Bowel Cancer: Pathology and the Screening Process

Question 1

What are the three parts of the large bowel?

Answer 1

The three parts of the large bowel are the colon, rectum, and anus.

Question 2

Are there different forms of colorectal cancer?

Answer 2

Yes, there are both primary and metastatic forms of colorectal cancer.

Question 3

Which side of the colon is most commonly affected by cancer?

Answer 3

Cancer most commonly affects the left side of the colon.

Question 4

Are small bowel cancer and cancer of the anus common or rare?

Answer 4

Small bowel cancer and cancer of the anus are rare.

Question 5

What is the ranking of bowel cancer in terms of its commonality among men and women?

Answer 5

Bowel cancer is the 3rd most common cancer among men and women, accounting for 11% of all cancers.

Question 6

How many new cases of bowel cancer are reported each year in the UK?

Answer 6

There are approximately 42,900 new cases of bowel cancer reported every year in the UK, averaging to 120 cases per day.

Question 7

How many deaths occur each year due to bowel cancer in the UK?

Answer 7

Over 16,800 deaths occur each year in the UK due to bowel cancer, which is an average of 46 deaths per day.

Question 8

What is the ranking of bowel cancer as a cause of cancer death?

Answer 8

Bowel cancer is the 2nd most common cause of cancer death, accounting for 10% of all cancer deaths.

Question 9

How has the ten-year survival rate for bowel cancer changed over the last 40 years?

Answer 9

The ten-year survival rate for bowel cancer has doubled in the last 40 years, reaching up to 53% in adults.

Question 10

Where can polyps develop in the body?

Answer 10

Polyps can develop in various parts of the body, including the colon and rectum, ear canal, cervix, stomach, nose, uterus, throat, and bladder.

Question 11

Are all polyps in the large bowel precancerous?

Answer 11

No, not all polyps in the large bowel are precancerous. However, adenomatous polyps in the large bowel are considered precancerous types.

Question 12

What percentage of adenomas progress to cancer in the large bowel?

Answer 12

Only around 5% of adenomas in the large bowel progress to cancer.

Question 13

How long does it typically take for an adenoma to evolve into cancer?

Answer 13

It can take 10 or more years for an adenoma in the large bowel to evolve into cancer. However, this timeframe may be shorter for younger patients with colorectal cancer (CRC) and genetic abnormalities.

Question 14

What is the initial step in the development of colorectal cancer (CRC)?

Answer 14

The development of colorectal cancer (CRC) begins with the formation of a small fixed adenoma.

Question 15

How can small adenomas progress in the pathogenesis of bowel cancer?

Answer 15

Small adenomas can progress into more advanced, larger fixed adenomas.

Question 16

Do all adenomatous polyps have dysplasia, and does the size of the polyp matter?

Answer 16

Yes, all adenomatous polyps have dysplasia, and the size of the polyp is not relevant. However, larger polyps may be more likely to have high-grade dysplasia and cancer.

Question 17

Is the presence of cancer or high-grade dysplasia limited to larger polyps?

Answer 17

No, some cancers can be found in very small polyps, and it’s important to note that not all large polyps have cancer or high-grade dysplasia.

Question 18

What factors contribute to the development of colorectal cancer?

Answer 18

Both genetic and environmental factors play a significant role in the development of colorectal cancer.

Question 19

What is the sequence of progression in the adenoma-carcinoma pathway?

Answer 19

The adenoma-carcinoma sequence involves the following progression: low-grade dysplasia, high-grade dysplasia, and eventually colorectal cancer (CRC).

Question 20

What accompanies or likely results from the development of colorectal cancer (CRC)?

Answer 20

The development of CRC is accompanied by, and probably results from, the accumulation of several genetic mutations.

Question 21

What is the evidence supporting the adenoma-carcinoma sequence?

Answer 21

Populations with an increased incidence of adenomas also have an increased incidence of bowel cancer.
The distribution of adenomas in the colon matches the distribution of bowel cancer, with 60-70% occurring in the left colon (predominantly sigmoid and rectum) and 20-25% in the right colon.
The peak incidence for polyps is age 60, while the median age for bowel cancer is 71, indicating that polyps often precede the development of cancer.
Two-thirds of polyps are adenomas, and their prevalence is about 25% by age 50 and 50% by age 70.
Adenomatous tissue is found in bowel cancers, and some cancers are detected in adenomatous polyps.
The risk of cancer increases with the number of polyps, as seen in conditions like familial adenomatous polyposis (FAP) where the cancer rate is 100%.
Removal of polyps and regular screening can reduce the risk of bowel cancer.

Question 22

How does the prevalence of adenomas change with age?

Answer 22

The prevalence of adenomas increases with age, reaching about 25% by age 50 and 50% by age 70.

Question 23

What is the impact of removing polyps and screening on bowel cancer risk?

Answer 23

Removing polyps and regular screening can help reduce the risk of developing bowel cancer.

Question 24

What is the importance of the adenoma-carcinoma sequence in relation to bowel cancer?

Answer 24

It allows for screening and prevention of bowel cancer.
It helps in identifying the pre-malignant phase, which is the presence of polyps.
There is an effective and widely accepted screening test available, such as colonoscopy.
There is an agreed and acceptable treatment option for polyps, known as polypectomy.

Question 25

What are Wilson’s criteria for screening and prevention of bowel cancer?

Answer 25

Identification of a pre-malignant phase (polyp) in the adenoma-carcinoma sequence.
Availability of a good and acceptable screening test, such as colonoscopy.
Presence of an agreed and acceptable treatment method, which is polypectomy.

Question 26

What factors influence a person’s risk of developing colorectal cancer (CRC)?

Answer 26

A person’s risk of developing CRC depends on factors such as age, genetics, and exposure to risk factors.

Question 27

What is the Two Hit Hypothesis in the genetics of CRC?

Answer 27

The Two Hit Hypothesis suggests that the development of CRC involves two separate genetic hits or mutations.

Question 28

Is colorectal cancer a multifactorial and heterogeneous disease?

Answer 28

Yes, colorectal cancer is considered a multifactorial and heterogeneous disease, meaning it is influenced by multiple factors and exhibits variation in its characteristics.

Question 29

What percentage of CRC cases are sporadic?

Answer 29

Approximately 75% of CRC cases are sporadic, meaning they occur without a known family history.

Question 30

What percentage of CRC patients report a family history of the disease?

Answer 30

Around 20% of CRC patients report a family history of the disease, indicating a genetic component in these cases.

Question 31

What are some well-defined cancer-predisposing syndromes associated with hereditary CRC?

Answer 31

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome (1-3%)
Familial adenomatous polyposis (FAP) (<1%)
Hamartomatous polyposis syndrome, which has the lowest incidence (<0.1%)

Question 32

What are the two well-described forms of hereditary CRC related to polyposis?

Answer 32

Familial adenomatous polyposis (FAP) and Attenuated FAP (AFAP): These conditions are caused by pathogenic variants in the APC gene located on Chromosome 5q21.
MUTYH-associated polyposis: This condition is caused by pathogenic variants in the MUTYH gene.

Question 33

What is Lynch syndrome (hereditary nonpolyposis colorectal cancer) and what causes it?

Answer 33

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is caused by germline pathogenic variants in DNA mismatch repair genes (MMR genes) and EPCAM.

Question 34

What is the Two Hit Hypothesis proposed by Knudson?

Answer 34

The Two Hit Hypothesis states that two genetic abnormalities, affecting both copies of a specific gene, are required for the development of certain cancers.

Question 35

What is the mode of inheritance for Familial Adenomatous Polyposis (FAP)?

Answer 35

Familial Adenomatous Polyposis (FAP) follows an autosomal dominant inheritance pattern, accounting for 1% of colorectal cancers (CRCs).

Question 36

At what age do individuals with FAP typically develop over 100 polyps?

Answer 36

Individuals with FAP typically develop over 100 polyps by their late teens.

Question 37

What is the lifetime risk of bowel cancer for individuals with FAP?

Answer 37

Individuals with FAP have an almost 100% risk of developing bowel cancer by the age of 30.

Question 38

At what age is surgery recommended for individuals with FAP?

Answer 38

Surgery is typically recommended in the 20s for individuals with FAP to remove the colon and prevent the development of cancer.

Question 39

Besides the colon, what other areas are screened for polyps and cancers in FAP?

Answer 39

Screening is also conducted for polyps and cancers in the stomach, small bowel (especially the duodenum), and thyroid.

Question 40

Which genes are associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer)?

Answer 40

Lynch syndrome is caused by mutations in DNA mismatch repair genes (MMR genes) and EPCAM.

Question 41

What percentage of Lynch syndrome cases are new mutations?

Answer 41

Approximately 20% of Lynch syndrome cases occur as new mutations, meaning there is no family history of the condition.

Question 42

Does Lynch syndrome follow the two-hit hypothesis?

Answer 42

Yes, Lynch syndrome follows the same two-hit hypothesis as other cancer syndromes, where both copies of the affected gene need to acquire mutations for the disease to develop. In Lynch syndrome, these mutations are easier to acquire.

Question 43

What percentage of bowel cancers are attributed to Lynch syndrome?

Answer 43

Lynch syndrome accounts for approximately 3% of all bowel cancers.

Question 44

Which part of the colon is predominantly affected in Lynch syndrome?

Answer 44

Lynch syndrome shows a predominance for the right colon. Genetic testing for MMR genes is now performed to assess the risk.

Question 45

Besides colorectal cancer, what other types of cancer are individuals with Lynch syndrome at an increased risk for?

Answer 45

Individuals with Lynch syndrome have an increased risk of developing endometrial and renal cell cancer. They may also have a higher risk, although less frequently, for breast, upper gastrointestinal, and prostate cancers. The specific cancer phenotypes can vary among affected families.

Question 46

Why is it necessary to stage cancers, including bowel cancer?

Answer 46

Prognosis: Staging helps predict the likely outcome or prognosis of the cancer.
Treatment: The stage of cancer guides treatment decisions and helps determine the most appropriate treatment approach.
Research: Staging provides standardized information for research purposes, enabling comparison of outcomes across different studies.
International terminology: Staging systems provide a common language for healthcare professionals globally to discuss and document cancer cases.

Question 47

What does the TNM staging system assess in bowel cancer?

Answer 47

Tumour: It assesses how far the tumor has grown into the wall of the colon or rectum and determines the number of layers involved.
Node: It determines whether the tumor has spread to nearby lymph nodes, and if so, identifies the location and number of affected nodes.
Metastasis: It examines whether the cancer has spread to other parts of the body and identifies the sites and extent of metastasis.

Question 48

How are the results from diagnostic tests, biopsy, and surgery combined to determine the stage of bowel cancer?

Answer 48

The results of diagnostic tests, biopsy, and surgical procedures are integrated to determine the stage of bowel cancer for each individual. The tumor characteristics, lymph node involvement, and presence of metastasis are considered collectively to assign an appropriate stage.

Question 49

How does the stage of presentation impact survival in bowel cancer?

Answer 49

The stage of bowel cancer at the time of diagnosis strongly influences survival. Generally, early-stage cancers have a better prognosis compared to advanced-stage cancers.

Question 50

How does ethnicity relate to the incidence of bowel cancer?

Answer 50

Bowel cancer has a higher incidence in the Western world and among White populations, while it is less common in Asia and Africa.

Question 51

Is there a difference in the incidence of bowel cancer between men and women?

Answer 51

The incidence of bowel cancer is roughly equal in men and women.

Question 52

What is the age distribution of bowel cancer cases?

Answer 52

Approximately two-thirds of bowel cancer cases occur in people over the age of 60.

Question 53

What are some genetic risk factors for bowel cancer/

Answer 53

Genetics can contribute to the risk of developing bowel cancer. Certain genetic conditions and family history of the disease can increase the likelihood of developing it.

Question 54

How does longstanding inflammatory bowel disease, such as ulcerative colitis, relate to bowel cancer risk?

Answer 54

Longstanding inflammatory bowel diseases, particularly ulcerative colitis, increase the risk of developing bowel cancer.

Question 55

How does high dietary fiber intake reduce the risk of bowel cancer?

Answer 55

Increasing the formation of short-chain fatty acids that promote healthy gut bacteria, induce cell differentiation, arrest cell growth, and cause apoptosis.
Reducing the proliferation of neoplastic cells.
Reducing stool transit time, which limits the exposure of the bowel mucosa to carcinogens found in food.
Decreasing the formation of secondary bile acids, which have potential carcinogenic properties.

Question 56

What screening method was introduced in 2013?

Answer 56

In 2013, flexible sigmoidoscopy was introduced as a one-off test for individuals at the age of 55. However, it will miss over 25% of cancers located beyond the splenic flexure.

Question 57

What is the rationale behind the current bowel cancer screening program since 2018?

Answer 57

The current bowel cancer screening program aims to prevent colorectal cancer by removing adenomatous polyps and to increase the surgical cure rate by detecting localized, superficial cancers in asymptomatic individuals. This is especially important for individuals with a family history of the disease in first-degree relatives, as their relative risk for developing colorectal cancer increases to 1.75 or even higher if the relative was affected before the age of 60.

Question 58

What does the Quantitative Faecal Immunohistochemical Test (qFIT) detect?

Answer 58

The qFIT detects human globin, which is a marker for blood in the stool.

Question 59

How does the qFIT test differ from other screening tests?

Answer 59

Unlike other screening tests that provide a positive or negative result, the qFIT test gives a quantitative number as a result.

Question 60

What is the recommended screening interval for the qFIT test?

Answer 60

For individuals aged 60-74, the qFIT test is recommended every two years. Individuals over the age of 75 can also request the qFIT test every two years.

Question 61

Is there an expansion plan for the bowel cancer screening program?

Answer 61

Yes, the program is expanding to make the qFIT test available to everyone aged 50 to 59 in the next four years. The expansion started in April 2021.

Question 62

What follow-up tests are required if the qFIT test is positive?

Answer 62

If the qFIT test is positive, further investigations and follow-up tests are required to determine the reason for the presence of blood in the stool.

Question 63

What are the major limitations of the faecal occult blood test as a screening technique?

Answer 63

The faecal occult blood test has major limitations as a screening technique, even when performed optimally. One limitation is that approximately 50% of patients with documented colorectal cancers may have a negative faecal occult blood test, which is consistent with the intermittent bleeding pattern of these tumors.

Question 64

What are some further investigations conducted after a positive qFIT test?

Answer 64

Further investigations may include physical examination, colonoscopy (considered the “gold standard” lower gastrointestinal test), biopsy, biomarker testing (to identify specific genes, proteins, and other factors unique to the tumor), blood tests (such as checking for anemia and levels of carcinoembryonic antigen, which may indicate metastasis), as well as imaging techniques like ultrasound, chest x-ray, CT scan, CAT scan, and MRI.