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what are possible ddx for 65yoM w/6mo h/o progressively worsening fatigue, abd welling, dull RLQ ache. 40packyr h/o smoking. Large polyps & fam h/x of GI cancer. Occult blood, Hb 11/ Hct 33/ MCV 73.
- Colorectal Carcinoma
- IBD w/ rt sided abscess
- Ischemic colitis
- diverticular abscess
describe the pathogenesis of colon carcinoma.
- loss of 1nL copy APC occurs early (either born with it, or later in life) : "first hit"
- random loss of 2nd (last) good copy: "2nd hit"
- --> mucosa at risk!
- now, pair above with:
- K-RAS protooncogene mutation
- Homozygous loss of p53, SMAD2/4, & overexpression of COX-2
- +telomerase & other mutations
describe the microsatellite instability pathway in reference to colon cancer.
- starts as germline or somatic mutations of mismatch repair genes
- alteration of 2nd allele
- --> microsatellite instability --> Sessile serrated adenoma
- accumulated mutations in genes for cell survival & proliferation
what are the risk factors for colon cancer?
- diet high in animal fat
- genetics: polyposis coli, nonpolyposis syndrome
- step bovis bacteremia
- ??tobacco use
what kind of polyps are the most common and clinically important polyps that are precursos to majority of colorectal adenocarcinomas?
describe the types of colon polyps and how to differentiate them.
- Hyperplastic Polyps:
- -usually left, small
- -looks like serrated but ONLY on top (doesNOT extend to the bottom)
- all --> cancer
- --villous: finger-like/pedunculated; hyperplastic cells look red compared to nL (white, clear goblet cells)
- --Sesile serrated (see image)
describe these images:
- adenomatous polyps
- hyperplastic cells = red
what are dark-freckle-like spots on lip mucosa? what might it indicate? What are the clinical manifestations & pathophys?
- shows characteristic mucocutaneous hyperpigmentation in a pt w/Peutz-Jeghers Syndrome.
- clinical manifestations
- "freckles" & hemartomatous polyps in small intestine
- +famHx = key to dx
what is Gardner's syndrome?
- inherited colonic adenomatosis with extracolonic
- growths, including osteomas, epidermal cysts and fibromas . Dental abnormalities, desmoid tumors and other lesions were later recognized as additional manifestations of the underlying genetic defect
what are the clinical features of colonic carcinoma?
features can be divided by "sidedness":
- b/c stool is almost liquid in the ileacecal area, cancers in cecum & ascending colon may become LARGE before any obstructive Sx's are noticed
- lesions commonly ulcerate --> chronic insidious blood loss w/o change in the appearance in stool
- --> presenting Sx's may be fatigue, palpatations, maybe angina pectoris WITH hypochromic, microcytic anemia (hemoglobin hematocrit <12-13 (M-F) g/dL, MCV <80, MCHC <30)
- abd cramping, occasional obstruction, possible perforation
- radiographs --> "apple-core" or "napkin-ring"
where does CRC metastasize most commonly?
- 20% have distant metastasis @ time of presentation
- spread via lyph, blood, & continuous/transperitoneal routes
- most common: liver, lungs, bone...*tumors in distal rectum may seed to lungs 1st b/c inferior rectal v drains to IVC rather than portal venous system
- *signs of RUQ pain, abd distention, early satiety, supraclavicular adenopathy or periumbilical nodules may indicate advanced dz
what are some tests for adenomatous polyps and cancer? tests that are specific for testing cancer?
flexible sigmoidoscopy, colonoscopy, double-contrast barium enema, or CT colonography
- specific for cancer:
- guaiac-based fecal occult blood test
- fecal immunochemical test
- stool DNA test
describe tx/management steps for CRC.
what surgical measures are taken in CRC?
surgery will include 2cm on each side of tumor to include the lymphnodes.
what are predictors of poor outcome following total surgical resection of CRC?
- Tumor spread to regional lymph nodes
- # of regional nodes invovled
- tumor penetration through bowel wall
- preoperative elevation of CEA titer (>5.0ng/mL)
when is CTX (chemotherapy) indicated in CRC? what specific drugs may be used for specific stages?
- IIA&B consider role of CTX
- IIIA/B Sx + CTX (5-FU + leucovorin + Oxaliplatin (FOLFOX)
- IV 1st line = FOLFOX or Irinotecan + bevacizumab; 2nd line = Irinotecan + Cetuximab +/- Palliative Sx
for someone w/o sx's of CRC but a personal hx (may also have IBD), what is the next step in management?
for someone w/o sx's of CRC but a family hx, what is the next step in management?
- genetic syndromes: early intense screening, genetic counseling/testing
- CRC or adenoma in 1 FRD <60 or CRC or adenoma in 2 or more FDR: colonoscopy starting 40yo or 10yr earlier than the youngest age of dxed relative
- CRC or adenoma in FDR >/=60 or CRC in 2 or more SDR: ave risk, start screening at 50yo
for someone w/o sx's of CRC but >50yo, what is the next step in management? what if some of these tests are positive?
- prevention & early detection: colonoscopy/10yr, and CTC, flexible sigmoidoscopy, & DCBE every 5yrs
- Alternative (early detection only): gFOBI, FIT, sDNA
- if positive: colonoscopy
what screening test(s) have the highest sensitivity, specificity for CRC?
- colonoscopy = highest
- CT colonography = high, similar to colonoscopy
- Flexible sigmoidoscopy + FOBT = high for up to 1/2 of colon
- intermediate = doulbe contrast barium enema, stoolDNA, fecal immunochem, fecal occult blood (lowest effectiveness).
what is the ddx for a 20yoM w/3mo hx of increasingly frequent bloody diarrhea (6-10x/d), fever, no palpable masses, but frank blood w/ hct 30%?
- 1.Ulcerative Colitis
- 2.Crohns Disease
- 3.Bacterial enteritis
- 4.C Difficile colitis
- 5.Ischemic colitis
- 6.Diverticular bleed
what steps need to be taken in a person with frank rectal bleeding?
- good Hx
- 2 large bore IV lines
- type & cross match blood
- contact GI
- consider NG lavage
what are the differentiating features b/w UC and Crohn's Dz?
- continuous colonic involvement start from rectum
- surface involvement, pseudopolyp/ulcers
- usually gross blood in stool w/mucus
- often ANCA-positive
- skip lesions
- transmural inflammation, ulcerations, fissures
- occasional blood in stool w/mucus
- osten systemic Sx & pain
- often have SI & colonic obstructions
- often ASCA-Positive
- will see "cobblestoning" w/rectal sparing
what are the risk factors for IBD (specifically, compare UC with Crohn's).
- age onset: 15-20, 60-80
- ethnicity: jewish>non-jew caucasion>AfAm >hisp>Asian
- smoking may prevent!!
- apendectomy is protective
- not inherited
- smoking may cause dz!
- may be inherited
describe the pathogenesis of IBD? compare UC and Chrohn's.
- the 2 dz's result from a combo of defects in host interactions w/intestinal microbes, intestinal epithelial dysfn, & aaberrant mucosal immune responses.
- Chrohn's: polarization of helper Tcells TH1 and TH17 contribute to disease pathogenesis
- UC: data suggests TH2 plays a role...but may be roles in TH1 & 17 as well as IL-10gene polymorphisms
what are the pathologic findings of UC?
- erythema & ulceration
- cryp abscesse (center, dark center)
name & describe extraintestinal manifestations of UC.
- erythema nodosum: symmetric painful nodules on legs, can be pigmented
- pyoderma gangrenosum: early & late
- anterior uveitis: opacity of anterior chamber
- thromboembolic d/o's
- endocarditis, myocarditis, pleuropericarditis
describe treatment options of UC.
- starting with first-line:
- 5-ASA PR or PO > rectal GCCs > oral GCCs > IV GCCs > 5-mercaptopurine or axathioprine > IV cyclosporine or infliximab
- tx's are for distal and extensive
what are the indications for surgery in UC?
- intractable dz
- fulminant dz
- toxic megacolon
- massive colonic hemorrhage
- extracolonic dz
- colonic obstruction
- as prophylaxis for CRC
- if have colon dysplasia or cancer
what are indications for surgery in Crohn's dz?
- in SI:
- stricture & obstruction unresponsive
- massive hemorrhage
- refractory fistula
- in Colon & rectum:
- intractable dz
- fulminant dz
- perianal dz unresponsive
- refractory fistula
- colonic obstruction
- cancer prophylaxis
- colon dysplasia or cancer
a 67-year-old female with a history of T2DM, Hypertension, and End Stage Renal Disease secondary to ADPKD. She chronically takes glipizide, aspirin, and metoprolol for her chronic conditions. The patient presents to the ED complaining of blood in her stool. Yesterday she had an episode of ”red bloody stool”, and states that the blood filled the bowl. Overnight, she has had "diarrhea" reporting a stool every 2 hours, all of them have been red and "bloody". Within the last 4 hours she has began to experience lightheadedness, dizziness, and increasing fatigue...What other questions should you ask?
- 1.Are you taking blood thinners or NSAIDs (ibuprofen, naproxen, aspirin)
- 2.Have you had any trauma to the abdomen or rectum, or have you swallowed a foreign object accidentally?
- 3.Have you eaten black licorice, lead, Pepto-Bismol, or blueberries?
- 4.Have you had more than one episode of blood in your stool? Is every stool this way?
- 5.Have you lost any weight recently?
- 6.Is there blood on the toilet paper only?
- 7.What color is the stool?
- 8.When did it develop?
- 9.What other symptoms are present -- abdominal
- pain, vomiting blood, bloating, excessive gas, diarrhea, or fever?
what should be done during PE of a pt w/GI bleeding?
- digital rectal exam
- anoscopy should be considered to evaluate for internal hemorroids or fissures.
in a pt. with rectal bleeding and a hx or heart &/or kidney dz what are some concerning Sx's?
- Symptomsof Volume depletion (Murmur??)
- Blood on Rectal Examination
- SevereSymptoms to look out for:
- 1.Chest pain
for the following case, what are the next steps in management?
a 67-year-old female with a history of T2DM, Hypertension, and End Stage Renal Disease secondary to ADPKD. She chronically takes glipizide, aspirin, and metoprolol for her chronic conditions. The patient presents to the ED complaining of blood in her stool. Yesterday she had an episode of ”red bloody stool”, and states that theblood filled the bowl. Overnight, she has had "diarrhea" reporting a stool every 2 hours, all of them have been red and "bloody". Within the last 4 hours she has began to experience lightheadedness, dizziness, and increasing fatigue...
- 2 large bore IVs, stabalize hemodynamics
- resus w/ crystalloid
- labs: CBC, blood type & cross-match, INR, PT, PTT; BUN/Cr, FOBT?
- PRBCs for pt's w/Sx's or based on Hgb/Hct & comorbidities
- EKG for pt >50, CP, SOB, or Hx of ASCAD
- NGT & NG lavage w/LGIB b/c concerned for UGI
for the following case, what are the DDx's?a 67-year-old female with a history of T2DM, Hypertension, and End Stage Renal Disease secondary to ADPKD. She chronically takes glipizide, aspirin, and metoprolol for her chronic conditions. The patient presents to the ED complaining of blood in her stool. Yesterday she had an episode of ”red bloody stool”, and states that theblood filled the bowl. Overnight, she has had "diarrhea" reporting a stool every 2 hours, all of them have been red and "bloody". Within the last 4 hours she has began to experience lightheadedness, dizziness, and increasing fatigue...
- Ischemic colitis
- Anal Fissures
- Colon Cancer/ Polyps
- Colitis( ulcerative, radiation, infectious)
explain the pathophys of diverticulosis
- diet: low fiber
- myo-electrical activity: loss of muscular support
- Law of Laplace: T = (P*R)/M
- T=tension; p=transmural pressure; r=radius; m=wall thickness
- increased wall tension increases transmural pressure gradient
- decreased radius (wall thinning) increases transmural presure gradent **sigmoid colon has smallest luminal radius of the colon
why do pt's w/diverticulosis bleed?
- diverticula are only a source of bleeding in 3-5% of pt's w/diverticulosis
- HOWEVER, it is the most common cause of LGIBleeding in the elderly
- *the bleeding is typically painless
what is the management of bleeding diverticula?
- ~80% of LGI stop bleeding spontaneously
- endoscopic epi, clips, or cautery
- angiographic selective intra-arterial embolization
- for persistant/recurrent LGIB: surgery
what other d/o's is angiodysplasia associated with?
- Von Willebrands Dz
- Aortic Stenosis
describe the pathophys of angiodysplasia.
- mucosal & submucosal venous drainage is intermittently obstructed by muscular contraction or increased intraluminal pressure and increased wall tension
- *cecum has the largest luminal radius in the colon
- after years of intermittent obstruction, submucosal vv may become dilated & tortuous & involve more vv and venules
- eventually, capillary ring dilates & the precapillary sphincter becomes incompetent resulting in a small arteriovenous communication lesion
what types of GI bleeds can be managed as OUTpt?
- NO active bleed
- (-)NG lavage
- Hct >30%
- etiology is anal fissures or mild hemorrhoidal bleed
describe the presenting characteristics of angiodysplasia.
- painless bleeding from melena or hematochezia to occult blood
- most often in cecum & ascending colon
- flat, red lesions, preipheral vessels radiating from central red spot
- most common >60-70yo & h/o chronic renal failure
pt. presents with: episodes of bloody diarrhea interspersed w/periods of healing and abd pain, is older w/significant cardiac & peripheral vascular dz.
think Ischemic colitis
what dxic tests may be necessary in the evaluation of angiodysplasia when source of the bleed can't be localized by endoscopy or colonoscopy?
- radio Tc99-RBC imaging*for ongoing bleeding w/o identifiable source after upper endoscopy and colonoscopy; can detect bleeds of 0.1-0.5mL/min
- angiography: requires 1mL/min for adequate visualization
- CT angiography