western Africa
50
40
30
20
10
0
10
20
30
40
50
Estimated age-standardized rates (World) per 100,000
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality
Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available
from: http://globocan.iarc.fr, accessed on 15/09/2013.
Survival rates for CRC have been steadily improving1
Five-year survival trend
100
Colorectal
cancer
Percentage
80
60
40
Lung
cancer
20
0
1975
1990
2005
Survival rates vary
depending on stage
at diagnosis. The
later the stage of
diagnosis the
lower the survival
rates tend to be.
1. SEER. Fast Stats Online. 5 year survival by diagnosis. 1975-2010. All races. All ages. Male and Female. Available online from
seer.cancer.gov/faststats/selections.php, last accessed on 17/03/2015.
Adenocarcinomas make up more than 95% of CRC1
CRC
(100%)
Adenocarcinomas start in
gland cells that make mucus
to lubricate the inside of the
colon and rectum
Less common types of CRC:
•Carcinoid tumours
•Gastrointestinal stromal
tumours (GISTs)
•Lymphomas
•Sarcomas
Adenocarcinoma
(>95%)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
CRC: CLASSIFICATION AND PATHOLOGY
Slides last updated: March 2015
Adenocarcinomas make up more than 95% of CRC1
Adenocarcinomas start
in gland cells that make
mucus to lubricate the
inside of the colon and
rectum
Less common types of
CRC:
•Carcinoid tumours
•Gastrointestinal stromal
tumours (GISTs)
•Lymphomas
•Sarcomas
CRC
(100%)
Adenocarcinoma
(>95%)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Less common types of CRC1
Carcinoid tumours start from specialised hormone-producing cells in the
intestine
Gastrointestinal stromal tumours (GISTs) start from specialised cells in
the colon wall called the interstitial cells of Cajal. They can be found
anywhere in the digestive tract, and are rare in the colon
Lymphomas are cancers of the immume system that usually start in
lymph nodes, but may also start in the colon, rectum and other organs
Sarcomas start in blood vessels or in the muscle and connective tissue
in the wall of the colon and rectum. Colorectal sarcomas are rare
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Most CRCs develop slowly over several years1
Before a cancer develops, growth of tissue or tumour usually begins as a
non-cancerous polyp on the inner lining of the colon or rectum
Some polyps can become malignant (cancerous), but some remain benign
(not cancerous)
The two main types of polyps are:
•Adenomas (adenomatous polyps) – develop into cancer
•Hyperplastic polyps and inflammatory polyps – not pre-cancerous but
might be considered as a sign of having a greater risk of developing
adenomas
Dysplasia is a pre-cancerous condition often seen in patients with
inflammatory bowel disease. Cells in the lining of the colon or rectum may
look abnormal under a microscope and develop into cancer over time
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Loss of genomic stability can drive CRC1
Chromosomal instability:
•Causes physical loss of a wild-type copy of tumour-suppressor genes
such as APC, TP53 and SMAD4
•Unlike some other cancers, CRC does not commonly involved
amplification of gene copy number or gene rearrangement
DNA-repair defects:
•Inactivation of genes required for repair of base-base mismatches in
DNA, known as mismatch-repair genes
•Can be inherited (HNPCC) or acquired
•Leads to microsatellite instability (MSI)
Aberrant DNA methylation:
•Leads to gene inactivation
•A methylated form of cytosine is observed in 15% of CRC cases
1. Markowitz SD, et al. N Eng J Med 2009;361:2449-60.
Sequencing of CRC has shown its wide heterogeneity1
The average stage IV CRC genome has 15 mutated candidate cancer
genes, and 61 mutated passenger genes (very low frequency mutational
events)
In the progression of CRC, genetic alterations target the following genes to
either turn on oncogenic mediators or turn off tumour-suppressor factors:
MSI
(MMR mutation)
(MLH1 methylation)
Normal
epithelium
APC,
-Catenin
Chromosomal
instability
(eg, CDC4)
Small
adenoma
KRAS,
BRAF
PIK3CA,
PTEN
Large
adenoma
TP53,
BAX
SMAD4,
TGFBR2
Cancer
Growth factors:
•Oncogenic mediators that are turned on in CRC are COX-2 and EGFR
•Tumour-suppressor factors that are turned off are 15-PGDH and TGF-
1. Markowitz SD, et al. N Eng J Med 2009;361:2449-60.
Key pathways in CRC1
•
APC mutations are present n 85% of CRCs
•
Result in the activation of the Wnt signalling pathway, regarded as the
initiating event in CRC
•
TP53 mutations are present in 35-55% of CRCs
•
Lead to inactivation of the p53 pathway, which often coincides with the
transition of large carcinomas into invasive carcinomas
•
KRAS and BRAF mutations are present in 37% and 13% of CRCs,
respectively
•
The mitogen-activated protein kinase (MAPK) pathway is activated
•
BRAFV600E activating mutation is present in 8-12% of CRCs
•
PI3KCA activating mutations are present in one third of CRC cases
•
PTEN inactivating mutations lead to identical results (activation of PI3K)
1. Markowitz SD, et al. N Eng J Med 2009;361:2449-60.
Key pathways in CRC1
•
TGFBR2 is inactive in one third of CRCs, inactivating the TGF- pathway
(mediator of growth arrest and apoptosis)
•
TGF- pathway inactivation coincides with the transition of an adenoma
to high grade dysplasia or carcinoma
•
Approximately two-thirds of CRC cases show increased levels of COX2, an enzyme involved in the activation of prostaglandin signalling
•
This signalling pathways is a critical step in the development of an
adenoma
•
The vascular endothelial growth factor (VEGF) and its receptor (VEGFR)
stimulate angiogenesis
•
Angiogenic pathways appear to be involved in the growth and lethal
potential of CRC
1. Markowitz SD, et al. N Eng J Med 2009;361:2449-60.
CRC: RISK FACTORS
Slides last updated: March 2015
Lifestyle-related risk factors in CRC1,2
•
Diets that are high in red meats and processed meats
-Conversely, diets that are high in vegetables, fruits and whole
grains have been linked with a decreased risk of CRC
•
Physical inactivity
•
Obesity/high body mass index
•
Long-term smoking
•
Heavy use of alcohol
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer. Version 2.2015. Available online
from http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf, last accessed on 17/03/2015.
Personal and family history-related risk factors in CRC1,2
•
Personal history of CRC or adenomas
•
Personal history of inflammatory bowel disease
•
Family history of CRC or adenomas
-
•
The majority of
CRC cases are
sporadic; only 25%
of CRC cases have
a family history3
Screening for CRC before the age of 50 may be an option
Inherited syndromes
-
5-10% of CRC patients have inherited gene mutations
-
Includes familial adenomatous polyposis (FAP), hereditary nonpolyposis colon cancer (HNPCC, or Lynch syndrome), Turcot
syndrome, Peutz-Jeghers syndrome and MUTYH-associated
polyposis
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer. Version 2.2015. Available online
from http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf, last accessed on 17/03/2015.
3. Migliore L, et al. J Biomed Biotechnol 2011;Article ID 792362.
Other risk factors in CRC1,2
•
Age
-
90% of people diagnosed with CRC are ≥50 years old
•
Type 2 diabetes
•
Metabolic syndrome
-
•
Combination of diabetes, high blood pressure and obesity
Certain racial and ethnic backgrounds
-
African-Americans have the highest CRC rates in the US
-
Ashkenazi Jews (of Eastern European descent) have one of the
highest CRC risks of any ethnic group in the world; several
gene mutations associated with CRC risk have been found
within this group
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer. Version 2.2015. Available online
from http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf, last accessed on 17/03/2015.
CRC: CLINICAL FEATURES
Slides last updated: June 2015
CRC diagnosis includes several assessments1
•
Complete medical history, as well as family history
•
Physical exam to look for masses in the abdomen and enlarged
organs
•
Blood tests
•
Colonoscopy
•
Biopsy and lab tests of samples
•
Imaging tests
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Colonoscopy and blood tests1
Colonoscopy:
•Main procedure for diagnosis2
•Can determine the exact location, detect further lesions and remove
polyps
•If a complete colonoscopy is not possible, colonoscopy of the rectum
and sigmoid colon should be combined with a barium enema2
Blood tests:
•Complete blood count – to detect anaemia
•Liver enzymes – to assess liver function
•Tumour markers – most commonly in patients with a history of CRC
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
2. Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.
Tests of biopsy samples and imaging tests1
Tests of biopsy samples:
•Gene tests – to detect specific mutations that impact treatment decisions,
e.g., KRAS
•MSI testing – detection of microsatellite instability may identify conditions
such as HNPCC and affect treatment choice
Imaging tests:
•CT scans, ultrasounds, MRI scans and PET scans – to assess the presence
and spread of cancer
•Chest X-ray – to check if cancer has spread to the lungs
•Angiography – to visualise blood supply to the cancer (particularly
relevant if cancer has spread to the liver)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Some common CRC symptoms1,2
Most people with early CRC do not display
symptoms of the disease. Symptoms are
typically associated with relatively large
tumours and/or advanced stages and tend
not to be specific to the disease
It is very important to
discuss any potential
CRC symptoms with a
healthcare provider
Change in bowel habits (persistent diarrhoea,
constipation or narrowing of stool)
Cramping and abdominal pain
Blood in faeces (that may lead to
darker faeces than normal)
Rectal bleeding
Unexplained weight loss
Iron deficiency and anaemia
Weakness and fatigue
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
2. Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.
Screening aims to find benign adenomas or early CRC1,2
Screening tests can be structural or faecal-based
•Structural
-
Colonoscopy – most complete screening procedure
-
Flexible sigmoidoscopy – limited to the lower part of the bowel
-
Computed tomographic colonography (CTC) – virtual
colonoscopy, under evaluation
•Faecal-based
-
Faecal occult blood tests (FOBT) – test for blood in faeces; can
be guaiac-based (gFOBT) or immunochemical (iFOBT or FIT)
-
Stool DNA test – test for known DNA alterations during CRC
progression, under evaluation
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2014.
Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 17/03/2015.
2. Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.
NCCN (US) screening recommendations1
A risk-based approach is recommended, with patients assigned to one of
the following categories:
•Average risk
-
≥50 years of age
-
Negative family history
-
No history of adenoma, CRC or inflammatory bowel disease
•Increased risk
-
Either a personal history of adenomas or sessile serrated polyps
(SSPs), CRC or inflammatory bowel disease
-
Or a positive family history of CRC or advanced adenomas
•High-risk syndromes
-
Either a family history of HNPCC
-
Or a personal or family history of polyposis syndromes
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2015.
Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 16/06/2015.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Genetic/Familial High-Risk Assessment:
Colorectal. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf, last
accessed on 16/06/2015.
NCCN (US) screening recommendations1
Guidance is provided for the following groups:
•
Average risk
-
•
Recommended screening options include
•
colonoscopy every 10 years
•
annual faecal-based tests
•
flexible sigmoidoscopy every 5 years with or without an
interval faecal-based test at year 3
Increased risk or high-risk syndromes
-
Surveillance programme tailored to the patient’s personal history
and preferences as well as their detailed family history
-
Screening intervals (mostly colonoscopy) adjusted to match
each case
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Colon Cancer Screening. Version 1.2015.
Available online from http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, last accessed on 16/06/2015.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines on Genetic/Familial High-Risk Assessment:
Colorectal. Version 1.2015. Available online from http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf, last
accessed on 16/06/2015.
ESMO (European) screening recommendations1
Guidance for average-risk populations is provided:
•Screening interval for gFOBT should not be >2 years
-
if iFOBT, the interval should be the same as for gFOBT or <3
years
•Screening interval for flexible sigmoidoscopy and colonoscopy should
not be <10 years and can be extended to 20 years
New screening techniques such as CTC and stool DNA tests are still
under evaluation and not recommended for screening in the average-risk
population
1. Labianca R, et al. Ann Oncol 2013;24(Suppl 6):vi64-72.
CRC: STAGING
Slides last updated: March 2015
How colorectal cancer (CRC) is staged1
Stage describes the extent of cancer, and is one of the most important
factors in determining prognosis and treatment options
For CRC, stage is based on how far the cancer has grown into the
intestinal wall, if it has reached nearby structures, and if it has spread to
distant organs
Staging is the process of determining how far the cancer has spread, and
involves physical exam, biopsies, imaging tests and results of surgery
Clinical staging uses results of the physical exam, biopsy and imaging
tests. Pathologic staging combines these tests with results from surgery
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
TNM classification is the most commonly used system1
Growth
Primary tumour (T)
Spread
Regional lymph nodes (N)
Metastasis
Distant metastasis (M)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
The TNM staging system for CRC: T1
T categories describe the extent of spread through the layers that
form the wall of the colon and rectum
These layers, from inner to outer, include:
•Mucosa – inner lining
•Muscularis mucosa – a thin muscle layer
•Submucosa – the fibrous tissue beneath this muscle layer
•Muscularis propria – a thick muscle layer that contracts to force the
contents of the intestines along
•Subserosa and serosa – the thin outermost layers of connective
tissue that cover most of the colon
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
The TNM staging system for CRC: T1
Tx: No description is possible due to incomplete information
Tis: The cancer is at its earliest stage (in situ) and involves only the
mucosa; it has not grown beyond the muscularis mucosa
T1: The cancer has grown through the muscularis mucosa and extends
into the submucosa
T2: The cancer has grown through the submucosa and extends into the
muscularis propria
T3: The cancer has grown through the muscularis propria and into the
outermost layers of the colon or rectum, but not through them
T4a: The cancer has grown through the serosa, the outermost lining
T4b: The cancer has grown through the wall of the colon or rectum and is
attached to or has invaded nearby tissue or organs
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
The TNM staging system for CRC: N1
N categories indicate whether the cancer has spread to nearby lymph
nodes, and if so, how many lymph nodes may be involved
For an accurate estimation of lymph node involvement, ≥12 lymph nodes
are removed during surgery and examined under a microscope
Nx: No description is possible
N0: No cancer cells in nearby lymph nodes
N1: Cancer cells found in 1-3 nearby lymph nodes
•N1a: 1 lymph node
•N1b: 2-3 lymph nodes
•N1c: Small deposits of cells found in areas of fat near lymph nodes,
but not in the nodes themselves
N2: Cancer cells found in ≥4 nearby lymph nodes
•N2a: 4-6 lymph nodes
•N2b: ≥7 lymph nodes
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
The TNM staging system for CRC: M1
M categories indicate whether the cancer has spread (metastasised) to
distant organs such as the liver, lungs or distant lymph nodes
M0: No distant spread is seen
M1a: Cancer has spread to one distant organ or set of lymph nodes
M1b: Cancer has spread to more than one distant organ or set of lymph
nodes, or to distant parts of the peritoneum (lining of the abdominal
cavity)
Once the T, N and M categories have been determined – usually after
surgery – the information is combined in a process called stage grouping
Stages range from stage I (least advanced) to stage IV (most advanced)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Stages in CRC1
Cancer progression
Stage 0
Stage I
Stage IIA
Stage IIIA
Stage IVA
Tis, N0, M0
T1-T2, N0, M0
T3, N0, M0
T1-T2, N1, M0
T1, N2a, M0
Any T, any N,
M1a
Stage IIIB
Stage IVA
T3-T4a, N0, M0
T2-T3, N2a, M0
T1-T2, N2b, M0
Any T, any N,
M1b
Stage IIB
T4a, N0, M0
Stage IIC
T4b, N0, M0
Stage IIIC
T4b, N0, M0
T3-T4a, N2b, M0
T4b, N1-N2, M0
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Survival rates for CRC by stage1
Five-year relative survival rate
100
Colon cancer
Survival rate (% )
80
Rectal cancer
Refers to the
percentage of
patients who live at
least 5 years after
diagnosis
60
40
20
0
I
IIA
IIB
IIIA
IIIB
IIIC
IV
Relative survival
rates compare
observed survival
with what would be
expected without
cancer
Stage
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
Grades of CRC1
Survival is also affected by the grade of cancer
Grade describes how closely the cancer looks like normal tissue when
viewed under a microscope
•Grade 1 (G1): cancer looks much like normal colorectal tissue
•Grade 4 (G4): cancer looks very abnormal
•Grades 2 and 3 (G2 and G3) fall in between G1 and G4
Often simplified to either low grade (G1, G2) or high grade (G3, G4)
Low-grade cancers tend to grow and spread more slowly than highgrade cancers
The outlook for low-grade cancers tends to be better than for high-grade
cancers
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.
CRC: ANATOMY OF THE GASTROINTESTINAL TRACT
Slides last updated: March 2015
The wall of the GI tract is composed of four layers1
GI tract wall
1. Mucosa
2. Submucosa
Lumen
3. Muscularis
4. Serosa
1. Tortora GJ, et al. Principles of Anatomy and Physiology. 11th Ed. Hoboken: John Wiley & Sons;2006:895-946.
The wall of the GI tract is composed of four layers1
1. Mucosa
•
Mucous membrane that lines the lumen of the GI tract
•Further divided into the epithelium, lamina propria and muscularis
mucosa
2. Submucosa
•Areolar connective tissue that binds the mucosa to the muscularis
•Contains blood and lymphatic vessels that receive the absorbed
nutrients
•Also contains glands, lymphatic tissue and an extensive network of
neurons
1. Tortora GJ, et al. Principles of Anatomy and Physiology. 11th Ed. Hoboken: John Wiley & Sons;2006:895-946.
The wall of the GI tract is composed of four layers1
3. Muscularis
•Contains either skeletal muscle for voluntary control of movement, or
smooth muscle organised in two sheets of perpendicular fibres to
generate involuntary contractions
4. Serosa
•Superficial layer of the GI tracts segments that are suspended in the
abdominopelvic cavity
•Also called the visceral peritoneum
•Composed of areolar connective tissue and simple squamous
epithelium
1. Tortora GJ, et al. Principles of Anatomy and Physiology. 11th Ed. Hoboken: John Wiley & Sons;2006:895-946.
Stage is determined by how far the cancer has spread1
Cancer progression
Stage 0
Cancer is in the
mucosa only
Stage
IA-B
Stage
IIA-C
Stage
IIIA-C
Stage
IVA-B
Cancer has
grown through
the muscularis
mucosa or
submucosa
Cancer has
grown through
the muscularis
propria, serosa,
or through the
colon or rectum
wall
Cancer has
grown through
at least the
muscularis
mucosa, and
has been found
in nearby
lymph nodes
Cancer has
grown through
at least the
muscularis
mucosa and
has spread to
distant organs
(metastasised)
1. American Cancer Society. Colorectal Cancer Detailed Guide, 2014. Available online from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003096-pdf.pdf, last accessed on 17/03/2015.