Definition - The majority of colorectal cancers are adenocarcinomas derived from epithelial cells
- About 71% of new colorectal cancers arise in the colon and 29% in the rectum
- Less common types of malignant colorectal tumours are carcinoid tumours, GI stromal cell tumours, and lymphomas
- Increasing age is the greatest risk factor for sporadic colorectal adenocarcinoma with 99% of cancers occurring in people aged 40 years or over
Risk Factors - Strong
- Increasing age
- APC mutation
- Lynch syndrome (HNPCC)
- MYH-associated polyposis
- Hamartomatous polyposis syndromes
- Inflammatory bowel disease
- Obesity
- Weak
- Acromegaly
- Limited physical activity
- Lack of dietary fibre
Differential diagnosis - Irritable bowel syndrome (IBS)
- A clinical diagnosis is based on the Rome III Criteria:
- at least 3 months' duration
- onset at least 6 months previously
- recurrent abdominal pain or discomfort associated with 2 or more of:
- improvement in abdominal pain with defecation
- change in frequency of stool
- change in form (appearance) of stool
- There is no specific diagnostic test for IBS
- Patients who fulfil the clinical criteria for IBS and have no alarm features have a very low probability of organic disease
- Colonoscopy or colonic imaging is recommended for patients older than 50 years of age due to higher pre-test probability of colorectal cancer
- Ulcerative colitis
- Average age of onset of inflammatory bowel disease (20 to 40 years) is younger than with colorectal cancer
- Patients with inflammatory bowel disease frequently have watery diarrhoea
- However, patients with colitis are at higher risk of colorectal cancer and may need reassessment if symptoms are atypical or do not respond to treatment
- Colonoscopy will show:
- rectal involvement
- continuous uniform involvement
- loss of vascular marking
- diffuse erythema
- mucosal granularity
- normal terminal ileum (or mild 'backwash' ileitis in pancolitis)
- Crohn's disease
- Average age of onset of inflammatory bowel disease (20 to 40 years) is younger than with colorectal cancer
- Patients with inflammatory bowel disease frequently have watery diarrhoea
- Patients with colitis are at higher risk of colorectal cancer and may need reassessment if symptoms are atypical or do not respond to treatment
- Colonoscopy with intubation of the ileum is the definitive test to diagnose Crohn's disease
- Will show mucosal inflammation and discrete deep superficial ulcers located transversely and longitudinally, creating a cobblestone appearance
- The lesions are discontinuous, with intermittent areas of normal-appearing bowel (skip lesions)
- Haemorrhoids
- Causes bright red rectal bleeding that is separate from the stool
- There is no abdominal discomfort or pain, altered bowel habits, or weight loss
- Colonoscopy or colonic imaging is recommended in patients with abdominal symptoms in addition to rectal bleeding and in those older than 50 years of age
- Anal fissure
- Severe pain on defecation
- Blood is usually on wiping
- There is no abdominal discomfort or pain, altered bowel habits, or weight loss
- Colonoscopy or colonic imaging is recommended in patients with abdominal symptoms in addition to rectal bleeding and in those older than 50 years of age
- Diverticular disease
- Diverticular stricture or inflammatory mass may be clinically indistinguishable from colorectal cancer
- Colonoscopy with biopsies and CT imaging will usually differentiate
Epidemiology - Colorectal cancer is the third most common cancer in the Western world
- Worldwide, the highest incidence rates for colorectal cancer are seen in Europe, North America, and Australasia and are lowest in Africa and Asia
- The lifetime risk of developing colorectal cancer is 5.42% and it is the third leading cause of cancer deaths in the US in men and women
- In 2002, 34,889 new colorectal cancer cases were diagnosed in the UK where in 2006, 15,957 deaths were due to colorectal cancer
- Age is a major risk factor for sporadic colorectal cancer and it is rare before 40 years of age
- Between 2000 and 2004 in the US, the median age at diagnosis for cancer of the colon and rectum was 71 years of age
- The age-adjusted incidence rate was 51.6 per 100,000 men and women per year
- Incidence and mortality rates are much lower in Hispanics, Asians, Pacific Islanders, American Indians, and Alaskan natives compared with white people and black people
- Some of these disparities may be due to differences in genetic susceptibility
- Over the past decade, colorectal cancer incidence and mortality rates have decreased in all populations except American Indians and Alaskan natives
- The incidence and mortality rates are similar in men and women until 50 years of age and after this time rates are higher in men
Aetiology - Colorectal cancer represents a complex interaction of genetic and environmental factors
- Genetic factors:
- The majority of colorectal cancers are sporadic rather than familial, but next to age, family history is the most common risk factor
- There is a 2- to 3-fold increased risk of colorectal cancer in people with a family history in a single first-degree relative
- The risk is further increased if cancer developed at a young age (<45 years)
- There is a 3- to 4-fold increased risk of colorectal cancer with 2 affected first-degree relatives
- The well-defined family cancer syndromes such as familial adenomatous polyposis (FAP) and Lynch syndrome are the most common of the family cancer syndromes
- These are associated with single gene defects
- However, these syndromes account for only about 5% to 6% of colorectal cancer cases
- Obesity confers a 1.5-fold increased risk of developing colon cancer compared with normal weight individuals
- Obesity is also associated with a greater risk of dying from the disease
- Obesity, high energy intake, and physical inactivity are probably synergistic risk factors
- Most studies (but not all) suggest an inverse relationship between dietary fibre intake and colorectal cancer risk
- Large prospective studies with long follow-up periods have shown that a high intake of red and processed meat is associated with an increased risk of colorectal cancer risk
Clinical features - Iincreasing age
- Less than 5% of cases are in patients who are younger than 44 years of age and the mean age at diagnosis is 71 years
- Rectal bleeding
- Rectal bleeding is usually due to benign disease, but it is a common symptom in patients with colorectal cancer
- A new episode of rectal bleeding in patients older than 45 years of age has a positive predictive value for colorectal cancer of 5.7%
- Change in bowel habit
- Increased frequency or looser stools, particularly combined with rectal bleeding, is common in left-sided cancers
- However, a change in bowel habit to reduced frequency and hard stools has a low predictive value for colorectal cancer
- Rectal mass
- There is a palpable rectal mass in 40% to 80% of patients with rectal cancer
- Digital rectal examination to assess tumour involvement of the pelvic wall and suitability for surgery is unreliable
- Better assessed by MRI and transrectal endoscopic ultrasound
- Positive FHx
- For individuals with one affected first-degree relative, the relative risk of developing colorectal cancer is 2.24
- This increases to 3.97 with 2 affected first-degree relatives
- However, only about 10% to 20% of patients give a family history of colorectal cancer
- Abdominal mass
- Usually the abdominal examination is normal
- Occasionally a tumour a mass is felt, typically in advanced disease
- Anaemia
- Almost 90% of patients with right-sided colon cancer are anaemic at diagnosis
- Male gender
- Until 50 years of age, men and women have similar rates for bowel cancer, but in later life male rates are higher
- Uncommon features
- Abdominal pain
- Weight loss and anorexia
- Abdominal distension
- Palpable lymph nodes
Investigations- FBC
- Liver biochemistry
- Normal, except if liver metastases present
- Renal function
- Normal, except if advanced pelvic disease is compressing ureters
- Colonoscopy
- Ulcerating exophytic mucosal lesion that may narrow the bowel lumen
- Double-contrast barium enema
- Mass lesion in the colon and/or as a characteristic 'apple core' lesion
- CT colonography
- Appearances similar to conventional colonoscopy, with an ulcerating exophytic mucosal lesion that may narrow the bowel lumen
- CT scan of thorax, abdomen, and pelvis
- Colonic wall thickening, enlarged lymph nodes, liver metastases, ascites, lung secondaries
- Pelvic MRI
- Tumour invasion of mesorectal fascia
- Transrectal endoscopic ultrasound (TRUS)
- Enlarged perirectal lymph nodes indicate malignant involvement
- Invasion through the submucosa and into muscularis propria identifies a T2 tumour
- Extension of tumour into perirectal space identifies a T3 tumour
- Biopsy
- Confirms the diagnosis with characteristic pathological appearances
- The degree of tumour differentiation (i.e., well, moderate, or poorly differentiated) will also be reported
- Carcinoembryonic antigen (CEA)
- Elevated; normal range for CEA:
- Adult non-smoker <2.5 micrograms/L (<2.5 nanograms/mL)
- Adult smoker <5.0 micrograms/L (<5.0 nanograms/mL)
- Reference range may vary between laboratories depending on assay
- PET scan
- Focal areas of increased uptake of 18-fluoro-2-deoxyglucose (FDG) detects metabolic changes of malignancy
Managementa) conservativeb) medical - Pre-operative radiotherapy
- Short course pre-operative radiotherapy is given in some centres, although the benefits of this approach remain unclear
- It may reduce local recurrence, but can impair wound healing and increase the rate of faecal incontinence and sexual dysfunction
- It is used more in Europe than in North America
- Pre-operative chemoradiotherapy
- For patients with rectal cancer stage II and III in many centres
- Pre-operative radiotherapy or fluoropyrimidine-based chemoradiotherapy followed by a sphincter-preserving LAR
- Long-term outcomes in terms of survival are improved with short course radiotherapy (5 x 5 Gy), but at the expense of toxicity and a higher risk of second malignancies
- See local specialist protocols for chemoradiotherapy dosing guidelines
- Postoperative chemotherapy
- No trial has demonstrated conclusively that adjuvant chemotherapy improves outcome in patients who have received pre-operative chemoradiotherapy
- However, based largely on retrospective data, National Comprehensive Cancer Network guidelines recommend postoperative chemotherapy in all patients who receive pre-operative therapy regardless of the pathological stage in the resected specimen
- Generally, pre-operative therapy with either short-course radiotherapy or chemoradiotherapy is preferable to postoperative chemoradiotherapy
- Bevacizumab
- Monoclonal antibody that has anti-angiogenic properties, alters vasculature to improve delivery of chemotherapeutic agents to cancer cells
- May directly inhibit VEGF-dependent growth of cancer cells
c) surgical- Local excision
- Stage I tumours are T1, N0, M0
- As a consequence of the localised nature of T1 tumours without lymph node involvement, patients may be suitable for complete local removal
- The limiting factor for transanal excision using conventional instruments is access
- This is restricted to the distal 8 cm of the rectum (transanal resection of tumour, TART)
- Transanal endoscopic microsurgery (TEM) allows better exposure and access to lesions in the proximal rectum than conventional approaches
- Uses a device that insufflates the rectum with carbon dioxide, maintains the distension and allows suction and water irrigation
- The margin of excision around the tumour is marked using cautery, the lesion excised and the wound sutured
- No further treatment is necessary if:
- The margins of excision are clear on the resected specimen with pathological grade T1 (pT1)
- There are no unfavourable features (poorly differentiated, lymphovascular invasion)
- A meta-analysis of available data suggests TEM has fewer complications, but a higher local recurrence compared with standard surgery
- Surgical resection
- Patients with rectal cancer that do not meet the requirements for local excision alone should be treated with a transabdominal resection with sphincter preservation if possible
- Tumours in the upper third of the rectum are removed by high anterior resection
- Rectum and mesorectum are removed to 5 cm below the tumour
- A colorectal anastomosis is fashioned
- Tumours in the mid and lower third require low anterior resection
- All of the rectum and mesorectum is removed, using a technique called total mesorectal excision (TME)
- Refers to the surgical removal of the complete perirectal soft tissue envelope
- A colo-anal anastomosis is performed, in some cases with a colonic pouch or coloplasty to improve function
- Such a low anastomosis is usually defunctioned with a temporary ileostomy
- Reduces the incidence of an anastomotic leak and the need for further, emergency surgery following an elective resection
- Abdominoperineal resection (APR) with permanent colostomy is required if the tumour invades the pelvic floor, sphincter complex or anal canal
- Stenting
- Stenting may be appropriate for some patients with obstructing tumours of the rectum
Prognosis- There has been a documented increase in survival in patients with colorectal cancer
- This improvement is attributed to surgical technique, increased use of neoadjuvant and adjuvant therapy, and screening of asymptomatic individuals
- The outcome of colorectal cancer depends on the stage at diagnosis
- About half of patients presenting with symptoms have advanced local (stage III) or metastatic disease (stage IV) at diagnosis
- In contrast, cancers detected by screening are usually at an earlier stage (mostly stage I to II)
- Rectal cancer survival rates also vary by country
- While the overall 5-year survival rate for rectal cancer in the US is 59%, it is 42% in Europe
- Within Europe, 5-year survival rates for colon cancer are lower in the UK, Denmark, and Eastern European countries compared with the European average of about 50%
- Analysis of the EUROCARE data suggests that lower survival in the UK is due to later stage at presentation and diagnosis rather than inferior treatment for a similar stage
- Overall, 5-year survival rates for colorectal cancer are:
- 93% to 97% for stage I disease
- 72% to 85% for stage II disease
- 44% to 83% (depending on nodal involvement) for stage III disease
- <8% for stage IV disease
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