Colorectal carcinoma

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%) o Older age o Male sex o Cholecystectomy o Ureterocolic anastomosis o Diet rich in meat and fat o Obesity o Smoking o History of colorectal polyps o History of colorectal cancer o History of small bowel, endometrial, breast and ovarian cancer o 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%) o Ulcerative colitis o Crohn's disease Hereditary colorectal cancer (5-10%) o Polyposis syndromes - FAP o Hereditary non-polyposis colorectal cancer (HNPCC) o 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: o Duodenal adenomatous polyps o Upper GI malignancy o Congenital hypertrophy of the retinal pigment epithelium

o Desmoid tumours o 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 o Colorectal o Gastric o Endometrial o Ovary o Urothelial Amsterdam criteria were developed to standardise diagnosis o At least three relatives with colorectal cancer o One must be first-degree relative of the other two o At least two successive generations should be affected o One colorectal cancer should be diagnoses before the age of 50 years

Adenoma - carcinoma sequence

Of all adenomas o 70% tubular o 10% villous o 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 o Iron deficiency anaemia due occult GI Blood loss o Weight loss o Right iliac fossa mass Left-sided lesions present with o Abdominal pain o Alteration in bowel habit o 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: o Rigid sigmoidoscopy o Flexible sigmoidoscopy o Colonoscopy o 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 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: o Caecum, ascending colon, hepatic flexure Right hemicolectomy o Transverse colon Extended right hemicolectomy o Splenic flexure, descending colon Left hemicolectomy o Sigmoid colon High anterior resection o Upper rectum Anterior resection Consider defunctioning loop ileostomy is anastomosis <12 cm from anal margin o Lower rectum Abdomino-perineal resection o 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: o Local extent of tumour o Nodal involvement o 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 o Reduces local recurrence o Increases time to recurrence o 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 o 5FU and folinic acid is effective as adjuvant therapy o High dose folinic acid rescue confers no additional benefit o The use of levimasole confers no additional benefit

Colorectal cancer screening

Screening for colorectal cancer can be divided into two categories o Screening of high risk groups o Population screening Screening of high risk groups This includes o Patients with family history o Sporadic adenomatous polyps o 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 o Faecal occult blood testing o 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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