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Sunday, August 21, 2016

Colorectal cancer



Introduction
·         Second most common cause of cancer deaths in the UK.
·         Each year 30,000 new cases diagnosed (68% colon, 32% rectal)
·         Disease more common in westernises countries then Asia or Africa




Aetiology
·         Age (56% >70yrs old)
·         Colorectal polyps
·         Family history
Genetic
o        Hereditary non-polyposis colorectal cancer (HNPCC): autosomal dominant disorder due to mutations in the MMR genes. Associated malignancies found in endometrium and ovaries. Precursor lesion is single colonic adenoma rather then multiple as found in FAP.
o        Familial adenomatous polyposis (FAP): Autosomal dominant mutation in the APC gene leads to hundreds/thousands of colorectal adenomas. Average age of developing colorectal cancer is 39yo. Affected people can have prophylactic colectomies.
·         Previous colorectal cancer
·         Ulcerative colitis /colonic crohn’s disease
·         Diet – hit fat/low fibre
·         Smoking
·         Alcohol drinking
·         Lack of exercise

Pathology/Pathogenesis
·         “Adenoma-carcinoma sequence” majority of adenocarcinomas start as benign adenomas that grow and acquire genetic changes that lead to the development of uncontrolled growth leading to adenocarcinomas.
·         Synchronous tumours found in 2% of cases
·         Most of the tumours found on the left side of the colon
·         Spread is through local invasion through the bowl wall and via local lymphatics, blood (portal vein into liver) and transcoelomic.
·         Histology shows well differentiated glandular epithelium with mucin production. Signet rings common characteristics

Symptoms
Left sided tumour:
  • Tenesmus
  • Blood in stool (fresh red blood)
Obstructive symptoms:
  • Change in bowl habit
  • Colicky abdominal pain
  • Nausea vomiting

Right sided tumour:
  • Weight loss
  • Anaemia
  • Abdominal mass (late stage)

Investigations
·         Rectal examination
Bloods tests:
- FBC (can show anaemia)
- CEA (carcino embryonic antigen – tumour marker normally used to monitor treatment)
- LFTs (show liver secondaries)
- faecal occult blood
·         proctoscopy
·         Barium enema
·         Sigmoidoscopy – tumours in the last 15cm of GI tract
·         Colonoscopy – can take biopsy’s
·         Ultrasound/CT – used to stage look for metastasis (liver)
·         CT colonography – less invasive then colonoscopies

Staging
Dukes
Type A – tumour confined to mucosa/sub mucose
Type B – invaded through bowl wall but lymph nodes clear
Type C – regional lymph nodes involved
Type D - Distant metastasis

TNM Staging System (Tumor, Node, Metastisis)
Tumor
T1: Tumor invades submucosa.
T2: Tumor invades muscularis propria.
T3: Tumor invades through the muscularis propria into the subserosa, or into the pericolic or perirectal tissues.
T4: Tumor directly invades other organs or structures, and/or perforates.

Node
N0: No regional lymph node metastasis.
N1: Metastasis in 1 to 3 regional lymph nodes.
N2: Metastasis in 4 or more regional lymph nodes.

Metastasis
M0: No distant metastasis.
M1: Distant metastasis present.

Stage Groupings
Using the TNM criteria colorectal cancers are placed in to 4 stages:

Stage I: T1 N0 M0; T2 N0 M0
Cancer has begun to spread, but is still in the inner lining.
Stage II: T3 N0 M0; T4 N0 M0
Cancer has spread to other organs near the colon or rectum. It has not reached lymph nodes.
Stage III: any T, N1-2, M0
Cancer has spread to lymph nodes, but has not been carried to distant parts of the body
Stage IV: any T, any N, M1
Cancer has been carried through the lymph system to distant parts of the body. This is known as metastasis. The most likely organs to experience metastasis from colorectal cancer are the lungs and liver.

Management
Surgery:
·         Right colon tumours – right hemicolectomy
·         Transverse colon tumours – extended right hemicolectomy
·         Descending colon tumours – left hemicolectomy
·         Sigmoid tumours - Sigmoid colectomy
·         Right rectal tumour – anterior resection (tumour removed colon anastomosed with remaining rectum) if anastomosis in doubt put in temporary stoma (iliostomy/transverse colostomy) mesentery of rectum also removed (mesorectal excision) avoid local recurrence.
·         Low rectal tumour - Abdomioperoneal resection – excise rectum and anus leaving patient with a permanent colostomy

The idea is to remove entire section of bowl supplied by same blood vessel as tumour to ensure clearance of all cancer cells.
Adjuvant chemotherapy increases survival in Dukes B and C.
Neo-adjuvant radiotherapy can be used for rectal tumours, difficult to use with colonic tumours due to the colon not being fixed in a certain position.
Total mesorectal excision gives better prognosis as it ensures the removal of all cancer cells that may have spread radially to the mesorectal tissue

Prognosis
·         Depends upon stage of the cancer
·         Over 95% survival in dukes A tumours that have been resected
·         When cancer has spread to lymph nodes far from the colon or rectum, to the lining of the abdominal cavity, or to other organs, the cancer cannot be cured by surgery alone. Survival time is typically only about 7 months