Gastrointestinal disease - Colorectal Carcinoma

Genetics of colorectal cancer

Genetic of colorectal cancer
Most colorectal cancers develop as a result of a stepwise progression from normal muscosa to adenoma to invasive cancer. This progression is controlled by the accumulation of abnormalities in a number of growth regulating genes. These include APC mutation and loss, K-ras mutation, Smad2/4loss and TP53 mutation and loss, and altered DNA methylation with progression to carcinoma. Microsatellite instability (MSI) and chromosomal instability (CIN) are frequently detected in colon cancers. CIN indicates loss of heterozygosity (LOH) in a number of cancer related genes. About 15% of sporadic colorectal cancers show MSI and 50% exhibit LOH.

Cancer families
FAP is the best-recognized syndrome predisposing to colorectal cancer. Hereditary non-polyposis colorectal cancer (HNPCC) accounts for 3-10% of familial cancer.

Pathology
CRC, which is usually a polypoid mass with ulceration, spreads by direct infiltration through the bowel wall. It involves lymphatic and blood vessels with subsequent spread, most commonly to the liver and lung.

Clinical features
Symtpoms suggestive of colorectal cancer include change in bowel habit with looser and more frequent stools, rectal bleeding, tenesmus and symptoms of anemia.

Investigation

• Colonoscopy is the golden standard.
• Double-contrast barium enema
• Endoanal ultrasound and pelvic MRI
• Chest, abdominal and pelvic CT
• PET scanning
• MR
• Serum carcinoembryonic antigen (CEA)
• Faecal occult blood tests

Treatment
About 80% of patients with colorectal cancer undergo surgery, though fewer than half of these survive more than 5 yrs.

• Total mesorectal excision (TME) is required for rectal cancers and removed the entire package of mesorectal tissue surrounding the cancer.
• A segmental resection and restorative anastomosis
• Local transanal surgery used for early superficial rectal cancers
• Surgical or ablative treatment of liver and lung metastases
• Radiotherapy is not helpful for colonic cancers proximal to the rectum because of difficulties delivering a sufficient dose to the tumour without excess toxicity to adjacent structures, particularly the small bowel.
• Adjuvant postoperative chemotherapy

Screening

• Faecal occult blood (FOB) tests
• Flexi-sigmoidoscopy
• Colonoscopy (high risk patients)
• CT colonography
• Genetic testing and stool DNA tests