COLORECTAL CANCER

Question 1

Overview (3)

Answer 1

• 3rd most common cancer and 2nd most common cause of cancer deaths
• Most common type of gastrointestinal cancer, usually Adenocarcinoma
• May be due to genetic factors, environmental exposures (including diet), and inflammatory conditions of the digestive tract

Question 2

Inheritance (3)

Answer 2

• Adenoma to carcinoma sequence (in 75% of cases): stepwise accumulation of abnormalities in a number of critical growth-relating genes. Sporadic mutations in APC, k-ras, and p53 (tumor suppressor genes)
  Normal —> (APC) Small Adenoma —> (k-ras) Large Adenoma —> (p53) AdenoCa
• Microsatellite instability from faulty DNA mismatch repair function (e.g. in Lynch)
• Hypermethylation of DNA promotor regions (CIMP): serrated methylated pathway

Question 3

Risk Factors (10)

Answer 3

• Increasing age: major risk factor for sporadic CRC (incidence begins increasing after age 40, and average age at diagnosis is 60-65 years)
• Family history (most significant risk factor next to age)
• Personal or family history of sporadic CRCs or adenomatous polyps or gonadal/breast cancer
• African americans (higher rates, higher mortality, earlier disease)
• DM and Acromegaly (insulin and IGF-1 are growth factors for colonic mucosal cells)
• Smoking and alcohol
• Diet (increased fat, red meat, and decreased fiber)
• Neoplastic/Adenomatous polyps (especially if >1cm, villous, multiple)
• Inflammatory bowel disease (especially UC)
• Genetic predisposition (e.g. FAP, HNPCC, polyposis syndromes)

Question 4

Presentation (6)

Answer 4

• May present in 3 ways:
  
  • Patients with suspicious symptoms and/or signs
  • Asymptomatic: discovered by routine screening
  • Emergency admission (intestinal obstruction, peritonitis, acute GI bleed)
• Symptoms and signs depend on tumor location:
  
  • Right masses: occult blood loss, IDA, and in advanced cases palpable mass
  • Left masses: obstruction and macroscopic bleeding (hematochezia)
  • Rectal masses: rectal bleeding, obstruction, alternating diarrhea and constipation, and in advanced cases tenesmus
• Most cases are diagnosed after symptoms onset
• Most common presentation is rectal bleeding, abdominal pain, otherwise unexplained iron deficiency anemia, and/or a change in bowel habits
• 1/5th of patients present with metastatic disease (most commonly to regional lymph nodes, liver, lungs, and peritoneum)
• Unusual presentations of CRC include malignant fistula formation, fever of unknown origin, and sepsis from Streptococcus bovis and Clostridium septicum

Question 5

Investigations (7)

Answer 5

• CBC: microcytic anemia, LFTs abnormal if liver mets
• Fecal occult blood positive
• CEA (pre-operative for baseline not for diagnosis, useful in monitoring after surgery, >5ng/mL have worse prognosis
• Colonoscopy: gold standard —> localize and biopsy lesions for histological diagnosis, detect synchronous neoplasms, remove polyps
• If colonoscopy is unavailable or tumor cannot be reached —> CT colonography is preferred over barium enema
• Staging: CT chest/abdomen/pelvis; bone scan
• MRI and endoanal US are used to locally stage rectal cancer

Question 6

Treatment (5)

Answer 6

• Treatment is surgical: removal of the tumor with its lymphovascular supply —> wide resection of lesion (5cm margins) with regional lymphatic drainage (>12 nodes) and mesentary; usually colectomy with primary anastomosis
• Type of surgery depends on the location of the tumor:
  
  • Cecum or right colon: right hemicolectomy
  • Splenic flexure or left colon: left hemicolectomy
  • Sigmoid or rectosigmoid: sigmoid colectomy
• Adjuvant chemotherapy is beneficial in stage 3 + high risk stage 2
• Stage 4: metastatic palliative chemotherapy. Hepatic mets resection in up 3 liver mets in the same lobe. Palliative surgery for complications.
• Stage 2 and 3 rectal cancer: neoadjuvant chemoradiation 5-FU, surgical resection, and adjuvant chemotherapy