• Colorectal cancer is second commonest cancer causing death in the UK
• 20,000 new cases per year in UK 
• 40% are rectal and 60% are colonic tumours
• 3% patients present with more than one tumour (=synchronous tumours)
• A previous colonic neoplasm increases the risk of a second tumour (=metachronous tumour)
• Some cases are hereditary
• Most related to environmental factors

Risk factors

• Sporadic colorectal cancer (85%)
  • Older age
  • Male sex
  • Cholecystectomy
  • Ureterocolic anastomosis
  • Diet rich in meat and fat
  • Obesity
  • Smoking
  • History of colorectal polyps
  • History of colorectal cancer
  • History of small bowel, endometrial, breast and ovarian cancer
  • Familial colorectal cancer (20%)
    • First or second degree relatives with cancer but criteria for HNPCC not fulfilled
    • One first-degree relative increases risk by 2.3
    • Two or more first degree relatives increases risk by 4.3
    • Index case <45 years increases risk by 3.9
    • Family history of colorectal adenoma increases risk by 2.0
• Colorectal cancer in inflammatory bowel disease (1-2%)
  • Ulcerative colitis
  • Crohn's disease
• Hereditary colorectal cancer (5-10%)
  • Polyposis syndromes - FAP
  • Hereditary non-polyposis colorectal cancer (HNPCC)
  • Hamartomatous polyposis syndromes

Inherited syndromes

Familial adenomatous polyposis syndrome

• FAP accounts for less than 1% of all colorectal cancers
• Patients have widespread colonic polyps that inevitably progress to malignant disease
• Polyps usually appear in second or third decade of life
• Also associated with:
  • Duodenal adenomatous polyps
  • Upper GI malignancy
  • Congenital hypertrophy of the retinal pigment epithelium
  • Desmoid tumours
  • Tumours of the CNS, thyroid and adrenal cortex
• Due to mutation of tumour suppressor gene
• Inherited as an autosomal dominant
• At risk family member should undergo genetic testing
• Affected individuals should have prophylactic surgery

Hereditary non-polyposis colorectal cancers (Lynch syndrome)

• Heterogeneous group of familial cancers
• Account for 3-5% of colorectal cancers
• Tumours arise from polyps
• Widespread polyposis seen in FAP is not present
• Accelerated progression from polyps to cancer occurs
• Due to microsatellite instability due to inheritance of mutated mismatched repair gene
• Increases risk of following cancers
  • Colorectal
  • Gastric
  • Endometrial
  • Ovary
  • Urothelial
• Amsterdam criteria were developed to standardise diagnosis
  • At least three relatives with colorectal cancer
  • One must be first-degree relative of the other two
  • At least two successive generations should be affected
  • One colorectal cancer should be diagnoses before the age of 50 years

Adenoma - carcinoma sequence

• Of all adenomas
  • 70% tubular
  • 10% villous
  • 20% tubulovillous
• Most cancers believed to arise within pre-existing adenomas
• Risk of cancer greatest in villous adenoma
• Series of mutations results in epithelial changes from normality, through dysplasia to invasion
• Important genes - APC, DCC, k-ras, p53.

Clinical presentation

• Right-sided lesions present with
  • Iron deficiency anaemia due occult GI Blood loss
  • Weight loss
  • Right iliac fossa mass
• Left-sided lesions present with
  • Abdominal pain
  • Alteration in bowel habit
  • Rectal bleeding
• 40% of cancers present as a surgical emergency with either obstruction or perforation
• Emergency presentation is associated with a poorer outcome

Picture supplied by Mr N P J Cripps, Consultant Colorectal Surgeon, Chichester, United Kingdom

Picture provided by Mr David Anderson, St John's Hospital, Livingston, Scotland

Investigation

• In elective cases diagnosis can be confirmed by a combination of:
  • Rigid sigmoidoscopy
  • Flexible sigmoidoscopy
  • Colonoscopy
  • Double contrast barium enema
• In patients presenting with large bowel obstruction single contrast enema (after rigid sigmoidoscopy) is the investigation of choice

Surgical options

• Any surgical resection requires 5 cm proximal and  2 cm distal clearance for colonic lesions
• 1 cm distal clearance of rectal lesions is adequate if mesorectum resected
• Radial margin should be histopathologically free of tumour if possible
• Lymph node resection should be performed to the origin of the feeding vessel
• En Bloc resection of adherent tumours should be performed
• The value of a 'no-touch' techniques remains unproven
• Depending on site of lesion surgical options are:
  • Caecum, ascending colon, hepatic flexure – Right hemicolectomy
  • Transverse colon – Extended right hemicolectomy
  • Splenic flexure, descending colon – Left hemicolectomy
  • Sigmoid colon – High anterior resection
  • Upper rectum – Anterior resection
• Consider defunctioning loop ileostomy is anastomosis <12 cm from anal margin
  • Lower rectum – Abdomino-perineal resection
  • Small lower rectal cancers may be resectable by transanal microsurgery
• Laparoscopic surgery is unproven
• Early studies raised concerns about port site recurrence
• Recent studies suggest equivalent overall and disease-free survival

Surgery for upper rectal cancers

• Risk of local recurrence reduced by performing total mesorectal excision (TME)
• Pelvic peritoneum and lateral ligaments divides
• Plane between visceral (rectum, mesorectum) and somatic structures dissected

• Middle rectal vessels divided laterally
• Rectal stump washed out with cytocidal fluid (water, Betadine) from below
• Anastomosis can be either hand-sown or stapled
• It can be either an straight anastomosis or a colonic pouch can be fashioned
• This is often a J-pouch and provides a better functional outcome

Picture provided by Prof Ian Bradford, Prince of Wales Hospital, Shatin, Hong Kong

Dukes Classification

• Developed by Cuthbert Duke in 1932 for rectal cancers
• Dukes staging of colorectal cancer

• Stage A - Tumour confined to the mucosa
• Stage B - Tumour infiltrating through muscle
• Stage C - Lymph node metastases present
• Five year survival - 90%, 70% and 30% for Stages A, B and C respectively

Adjuvant radiotherapy

• In patients with rectal cancer 50% undergoing curative resection develop local recurrence
• Median survival with local recurrence is less than one year
• Risk factors for local recurrence include:
  • Local extent of tumour
  • Nodal involvement
  • Circumferential margin status
• Risk of local recurrence can be reduced by radiotherapy
• Can be given either preoperatively or postoperatively
• Preoperative radiotherapy given as short course immediately prior to surgery
  • Reduces local recurrence
  • Increases time to recurrence
  • Improves 5-year survival
• Combination chemotherapy and radiotherapy may produce better outcome

Adjuvant chemotherapy

• Improves survival in Duke's C tumours
• Not required in Duke's A tumours which already have a good prognosis
• Role in Duke's B tumours remains to be defined
• Currently being investigated in the QUASAR (Quick and Simple and Reliable) trial
• Results of QUASAR study to date have shown
  • 5FU and folinic acid is effective as adjuvant therapy
  • High dose folinic acid rescue confers no additional benefit
  • The use of levimasole confers no additional benefit

Colorectal cancer screening

• Screening for colorectal cancer can be divided into two categories
  • Screening of high risk groups
  • Population screening

Screening of high risk groups

• This includes
  • Patients with family history
  • Sporadic adenomatous polyps
  • Inflammatory bowel disease
• Definition of the high risk group is difficult
• High risk patients should undergo colonoscopy at approximately 50 years
• Patients with family history of FAP or HNPCC should undergo genetic testing
• If mutation present should undergo intensive colonoscopic screening from adolescence

Population screening

• The role of screening is currently being investigated by either
  • Faecal occult blood testing
  • Colonoscopy
• Nottingham study has recruited over 150,000 patients
• 75,250 underwent biennial FOB testing
• Resulted in 1774 colonoscopies
• Seven complications occurred requiring operations in 6 patients
• No difference identified in stage of presentation in screened group
• Survival in screened group was significantly improved

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