162b/163b/164b/165b - Colon Stuff (Path, Clin features, IBD, Colon cancer) Flashcards
What imaging method is preferred to evaluate colorectal cancer?
Colonoscopy
- Allows for localization, biopsy, and removal of polyps
- Diagnostic of colon cancer
- Other modalities prompt need for colonoscopy if findings are suspicious
Which genetic mutation is asociated with flat or depressed adenomas?
What is the treatment?
Lynch syndrome (HNPCC)
Mutation in one of the mismatch repair genes
- Prophylactec sub-total colectomy
(can leave the rectum in place) - Screening for other cancers (esp endometrial, ovarian)
Which of the following is true?
- The incidence of colorectal cancer is generally lower in more developed countries
- In the US, colorectal cancer is the most common gastrointestinal cancer
- A diet high in fiber has been associated with a higher risk of colorectal cancer
- Obesity has been associated with a lower risk of colorectal cancer
b.
In the US, colorectal cancer is the most common gastrointestinal cancer
Which of the following is true regarding microscopic colitis?
- It is predominantly seen in young, male patients
- Abdominal pain is a common symptom
- Ranitidine has been implicated as a possible trigger
- Presence of > than 10 intraepithelial lymphocytes per high power field is diagnostic of lymphocytic colitis
c. Ranitidine has been implicated as a possible trigger
* PPIs, H2 blockers, and NSAIDs are implicated as triggers
Which two syndromes have multiple harmatomatous polyps?
How can you differentiate between them on presentation?
-
Peutz-Jeghers (STK11 mutation, autosomal dominant)
- Mucocutaneous hyperpigmentation
- May present with intussusception
- More “arborization” on histology due to smooth muscle predominance
-
Juvenile polyposis (SMAD4 mutation, autosomal dominant)
- Rectal bleeding + digital clubbing
What is the dignostic test of choice for diverticulitis?
What findings would confirm the diagnosis?
CT scan
- Presence of diverticula
- Thickened colonic wall >4mm
- Inflammation within pericolic fat +/- fluid collection
**Barium enema and colonoscopy are contraindicated if diverticulitis is suspected; risk of perforation**
Crohn’s or Ulcerative Colitis?
More likely to have anal lesons
Crohn’s
Crohn’s or Ulcerative Colitis?
Skip lesions
Crohn’s
What is the treatment of choice for colorectal cancer?
Surgery
- Completely remove lesion w/clear margin + vessels and nodes
- Even if surgery is not curative, operate to treat obstruction and bleeding
- In some patients, resect mets to liver and/or lung
Chemotherapy and radiation are usually adjuvants or for palliation
What are crypts supposed to look like?
“Tubes in a rack”
If they look like anything else, something is wrong
Crohn’s or Ulcerative Colitis?
Crypt abscesses filled with neutrophils
Ulcerative Colitis
Why are diverticula most prevalent in the sigmoid colon?
Smallest diameter = highest pressure during segmentation
Is a colonoscopy indicated after the first episode of diverticulitis?
Yes
But not immediately! Wait for episode to subside, then colonoscopy later to figure out what’s going on
What histologic findings are diagnostic of microscopic colitis?
- Lymphocytic colitis:
- Collagenous colitis:
- Lymphocytic colitis: >20 lymphocytes/hpf
- Collagenous colitis: collagen band >10 micrometers
Crohn’s or Ulcerative Colitis?
Inflammation limited to the mucosa
Ulcerative Colitis
What gene is associated with Crohn’s disease?
What does the gene do?
NOD2 (aka CARD 15) on Chromosome 16
- Encodes for a protein that binds bacterial peptidoglycan
- -> Activation of NFK-b
- -> Transcription of proinflammatory and protective molecules
- When this is disrupted -> Crohn’s
- Implicated in 20% of Crohn’s in Caucasian and Jewish populations
Diverticular bleeding is most likely coming from a diverticulum in which location?
Right colon (usually divirticula here are wider-mouthed?)
(Even though the most common location for diverticula formation is the sigmoid colon)
What diagnostic tests are useful in diagnosing ishcemic colitis?
- Imaging
- Look for thumb-printing (edema) and pneumomatosis
- Colonoscopy is diagnostic
- And helpful in determining whether parts need to be removed
- Single stripe sign is diagnostic
Describe the signs and symptoms of colon cancer (6)
How does presentation differe in right-side vs. left side?
- Abdominal or rectal pain
- Change in bowel movement pattern
- Hematochezia
- Anemia
- Weight loss/fatigue
- Obstruction
- Right
- More blood loss, fatigue, anemia
- Left
- Obstruction more likely
- More hematochezia
Crohn’s or Ulcerative Colitis?
Must involve the rectum
Ulcerative Colitis
(UC involves the rectum by definition; Crohn’s can affect any part of the GI tract, including the rectum)
Crohn’s or Ulcerative Colitis?
More likely to cause perforation, fistula, or stricture
Crohn’s
(inflammation is transmural, vs UC is limited to the mucosa)
If a patient with a family history of colon cancer diagnosed before age 50 has congenital hypertrophy of retinal pigment epithelium, what should you do?
What genetic mutation do they likely have?
Early screening for colon cancer!!
They likely have FAP (mutation in APC gene)
-> basically 100% lifetime risk of colon cancer
List 4 neoplastic polyps
Are they precursors to colon cancer?
- Tubular adenoma
- Villous adenoma
- Tubulovillous adenoma
- Sessile serrated adenoma
These ARE precursors to colon cancer
Crohn’s or Ulcerative Colitis?
Non-caseating granulomas
Crohn’s
List the extra-intestinal manifestations of IBD (both Crohn’s and UC)
(4 organ systems)
- Spondyloarthropathy
- Metabolic bone disease
- Skin
- Pyoderma gangrenosum
- Erythyma nodosum
- Eyes
- Episcleritis
- Uveitis
A 65-year-old male with history of coronary artery disease presents with sudden onset abdominal pain, urgency and diarrhea following a syncopal episode at home. He subsequently develops bloody diarrhea and is admitted to the hospital. He has never had a colonoscopy.
Which of the following is the most likely cause of his bleeding?
- Diverticular bleeding
- Microscopic colitis
- Ischemic colitis
- Colon cancer
- Hemorrhoids
c. Ischemic colitis
What are the two types of microscopic colitis?
What will they look like?
- Lymphocytic colitis
- More lymphocytes (purple cells) between epithelial cells
- Expanded lamina propria
- Collagenous colitis
- Sub-epithelial collagen deposition (pink stuff)
What are the 2 most important prognostic factors in colorectal cancer?
Depth of penetration (stage)
Lymph node metastasis
Why is rectal cancer more likely to spread outide of the GI tract?
The rectum has no serosa
A 49-year old man is at his primary care doctor’s office for an annual visit, with no other complaints except fatigue, which he attributes to a busy work schedule. His exam is normal except for pale skin and conjunctivae. Blood work reveals a new moderate microcytic anemia, with iron indices consistent with iron deficiency. He has no family history of colorectal cancer or polyps. What would you suggest next?
- Iron supplementation and recheck hemoglobin and iron studies in 3 months
- Reduce work hours, get more rest, and when he turns 50 should have colorectal cancer screening
- Referral to gastroenterologist for evaluation, including colonoscopy
- Emergent admission to the hospital for blood transfusion
c.
Referral to gastroenterologist for evaluation, including colonoscopy
- New anemia in a man or post-menopausal woman is never normal!
Which gene is mutated in familial adenomatous polyposis?
What is the prognosis?
APC gene (chromosome 5)
- This is the “first hit” in the adenoma -> carcinoma sequence
- Loss of heterozygosity (2nd hit) -> many adeonomas
- Basially 100% chance of colorectal adenocarcinoma
- Treatment is prophylactic cholectomy
Crohn’s or Ulcerative Colitis?
Starts in the rectum
Ulcerative Colitis
Describe the adenoma-carcinoma sequence
- First hit = loss of a tumor suppressor gene allele
- Usually APC on chromosome 5 (85%) or MMR inactivation (15%)
- May be inherited (FAP or HNPCC) or acquired
- Second hit = loss of heterozygosity
- Loss of the normal APC allele
- -> Adenoma formation
-
Malignant transformation due to additional mutations
- Commonly KRAS or p53
- -> Adenocarcinoma
- More mutations
- Progression and growth
Why do diverticula develop in the colon vs. other areas of the GI tract?
Which are of the colon has the highest risk?
There are points of weakness in the colon due to:
- Vasa recta penetrating the inner (circular) muscularis propria
- The outer (longitudinal) muscularis propria is not continuous; forms 3 bands of muscle
- No circumferential support
Specifially, most common in the sigmoid colon bc it has the smallest diameter -> highest pressure during abnormal segmental contraction
CRC screening guidelines for people with family hx of CRC
For anyone with fhx of CRC or advanced adenoma in a) a first-degree relative <60 y/o or b) in 2 first degree relatives, any age
- Begin colonoscopies at age 40 or 10 years younger than youngest affected relative
- Repeat every 5 years
For anyone with fhx of CRC or advanced adenoma in a first degree relative >60 y/o
- Any tier 1 test starting at age 40
- Repeat at same interval as average age
When should colonoscopy screening be discontinued?
- Patients >75 y/o with aprior negative screening
- Patients >85 y/o even if no prior negative screening
A 55-year old man had a screening colonoscopy, revealing 3 adenomatous polyps which were completely removed. With respect to the pathogenesis, familial risk, and need for future follow up, which is the most appropriate recommendation:
- No further evaluation required in the future, since the polyps were all removed
- This patient’s 2 brothers, ages 51 and 53, are not at increased risk and do not need to be screened for colorectal cancer.
- He should have genetic testing performed now, as most colorectal polyps are found in individuals with genetic syndromes
- He should undergo surveillance colonoscopy at the interval recommended by his physician
d
He should undergo surveillance colonoscopy at the interval recommended by his physician
Which medications increase risk of microscopic colitis? (4)
- NSAIDs
- PPIs
- Ranitidine
- Sertraline
Crohn’s or Ulcerative Colitis?
Associated with calcium oxalate kidney stones
Crohn’s
Which of the following should be recommended to a patient after their first episode of diverticulitis?
- Avoidance of nuts and seeds
- Surgery to prevent recurrence
- Colonoscopy in 2-4 weeks
- CT scan in 4 weeks to ensure resolution of inflammation
- High fiber diet
e. High fiber diet
List 4 environmental risk factors for colon cancer
- Smoking
- Dietary factors (high fat, low fiber)
- IBD
- High alcohol consumption
Which gene is mutated in Hereditary Nonpolyposis Colorectal Cancer (aka Lynch Syndrome)?
What is the prognosis/
Mutation in a mismatch repair gene; may be:
- MLH1
- MSH2
- MSH6
- PMS2
Increased risk of cancery at many different sites
Increased risk of cancer in the right colon that develops from a sessile serrated adenoma
Crohn’s or Ulcerative Colitis?
Positive family history is more common
Crohn’s
What is the most important prognostic factor for malignant potential of an adenoma?
Size
Larger adenomas = more potential for malignant transformation
Which genetic mutation is asociated with 100’s-1000’s of polyps carpeting the colon?
What is the treatment?
APC mutation on chromosome 15
Resulting in Familial adenomatous polyposis (FAP)
Prophylacted subtotal or total colectomy - also check the small bowel for polyps/adenomas!
A 51-year old woman presents to her primary care physician for her annual visit. She feels well and has no family history of colorectal cancer. She wants to know if she is at risk for colorectal cancer and what she can do to prevent it or reduce her risk of dying of this disease. What would be the appropriate recommendation?
- Since she has no family history of colorectal cancer her risk is very low, so she should not worry about it.
- She should consider screening for colorectal cancer now, since she is over 50 and has no family history
- She should consider genetic testing; if negative, she’s not at risk for colorectal cancer.
- She does not have to worry about it, since colon cancer is much less common in women.
b. She should consider screening for colorectal cancer now, since she is over 50 and has no family history
Crohn’s or Ulcerative Colitis?
Transmural inflammation
Crohn’s
CRC screening guidelines for average risk individuals:
Begin at age 45 for African Americans, age 50 for all other races
- Tier 1 (one of the following?)
- Colonoscopy every 10 years
- Annual FIT
- Tier 2 (one of the following?)
- CT colonogroaphy every 5 years
- FIT-fecal DNA every 3 years
- Flexible sigmoidoscopy every 5-10 years
- Tier 3
- Capsule colonoscopy every 5 years
Which precancerous polyp is associated wtih Lynch syndrome?
Sessile serrated adenoma in the right colon
How is microscopic colitis managed?
Goal = symptomatic improvement
Give antidiarrheal
- No risk of colon cancer or IBD
- No need to monitor or do f/u colonoscopy
- Histologic remission not necessary
List 3 non-neoplastic colon polyps
Are they precursors for colon cancer?
- Hyperplastic
- Inflammatory
- Harmatomatous*
Not precursors to colon cancer
However, multiple harmatomatous polyps =
Peutz-Jeghers (risk of malignancy in many organs)
OR
Juvenile polyposis (risk malignant transformation)
Crohn’s or Ulcerative Colitis?
More strongly associated with risk of colorectal cancer
Ulcerative colitis
- Especially if longstanding
- Especially w/right-sided involvement
What is the earliest event in the adenoma-carcinoma sequence?
Usually a mutaiton ot the APC gene on chromosome 5
Hereditary mutation = Familial adenomatous polyposis (FAP)
What are the two most common forms of familial colon cancer?
- Familial adenomatous polyposis (FAP)
- APC mutation
- Heretitary non-polyposis colorectal cancer (HNPCC)
- Mismatch repair mutation
What is the treatment for diverticulitis?
How does it differ between uncomplicated and complicated cases?
- Uncomplicated
- Bowel rest + supportive care
- Complicated
- Bowel rest + hospitalization
- IV antibiotics +/- abscess drainage +/- surgery
Key: you don’t need to give abx for uncomplicated diverticulitis
Which part of the colon has paneth cells?
Rigth colon
If they are anywhere else, it’s metaplasia
What kind of polyps?
Hyperplastic polyps
Which two locations in the colon are most susceptible to ischemic colitis?
- Splenic flexure (aka left colic flexure, aka Griffith’s point)
- Rectosigmoid junction (aks Sudeck’s point)
