Ch. 21 Pencil-Thin Stools and Intermittent Constipation

Question 1

1. What screening is recommended for CRC?
2. What screening is recommended for CRC in pts with a 1st degree family member with CRC?

Answer 1

1. Screening in all adults of average risk, beginning at age 50 until age 75 (In pts with IBD, the screening recommendations vary)
2. These pts should begin screening at age 40 or 10 yrs prior to onset of CRC in 1st-degree relative… they should continue screening every 5 years after

Question 2

Where does colon cancer rank in terms of the most common cancers in the USA? In terms of highest overall mortality?

Answer 2

Question 3

Are Right- or Left-Sided Colon Cancers more common and how do the presentations differ?

Answer 3

Majority of colon cancers = L-sided and occur near rectosigmoid jxn

• L-sided more likely to cause change in bowel habits + sx of obstruction
  
  • When stool reaches sigmoid, it is often hard and devoid of excess fluid
  • Caliber of lumen is also narrower on L side, and with a circumferential tumor causing partial obstruction, pts report pencil-thin stools, often tinged with blood
• R-sided - most common finding is an insidious onset of iron deficiency anemia 2/2 chronic GI blood loss

Question 4

Pathophysiology:

1. What is a polyp and how are they generally classified?
2. Describe the non-neoplastic polyps?

Answer 4

1. Polyp = mass that protrudes into the lumen of GI tract and can either be pedunculated (with a stalk) or sessile (flat)
   
   1. Non-neoplastic polyps can arise from abnormal mucosal maturation, inflammation, or colonic architecture… however, polyps arising from epithelial proliferation and dysplasia = TRUE neoplasms and may have malignant potential –> collectively known as adenomatous polyps or adenomas
2. Type:
   
   1. Hyperplastic
      
      1. Small (<5 mm in diameter) and smooth; most common type (BENIGN–NORMAL CELLS–NO MALIGNANT POTENTIAL)
   2. Juvenile (hamartomatous)
      
      1. Rounded, smooth, sometimes have a stalk (< 2 cm); occur most commonly in children (<5 y/o); usually present as a solitary rectal polyp that prolapses (NORMAL TISSUE IN ABNORMAL CONFIGURATION)

Question 5

1. From which site is melena more common?
2. From which site is hematochezia more common?
3. What tests help find mets?
4. What are the means by which the cancer spreads?
5. Is CEA useful?

Answer 5

1. Melena = R-sided colon cancer
2. Hematochezia = L-sided colon cancer
3. Tests:
   
   1. CXR (lung)
   2. LFTs (liver)
   3. Abdominal CT (liver)
4. Spread:
   
   1. Direct extension: circumferentially and then through bowel wall to later invade other abdominoperineal organs
   2. Hematogenous: portal circulation to liver; lumbar/vertebral veins to lungs
   3. Lymphogenous: regional lymph nodes
5. CEA useful NOT for screening but for baseline and recurrence surveillance (but offers no proven survival benefit)

Question 6

How do colon cancers develop?

Answer 6

1. Chromosome instability pathway (stepwise accumulation of mutations leading to carcinoma)
2. MSI (impaired DNA mismatch repair enzymes are unable to ensure fidelity of copied DNA strand, inc. risk for developing cancer)

Question 7

What features of an adenoma are associated with an increased malignant risk?

Answer 7

• Four subtypes of adenomas that are based on their epithelial architecture
• Risk of malignancy is dependent on polyp size, architecture, dysplasia severity

Question 8

What are the most common metastatic sites for CRC?

Answer 8

Regional mets are to the mesenteric lymph nodes (the N in the TNM system)

Liver = most common location of distant metastasis, owing to venous drainage of colon to liver via mesenteric veins draining to portal system and tendency for these cancers to spread hematogenously

Question 9

What hereditable conditions are associated with colon cancer?

HNPCC

FAP

Answer 9

HNPCC = Hereditary NonPolyposis Colon Cancer

• AD inheritance of high risk for development of colon cancer
  
  • Also: endometrial, ovarian, stomach, breast, etc….
• Lynch type 1 caused by heterozygous mutation in DNA mismatch repair genes and results in more colonic cancers, often on R side and typically in 4th decade of life
• Lynch type 2 caused by mutations in MLH1 gene and results in more extracolonic cancers

FAP = FAMILIAL ADENOMATOUS POLYPOSIS

• AD condition in which pts develop hundreds to thousands of polyps in the colon (beginning at rectum), which if left untreated, can develop into cancer
• Mutation is in APC gene
• Polyps begin on average in mid-teens but can apear as early as age 7
• Tx = prophylactic colectomy often recommended to prevent cancer development –> if left untreated, 100% of pts develop cancer by 4th or 5th decade of life

Question 10

What hereditable conditions are associated with colon cancer?

GARDNER’S SYNDROME

TURCOT SYNDROME

Answer 10

GARDNER’S SYNDROME

• AD condition of neoplastic polyps of small bowel + colon
• Cancer by age 40 in 100% of undiagnosed pts, as in FAP
• Associated findings:
  
  • Sebaceous cysts
  • Osteomas of skull
  • Desmoid tumors (tumor of musculoaponeurotic sheath, usually of abdominal wall)

TURCOT SYNDROME

• Cafe au lait spots
• Malignant CNS tumors (GBM)
• Neoplastic colon polyps that progress to cancer

Question 11

A 42 y/o man has bouts of intermittent crampy abdominal pain and rectal bleeding. Colonoscopy is performed and demonstrates multiple hamartomatous polyps. The pt is successfully treated by removing as many polyps as possible with the aid of intraoperative endoscopy and polypectomy. Which of the following is the most likely diagnosis?

A. UC

B. Villous adenomas

C. Familial polyposis

d. Peutz-Jeghers syndrome
e. Crohn colitis

Answer 11

d. Peutz-Jeghers syndrome

PJS = intestinal polyposis and melanin spots of the oral mucosa

Unlike adenomatous polyps seen in familial polyposis, the lesions in this condition are hamartomas, which have no malignant potential. Surgery for symptomatic polyps involves polypectomy.