IBD/other non-malignant/non anorectal

Question 1

What blood tests can help in the diagnosis of Crohns and UC?

Answer 1

ASCA +ve in 35-50% of Crohns pts cf <1% UC.

p-ANCA often raised in UC (sens 55%, spec 90%); if raised in Crohns, only with colitis

Question 2

What is faecal calprotectin?

Answer 2

A protein with antimicrobial properties released by squamous cells in response to inflammation

Question 3

What is the aetiology of Crohn’s disease?

Answer 3

Interplay between environmental and genetic factors; probably results from a genetic predisposition to an abnormal interaction between immune system & environmental factors, espec gut microbiota. Specific cause of exaggerated inflam response at mucosal level unclear. Number of potential causes proposed - most likely being infectious, immunologic & genetic; other possibilities environmental & dietary factors, smoking, psychological factors

Question 4

How is Crohn’s disease classified?

Answer 4

Montreal classification

• Age at diagnosis: A1 <16, A2 17-40, A3 >40
• Location: L1 ileal, L2 colonic, L3 ileocolonic, L4 isolated upper disease (modifier that can add to L1-3 when present)
• Behaviour: B1 non-stricturing and non-penetrating, B2 stricturing, B3 penetrating, P = perianal disease modifier

By phenotype: inflammatory, fibrostenotic, fistulising

Crohn disease activity index (CDAI) – to quantitate symptoms

• 8 clinical & lab variables, incl no of BM/day, presence of abdo pain, haematocrit, weight loss, 7 day symptom diary
• score <150 = clinical remission; score >450 = severe disease

Harvey-Bradshaw index

Question 5

What are the operative options for UC?

Answer 5

• Total abdominal colectomy and end ileostomy (acute operation)
• Proctocolectomy & end ileostomy (pt preference, low rectal ca, poor sphincter function)
• Proctocolectomy + IPAA (stapled better QOL but higher risk dysplasia/malignancy in retained mucosa (v rare) cf handsewn)
• Proctocolectomy + continent ileostomy
• Total abdominal colectomy + IRA (only if rectum minimally inflamed, no rectal dysplasia, intact sphincter mechanism, willing to adhere to strict f/u - risk of rectal ca 20% by 30yrs)

Question 6

What are the factors which increase the risk of CRC in IBD?

Answer 6

3-5x increased risk colon ca, tend to get at younger age and higher mortality

Factors which increase risk:

• disease duration + extent
• severity of inflammation
• PSC
• FHx of CRC
• Presence of dysplasia

Question 7

What are the two biologics used in IBD in NZ?

Answer 7

Anti-TNF alpha antibody
Infliximab (Remicade) = mouse-human chimeric monoclonal antibody, IV infusion 8wkly
Adalimumab (Humira) = fully human monoclonal antibody, SC injection fortnightly

Question 8

What is ulcerative colitis?

Answer 8

An idiopathic and relapsing inflammatory bowel disease involving the lamina propria of the rectum and variable extent of the proximal colon - characterised by remissions & exacerbations. The inflammation spares the anus and is continuous to its proximal extent. Can be associated with extra-intestinal manifestations.

Question 9

What is Crohn’s disease

Answer 9

A chronic, transmural inflammatory process that can affect GIT anywhere from mouth to anus with skip lesions & can be associated with extraintestinal manifestations.

Question 10

What are the causes of colitis?

Answer 10

Infectious
Bacteria
- Campylobacter – spiral microaerophilic gram +ve rod
- C diff – anaerobic, spore forming, gram +ve rod
- Salmonella – gram –ve facultatively anerobic rod
- Shigella – gram –ve facultative anaerobic rod
- Enterotoxic E coli – gram –ve facultative anaerobic rod
- Yersinea – gram –ve coccobacillus

Parasitic

• Entaemoeba histolytica
• Cryptosporidium

Viral
- CMV

Inflammatory
- UC, Crohn’s

Ischaemic
Microscopic colitis
Behcet’s
NSAIDs

Question 11

How is colitis severity classified

Answer 11

Clinical: Truelove and Witt’s criteria (she hasn’t even finished pooping)

• Severe = ≥6 bloody stools a day and one of Hb <105, ESR/CRP >30, Febrile >37.8, Pulse >90
• Moderate =
• Mild =

Endoscopically: Mayo criteria

Question 12

What is toxic megacolon?

Answer 12

Dilation of the colon in the setting of systemic toxicity, secondary to any infectious or inflammatory disease of the colon

Pathogenesis

• as mucosa sloughs, endotoxins within bowel lumen are absorbed –> septic state characterised by leukocytosis, tachycardia, fever +/- haemodynamic instability
• colonic inflammation increases production of inducible nitric oxide synthase by macrophages & SM cells - NO inhibits SM tone which contributes to colonic dilation
• while only mucosa is inflamed in typical UC, SM layer is inflamed & paralysed in toxic megacolon which can contribute to colonic dilatation
• inconclusive whether myenteric plexus of colon is damaged in toxic megacolon

Diagnosis

• Suspect if distension and diarrhea
• Criteria:
  
  • Transverse colon diameter >6cm AND
  • Plus any 3 of following:
    
    • Fever >38, tachycardia >120, WC >10.5, anaemia <60% of normal
  • Plus any 1 of the following:
    
    • Dehydration, electrolyte imbalances, altered mental state, hypotension

Question 13

How do you decide if IV steroids are working in acute severe colitis?

Answer 13

Travis criteria – on day 3 if stool frequency >8 or stool frequency 3-8 and CRP >45, 85% require colectomy (but from a time where corticosteroids were only thing in toolbox from medical point of view)

Question 14

What is the aetiology of ischaemic colitis

Answer 14

• Physiological – low-flow states
  
  • Eg hypotension (incl sepsis), hypovolaemia, haemorrhage, cardiovascular, heart failure, atherosclerosis)
• Hypercoagulable
  
  • Factor V Leiden, Protein C&S deficiency, Prothrombin G2010A mutation, antiphospholipid syndrome (Lupus anticoagulant), Antithrombin III deficiency, PCV, DIC, HITT
• Autoimmune disease
  
  • SLE
• Tobacco (acquired)
• Drugs
  
  • Vasopressors, OCPs, diuretics, antiarrhythics, antihypotensives
  • Immunomodulatory drugs eg anti-TNF-a inhibitors can affect thrombogenesis
  • Illicit drugs eg cocaine & meth – thru vasoconstriction, hypercoagulation, direct endothelial injury
• Surgery/procedural
  
  • Cardiac, aortic
  • Pts undergoing aortic reconstructive surgery or abdo surgery in which IMA is ligated if collateral circulation not sufficient

Question 15

What are the two well-described collateral networks that aid in preventing colonic ischaemia?

Answer 15

• Marginal artery of Drummond – runs parallel & close to mesenteric margin of colon from caecocolic junction to rectosigmoid junction – colon can receive collateral blood supply through this artery when one of larger arteries is obstructed
  
  • Important when resecting a section of colon to preserve this since only vasa recta are located between it and colon
  • When compromised, ischaemia of that section of colon may result
• Arc of Riolan (meandering mesenteric artery) = found in prox region of large arteries – traverses close to mesenteric root, connects SMA or middle colic to IMA or left colic
  
  • Can have critical role in situations of SMA or IMA occlusion
  • Presence of large arc of Riolan commonly indicates obstruction of one of the major mesenteric arteries

Question 16

What are the two watershed areas of the colon?

Answer 16

• Found at edge of region supplied by the SMA & IMA – these zones are frequently dependent upon collateral circulation
• Splenic flexure (Griffiths point) – up to 50% lack a marginal artery in region where SMA & IMA circulations meet
• Rectosigmoid junction (Sudeck’s point) – receives blood supply from superior haemorrhoidal artery & distal sigmoid branches, both terminal branches of IMA & prone to atherosclerotic changes
• Right colon, though not classically considered a watershed area, is also vulnerable to ischaemia from embolic occlusion bc ileocolic is terminal branch of SMA; so R colon also particularly prone to low-flow conditions eg heart failure, haemorrhage, sepsis

Question 17

How is ischaemic colitis classified and managed?

Answer 17

• Mild disease: segmental, not isolated to right colon, and lacking poor prognostic factors observed in moderate disease
• Moderate disease includes any 3 of the following:
  
  • Tachycardia
  • Abdo pain w/o rectal bleeding
  • Hypotension
  • Male sex
  • BUN >20mg/dL
  • Na <136
  • WCC >15
  • Hb <12
  • Colonoscopically identified ulceration
• Severe disease: >3 of moderate disease criteria or peritoneal signs, pneumatosis or portal venous gas w CT imaging, gangrene on colonoscopy, and pancolonic or isolated right colon ischaemia on CT or endoscopy
• mild and moderate: treat supportively + treat underlying cause (abx can be considered to decrease sequelae of bacterial translocation but lack of robust data to support this)
• full thickness necrosis and gangrene, peritonitis, pneumoperitoneum or haemodynamic instability: immediate surgery
• in contrast to mesenteric ischaemia of small intestine, usually no indication for revascularising the large bowel in primary colonic ischaemia, which is not generally related to large artery obstruction
• (only need CTA if acute mesenteric ischaemia suspected w pain out of proportion and lack of haematochezia, or if isolated right sided)

Question 18

What are the absolute indications for colectomy in acute severe colitis?

Answer 18

Toxic megacolon

Perforation

Haemorrhage

Multiorgan dysfunction

Question 19

What are the indications for colectomy in colitis in general?

Answer 19

• Failure to respond to maximal medical therapy
  
  • Pts w severe disease – multiple BMs, poor nutritional status, failure to thrive, poor QOL
  • Pts w acute severe colitis
• Perforation
• Significant GI bleeding
• Toxic megacolon
• Drug intolerability
• Growth impediment in children
• Dysplasia or malignancy
• For attempted improvement of some extra-intestinal manifestations refractory to medical treatment

Question 20

Outline the principles of medical management of IBD

Answer 20

• Short term: Induce remission
  
  • Corticosteroids (UC and Crohn’s)
  • 5-Aminosalicylates (UC only)
• Long term: maintain remission
  
  • 5-aminosalicylates (Pentasa/Asacol) (minor benefit in crohn’s colitis only)
  • thiopurines (azathioprine)
  • methotrexate/cyclosporine
  • biologics (infliximab/adalimumab)
• symptomatic response alone not predictive of clinical course; now want to see
  
  • symptomatic remission and normalization of CRP
  • decrease faecal calprotectin to acceptable range, normal growth in children
  • endoscopic healing, normalized QOL
  • consider histologic healing also

Question 21

Outline the medical treatment of UC

Answer 21

Disease severity at presentation

• Mild – induction w aminosalicylate, maintenance w aminosalicylate
• Moderate – induction w corticosteroid, maintenance w aminosalicylate & thiopurine (MTX)
• Severe – induction w anti-TNF, cyclosporine, maintenance w anti-TNF, thiopurine, vedolizumab
• Very severe at presentation – colectomy
• NB for proctitis and mild-mod distal colitis, topical mesalamine supps/enemas = better than oral, +/- add topical steroids +/- add oral mesalamine
• For mild-mod extensive colitis, give oral asacol + topical therapy too

Question 22

Outline surveillance for colorectal cancer in IBD

Answer 22

• Starting time for surveillance in at risk pts
  
  • UC beyond sigmoid OR CD >1/3 of colon or complicated anorectal disease = no later than 8yrs after onset sx
  • If PSC detected = at time of dx of PSC
  • If strong FHx of CRC = before 8yr after onset of sx
• Optimal surveillance intervals
  
  • Group 1 = any high risk feature
    
    • Chronically active UC
    • PSC
    • CRC in FDR at <50y age
    • Stricture, multiple inflammatory polyps or shortened colon
    • Previous dysplasia
    • = 1yrly colonoscopy
  • Group 2:
    
    • Quiescent UC w/o high risk features
    • = 3yrly colonoscopy
  • Group 3:
    
    • UC w/o high risk features when 2 previous colonoscopies are macroscopically inactive and histologically negative for dysplasia
    • = 5yrly colonoscopy

Question 23

What are the extraintestinal manifestations in Crohn’s disease?

Answer 23

• Related to disease activity
  
  • Aphthous ulceration (10%)
  • Erythema nodosum (5-10%) – see UC for more details
  • Pyoderma gangrenosum (0.5%) – see UC for more details
  • Acute arthropathy (6-12%)
  • Eye complications (conjunctivitis etc) (3-10%)
  • Amyloidosis (1%)
• Unrelated to disease activity
  
  • Sacroiliitis (often minimal sx) (10-15%)
  • Ankylosing spondylitis (1-2%)
  • PSC (rare)
  • Chronic active hepatitis (2-3%)
  • Cirrhosis (2-3%)
  • Gallstones (15-30%)
  • Renal calculi (5-10%)

Question 24

What are the extracolonic manifestations of UC?

Answer 24

20% of those w UC will get; slightly less than Crohn’s

• those that respond to colectomy: peripheral arthropathy, erythema nodosum, episcleritis
• sometimes: pyoderma gangrenosum
• don’t respond: axial arthropathy, PSC, uveitis, scleritis

D. MOTH

Derm

• erythema nodosum (related to bowel activity)
  
  • 10-20% of UC, can precede bowel stuff
• pyoderma gangrenosum (sometimes related)
  
  • 10-10%
  • plaques or pustules that break down & form painful ulcerations w undermined borders & necrotic centers
  • legs most common but can happen anywhere incl peristomally
  • get worse w surgery - non op tx incl intralesional steroids, topica tacrolimus, systemic biologics

MSK (most common)

• asymmetrical peripheral arthropathy involving small & large joints (related to disease activity)
• ank spond
• asymptomatic sacroileitis (both not related)

Ophthal

• episcleritis (responds) and uveitis (doesn’t) most common
• also scleritis, conjunctivitis

Thromboembolic

• VTE risk 3x higher
• rare = cerebral venous & dural sinus thrombosis
• hypercoagulable state

HPB

• PSC (not related)
  
  • idiopathic, chronic & progressive disorder - stricturing, inflam, fibrosis of intra and extrahepatic bile ducts
  • 5% of pts w UC get PSC; >5% of pts w PSC have UC
• cholangiocarcinoma rare assoc w UC & PSC

Question 25

What is the medical management of Crohn’s

Answer 25

• Concept = induce remission then maintain it
• Most effective agent for inducing remission = a corticosteroid, and 2^nd-line agents = TNF inhibitors, infliximab or adalimumab
• For moderate to severe disease, steroids are commenced & at the same time immunomodulators (usually azathioprine)
  
  • After some weeks or months, when therapeutic benefit of immunosuppression commences, steroids can be removed
• Aminosalicylates (sulfasalazine & 5-ASA) have modest efficacy for mild to moderate Crohn’s colitis

INDUCTION OF REMISSION:

Mild to moderate disease

• Prednisone 20-40mg daily for 2-3 weeks then tapering
• Ileal and/or right colon: budesonide 9mg per day
• Crohn’s colitis: appropriate salicylate compound (oral and/or enema)
• Perianal disease: metronidazole 400mg tds or Cipro 500mg BD

Severe disease

• IV hydrocortisone 400mg daily in divided doses
• Infliximab, adalimumab or other biological (second-line)

MAINTENANCE OF REMISSION

• Azathioprine, 6-mercaptopurine, methotrexate, budesonide 6mg per day (ileal and/or right colon), infliximab or adalimumab

Question 26

Differential diagnoses for terminal ileitis

Answer 26

• Infection: TB, Yersinia, Salmonella, CMV, neutropenic enterocolitis
• NSAID enteropathy
• Malignancy: lymphoma, carcinoid
• Lymphoid nodular hyperplasia
• Crohn’s
• UC with backwash ileitis

Question 27

Crohns in pregnancy

Answer 27

in absence of active disease, outcome of pregnancy = that of matched controls

w active disease at conception, ­ in spont abortions & premature delivery, and a 50% chance of relapsing disease during pregnancy

risk of relapse only 20-25% if disease inactive at conception – ie avoid conception during acute phase of disease

pregnancy probably doesn’t affect long-term course of disease

Question 29

How can diarrhoea be classified?

Answer 29

• Acute - 14 days duration or less
• Persistent - Between 14-30 days duration
• Chronic - More than 30 days duration
• Secretory:
  
  • S. aureus, Cholera, VIPoma, Carcinoid syndrome, Adenomas
• Exudative:
  
  • IBD, Colorectal cancer, Campylobacter
• Osmotic:
  
  • Lactose intolerance
  • Laxatives
  • Surgical changes
• Abnormal motility:
  
  • Irritable bowel syndrome
  • Thyrotoxicosis

Question 30

How are the different phenotypes of Crohn’s classified?

Answer 30

The Montreal (nee Vienna) classification system. Classifying phenotype is relevant for studying the outcome of therapy, medical or surgical.

p is added if perianal disease is present.

Question 31

What are the factors that contribute to anal continence?

Answer 31

1. Tonic contraction of puborectalis and the external anal sphincter
2. Maintenance of the angle between the rectum and anal canal, where abdominal pressure flattens the rectum against the sacrum
3. Mucosal cushions in the anal canal

Not dissimilar to the anti-reflux mechanisms at the GOJ; tonic contraction of the muscular hiatus, maintenance of the angle of His, an intra-abdominal oesophagus flattening with pressure, and the oesophageal rosette, respectively.

Question 32

Describe the classification system used for Acute Diverticulitis?

Answer 32

Primary reconstruction may be considered in Hinchey grade I and II but is contraindicated in grade III or IV disease.

Question 33

Describe the radiological classification system used in diverticulitis

Answer 33

Ambrosetti classification.

Mild - wall thickening >5mm, pericolic fat stranding

Severe - same as mild plus: abscess, extraluminal air, extraluminal contrast

Question 34

What is the distribution of Lower GI Bleeding aetiology?

Answer 34

• Anorectal ~10%
• Colonic
  
  • Diverticular 33%
  • Angiodysplasia 20%
  • Tumours 10-15%
• IBD ~10%
• Unknown ~10%
• Small bowel, coagulopathy etc make up the remainder.

Question 35

What are the new treatments for IBD (in Aus)

Answer 35

Vedolizumab (a4b7 integrin inhibitor)

Ustekinumab (monoclonal Ab Il-23)

Question 36

What is the CDAI used in Crohn’s?

Answer 36

Crohn’s disease activity index. Uses clinical and lab values.

>450 severe

<150 mild

<70 disease response

Question 37

Describe the modified Hinchey criteria

Answer 37

0. = Mild clinical diverticulitis

Ia. = Confined pericolic inflammation or phlegmon

Ib. = Confined pericolic abscess

II. = Pelvic, distant intra-peritoneal or retroperitoneal abscess

III. = Generalised purulent peritonitis

IV = Generalised faeculant peritonitis

Question 38

List the Alavarado score

Answer 38

Migration of pain (1pt)

Anorexia (1pt)

Nausea or vomiting (1pt)

RLQ tenderness (2pts)

Rebound tenderness (1pt)

Fever 37.3 (1pt)

Leucocytosis (2pts)

WBC left shift (1pt)

Cutoffs differ by study, but one validated stratification assifns the highest risk to scores ≥9 in males or ≥10 in females and lowest risk to scores ≤1 in males or ≤2 in females

≥9 = definite, 7-8 = probable/likely, 5-6 = possible, ≤4 = unlikely

Question 39

What are the indications for emergent surgery in Ulcerative Colitis?

What are the indications for elective surgery in Ulcerative Colitis?

Answer 39

Emergent indications (BUMP):

• Bleeding
• Unresponsive to medical therapy
• Mega-colon
• Perforation

Elective indications (3Ms):

• Malignancy or dysplasia
• Medical therapy failure
• Maturation failure

Question 40

How do you classify anal incontinence?

Answer 40

By degree of incontinence:

1. Flatus
2. Mucus
3. Motion

By clinical presentation:

1. Urge incontinence
2. Passive incontinence
3. Mixed pattern incontinence

Question 41

How can “constipation” be more accurately classified?

Answer 41

As a problem of colonic inertia, rectal evacuatory dysfunction, or a combination of the two.

Colonic inertia:

• Opiates, anticholinergics, Iron tabs, Anti-HTN meds, NSAIDS
• Slow transit

Rectal evacuatory dysfunction:

• Rectal prolapse, intussusception, Paradoxical anal sphincter contraction, Impaired pelvic floor relaxation

Combined:

• Neurological issues (Parkinson’s, diabetic autonomic neuropathy)

Question 42

How would you categorise the clinical manifestations of Crohn’s disease?

Answer 42

1. Gastrointestinal
   
   • The GI symptom profile will reflect the diease location
2. Systemic
   
   • Weight loss, anorexia, malaise, vitamin deficiency (osteomalacia, scurvy, coagulopathy)
3. Extra-intestinal
   
   • Cutaneous (EN, PG, conjunctivitis)
   • Arthropathy (SI, migratory polyarthropathy)
   • Stone disease (gallstones, renal stones)
   • Prothrombotic state
   • Liver disease (TPN-NASH, PSC)

Question 43

Discuss the investigation of anal incontinence as it relates to pathophysiology

Answer 43

1. Mechanics and structure
   
   • Defacating proctogram
     
     • Gives information about the pelvis floor, can detect rectocoele, intussusception.
2. Anal Anatomy
   
   • Endoanal USS
     
     • Identifies sphincteric injuries
     • Provides information about support structures (puborectalis, transversus perineii)
   • Endoanal MRI
     
     • Very good for external sphincter
3. Physiology
   
   • Anal manometry
     
     • Resting anal tone
     • Voluntary and involuntary squeeze pressures
     • Rectal distension sensitivity
   • Pudendal nerve motor latency testing - not useful
   • EMG as part of SNS testing.

Question 44

Describe the classification of Ulcerative Colitis

Answer 44

The Montreal Classification:

• E1 - Ulcerative proctitis (25%)
• E2 - Distal Ulcerative Colitis, up to splenic flexure (50%)
• E3 - Pancolitis, beyond splenic flexure (25%)
• S0 - Asymptomatic
• S1 - Mild UC - Passage of 4 or fewer stools per day, no systemic symptoms, no WCC/CRP
• S2 - Moderate UC - >4 stools per day but minimal signs systemic toxicity
• S3 - Severe UC - At least 6 stools per day, SIRS, low Hb or high inflammatory markers.

Question 45

How is Crohn’s disease distributed?

Answer 45

4 main patterns of distribution:

• Small bowel alone 30-35%
• Colon alone 25-35%
• Both (usually ileocolic) 30-50%
• Perianal lesions in >50%
• Elsewhere (duodenum, oral, etc) 5%

Question 46

How do you classify anorectal sexually transmitted infections?

How are they treated?

Answer 46

1. STDs with proctitis:
   
   • Gonorrhoea (Rx Ceftriaxone)
   • Chlamydia (Rx Azithromycin)
   • Herpes simplex virus (Rx Aciclovir)
   • Syphilis (Rx Penicillin)
2. STDs with ulcers:
   
   • AIDS-associated ulcers (Rx symptomatic)
   • Lymphogranuloma venereum (Rx Doxyclycline 21 days)
   • Primary syphilis (Rx Penicillin)
   • Chancroid (haemophylis ducreyi) (Rx Azithromycin)
   • Granuloma inguinale (Rx Doxycycline)
   • Herpes simplex virus (Rx Aciclovir)
3. STDs with fistulas:
   
   • Lymphogranuloma venereum (Rx Doxycycline 21 days)
   • Complex Bushke-Lowenstein tumours (giant condyloma accuminatum) (RTx or surgery)
   • AIDS-associated fistulas (Rx AIDS meds)

Question 47

What are the causes of anal stenosis

Answer 47

Neoplastic

1. Adenocarcinoma
2. SCC
3. Paget’s
4. Melanoma

Inflammatory

1. HPV
2. Crohn’s disease
3. TB
4. Actinomycosis

Iatrogenic

1. Post surgery for haemorrhoids, fissue, fistula-in-ano
2. Radiation

Congenital

1. Anal atresia
2. Imperforate anus

Question 48

What is in St Mark’s formula?

Answer 48

To one litre of water add:

• 20g of glucose (6 TBSPs)
• 3.5g of sodium chloride (~heaped tspn)
• 2.5g of sodium bicarbonate (~level tspn)

Question 49

What is in “Proctosedyl”?

What is in “Ultraproct”?

Answer 49

Hydrocortisone 0.5% + Cinchocaine 0.5%

Cinchocaine 0.5% + fluocortolone hexanoate 0.095% + fluocortolone pivalate 0.092%

(both are banned sports substances!!)

Question 50

Describe your approach to siting a stoma

Answer 50

Placing a stoma in the correct site is crucial for minimizing appliance application difficulties.

Using the stoma appliance, a site should be marked on the skin within the right (ileostomy) or left (colostomy) lower quadrant rectus muscle outline on the infraumbilical fat roll. The patient should be observed in a sitting position, which allows full apposition of the faceplate, specifically away from the costal margin, anterior superior iliac spine, umbilicus, and any scars or creases on the abdominal surface.

Below the belt line is preferable as the bag can be hidden.

If morbidly obese, use the upper quadrants.

Question 51

What are the complications of ileo-anal J-pouches?

Answer 51

• Pouch failure in ~5-10%
  
  • Pouchitis
    
    • ~50% will suffer from this at some point
    • Treated with ABx and anti-inflammatory enemas, predisposes to dysplasia.
  • Poor function
    
    • Expect 6-8 BM per 24 hours
    • Tendency to improve over time
  • Pouch complications
    
    • Sepsis from leak
    • Stricture at anastomosis ~5-20%
    • Fistula to vagina or sinus to pelvis

Question 52

Which antibodies are used in the investigation of IBD?

Answer 52

1. Anti-saccharomyces-cervisiae antibodies (ASCA)
2. Perinuclear antinuetrophil-cytoplasmic antibody (p-ANCA)

ASCA is positive in 35-50% of Crohns versus 1% of UC. Specificity is around 90%.

p-ANCA is raised in UC, with sensitivity of 55% and specificity of around 90%.

Question 53

Describe some of the pathophysiological anatomical features often seen in rectal prolapse?

Answer 53

1. Diastasis of levator ani
2. Abnormally deep pouch of Douglas
3. Redundant sigmoid
4. Patulous anal sphincter
5. Loss of sacral attachments

Question 54

Describe the pathophysiology of Crohn’s disease and Ulcerative colitis.

What are the differences between the two?

Answer 54

The pathophysiology of Crohn’s diseaseand Ulcerative colitis is incompletely understood; the most widely accepted hypothesis purport both as immune-mediated conditions in genetically susceptible individuals, where disease onset is triggered by environmental factors that perturb the mucosal barrier, alter the healthy balance of the gut microbiota, and abnormally stimulate gut immune responses.

Whereas Crohn’s disease may affect any part of the GI tract, UC typically affects the rectum and demonstrates contiguous spread proximally, only involving the mucosal layer. Crohn’s therefore causes “skip lesions” and “cobble-stoning”, whereas UC is more uniform.

Because Crohn’s is transmural, it may cause stricturing or fistulating disease, which is not demonstrated by UC.

Macroscopically, Crohn’s is characterised by trans-mural inflammation, lymphocytic infiltration, and non-caseating granulomata.

Question 55

Outline your approach to the management of fulminant colitis

Answer 55

1. Establish the diagnosis and severity
   
   • Montreal or Truelove and Witt criteria
   • Exclude infectious causes inc. C. diff.
2. Optimise metabolic and medical management
   
   • Fluid resuscitation
   • NG tube and IDC
   • Involve Colorectal and Gastro
   • Optimise nutrition
   • Steriods; Prednisone 60mg or Hydrocort. 300mg per day
   • Antibiotics; Cipro and Metronidazole (ID)
   • VTEP
   • Cyclosporine or Infliximab as per IBD team
3. Indications for surgery
   
   • Toxic megacolon
   • Failure to respond to best medical therapy after 4-7 days
4. Type of surgery
   
   • Total abdominal colectomy with end ileostomy
   • Either a mucous fistula or a Malecot per rectum
5. Technical points
   
   • Midline to preserve stoma sites
   • Cautious handling, especially at flexures
   • Preserve the ileocolic for pouches
   • Take the rectum at the sacral promontery
   • Do NOT open the pelvis

Question 56

What are the success rates for colonic embolization for lower GI bleeding?

What are the rates of colonic necrosis?

Answer 56

• 82-97% success rate when bleeding point identified
• 7% risk of colonic ischaemia

Question 57

What is the aetiology and pathogenesis of pseudomembranous colitis?

Answer 57

• broad spec abx, particularly penicillins, cephalosporins and clindamycin, leads to changes in normal colonic flora with resultant overgrowth of other commensals
• toxins & bacterial activity causes inflammation –> results in pseudomembranes composed of bacteria, fibrin, mucous and neutrophils from intercrypt erosions
• oedema and extensive lamina propria neutrophil infiltration
• rectum spared in 1/4 of cases
• usually caused by Cdiff, a spore forming anaerobic gram positive organism; also salmonella, candida and staph aureus
• C Diff is resident in the gut of 3% of general population and 10% of pts in hospital
• produces cytotoxins A (enterotoxin) and B (cytotoxin) which causes inflammation & mucosal damage

Question 58

What is your initial management for suspected pseudomembranous colitis?

Answer 58

• confirm dx w stool spec
  
  • for C Diff undertake GDH (glutamate dehydrogenase) for screen: if neg then no C diff
  • if positive test toxin A/B: if positive then C Diff
  • if negative can do PCR if clinical suspicion which can say there is toxigenic C Diff present but not producing toxin
• flexi sig: elevated yellow pseudomembranes w mucosal alteration
• correct fluids & electrolytes, contact isolation, stop abx ideall, start metronidazole 400mg po tds for 14 days
• monitor for complications such as toxic megacolon or perforation & avoid antiperistaltics

If initial management fails:

• vancomycin 125mg qid
• adjuncts to normalise colonic flora
• consult ID &U exclude resistant strain, consider vanc enemas
• cholestyramine may be useful in refractory cases as binds toxin
• 20% will require colectomy
• if coloectomy, mortality rate 35-80%
• recurrence in 20%
• consider faecal transplant

Question 59

Discuss genetics in Crohn’s

Answer 59

• strongest risk factor for development of disease = first degree relative w Crohns
• greater concordance for IBD in monozygotic cf dizygotic twins
• clinical pattern of disease (type, extent, extraintestinal manifestations) often concordant amongst relatives
• relatives of pts w Crohns also have increased risk of UC; polygeneic disorders that share some susceptibility genes
• >70 genes assoc w Crohn’s identified; one of those most strongly & frequently replicated = NOD2
  
  • NOD2 = associated w ileal disease, younger age at onset, ileocaecal resections & reop, and displays ethnic variation
  • NOD2 variants prob impair innate immune system at the mucosal level, limiting ability to deal w some gut microbiota

Question 60

Discuss the pathogenesis of Crohn’s

Answer 60

• gut normally exists in state of tolerance to stream of microbial, dietary and other antigens in contact w mucosa but this tolerance & ability to suppress an immune-mediated inflam response = lost in IBD
• in Crohn’s there are defects in immunoregulation and increased mucosal permeability secondary to leaky paracellular pathways
• defects in immunoregulation may include:
  
  • disturbed innate immune mechanisms at epithelial barrier
  • problems w antigen recognition & processing by dendritic cells
  • effects of psychosocial stress via neuroimmunological interaction
• cell-mediated response in Crohn’s is predominant
  
  • excessive activation of effector T cells (Th1) that predominate over regulatory T vells (Th3, T3) that turn off processes
  • T cells release proinflammatory cytokines which stimulate macrophages to release TNF alpha, IL-1, IL-6 and abnormal dendritic cell function may further drive inflammatory response
  • leukocytes enter from local circulation releasing further chemokines, amplifying inflammatory response
  • local & systemic response includes fever, acute phase response, hypoalbuminaemia, weight loss, increased mucosal epithelial permeability, endothelial damage, increased collagen synthesis
  • due to immune dysregulation, the inflammatory response in the intestinal mucosa proceeds unchecked –> chronic inflammatory state

Question 61

What is the distribution of Crohn’s disease

Answer 61

SB alone 30%, colon alone 30%, SB and colon 40%

Perianal 50%

Stomach & duo 5%

Can also include mouth, oesophagus, appendix

Extraintestinal manifestations

Question 62

What are the macroscopic features of Crohn’s?

Answer 62

Macroscopic

• stiff, thick-walled segment of bowel with fat wrapping +/- upstream dilatation (part of connective tissue changes that affect all layers of bowel wall)
• can have fibrinous exudate & adhesions on serosal surface (bc full thickness inflammation)
• skip lesions - areas of grossly normal bowel
• aphthous ulcers (usu develop on surface of submucosal lymphoid nodules) - earliest macroscopic lesions
• ulceration - discrete & serpiginous linear ulcers usu run along mesenteric aspect of lumen –> deep fissuring from linear ulceration may lead to formation of fistulae through bowel wall
• narrow linear ulcers w intervening islands of oedematous mucosa = cobblestone mucosa
• strictures (may be stiff like hose pipe w turgid oedema or tight fibrotic strictures from burnt-out inflammation)
• fistulae, sinuses & abscesses often present in ileocaecal region but may arise from any segment of acute disease & communicate w other loops of bowel, stomach, bladder, vagina, skin or intra-abdo abscess cavities

Question 63

What are the microscopic features of Crohn’s and UC?

Answer 63

Crohn’s

• mucosal & submucosal oedema
• full thickness/transmural inflammation with chronic inflammatory infiltrate
• skip lesions
• focal crypt abscesses
• mucosal lymphoid aggregates w overlying ulceration (aphthous ulcers)
• preservation of goblet cell mucin
• deep non-caseating granulomas w Langerhan’s giant cells - appear late, only in 60-70% - diagnostic unless adjacent to ruptured crypts

​UC

• diffuse inflammation w/o intervening normal mucosa (no skip lesions), involving only mucosa & lamina propria
• goblet cell depletion
• crypt distortion and abscesses
• no deep fissuring ulcers

Question 64

What are the endoscopic/macroscopic appearances in UC?

Answer 64

• quiescent phase - mucosa appears relatively normal except for neovascular changes
• mild inflammation - oedema, erythema, abnormal mucosal vascular pattern
  
  • loss of vasc pattern (submucosal vessels seen through transparent mucosa) = as a result of mucosal oedema (makes it appear opaque)
  • oedema can also cause fine granularity - stippled appearance
• mod inflammation - superficial erosions, ulcerations and contact bleeding from scope trauma
  
  • inflamed & regenerated mucosa surrounded by ulcerations –> development of pseudopolyps
• long-standing chronic inflammatory changes
  
  • ‘featureless microcolon” - mucosal atrophy, muscular hypertrophy, decreased luminal diameter, loss of haustral folds
• continuous inflammation from rectum, confined to rectum & colon
  
  • can get rectal sparing if trans-annaly applied anti-inflam agents
  • backwash ileitis only in cases w extension to IC junction

Mayo score:

• grade 1 = normal endoscopic appearance
• grade 2 = slightly more erythematous
• grade 3 = even more erythematous w touch bleeding
• grade 4 = significant bleeding & friability

(as disease becomes more severe there’s increasingly erythematous mucosa w progressive mucosa ulceration)

Question 65

Aetiology of UC?

Answer 65

IBD in general is an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host

Aetiology in UC still a bit mysterious; multiple factors potentially causative/protective; include

• diet - no consensus
• alcohol - inverse effect
• smoking - ex smokers 70% more likely to develop than never smokers but in those that have it, smoking is protective against disease severity & those who quit = more likely to relapse
• hygiene hypothesis - more common in urban pops, indoor living, smaller families & middle upper SES
• antibiotic use - children w UC more likely to have had abx in 1st yr of life
• genetic predisposition - 29% of those w 1st degree rel get it; 10-20% of those w UC have 1st degree rel

Question 66

What is the distribution of UC?

Answer 66

Varies by geography but in US: 46% proctitis/proctosigmoiditis, 17% left-sided colitis, 37% pancolitis.

Question 67

What are 5-aminosalicylates and what is their role in IBD?

Answer 67

• Mesalazine (pentasa, asacol) = most common here
• come in variety of forms - tablets, granules, suppositories, enemas
• MOA unclear
• well tolerated; diarrhoea 3%, headache 2%
• UC:
  
  • induce and maintain remission in mild-mod UC
  • rectal more effective for distal UC
  • combination oral/rectal most effective
• Crohn’s
  
  • little evidence, not really used
  • minor benefit in mild colonic Crohn’s

Question 68

What are thiopurines and how are they used in IBD?

Answer 68

• Azathioprine or 6MP
• don’t induce remission but maintain it and decrease amount of steroids & hospitalisation
• MOA
  
  • inhibit purine synthesis
  • inhibit T&B cell proliferation
  • induce T cell apoptosis
• Adverse effects: nausea 2%, leucopenia 2-5%, hepatitis 2%, panc 1%, serious infections 8%, Non-Hodgkin’s lymphoma 0.04%, non-melanoma skin cancer 0.2%
• Azathioprine is metabolised to 6-MP which in turn is metabolised to one of 3 other things
  
  • if 6-MP high, can get hepatitis
  • if TPMT enzyme absent, get high 6-thioguanines and leucopenia
  • NUDT15 enzyme = more recently identified; if defective also get leucopenia (with normal TPMT enzymes, Asian pts)

Question 69

What is the role of methotrexate in IBD?

Answer 69

• folic acid analogue
• induces & maintains remission in Crohn’s
• less data in UC
• toxicity: nausea/headaches, hepatotoxicity/myelotoxicity, pneumonitis, teratotoxicity
• not used v often

Question 70

What is the role of cyclosporine in IBD?

Answer 70

• Calcineurin inhibitor
• rescue therapy for severe steroid refractory UC; only used for 3mo - not efficacious after this and also quite a toxic drug
• bridge to thiopurine maintenance
• toxicity: nephrotoxicity, HTN, neurotoxicity, infections, drug interactions

Question 71

What are the indications for, benefits of and adverse effects of biologics in IBD?

Answer 71

• Indications
  
  • inflammatory Crohn’s disease refractory to steroids & AZA/MP/MTX
  • refractory fistulising Crohn’s disease
  • acute severe UC failing IV steroids (IFX only)
  • mod-severe chronic UC failing 5-ASAs/thiopurine
• Benefits
  
  • induce clinical remission
  • maintain clinical remission
  • achieve mucosal healing
  • reduce drainage & heal fistulae
  • reduce need for steroids
  • reduce rate of hospitalisation and surgery
  • improve QOL
• Adverse effects:
  
  • infusion site reactions (3-20%)
  • serious infections 3%
  • TB (0.05%) - screen for this before starting
  • melanoma (0.1%)
  • MS, heart failure, severe liver injury (case reports)
  • don’t start if demyelinating disease eg MS or severe HF
• if loss of response to anti-TNF
  
  • measure trough drug levels and anti-drug antibodies
  • if therapeutic drug levels - switch out of class
  • if sub-therapeutic drug levels and ADA present, switch to another anti-TNF
  • if sub-therapeutic drug levels and ADA absent, dose escalate

Question 72

Categorise the causes of colitis

Answer 72

Most common:

• Infective colitis (usually self limiting)
• Ischaemic colitis

Infective

• Bacterial
  
  • Campylobacter
  • Clostridium
  • E. coli
  • Salmonella
  • Shigella
  • Vibrio cholera
• Viral
  
  • Rotavirus (resthomes)
  • CMV (immunocompromised)
• Parasitic
  
  • Amoeba
  • Giardia
  • Cryptosporidium
  • Schistosomiasis

Non Infective:

• IBD
• Ischaemic colitis
• Diversion colitis
• NSAID induced
• Behcet’s disease
• Collagenous colitis

Question 73

How is colitis severity classified?

Answer 73

Both the Montreal and Truelove & Witt classification systems use a combination of clinical and biochemical parameters to assess severity.

Mild

Patients with mild clinical disease have four or fewer stools per day with or without blood, no signs of systemic toxicity, and a normal erythrocyte sedimentation rate (ESR). Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease.

Moderate

Patients with moderate clinical disease have frequent loose, bloody stools (>4 per day), mild anemia not requiring blood transfusions, and abdominal pain that is not severe. Patients have minimal signs of systemic toxicity, including a low-grade fever. Adequate nutrition is usually maintained, and weight loss is not associated with moderate clinical disease.

Severe

Patients with a severe clinical presentation typically have frequent loose, bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5°C), tachycardia (HR ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30 mm/hour). Patients may have rapid weight loss.

Question 74

Categorise treatment options for anal incontinence

Answer 74

1. Conservative measures
   
   • Dietary and bulking agents
   • Biofeedback and pelvis floor training
   • Anal plugs
2. Injectable bulking agents
   
   • May enhance other efforts but probably no use
3. Sphincter surgery
   
   • Sphincteroplasty
   • Artifical sphincter systems
   • Magnetic link systems
   • Sacral nerve stimulation
4. Colostomy or ACE