Updated: 1/11/2019

Colorectal Cancer (CRC)

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Introduction
  • 3rd leading cause of cancer deaths (male and female)
  • Most commonly located in rectum and sigmoid colon
  • Risk factors
    • family history
    • IBD
      • ulcerative colitis has greater risk than Crohn's
    • colorectal polyps
    • diet low in fiber
    • Streptococcus bovis bacteremia
    • tobacco use
    • large villous adenomas
    • polyp syndromes
      • e.g., Familial adenomatous polyposis (FAP)
  • Decreased risk associated with
    • NSAID use
    • estrogen
    • statins
  • Pathogenesis
    • 2 molecular pathways that lead to CRC
      • microsatellite instability pathway 
        • loss-of-function mutations in DNA mismatch repair genes 
          • leads to sporadic and HNPCC syndrome (see below)
      • APC/β-catenin (chromosomal instability) pathway
        • leads to FAP 
    • Follows the adenoma-carcinoma sequence - begins with APC mutation, with a step-wise accumulation of genetic mutations, ultimately concluding with p53 inactivation as the deciding factor in the progression from adenomatous polyp to carcinoma 
Presentation
  • Symptoms
    • Right sided lesions
      • more likely to bleed, less likely to obstruct
        • due to wider lumen
      • fecal occult blood
        • leading to iron deficiency
      • postprandial discomfort
    • Left sided lesions
      • more likely to obstruct, less likely to bleed
        • due to narrower lumen
      • change in bowel habits
      • pencil thin stools
      • abdominal mass
      • Strep. bovis endocarditis
    • systemic symptoms (malaise, fatigue, weight loss)
  • Physical exam
    • palpable mass on rectal exam (if large enough)
Evaluation
  • Barium enema X-ray
    • "apple core" lesion 
  • Colonoscopy
    • gold standard
  • Labs
    • microcytic anemia
      • iron deficiency anemia in an elderly male is colon cancer until proven otherwise
    • fecal occult blood test
      • lacks sensitivity and specificity as it only tests for globin with a peroxidase
        • false positive with high meat diet (myoglobin), radishes (peroxidase)
Differential
  • Hereditary Nonpolyposis Colorectal Cancer (HNPCC) / Lynch syndrome
    • single polyp can turn to cancer
    • due to loss-of-function in DNA mismatch repair genes (MLH1, MSH2/6, PMS3)
    • Lynch Syndrome I (HNPCC I)
      • AD inheritance
      • predisposition to right sided CRC 
    • Lynch Syndrome II (HNPCC II)
      • same features of Lynch I
      • plus extra-colonic cancers, especially
        • carcinoma of ovary, endometrium, small bowel, stomach, pancreas
        • transitional cell CA
Treatment
  • Surgical
    • resection
  • Medical
    • chemotherapy
Prognosis, Prevention, and Complications
  • Screening
    • screen patients > 50 years of age with stool occult blood test and colonoscopy
    • begin at age 40 with patients who have family history of CRC
    • annual digital exam
  • Recurrence monitoring
    • use CEA tumor marker 
      • not used for diagnosis
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.60) A 72-year-old male visits his gastroenterologist for a check-up one year following resection of a 2-cm malignant lesion in his sigmoid colon. Serum levels of which of the following can be used in this patient to test for cancer recurrence? Review Topic

QID: 101117
1

Alpha-fetoprotein

7%

(5/73)

2

Carcinoembryonic antigen

58%

(42/73)

3

Cancer antigen 125 (CA-125)

22%

(16/73)

4

Gamma glutamyl transferase

0%

(0/73)

5

CA-19-9 tumor marker

11%

(8/73)

M1

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