Suspected Colorectal cancer can only be excluded with either a Ba enema + rigid sigmoidoscopy, CT pneumocolon or colonoscopy. Serial monitoring of CEA can help detect recurrence
- Common cause of cancer in older patients due to a series of Genetic defects which lead to cancer
- Most if not all CRCs are derived from Colorectal Adenomas which undergo and accumulate genetic defects
- Exceptions being possibly HNPCC and those related to Ulcerative colitis
- Male sex, diet low in fibre, fruit and vegetables
- High fat and red meat, Cholecystectomy - "bile salts"
- Sporadic 70%
- Ulcerative colitis > 10 years
- Crohn's colitis over many years
Familial Risks 10-30%
- Sporadic 70%, Familial 10-30%
- Hereditary non polyposis coli cancer 2-3%
- Familial adenomatous polyposis < 1%
- Gardner's syndrome
- Hamartomatous < 0.1%
- Dietary factors - low fibre, high fat
- Genetic factors e.g. FAP, HNPCC
- Inflammatory bowel disease
- NSAIDS/Aspirin may be protective
- Activation of tumour promoting genes / oncogenes K-ras, c-myc
- Loss of suppression of tumour suppressor genes p53, MCC, DCC
- Mismatch repair gene mutations (hMSH2 and hMLH1)
- Adenoma eventually becomes carcinoma
- Normal Epithelium ? Dysplastic Epithelium ? Adenoma ? Adenocarcinoma
- Increased right-sided tumours with Familial or FAP or HNPCC
- Loss of DNA methylation, Aneuploidy, Mutations of proto-oncogenes
- Mutations of tumour suppressor genes e.g. Adenomatous polyposis gene (APC) and Mutated in colonic cancer (MMC gene) all on chromosome 5 , Deleted in Colon cancer (DCC gene) and loss of p53 gene.
- There is a need for both copies of the alleles to be affected by mutations "double hit"
- Ulcerating - bleeding, anaemia
- Annular - can obstruct
- Colloid - secretes mucous
Polyps risk of malignant change
- Histology: Villous > Tubulovillous > Tubular
- Size: Increasing Size
- Degree of epithelial dysplasia of the adenoma
- Grade I: Well differentiated
- Grade II/III: Moderately differentiated
- Grade IV: Anaplastic
- Rectum and sigmoid colon 60%
- Ascending colon 20%
- Transverse and descending colon 20%
Cancer Spread and Metastases
- Along with bowel usually within 2 cm of margin
- Spread to Liver, Lungs, Adrenal, kidneys, bone
- Lymphatic to paraaortic, supraclavicular nodes
- Tumour spread to ovaries forms Krukenburg tumours
- Implanted into surgical wounds/colostomy/laparoscopy ports
- Rectal lesion - visible blood loss on stool or after defaecating, tenesmus. Altered bowel habit. Mass on PR exam.
- Left sided colonic lesion - altered bowel habit, constipation, blood mixed in stool, Iron deficiency anaemia or a sigmoid mass.
- Right sided lesions - more occult than left sided lesions classically with anaemia and only very later with Intestinal obstruction as contents more liquid. Altered bowel habit may be seen. Weight loss and malaise, abdominal pain.
- Emergency presentation with obstruction, perforation and peritonitis or haemorrhage
- Fistula to bladder or vagina with UTI and faecalent vaginal discharge
- Tumour spreads to lymphatic locally and then on to liver and beyond so presentation may be with hepatomegaly and cachexia
- FBC - Iron deficiency anaemia
- Ferritin, B12, folate to investigate anaemia
- LFTS - ? ALP may suggest liver metastases
- Abdominal USS - may show liver involvement
- Ba enema + rigid sigmoidoscopy* may show a lesion classically "applecore" stricture.
- Rigid sigmoidoscopy as Ba enema cannot reliably detect very distal disease
- CT pneumocolon* is a less invasive way of identifying tumour
- Colonoscopy* enables visualisation, marking and biopsy.
- FOBs are only used as screening tools in screening trials
- Elevated Carcinoembryonic antigen is not diagnostic as it is raised in Inflammatory bowel disease, Colorectal Cancer, Smokers and those with high alcohol intake. Carcinoembryonic antigen is however very useful for monitoring response to treatment in those with proven disease.
- CT, CXR, MRI for Staging
- Endorectal USS for rectal disease
Summary of Management
- Management is Multidisciplinary
- Surgeons, Physicians, Pathologist, Radiologist, Oncologist
|Stage/extent ||Treatment|| Survival at 5 yrs
|A|| limited to mucosa|| Surgery only|| >90%
|B1|| muscularis propria|| Surgery + RXT (+/- DXT) ||85%
|B2|| serosa|| ||75%
|C1|| 1-4 regional LN ||Surgery + DXT (+/- RXT) ||65%
|C2|| >4 regional LN|| ||40%
|D|| distant mets|| palliative||5-10%
- Preventative surgery in FAP : Colectomy and ileorectal anastomoses the life expectancy of FAP has risen from 35 to 65 years old
Disease Management: Tumour resection and reanastomosis
- Right hemicolectomy for caecal/ascending colon and proximal transverse colon lesion.
- Left hemicolectomy for distal transverse colon and descending colon disease.
- Sigmoid colectomy for sigmoidal disease.
- Anterior resection for High rectal disease.
- Low rectum requires abdominoperineal resection and colostomy.
- Resection limits once where 5 cm but now reduced to 2 cm.
- Single hepatic metastases have been resected.
Optimise fitness for surgery - nutrition, hydration. Where cure is possible wide resection of the tumour with regional lymphatics.
- Obstructive emergency cases require initially relief if the obstruction followed by elective surgery if needed or appropriate
Chemotherapy: They are used in those with Dukes stage C and some with Dukes B.
- Chemotherapy used includes 5 fluorouracil and leucovorin have been used.
- Other drugs used include oxaliplatin and innotecan.
- Cetuximab a biological agent against EGFR receptor and bevacizumab against VEGF have been used.
- Radical surgical excision is not contraindicated with peritoneal or hepatic metastases as it may help with palliation.
- Colostomy is performed for tumours which cannot be resected and it may allow palliative high dose radiotherapy to the tumour
- Radiotherapy is useful for palliation of pain and rectal bleeding. Its use is mainly limited to the management of rectal disease.
- It can be used before rectal tumour resection preoperatively or post op in those with high risk of rectal tumour recurrence.