Colorectal cancer

Colorectal cancer

1. Anatomy of large intestine

   • Arteries
   • Veins
   • Lymphnoes
   • Nerves

2. Histology of large intestine

3. Defecation reflex

   • Intrinsic reflex
     • Enteric nervous system
       • Myenteric plexus
         • Ascending pathway
           • Increase mass movement
         • Descending pathway
           • Relax internal anal sphincter
     • Not enough alone
   • Parasympathetic defecation reflex
     • Amplifiy the intrinsic reflec
     • Through S2 S3 S4
     • More mass movement
       • More inhibition of the internal anal sphincter
   • Voluntary control of external anal sphincter
     • through pudendal nerve

4. Risk Factors

   • Inherited gene mutations
     • FAP
     • HNPCC
   • Older age
   • IBD
   • Low-fiber, high-fat diet
     • Increase transit time
   • Sedentary lifestyle

5. Pathophysiology

   • APC/B-catenin pathway
     • Loss of APC gene
       • accumulation of B-catenin
         • Promote transcription of growth promoting genes
           • Cyclin D1
           • MYC
     • Kras mutation
     • P53 mutation
     • SMAD2 AND SMAD4 mutation
     • Mutation in telomerase
     • Left side
   • Micro-sattelite instability-MSI(MSH2-MLH1)
     • Right side
     • Mutation in DNA mismatch repair genes (MSH1-MLH2)
       • Microsatellite in the coding region of type II TGF-B receptor and pro-apoptotic BAX….cell proliferation

6. Investigations

   • Blood test
   • Colonoscopy
     • Biopsy
   • CT scan
     • Metastasis
   • Tumor markers
     • CEA
     • CA 19-9
   • Chest X-ray
     • Metastasis to the lungs

7. Complications

   • Blockage of the colon
   • Cancer returning
   • metastasis
   • Development of a second primary colorectal cancer

8. chemotherapy

   • 5-fluorouracil
     • DNA >prevents thymidylate synthetase action: 5-FdUMP forms a covalently bound complex with the enzyme & its cofactor
       • inhibition of DNA synthesis
     • RNA > incorporation into RNA: 5-FUTP gets incorporated > heavier than the normal uracil > instability of the RNA & interferes with RNA’s processing & functions
   • Capecitabine
     • Allows for selective 5- FU activation in tumor tissue
     • Activated through 3 steps mainly by thymidine phosphorylase
   • Oxaliplatin
     • results in distortion of structure of DNA & blocking of the path of replication & transcription
   • Monoclonal antibodies
     • Cetuximab
       • IgG monoclonal antibody directed against the EGFR
     • Panitumumab
       • IgG monoclonal antibody directed against the EGFR
     • Bevacizumab
       • Binds all isoforms of circulating VEGF > inhibits permeability & angiogenesis
   • Camptothecins
     • Stabilize the topoisomerase I-DNA complex > allow it to cut one DNA strand to release the stress of supercoils, but inhibits it from repairing (or resealing) the cut > converts transient DNA cuts into permanent ones >replication fork encounters a stabilized cleavable complex > more lethal DNA damage occurs > cell death

9. Surgical treatment

   • Right hemicolectomy
     • tumors from cecum to splenic flexure
   • Left hemicolectomy
     • tumors of descending and sigmoid colon
   • Anterior resection
     • tumors of rectosigmoid junction/ rectum
   • Abdominoperineal resection
     • very low rectal and anal canal tumors
   • Hartman’s procedure
     • emergency surgery

10. screening and surveillance

11. prognosis

12. Signs and symptoms

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