Colorectal cancer

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Introduction0:00–0:56

Colorectal carcinoma, also known as colon cancer, is when malignant or cancerous cells arise in the large intestines, which includes the colon and rectum.
It is the most common type of cancer of the gastrointestinal tract, and a major cause of death and disease around the world.
The large intestine is found in the abdominal cavity, which can be thought of as having two spaces - the intraperitoneal space and the retroperitoneal space.
The intraperitoneal space contains the first part of the duodenum, all of the small intestines, the transverse colon, sigmoid colon, and the rectum; the retroperitoneal space contains the distal duodenum, ascending colon, descending colon, and anal canal.
So the large intestines essentially weave back and forth between the intraperitoneal and retroperitoneal spaces. Now, the walls of the gastrointestinal tract are composed of four layers.

Physiology0:56–1:44

The outermost layer is the called serosa for the intraperitoneal parts, and the adventitia for the retroperitoneal parts.
Next is the muscular layer, which contracts to move food through the bowel. After that is the submucosa, which consists of a dense layer of tissue that contains blood vessels, lymphatics, and nerves.
And finally, there’s the inner lining of the intestine called the mucosa; which surrounds the lumen of the gastrointestinal tract, and comes into direct contact with digested food.
The mucosa has invaginations called intestinal glands or colonic crypts, and it’s lined with large cells that are specialized in absorption.

Pathology1:44–4:31

Most colorectal carcinomas are adenocarcinomas, meaning that they arise from the cells lining the intestinal glands. Most cases of colorectal tumors happen because of sporadic mutations, but a small number are caused by known genetic mutations that run in a person’s family.
An example of this is the adenomatous polyposis coli gene, or APC gene, which is a tumor suppressor gene. Normally, the APC protein identifies when a cell is accumulating a lot of mutations and forces it to undergo apoptosis, or programmed cell death.
But when the APC gene is mutated, the mutated bowel cells don’t die, and instead some start dividing uncontrollably, giving rise to polyps.
Over time, these polyps might accumulate more mutations in other tumor suppressor genes like the K-ras gene or the p53 gene, and ultimately it might might become a malignant tumor - meaning that the cells might be able to invade neighboring tissues.
Another well known example are genetic mutations in DNA repair genes which help fix up mutations in cellular DNA. When they’re out of action - cells accumulate mutations and over time can develop into polyps and eventually adenocarcinomas.
So, broadly speaking, adenocarcinomas are the malignant evolution of polyps, and polyps arise when cells start dividing faster than usual.
There are many different types of polyps, and some are more prone to become malignant; those are called pre-malignant or neoplastic polyps.
These pre-malignant polyps can be classified into adenomatous and serrated, according to how they look under the microscope.
Typically, adenomatous polyps have an APC mutation and the cells look like normal colonic mucosa cells, whereas serrated polyps have defects in DNA repair genes and have a saw-tooth appearance.
When tumors become cancerous, they can be categorized into stages. Stage 0 is carcinoma in situ, meaning that the tumor has not grown beyond the mucosa.
Stage 1 is when the tumor has grown beyond the mucosa, but has not spread to lymph nodes or distant organs. Stage 2 is when the tumor has invaded the whole colonic or rectal wall, and may have reached nearby organs or tissues, but still hasn’t spread to lymph nodes or distant organs.
Stage 3 is when the tumor had spread to lymph nodes, but still hasn’t spread to distant organs. Finally, stage 4 is metastatic, meaning that the tumor has spread to distant organs.
The most common site of metastasis for colon cancer is the liver, and for rectal cancer it’s the lungs. There are some non-modifiable risk factors for colorectal cancer like being an elderly male and having inflammatory bowel disease, but there are some modifiable risk factors as well, like smoking cigarettes, eating a lot of red meat, not eating a lot of fiber, and being obese.

Risk Factors4:31–5:01

Colorectal cancer are also also associated with specific disorders like familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

Symptoms5:01–6:04

Initially, colorectal carcinoma is often asymptomatic, but as the disease progresses, symptoms can develop depending on the tumor’s location.
Tumors in the ascending or right colon generally grow outward beyond the surface of the mucosa, and that can cause vague abdominal pain and weight loss.
Typically, these tumors don’t cause bowel obstruction, which means that they can grow quite large before causing symptoms and that also means that there’s often a late diagnosis.
These tumors can ulcerate and bleed, and over time, the bleeding can lead to iron deficiency anemia. Tumors located on the descending or left colon are generally infiltrating masses, meaning that they tend to be ring-shaped masses that involve the whole circumference of the colonic wall.
This causes lumen narrowing, referred to as napkin-ring constriction, so symptoms of bowel obstruction typically happen early on.
Bowel obstruction can cause colicky abdominal pain, and blood-streaked stools, called hematochezia. Diagnosis of colorectal cancer typically requires colonoscopy, which is when a camera is inserted retrograde into the colon and rectum and to take pictures of abnormal looking polyps and a biopsy.

Diagnosis6:04–7:21

In addition, fecal occult blood testing is often done to look for evidence of gastrointestinal bleeding. Typically, in colorectal cancer there’s an elevation in the tumor marker CEA, which is a glycoprotein involved in cell adhesion.
However, this is not a very specific finding. A barium enema can be useful as well.
That’s where a liquid is injected into the rectum through a small tube, and an X ray is taken to look for abnormalities in the large intestines.
On a barium enema, a classic sign of colorectal cancer is the apple core sign, which shows the constriction of the lumen - most often in the descending colon.
To identify colorectal cancer early, routine colonoscopy and fecal occult blood test can be done to look for neoplastic polyps or early carcinomas so that they can be removed at an early stage.
This is particularly important for individuals with relatives with colorectal cancer and those with disorders like familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

Treatment7:21–7:44

Treatment for colorectal cancer depends on the stage of the cancer. Early cancers that are confined to the wall of the colon are often surgically resected, and those that have spread to nearby lymph nodes are often treated with chemotherapy.
Unfortunately, metastatic cancers are typically incurable, but sometimes chemotherapy or surgery can be used to ease symptoms.

Review7:44–9:02

All right, as a quick recap, colorectal carcinoma is a very common and deadly cancer that affects the large intestines. The majority of cases are sporadic and do not have a clear cause, but modifiable risk factors include smoking cigarettes, eating a lot of red meat, not eating a lot of fiber, and being obese.
Symptoms can vary based on the tumor’s size and location. Tumors of the right colon generally don’t cause bowel obstruction, and instead can cause occult bleeding, which can lead to iron-deficiency anemia.
Whereas tumors of the left colon are generally ring-shaped masses, which can cause bowel obstruction, with constipation and abdominal pain.