Sabiston IBD

Question 1

Etiology of Crohns

Answer 1

-infectious : Mycobacterium paratuberculosis and enteroadherent E. coli.

-immunologic : Humoral and cell-mediated immune reactions , cytokines, such as interleukin (IL)-1, IL-2, IL-8, and TNF-α

genetic : NOD2, MHC, and MST1 3p21

Environmental factors : smoking

Question 2

the single strongest risk factor for development of Crohns disease

Answer 2

-is having a first-degree relative with Crohn disease

-The most important gene in Crohn disease development is NOD2

Question 3

The NOD2 gene is associated with a decreased expression of

Answer 3

antimicrobial peptides by Paneth cells.

Question 4

Which Gene is a predictor of ileal disease, ileal stenosis, fistula, and Crohn-related surgery.

Answer 4

NOD2

Question 5

Which gene can distinguish Crohn disease from ulcerative colitis

Answer 5

CARD15 > strongly associated with Crohn disease

Question 6

CARD15, leads to impaired activation of

Answer 6

the transcription factor nuclear factor kappa B (NF-κB)

Question 7

tumor suppressor gene play a role in the pathogenesis of Crohn disease and development of Crohn disease–related cancers

Answer 7

The FHIT gene located on 3p14.2

Question 8

Environmental factors that increase the risk of Crohn disease

Answer 8

medications (oral contraceptives, aspirin, [NSAIDs]), decreased dietary fiber, and increase fat intake.

Question 9

dysbiosis in which organisms increase the risk

Answer 9

decrease in intraluminal Bacteroides and Firmicutes

increase in Gammaproteobacteria and Actinobacteria

Question 10

Ileal involvement has been shown with mutations of

Answer 10

IL10, CRP, NOD2, ZNF365, and STAT3

Question 11

ileocolonic involvement has been shown with mutations

Answer 11

ATG16L1, TCF4, and TCF7L2

Question 12

colonic involvement has been associated with mutations

Answer 12

HLA, TLR4, TLR1, TLR2, and TLR6.

Question 13

What characteristic can distinguish it from ulcerative colitis

Answer 13

rectal sparing

Question 14

Gross pathologic features at exploration

Answer 14

1- thickened gray-pink or dull purple-red loops of bowel
2- areas of thick gray-white exudate or fibrosis of the serosa.
3- skip areas
4- extensive fat wrapping caused by the circumferential growth of the mesenteric fat around the bowel wall, (creeping fat)
5- bowel wall thickened, firm, rubbery, and almost incompressible
6- uninvolved proximal bowel may be dilated secondary to obstruction
7- Involved segments adherent to adjacent intestinal loops or other viscera, with internal fistulas
8- The mesentery of the involved segment is thickened, with enlarged lymph nodes
9- On opening of the bowel, the earliest gross pathologic lesion is a superficial aphthous ulcer noted in the mucosa.

Question 15

on opening the bowel, the earliest gross pathologic lesion is

Answer 15

superficial aphthous ulcer noted in the mucosa.

With disease progression, the ulceration becomes results in transmural inflammation

Question 16

characteristics of The ulcers

Answer 16

linear
may join to produce transverse sinuses with islands of normal mucosa in between

thus giving the characteristic ‘‘cobblestone appearance’’

Question 17

Characteristic histologic lesions of Crohn disease are

Answer 17

noncaseating granulomas with Langerhans giant cells.

Granulomas appear later in the course and are found in the wall of the bowel or in regional lymph nodes

Question 18

massive gastrointestinal bleeding in CD can occasionally occur, particularly in

Answer 18

duodenal Crohn disease > chronic ulcer formation

Question 19

long-standing Crohn disease can develop

Answer 19

Dysplasia
Adenocarcinoma

MC in the Ileum

Question 20

Extraintestinal cancer with CD

Answer 20

squamous cell carcinoma of the vulva and anal canal
Hodgkin and non-Hodgkin lymphomas

especially those treated with immunomodulators

Question 21

Serologic markers useful in the diagnosis of Crohn disease.

Answer 21

-Perinuclear antineutrophil cytoplasmic antibody
(target proteins bactericidal/permeability increasing protein [BPI], lactoferrin, cathepsin G and elastase)

-Anti–Saccharomyces cerevisiae antibody (ASCA)
useful in differentiating Crohn disease from ulcerative colitis

-outer membrane porin of flagellin (anti-CBir1),

-outer membrane porin of E. coli (OmpC-IgG)
> predict development of IBD even in Low risk patients

Question 22

inflammatory markers specific to the intestine

Answer 22

• Stool lactoferrin, an iron-binding protein in the secretory granules of neutrophils
• fecal calprotectin, a protein with antimicrobial properties released by squamous cells in response to inflammation,
• both calprotectin and lactoferrin levels correlate with CT enterography (CTE)
  -Helpful screening tools for detecting early small bowel Crohn disease

Question 23

Montreal classification of Crohn disease

Answer 23

see

Question 24

MRE may be superior to CTE in detecting

Answer 24

intestinal strictures and ileal wall enhancement

Question 25

the gold standard for the diagnosis of Crohn disease.

Answer 25

Ileocolonoscopy with biopsies of the terminal ileum

Question 26

Endoscopic advances that allow better evaluation of the small intestine include

Answer 26

-single-balloon enteroscopy -double-balloon enteroscopy -spiral enteroscopy the most well-established technique is double-balloon enteroscopy, which allows increased enteral intubation (240–360 cm) push enteroscopy (90–150 cm) ileocolonoscopy (50–80 cm)

Question 27

Best Modality for identification of intestinal ulceration.

Answer 27

capsule endoscopy has been found to be superior to any other modality in the identification of intestinal ulceration. criterion for an abnormal finding is the presence of three or more ulcers in the absence of NSAID use.

Question 28

Aminosalicylates

Answer 28

-Sulfasalazine (azulfidine) is an aminosalicylate with 5-aminosalicylic acid -use in maintenance therapy has fallen out of favor -Mesalamine, a slow release of 5-aminosalicylic acid -If remission is achieved with induction,continued for maintenance -SE: interstitial nephritis (1%)

Question 29

Corticosteroids

Answer 29

-Budesonide, high first-pass hepatic metabolism, allows targeted delivery to the intestine mitigating the systemic effects of steroid therapy. -The preferred primary treatment for patients with mild to moderately active Crohn disease with localized ileal disease -9 mg/day -prednisone, in moderate to severe CD. -not ideal for maintenance therapy (50% become “steroid dependent,”) -Parenteral corticosteroids indicated for severe disease once the presence of an abscess has been excluded -40–60 mg daily

Question 30

How to taper Steroids ?

Answer 30

tapered by 5 to 10 mg/ week until 20 mg and then by 2.5 to 5 mg weekly until cessation

Question 31

What Should you do when starting steroids ?

Answer 31

-Dual-energy x-ray absorptiometry scan -calcium and vitamin D supplementation -consideration of bisphosphonate therapy

Question 32

Antibiotics

Answer 32

-metronidazole -ciprofloxacin -rifaximin -clofazimine -ethambutol -isoniazid, -rifabutin -used in septic complications and beneficial in perianal disease.

Question 33

Immunosuppressive agents

Answer 33

-AZT and 6-MP are effective for maintaining steroid-induced remission -weekly IV MTX is effective for both induction and maintenance therapy. SE: pancreatitis, hepatitis, fever, and rash. chronic liver disease, bone marrow suppression, and the potential for malignant transformation.

Question 34

What regulates Immunosupressive Therapy ?

Answer 34

thiopurine methyltransferase (TPMT), which is the primary enzyme that metabolizes AZT and 6-MP decreased TPMT activity > increased risk of fatal bone marrow suppression

Question 35

Any test can be done before starting immunosupressive therapy ?

Answer 35

TPMT genotype testing > determine genetic predisposition to adverse outcomes

Question 36

MTX side effects

Answer 36

hepatotoxicity myelosuppression not used in pregnant women.

Question 37

Other agents help in fistula?

Answer 37

FK-506 inhibits the production of IL-2 by helper T cells effective for fistula improvement, but not fistula remission

Question 38

patients with severe disease who do not respond to IV steroids, what to give ?

Answer 38

cyclosporine and FK-506

Question 39

Anti-TNF therapy

Answer 39

-Infliximab for moderate to severe Crohn disease -For induction and maintenance agent -can results in perineal fistula closure

Question 40

Which agent is ideal in pregnant and nursing women

Answer 40

certolizumab (humanized antibody fragment) does not cross the placenta and is not excreted in breast milk

Question 41

Anti TNF Concern

Answer 41

-increased risk for TB reactivation -invasive fungal and opportunistic infections, -demyelinating CNS lesions -activation of latent multiple sclerosis -exacerbation of congestive heart failure -concerns for increased risk of melanoma

Question 42

Patients who develop a flare while on anti-TNF agents

Answer 42

measurement of serum drug concentrations and antidrug antibodies increase dosage (if low drug concentration and low antibodies) switch to another anti-TNF agent (high antidrug antibodies) switch to another drug class (normal drug concentration).

Question 43

Novel therapies

Answer 43

-used if the patient has failed or is unable to tolerate anti-TNF therapy -Natalizumab -vedolizumab -Ustekinumab

Question 44

What extraintestinal complications of Crohn disease Does not Subside after resection

Answer 44

ankylosing spondylitis and hepatic complications.

Question 45

Do Fistulizing disease requires operative intervention

Answer 45

rarely requires operative intervention unless the fistula involves the bladder, vagina or skin

Question 46

New Technique minimize anastomotic restenosis in Crohn disease

Answer 46

antimesenteric functional end-to-end hand-sewn anastomosis (known as Kono-S anastomosis)

Question 47

Why anastomotic recurrence happens in CD

Answer 47

fecal stasis and subsequent bacterial overgrowth

Question 48

At exploration, the appendix is found to be normal, but the terminal ileum is edematous and beefy red with a thickened mesentery and enlarged lymph nodes

Answer 48

this patient has acute ileitis, Due to early CD or Bacteriologic > Campylobacter and Yersinia Intestinal resection should not be performed In the absence of acute inflammatory involvement of the appendix or the cecum, appendectomy should be performed.

Question 49

In patients for whom it is difficult to determine whether the site of obstruction is caused by an acute exacerbation or a chronically strictured segment

Answer 49

stool lactoferrin and calprotectin levels may help identify acute inflammation

Question 50

There are two types of bypass operations: exclusion bypass and simple (continuity) bypass

Answer 50

-proximal transected end of the ileum is anastomosed to the transverse colon in an end-to-side fashion with or without construction of a mucous fistula using the distal transected end of the ileum (exclusion bypass) -or an ileotransverse colonic anastomosis is made in a side-to-side fashion (continuity bypass).

Question 51

Indications for Bypass

Answer 51

-severe gastroduodenal CD not amenable to strictureplasty -older poor-risk patients -patients who have had several prior resections and cannot afford to lose any more bowel -those in whom resection would necessitate entering an abscess or endangering a normal structure.

Question 52

Sx for Fistula

Answer 52

-fistula between two or more adjacent loops of diseased bowel > segments should be excised -fistula involves an adjacent normal organ (bladder or colon) > only the segment of the diseased small bowel and fistulous tract should be resected, and the defect in the normal organ should simply be closed -ileosigmoid fistulas do not necessarily require resection of the sigmoid because the disease is usually confined to the small bowel. -However, if the segment of sigmoid is also found to have Crohn disease, it should be resected along with the segment of diseased small bowel.

Question 53

Abscess Tx

Answer 53

abscess < 3 cm and have not been on biologics or have an associated fistula can be treated with antibiotics alone. Abscesses that do not meet these criteria should undergo percutaneous drainage

Question 54

Patient with generalized peritonitis

Answer 54

safer option > create an ostomy until the intraabdominal sepsis is controlled Then return for restoration of intestinal continuity after a period of 4 to 6 weeks

Question 55

The most common urologic complication in CD

Answer 55

-ureteral obstruction, secondary to ileocolic disease with retroperitoneal inflammatory compression

Question 56

after abdominoperineal resection in patients with Crohn disease

Answer 56

Wound filled with well-vascularized pedicles of muscle (e.g., gracilis, semimembranosus, rectus abdominis) or omentum or by using an inferior gluteal myocutaneous graft.

Question 57

Tx for perianal

Answer 57

-nonoperative unless an abscess or complex fistula develops -Nonsuppurative, chronic fistulization or perianal fissuring treated with antibiotics, immunosuppressive agents (e.g., AZT or 6-MP), and infliximab Several uncontrolled studies have shown some benefit with cyclosporine or FK-506 treatment.

Question 58

Fistula Tx

Answer 58

fistulotomy > superficial, low trans-sphincteric, and low intersphincteric fistulas High transsphincteric, supra-sphincteric, and extrasphincteric fistulas > noncutting seton

Question 59

Fissure Tx in CD

Answer 59

usually lateral, relatively painless, large, and indolent and often respond to conservative management

Question 60

Duodenal disease in CD

Answer 60

Gastrojejunostomy to bypass the disease rather than duodenal resection is the procedure of choice

Question 61

the leading cause of disease-related deaths in patients with Crohn disease

Answer 61

Gastrointestinal cancer