colorectal cancer

Demographics: 

Colon cancer is a common malignancy, it primarily presents in older patients, however it may occur earlier in two hereditary conditions which leads to colon cancer. Familial adenomatous polyposis (FAP) is a autosomnal dominant condition which causes the formation of multiple polyps in the colon. The condition tends to cause cancer in patients by the age of 40. Hereditary non-polyposis colorectal cancer (HNPCC) also causes colon cancer in younger patients. HNPCC is also associated with endometrial, gastric, renal, uteric and CNS cancers. 

Risk factors and causes

• Crohn's and Ulcerative colitis increases colorectal cancer risk
• History of small bowel cancer, endometrial cancer, breast cancer or ovarian cancer
• Family history - family member with cancer before the age of 60
• Specific hereditary causes : FAP and HNPCC
• Low fibre diet and high red meat diet is thought to increase risk
• Sedentary lifestyle, obesity, smoking, high alcohol intake
• Diabetes mellitus
• Aspirin may have a protective effect on colorectal cancer. 
• Hormonal: nulliparity, late age at first pregnancy, early menopause
• Irradiation, occupational hazards. 

A number of gene mutations are thought to contribute greatly to colon cancer susceptibility. These include p53, DCC, K-Ras and APC genes. 

Presentation

Right sided lesions tend to bleed, but the blood is usually mixed into stools and may cause tarry stools. It may present with anaemia, or cause diarrhoea. The patient may also present with a mass  or weight loss. Right sided cancers tend to be more advanced when diagnosed.  Left sided lesions tend to cause obstruction causing colicky pain, bowel obstruction and rectal bleeding, It may present as changes in bowel habits, or as a mass. Cancers in the rectum may cause a sense of needing to void even after emptying bowels. 

55% of patients will present with late disease, which may cause an enlarge liver, jaundice or ascites. 

Examination findings vary with the severity of the disease

Findings may be general such as weight loss, or the patient may present with tenderness, a palpable mass, enlarged liver, ascites, and jaundice, or blood on PR examination

Referral criteria for GPs

an urgent 2 week referal should be made if any of these criteria are met. 

• Person over the age of 40 presenting with change in bowel habit towards looser and more frequent stools and bleeding for over 6 weeks
• Person over the age of 60 presenting with either change in bowel habits OR rectal bleeding for over 6 weeks
• Person of any age presenting with a right lower abdominal mass
• Person of any age presenting with a rectal mass palpable on PR examination (if pelvic mass consider gynaecological/urological condition and urgent referral to them) 
• Men of any age with unexplained iron deficient anaemia and Hb<110 span="">
• Woman of who is not menstruating with unexplained iron deficient anaemia and Hb < 100/L

Differential diagnosis

Diverticular disease

Irritable bowel syndrome

Inflammatory bowel disease

Lower rectal problems eg. haemorrhoids

Anal cancer

Ischaemic colitis

Investigations

Blood tests- fbc may show anaemia, renal function, liver function, CEA

Chest x ray

barium enema - may show narrowing. 

Proctoscopy and sigmoidoscopy or colonoscopy with biopsy. 

Management

Staging- Duke's stageA - tumour confined to mucosa

Dukes stage B- tumour perforates serosa

Dukes stage C - lymph node involvement

Also TNM staging- T0- no primary

T1 Invades submucosa

T2 Invades muscularis

T3 Invades through muscular is

T4 perforates peritoneum

N0 no nodes

N1 1-3 pericolic nodes

N2 4+ pericolic nodes

N3 met in any other lymph nodes

M0 no distant mets

M1 Distant metastases. 

Grading - well differentiated, moderately differentiated, poorly differentiated

When malignancy is confirmed, operability should be assessed with CT scan. 

Curative treatment is primarily through surgery, different procedures are performed depending on the site of the cancer (R hemicolectomy, L hemicolectomy, transverse colectomy, etc. ). In the procedure the portion of bowel supplied by one artery is removed and the two ends of the remaining bowel joined to form an anastamosis. If the anastamosis is not thought to be strong enough, a stoma may be formed proximally to allowed the portion of bowel to heal. 

Upper rectal cancers are treated with a anterior resection whereas a lower rectal cancer is treated with a abdominoperineal resection which leaves a permanent colostomy as it removes the anal spinchter. 

Adjuvant chemotherapy is given to patients with dukes C tumours, as this improves survival. This is usually with 5-fluorouracil. This may be given with folinic acid and irinotecan or folinic acid and oxaliplatin. Radiotherapy is not appropriate for bowel cancer due to the mobility of the bowel and the low radio sensitivity of the cancer. Although patients with rectal cancers are often treated with radiotherapy after surgery as this reduces pelvic recurrence.  additional chemotherapy is also given  if the tumour are T3-4, 

Metastatic disease

If patient is fit but has limited liver metastases, curative surgical treatment may be attempted with 5 year survivals of up to 40%. However generally metastatic disease has a poor prognosis. 

5FU and either irinotecan or oxaliplatin may improve survival. The addition of Bevacizumab, a human monoclonal antibody agaist vascular endothelial growth factor, may further improve survival.  Cetuximab, or panitumumab, antibodies against epidermal growth factor receptor (EGFR) may also improve survival if the patient does not have mutations in K-Ras. with treatment, survival is between 18 months and 2 years. 

Prognosis

Dukes A: 90% 5 year survival rate

Dukes B- 60% 5 year survival

Dukes C - 30% 5 year survival

Metastatic - 5-10% 5 year survival

References:
Goldberg A, Stansby G, Surgical talk, surgery for finals, London, Imperial college press, 2004.
Bower M, Waxman J, Lecture notes: Oncology, 2nd ed. Oxford, Wiley-Blackwell, 2010
http://www.patient.co.uk/doctor/colorectal-cancer
http://emedicine.medscape.com/article/277496-overview