QuestionSBA
QuestionChoice
A flexible sigmoidoscopy only passes through the rectum, sigmoid colon and proximal parts of the descending colon. Therefore, colon cancer could be missed further up in the ascending or transverse sections. Thus, a colonoscopy should be conducted. This patient has symptoms that are concerning for an underlying colon malignancy. The National Institute for Health and Care Excellence (NICE) guidelines state that patients over 60 with iron deficiency anaemia or changes in their bowel habit should be referred for investigation under a 2-week wait pathway.
52922
a
Colonoscopy
QuestionChoice
A positron emission tomography scan can be useful for the evaluation of metastases, particularly in the case of bowel cancer to nearby lymph nodes and the liver. However, the primary site of malignancy has not been confirmed; therefore, it would be inappropriate to expose a patient to radiation at this stage.
52926
e
Fluorodeoxyglucose-positron emission tomography scan
QuestionChoice
This patient is presenting with chronic symptoms and there is nothing in the history suggestive of infection. A colorectal malignancy should therefore be ruled out.
52924
c
Stool cultures
QuestionChoice
A flexible sigmoidoscopy can only evaluate part of the colon for malignancy and therefore this is insufficient to rule out a malignancy of the colon. In the context of his age and the recent change in bowel habit, the NICE guidelines state this patient needs evaluation for colorectal malignancy. A colonoscopy is required.
52925
d
Discharge with lifestyle advice
QuestionChoice
Carcinoembryonic antigen (CEA) is only used when monitoring response to treatment for a confirmed colorectal malignancy. It is not a good screening or diagnostic test because its specificity is low. Furthermore, a negative result does not exclude malignancy; therefore, it does not exclude the need for colonoscopy.
52923
b
Measure carcinoembryonic antigen
Concept
Chapter
# Summary

Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the UK. The disease is characterized by malignant growth in the colon or rectum. Risk factors include age, hereditary syndromes, increased alcohol intake, smoking, processed meat intake, obesity, previous radiation exposure, and inflammatory bowel disease. Signs and symptoms may include rectal bleeding, weight loss, change in bowel habit, abdominal pain, and iron-deficiency anaemia. Diagnosis typically involves colonoscopy, biopsies, and CT scanning. Management strategies depend on the stage and location of the cancer, and the patient's overall health. Treatment options include surgery, chemotherapy, and radiotherapy.

# Definition

Colorectal cancer is a type of malignancy that starts in the colon or rectum. It is a result of uncontrolled cell growth in the lining of the colon or rectum. It may start as benign polyps, which can over time progress to cancerous tumours if not removed.

# Epidemiology

Colorectal cancer is the fourth most common cancer in the UK. It is also the second most common cause of cancer death.

**Strong risk factors**

- Increasing age
- Hereditary syndromes
  - Familial adenomatous polyposis
  - Hereditary nonpolyposis colorectal cancer (Lynch Syndrome)
  - Juvenile polyposis
  - Peutz-Jeghers syndrome
- Increased alcohol intake
- Smoking tobacco
- Processed meat
- Obesity
- Previous exposure to radiation
- Inflammatory bowel disease

**Weak risk factors**

- Lack of dietary fibre
- Limited physical activity
- Asbestos exposure
- Red meat (non-processed)

# Signs and Symptoms

* Rectal bleeding: Often noticed as blood in the stool.
* Unexplained weight loss 
* Change in bowel habit: Patients might experience alterations in their bowel movements, such as diarrhea or constipation.
* Abdominal pain: Persistent abdominal discomfort or pain may be present.
* Iron-deficiency anaemia: This can result from chronic bleeding.
* Bowel obstruction: advanced tumours can obstruct the bowel, resulting in abdominal pain, nausea and vomiting



# TNM staging 

The TNM (tumour, node, metastases) is a more recent classification system (replacing the Duke's classification), which provides a more uniform classification of colorectal cancer.

- T: Tis (carcinoma in situ/intramucosal cancer), T1 (extends through the mucosa into the submucosa), T2 (extends through the submucosal into the muscularis), T3 (extends through the muscularis into the subserosa), T4 (extends into neighbouring organs or tissues).
- N: N0 (no regional lymph node involvement), N1 (metastasis to 1-3 regional lymph nodes), N2 (metastasis to 4 or more regional lymph nodes).
- M: M0 (no distant metastasis), M1 (distant metastasis).
Staging informs both the prognosis and the treatment plan.

Patients with Duke's stage C or stage III (T1-4, N1-2, M0) colon cancer benefit from adjuvant chemotherapy. Note that patients without lymph node involvement but with high risk features (such as vascular or perineural invasion) also show improved survival with adjuvant chemotherapy.

# Screening

The aim of screening is to detect cancer at an earlier (asymptomatic) stage, when it is easier to treat and patients have a better chance of survival.

Current NHS screening programmes include:

- Faecal immunochemical test (FIT) every 2 years for men and women age 54-74. If positive patients are referred for colonoscopy.
- One-off flexible sigmoidoscopy has now been _discontinued_.

This screening programme reduces the risk of dying from bowel cancer by 16%. NB: screening will soon be changed so that it is offered from the age of 50-74.

# Urgent 2 week wait referral criteria

NICE Guidance now recommends faecal immunochemical testing (FIT) to guide referral for suspected colorectal cancer in adults:

* With an abdominal mass.
* With a change in bowel habit.
* With iron-deficiency anaemia.
* Aged 40 years and over with unexplained weight loss and abdominal pain.
* Aged under 50 years with rectal bleeding and either of the following unexplained symptoms:
	* Abdominal pain.
	* Weight loss.
* Aged 50 years and over with any of the following unexplained symptoms:
	* Rectal bleeding.
	* Abdominal pain.
	* Weight loss.
* Aged 60 years and over with anaemia even in the absence of iron deficiency.

If they have a FIT result of at least 10 micrograms, they should be referred for an urgent (within 2 weeks) colonoscopy.

- FIT testing should be offered even if they have had a negative result from the screening programme previously.
- Adults with a rectal mass should still be considered for a suspected cancer pathway referral (for an appointment within 2 weeks) and do not need a prior FIT test.



# Investigations

- Bloods - FBC (anaemia), iron studies, and carcinoembryonic antigen (CEA) are useful initial investigations
	- CEA is not used as a diagnostic tool but is a tumour marker that can be used to monitor therapeutic response to interventions.
* The gold standard investigation is a **colonoscopy**. It allows 
	* Direct visualisation of the colon
	* Biopsies to be taken
	* Removal of any polyps seen
* If colonoscopy cannot be performed, either due to technical difficulties, poor tolerance of bowel preparation or there is an increased risk of colonic perforation a CT colonoscopy is a suitable alternative but does not allow biopsy.
* After a histological diagnosis is made, a CT chest, abdomen and pelvis should be performed to stage the disease, so an appropriate intervention can be planned.
* In rectal disease, a pelvic MRI or endorectal ultrasound are preferred over CT scan, as are better for identifying locally invasive disease.


# Management

Management depends on factors relating to both the tumour (the stage and location) and the patient (surgical fitness).

# Surgery for Colon Cancer

For patients with **colon cancer** suitable for surgery:

- **Stage I-III disease:** surgical resection ± adjuvant chemotherapy.
The type of surgery depends on the tumour site: right hemicolectomy for tumours of the caecum and ascending colon, left hemicolectomy for tumours of the distal transverse colon and descending colon, and sigmoid colectomy for tumours of the sigmoid colon.
- **Stage IV disease (metastases):** treatment is as above, but neoadjuvant chemotherapy may also be performed. The staged colectomy and resection of metastatic disease is performed after neoadjuvant chemotherapy.
- In terms of specific surgical procedures, patients with caecal and ascending colon tumours undergo right hemicolectomy

# Surgery of Rectal Cancer

For patients with **rectal cancer** suitable for surgery:
Anterior resection for tumours >8 cm from the anal canal or involving the proximal 2/3 of the rectum.
Abdomino-perineal (AP) resection for tumours <8 cm from the anal canal or involving the distal 1/3 of the rectum.

Patients with stage III disease benefit from adjuvant chemotherapy.

Patients with stage IV disease benefit from adjuvant chemoradiotherapy

# Non-surgical management

For patients unsuitable for surgery management is with chemotherapy (FOLFOX or FOLFIRI i.e. oxaliplatin/irinotecan plus folinic acid plus fluorouracil are the preferred regimens).

New monoclonal antibody therapies are becoming available. Note that NICE concluded that cetuximab (anti-EGFR), but not bevacizumab (anti-VEGF), is cost effective in combination with chemotherapy for metastatic colorectal cancer.

Note that stenting may be used as a palliative measure for patients with obstructing tumours of the sigmoid colon or rectum.
If the patient presents with acute bowel obstruction, a Hartmann's procedure may be required as an interim measure (resection of the rectosigmoid colon with formation of a temporary end colostomy and anorectal stump).


# Familial adenomatous polyposis (FAP)

Caused by a mutation in the adenomatous polyposis coli (APC) gene and has an autosomal dominant inheritance pattern.

Patients develop hundreds of adenomatous polyps in their teens and are _virtually guaranteed_ to develop colorectal cancer by their 20s, unless they undergo prophylactic proctocolectomy.

Note that there is a high risk of developing duodenal cancer, so patients undergo regular endoscopic surveillance.

> _Gardener's syndrome_ is a variant of FAP in which patients may also develop epidermal cysts, supernumerary teeth, osteomas, and thyroid tumours.

# Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome

Is caused by a mutation in the mismatch repair genes MLH1/MSH2 and has an autosomal dominant inheritance pattern.

Patients have an 80% risk of developing colorectal cancer by their 30s.

There is increased risk of additional cancers such as gastric, endometrial, breast, and prostate cancer.

Patients are managed with regular endoscopic surveillance.

# Peutz-Jeghers syndrome

Is caused by a mutation in the STK11 gene and has an autosomal dominant inheritance pattern.

Patients typically present in their teens with mucocutaneous pigmentaiton and hamartomatous polyps.

Note that the risk of neoplastic transformation of hamartomatous polyps is low, but many polyps are present so patients are at increased risk of developing colorectal cancer. They are managed with regular endoscopic surveillance.

# References

[Click here to see diagrams of colonic resections on Bowel Cancer UK](https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/surgery/types-of-surgery/)

[Click here to see the NICE guidelines on lower GI cancers](https://cks.nice.org.uk/topics/gastrointestinal-tract-lower-cancers-recognition-referral/)
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10645
A 64-year-old man undergoes a flexible sigmoidoscopy after a 4-month change to his bowel habit, where he reports intermittent constipation and loose stools. He denies any blood in the stool or any systemic symptoms. On flexible sigmoidoscopy no abnormality is found.

What is the next best step in his management?
a