Colorectal cancer

Colorectal cancer (CRC) is the 4th most common cancer in the UK with the 2nd highest mortality. It’s incidence in patients <40 is increasing.

Pathophysiology

The cancer originates from the epithelial cells that line the colon/rectum, i.e. adenocarcinoma.

Let’s take a look at the progression of CRC (adenoma-carcinoma sequence):

1. Early adenoma/colorectal polyp - less than 1cm. Grows into the lumen of the colon. It is made up of glandular tissue.
2. Late adenoma - greater than 1cm, containing tumour cells, but is still benign at this stage
3. Adenocarcinoma - malignant tumour.
4. Invasive adenocarcinoma - referred to as invasive/infiltrating if it surpasses the mucosa (inner lining) of the colon.

⚠️ Risk factors

1. Sporadic - due to a series of genetic mutations. Most show loss APC gene followed by a series of genetic mutations such as activation of K-ras and loss of p53.

2. Lynch syndrome - the most common form of hereditary colon cancer. The HNPCC (hereditary nonpolyposis colorectal cancer) gene is a DNA mismatch repair gene. Mutation results in defective DNA repair leading to instability. Other mutations which have been identified are MSH2 and MLH1. The most common extra-colonic manifestation of HNPCC is endometrial cancer.
1. The Amsterdam criteria may be used to aid diagnosis (but this shall not be discussed here).
3. FAP (Familial Adenomatous Polyposis) - APC (adenomatous polyposis coli) is a tumour suppressor gene. When mutated, it causes adenomatous tissue growth, as seen in FAP. Duodenal cancer is the 2nd highest risk of cancer with FAP. Duodenal cancers may present with weight loss, nausea and vomiting, abdominal pain and obstructive jaundice.
1. Gardner's syndrome - is a variant of familial adenomatous polyposis (FAP) and is accompanied by lipomas, supernumerary teeth, osteomas, epidermoid cysts, thyroid carcinoma and retinal pigmentation.

Other risk factors include: older age family history IBD low fibre diet processed meat intake alcohol, streptococcus bovis infection (also causes infective endocarditis).

👀 Screening

Screening for CRC has reduced mortality rate by 16%.

Within the NHS, a Faecal Immunochemical Test (FIT) is offered to patients aged 60 - 74 years every 2 years. It is used to identify the amount of blood in a a stool sample. Any patient with an abnormal result is offered a colonoscopy.

At the colonoscopy, approximately 10% will have cancer, 40% will be found to have polyps, and 50% will be normal.

😷 Presentation

Common features include:

• Changes in bowel habit
• Rectal bleeding
• Weight loss (usually only seen in metastatic CRC cases)
• Abdominal pain
• Iron-deficiency anaemia (IDA) [due to blood loss and impaired iron homeostasis]

Depending on if its left-sided or right-sided, features can differ:

⬅️

Right-sided colon cancer

1. Abdominal pain
2. IDA
3. Palpable mass in RIF
4. Later presentation

➡️

Left-sided colon cancer

1. Rectal bleeding
2. Changes in bowel habit
3. Tenesmus (feeling that you need to pass stool even when bowels are empty)
4. Palpable mass in LIF or in rectum on PR exam

🦮 Referral guidelines

🔍 Investigations

📷

Imaging 🏆 Colonoscopy with biopsy is the gold standard. CT or double-contrast barium enema are other options if colonoscopy is not possible for whatever reason.

🧪

Laboratory tests FBC - looking for microcytic anaemia. This is seen with a low Hb and low MCV. LFTs + clotting profile Carcinoembryonic Antigen (CEA) - not a diagnostic test as it has poor sensitivity and specificity. But can be used to analyse disease progression as well as recurrence.

🔢 Staging/Classification

Biopsies and CT scans can be used for classification using TNM or Duke’s staging:

TNM

🔢

Tumour (T)

Tumour describes the size of the tumour. This is a simplified description of the T stage.

Tis means carcinoma in situ. The cancer is at its earliest stage and only in the mucosa.

T1 means the tumour is only in the inner layer of the bowel.

T2 means the tumour has grown into the muscle layer of the bowel wall.

T3 means the tumour has grown into the outer lining of the bowel wall but has not grown through it.

T4 is split into 2 stages, T4a and T4b:

• T4a means the tumour has grown through the outer lining of the bowel wall and has spread into the tissue layer (peritoneum) covering the organs in the tummy (abdomen)
• T4b means the tumour has grown through the bowel wall into nearby organs

Duke’s staging

Stage	Description	5 year survival
A	Invasion into but not through the bowel wall	90%
B	Extension through the muscularis propria	65%
C	Involvement of regional lymph nodes	30%
D	Distant metastasis	10%

🧰 Management

The only curative option is surgery, but chemotherapy and radiotherapy are important as neoadjuvant (before surgery/main treatment) and adjuvant (after surgery/main treatment)

🔪

Surgical therapies: Regional colectomy is the plan for most treatment plans. The rest of the colon needs to be anastomosed or a stoma needs to be formed.

• Right hemicolectomy - for caecal tumours/ascending colon tumours. An extended right hemicolectomy may be used for transverse colon tumours. The ileocolic, right colic, and right branch of the middle colic vessels are divided and removed with their corresponding mesenteries.
• Left hemicolectomy - for descending colon tumours. The left branch of the middle colic vessels, left colic vessels, and inferior mesenteric vein are divided and removed with their mesenteries.
• Sigmoidectomy - for sigmoid colon tumours. The inferior mesenteric artery is removed with the tumour.
• Anterior resection - for high rectal tumours (>5cm from the anus). It is favoured as it leaves the rectal sphincter intact.
• Abdominoperineal (AP) resection - for low rectal tumours (<5cm from the anus). In an AP resection the anus and rectum are completely removed. All bowel distal to the lesion site is removed. The patient will therefore require a permanent end colostomy
• Hartmann’s procedure - for emergency bowel obstruction/perforation. The recto-sigmoid colon is completely resectioned and a colostomy is formed while the rectal stump is closed. 100% of untreated FAP patients will develop adenocarcinomas by <50 years old. Therefore, prophylactic colectomy is usually necessary to prevent CRC. Ampulla of Vater and stomach are common extracolonic sites of adenomas in these patients.

⚠️ In an emergency setting with a colonic tumour that is associated with perforation, the risk of anastomosis is greater, and therefore and end colostomy is performed instead. Otherwise, a loop colostomy is done in an emergency setting usually.

💊

Chemotherpay: FOLFOX is an example of a regime for metastatic colorectal cancer: FOLinic acid Fluorouracil OXaliplatin

Patients with Duke's C (lymph node involvement) or stage III cancer should be offered post-operative adjuvant chemotherapy.

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Radiotherapy: Rarely done in rectal cancer as it may damage small bowel. Most often done alongside chemo or as a neo-adjuvant therapy.

• Palliative care is the focus in very advanced colorectal cancers, ensuring symptom control.
• We can use gastrograffin to check for anastomotic leaks after surgery. This is preferred over a barium enema as it is less toxic.
• Epidural analgesia is given as this allows for a faster return to normal GI function. Normal GI function is measured by the first flatus post-operatively.

🚨 Complications

• Perforation
• Bowel obstruction
• Acid-base abnormalities, electrolyte imbalance and volume depletion - with high-output stomas.
• Anastomotic leak - anastomotic leaks most typically occur 5-7 days after the surgery and patients may present with abdominal pain, fever, delirium or prolonged ileus and may shows signs of sepsis.
• Refeeding syndrome