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Epidemiology:-
Epidemiology of colorectal cancer is essential to know the size of the
problem and why it is important.
The incidence of colorectal cancer varies widely. It is one of the diseases
with a known geographical variation.
The incidence varies between 4/100,000 and 40/100,000.
The countries that are having the highest incidence are the United
States, New Zealand, Australia, Scandinavian countries, while the
countries with the low incidence are the African and South American
countries.
So, it is clear that as you go up with the development of the country
the incidence of colorectal cancer increases.
It is important to differentiate between the contribution of cancer
to death and the incidence of the cancer.
In the United States for example, colorectal cancer is considered the 2nd
cause of death because of the so many statistics there, while it is the 3rd
most common cancer there.
In female it is preceded by lung and breast cancers, in male it is
preceded by lung and prostate cancers.
The incidence in the United States is around 4/100,000.
There is nearly equal incidence in both sexes, some statistics showed
slight male predominance and the mean age in the west is 63.
In that year (2007) more than 500 new cases have been diagnosed.
The surprise is that colorectal cancer contributes to 12% of all cancers in
Jordan. This includes solid tumors and blood malignancies.
Taking into account all males and females together, it is the second
most common cancer. In females it is preceded only by breast cancer, in
males it is number one. Even, it is exceeding lung cancer.
So, in males colorectal cancer is cancer number one and in females the
high numbers of breast cancers shift colorectal cancer to be cancer
number two.
The male to female ratio is 1.2/1. As mentioned above, some
statistics showed slight male predominance.
The median age in Jordan is 61. This is important to notice because
as you see it is not much less than it is in the west.
Before 10-15 years ago the average age in Jordan was at least 10 years
earlier or younger than the west. But it seems that Jordan is catching
up. However, it did not reach the median age in the west.
Known that the incidence varies between 4-40/100,000 and out of
the high incidence in Jordan we expect to find a high incidence per
100,000, surprisingly the age specific incidence is 17.2/100,000 and
the root incidence is no more than 12/100,000.
So, per 100,000 Jordan lies in the low figures zone. But as an
incidence or contribution to cancer it is number 2.
An explanation for that: The Jordanian population is a young
population, more than 37% of the population is under 15 years of age
and only 3.2% is above 65.
Relating to that colorectal cancer is a disease of the elderly, when we
say that the incidence is 17.2/100,000 we are taking the whole
population into account, but if we take the elderly group alone the
incidence will be high.
It is also worthy to notice from the statistics the number of cases in the
young, more than 13% of the patients are below 45 years of age in
Jordan.
In the west this number is no more than 6%. That is because we are
having huge number of young patients in Jordan, so even if the
incidence in them is low their contribution to the population is high
resulting in a higher number of cases than the west.
In brief out of epidemiology, colorectal cancer is number two. It is
number one in males. The median age is in the early 60's, in Jordan it is
a little bit younger than the west and we are having a greater
contribution of patients towards the young age group.
Risk Factors:-
1- Age:- any patient who is getting older and older will have a higher
risk of developing colorectal cancer.
People or scientists use the age of 50 as a landmark for screening,
screening means investigating people who are asymptomatic, because
we can't screen everybody for colorectal cancer.
The reason for the limitation of using screening is that we don’t have
an ideal screening test. Ideal screening test is a test that is cheap, not
invasive, can be easily done with good sensitivity, good specificity, the
cost is low and the acceptance from the population is high. Such
screening test we lack for colorectal cancer.
The best tool to diagnose colorectal cancer is colonoscopy. But
colonoscopy is not cheap, it is invasive and the compliance from the
population is low.
So, we have to limit the group of patients on whom we can do
screening, that’s why the idea of risk factors came about, which is to
decrease the number of people on whom it is justifiable to do screening.
2- Family history:- whether the family history of colorectal cancer
or even other cancers.
3- Polyps:- once a patient develops polyps he needs follow up for
the possibility of cancer.
4- Ulcerative colitis:- specially if ulcerative colitis has been there for
around 10 years and it involves the whole colon, these patients are
more liable to develop colorectal cancer.
5- Hereditary conditions:- like familial adenomatous
polyposis (FAP) and hereditary nonpolyposis colon cancer
(HNPCC).
Polyps:-
More than 95% of colorectal cancers occur on top of one type of polyps
which is adenoma, we have a lot of polyps. The term polyp is not a
pathological term, it is a descriptive term, any elevation in the
mucosa is called polyp.
What is related to colorectal cancer are the adenomatous polyps,
they are the premalignant ones. Again, it is important to remember
that more than 95% of colorectal cancers occur in these polyps.
• Grossly:- they are divided into sessile or pedunculated,
depending on whether they have a stalk or not.
• Pathologically:- they are divided into tubular, villous or
tubulovillous (combination of both).
Villous adenoma
Tubular adenoma
Tubular adenoma with
few septations, this is
up view.
Pedunculated Vs Sessile
Pedunculated:- not in direct touch with the mucosa of the colon and has a stalk.
Sessile:- in direct touch with the mucosa of the colon and has no stalk.
Adenomatous Others Tubular Villous Both
Polyp description
Colonoscopic polyps
If 95% of the cases occur on top of polyps what about the other 5%?
The other 5% of cases inherit the cancer itself, not requiring going
through the adenoma-carcinoma sequence.
Inheritance of the cancer is similar to the inheritance of thalassaemia
or sickle cell anemia.
Role of diet:-
1- High animal fat:- It was noticed in countries with high incidence
like United States and New Zealand that the more you have animal fat
the higher is the incidence.
In these countries they eat a lot of meat like beef. But actually the
criminal here as we said is the animal fat.
Even if the gross fat is removed, in between the meat parts there is
plenty of fat.
What is the problem with animal fat?
Animal fat will cause the secretion of bile, bile acids will change into
bile salts, bile salts will be acted upon by bacteria and the result of
that is carcinogenic.
So the problem here is not the fat or bile itself, the bile which is acted
upon by bacteria is the source of the problem.
2- Refined carbohydrates:- the more you have refined
carbohydrates the higher is the incidence.
What is the problem with refined carbohydrates?
They contain a lot of additives, these additives are carcinogenic.
3- Low vegetable fibers:- the vegetable fibers are protective, the
more you have fibers the less is the chance of malignancy.
Why the fibers are protective?
The rule of fiber is purely mechanical:-
• Some fibers will bind to the carcinogenic agents making them
inactive and decreasing their concentration.
• Some fibers will make the stool bulky. Accordingly, fibers will
increase the bowel motions.
The end result will be decreasing the contact between the carcinogens
and the mucosa.
4- Alcohol and smoking:- the more you have alcohol and smoking
the higher is the incidence and these are accused for most cancers.
5- Aspirin and non-steroidal:- aspirin and non-steroidal provide
some protection.
Why aspirin and non-steroidal are protective?
A possible theory is through inhibiting cox-2 (cyclooxygenase
enzyme).
It was noticed that the cox-2 is high in
90% of cases of colorectal cancer and is high in 40-90% of patients with
adenoma.
Why cox-2 increases the production of colorectal cancer?
Actually, it mediates the production of prostaglandin E2. It was
found that prostaglandin E2 increases cell proliferation and
angiogenesis, which is important for the development of malignancy.
Pathology:-
Histopathology:-
• More than 98% of colorectal cancer is adenocarcinoma, this is
the cancer that occurs in mucosa having columnar cells.
• The other 2% includes rare tumors like carcinoids,
leiomyosarcoma, lymphoma and others.
Adenocarcinoma is the one that occurs on top of adenomatous polyp.
So, as you see a polyp is an adenoma. If it progresses, it is going to
progress to adenocarcinoma.
Gross pathology:-
• Fungating.
• Ulcerating.
• Stenosing.
One presentation grossly is a stenosing lesion. The lumen of the
bowel becomes narrower, so proximal to it the colon dilates and distal
to it the colon collapses.
What do we expect from a patient with a narrowed lumen to
complain of?
• Changing of the bowel habit in the form of constipation.
• Difficulty in passing stools.
Another presentation grossly is polypoidal or a mass lesion. This is
more commonly found in the right side of the colon and the cecum
because it has a wide diameter.
Again, we expect from a patient with a mass lesion to have
obstructive symptoms.
All the lesions whether they are stenosing or mass like may ulcerate
and lead to bleeding.
As conclusion, the most common symptoms of colorectal cancer are
changing in the bowel habit and bleeding.
In addition to the fungation of the lumen, the tumor can go through
the wall till it reaches the surface or the serosa of the colon.
Always Remember:-
• Synchronous:- another primary at the same time,
the incidence is 3-15%.
• Metachronous:- another primary later on in life,
the incidence is 3-4%.
• The incidence of these is more in the inherited
type of colorectal cancer.
Signs:-
Unfortunately, when it comes to signs it usually indicates a late
diagnosis.
1- Pallor:- it means that the patient has been bleeding for a good
period of time.
2- Abdominal mass:- it means that the tumor has gone outside the
wall into the adjacent abdominal wall or viscera.
3- Jaundice and nodular liver:- it means that there is metastasis
to the liver.
4- Ascites:- it means that there is metastasis to the peritoneal cavity.
5- PR mass:- of course a mass through the PR can be both early or
late, it depends.
Always remember:-
• Don't wait till the signs appear, the diagnosis will be late.
• Don't forget to do PR examination, the diagnosis may be
missed.
Annular lesion
Annular lesion will leave a little
bit of the lumen and the remaining
is the tumor, this is called apple
core appearance.
Later on, the tumor is going to
obstruct the lumen completely.
Apple core appearance
The tumor left narrowed lumen at the centre.
The lumen from both sides is still wide because it is
not occupied by the tumor.
• This is a classical apple core appearance of colorectal cancer.
Sigmoidoscop vs Colonoscope
Flexible sigmoidoscope can travel
limited distance, it shows the rectum,
the sigmoid and part of the descending.
Full colonoscope can travel longer
distance, it shows the whole colon.
Today, we use TV screen
to see the colon.
Head of the colonoscope
Contains the light, lens and
channel to take biopsies,
inject air or even fluids.
Endorectal ultrasound
• It shows the layers of the
rectal wall from the
mucosa to the fat.
• It helps reaching diagnosis.
• It shows how far the tumor
has gone through the wall
(depth of invasion).
Mode of Spread:-
1- Direct:- the tumor spreads directly to adjacent structures causing for
example fistulas (colovesical fistula, rectovaganial fistula or
enterocutaneous fistula).
2- Lymphatic:- the tumor spreads through lymphatic channels to
lymph nodes.
3- Vascular system:- the tumor spreads through vessels to distant
organs, the commonest sites are:-
• Liver.
• Lung.
• Bone.
• Brain.
• Others.
Why the liver is number one?
The colon whether the right or the left drains into the portal circulation
and the portal circulation is received by the liver.
4- Transcoelomic:- The malignant cells are shed into the peritoneal
cavity. Patients with transcoelomic spread present with ascites.
Treatment:-
Always keep in mind that the treatment of colorectal cancer is
individualized.
It is not an appendicitis treated by appendectomy or gallstones
treated by laparoscopic cholecystectomy.
1- Surgery:- The main treatment option is surgery, a patient with
colorectal cancer will not be cured or improved without surgery.
The term surgery in colorectal cancer is not one thing, It is not
appendectomy or cholecystectomy. In colorectal surgery there are
many options, you can:-
• Remove the right colon which is right hemicolectomy.
• Remove the left colon which is left hemicolectomy.
• Remove the sigmoid which is sigmoidectomy.
• Remove the rectum which is anterior resection.
• Remove the rectum and the anal canal which is
abdominoperineal resection.
• Remove the whole colon which is total colectomy.
• Put a colostomy.
• Put an ileostomy.
• Put any other stomy.
The colostomy or ileostomy can be permanent or temporary.
2- Chemotherapy:- The other modality is chemotherapy.
• Chemotherapy which is given before surgery is called
neoadjuvant.
• Chemotherapy which is given after surgery is called adjuvant.
3- Radiotherapy:- It can be given also before and after therapy.
4- Combination:- chemotherapy can be given together with
radiotherapy which is called chemoradiotherapy.
As conclusion, there are a lot of treatment options depending on:-
• Type of surgery.
• Type of chemotherapy (before or after surgery).
• Type if radiotherapy (before or after surgery).
What will decide the treatment option?
• The criteria of the tumor.
• The location of the tumor.
• The invasion and the metastasis of the tumor.
• The general condition of the patient.
• The available resources.
• The experience of the treating physician.
All of these will affect the type of treatment offered to that patient.
In the past, before the start of doing hepatic resection this patient
was dead within few months.
Nowadays, we do surgery. It doesn’t mean that stage IV is a curable
disease, only minority of the patients with metastasis are candidate for
surgery.
Resection is not limited to the liver, it can be done for the lung, the
brain etc…
Metastatic Liver
The patient was having only
one lesion in the left lobe of
the liver.
The left lobe of the liver was
removed and the patient is
still alive since 3 years after
the surgery.
Students' questions
Is it worth it to resect metastasis even if the 5 years survival rate was
5%?
You are selective, you are not doing surgery for 100 to have a 5
years living. You are selecting the ones from the start.
So, out of these 3 patients on whom I have done liver resection I
have 20% on whom I haven’t done anything.
So, I select to have a relatively good outcome. I can tell you that
20% of the patients who had liver resection will live for 5 years, but the
patients that will have the resection are less than 20%.
Do we investigate every 50 years old patient who comes with
general signs and symptoms of gastrointestinal tract?
Yes we do, I will investigate any patient above 50 who is having
bowel symptoms. Otherwise, you will diagnose the patient late and you
will miss a lot of patients.
Elderly people usually have constipation, so why to do
investigations?
A recent change in the bowel habit is more important than
somebody who is having constipation for the last 20 years.
Any change in the bowel habit is important, it is much more
important than a chronic problem, so you have to respect any change
in the bowel habit.
What is the proper age for doing investigations in patients
complaining of change in bowel habit?
If there is change in bowel habit we do investigations regardless of
the age, above 50 u have to do screening for asymptomatic patients.
If you are investigating somebody who is having change in bowel
habit this is not screening this is investigation.
If the patient has a recent change in bowel habit without any other
associated symptoms, do we do investigations?
We do investigations even if he has only recent change in bowel
habit. This is how you get patients who are amenable for treatment
and good outcome.
If you wait for complete obstruction it is too late. Obstruction by the
way is a bad sign. Perforation is a bad sign also. It is one of the other
factors other than staging that will affect the outcome.
If you have a patient with one villous polyp in the rectum do we do
resection for the rectum or the colon?
Most of the polyps nowadays are removed through the colonoscope
and very few polyps need surgery, so we can remove the polyps only
without resection. That’s why we decreased the incidence of colorectal
cancer, especially on those patients who are having screening.