Gastroenterology Flashcards
Indications for treatment in Haemachromatosis either with;
- Phlebotomy
- Chelation (if unable to undergo phlebotomy)
Ferritin persistently > 500 (Absolute if >1000)
End Organ involvement
- Liver: LFT derangement, biopsy or MRI
- Cardiac: MRI
Indications for Liver Biopsy in Haemachromatosis
Abnormal LFTs
Ferritin >1000
Hepatomegaly or other signs of CLD
Indications for chelation
Phelbotomy contraindicated
- Severe Anaemia
- Haemodynamic Compriomise
- Limited life expectancy
Findings of NASH on liver biopsy
Hepatic Steatosis
Hepatic Ballooning
Hepatic lobular degeneration
Findings of NAFL on liver biopsy
Steatosis with hepatocyte balling or portal inflammation (but not both)
Findings of Cirrhosis on liver biopsy
Bridging fibrosis
Stellate cell activation
Findings of PBC on liver biopsy
Peri-portal inflammation
Findings of ASH on liver biopsy
Steatosis
Mallory Hyaline bodies
Findings of AIH on liver biopsy
Interface hepatitis
Portal tract inflammation (lymphocytic, plasma cells and multinucleate giant cells)
HCC screening surveillance benefit
Hepatitis B carriers - Asian males >40 - Asian females > 50 - Family hx of HCC - With cirrhosis African/North American blacks with Hep B Cirrhosis - Hepatitis C cirrhosis - Genetic Haemachromatosis - Alpha 1 antitrypsion Stage 4 PBC
HCC screening algorithm
6 monthly ultrasound +/- AFP
Lesion found of US
<1cm: Repeat U/S in 3 months
>1cm: CT or MRI
Primary Billiary Cirrhosis diagnostic criteria
2/3
- ALP elevated
- AMA elevated
- Histology of biopsy (Peri-portal inflammation)
Treatment for PBC
Urosodeoxycholic Acid
Main side effects of PPI’s (eight)
1) Pneumonia
2) Gastroenteritis
3) Osteoperosis
4) Hypomagnasaemia
5) Interstitial nephritis
6) Microscopic colitis
7) C Diff Colitis (more likely to get recurrent C Diff colitis if on PPI)
8) Hypergastrinaemia - unknown clinical effect
Diagnosis of Zollinger Ellison Syndrome
1) Fasting Gastrin >10000
2) Gallium 68 Dotate CT-PET
Note: 1/3 patients with ZE have MEN 1
Diagnostic test for chronic pancreatitis
Faecal elastase
Note Faecal elastase is not disrupted by creon.
Hereditary pancreatitis
Autosomal dominant
Recurrent mild attacks of pancreatitis age > 5
Chromosone 7q35
Pre-malignant pancreatic cysts
1) IPMN: Location - head of pancreas
2) MCN: Tail of pancreas.
Both Mucin producing and pre-malignant
Risk factors for pancreatic cancer
1) Modifiable > Smoking 2) Non-modifiable > Cystic Fibrosis > BRCA1/2 > Lynch Syndrome > FAMMM > Hereditary pancreatitis > Peutz-Jeghers syndrome > Familial history of pancreatic cancer
Findings of Esophageal Eosinophilia on histology
> or equal to 15 intraepithelial eosinophils per high powered field
Finding on biopsy of IBD
Architectural change
Lymphoplasmacit infiltrate
Which gene is associated with chrons disease
NOD2
They have more fibrostenotic complications of the bowel
Smoking effect on CD vs UC
CD:
- Refractory
- Fistulising disease
- Surgical recurrence
–> smoking cessation is a therapy for CD
UC
- protective
Which subset of IBD has the worst risk of cancer?
Patients with PSC
Colonoscopy’s in patient sixth IBD
3 yearly baseline (Commence 8 years after diagnosis)
Annually
- PSC
- Fhx CRC in first degree relative <50 yo
- Colonic stricture or multiple pseudopolyps
- Active Disease
- Prvious dysplasia
ASCA vs ANCA for differentiating UC from CD
pANCA+/ASCA- = Ulcerative Colitis ASCA+/pANCA- = Chrons Disease
Therapy for UC
First line: 5ASA (oral + rectal)
Second line: Thiopurines (if patients need more than 1 Course of steroids in a year)
Third line: Infliximab/Vedolizumab
Can use corticosteroids
Chron’s Disease therapy
Individualised approach
Treat to target approach
Steroids: Induction
Steroid sparing agents: Thiopurines, methotrexate
ASA not effective
Adverse effects of ASA
Intersitial nephritis (annual UEC)
Diarrhoea
Azospermia (reversible)
Steroids in IBD
Only for induction, not for maintenance
Prednisolone 40mg/day with slow taper
Nb Budesonide good in mild ileocolonic CD or UC - releases at the ileum with high first pass metabolism (not on the PBS)
Risk of elevated 6MMPR metabolite
Hepatoxicity (measure metabolites)
Measure TPMT prior to commencement, rationale being that if there are low TPMT they are at risk of rapid leukopenia.
Heterozygotes - half the dose
Which metabolites of Azathioprine has a therapeutic effect in IBD
TGN
Adverse effects of thiopurines
1) Myelo suppression
2) Hepatitis
3) Pancreatitis
4) Nausea/Vomiting
5) Lymphoma - hepatosplenic t-cell lymphoma
6) Non-melanoma skin cancers
Thiopurine metabolite testing
High MMP, Low TGN = shunter
Given allopurinol
Which drugs are responsible for hepatosplenic t-cell lymphoma in young males with IBD?
Thipurine + Anti-TNF
What does adalimumab target
TNF (anti-tif drug)
Vedolixumab better in CD or UC?
UC
Ustekinimab use in Australia
CD
Anti-TNF drugs for fistulizing CD
1) Infliximab or adalimumab
Adverse effects of Anti-TNF
1) Reactivate TB (need screening prior)
2) Lymphoma
3) Melanoma (!!!)
4) Demyelinating disorders
5) Lupus like syndrome
6) Heart failure in pre-existing NYHA 3-4
Vedolizumab mechanism of action
Blocks alpa4beta7-MADCAM which stops diapesis of the T cells into the gut tissue
Gut specific = no systemic immunosuppression
UC or CD
Ustekinumab mechanism of action
Blocks IL12/23 via p40 subunit
Biologics in IBD
TNF blockers
Vedolizumab
Ustekinumab
Only indication for Fecal transplant (FMT)
Refractory C.Diff
Which treatments for IBD increase risk of skin cancer?
1) TNF: Melanoma
2) Thiopurines: Non-melanomatous skin cancer
Acute severe ulcerative colitis
Initially
1) QID hydrocortisone
2) Clexane
3) IV Fluids
4) Aim HB>100
Flexible sigmoidoscopy for CMV
No response at 3-5 days
1) Surgery
Nb: Mortality = 1%
Which treatment do you start in peri-anal disease with CD
Anti-TNF (Infliximab)
Indication for C-section in patients with CD
Active perianal disease
Safest biologic during pregnancy
Anti-TNF
Vaccinations at diagnosis for patients with IBD
“the big five”
1) Hep B
2) HPV
3) VZV - note live and therefore not able to be given on immunomodulator
4) Pneumococus
5) Infuenza
Indications for 6 monthly ultrasound screening in Hep B
1) Cirrhosis
2) Asian male >40
3) Asian female >50
4) African descent
5) HBD +
6) First degree family member with HCC
Treatment indications for Chronic Hep B
1) HBE Ag+
- HBV >20,000 DNA
- ALT > 2 times ULN
2) HBE Ag-
- HBV >2,000
- ALT >2 times ULN
Which is the most suggestive of chron’s disease over ulcerative colitis?
Perianal fistula
Best first test in patient with chronic diarrhoea?
Fecal calprotectin
(released by neutrophils migrating into the lumen)
Early predictor of flares
Which extraintestinal manifestation is most highly associated with disease activity in CD
large joint arthritis (knees, hands and wrists)
Treatment for Pyoderma Gangrenosum
Topical steroids
Topical Tacrolimus
Treatment for PSC
Liver Transplant
HLH On azathioprine (thiopurines)
Commonly triggered by EBV infection
Oxford criteria for failure of treatment for acute sever UC
- > 8 stools per day
- Ongoing blood in stool
- CRP > 44
How does Vedolizumab act?
Binds to and inhibits alpha 4 beta 7 trafficking into the gut
Follow up colonoscopy for
> 1-2 adenomas <10mm with no villous/high grade dysplasia
> 3-4 or any with villous, high grade dysplasia or >10mm
> 5-9
> 10+
As per the Cancer Council Guidelines > 1-2: 5 years > 3-4 or concerning features: 3 years > 5-9: 1 year > 10+: <1 year
Grades of immunotherapy induced colitis (number of stools greater than normal)
> Grade 1: < 4 movements/day > Grade 2: 4-6 bowel movements/day > Grade 3: 7 bowel movements/day > Grade 4: Life threatening hypovolaemia or electrolyte disturbance > Grade 5: Death
Treatment for checkpoint induced colitis
Always exclude infectious cause of diarrhoea
Grade 1: Symptomatic management (loperamide), continue ICI
Grade 2: Observation, withhold ICI
Grade 3: Oral prednisone 1mg/kg, withhold ICI (asses response at D5)
Grade 4: IV methylprednisone 1mg/kg, withhold ICI (assess response at D3)
If failure to improve at the discussed reassessment period (usually 72 hours) then consider starting steroid sparing agent, i.e Infliximab at 5mg/kg. There can be two doses of Infliximab given.
For grades 3-4 checkpoint inhibitors should be permanently discontinued.
