CM- Colorectal Cancer Flashcards
What is proposed to be a substantial risk for the development of colorectal cancer?
What is the believed mechanism for why this is?
High fat, low fiber diets are proposed to be a cause because colorectal cancer is more prevalent in developed countries. People that move from areas where it is NOT endemic to areas where it is are at an increased risk for development suggesting diet and environment.
Fat: increased cholesterol and bile acid delivery to the intestine where they are metabolized by endemic bacteria into carcinogens
Fiber: should increase stool bulk, diluting the carcinogens. Also, increased transit time through the colon decreasing the time carcinogens are exposed to the colon
In addition to increased fiber, what else is hypothesized to decrease the risk for colorectal cancer?
- vitamins- ACE
- cruciferous vegetables (green/leafy)
- calcium
- chronic use of NSAIDs/aspirin
Adenocarcinomas do NOT often arise de novo from normal colonic epithelium.
Describe the adenoma-carcinoma progression.
How long does the progression from normal cells to adenocarcinoma usually take?
- normal epithelium gets mutations that activate proto-oncogenes or inhibit tumor suppressors
- hyperproliferating cells get additional gene mutations that lead to a clone of autonomous, neoplastic cells
- Neoplastic cells are dysplastic (seen on histology) and accumulate to form an adenamatous polyp (adenoma)
- Additional mutations occur in the adenoma and the cells become highly dysplastic
- Some cells acquire mutations enabling invasion of other tissues [malignant adenocarcinoma]
This whole progression takes 7-12 years
What genes are typically found to be mutated in the adenoma-carcinoma sequence? Put them in order of proposed sequence of mutation.
- APC deletion (loss of a tumor supressor)
[normal to hyperproliferative epithelium] - KRas (oncogene)
[early adenoma –> intermediate] - DCC (tumor suppressor loss)
[intermediate–>late adenoma] - p53 (tumor suppressor)
[late –> carcinoma]
What are the 6 factors that predispose to CRC?
- Age
- Diet [high fat, low fiber]
- Genetic disorders [FAP/HNPCC]** highest risk
- chronic IBD [crohn or UC]
- personal Hx of adenomas or prior CRC
- FHx of CRC or adenoma
For a person with chronic IBD, what 2 things increase the risk of colorectal cancer?
- extent of colonic involvement [pancolitis»_space; left sided only]
- duration of disease [appreciable risk after 7 yrs]
A personal history of adenomas or prior CRC is associated with an increased risk of developing what?
What factor determines the risk?
They are at risk for developing subsequent metachronous tumors.
Risk increases with the # of adenomas on initial colonoscopy
FHx can predispose to colorectal carcinoma even in the absence of FAP and HNPCC. The risk increases with what 2 things?
- the number of first degree relatives with CRC
2. family members that got it before the age of 50
What is the most common NON-neoplastic polyp of the colon?
What size are they and what part of the colon are they generally found?
What is their potential for malignancy?
Hyperplastic polyps are usually less than 5mm and are found in the rectosigmoid.
They have little [if any] malignant potential EXCEPT for:
**>1cm, Serrated hyperplastic polyps in the right colon.
[there serrated polyps were first noted to lead to malignancy in HNPCC and hyperplastic polyposis syndrome]
What three features of the adenomatous polyp correlate with malignant potential?
What is considered low, medium and high risk for malignancy?
- Size
- low = less than 1cm
- med = 1-2 cm
- high = over 2 cm - Histology
- low = tubular [branching network of glands]
- med = tubulovillous [ combo]
- high = villous [ fingerlike glands projecting straight down to the center of the polyp] - Dysplasia
Mild -> intermediate-> high degree of dysplasia
What symptoms are usually associated with adenomotous polyps?
What are rare exceptions?
How are adenomas usually discovered?
Usually, they have no symptoms.
Bleeding is VERY rare (esp. with small polyps) so iron deficient anemias and GI bleeds should NOT be caused by adenomatous polyps.
Rarely, large polyps may cause obstruction or intussusception.
They are discovered incidentally in sigmoidoscopic, colonoscopic or barium enemas for cancer screening.
How do symptoms of colon cancer change depending on which part of the colon is involved?
Although uncommon, what can happen in any part of the colon?
Right colon is larger diameter and the stool is still majority liquid so tumors can grow longer w/o causing obstruction. The most common manifestation in the cecum and ascending colon is slow bleeds and iron deficient anemia.
Left colon is more narrow and has more solid stool. Tumors that grow circumferentially interfere with the movement of bowel causing:
- cramping
- alternating diarrhea and constipation
- bowel obstruction
- bleeding (hematochezia)
Uncommonly perforation and peritonitis can occur in both the ascending AND descending colon?
What are the 3 diagnostic tests used for colonic polyps and CRC?
- barium enema
- sigmoidoscopy
- colonoscopy
What are the pros and cons of barium enemas for identifying polyps?
Pros:
- inexpensive
- good sensitivity (60-80%)
- no sedation
- widely available
Cons:
- if you find a polyp, you need to do a colonoscopy anyway to biopsy/remove
- false + due to retained stool in the bowel
What are the pros and cons of sigmoidoscopy for identifying colon polyps?
Pros:
- highly sensitive (90%)
- can biopsy/remove polyps if they’re found
Con:
1.Only does the distal colon/rectum and polyps are usually evenly spread out throughout the colon
What are the pros and cons of colonoscopy for identifying colon polyps/CRC?
Pros:
- highly sensitive (90%)
- can biopsy/remove polyps
Cons:
- expensive
- require sedation and extensive bowel prep (time consuming)
What is treatment for hyperplastic polyps? Why?
They are removed by colonoscopy because they cannot be differentiated grossly from adenomatous (neoplastic) polyps.
After you do histology exam on the polyp, you see that it is a benign lesion and the person is not required to be entered into regular surveillance program for detecting neoplasm
What is treatment for adenomatous polyps?
Remove them at colonoscopy.
Diminutive polyps (less than 5mm) rarely harbor malignancy, however, until techniques are developed to predict biological behavior of adenomas, remove ALL polyps.
What is considered to be “carcinoma in situ”?
What is intramucosal carcinoma?
How are they treated?
Carcinoma in situ = highly dysplastic/malignant appearing epithelial cells that do not extend below the basement membrane of their glands.
Intramucosal carcinoma = malignant looking cells penetrate the BM and extend into the lamina propria but do not go past the muscularis mucosa.
Both are considered non-invasive because lymphatics are not in the mucosa (therefore there is essentially no metastatic potential). Removal of these lesions is CURATIVE.
What is treatment for malignant polyps? What features have been identified that can estimate the risk of leaving residual tumor?
Malignant tumors extend below the muscularis mucosa and therefore have access to lymphatics (metastatic potential)
Treatment:
colonoscopic polypectomy is curative for MOST however there is potential for residual cancer in the bowel wall and regional lymphatics.
The chance of residual is increased with:
- degree of differentiation
- invasion of veins/ lymphatics
- involvement of polypectomy margin
- invasion of the subucosa in the bowel wall
Are pedunculated or sessile malignant polyps more likely to have an adverse outcome?
Sessile because they lack a stalk and therefore is higher chance of submucosal involvement
Pedunculated have a stalk and the risk for adverse outcome is low if the carcinoma is confined to the submucosa of the stalk and does not reach the submucosa of the bowel wall
What are the 4 indications for surgical resection in patients with endoscopically-removed malignant polyps?
- poorly differentiated
- cancerous cells within 2mm of polypectomy margin
- invades lymphatics or veins
- invades submucosa of the bowel wall
A patient is found to have colorectal cancer. What should you do before initiating definitive therapy?
A complete colonoscopy to look for:
- synchronous masses
- adenomatous polyps
What is the treatment for colorectal cancers?
What adjuvant can be given for higher stage tumors? (that have regional/distal mets)?
Surgical removal of:
1. the involved bowel (with 5cm of uninvolved bowel on each side)
[if doing sphincter-sparing, need 2cm blow tumor]
- lymphatics associated with that region of bowel
For stage C (III)- patients get 5-FU and levamisole
For B and C - patients get chemo and radiation
