causative agent (pathogen), modifying factors (env, genetic - predisposed) - lumenal factors
When does surgery for rectal cancer fail?
usuall local reccurrance or distant metastases
confined space - hard to get good margins
classic features of crohn's disease
diarrhea with nocturnal stools
can have a palpable mass on exam
children may present with failure to thrive, failure to develop secondary sex characteristics, growth retardation
MLH1 and MSH2
There are other mutations that occur, MLH1 and MSH2 lead to microsatellite instability. Those are also associated with cancer, but slightly different than the adenoma pathway.
Side effects of steroids in IBD
greatest predictor of infection!
lots of side effects
need slow taper (2-3 months)
must have exit strategy
What kind of T cell response is Chrons?
phases of IBD treatment
reduce need for surgery and reduce risk of cancer development
CRC screening if family history of colon cancer?
40 years of age or 10 years before index case
also if family history of large or high grade adenoma
even polyp w high grade adenoma!
Location of CD lesions
any part of the GI tract
rectum in 10%
insidious onset (belly pain, anemia)
histo of IBD
inflammatory cells in lamina propria
plasma cells near crypt base
Physical Exam signs for IBD?
perineum/rectal (skin tags, abcesses, fistula)
apthi in mouth (common in CD
•Skin-tag – Has a shiny surface with a waxy appearance at the anus [middle]
•Skin tags are a very common feature
•Can also see a fistula [left]
•Opening right here
•If you were to probe it, you would track it back into the colon
•This is nice clean, not bad looking one
•It can be really mean and angry looking
•Sometimes if you push it, it can express either purulent material because they can get an abscess, or stool will leak out of these areas
•Can imagine what this does for patient’s QoL
How does CRC present?
Abdominal pain (partial obstruction, peritoneal involvement)
change in bowel habits (especially in distal colon, stool is really thin This is seen more often in cancers of the distal colon because on the right side of the colon (proximal colon) it still has to be liquid. so even if you have a blockage, don’t really feel it because its liquid so it still goes by the obstruction. But if there is a lesion that is blocking in the distal colon, you see more bowel changes because its solid forming there)
hematochezia (ulcerate and bleed easily)
CRC screening if no risk factors?
50 years of age (45 for african americans?)
low anterior resection
Surgeries in the rectum are often dictated by how low the cancer is. If there is enough room from the cancer to the anal verge, they can reconnect the colon, which is called a low anterior resection
symptosm seen more in UC than CD?
rectal bleeding (hematochezia)
humanized ab vs VEGF - best data for metastatic disease
delays wound healing
Fecal occult blood test
put stool on a card, put droppers on it and see if it turns blue – just tells you if there is a bleed in the GI tract, not necessarily colon cancer.
when to use immunomodulators?
in mild-moderate crohn's and moderate UC
take 12 wks to take effect
side effects = infection, hepatitis, pancreatitis, bone marrow suppression
cyclosporine - when to use?
severe, steroid refractory UC
in IV formed then tansitioned to oral to induce remission
NOT for maintence
majority of patients require colectomy
side effects: hypertension, renal failure, seizures, infection
changed gut epithelial imparment effecting tight junctions
antigens come through - present - cascade
mostly in lamina propria
increased permeability and antigen uptake
you have to prep yourself. Then they inject barium through the rectum which coats the colon. Look for things called apple core lesions.
CRC chemo mainstay
5-fluorouracil is backbone of treatment
post surgical adjuvant therapy:
When you look at the data, the adjuvant therapy has the most benefit with patients with Stage III disease.
Stage 3 – beyond the colon (into the nodes) but don’t have distant metastasis.
not sure if it's worth it at lower stages
CRC repeat intervals for various tests
fecal occult blood
colo - 10 years
flex sigmoidoscopy - 5 years
barium enema - 5 years
fecal occult blood - every year
repeat in shorter intervals if fine things! every 3 years if one or more adenomatous polyp >1 cm, 3 or more of any size
Mot common locations fo crohns?
right colon and distal ileum!
•The most common area of involvement is going to be the small bowel, the distal/terminal ileum, and the right colon
•So ileocolonic disease is the most common areas here
•About 35% patients have distal ileum disease and 35% of patients have right colonic disease
•20% of patients will just have colonic disease
•That being said, almost all patients who have CD do not have the rectum involved
•Rectal sparing is a big important feature of CD
•Only 10% of patients will have inflammation in the rectum
•This can help you tease out UC and CD
Again, not everybody reads the book
abdominal perineal resection.
some colon cancers are very distal and extend right to the anal verge, so don’t have enough room to stitch the colon together, so have to have a colostomy bag forever. This is an abdominal perineal resection. Resect the entire distal rectum and perineum.
CD on colonoscopy
first line for inducing and maintaining remission in UC, no evidence to support use in Crohn's but can be used for mild disease - •If patients have disease in their small bowel or the peri-anal area, this medication will not work
reduce inflammation in the local environment
best when oral and topical - •5-ASA pills are given, but patients who have UC have disease in their distal bowel, in the rectum, and tend to do best either when you give them a suppository and a pill, or an enema and a pill
side effects: headache, nausea, rash, hypersensitivity
Staging of CRC
Think of stage 1,2,3, and 4.
Stage 0 hasn’t invaded. mucosa only
Stage 1, invaded into the muscularis
Stage 2 has invaded through the muscularis, propria, or through the colon itself but doesn’t have anything in the nodes.
Stage 3 – once you have nodes
Stage 4 – Metastasis.
Gold standard fo diagnosing CRC?
Colonoscopy or flexible sigmoidoscopy
Colonoscopy vs flexible sigmoidoscopy?
Endoscopy is the gold standard.
Colonoscopy or flexible sigmoidoscopy. Colonoscopy is done with a longer tube, but it’s the same instrument. Flexible sigmoidoscopy – only see about half of your colon.
top down therapy
(if high risk for complications)
Risk factors for CRC
age (rare before 40)
hereditary syndromes (i.e. FAP, Lynch)
Diabetes, alchol, S bovis
ileal pouch anal anastomosis
most common surgery for UC patients (30%)
refractory disease, dysplasia, hemorrhage
ileum pulled into pelvis and anastamose
•They can get what is called a J-pouch
•The ileum is pulled down into the perineum, and they get a reservoir
•They can get a normal bowel movement out of the anus
•This can work for many patients, but many patients will get inflammation in their pouch
•They can develop Crohn’s in their pouch after removing what was thought to be UC previously
•End ileostomy is absolutely curative
•A pouch can work for people, but there are consequences
appendectomy and IBD
•History of an appendectomy, primarily in a young male for the true indication of appendicitis
Uncertain for CD
•May actually have protective effects in the development of UC
symptoms seen more in CD than UC?
weight loss fatigue
UC on colonoscopy
pseudopolyps = surviving mucosa
loss of haustra
Progression of crohn's disease
2. stenosis - from scarring and fibrosis! obstruction and narrowing
3. fistula - develop to relieve pressure in scarred areas - to adjacent organs or skin, inflammed, tunnel to skin
can have all sep
•The inflammatory portion is just where you see transmural inflammation of the bowel wall (Image B)
•Stenosis is when you basically can describe as a scar in your intestines (Image A)
•It becomes fibrostenotic
•There is no medication you can give a fibrostenotic scar
•If it is causing symptoms, it has to come out surgically
•There is nothing you can do to reverse it
•It is unclear if you catch it in the inflammatory phase whether you can avoid this scar formation
•In theory yes, but we do not know
•Patients can present with what seems like a stenotic area, they come in obstructed
•You think that maybe they have a scar, but you give them some steroids or rest their bowel and it resolves
•Suggests that maybe it was just an inflammatory process and you can avoid surgery
•Important to tease that out
•There are clinical factors, lab factors, patient history and all those kinds of things that can help you work it out
•Other important type of CD is that of a fistulizing CD (Image C)
•A fistula is an abnormal connection between two organs
•You can develop fistulas between two portions of the bowel as seen here as an enteroenteric fistula
•Here you are seeing a fistula develop between in the distal ileum in the sigmoid colon
•You can also have enterocutaneous fistula where the bowel fistulizes to the skin
•Can see enterovesicular where it fistulizes to the bladder
•The most common area where we see fistulas is the peri-anal area, which is basically eneterocutaneous fistula making an abnormal connection between the rectum and the skin around the rectum
•See this in up to a 1/3 of our patients with CD
•Can be very difficult to manage
•Often a palliative management as an opposed to a definitive management
infliximab, adalimumab, golimumab
monoclonal antibodies that bind TNFalpha
must check TB and HBV status
side effects: infusion reaction, hep, infection, malignancy
step up therapy
Antibiotics in Crohns
some postiive data for use in inducing and maintaining remission in crohn's
no specific class!
risk of c. diff and resistance combined w poor quality of evidence has lead to lack of rec
Chronic, systemic, inflammatory process with a relapsing and remitting course affecting various parts of the GI tract
not always limied to the bowel
a disease of the developed world
azathioprine (immunomodulator) + infliximab (anti-TNF ab)
diminish infusion reaction and increase efficacy!
may be seen in UC
•You can get an inflammatory patch right here [right above the appendix] even though this portion of the colon is spared [pointing to ascending colon]
backwash ileitis may occur
for **maintanence of UC or CD
monoclonal ab that binds alpha4bta7 integri and inhibits t cell movement across the endothelium to inflammed GI tissue
best marker for neutrophil degredation
taking over for barium imaging
CT or MR based studies
consume a large volume of water soluble contrast to distend the small bowel prior to scanning
exposed to radiation!!
•The area of interest that we really need to focus on is the small intestines
•Our upper endoscope goes to the proximal small intestines
fat wrapping around!!
•Our colonoscope goes to the bottom of our small intestines
There is a whole segment in between that is less easy to gain info on
tobacco use and IBD
•Shown to increase, as well as worsen, Crohn’s disease course
•Can improve UC
•Or when someone stops smoking, their UC can present or flare
classic features of UC
usually more acute presentation
always involves the rectum and ascends in a continuous pattern
can have disease limited to the rectum, left colon, or entire colon
inflammation is localizedto the mucosa or submucosa
•This disease starts in the rectum and ascends up
•Can have a condition where you also have a clear delineation of the end of the colitis, somewhere distal to the right side of the colon [pointing to where the start of the word transverse], and have what is called an isolated cecal patch or a periappendiceal patch
•See the little tail of the appendix
•You can get an inflammatory patch right here [right above the appendix] even though this portion of the colon is spared [pointing to ascending colon]
C reactive protein
increased more in crohn's because it's transmural
video capsule endoscopy (VCE)
in CD - no role in UC! (worried about perforation)
pill camera - 8-10 hours
NSAIDs can produce similar lesions
capsule can be retained or obstruct in those with stricuturing disease!!
Radiation therapy in CRC?
Best in stage II and III
CRC Screening of HNPCC?
Every 2 years beginning at age 20-25 until 40, then annually
immunomodulators in IBD
6-MP, methotrexate, azathioprine
•Can be used both in moderate CD and 5-ASA refractory UC
halt DNA replication and interfere with purine synthesis
TPMT level required prior to initiating treatment - •TPMT levels helps predict if patients will have bone marrow toxicity from this drug
tons of scary side effects
Steroid use in IBD
used in UC with 5-ASA failure or need for urgent respponse (not for maintenence)
used in Crohns for severe inflammatory
oral, parenteral, topical
hard to use!!
Colon cancers develop through a stepwise accumulation of somatic mutations and so this diagram is called the Volgermer after him, and it describes the stepwise mutations that occur through an adenoma pathway.
surgical management of CD
80% will require
abscesses, stricture, relief of obstruction
post-op recurrence always in neoterminal ileium
Most frequent CRC mets?
regional lymph nodes
liver - Because of portal drainage – colon drains into the portal system, which go to the liver first, which acts as a sieve for cancer cells and they implant there and then they metastasize.
lungs - In distal colon cancers near the rectum, that part of the colon has drainage through the vertebral veins. Not through the portal system, but through the systemic system, so bypass the liver and end up in the lungs.
It’s a bacteria that has been associated with the presence of colon cancer. People don’t know if its caused by it or not, it doesn’t seem like it is, but the recommendations right now, if you have ever had S. bovis in your blood stream, the recommendation is to get a colonoscopy to look for a malignancy there.
maybe just colonizes cancer tissue
Common pathway of CRC stepwise mutations
APC - KRAS - p53
CRC Screening of FAP?
Annula flexible sigmoidoscopy r colonoscopy starting at age 12 or until colectomy
100% of developing!
Top- want to reconnect the two sides of the colon after you have taken out some of it.
Might not want to do it immediately after surgery:
Anastomosis might not hold very well.
But do want to reconnect. Called a primary anastomosis because do it in one step.
Bottom pictures: Sometimes can’t do that: can’t prep, too much inflammation, other complications. Instead, take out the part with the cancer, seal it off for a little bit, then bring the distal end of the colon to the abdominal wall and they end up with a colostomy bag. Sometimes can later reconnect, sometimes not.
Barium studies for IBD
determine location of disease and extent of inflammation and changes to lumen caliber
may show aphthous ulcers, coarseed villous folds or thickening
may also see fistulas and strictures
also perforations and anscesses
falling out of favor!!
Location of UC lesions
colon and rectum - rectum ascending prox
rectum universally involved
mucosal and submucosal injury
continuous pattern of inflammation
acute onset! bleeding, obvious
carcionembryonic antigen (CEA)
antigen that is elevated in certain people who have colon cancer (about 30%). Useful if you have an elevated CEA at diagnosis, and then resected successfully, your CEA should drop. Usually use as follow up, if it starts to elevate again, you are worried it’s a recurrence of the tumor.
If there is a metastasis, CEA will be elevated as well.