Diagnosis

Colorectal cancer

Etiology

Cause [cmb]

• Usually sporadic [95%)

• Hereditary malignancies (5%):

  • Lynch syndrome (hereditary nonpolyposis colon cancer - HNPCC)

  • Familial adenomatous polyposis (FAP)

Pathophysiology

1. Normal mucosa -> chronic inflammation

2. Hyperproliferation -> accumulation of mutation (MMR, APC, KRAS, TP53, and BRAF)

3. Early adenoma -> intermediate adenoma -> late adenoma

4. Carcinoma (-> metastatic disease)

Risk factors [cmb]

• Age

• Race

• Diet

• Inflammatory bowel disease

• Family history

• Inherited mutations: HNPCC, FAP, and Peutz-Jegher polyposis

• Adenomas on screening colonoscopy

• Lifestyle factors: Alcohol consumption, cigarette smoking, obesity, diets rich in processed red meat, insulin resistance, history of prior radiation, and immunosuppression

Protective factors [cmb]

• Physical activity

• Diet: Fruits, vegetables, fiber, resistant starch, and fish

• Supplementations: folate, folic acid, pyridoxine, calcium, vitamin D, and magnesium

• Garlic

• Coffee

• Aspirin, NSAIDs, hormonal replacement therapy, statins, bisphosphonates, and angiotensin inhibitors

Epidemiology

Incidence per 100.000 [dr8]

Approach

• Blood test

• Rectal exam

• Hemofec

• Colonoscopy

• CT abdomen

Treatment

1. Surgery

   • The only curative modality for localized cancer (stage I-III) -> Hemicolectomy

   • Stage IV:

     • Colonic stenting

     • Resections of liver metastases

     • Partial hepatectomy + Hepatic arterial infusion of chemotherapeutic agents

     • Cryotherapy

     • Radiofrequency ablation

     • Liver transplantation

2. Adjuvant chemotherapy: 5-fluorouracil + levamisole/leucovorin or Capecitabine

   • Standard if stage III disease and metastatic colorectal cancer (stage IV)

3. Radiation therapy: 

   • Limited to palliative therapy for selected metastatic sites such as bone or brain metastases

4. Biologic agents:

   • Bevacizumab (Avastin, Mvasi)

   • Cetuximab (Erbitux)

   • Nivolumab (Opdivo)

   • Panitumumab (Vectibix)

   • Pembrolizumab (Keytruda)

   • Tucatinib (Tukysa)

   • Fruquintinib (Fruzaqla)

Differential diagnoses

Arteriovenous malformation, Carcinoid tumor, Colorectal polyp, Crohn disease, Diverticulitis, Familial adenomatous polyposis, Gardners syndrome, Gastrointestinal lymphoma, Gastrointestinal obstruction, Hereditary nonpolyposis colon cancer syndrome, Ischemic colitis, Peutz-Jeghers syndrome, Small bowel cancer, Turcots syndrome, Ulcerative colitis, Volvulus