Colorectal Cancer

December 17, 2018

Most colorectal cancers develop from polyps via the adenoma-to-carcinoma pathway. In the United States, 30-50% of adults develop adenomatous polyps during their lifetime, although only 1 in 20 polyps will progress to cancer. This progression to cancer and metastasis results from an accumulation of genetic mutations that occur over a decade or more (for example tumor suppressor genes: APC and p53 , oncogene: K-ras and DNA mismatch repair genes that occurs during cellular replication). 

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch syndrome or Muir-Torre syndrome

Characterized by having a few polyps (hence nonpolyposis). In the US, there are 140,000 new cases of colorectal cancer diagnosed each year and approximately 3-5% of these are caused by Lynch syndrome. Usually multiple family members on the same side of the family will be diagnosed with colorectal and/or endometrial cancer at a young age (usually before the age of 50).  

Cause

Autosomal dominant disorder that increases the risk of many other cancers during the patients lifetime:

Variations in the following DNA repair genes prevents proper DNA repair after cellular replication:

  • MLH1

  • MSH2

  • MSH6

  • PMS2

  • EPCAM

Not all individuals with mutations in these genes will develop cancer. 

Diagnosis

  • blood test - confirmatory testing

  • Microsatellite instability testing (MSI) - screening test

  • Immunohistochemistry testing (IHC) - screening test

Muir-Torre Syndrome

  • sebaceous adenomas

  • sebaceous epitheliomas

  • sebaceous carcinomas

  • keratocanthomas

Turcot syndrome

  • brain tumors

Familial Adenomatous Polyposis (FAP)

Characterizes as having thousands of polyps.

Cause

APC gene mutation

Treatment

Colectomy because there are thousands of polyps. 

Li-Fraumeni Syndrome

Cause

p53 gene mutation

G​eneral Colon Cancer Treatment

Treat according to stage

  • Stage I: partial colectomy

  • Stage II: partial colectomy +/- adjuvant therapy

  • Stage III: partial colectomy + adjuvant therapy (because of lymph node involvement)

  • Stage IV: palliative colectomy or colon diversion to prevent obstruction. If chemotherapy done its usually for palliative reasons. The exception is if there is resectable hepatic metastases which can still be curable with resection and thus surgery should be aggressively pursued. 

Chemotherapy

  • 5-FU

  • Leucovorin (folinic acid)

  • Oxaliplatin 

  • FOLFOX (FU/Leucovorin/Oxaliplatin)

Rectal cancer

Because of the anatomy of the rectum, there is generally less room for surgical approaches to obtain adequate margins and preservation of the rectal sphincter if possible. Therefore radiation therapy and chemotherapy used. 

... but I would more especially commend the clinician who, in acute diseases, by which the bulk of mankind are cutoff, conducts the treatment better than others.
 
Hippocrates, 400 BC