Gastro SCE Flashcards
1
Q
Forrest classification, description and rebleed risk
A
IA: active haemorrhage, 23.6% rebleed risk
IB: ooze, 19% rebleed risk
IIA: visible vessel, 19.5% rebleed risk
IIB: adherent clot, 17% rebleed risk
IIC: haematin base, 9.7% rebleed risk
III: clean base, 1.1% rebleed risk
2
Q
Based on forrest classification, which ulcers ALWAYS require dual endoscopic therapy?
A
IA (active haemorrhage), IB (ooze), IIA (visible vessel)
3
Q
How do you endoscopically manage a IIB ulcer?
A
Cold snare to remove clot followed by therapy according to revealed forrest classification OR 72 hour PPI infusion
4
Q
List the features, and scoring for the Glasgow blatchford score
A
Urea
6.5-8 +2
8-10 +3
10-25 +4
>25 +6
Haemoglobin
- Men
>130 +0
120-130 +1
100-120 +3
<100 +6
- Women
>120 +0
100-120 +1
< 100 +6
Systolic blood pressure
≥110 +0
100-109 +1
90-99 +2
<90 +3
Pulse ≥ 100 +1
Melaena +1
Syncope +2
Cardiac disease +2
Liver disease +2
5
Q
List the features and scoring of the Rockall (pre-endoscopy) score
A
Maximum 7
Age
<60 +0
60-79 +1
≥80 +2
Shock
No shock +0
Tachycardia only HR >100 +1
Hypotension SBP <100 +2
Comorbidities
Any major co-morbidity +2
Renal failure, liver failure, disseminated malignancy +3
6
Q
What are the additional features and scoring post endoscopy that make up the complete Rockall score?
A
Total max (11)
Diagnosis
Nil or mallory weiss +0
All other diagnoses +1
Malignancy of upper GI tract +2
Signs of GI haemorrhage
Dark spot only +0
Blood in upper GI tract +2
Adherent clot +2
Visible vessel or spurting +2
7
Q
What percentage of peptic ulcers are H Pylori associated?
A
55-70%
8
Q
What duration can you leave in a Sengstaken-Blakemore tube?
A
24-36 hours
9
Q
What are the benefits of DANIS/SEMS over balloon tamponade?
A
- safer + just as effective
- can remain in for up to a week
- can resume oral intake after deployed
10
Q
Label these varices
A
11
Q
What conditions is angiodysplasia associated with?
A
Aortic stenosis - (+acquired coagulopathy = Heyde’s syndrome, occurs in elderly patients)
VW disease
ESRF
Ventricular assist devices
Hereditary haemorrhagic telangiectasia
12
Q
Based on shock index (and define this), what is an unstable bleed?
A
Shock index ≥1 (HR / systolic blood pressure)
13
Q
What is the most common GI malformation, and what is it’s prevalence?
A
Meckel’s diverticulum
Most common GI malformation - prevalence 0.3-2.9%
14
Q
What is the anatomical location of Meckel’s diverticulum?
A
Mid-distal ileum (within 2 feet / 61cm of IC valve)
15
Q
What is the embryological origin of Meckel’s diverticulum?
A
Remnant of omphalomesenteric duct which connects midgut to yolk sac in fetus
16
Q
What is the vascular supply to Meckel’s diverticulum?
A
Rich blood supply from vitelline artery (branch of SMA)
17
Q
What are the complications of Meckel’s diverticulum?
A
Bleeding, pain, and obstruction
18
Q
What predisposes Meckel’s diverticulum to bleeding?
A
Often associated with ectopic gastric tissue (sometimes pancreatic), with increased acid production
19
Q
What are the diagnostic options for Meckel’s diverticulum?
A
CT but not always works
Histo from surgical specimens
99m technetium pertechnetate scan (Meckel’s scan), but requires functional ectopic gastric mucosa
20
Q
What is the management of Meckel’s diverticulum?
A
Surgical excision
21
Q
What percentage of people will experience PR bleeding after pelvic radiotherapy?
A
50%
22
Q
What are the endoscopic features of radiation proctitis?
A
Pale mucosa
Telangiectasia
Oedema
Ulceration
+/- scarring
23
Q
What are the histological features of radiation proctitis?
A
Fibrosis of the lamina propria
Variable degree of epithelial injury, crypt distortion, and Paneth cell metaplasia
Lack of inflammatory cell infiltrate
24
Q
What is the management of radiation proctitis?
A
Conservative
- Optimise bowel function, stool softeners
Topicals
- Sucralfate enemas
- PR metronidazole
Endoscopic: APC, heat, formalin
Hyperbaric oxygen
25
What are the criteria for pre-emptive TIPSS?
Variceal bleed
AND
Child-Pugh C 10-13
OR
Child-Pugh B 8-9 AND active variceal haemorrhage at the time of endoscopy
DESPITE use of terlipressin / other vasoactive agents (as rebleed risk very high)
26
How long can the effect of warfarin typically last for?
3-5 days
27
What is the approach to reversal of warfarin in an unstable bleed?
Prothrombin complex concentrate (e.g. beriplex, octaplex) - 25-50 units/kg & vitamin K
28
What is the approach to reversal of warfarin in an stable bleed?
Withhold wafarin, vitamin K
29
What is the approach to restarting warfarin post procedure after haemostasis achieved following an upper GI bleed)?
Low thrombotic risk (e.g. AF) consider restarting warfarin only after 7 days
High thrombotic risk (e.g. valves, mitral stenosis, <3 months VTE) consider LMWH at 48 hours
30
What is the approach to aspirin after GI bleed and post-procedure?
Permanently discontinue if for primary prophylaxis
Generally continue throughout if for secondary prophylaxis
If stopped, it should be restarted as soon as haemostasis is achieved
31
What is the approach to clopidogrel management after GI bleed and after haemostasis achieved?
For DAPT in patients with coronary stents should be in liaison with cardiology
If stopping, even if unstable bleed, aspirin should continue
Should restart in 5 days after haemostasis achieved
32
For what DOACs can andexanet work as reversible, and what are it's indications?
Rivaroxaban & apixaban, life threatening bleeds
33
What reversal agent can be used for life threatening bleeds associated with dabigatran?
Idarucizumab 5mg
34
What is the reversal agent for edoxaban?
None. Can try 50ui/kg 4F-prothrombin complex concentrate
35
What risk stratification tool can be used for lower GI bleeding, and what is the utility of it?
Oakland score ≤8 consider discharge
36
What is the approach to patients on UFH presenting with GI bleed?
Unfractionated heparin - 12 hour effect
Can usually just discontinue
Severe bleeds: protamine sulfate
37
What is the approach to LMWH after GI bleeding occurs?
LMWH - 24 hour effect
Can usually just continue
Protamine sulfate less effective than in UFH
38
For low risk endoscopic procedures, what is the target platelet count?
30
39
What is an alternative to platelet transfusion for platelet incrementation pre-procedure? How does it work?
Eltrombopag = thrombopoeitin receptor antagonist
40
What endoscopic procedures carry a high risk of bleeding?
Endoscopic polypectomy
ERCP with sphincterotomy
Ampullectomy
EMR
ESD
Lower GI stricture dilatation
Endoscopic therapy for bleeding (especially varices)
EUS biopsy/intervention
Oesophageal/gastric RFA
PEG insertion
41
What endoscopic therapies carry a low risk of bleeding?
Diagnostic procedures +/- biopsy
Biliary/pancreatic stenting
Device assisted enteroscopy
Oesophageal, enteral or colonic stenting
EUS without biopsy/intervention
42
For what procedures should aspirin NOT be routinely continued?
ESD
>2cm colonic EMR
Upper GI EMR
Ampullectomy
43
What is the approach to clopidogrel pre- and post-endoscopy in high risk procedures in low risk conditions?
Stop 7 days prior, restart 1-2 days after
44
What are the high risk conditions pertaining to antiplatelet usage?
Drug eluting coronary artery stent within 12 months
Bare metal coronary artery stent within 1 month
45
What are high risk thromboembolic conditions with respect to warfarin discontinuation pre-procedure?
Metallic mitral or aortic valves
Prosthetic valve and atrial fibrillation
Atrial fibrillation and mitral stenosis
AF + CVA/TIA with 3+ CV risk factors
AF and CVA/TIA within 3 months
<3 months of VTE
Previous VTE on warfarin
46
What is the approach to warfarin discontinuation pre-endoscopy for a low risk procedures?
Do not discontinue as long as in therapeutic range 1 week prior
47
What is the approach to warfarin discontinuation pre-endoscopy and restarting post-endoscopy for a high risk procedure in a low risk condition?
Stop warfarin 5 days prior to procedure, and check to ensure INR <1.5.
Restart warfarin on the evening of the procedure
48
What is the approach to warfarin discontinuation pre-endoscopy and restarting post-endoscopy for a high risk procedure in a high risk condition?
Stop warfarin 5 days prior
After 2 days bridge with LMWH
Withhold LMWH on morning of procedure
Check INR to ensure INR <1.5 prior to procedure starting
Restart warfarin on evening of procedure with LMWH bridge until therapeutic range achieved
49
What is the approach to DOAC discontinuation pre-endoscopy for low risk procedures?
Omit on morning of procedure
50
What is the approach to DOAC administration in high risk procedures, and restarting post-endoscopy?
Dabigatran, rivaroxaban, apixaban, edoxaban - take last dose 3 days prior to procedure
If Dabigatran crcl 30-50ml/min then last dose 5 days pre-procedure
Restart 2-3 days post procedure
51
What is the most common type of oesophageal cancer worldwide? And what proportion?
SCC (90%)
52
What proportion of oesophageal cancer is adenocarcinoma in high income countries?
2/3
53
Are males or females more commonly affected in oesopageal adenoCa and SCC?
Equal in SCC, significantly more males in adenoCa
54
What lifestyle factors are associated with oesophageal adeno Ca?
Obesity, smoking, NOT alcohol
55
What GI conditions are associated with oesophageal adenoCa?
Barrett's, GORD >5-10 years, hiatus hernia, NOT H pylori
56
What lifestyle factors are associated with oesophageal SCC?
Smoking, alcohol, poor oral hygeine
57
What dietary factors are associated with oesophageal SCC?
N-nitroso compounds (pickled foods), areca nuts, betel quid, hot liquids, low zinc/selenium/folate, low fruit/vegetable intake
58
What GI conditions are associated with oesophageal SCC?
Previous partial gastrectomy, achalasia, atrophic gastritis
59
Which histological subtype of oesophageal cancer is associated with HPV? And which genotypes?
SCC - HPV 16 and 18
60
Describe the T staging for oesophageal cancer
T1a tumour invades mucosa or lamina propria
T1b tumour invades submucosa
T2 tumour invades muscularis propria
T3 tumour invades adventitia
T4a tumour extends outside of oesophagus into pleura, pericardium, diaphragm, peritoneum
T4b tumour invades trachea, spine, aorta
61
What is the investigational approach to staging oesophageal cancers?
PET-CT (for all with potentially resectable disease to exclude nodes)
EUS to stage TN stages including invasion depth
- NB: this may be altered for after endoscopic resection
Tracheobronchoscopy may be required for proximal oesophageal tumours (ie above carina, <25cm from incisors) - to exclude tracheal invasion
Staging laparoscopy indicated for locally advanced (T3/4) GOJ tumours to exclude peritoneal mets
62
What stages of oesophageal cancers can be endoscopically resected? What procedure should be used?
T1a+b N0 M0
- EMR <15mm
- ESD >15mm
63
What stages of oesophageal cancer can theoretically be surgically resected?
T2-4a AND N1-3 AND M0
64
What surgial procedures are used for upper and lower oesophageal cancer resections respectively?
Upper - McKeown
Lower - Ivor Lewis
65
What is the role for chemotherapy and radiotherapy in the management of oesophageal cancer in the non-palliative setting?
Chemoradiotherapy (platinum based) should be used pre- and post-operatively in advanced oesophageal cancer
OR definitive chemoradiotherapy can be as an alternative to surgery in resectable but locally advanced cancers (T2-T4a OR N1-3 M0)
66
What is first line chemoradiotherapy for potentially resectable oesophageal SCC?
Cisplatin + 5FU + RT
67
What is first line chemoradiotherapy for potentially resectable oesophageal adenocarcinoma?
Carboplatin + paclitaxel + RT
68
What are the chemotherapy options for unresectable oesophageal cancers?
SCC
- PDL1 expressing: pembrolizumab or nivolumab
- otherwise cisplatin + 5FU
AC
- cisplatin + 5FU
+ trastuzumab if HER2+
+ nivolumab if PDL1+
69
What are the palliative options for oesophageal cancer?
Fully covered metal stent
Brachytherapy
Chemotherapy
70
What decisions guide the palliative use of stent insertion vs brachytherapy vs chemotherapy in oesophageal cancer?
Chemotherapy
- good PT only
Brachytherapy
- better long-term relief of dysphagia, but not to be used when life expectancy is very short
Stent
- quicker relief of symptoms
- not to be used concurrently with radiotherapy
71
What is a cervical inlet patch histologically?
Heterotopic gastric tissue, usually fundic type
72
What symptoms and signs may be associated with a cervical inlet patch?
Symptoms
- laryngopharyngeal reflux
- globus
Associations
- Barrett's oesophagus
- very rare transformations into oesophageal adenocarcinoma
73
Based on pH studies, how is reflux defined?
Percentage of time oesophagus exposed to ph <4
- Normal <4%
- Inconclusive 4-6%
- Abnormal >6%
DeMeester score (integral of number of events, longest event, overall time exposed to acid)
<14.7 is normal
>14.7 is pathological
74
What types interventions exist as anti-reflux surgery, and what are their benefits?
Nissen fundoplication
- laparoscopic is equally efficacious to open, but shorter hospital stay and lower mortality
Toupet fundoplication
- posterior 270 degree wrap vs 360 for nissen - preferred for patients with dysphagia
Endoscopic - transoral incisionless fundoplication
Laparoscopic magnetic sphincter augmentation
- lower rates of bloating
75
What is the diagnostic definition of Barrett's oesophagus?
Interruption of normal squamous epithelium by columnar metaplasia extending ≥1cm above GOJ, visible endoscopically and histologically
NB: BSG says any columnar type, whereas AGA says has to be intestinal type (defined by presence of goblet cells)
76
What are the risk factors for Barrett's oesophagus?
Demographic
- Age >50
- Males
- White race
Lifestyle
- Obesity
- Smoking
- NOT alcohol
GI conditions
- GORD >5-10 years
- Hiatus hernia
- FHx: barrett’s or oesophageal adenocarcinoma
- NO association with H Pylori
77
What is the prevalence of Barrett's oesophagus?
1.5%
78
What is the yearly risk of progression to oesophageal cancer of Barrett's oesophagus overall, in non-dysplastic cases, and in high-grade dysplasia?
Overall: 0.5%
Non-dysplastic: 0.3%
High-grade dysplasia: 10%
NB: >20% of patients with visible dysplasia will develop metachronous lesions within 2 years (indication for RFA of residual Barrett's)
79
What groups of patients should be screened for Barrett's oesophagus?
Chronic GORD, ≥50 years old and one of the following:
- FHx 1st degree relative
- White race
- Males
- Obesity
- Smoking
80
What is the Prague criteria?
Barrett's endoscopic description
- C: circumferential extent
- M: maximal extent above GOJ (cm)
+ any other islands above main noted columnar segment
81
How should biopsies be taken in Barrett's oesophagus?
Seattle protocol using NBI or acetic acid
- targeted biopsies (distal -> proximal order) of macroscopically visible lesions
+ random biopsies every 2cm, starting 1-2cm above GOJ
82
How should surveillance be arranged for Barrett's without evidence of dysplasia?
Consider discharge if
- maximum length <3cm
- AND gastric metaplasia only seen on 2x OGDs
Every 3-5 years
- maximum length <3cm
- AND intestinal metaplassia
Every 2-3 years
- maximum length ≥3cm
Yearly at regional centre
- maximum length ≥10cm
Stop surveillance at age 75
83
What is the approach if histology of Barrett's segment shows 'indefinite for dysplasia'
Repeat OGD at 6 months, and follow no dysplasia surveillance if no definite dysplasia found (confirmed by 2 different GI pathologists)
84
What is the management, and subsequent surveillance of Barrett's with low grade dysplasia found histologically?
Repeat OGD in 6 months
If no definite dysplasia seen, then repeat OGD in another 6 months + follow pathways according to findings
If confirmed low grade dysplasia then RFA OR cryoablation
After this, 2x subsequent OGDs should confirm Barrett's eradication, then OGD at 2 years, 4 years and then 5 year surveillance (unless recurrence of Barrett's)
85
What is the management of Barrett's with associated high grade dysplasia or low-risk cancer?
If no visible lesion - RFA
If visible lesion
- Band-assisted EMR for Paris 0-IIa/b <2cm without features of submucosal invasion
- ESD if
---> suspicion of submucosal invasion
---> Paris 0-Is/0-IIc
+ all followed by RFA
Then surveillance
- 2x OGDs confirming Barrett’s and dysplasia / cancer eradication
- then OGDs at 6 months, 1 year, 2 year, 3 year, 4 years
86
Fill in the blanks in the Paris classificaiton system
87
What is the histological definition of EoE diagnosis and remission?
Diagnosis: ≥15 eosinophils per HPF
Remission: <15 eosinophils per HPF
88
For accurate EoE diagnosis, what should be done with PPIs pre OGD?
Discontinue for 3 weeks
89
In addition to eosinophilia, what are histological features are supportive of EoE?
- basal cell hyperplasia
- oedema (spongiosis)
- eosinophil microabscesses
- eosinophil layering
- eosinophil degranulation
- subepithelial sclerosis
90
Detail the contents of 2-food, 4-food and 6-food elimination diets, and their indications
EoE management, stepwise increase
2-food: milk and wheat/egg
4 food: milk, wheat, egg, soya
6 food: milk, wheat, egg, soya, nuts, seafood
91
How long after intervention for EoE should repeat OGD + biopsy be performed?
8-12 weeks
92
What is the DeMeester score?
For pH studies it is the integral of number of events, longest event, time exposure to acid
<14.7 is normal
>14.7 is pathological
93
Describe the distribution of striated and smooth muscle in the oesophagus
Upper 1/3: striated
Lower 2/3: smooth
94
Name the key measurements of oesophageal manometry, what they measure, and their normal limits
Integrated relaxation pressure (IRP)
- measure of LOS relaxation during a swallow
- upper limit of normal 15mmHg or 25mmHg (depending on kit)
Distal latency (DL)
- measure of time for a peristaltic wave to propagate
- lower limit of normal 4.5s
Distal contractile integral (DCI)
- measure of contractile vigour in the distal oesophagus (units mmHg/s/cm)
---> Normal: 450-8000
---> Failed: <100
---> Weak: 100-150
---> Hypercontractile: >8000
95
What is the diagnosis?
Achalasia I
96
What is the diagnosis?
Achalasia II
97
What is the diagnosis?
Achalasia III
98
What are the manometric diagnostic features of achalasia I?
Classic type
Non-relaxing LOS
- Raised IRP
Aperistalsis
- complete failure of oesophageal pressurisation, <30mmHg, blue on trace
99
What are the manometric diagnostic features of achalasia II?
Achalasia with oesophageal compression / pressurisation
Non-relaxing LOS
- Raised IRP
Non-motile oesophageal body pressurisation
- 100% failed peristalsis
- ≥20% pan oesophageal pressurisation (green/yellow/red on manometry)
100
What are the manometric diagnostic features of achalasia III?
Spastic type
Non-relaxing LOS
- raised IRP
No normal peristalsis
Spasms
- ≥20% premature contractions (DL <4.5s) of normal contractile vigour (DCI ≥450)
101
What drugs can be used for achalasia?
Calcium channel blockers, nitrates and phosphodiesterase inhibitors were used historically but have very little evidence base and are now recommended against
102
What endoscopic interventions are there for achalasia, and what are their relative benefits/drawbacks?
Botox to LOS
- safe
- effective
- short lived (6 months)
Dilatation
- safe
- effective
- more durable than botox, less than POEM/Heller's
POEM
- higher risk
- higher chance of GORD
- more durable
103
What size balloon should be used for achalasia?
Start with 30mm and then progress to 35mm in same procedure
104
What procedure is preferred for achalasia in the presence of megaoesophagus >6cm?
Heller's myotomy
105
What are the manometric features of GOJ obstruction?
Non-relaxing LOS (raised IRP)
Normal oesophageal peristalsis
106
List the major motor disorders, and their classification based on manometry
Absent peristalsis
- normal IRP
- 100% failed peristalsis
Distal oesophageal spasm
- normal IRP
- decreased DL (<4.5s) on >20% swallows
- normal contractile vigour (DCI 450-8000)
Hypercontractile oesophagus (nutcracker oesophagus)
- at least 2 swallows with DCI >8000
- can be single peaked, jackhammer type, or with vigorous LOS after contraction
107
Fill in the blanks
108
What are the treatments for major motor disorders of the oesophagus?
Drugs
- prokinetics
- CCBs
- nitrates
Botox injections to distal oesophagus
POEM
Surgical myotomy
109
What is the minor motor disorder of the oesophagus, and its definition based on manometry?
Ineffective oesophageal motility
- at least half of contractions have DCI <450
- OR frequent wide breaks in contraction
- OR alternating normal and failed peristalsis
110
What is the cause and geographical location of Chagas disease?
Central and South America
Chronic trypanosoma cruzii infection
111
What is the treatment of Chagas disease
Benznidazole
Treat the symptoms/complications which are already established
112
What are the GI manifestations of Chagas disease?
Progressive destruction of ENS
Oesophageal
- dysphagia with progressive dysmotility, initially with relative distal hypertonicity, and then aperistalsis, with progressive dilatation
Colonic
- constipation with progressive dilatation leading to megacolon/rectum
113
How is acute (Chagas) diagnosed
Thick and thin films with giesma stain
114
What foreign bodies should be endoscopically removed within 2-6 hours?
Oesophageal obstruction
OR batteries or sharp points in oesophagus
115
What foreign bodies should be endoscopically removed within 24 hours, but not immediately?
Objects in the stomach which are sharp, large (>2cm diameter, >5cm length), magnets or batteries
116
Which foreign bodies can be monitored only without intervention
Blunt objects ≤2cm diameter and ≤5cm length
117
What is the diagnosis? What are the symptoms? What are the histological features? What is the treatment?
Lymphocytic oesophagitis
Dysphagia
>20 lymphocytes per HPF, epithelial damage, without granulocytes
As for EoE: PPI or dispersible steroids
118
What is the grading of oesophageal candidiasis?
Kodsi's classification
I: few raised plaques ≤2mm
II: multiple raised plaques >2mm without ulceration
III: confluent, linear and nodular plaques +/- ulceration
IV: grade III + mucosal friability +/- narrowing of the lumen
119
What is the management of oesophageal candidiasis?
Grade I: nystatin
Grade II-IV: fluconazole
Systemically unwell: amphotericin B
120
What are the features of oesophageal lichen planus histologically, endoscopically, and clinically? What is the management?
Typically females, 60-70s
Associated oral/genital lesions
Oesophageal ulcers with lacy appearance of lesions +/- strictures
Histology
- raised IELs
- Civatte bodies (dyskeratotic keratinocytes)
- Junctional split at epithelium and lamina propria
Management
- local steroid injection
- systemic steroids
- dilatations
- ?surveillance due to SCC risk
121
What is the diagnosis, symptoms, aetiology and treatment?
Oesophagitis dessicans superficialis or exfoliative oesophagitis
Symptoms: asymptomatic, dysphagia or vomiting casts of oesophagus
Normal underlying mucosa
Causes
- medications: dabigatran, bisphosphonates, sunitinib
- frailty
- coeliac
- HSV
- GVHD
- amyloidosis
Management
- PPI
- stop offending agent
- treat underlying condition
122
What are the endoscopic and histological diagnostic features of oesophageal pemphigus vulgaris, how does it differ from exfoliative oesophagitis, and what is the treatment?
Similar endoscopic appearance to exfoliative oesophagitis but inflamed underlying mucosa which peels back on biopsy
Histology: tombstoning appearance
Management: steroids / immunosuppression
123
What is the diagnosis? What is the aetiology? What should be done about it?
Oesophageal papilloma
Often HPV associated
Surveillance because of SCC risk is reasonable
124
How should you advise a patient with previous PUD before starting NSAIDs?
Check H Pylori
Recommoned 40mg (full dose) PPI for high risk patients
- >60 years
- PMHx PUD
- Concomitant steroids / anticoagulation
- Comorbidity
125
What is the role of celoxocib as an alternative to NSAIDs?
Could be considered for high risk patients, but must be balanced against adverse CV risk profile (CV death including MI and stroke)
126
Name 4 DDx causes of thickened gastric folds
Menetrier's disease
Linitis plastica
Eosinophilic gastritis
Zollinger Ellison
127
What fasting serum gastrin level would you expect for zollinger ellison syndrome off PPI, and what is the normal range?
>1000 pg/ml
Normal range <55pg/ml
128
What effect would you expect a PPI to have on fasting serum gastrin levels
Intermediate rise >55pg/ml
129
Other than zollinger ellison syndrome, what other causes of (moderately) elevated serum gastrin levels are there?
Atrophic gastritis, pernicious anaemia, gastric outlet obstruction, renal failure, small bowel resection, PPI
130
What pattern of ulceration might you see in zollinger ellison?
D2 or more distally as well as exensive gastric
130
What syndrome is associated with Zollinger Ellison syndrome, and what proportion of Zollinger Ellison patients does it account for?
MEN1 - parathyroid hyperplasia, pituitary adenomas, pancreatic neuro-endocrine tumours
20% of ZES patients have MEN1
50% of MEN1 patients have ZES
131
How might you confirm a diagnosis of zollinger ellison syndrome?
Imaging - MRI pancreas / EUS confirming pancreatic nodule
Endocrine stimulation test - secretin provocation test (failure to suppress gastrin <200pg/ml)
131
In H Pylori, what factors are associated with treatment failure?
- Insufficient gastric acid suppression - ?higher dose twice daily regimens are better
- Raised BMI (decreased drug bioavailability)
- Active smoking (decreased drug bioavailability)
- Host genetic factors - Host IL1beta-511 polymorphism (T/T types have better eradication vs C/C and C/T genotypes)
- H Pylori virulence factors (CagA protein and VacA toxin)
- Antimicrobial resistance
- Compliance
- Duration (10-14 days have 4-6% higher eradication vs 7 days)
132
Fill in the blanks
133
Which type of anaemia is most common post gastrectomy, at what is the mechanism?
Iron deficiency anaemia, occurs 10 years before b12 deficiency because the body has substantial b12 stores.
The mechanism: gastric acid is required to make ferrous -> ferric iron and thus soluble and absorbable. Thus with reduced acid secretion post gastrectomy, there is decreased iron absorption
134
What is the mechanism of b12 deficiency post gastrectomy?
Decreased intrinsic factor production by parietal cells of the stomach.
Deficiency takes many years to occur because the body has substantial b12 stores
135
How might folate deficiency occur post gastrectomy?
B12 is required for conversion of inactive methyletrahydrofolic acid to active tetrahydrofolic acid
136
What are the complications post gastrectomy?
Anaemia
- iron
- b12
- folate
Dumping syndrome
- early: <1 hour, GI (nausea / vomiting / diarrhoea) and vasomotor (flushing / presyncope)
- late: reactive hypoglycaemia 1-2 hours post
137
How common is early dumping syndrome post gastrectomy? When does it occur post-op? What is it's prognosis
40%, can occur within 6 weeks, usually disappears within a year
138
How do you treat early dumping syndrome?
Reduce meal size
Increase/fibre/protein
Decrease carbs
Octreotide
Guar gum
139
How common is malignancy in gastric remnant post gastrectomy?
3% over 15 years
140
What are the causes of atrophic gastritis?
Environmental
- H pylori
- dietary
Autoimmune
- T cell and B-cell vs parietal cells (anti-IF antibody and anti gastric parietal antibodies)
141
What are the risks / complications associated with atrophic gastritis?
Cancer
- gastric adenocarcinoma
- neuroendocrine tumours from gastrin-stimulated enterochromaffin-like cell hyperplasia
Anaemia
- iron (decreased acid production)
- b12 (decreased IF production)
142
What is the diagnosis? Describe the key endoscopic appearances that you would expect to find in this condition.
Atrophic gastritis
Loss of rugal folds (seen)
Prominent submucosal vessels (not seen)
143
What is the diagnosis?
Intestinal metaplasia in chronic atrophic gastritis
144
How would you biopsy a patient with atrophic gastritis?
NBI image enhancement
Sydney protocol
- biopsy any visible lesions
- greater and lesser curve of
---> antrum + incisura (one pot)
---> body (another pot)
145
What is the diagnosis?
Atrophic gastritis with intestinal metaplasia
146
What prognostic scoring systems are there for atrophic gastritis / intestinal metaplasia? What is their relavence?
Operative link on gastritis assessment
Operative link on gastric intestinal metaplasia
Stage III and IV have higher associations with gastric cancer
147
What abnormalities might you see in the bloods of someone with atrophic gastritis?
Anaemia
- iron
- b12
Elevated serum gastrin
Decreased serum pepsinogen I and decreased pepsinogen I/II ratio
Antiparietal cell and anti-intrinsic factor antibodies (autoimmune subtype)
148
What is the management approach to atrophic gastritis without dysplasia?
Eradicate H Pylori + rescope
Ongoing 3 yearly surveillance for
- atrophic gastritis extending to the body
- intestinal metaplasia
- FHx gastric cancer
- persistent H Pylori
Discharge the rest
149
What is the endoscopic approach to gastric intestinal metaplasia with non-visible dysplasia?
Low grade
- annual surveillance
- if 3x consecutive remain low grade then 3 yearly surveillance
High grade
- 6 monthly surveillance
150
In cases of atrophic gastritis, what is the approach to visible dysplastic lesions in areas of intestinal metaplasia?
EMR ≤1cm
ESD ≥1cm
Annual surveillance thereafter
151
What is the all-stage 5 year survival rate for gastric adenocarcinoma? Vs stage IA 5 year survival rate
18% vs 80%
152
What are the alarm symptoms of gastric cancer requiring urgent OGD?
Dysphagia
Age > 55 AND weight loss and any of
-Abdo pain
-Reflux
-Dyspepsia
Consider, ie not absolute indications, the below:
Age >55 with dyspepsia/reflux non-responsive to PPI treatment or H pylori eradication, especially if
-Previous gastric ulcer
-Previous gastric surgery
-Ongoing NSAID need
-Anxiety about cancer
-RFs for GC
153
What is the annual incidence of progression of atrophic gastritis to gastric adenocarcinoma?
<1%
154
What are the demographic risk factors for gastric adenocarcinoma?
-Non-white ethnicity
-Residence/migration from high risk areas
-Male sex
-≥45 years old
155
What are the lifestyle risk factors for gastric adenocarcinoma?
Smoking
High salt intake
156
What are the endoscopic and aetiological risk factors for gastric adenocarcinoma?
H Pylori (only for non-cardia GC)
Autoimmune chronic atrophic gastritis (pernicious anaemia with gastric atrophy)
Dysplasia on biopsy
OLGA / OLGIM stage III/IV
Extensive IM on biopsies (essentially the same as above)
157
What are the genetic risk factors and familial syndromes for gastric adenocarcinoma?
FHx gastric adenocarcinoma
Hereditary diffuse gastric cancer
- AD CDH1 mutation
Familial intestinal gastric cancer
- genetic basis not known
Single gene syndromes e.g.
- Li-Fraumeni syndrome
- Familial adenomatous polyposis
- Peutz-Jeghers syndrome
- Lynch syndrome
158
What non-familial GI conditions are risk factors gastric adenocarcinoma?
Atrophic gastritis
Gastric ulcers
Polyps
Previous gastric surgery
Menetrier’s disease
159
What are the criteria for referring to genetics services regarding gastric cancer?
160
What is the staging system for gastric adenocarcinoma?
0 = T(in situ)N0M0
IA = T1N0M0
- Tumour invasion to lamina propria, muscularis mucosa or submucosa
IB = T1N1M0 OR T2N0M0
- Either T1 with 1-2 lymph nodes
- OR no lymph nodes but invasion into muscularis propria
IIA = T2N1M0 or T3N0M0
- T3 = tumour growing into serosal layer
IIB = T1N3aM0 or T2N2M0 or T3N1M0 or T4aN0M0
- N3a = 7-15 lymph nodes
- N2 = 3-6 lymph nodes
- T4a = has grown through whole serosa but not invading adjacent organ structures
IIIA = T2N3aM0 or T3N2M0 or T4aN1M0 or T4aN2M0 or T4bN0M0
- T4b = tumour invading adjacent structures
IIIB = T1N3bM0 or T2N3bM0 or T3N3aM0 or T4aN3aM0 or T4bN1M0 or T4aN2M0
- N3b = ≥16 lymph nodes
IIIC = T3N3bM0 or T4aN3bM0 or T4bN2M0 or T4bN3aM0 or T4bN3bM0
IV = any M1
161
What is the role of endoscopic resection in gastric adenocarcinoma?
Tumours confined to the mucosa (Tis/T1 i.e stage 0 / stage IA), well differentiated (G1-G2 i.e ki67 <20%) , non-ulcerated and ≤2cm
ESD preferred but EMR can be considered for smaller lesions <15mm and with Paris 0-IIa polyp morphology suggesting low probability of advanced histology
162
What is the role of surgical resection in gastric adenocarcinoma?
T1 tumours which do not meet endoscopic criteria i.e. >2cm, ulcerated, or G3
Stage IB-III require radical gastrectomy (OR sometimes subtotal gastrectomy as long as >3-5cm resection margin can be obtained) as part of multimodal therapy
---Includes lymph node dissection
163
What is the role of chemotherapy in gastric adenocarcinoma?
Pre + post-operative chemotherapy for stage IB (T2N0 or T1N1) resectable GC
- Fluoropyrimidine + platinum based + docetaxel is preferred
Advanced / unresectable
- Fluoropyrimidine + platinum based + other agent
--> HER2+ - trastuzumab
--> PDL1+ - nivolumab
- 2nd line = pembrolizumab if microsattelite instability
164
What is the role of radiotherapy in gastric adenocarcinoma?
If an R1 resection is done
165
What is the diagnosis?
Fundic gland polyp
166
What is the endoscopic approach to fundic gland polyps? What would make you think of a diagnosis of FAP?
Can be an endoscopic diagnosis not requiring biopsy
Endoscopic resection should be performed for
- antral polyps
- ulcerated/dysplastic looking polyps
- those >1cm
EMR <2cm
ESD ≥2cm
If dysplasia was found in the polyp, then annual surveillance thereafter
If no atypical endoscopic features - discharge
Consider FAP if
- >20 polyps
- age <40
- dysplasia present
- duodenal adenomas also seen
167
What is associated with fundic gland polyps?
PPI usage
FAP
MUTYH-AP (MAP)
168
What is the diagnosis?
Hyperplastic polyp
169
What is the typical description macroscopically of a hyperplastic polyp?
<1cm, smooth, dome shaped, red
170
What are the associations with hyperplastic polyps?
Anaemia (through ulceration and bleeding of the polyp)
H pylori
Atrophic gastritis / pernicious anaemia
171
Which gastric polyps carry a malignancy risk?
Fundic gland polyps ≥1cm or associated with polyposis syndrome
Hyperplastic polyps
Gastric adenomas
Previous ulcer sites
172
What is the histological description of a hyperplastic polyp?
Hyperplasia of gastric foveolar cells (mucin producing)
+/- have inflammatory cell infiltrate (inflammatory polyps)
173
What is the management approach to hyperplastic polyps?
Biopsy all to confirm diagnosis
Eradicate H Pylori if present, and if negative, or confirmed eradication then resect the following:
- symptomatic polyps
- >1cm
- pedunculated polyps
Resect all polyps >3cm regardless of H pylori status
If dysplasia is present then annual surveillance
174
What is the diagnosis?
Gastric adenoma
175
What is the diagnosis?
Gastric adenoma
176
What is the diagnosis?
Linitis plastica (diffuse type gastric carcinoma)
177
What is the diagnosis? What is the characteristic cell type seen? Are they always seen?
Linitis plastica (diffuse type gastric carcinoma)
Signet ring cell. Not seen in poorly differentiated subtypes
178
What is the typical macroscopic description of a gastric adenoma?
Single, <2cm, antrum and incisura location, velvety pink lobulated appearance, can be sessile or lobulated
179
What are the associations with gastric adenomas?
H Pylori
Atrophic gastritis
Gastric intestinal metaplasia
180
What is the management approach for gastric adenomas
Check H pylori and eradicate if present
Biopsy all suspicious lesions
If diagnosis confirmed, then en bloc resection
- ESD for sessile polyps >15mm
6-12 months post endoscopic resection repeat OGD + annual ongoing surveillance thereafter
181
What is the diagnosis?
Gastric NET on background atrophic gastritis
182
What is the macroscopic description of gastric NET? Where in the stomach are they usually found?
Small reddish/multiple nodules
Usually found on the body and fundus
May be associated with atrophic gastritis
G3 NETs usually >2cm, single and can be found anywhere in the stomach
183
What disorders are associated with gastric neuroendocrine tumours?
Atrophic gastritis (pernicious anaemia in particular driving hyperplasia of ECL cells in response to increased gastrin levels)
Zollinger-Ellison syndrome (either as cause of, or result of gNET)
MEN1 (G2 NETs only)
VHL
NF1
Tuberous sclerosis
184
What immunohistochemical markers are useful in NETs?
Chromogranin, synaptophysin, cytokeratin, peptide hormones e.g. gastrin, somatostatin receptors
185
Define the G1-3 NETs histologically
G1: well differentiated & <3%
G2: well differentiated & 3-20%
G3a: well differentiated & >20%
G3b: poorly differentiated & >20%
186
What is the cellular origin of gastric NETs?
Usually enterochromaffin-like cells (histamine producing)
Also can be (non-functional) serotonin producing enterochromaffin cells
Also can be gastrin producing G cells (seen in zollinger-ellison) --- ZES usually from pNET gastrinomas though
187
What is the management of G1 gNETs?
Annual surveillance <1cm lifelong
Endoscopic resection >1cm after EUS to define invasion depth
If not amenable to ESD, then can consider sleeve gastrectomy
188
What is the management of G2 gNETs?
Annual surveillance <1cm lifelong
Endoscopic resection >1cm after EUS
PPI for ZES
Surgery only if both primary and met can be resected with R0
Antisecretories (octreotide) esp if metastases or functionality
PRRT (lutetium) or chemotherapy if progression despite the above
189
What is the management of G3 gNETs?
Surgery if no mets
- Adjuvant chemo for poorly differentiated ca (G3b)
Systemic treatment if unresectable / mets
- PRRT for well differentiated
- Chemo if poorly differentiated
190
What is the ix approach for G2 gNETs?
EUS for all, gut peptides, PTH and Ca (MEN1 association), DOTATAE PET for LN mets, CT or MRI for general cross-sectional imaging / staging
191
List the differential diagnoses for thickened gastric folds
Menetrier's disease
Linitis plastica
Eosinophilic gastritis
Lymphocytic gastritis
Zollinger Ellison syndrome
192
What are the histopathological changes in Menetrier's?
Foveolar hyperplasia with corkscrew morphology
Preserved linear architechture
Oxyntic gland atrophy
Lamina propria predominantly chronic inflammatory cell infiltrate with scattered eosinophils
193
What is the clinical and biochemical presentation of Menetrier's?
Abdominal pain, malabsorption
Hypoalbuminaemia
Positive faecal A1AT
194
What are the associations with Menetrier's?
CMV, H pylori, IBD, ankylosing spondylitis
Carries gastric cancer risk
195
What is the management of Menetrier's?
Treat any associated CMV/H pylori
Octreotide may reduce protein loss
Total gastrectomy may be required for debilitating disease
196
What are the endoscopic features of eosinophilic gastritis?
Deep cratered ulcers + surrounding thickened folds
197
What is the histological definition of eosinophilic gastritis?
≥30 eosinophils/HPF
198
What are the eosinophil cutoffs for eosinophilic gastroenterocolitis?
Stomach: ≥ 30 eosinophils/high power field in 5 high power fields
Duodenum: > 52 eosinophils/high power field
Ileum: > 56/high power field in the ileum
Right colon: > 100/high power field
Transverse and descending colon: > 84/high power field
Rectosigmoid colon: > 64/high power field
199
What is the management of eosinophilic gastritis?
PO prednisolone 20-40mg OD
VS 6 food elimination diet
200
What is the diagnosis?
Lymphocytic gastritis
201
What is the histological description of lymphocytic gastritis?
≥25 IELs per 100 gastric surface / foveolar epithelial cells
IELs are small and halo appearance and CD3+CD8+
Foveolar epithelial hyperplasia, epithelial proliferation and intestinal metaplasia may be seen
202
What are the associations with lymphocytic gastritis?
Coeliac disease
H Pylori
203
What is the management of lymphocytic gastritis?
GFD
H pylori eradication
PPI
204
List examples of submucosal lesions
GIST
Leiomyoma/sarcoma/lipoma
Pancreatic rest
205
What is the most likely diagnosis?
GIST
206
What is the diagnosis?
Pancreatic rest
207
What is the best workup of a suspected GIST?
EUS and biopsy to confirm diagnosis
CT enterography for staging
208
What are the histological markers of GISTs?
CD117 (c-KIT), CD34, and/or DOG-1
209
What are the histological subtypes of GISTs?
Spindle (70%)
Epithelioid (20%)
Mixed type (10%)
210
What is the management approach to GISTs?
Low risk: laparoscopic resection
- Consider endoscopic surveillance for GISTs <2cm with no adverse features (ulceration, irregular borders etc)
High risk/metastatic tumours: resection + imatinib 400mg daily 12 months
Unresectable tumours may have partial resection + imatinib
211
List the layers seen on EUS, and their colour
1) Interface: bright layer between probe and mucosa
2) Mucosa: dark
3) Submucosa: bright
4) Muscularis propria: dark
5) Serosa: bright
212
What is the most common aetiology of gdenomas?
FAP (60%), the rest are sporadic
213
What is the diagnosis?
Duodenal adenoma
214
What is the malignant potential of duodenal adenomas?
30-85%
215
What is the management of duodenal adenomas?
Endoscopic resection - EMR vs ESD
Surgical resection for large / local infiltration / site of recurrence
FU endoscopy at 3-6 months post resection
216
What are the OGD KPIs?
Fasting instructions prior to UGI endoscopy
Documentation of procedure duration
Photo documentation of anatomical landmarks and abnormal findings
Accurate application standardised disease-related terminology
Application of Seattle protocol in Barrett’s surveillance
Accurate registration of complications after therapeutic OGD
217
What are the OGD minor performance measures?
Minimum 7 minute procedure time for first diagnostic, and follow up of gastric IM
Minimum 1 minute inspection time per cm circumferential Barrett’s
Lugol chromoendoscopy for curatively treated ENT or lung Ca patients to exclude second primary oesophageal cancer
Application of validated biopsy protocol for GIM
Prospective registration of Barrett’s patients
218
In what proportion of the general population are gallstones found?
10-20%
219
What chance do asymptomatic gallstones have of becoming symptomatic in the next 10 years?
20%
220
What chance to asymptomatic gallstones have of becoming complicated by pancreatitis, cholecystitis or biliar obstruction?
2-3%
NB: symptomatic gallstones have a higher chance
221
What is the management of mirizzi syndrome?
Cholecystectomy
222
What is the ix and mx approach to someone with suspected biliary microlithiasis
EUS (if MRCP negative)
Mx: ERCP, sphincterotomy + cholecystectomy
223
What is caused by ABCB4 mutation? What are the features? What is it's management?
Low phospholipid associated cholelithiasis / progressive familial intrahepatic cholestasis type 3
AR
Presents in adulthood
Gallstone disesase <40 years
Intrahepatic lithiasis and biliary colic post cholecystectomy
Mx: UDCA 15mg/kg/day, liver transplant if secondary biliary cirrhosis occurs
224
What is adenomyomatosis of the gallbladder? What is the histology? What imaging is best?
Benign cause of gallbladder thickening which is commonly asymptomatic
Histology
Outpounchings of the mucosa (epithelial proliferation) into thickened (hypertropied) muscle wall (Rokitansky-Aschoff sinuses)
MRCP can help differentiate gallbladder ca from adenomyomatosis, as can USS (but not always)
225
What is the management of adenomyomatosis of the gallbladder?
Cholecystectomy if symptomatic
NB: >50% associated with gallstones
226
What is porcelaine gallbladder? How is it diagnosed? Why is it relevant? What is its management?
Calcification of the gallbladder
Best imaging to confirm - CT
Associated with gallstones 95%
Associated with gallbladder cancer and thus cholecystectomy is advised
- Variable range 3-20%
Spotty calcification has higher malignancy risk than homogenous complete calcification
May be an argument for observation in complete calcification cases, especially if older/poorer functional status
227
What is the management of asymptomatic gallbladder polyps?
Cholecystectomy if ≥10mm polyp
Cholecystectomy if 6-9mm AND any of
- age >60
- PSC
- asian
- sessile polypoid lesion >4mm
6 month, 1 year, 2 year FU for
- polyp 6-9mm
- AND no RFs above
OR polyp ≤5mm but some of RFs above
Discharge if
- polyp ≤5mm
- AND no RFs above
228
What is the management of symptomatic GB polyps?
Cholecystectomy
229
What are some benign causes of biliary strictures?
Inflammatory
- PSC
- IgG4-RD
- Choledocholithiasis
- infectious e.g. ascaris
Ischaemic (e.g. critical care cholangiopathy)
Traumatic
Post surgical/LT
230
What are some malignant causes of biliary strictures?
Intrinsic
- Cholangiocarcinoma
Extrinsic
- Pancreatic
- Lymphoma
- HCC
- metastasis
231
What are the relative benefits of covered vs uncovered metal biliary stents?
Covered
- More likely to migrate (less of an issue with tumours)
- If traverses cystic duct can cause cholecystitis
- No tumour ingrowth
- Can be removed
Uncovered
- Cannot be removed because of tissue ingrowth
232
What proportion of PSC patients with large duct disease will develop a dominant stricture?
50%
233
What is the treatment of choice for biliary strictures in PSC?
Balloon dilatation
234
Which ERCP procedures are not high risk for bleeding?
Without sphincterotomy
235
Which endoscopic procedures may require interruption of aspirin?
ESD
large colonic EMR (>2 cm)
upper gastrointestinal EMR
ampullectomy
236
What are the differences in cholangioscopy vs ERCP risk?
Increased cholangitis due to ductal irrigation
- prophylactic abx always given
Direct cholangioscopy (not usual) can cause air embolism and CVA from intrabiliary air insufflation
237
What are the causes of bile duct stricturing post liver transplant?
Anastomotic
- surgical technical issues including donor-recipient duct size mismatch
Non-anastamotic
- due to blood supply issues
- hepatic artery thrombosis
- ischaemic cholangiopathy
238
When do anastomotic LT biliary strictures present?
Within 1 year post transplant
239
What is the management of LT biliary anastomotic strictures?
ERCP - dilatation or stent
240
When do non-anastomotic LT bile duct strictures present?
Hepatic artery thrombosis
- acute
Ischaemic cholangiopathy
- within 12 months of transplant
241
What is the presentation of ischaemic cholangiopathy post LT?
Initially asymptomatic
Progressive cholestasis
Recurrent biliary sepsis
Within 12 months of transplant
242
What are the risk factors for ischaemic cholangiopathy?
Prolonged ischaemia time
DCD
CMV infection
243
What are the causes of secondary sclerosing cholangitis?
244
What is the management of sclerosing cholangitis of the critically ill patient?
UDCA 10-15mg/kg probably OK
ERCP can be considered if there is an amenable area to stent
Liver transplant is the only treatment for advanced diease
Overall poor prognosis
245
How are cholangiocarcinomas subclassified?
Intrahepatic
Distal
Perihilar
(gallbladder)
246
What are the subclassifications of intrahepatic cholangiocarcinoma?
Mass forming
Mass forming and periductal infiltrating - worse outcomes with surgery vs mass forming alone due to lymphatic invasion
Periductal infiltrating
Intraductal growing
247
What are the histological subtypes of intrahepatic cholangiocarcinoma? Which macroscopic subtypes fit in to these?
Large duct
- mass forming and periductal infiltrating
- periductal infiltrating
- intraductal growing
Small duct
- mass forming (always)
248
What are the risk factors for intrahepatic cholangiocarcinoma?
249
How often are risk factors found that can attribute cases of intrahepatic cholangiocarcinoma?
30-40%
250
What is the investigation approach for a suspected intrahepatic cholangiocarcinoma?
MRI liver/MRCP
CT chest and abdomen
(Ca19-9)
Biopsy and/or liquid biopsy
Molecular profiling of biopsy (to suggest suitability for FGFR based therapies)
FDG PET to evaluate lymph node involvement for potentially resectable disease
Consider EUS for LN sampling based on FDG PET findings
251
What curative options are there for intrahepatic cholangiocarcinoma? What is the 5 year survival for these?
R0 resection with lymphadenectomy + adjuvant chemotherapy (capecitabine) for 6 months
25-40% 5 year survival
Liver transplant can also be considered in select cases - trials ongoing. Some have suggested 65% 5 year survival
252
What factors affect decision as to whether an intrahepatic cholangiocarcinoma is resectable?
Anatomical distribution + technical resectability (peripheral location)
Future liver remnant ≥25% in normal liver ≥40% in chronic liver disease
Solitary lesion
Absence of distal lymph nodes or metastases
Absence of significant portal hypertension
PV embolisation can be done pre-surgery to induce residual liver hypertrophy pre-op
253
What are the indications for liver transplant in iCCA management?
Currently not a standard therapy, but trials are ongoing
Unresectable tumours
Early stage iCCA (single tumour ≤2cm)
OR locally advanced iCCA with response to neoadjuvant chemotherapy and favourable tumour biology
Absence of
- vascular invasion
- extrahepatic disease
- lymph node spread
254
What is the management of metastatic iCCA?
If PS >2 and/or decompensated liver function - best supportive care
If PS ≤2 and preserved liver function - chemo
1) gemcitabine/cisplatin/durvalumab
255
What is the management of unresectable advanced liver-limited disease of intrahepatic cholangiocarcinoma (multinodular OR single lesion >2cm)
Evidence is lacking
Thermal ablation
OR
systemic therapy
- gemcitabine/cisplatin/durvalumab
256
What is the management of a single or 2-3 HCC nodules ≤3cm in a patient not fit for surgery with cirrhosis? What is this in BCLC staging?
BCLC A
Consider transplant
Otherwise consider ablation
257
What second line / target chemotherapeutics are available for iCCAs?
Pembrolizumab for patients with mismatch repair gene mutations or microsatellite instability
FGFR inhibitors e.g. the 'nibs' for FGFR2 mutations
Many of the above are still in clinical trials
258
What is the investigational approach for extrahepatic cholangiocarcinomas?
ERCP + brushings or cholangioscopy + intraductal biopsy
EUS WITHOUT biopsy of mass (risks seeding)
MRCP+MRI liver
CT chest
EUS / FDG PET for LN assessment +/- biopsy
Consider staging laparoscopy for advanced T2 or T3 disease to exclude peritoneal metastases (or just use FDG-PET instead for this)
259
What curative options are there for extrahepatic cholangiocarcinomas?
Surgical resection + lymphadenectomy + adjuvant chemotherapy (capecitabine)
260
What decisions will be made when considering choice for surgery in hilar cholangiocarcinoma?
Anatomical contraindications
- involvement of the portal vein and hepatic artery on the side of the future remnant liver (contralateral) without the possibility of a vascular reconstruction (T4)
- extensive bilateral proximal infiltration of the tumour into secondary biliary radicles (segmental bile ducts)
- Massive liver parenchymal infiltration
- Distant lymph node metastases beyond the hepatoduodenal ligament (N2 nodes) - usually a contraindication
- Distant metastases (M1)
- NB: abutment of the vasculature is not a contraindication
How much liver would need to be resected? Would ≥25% for normal liver or ≥40% for chronic liver disease liver be left?
Other co-morbidities
261
What is this classification system called? What is it for? Fill in the blanks
Bismuth-Corlette classification of hilar cholangiocarcinomas
262
What margins need to be resected for hilar cholangiocarcinomas?
5-10mm from affected bile ducts
263
What surgical procedure can be done for distal cholangiocarcinoma?
Whipple's, extensive bile duct resection + hepaticojejunostomy
264
Is there a role for liver transplant in hilar cholangiocarcinoma?
<3cm tumour without extrahepatic disease in PSC cases
265
What is the curative management of gallbladder cancer?
Cholecystectomy alone for stage T1a
+ lymphadenectomy +/- segment IVb/V lobectomy for stages >T1a
+ adjuvant chemotherapy for all potentially curative resections: Cisplatin/gemcitabine for PS<2
OR gemcitabine monotherapy for PS≥2
266
What is the role of chemotherapy and radiotherapy in extrahepatic cholangiocarcinoma and gallbladder cancer, and which agents are used?
Adjuvant chemotherapy for all potentially curative resections:
- Cisplatin/gemcitabine for PS<2
- OR gemcitabine monotherapy for PS≥2
Or palliative chemo for unresectable disease if liver function allows
Palliative radiotherapy (including SBRT) can be considered for symptomatic metastatic disease
267
What are these? Fill in the blanks
Choledochal cyst types
268
What are the subtypes of type 1 choledochal cysts?
A: cystic
B: focal
C: fusiform
269
What are choledochal cysts? What is their prognosis?
Congenital anomaly
Associated with risk of cholangiocarcinoma (10-30% lifetime)
Only 20% become symptomatic (usually if infected, obstructed or cholangiocarcinoma)
270
What is the Ix approach for choledochal cysts?
Usually just MRCP
HIDA scan or EUS may be needed to demonstrate continuity with biliary tree (to define it as a choledochal cyst)
271
What is the risk of cholangiocarcinoma with choledochal cysts? Which subtypes confer the greatest risk?
Associated with risk of cholangiocarcinoma (10-30% lifetime)
Greatest for type I and IV cysts
272
Is PBC a risk factor for cholangiocarcinoma?
No
273
What is the management of choledochal cysts (by type?)
Surgical excision for type I-IV
Type I
- roux-en-y hepaticojejunostomy
Type II
- cyst excision
Type III
- endoscopic resection or sphincterotomy to decompress acutely
Type IVA
- roux-en-y hepaticojejunostomy + hepatectomy (intrahepatic components)
Type IVB
- roux-en-y hepaticojejunostomy
Type V/Caroli disease
- supportive
- screen for PV thrombosis every 6 months
- partial hepatectomy for localised disease
- consider liver transplant
274
What are the complications for choledochal cysts?
Cholangiocarcinoma
Stones
Cholangitis
Strictures
Cyst rupture
Pancreatitis
Secondary biliary cholangitis/cholangiopathy
275
What is the aetiology of Caroli disease?
AR polycystic kidney disease associated
PKHD1 gene
276
What is the differential for Caroli disease? How could it be differentiated?
Polycystic liver disease - cysts do not communicate with biliary tree
Ix
- HIDA scan to demonstrate continuity
- liver biopsy
277
What are liver flukes? What disease result? What are the causative agents?
Flatworms which cause hepatobiliary disease
Clonorchiasis
- Clonorchis sinensis
- Opisthorchis species
Opisthorchiasis
- opisthorchis felineus
- opisthorchis viverrini
Fascioliasis
- Fasciola hepatica
NB: ascaris lumbricoides is NOT technically a liver fluke, but an intestinal nematode which can invade HPB system through ampulla
278
Where is clonorchiasis mostly seen? What is the reservoir?
East Asia and Russia
Dogs and cats
279
Where is Opisthorchiasis found? What is the reservoir?
South East Asia, South and Central Europe (former soviet Union)
Cats and dogs
280
What is the presentation of clonorchiasis and opisthorchiasis?
Many can be asymptomatic in acute infection
Increasing symptoms depend on higher dose/burden of disease
Common to all
- RUQ pain
- Flatulence
- Weight loss
- Nausea/vomiting/diarrhoea
- Additional: fever, hepatomegaly, ascites, myalgia, arthralgia
Chronic infection and complications
- Biliary obstruction
- Stricture
- Biliary stones
- Pancreatitis
- Hepatitis
- Cirrhosis
- Cholangiocarcinoma
281
What is the ix approach to suspected clonorchiasis and opisthorchiasis?
Liver USS
Stool OCP (eggs 3-4 weeks after infection)
- May not be present in light infections
- Urinary antigen tests are becoming available alternatives
- Serology exists but does not distinguish past from current infection and overlaps with other parasitic disease
FBC - eosinophilia may or may not be present
282
What is the mx for clonorchiasis and opisthorchiasis?
Praziquantel 25mg/kg TDS 2/7
Biliary intervention as required (e.g. strictures / obstruction)
283
Where does fascioliasis occur? What is the reservoir?
Cattle/sheep rearing areas (reservoirs)
50% on andean plateau
284
What is the presentation of fascioliasis?
Acute (liver)
- Usually benign
- Within 6-12 weeks of ingestion
- Fever, RUQ pain, hepatomegaly, (jaundice)
- Marked peripheral eosinophilia
Chronic (biliary)
- Begins 6 months after ingestion
- Often asymptomatic
- Bile duct obstruction, secondary pancreatitis can occur
- NOT associated with cholangiocarcioma
285
What is the ix approach for fascioliaisis? What might be seen on imaging?
Stool OCP
Duodenal aspirates
Flukes seen on ERCP
Imaging: hypodense branching lesions (path of parasite)
Serum serology
286
What are the management and preventative strategies for fascioliais?
Triclabendazole 10mg/kg 2/7
ERCP for biliary complications
Avoid ingestion of raw freshwater plants in endemic areas
287
What is ascaris lumbricoides? Where is it found?
Largest intestinal nematode (roundworm)
Common worldwide, especially in Asia, less so Europe
1 billion worldwide affected
288
What is the transmission of ascaris? And life cycle?
Faecal oral spread
Faeces -> soil -> intestines -> portal circulation -> systemic circulation -> lungs -> swallowed -> intestines (where they mature)
289
What is the clinical presentation of ascaris?
Most are asymptomatic
Larval stage (pulmonary) for those with no previous ascaris exposure
- Loeffler syndrome (inflammatory pulmonary pneumonitis to helminthic infection)
--->Dry cough, fever, SOB etc
---> Eosinophilic pneumonitis
Adult worm stage - intestinal, biliary, pancreatic - majority of symptomatic cases
- 6-8 weeks after egg ingestion
- General - nausea, vomiting, diarrhoea, visible worms in faeces
- Intestinal complications - obstruction, malnutrition
- Biliary - colic / cholangitis / obstruction
- Pancreatic - pancreatitis
290
What are the investigations for ascaris?
Peripheral eosinophilia in earlier disease
AXR - whirlpool effect of large collection of worms (see picture
USS - may see intestinal or HPB worms
CT/MRI - bullseye appearance of worms within lumen
Stool MCS
For pulmonary disease
- CXR: nodules
- sputum: ascaris larvae
- exclude strongyloides (guides use of steroids)
291
What is the management of ascaris?
Albendazole 400mg STAT
ERCP to clear biliary worms
For loeffler syndrome, steroids can be given (providing strongyloides excluded)
292
What liver lesion is described by the following radiology?
Anechoic, posterior acoustic enhancement, T2 hyperintense, hypodense on CT (<10 HU)
Simple liver cyst
293
What is the management for simple liver cysts?
Only intervene symptomatic cysts (which need to be ≥4cm)
Surgical deroofing preferred
294
What is the differential for a simple liver cyst with a soft tissue component?
Biliary cyst adenoma (mucinous) or carcinoma
295
In liver lesion imaging, what is the role of primovist?
Primovist retention may reassure diagnosis of FNH vs hepatic adenoma
In suspected cancers, primovist retention suggests HCC vs extrahepatic metastasis (contrast is taken up by hepatocytes)
296
List the causes of pancreatitis
Gallstone (40%)
Hypertriglyceridemia (>11mmol/L)
Alcohol (30%)
Drugs: azathioprine, 5-ASAs, metronidazole
AIP1 and 2 / IgG4-RD
ERCP
Congenital abnormalities
- pancreas divisum
- annular pancreas
Genetic factors
- PRSS1 associated AD 'hereditary pancreatitis'
- AR - SPINK1 gene mutation
- CF
- other complex genetic patterns
296
What biochemistry suggests gallstone pancreatitis?
>3x ULN ALT
296
What is the timing for cholecystectomy in gallstone pancreatitis?
Same admission for mild pancreatitis
296
What is described by the following radiology of a liver lesion?
CT: late arterial enhancement + rapid PV washout
MRI + GAD: T1 arterial enhancement with rapid washout
HCC
296
What is suggested by the following radiology of a liver lesion?
Moderate T2 hyperintensity
Nodular centripetal filling
Hepatic haemangioma
297
What is the role for acute ERCP in gallstone pancreatitis?
<72 hours for persistent obstruction or cholangitis
<24 hours for co-existing cholangitis with sepsis
Otherwise timing is not clear
298
What is para-duodenal/groove pancreatitis? What are the symptoms? What might investigations show? What is the management?
Pancreatitis in groove area between pancreatic head, duodenum and common bile duct, often surrounding minor ampulla and accessory duct
Predominantly affects males aged 40-50 with years of alcohol abuse
Symptoms: severe intermittent upper abdominal pain, nausea, vomiting (due to disordered gastric emptying and duodenal stenosis), weight loss
Oedematous/nodular duodenum or cobblestone appearance with stenosis on endoscopy
Histology: brunner gland hyperplasia, dilatation of santorini’s duct and protein plaques in the pancreatic duct
EUS or MRI may demonstrate focal D2 thickening and cystic change in the duodenal wall
Management
- Analgesia
- Stop smoking/drinking
- Endoscopic: stenting minor papilla
- Surgical - if hard to exclude cancer or persisting symptoms: Whipple’s - complete pain relief >75%
299
When does azathioprine induced pancreatitis usually occur? Is it dose related? In how many patients does it occur? Can it be re-introduced ?
Usually within 1 month
Dose independent
2-3% of patients
High recurrence if re-introduced
300
What imaging features might suggest IgG4-RD AIP1?
Diffuse sausage shaped pancreas is classical
Alternatively pancreatic head mass/bulkiness is common
Main pancreatic duct narrowing without upstream dilatation
Extra-pancreatic involvement
- biliary strictures
- retroperitoneal fibrosis
- renal involvement
- symmetrically enlarged salivary/lacrimal glands
301
What histological features are typical of AIP1?
Lymphoplasmacytic sclerosing pancreatitis
- periductal lymphoplasmacytic infiltrate without granulocytic infiltration
- obliterative phlebitis
- storiform fibrosis
- >10/HPF IgG4 +ve cells
302
What typical imaging features are seen in AIP2?
Diffuse sausage shaped pancreas is classical
Alternatively pancreatic head mass/bulkiness is common
Main pancreatic duct narrowing without upstream dilatation
No additional organ involvement per se, but higher IBD association
303
What histological features are seen in AIP2?
Idiopathic duct-centric pancreatitis
- granulocyte infiltration of duct wall
- <10/HPF IgG4 +ve cells
304
What is the IgG4 level in AIP 1 and 2?
>ULN in AIP 1 (often >2x ULN)
Normal in AIP 2
305
What is the presentation of AIP1?
Jaundice, abdominal pain, weight loss
306
What is the presentation of AIP2?
Abdominal pain, weight loss, pancreatitis
307
What is the induction, maintenance and second line treatment of AIP 1 and 2?
Same for both
Induction
Steroids: should respond within a week
Pred 1mg/kg/day (2 weeks) - then taper 2.5-5mg every 1-2 weeks
Maintenance - only if relapse? Or consider in AIP1 as higher chance of relapse (low chance in AIP2)
Immunomodulators
Azathioprine 2mg/kg/day
Further agents
Rituximab 1g D0, D15, and 6 months - only indicated type 1 AIP
308
What is the risk of pancreatitis in ERCP? Of these cases, what is the risk of death?
5% -> 3% of those die
309
What are the risk factors for ERCP pancreatitis?
Functional biliary sphincter disorder
Female gender
Previous pancreatitis
Prolonged cannulation attempts
Pancreatic guidewire passage and pancreatic injection
310
What is the recommended approach to ERCP pancreatitis prophylaxis?
Routine PR diclofenac to all pre or post procedure
311
What is a pancreas divisum? What is its relevance?
Failure of ventral and dorsal pancreatic ducts to fuse
- Major papilla - drainage of bile and smaller ventral pancreatic duct (Wirsung duct)
- Minor papilla - drainage of larger dorsal pancreatic duct (Santorini duct, majority of pancreatic drainage)
Poor pancreatic drainage through minor papilla results in recurrent pancreatitis
Present in 4-14% of the population - most common pancreatic congenital abnormality
Up to 26% of patients with idiopathic recurrent pancreatitis have this anomaly
312
What is the management of pancreas divisum?
Nil if asymptomatic
Minor symptoms
- low-fat diet, analgesics, anticholinergics
Major symptoms
- Endoscopic sphincterotomy of minor papilla
- Surgical (if endoscopic failure) minor papilla sphincterotomy or sphincteroplasty +/- cholecystectomy
- Endoscopic dilatation and stenting is not recommended
313
What is the approach to fluid management in acute pancreatitis?
Ringer's lactate is preferred
5-10ml/kg/hr fluid resuscitation
(less need for mechanical ventilation, abdominal compartment syndrome, sepsis, mortality, fluid overload vs 10-15ml/kg/hr)
1.5ml/kg/hr thereafter
314
What investigations should be performed for acute pancreatitis routinely? How would you risk stratify?
Abdominal USS acutely to look for gallstones
Lipid profile - triglycerides >11 mmol/L is significant
Abdominal CT at 72 hours in deteriorating patients to exclude pancreatic necrosis and/or collections OR if there is diagnostic uncertainty
SIRS is the recommendation for defining pancreatitis severity
315
What is the management of pancreatic necrosis?
If >30% necrosis consider strongly the use of antibiotics
They should also get image guided sampling for culture and consider debridement if infection present
316
What is the approach to enteral nutrition in acute pancreatitis?
Mild-moderate pancreatitis - solid food as early as clinically tolerated, but if unable to tolerate, then NG feeding within 24-48 hours
Severe pancreatitis / SIRS at baseline - early enteral feeding (reduces risk of systemic infections, multi-organ failure and mortality)
NJ tube only if delayed gastric emptying precludes NG
317
Are there any special considerations for PN if it is needed in acute pancreatitis
Additional parenteral L-glutamine required at 0.2g/kg/day
318
How common is a pancreatic pseudocyst?
10-20% of acute pancreatitis
20-40% of chronic pancreatitis (highest with alcohol as aetiology)
319
What is the prognosis of pancreatic pseudocysts?
70% pseudocysts resolve spontaneously
320
What is the management of pancreatic pseudocysts?
Only intervene in symptomatic cysts
EUS guided transmural stenting (e.g. LAMS to drain into stomach)
- Endoscopic > percutaneous drainage regarding re-intervention rates
Surgical cystogastrostomy (laparascopic or open) also possible but higher complication rates vs EUS
321
What is the risk of chronic pancreatitis after a single episode of acute pancreatitis?
10%
322
What are the complications of chronic pancreatitis?
Reduced bone mineral density
Malabsorption including fat soluble vitamins A, D, E and K and B12
Pain
Pancreatic pseudocysts
323
What is the management of chronic pancreatitis?
Treat cause
Creon (+/- PPI can aid efficacy)
Nutritional optimisation
Ensure vitamin A, D, E, K (fat solubles) and B12 (pancreatic trypsin requiring) replete
Baseline DEXA + repeat every 2 years if osteopenia
Screen for coeliac disease if no cause known
Treat pain
324
Name the two types of malignant pancreatic cysts. What are their imaging features? How are they diagnosed?
Ductal adenocarcinoma
- EUS + biopsy
pNET
- usually imaging defines NET
- EUS + biopsy if unsure
Cysts with solid component
325
What pancreatic cysts have malignant potential
IPMNs
- especially main duct
Mucinous cystic neoplasm
Solid psuedopapillary neoplasm
326
Name the benign pancreatic cyst types
Serous cystadenoma
Simple cyst
Lymphoepithelial cyst
Pseudocyts
327
What is the diagnosis?
Mixed branch and main duct IPMN
328
Define a main duct IPMN. Where is it usually found?
Main pancreatic duct >5mm with other causes for obstruction excluded
Mostly pancreatic head
329
Define a branch duct IPMN. Where is it usually found?
Grape like cysts >5mm which communicate with main duct
Usually uncinate process (under the head of the pancreas)
330
Which IPMNs should have EUS + FNA?
IPMN size ≥30 mm
Thickened or enhancing cyst walls on imaging
Presence of a non-enhancing mural nodule
Associated pancreatitis
A dilated main pancreatic duct that is 5 to 9 mm in diameter
An abrupt change in the calibre of the pancreatic duct with distal pancreatic atrophy
331
What might be seen on EUS FNA for an IPMN?
Elevated CEA
KRAS and GNAS
TP53, PTEN, PIK3CA mutations seen in malignancy
332
What are the absolute indications for surgical resections of IPMNs?
Jaundice
Pancreatic duct dilatation ≥10mm (main duct IPMN)
Solid mass >5mm
Positive malignant cytology
333
What is the surveillance protocol for patients with IPMNs not undergoing surgery?
MRI at year 1, 3 and 5 years. If cyst is stable, then discharge. Otherwise consider surgery
334
What are the imaging findings of a mucinous cystadenoma?
Septated cystic lesion, although they can be unilocular, may have perceptible wall vs simple cysts which are imperceptible. Fluid is lighter on CT than simple cyst
335
What pancreatic lesion is suggested by: mucinous epithelium with variable atypia and may contain eccentric calcifications
Mucinous cystadenoma
336
What are the EUS biochemical/DNA features suggesting mucinous cystadenoma?
Elevated CEA
KRAS mutations may be present
TP53, PTEN, PIK3CA mutations seen in malignancy
337
What is the management of mucinous cystadenoma?
Resect all due to significant pancreatic cancer risk (11-38%)
338
What are the imaging features of a solid pseudopapillary neoplasm?
Mixed solid + cystic lesion (variability in amounts)
Higher T2 than T1 intensity
Progressive enhancement on MRI (vs washout in carcinomas)
339
What is the management of solid pseudopapillary neoplasms of the pancreas?
Resect all due to malignant potential
340
What is the diagnosis?
Serous cystadenoma - microcytic subtype
341
What are the subtypes and imaging characteristics of serous cystadenomas?
Macrocytic - similar to mucinous lesions on imaging
Microcytic - typical honeycomb appearance with central scar / calcification
342
What are the EUS biochemical / DNA features of a serous cystadenoma?
Normal CEA
VHL mutation
343
What is the management of serous cystadenomas?
Conservative unless symptomatic.
No surveillance required due to low malignant potential
344
What is the role of FDG PET in pancreatic cancer workup?
For all who would potentially undergo treatment (surgical or systemic) to assess lymph node involvement
345
What is the role of EUS in suspected pancreatic cancer?
Histological confirmation of diagnosis if not going straight for surgery
Diagnostic information if MRCP/CT pancreas is unclear
Lymph node assessment +/- biopsy to clarify N status
346
What is the curative treatment of pancreatic cancer?
R0 resection, lymphadenectomy + adjuvant chemotherapy (FOLFIRINOX or gem-cap if elderly/PS2)
347
What is the approach to borderline resectable pancreatic cancer?
Induction chemotherapy with FOLFIRINOX or gemcitabine based combination
Measure Ca199 and if decreasing and good surgical candidate consider surgical resection with adjuvant chemotherapy
348
What is the management of advanced/metastatic pancreatic cancer
FOLFIRINOX if PS 0-1 and bili <1.5x ULN
Gemcitabine combination therapy if PS2 with bili <1.5x ULN
Gemcitabine monotherapy if PS2 with bili >1.5x ULN
349
What is the approach to pre-operative biliary decompression in pancreatic cancer?
If surgical candidate, pre-op fully covered metal stent only if bili >250 or complications
If non-surgical candidate then partially/uncovered metal stent
350
Is there a role for percutaneous biopsy of pancreatic cancer?
No. Risks seeding. EUS only
351
What are the confounding factors with CA199 in pancreatic cancer?
Positively correlated with bilirubin
Only produced by patients with particular ‘Lewis blood group antigens’ (alpha-beta+ or alpha+beta-)
- 6% caucasians and 22% black populations are alpha-beta- so don’t express it
352
Who should be offered pancreatic cancer surveillance?
Definite
- Hereditary pancreatitis and a PRSS1 mutation - CT
- BRCA1, BRCA2, PALB2 or CDKN2A (p16) mutations, and one or more first-degree relatives with pancreatic cancer
- Peutz–Jeghers syndrome
Consider
- 2 or more first-degree relatives with pancreatic cancer, across 2 or more generations
- Lynch syndrome and any first-degree relatives with pancreatic cancer
353
What is the aetiology of pNETs?
Most are sporadic
Main inherited cause = MEN1
Other inherited causes
- VHL
- NF1 (von Recklinghausen’s syndrome)
- Tuberous sclerosis
354
How common are pNETs?
<2% of pancreatic neoplasms
355
What is the imaging investigational approach to suspected neuroendocrine tumours?
Initially
- MRI preferred for pancreatic, liver and bone lesions
- CT preferred for lung lesions
Then
- DOTATATE PET to suggest well differentiated subtypes + nodal disease
- consider FDG PET if lesions/nodes are not DOTATATE avid - suggests poor differentiation
356
What is the role for biopsy in pNETs?
Usually done as part of surgical resection
In nodal or metastatic disease, it is done to assess potential indications for future surgical resection (ki67≤10%)
Otherwise if there is diagnostic uncertainty - EUS + biopsy
357
What is the role of surgery in pNET management?
Extensively used, both for primaries and resectable metastases in the liver - this is because these tumours are often slow growing with low nodal spread
Resectable >T1, N0 - resect with radical intent
Resectable T1-4, N0-1, M1 and ki67 ≤10% OR slow growing, with predominant liver mets - resect with radical intent
Unresectable metastatic / nodal disease? - consider palliative resection of primary pNET if the primary is resectable AND Ki67 ≤10% if surgically fit
358
Which pNETs can be conservatively managed?
Nonfunctioning/asymptomatic pNETs <2cm, G1 or some low G2s - low risk of nodal involvement
359
What is the management of functioning NETs?
Surgical resection for all if possible
Flushing/diarrhoea symptoms? - lanreotide/octreotide
Insulinoma? - diazoxide
If ongoing symptoms/non-response to lanreotide then consider PRRT and everolimus
360
What are the disease modifying agents for pNETs?
G1 or ki67<10%
- lanreotide
- CAPTEM/everolimus
- PRRT
G2 ki67>10%
- CAPTEM/everoliums
- PRRT
G3a
- CAPTEM
- everolimus
- PRRT
G3b
- cisplatin chemo
Any DOTATATE negative
- STZ/5-FU
- CAPTEM
- everolimus
361
What is the surveillance interval for pNETs?
6 monthly for a 2-3 years, then annual, then 2 yearly + continue surveillance lifelong
362
Define the grades of pNETs
G1: well differentiated & <3%
G2: well differentiated & 3-20%
G3a: well differentiated & >20%
G3b: poorly differentiated & >20% = neuroendocrine carcinoma
363
List the common causes of chronic diarrhoea
364
List the infrequent/rare causes of chronic diarrhoea
+ autoimmune enteropathy, CVID, olmesartan induced enteropathy
365
What is the mechanism through which ORT works?
Works via SGLT1 receptor
Glucose + sodium delivered together and allows water to follow + get reabsorbed
366
What is Vener-Morrison syndrome?
= VIPoma
367
What biochemical tests are suggestive of VIPoma? What VIP level?
Profound hypokalaemia
Serum VIP >75pg/ml
368
What is the management of VIPoma?
Lanreotide
Surgical resection
369
What is leptin? What is its function? Where is it produced? What is its clinical relevance?
Satiety hormone. Levels increase in response to eating.
Produced mainly by fat cells
Obese patients have a poor response to supraphysiological leptin doses
Leptin mutations lead to obesity and hyperphagia
370
What is ghrelin? What is its function? Where is it produced? What is its clinical relevance?
Hunger horone
Mainly produced by fundic glands of the stomach
Pre-meal surge -> stimulates appetite + gastric motility + emptying + GH secretion
Followed by sharp drop after eating
Basal levels are inversely related to BMI
Postprandial suppression of ghrelin is impaired in obese patients
After weight loss surgery basal and surge ghrelin is lower ?reason for improved energy balance
Ghrelin levels are higher in Prader-Willi syndrome - hyperphagia
371
What are the two plexuses of the enteric nervous system?
Myenteric plexus - between longitudinal and circular smooth muscle layers
Submucosal plexus - in submucosa
372
How do the CNS and ENS communicate?
Parasympathetic fibres (cholinergic, increases intestinal smooth muscle activity)
Sympathetic (noradrenergic, decreases smooth muscle activity)
373
Explain how a peristaltic wave propogates
Basic electrical rhythm set by interstitial cells of Cajal - contractions only occur as BER wave depolarises
Sensation of stretch -> activation of intrinsic primary afferent neurons (by mechanoreceptors or serotonin from enterochromaffin-like cells) -> activation of interneurons -> proximal excitatory motor neurons + distal inhibitory motor neurons
---> peristalsis
374
If required, what is the best test for small bowel physiology testing?
Catheter based manometry - preferred over wireless motility capsules as provide information on contractile patterns as well as amplitude, and can differentiate neuropathic (poor propogation) vs myopathic (low amplitude) motility disorders
375
What are the Rome IV criteria for IBS?
Recurrent abdo pain at least 1 day per week in the past 3 months on average, with 2+ of the following and onset at least 6 months
- Pain related to defecation (increasing or decreasing)
- Assoc change in stool frequency
- Assoc change in stool form
376
Which foods must be avoided in coeliac disease?
Barley, wheat or rye
Beer (contains barley malt)
Porridge oats (usually contaminated)
Couscous, bulgar wheat, semolina, spelt (all wheat based)
377
What is the heritability of coeliac disease?
10% 1st degree relatives
378
What proportion of patients with autoimmune disease will have coeliac?
5%
379
What is the HLA linkage of coeliac? What is their clinical utility?
DQ2, DQ8
Great negative predictive value, but poor positive predictive value, as 25% general population carry rate
380
What are the causes for persistent villous atrophy on GFD in coeliac?
Natural slow healing (normally 6-12 months to heal, but can take longer in 50%)
Supersensitive (GF labelling: <20 parts per million gluten)
Ongoing gluten
RCD
381
What is the approach to OGD/biopsy for coeliac disease?
Consider no biopsy approach if
<55 years old
No alarm symptoms
IgA TTG ≥10x ULN (NOT validated IgG TTG)
EMA as second line serological test to reduce false positives
If OGD done, take 3-4 biopsies, avoid double bites, ensure biopsy from D1
382
Detail the Marsh classification
1: >25 IELs/100 enterocytes, but normal crypt and villous architecture
2: increased IELs, crypt hyperplasia, but normal villous architecture
3a: increased IELs, crypt hyperplasia, mild villous atrophy
3b: increased IELs, crypt hyperplasia, moderate villous atrophy
3c: increased IELs, crypt hyperplasia, total villous atrophy
383
What are some causes of seronegative villous atrophy?
Coeliac disease (seronegative subtypes)
H pylori
Crohn’s
Drugs: NSAIDs, ARB inhibitors, MMF
Autoimmune enteropathy
CVID
384
What are the ix for carcinoid syndrome? What foods should be avoided during this?
24 hour 5HIAA
Avoid serotonin/tryptophan rich foods for 72 hours prior: pineapple, kiwi, aubergine, walnuts
385
What micronutrient deficiency is suggested by the following?
- Sore throat, hyperemia of pharyngeal mucous membranes, edema of mucous membranes, cheilitis, stomatitis, glossitis
- Normocytic-normochromic anaemia
- Seborrheic dermatitis
How can the diagnosis be confirmed? What are the dietary sources of this micronutrient?
Riboflavin (b2)
Erythrocyte glutathione reductase assay with co-efficient >1.4 suggesting deficiency
Dietary sources: milk, eggs, meats, fish, green vegetables, yeast, and enriched foods (fortified cereals and breads)
386
What micronutrient deficiency is suggested by the following?
Photosensitive dermatitis
Delirium/dementia
Diarrhoea
What are the dietary sources of this micronutrient?
Pellagra (niacin, b3)
Meat, fish, mushrooms, peanuts, yeast products, fortified cereals
387
What are the causes of folate / folic acid / vitamin B9 deficiency?
Nutritional
Increased utilisation
- Pregnancy
- Lactation
- Chronic haemolytic anaemia
Intestinal malabsorption
- Coeliac
- Small bowel crohn’s
- NB: small bowel overgrowth leads to high folate (low b12) due to bacterial production (classically)
Medications which inhibit dihydrofolate reductase
- Methotrexate
- Trimethoprim
388
What are the dietary sources of folic acid?
Leafy green vegetables and animal products (in polyglutamate form, cleaved to monoglutamate form in jejunum where it absorbed)
389
How long does it take for the symptoms of folate deficiency to emerge?
Weeks-months due to body stores
390
What are the causes of b12/cobalamin deficiency?
Dietary insufficiency (animal products, fortified cereals)
Gastric acid hyposecretion
- Autoimmune atrophic gastritis
- Chronic H pylori
- PPI (rarely H2 antagonist)
- Surgical gastrectomy
Pernicious anaemia (anti IF)
Pancreatic exocrine insufficiency
Terminal ileal disease/resection
Other drugs: metformin (altered calcium metabolism?)
NO - inhibits B12 function
391
How long does it take for the symptoms of B12 deficiency to become apparent?
Total body stores 2-5mg, 50% stored in the liver, deficiency manifests over years
392
What are the dietary sources of b12/cobalamin?
Liver, dairy, eggs
393
What are the biological roles of vitamin C?
Promotes iron absorption + promotes cross-linking in connective tissues
394
What micronutrient deficiency explains the following?
Follicular hyperkeratosis + perifollicular haemorrhage
Other petechiae, ecchymoses, haemorrhagic gums (gingivitis) and joints
Microcytic anaemia
Scurvy (vitamin C)
395
What ix for vitamin C deficiency?
Plasma and leukocyte vitamin C levels
396
What is the management of scurvy?
ascorbic acid 250mg daily (divided doses)
397
What micronutrient causes dilated cardiomyopathy?
B1 - wet beriberi
Selenium - Keshan disease. Also affects thyroid hormone production, and causes muscle weakness and mood changes
398
What are the dietary sources of selenium? Where in the gut is it absorbed?
Seafood, kidney liver and some grains/seeds
Small intestine
399
How is vitamin B12 absorbed?
Gastric acid cleaves B12 bound to dietary protein
Intrinsic factor produced by gastric parietal cells in oxyntic/fundic glands binds free b12
B12-IF complex absorbed in terminal ileum (process requires calcium)
400
What micronutrient deficiency is suggested by the following?
Impaired growth / sexual maturation
Skin changes including ulceration
Hair changes including loss
Impaired immune system
Diarrhoea
Zinc
401
What are the causes of zinc deficiency?
dietary, IBD/malabsorption syndromes, acrodermatitis enteropathica (AR zinc absorption problem)
402
What are the dietary sources of zinc?
Meat, chicken, nuts, lentils, fortified breakfast cereals (typical in the west)
403
What micronutrient deficiency is suggested by the following?
Fragile, abnormally formed hair
Depigmentation of the skin
Oedema
Hepatosplenomegaly
Osteoporosis
Normocytic anaemia
Muscle weakness (myeloneuropathy), neurologic abnormalities including ataxia, neuropathy, and cognitive deficits that can mimic vitamin B12 deficiency
Copper
404
What are the causes of copper deficiency?
Dietary deficiency, malabsorptive problems, bariatric/foregut surgery
405
What are the dietary sources of copper?
Vegetables, grains, pulses, meat, poultry, fish, liver
406
What are the syndromes caused by B1 deficiency
Wernicke's
Wet beriberi - cardiomyopathy
Dry beriberi - peripheral neuropathy
407
What are the dietary sources of thiamine?
Yeast, legumes, pork, brown rice, and cereals made from whole grains
408
What are the fat soluble vitamins?
A, D, E, K
409
What are the symptoms of vitamin A deficiency?
Night blindness
410
What are the symptoms of vitamin E deficiency?
Peripheral motor/sensory neuropathy, ataxia, retinal degeneration, haemolytic anaemia
411
What are the symptoms of vitamin K deficiency?
Haemorrhagic diesease
412
What determines lactose intolerance vs tolerance? What is the geographic distribution?
Lactase persistence is due to a dominant gain of function mutation in lactase gene
Highest rates in Scandinavian countries
Lower rates in far east
413
What is the approach to suspected lactose intolerance? What tests are available?
Therapeutic trial is preferred
Lactose hydrogen breath test generally not recommended
- some intolerant patients are hydrogen non-producers giving false negatives
- OR have altered bowel anatomy / SB overgrowth / rapid GI transit (false positive)
Alternatives
- genetic testing
- duodenal lactase activity
- serum gaxilose test
414
What are the symptoms of SIBO?
Non-specific abdominal pain, bloating, diarrhoea
415
What are the risk factors for SIBO?
Gut dysmotility
- DM
- Connective tissue dieasees
- Visceral neuropathy/myopathies
- Opioids, anticholingergics
- PD
- radiation enteropathy
Altered GI secretions
- PPIs
- chronic pancreatitis
- chronic liver disease
Abnormal GI anatomy
- roux-en-y (in blind loop)
- crohn's surgery
- small bowel diverticular disease
Impaired immunity
- Hypogammaglobulinaemia
- CVID
416
What biochemical picture might you see in SIBO?
Low b12, high folate
417
What tests are available for SIBO?
Therapeutic trial
Jejunal aspirate >10^5/ml bacteria (bacterioides, enterococcus, lactobacillus typical) OR atypical flora
Lactulose-hydrogen breath test
- peak ≤90 mins with a rise ≥20ppm (early peak or double peak)
418
What antibiotics can be used for SIBO?
Rifaximin 550mg BD
Ciprofloxacin 500mg BD
Metronidazole 250mg TDS
Co-trimoxazole 160/800mg BD
Norfloxacin 400mg QDS
Co-amox not preferred
419
What is the approach to retreating SIBO?
For an early recurrence <3 months offer a trial of another antibiotic
If recurrence is later than 3 months, then can retreat with the same antibiotic
Low dose rotating prophylactic antibiotics
- Can consider if ≥4 episodes within a year
- Administer antibiotics every other week or 5-10 days a week
- Rotate antibiotics monthly
420
What are the SEHCAT retention criteria?
10-15% mild
5-10% moderate
<5% severe
421
What other tests of bile acid diarrhoea exist?
Faecal bile acid measurement >2300 μmol/48hours
C4 blood test (fasting)
422
What is suggested by the following?
Abdo pain, bleeding, diarrhoea, microcytic anaemia, hypoalbuminaemia
Diaphragm like structures in small bowel
NSAID enteropathy
423
What is the management of NSAID enteropathy?
Stop NSAID
No role for PPI/H2 antagonist
If obstructive symptoms with diaphragm disease (stricture) - endoscopic dilatation, surgical resection or stricturoplasty
424
How much terminal ileum needs to be resected usually to cause bile acid diarrhoea?
>100cm
425
What are the causes and features of enteric fever?
Typhoid (salmonella typhi/enterica) and paratyphoid (salmonella paratyphi) fever
Faeco-oral transmission - women can be carriers
Asia, Africa, Central/South America
Presentation
- Fevers
- Rose spots
- Relative bradicardia
- Later: GI features (vomiting, diarrhoea, constipation)
- Intestinal perforation can result from necrosis of IC peyer’s patches
- relapse can occur if bacteria resides in gallbladder
426
What is the most specific test for enteric fever?
Bone marrow biopsy and culture
However, blood culture usually all that is done
Stool culture only positive in 50% of cases in the first week of illness
427
What is the diagnosis? What is the aetiology? What is the management
Duodenal adenoma
60% are FAP associated
(rest are sporadic)
Excision (EMR or ESD depending on size) given high malignant potential (30-85%)
+ repeat endoscopy at 6 months
428
What is the diagnosis? What is the management?
Lymphangiectasia - dilated lymph vessels, benign condition (primary intestinal lymphangiectasia = Waldemann's)
NB: if there are many of these areas a protein losing enteropathy can result
Management if protein losing enteropathy: low fat diet (prevents chyle leakage) and medium chain triglyceride supplementation. Octreotide can be used. Bowel resection may be indicated for segmental / localized disease
429
What is the diagnosis? What are the symptoms? What are the histological features? What is the treatment?
Whipple's disease
IDA, joint pains, abdo pain, vague neuro symptoms
PAS +ve macrophages
12 months doxy & hydroxychloroquine
OR co-trimoxazole
Frequent relapse up to 50% - lifelong abx may be required
430
The following patient presents with malabsorptive symptoms and general malaise. What is the diagnosis?
Whipple's disease
431
What is the diagnosis?
Lipoma
432
What is the diagnosis? What would the histology show? What are the risk factors?
Amyloid
Stain with congo red
Plasma cell dyscrasias
Inflammatory disorders
CKD with haemodialysis
433
In IBD, which immune cells are activated? What is the sequence of events?
Exposure to foreign antigens leads to activation of macrophages which in turn through cytokine production drive the differentiation of Th1, Th2, Th17, ILCs (innate lymphoid cells) and Tregs
434
In IBD, what cytokines are produced, and by which cells?
Th1: IL2, IL6, IFN-gamma (not UC), and TNF-alpha
Th2: regulate B-cell differentiation via production of IL-4, IL-5, and IL-13.
Th17: IL17, IL21, IL22 and IL23
- IL17 induces Th1 cells and thus proinflammatory cytokines
- IL22 promotes epithelial repair and antimicrobial defence
435
What is the dosage for IFX?
5mg/kg or 10mg/kg at 0, 2, 6 weeks and then every 8 weeks
Can use accelerated regimen (moving week 2 to week 1) for ASUC
Dose escalation to 10mg/kg can be done if low trough levels of IFX in absence of immunogenicity
436
What are the major concerns with anti-TNFs?
Lymphoma and skin cancer risk (compounded with azathioprine)
TB reactivation - usually put patients on rifampicin/eradicate latent TB pre treatment
Avoid in older patients if possible
437
What is the dosing of adalimumab?
Standard induction: 160mg week 0, 80mg week 2, 40mg week 4, then 40mg every 2 weeks
Can be escalated to every week
438
What predictor exists for anti-TNF antibody development?
HLA-DQA1*05 positivity
439
What is certolizumab? Who is it for?
Anti-TNF which doesn't induce apoptosis
Only for crohn's disease
440
What are the indications for tofacitinib?
Moderate-severe UC
Can be used as rescue therapy in ASUC
441
What is the dosing of tofacitinib?
10mg BD PO for 8 weeks and then 5mg BD
Can dose escalate to 10mg BD if secondary loss of response
NB: many early trials were with 10mg TDS induction…
442
What are the concerns re tofacitinib?
Avoid >65 if possible, or in CV disease hx, heavy smokers
VTE
Shingles
443
What is the mechanism of upadacitinib? Who is it for?
JAK 1 and JAK 1/3 inhibitor
UC and CD
Can be rescue therapy in ASUC due to early effectiveness
444
What is the dosing in upadacitinib?
45mg OD for 12 weeks and then 30mg or 15mg OD maintenance
30mg maintenance may have greater efficacy, but higher SEs/risks
If being given >65, 15mg BD recommended for patients
445
What are the concerns with upadacitinib? In whom should it be avoided?
Avoid >65 if possible, or in CV disease hx, heavy smokers
Herpes zoster is a risk
VTE also a risk
446
What is the mechanism of ustekinumab? Who is it for?
IL12/23 inhibitor
UC and crohns
447
What is the dosing of ustekinumab?
IV dose 1 - weight based
- 260mg <55kg
- 390mg 55-85kg
- 520mg >85kg
SC dose 2 at 8 weeks 90mg
Then SC 90mg every 8-12 weeks maintenance
Escalation from 12 weekly to 8 weekly if losing effect
448
Which IBD medication is a rare cause of lupus?
Ustekinumab
449
What is the mechanism of risankizumab? Who is it for?
Anti IL-23
CD only
450
What is the dosing of rizankizumab?
1st 3 doses IV: 600mg every 4 weeks
Then SC 360mg every 8 weeks
451
What is the dosing of vedolizumab?
Induction IV: 300mg at week 0, 2, 6 (+/- 10 for CD without sufficiency response)
Maintenance IV: 300mg every 8 weeks
Can be escalated to every 4 weeks
Can switch to maintenance SC: 108mg SC every 2 weeks
452
What is the advice around vaccinations in biologics?
Avoid live vaccines in all biologics including vedo
BCG (tuberculosis)
Chicken pox (varicella)
Measles, mumps and rubella (either as individual vaccines or as the triple MMR vaccine)
Yellow fever
Rotavirus (babies only)
Delay starting biologics by 4 weeks after live vaccine
Avoid live vaccines in babies for 6 months
Get varicella vaccine if not chicken pox exposed PRIOR to starting biologics
453
What is ozanimod? Who is it for? How is it taken? What are the major risks?
S1P inhibitor. Inhibits migration of immune cells out of lymph nodes
Taken orally OD in gradually increasing doses over a week
Beware lymphopenia and skin cancer risk
454
What is the heritability in CD?
If only one parent has CD - 9% offspring risk
30% if both parents
53% identical twin concordance
455
What is the heritability in UC?
If only one parent has UC - 6% offspring risk
30% if both parents
6-17% identical twin concordance
456
What are the key genes involved in IBD per GWAS studies?
NOD2
- fibrostenosing CD
- European/Ashkenazi jewish
IL23R
- UC and CD
HLA2 variants
- UC > CD
ATG16L1 and IRGM
- CD
Monogenic IBD
- 50 genes
- early onset IBD
- e.g. IL10R and XIAP
457
What percentage of UC patients with develop ASUC?
15-20%
458
What proportion of patients with ASUC require rescue therapy?
30-40%
459
What is the colectomy rate in UC overall (by year), in pancolitis, and in those with previous ASUC?
4% 1 year, 6% 5 year, 10% 10 year, 15% 20 year colectomy rates
25% of patients with pancolitis
33% with ASUC will require colectomy at some stage
460
What is the colectomy rate in ASUC with colonic dilatation (≥5.5cm or >9cm caecum) OR mucosal islands on endoscopy (areas of oedematous mucosa surrounded by deep ulceration)?
75%
461
What proportion of patients with UC flare each year?
50%
462
What proportion of patients with UC proctitis with have extending disease?
10% over 10 years
463
What is the dysplasia risk in UC?
20 years - 8%
30 years - 16%
464
What effect do 5-ASAs have on colorectal cancer?
50% reduction
465
What risks are associated with azathioprine?
Dose dependent
- Bone marrow suppression - 0.1% in TPMT replete
- Hepatotoxicity
---> Acute - transaminitis or cholestatic injury
---> Chronic - nodular regenerative hyperplasia (1% in IBD), veno-occlusive disease or peliosis hepatitis
Dose independent
- GI intolerance
- Pancreatitis (usually first 4 weeks)
Non-melanoma skin cancer
Lymphoma
- 2-5 fold increased incidence
466
Detail the role of TPMT in thioguanine metabolism. What is the clinical relevance of TPMT for thioguanines? How does it affect dosing?
Catalyses mercaptopurine -> inactive (but hepatotoxic) 6-methyl-mercaptopurine
Separate pathway -> 6-thioguanine (active drug which inhibits purine and protein synthesis in lymphocytes)
Separate pathway -> inactive thiouriate catalysed by xanthine oxidase
11% have low TPMT
- can start at 50% of dose
0.3% negligible TPMT
- avoid thioguanine drugs
467
Fill in the blanks for these thioguanine metabolite interpretations.
468
What should be checked prior to starting immunomodulators or biologics?
+ consider eosinophil/strongyloides serology in endemic areas prior to anti TNF
469
What are the typical doses of azathioprine and mercaptopurine for IBD?
Aza 2mg/kg
MP 1mg/kg
470
What monitoring is required for azathioprine?
RFTs/LFTs at weeks 2, 4, 8, 12, and three monthly
TGNs at week 4, 12-16, and annually (should be done 4 weeks after any change in dose)
471
What is the relevance of EBV screening prior to immunomodulator therapy?
Can lead to reactivation including haemophagocytic syndrome and post-transplant type lymphomas
472
Detail the different types of budesonide treatments and their indications
Budesonide MMX = cortiment
9mg dosing OD for up to 8 weeks
Mild-moderately active UC
Budenofalk
Ileum and ascending colon - crohn’s
3mg capsules
Autoimmune hepatitis
Microscopic colitis
Entocort
Jejunum - crohn’s
Microscopic colitis
?open capsule budesonide (mix with applesauce)
3mg capsules
Jorveza orodispersible
1mg BD
EoE
473
What affects decisions for mesalazine suppositories vs enemas and foams
Suppositories ineffective >10cm
Enemas and foams have effect up to splenic flexure
If patients can’t retain enemas, then foams can be used
474
What features might distinguish infectious from inflammatory colitis?
Infective colitis will often have more of a neutrophil predominant infiltrate and normal crypt architecture (acute features) vs lymphocyte infiltrate and crypt destruction in more chronic process of UC
475
What is the ASUC mortality rate?
About 1-2%
476
Detail the Truelove and Witts criteria
Bloody stool ≥6 per day AND any of
- Tachycardia >90bpm
- Temperature >37.8C
- Haemoglobin < 10.5g/dL
- ESR / CRP >30
477
What is the preferred induction regimen for IFX? What factors might make you consider a different induction dose?
IFX 5mg/kg week 0, 1 OR 2, 6 (then 8 weekly)
Consider 10mg/kg for low albumin
478
What factors might make you consider ciclosporin rescue therapy? What factors might make you favour IFX instead?
Favour ciclosporin
- History of TB, hepatitis B, MS or NYHA III or IV
Favour IFX
- Hypocholesterolaemia (<3mmol/L)
- hypomagnesaemia (<0.5mmol/L)
increased risk of neurotoxicity with ciclosporin
- Hyperkalaemia
- hypertension (ciclosporin worsens)
- Epilepsy (ciclosporin increases seizures)
- Renal/hepatic impairment
479
What is the best approach to prophylactic LMWH post discharge in UC post colectomy
4 weeks post discharge continue prophylactic dalteparin
480
Define toxic megacolon
Total or segmental non-obstructive dilatation of the colon (≥5.5cm or >9cm caecum) associated with systemic toxicity
481
What are the risk factors for toxic megacolon?
Hypokalaemia
Hypomagnesaemia
Bowel prep
Opioids
NSAIDs
Anticholinergics
Antidiarrhoeals
482
What is the mortality risk of toxic megacolon?
Up to 50%
483
Detail the montreal classification of crohn's
Age at diagnosis
- A1 <17
- A2 17-40
- A3 >40
Location
- L1: TI +/- limited caecal
- L2: colonic
- L3: ileocolonic
- L4: isolated UGI
Behaviour
- B1: non-stricturing, non-penetrating
- B2: strincturing
- B3: penetrating
- P: perianal disease modifier
484
What are the differentials for chronic diarrhoea with pancolitis involving the TI?
Ileocolonic crohn's
UC + backwash ileitis
485
What does a cryptolytic granuloma suggest diagnostically?
Non-specific. Can be UC, CD or diverticular inflammation
486
What is the approach to capsule endoscopy in the diagnostic work-up of crohn's disease?
Most sensitive and specific test for small bowel crohn's
Can use if high suspicion of crohn's with negative MRI small bowel or ileocolonoscopy
Patency capsule should be done before capsule endoscopy if obstructive symptoms
487
Prior to diagnostic colonoscopy and capsule endoscopy, what is the recommendation regarding NSAID use
Withhold 1 month prior to test
488
What changes might you expect to see on abdominal ultrasound in crohn's patients?
Mural changes
-Increased bowel wall thickness
-Altered echogenicity of the bowel wall
-Loss of normal wall stratification
-Increased colour doppler signal (if contrast enhanced US)
-Decrease in / lack of peristalsis
-Prominent submucosal layer
Extramural changes
-Thickened and hyperechoic mesenteric
-Vascularity of the mesentery (if contrast enhanced US)
-Enlarged mesenteric nodes
-Mesenteric fat hypertrophy
Complications
-Narrowed lumen/stenosis
-Abscesses
-Fistulae
489
What is the role of balloon enteroscopy in the diagnosis of crohn's? What is the complication rate?
Last line procedure due to high complication rate (0.15% perforation rate and 0.72% major complication rate)
490
What induction should be considered for mild-moderate ileocaecal crohn's
Budesonide (budenofalk)
- 8 weeks 9mg then taper over 1-2 weeks
- 3 month course 9mg, 6mg, 3mg monthly taper
Prednisolone
Consider EEN 8 weeks
491
What is the preferred induction for distal colonic mild-moderate crohn's?
Prednisolone
Consider Cortiment / budesonide MMX 9mg 8/52
492
What are the maintenance options for Crohn’s disease based on anatomical location?
Ileocolonic
- azathioprine (2mg/kg)
- MTX (SC > PO)
- stricturing disease: adalimumab
- penetrating/fistulising disease: infliximab
Jejunal / extensive small bowel disease
- early biologic therapy
- greater recurrence after surgery vs IC disease
UGI
- Search for and eradicate H Pylori
- Absence of strictures
- PPI
- Steroids
- Thiopurines / infliximab
493
What are the induction options for moderate-severe ileo-colonic CD?
8/52 prednisolone
EEN
Consider early biologic therapy if aggressive disease or one of the following
- Perianal disease
- Complex stricturing/fistulating disease at presentation
- Age under 40 at presentation
- Need for steroids to control index flare
- Use of PredictSURE IBD blood test in treatment naive patients (T cell stratification) —- ongoing PROFILE trial to prove efficacy
Consider early IC resection if ≤40cm TI disease if induction has not worked - LIR!C (similar efficacy vs IFX)
494
What DDx exist isolated oesopageal crohn's?
GORD
Sarcoidosis
TB
Disseminated fungal disease
Behcets
Malignancy
495
What is the management of crohn's associated oral apthous ulcers?
Topical hydrocortisone
496
What is orofacial granulomatosis? What is the management?
Crohn's associated
Nonspecific granulomatous inflammation presenting as facial or lip swelling, cheilitis, ulcerations, gingival enlargement, mucosal tags and sometimes lymphadenopathy
Mx
- if co-existent crohn's: biologics, usually IFX
- if does not respond to this, then
---> dietary: cinnamon & benzoate exclusion; EEN
---> intralesional triamcinalone injectino
497
What is the role of endoscopic or surgical interventions in stricturing disease?
In general, interventional approaches to strictures without significant inflammation and predominantly more fibrotic.
Endoscopic
- balloon dilatation: Most appropriate for strictures (primary or anastamotic) <5cm, avoid in context of ulceration\---> 80% success; 52% require repeat dilatation
- endoscopic stricturorotomy (+/- plasty - clips to incision site to maintain patency): strictures refractory to dilatations
Surgical
- stricturoplasty: ≤10cm: conventional Heineke-Mikulicz stricturoplasty; 10-25cm Finney procedure or Michelassi procedure; should be considered if there is a need to preserve small bowel length
- small bowel resection: can be considered for strictures >10cm or multiple strictures (one single resection); medically refractory disease
498
What is the approach to perianal crohn's?
Ix
- EUA + MRI (+/-endoanal US)
---> define anatomy, presence of abcesses + mucosal inflammation
Drain abscesses + place seton
Consider early IFX (trough levels >10mcg/ml)
Repeat flexi at 4-6 months to check mucosal healing + adjust medical management accordingly
499
List the different types of fistulae
Simple
Superficial perianal or ano-vaginal
Intersphincteric perianal or ano vaginal
Complex
Trans-sphincteric perianal
Suprasphincteric perianal
Extrasphincteric perianal
Enterocutanous
Entero-enteric
Enterovesical
Rectovaginal
500
Fill in the blanks
501
What procedures are possible for fistulas not healing with seton placement?
Advancement flap
Ligation of intersphincteric fistula
Collagen plug
Fibrin glue
Mesenchymal stem cells
Hyperbaric oxygen
Endoscopic closure (OTSC)
Defunctioning
502
What IFX dose / targets should be used in perianal disease?
Consider 10mg/kg dosing
Target trough level >10ug/ml
503
What is the role of antibiotics in crohn's disease?
For fistula associated abscesses
High rates of SIBO proximal to strictures
504
What risk factors exist for the recurrence of crohn's post resection?
Smoking
Genetics
Disease duration/exent
Previous surgery
Penetrating disease
Granulomatous disease
Myenteric plexitis
Surgical technique
- Kono-S anastomosis (anti mesenteric) better
- inclusion of mesentery in resection reduces recurrence
3 months metro 400mg TDS helps
Post-op aza vs anti-TNF can help
505
What is the post-op approach to resections in crohn's?
3 months metro 400mg TDS
Consider post-op aza 12 months +/- anti-TNF if multiple risk factors for recurrence
Ileocolonoscopy at 6 months post op + rutgeerts score
- escalate medical therapy if ≥i2 disease (15-20% recurrence rate for i2 disease)
506
What is the rutgeert's score?
Endoscopic assessment of recurrence at neo-terminal ileum
i0/i1 = remission
≥i2 = recurrence
i0: no lesions
i1: ≤5 apthous ulcers
i2: >5 apthous ulcers with normal intervening mucosa. Skip areas of larger lesions confined to ileocolonic anastamosis (15-20% recurrence rate)
i3: diffuse aphthous ileitis with diffusely inflamed mucosa
i4: diffuse inflammation with large ulcers / nodules / stenosis
507
Describe the colonoscopic surveillance in IBD
Start at 8 years post symptom onset OR at the time of diagnosis of PSC
Intervals
- 5 years: quiescent disease OR left sided colitis OR crohn's colitis affecting <50% of the colon
- 3 years: extensive colitis with mildly active endoscopic or histological inflammation or pseudopolyps OR FHx CRC 1st degree relative aged ≥50
1 year: extensive colitis with moderate-severe active colitis OR stricture/dysplasia in last 5 years OR PSC OR FHx CRC 1st degree relative <50 years
Ideally chromoendoscopy with targeted biopsies
Excise polyps as the appear, but if unresectable lesions consider colectomy
508
How would you establish a diagnosis of iron deficiency in IBD?
Ferritin <30ug/L (absence of inflammation)
OR <100ug/L (presence of inflammation)
509
What are the indications for IV iron in IBD patients with IDA?
Clinically active disease
Hb <100
Previous PO iron intolerance
Those who need EPO
510
List the extraintestinal manifestations of IBD NOT associated with disease activity
Pyoderma gangrenosum
Uveitis
Scleritis
Primary sclerosing cholangitis
Enteropathic arthritis
- axial subtype
- type 2 peripheral subtype (symmetrical, large + small joint, upper limb predominant polyarthritis)
511
List the extraintestinal manifestations of IBD which ARE associated with disease activity
Enteropathic arthritis (type 1 peripheral, assymmetrical large joint type oligoarthritis)
Episcleritis
Erythema nodosum
Apthous oral ulcers
512
Describe the different patterns of enteropathic arthritis and how they correlate with IBD activity
Peripheral arthritis - usually non-deforming, non-erosive
- Type 1
--> Correlates with IBD activity
--> Asymmetrical, lower limb, large joint-predominant oligoarthritis
- Type 2
--> Does not usually correlate with IBD activity
--> Symmetrical, large + small joint, upper limb-predominant polyarthritis
Axial arthritis
- Independent of IBD activity
- Inflammatory back pain, sacroiliitis, or ankylosing spondylitis (3-10% of patients with IBD)
513
How should IBD patients with backpain be investigated?
MRI for patients <40 with pain lasting > 3 months
514
What is the management of enteropathic arthritis?
Treat the underlying IBD
Responds to corticosteroids
Beware NSAIDs as these worsen IBD symptoms
Consider MTX in crohn’s
5-ASAs may help, particularly in UC
Anti-TNFs are usually required if refractory to the above
515
In which IBD subtype is pyoderma gangrenosum most common?
UC
516
Detail the neutrophilic dermatoses associated with IBD
Erythema nodosum
Pyoderma gangrenosum
Sweet's syndrome
517
What are the common sites for pyoderma gangrenosum?
Shins, around surgical stomas
Lesions typically occur at sites of trauma (pathergy)
518
What is the management of mild and moderate-severe pyoderma gangrenosum?
Mild disease
- Topical corticosteroids
- Topical tacrolimus (0.03% - 0.3% strength)
Moderate-severe disease
- Corticosteroids
- Anti-TNF - 90% response rate
- Ciclosporin
519
What would a biopsy show in erythema nodosum?
Panniculitis
520
What is described by the following?
Rapidly evolving tender, red, inflammatory papules
Lesions can occur at sites of trauma (pathergy)
Otherwise affect upper limbs, face, neck +/- oral ulcers +/- arthralgia
Fever also present
Sweet's syndrome
521
What investigations can be done for Sweet's syndrome?
Raised inflammatory markers
p-ANCA may be positive
Skin biopsy: pathognomonic angiocentric, vessel-based dermal neutrophilic infiltrate
522
What is the management of sweet's syndrome?
Topical or systemic corticosteroids
IFX in resistant cases
Others: potassium iodide, colchicine, dapsone
523
What is described by the following?
Painless hyperaemia of the sclera without visual disturbance
What is the management
Episcleritis
Usually self limiting, otherwise responds to topical corticosteroids and effective treatment of intestinal disease
524
What is described by the following?
Inflammation of the deep scleral vessels
Erythema, ocular pain and visual disturbance (rarely, only in severe cases)
Characteristically worse at night
What is the management?
Scleritis
NSAIDs (with caution), systemic steroids or immunosuppression
525
What is described by the following?
Insidious onset visual loss with pain
Red eye
What is the management?
Anterior uveitis (affects iris)
Corticosteroids, ciclosporin, thiopurines, anti-TNFs + requires prompt ophthal referral
526
What is described by the following?
Painless visual loss + red eye
What is the management?
Posterior (affects choroid and retina) or intermediate (between ciliary body and retina) uveitis
Corticosteroids, ciclosporin, thiopurines, anti-TNFs + requires prompt ophthal referral
527
What are the general outcomes for pouches?
BO 5x/day, 1x/night
50% minor treatable problems
Seepage in 20% requiring pads
20% struggle
10-15% pouch failure at 10 years
528
What issues / complications might result from a pouch? How do they present?
Acute/chronic pouchitis
- diarrhoea, urgency, seepage, cramping
Sphincter insufficiency
- incontinence
Incomplete emptying (due to pouch relying on increasing intra-abdominal pressure due to impaired peristalsis)
- incontinence
- high frequency
Difficulty emptying
- anastamotic stricture
- functional
529
How should acute pouchitis be approached? What are the key results which would confirm the diagnosis? What is the treatment?
Bloods, fcal, stol mcs/CDT, consider empirical cipro or metro
Pouchoscopy + biopsy including assessment of pre-pouch ileum
Histology suggestive of pouchitis: acute inflammation with neutrophil infiltration, crypt abscess, and mucosal ulceration often superimposed on a background of chronic changes, including villous atrophy, crypt distortion, or hyperplasia, pyloric gland metaplasia, and chronic inflammatory cell infiltration
If confirmed pouchitis: 2/52 course of either cipro or metro
If does not respond then increase up to 4 weeks abx
530
What antibiotic treatment options are valid for pouchitis?
Cipro 500mg BD
Metronidazole 400mg TDS
Rifaximin 1g BD
531
What is the definition of chronic pouchitis? What is the approach?
Unresolved symptoms/rapid relapse despite 4 weeks of antibiotics
Consider coliform testing + abx tailored to sensitivity
8 weeks budesonide (MMX)
Anti-TNF, tacrolimus if not responding
532
What is the management of pouch failure?
Ileostomy
- will be high output
Pouch excision
- risks erectile dysfunction 10-15%
- risks perineal sinus 40%
533
What is the approach to pouch surveillance?
Generally every 5 years
Consider yearly if highly inflamed pouch, or PSC
534
Which IBD drugs cannot be given in pregnancy? When should they be stopped pre-conception?
MTX - stop 3-6 months before
JAK inhibitors - stop 1-4 weeks prior
Ozanimod (no data, so currently avoid) 3 months pre
535
What are the contraindications to vaginal delivery in IBD?
Absolute: perianal fistulating disease or rectovaginal
Relative: IPAA (continence risk)
536
What is the approach to vaccinating children to mothers on biologics?
Avoid live vaccines (listed) for 6 months
537
What is the treatment of diversion colitis?
Restoration of gut continuity if possible
SCFA enemas
Topical 5-ASAs if no response to SCFAs, or in combination in cases of IBD
Corticosteroids
Completion proctectomy
Many cases self resolve without treatment
538
List the different types of E Coli and their symptoms in infective colitis
Enterotoxigenic - watery diarrhoea
Enteropathogenic - infantile diarrhoea
Enterohaemorrhagic - bloody diarrhoea - shiga toxin producing variant
Enteroinvasive - dysentry
Enteroaggregative - persistent diarrhoea in children or HIV infected / immunosuppressed patients
539
What are the late onset complications of campylobacter infection?
Reactive arthritis 2%
GBS (0.1%)
Immunoproliferative small intestinal disease (v rare!)
540
What is strongyloidiasis? Where is it found? What are the symptoms?
Nematode
Common in tropics, subtropics, (southern Europe and the USA)
Asymptomatic in 60%
Symptoms of acute infection (rare)
- Irritation of site of penetration through the skin
- Dry cough
- GI symptoms
Symptoms of chronic infection
- Pathognomonic rash - larva currens
--> Creeping eruption caused by subcutaneous migration of the larvae
--> Raised + itchy like a wheal
--> Transient
--> Usually develops on trunk
- Abdo pain, intermittent diarrhoea, weight loss
- Rarely dry cough or wheeze if larvae migrate to lungs
Rare complication = hyperinfection syndrome
- Patients with chronic infection who then become immunosuppressed
-> widespread dissemination
- Symptoms: bloody diarrhoea, bowel perforation, G-ve sepsis, pulmonary exudates, meningo-encephalitis
541
What key ix may be seen in strongyloidiasis?
Blood eosinophilia
Stool microscopy (low sensitivity 50% due to intermittent larval excretion)
S stercoralis serology
542
What is the management of strongyloidiasis?
Ivermectin
Supportive
543
What are the causes of CMV colitis?
CMV infection in immunosuppressed IBD patients or rare cause of diarrhoea in HIV CD4 <50
544
What are the histological features of a patient with CMV colitis?
'inclusion bodies'
545
What is the management of CMV colitis?
1st line IV ganciclovir (beware myelosuppression) followed by PO valcancyclovir 3-6 weeks
Second line - IV foscarnet (beware renal impairment and seizures)
Restart ART, but if co-morbid CMV retinitis give 2 weeks of CMV treatment prior to prevent IRAS
546
What are the causes of diarrhoea in HIV What are their treatments?
Cryptosporidium
Mx: nitazoxanide
Disseminated mycobacterium avium complex
Mx: clari + ethambutol
CMV colitis
Mx: IV ganciclovir -> PO valganciclovir
547
When does checkpoint inhibitor colitis present?
Can present at any time, but usually within weeks-months of starting
548
How is the severity of checkpoint inhibitor colitis graded clinically?
Grade 1: Increase of <4 stools per day over baseline; mild increase in ostomy output compared with baseline
Grade 2: Increase of four to six stools per day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADL
Grade 3: Increase of seven or more stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADL
Grade 4: Life-threatening consequences; urgent intervention indicated
549
What is the approach to suspected checkpoint inhibitor colitis?
Bloods, stool mcs/CDT, fcal
Flexi for grade 2-4 symptoms (+ biopsy to exclude CMV)
Grade 1:
- dietary modification
- loperamide
+/- withhold checkpoint inhibitor
Grade 2:
- discontinue ICI
- start pred 1mg/kg/day + taper once G1 symptoms achieved
Grade 3 without systemic symptoms:
- discontinue ICI
- start pred 1mg/kg/day + taper once G1 symptoms achieved
Grade 3 with systemic symptoms, grade 4:
- IV methylpred 1-2mg/kg daily (max 120mg) in 2x divided doses
- PO switch when G1 symptoms
- if no response at 72 hours then biologic
---> IFX 5mg/kg or 10mg/kg if hypoalbuminaemia <25 or G4/severe disease; 0, 2, 6 week dosing
---> VDZ 300mg 0, 2, 6 weeks
Biologics at the start if high risk endoscopic features
Biologics typically don't require maintenance
550
In checkpoint inhibitor colitis what are the adverse endoscopic findings?
Large ulcers >1 cm
Deep ulcers >2 mm
Multiple ulcers (3 or more)
Extensive colitis
551
What are the typical sites of ischaemic colitis?
splenic flexure and sigmoid (watershed)
552
What risk factors in ischaemic colitis are associated with a poor outcome with conservative management?
Right sided colitis, male sex, lack of rectal bleeding, renal dysfunction, colonic strictures, peritonitis
553
What is the typical patient with microscopic colitis?
Profuse watery diarrhoea
Woman in her 60s
Drugs: PPIs, NSAIDs, SSRIs
40% concomitant autoimmune disease
554
Describe the histological features of microscopic colitis
Collagenous
- Intact crypt architecture
- Increase in colonic mucosal subepithelial collagen layer
--- >10um
--- Usually type I or III collagen (type IV rarer)
Lymphocytic
- Increased IELs (>20)... NB: in IBD usually 4-5 lymphocytes per 100
- Absence of increased subepithelial collagen layer
- intact crypts usually, rarely acute cryptitis/crypt abscess
555
What is the diagnosis in this patient with watery diarrhoea?
Collagenous colitis
556
What is the management of microscopic colitis?
Remove drug cause
Antidiarrhoeals for mild disease
Budesonide
5-ASAs
No colonoscopy surveillance required
557
Fill in the blanks. What is the classification system called? What is it for?
Kudo pit pattern. For assessing neoplastic potential of colorectal lesions
558
What is the definition of serrated polyposis syndrome?
At least 5 serrated lesions proximal to rectum all 5mm in size with 2+ ≥10mm in size
> 20 lesions of any size distributed throughout the large bowel with at least 5 proximal to rectum
Any number of polyps proximal to the sigmoid in a patient with a 1st degree relative of SPS
Polyp count is cumulative over multiple colonoscopies
Included histological lesion types of serrated lesions/polyps
- Hyperplastic
- Sessile serrated lesion +/- dysplasia
- Serrated adenoma
- Unclassified serrated adenoma
559
What is the colonoscopic surveillance in serrated polyposis syndrome? What is the family screening of relatives of affected patients?
Annual to all SPS patients until the colon has been cleared of all lesions >5mm
If no polyps ≥10mm at subsequent surveillance, then interval can be 2 yearly
FDRs of patients should be offered index colonoscopy at age 40 and then five-yearly surveillance thereafter (but also dependent on polyp burden i.e. may be sooner)
560
What is the CRC risk in serrated polyposis syndrome
7-10% lifetime
561
What is the definition of Lynch syndrome? What is the cancer risk associated?
Autosomal dominant inherited condition due to germline mutations of DNA mismatch repair genes MLH1, MSH2, MSH6, PMS2, or loss of MSH2 expression due to mutation in EPCAM gene
Most common inherited condition of colorectal cancer
Also increases risk of UGI, pancreatic, skin (sebaceous and keratocanthoma), prostate, ovarian, endometrial, urinary tract cancers
Affects 1/450 in the UK
MLH1 (45%) and MSH2 (35%) have highest colorectal cancer risk
MSH6 (20%) and PMS2 (14%) have lower cancer risk but are more common
562
How is Lynch syndrome diagnosed?
Based on germline genomic testing
Patients are identified for germline testing based on testing for mismatch repair expression and microsatellite instability in identified colorectal cancers
All patients with colorectal cancer <40 years old are eligible for germline testing directly
563
What cancer surveillance should be offered to patients with Lynch syndrome?
2 yearly colonoscopy
Starting age 25 for MLH1 or MSH2 mutations
Starting age 35 for MSH6 or PMS2 mutations
OGDs
- not yet determined
564
What non-surveillance measures can be offered for Lynch syndrome
Gynae
- Offer TAH + BSO from aged 40
Aspirin
- Avoid if >70 years old
- Usual dose 150mg OD
- If obese 300mg OD
- Take for at least 2 years and up to 5 years total
565
Which patients with suspected polyposis syndromes should be considered for germ-line testing? What are the differentials?
Consider germline testing for:
– Patients under 60 years of age with lifetime total of ≥10
adenomas; or
– Patients from 60 years of age with lifetime total of:
–--- ≥20 adenomas, or
–--- ≥10 adenomas and a family history of colorectal cancer or polyposis
DDx
Multiple colorectal adenomas
MAP (MUTYH associated polyposis)
FAP
Peutz-Jeghers
Juvenile polyposis syndrome
566
What is MAP - MUTYH associated polyposis? What is the colorectal cancer risk?
What is the surveillance?
AR MUTYH mutation
100% CRC risk at 60
Annual colonoscopy starting at age 18-20
OGD starting at age 35 and then according to Speigelman criteria
567
What is FAP? What is the screening?
AD APC mutation
Annual colonoscopy starting at diagnosis or 12-14 years old
OGD starting at age 25 and then according to speigelman criteria
Pouchouscopy after colectomy every 1-3 years
568
What is the role of colectomy in FAP?
Consider
- polyps >10 mm in diameter, high grade dysplasia within polyps and a significant increase in polyp burden between screening examinations
Absolute
- documented or suspected cancer or significant symptoms attributable to the polyposis.
569
What is Peutz-Jeghers syndrome? What are the diagnostic criteria?
AD hamartomatous polyposis syndrome
Most common mutation = STK11, but 40-80% do not have this
GI cancer + breast cancer risk + pancreatic cancer risk + ovaries + testes
Diagnostic criteria
- ≥2 histologically confirmed PJ polyps
- Any number of PJ polyps in an individual with +ve FHx in a close relative
- Characteristic mucocutaneous pigmentation with +ve FHx
- Any number of PJ polyps in individual with characteristic mucocutaneous pigmentation
- Pathogenic variant in STK11
570
What is the surveillance for Peutz-Jeghers syndrome?
Commence at 8 years old
Gastroscopy - if normal, can defer next until age 18. Otherwise 3 yearly
Colonoscopy - if normal, can defer next until age 18. Otherwise 3 yearly
VCE - 3 yearly
Pancreatic cancer surveillance
571
What is juvenile polyposis syndrome?
Autosomal dominant condition of multiple hamartomatous polyps throughout the GIT
SMAD4 and BMPR1A genes involved
572
What is the endoscopic screening for juvenile polyposis syndrome?
Colonoscopy: starting aged 15 and every 1-3 years
OGD
- SMAD4 mutation: start aged 18 and every 1-3 years
- BMPR1A mutation: start aged 25 and every 1-3 years
573
What is the surveillance with non-syndrome multiple colorectal adenomas (≥10)?
From age of diagnosis, yearly until polyps cleared, then every 2 years
574
What is the approach to colonoscopic screening of patients with a family history of colorectal cancer?
Moderate risk - colonoscopy at 55 and then according to any polyps found
- 1x FDR <50
- OR 2x FDRs any age
High risk - 5 yearly (or sooner if polyps) from age 40
- 3x FDRs across >1 generation
575
Define the following terms:
- serrated polyp
- premalignant polyp
- advanced serrated polyp
- advanced adenomatous polyp
- advanced colorectal polyp
Serrated polyp: umbrella term used to describe hyperplastic polyps, sessile serrated lesions (SSLs), SSLs with dysplasia (SSLd), traditional serrated adenomas (TSA) and mixed polyps. Serration is a histological definition of the crypt architecture
Premalignant polyp: includes both serrated polyps (excluding diminutive (1–5mm) rectal hyperplastic polyps) and adenomatous polyps. It does not include other polyps such as post-inflammatory polyps
Advanced serrated polyp: serrated polyp of at least 10mm in size or containing any grade of dysplasia
Advanced adenomatous polyp (synonymous with advanced adenoma): adenoma of at least 10mm in size or containing high-grade dysplasia. Note: international definitions also include tubulovillous or villous histology, but these are not part of the UK definition.
Advanced colorectal polyp: includes both advanced serrated polyps and advanced adenomatous polyps.
576
What is the Haggitt classification? What is its relevance?
Grading extent of invasion of carcinoma into a pedunculated polyp
0: carcinoma in situ i.e. confined to mucosal layer only - no chance of lymph node metastasis
1: invasion through muscularis mucosa, but confined to head of the polyp - 0-2% lymph node involvement
2: invasion through muscularis mucosa to the neck of the polyp - <5% lymph node involvement
3: invasion to stalk of the polyp - 7-10% lymph node involvement
4: invasion into the submucosa of the bowel wall, but above the muscularis propria
577
Detail LST classification and the likelihood of submucosal invasion in each
578
What are the indications for ESD in colorectal lesions?
Colorectal lesions where en bloc resection is desired and snare EMR may be difficult
Laterally spreading tumors-nongranular
Vi-type pit pattern
T1 (SM) invasion
large depressed-type and protruded-type lesions suspected for carcinoma)
lesions with submucosal fibrosis
tumors occurring in chronic inflammation (Ulcerative Colitis)
residual/recurrent carcinoma after endoscopic resection
579
What are the guidelines for post colorectal polypectomy / colorectal cancer resection surveillance? Define pre-malignant and advanced colorectal polyps
Colorectal cancer colectomy: colonoscopy at 1 year, then 3 years later
Large non-pedunculated colorectal polyp (≥20mm)
- ESD with R0 resection: one off surveillance 3 years
- EMR: site check at 2-6 months and then another 1 year
High risk findings (≥2 premalignant polyps including ≥1 advanced colorectal polyp OR ≥5 premalignant polyps)
- repeat colonoscopy at 3 years
No high risk findings - participate in bowel cancer screening OR consider 5-10 years colonoscopy if >10 years away from bowel cancer screening
Premalignant polyp: serrated polyp excluding small rectal polyps 1-5mm, adenomatous polyps
Advanced colorectal polyps: adenomatous or serrated polyps >10mm , serrated polyps with dysplasia, or adenomatous polyp with high grade dysplasia
580
Describe bowel cancer screening in the UK
FIT testing every 2 years age 54-74 (expanding to 50 years in progress)
f-Hb≥10 ug Hb/g -> colonoscopy 2ww
Stop surveillance age 75 unless specifically requested to GP
581
What are the symptoms of radiation proctitis? How many will experience it? When does it present?
Typical proctitis symptoms
50% will experience some PR bleeding after pelvic radiotherapy
May present several years after treatment
582
Describe the histology of radiation proctitits
Fibrosis of the lamina propria and a variable degree of epithelial injury, crypt distortion, and Paneth cell metaplasia. Lack of inflammatory cell infiltrate
583
What is the management of radiation proctitis?
Optimise bowel function, stool softeners
Sucralfate enemas
PR metronidazole
Endoscopic: APC, heat, formalin
Hyperbaric oxygen
584
What is melanosis coli?
Lipofuscin = pigment in melanosis coli
More common in senna
Commonly affects proximal colon
Asymptomatic
585
What is brown bowel syndrome? What conditions is it associated with?
Lipofuscin deposition in tunica muscularis
Association with malabsorptive conditions and vit E deficiency
586
What is melanosis ilei?
Aluminium, silicon and magnesium found in Peyer’s patches
Haemosiderin found in lamina propria of the ileium in patient with melanosis ilei after chronic iron ingestion
587
What are the pathological results of bowel transit studies?
Slow transit =
≥ 6 markers in colon on transit study is diagnostic
Ingestion of 24 markers in a capsule on day 1
AXR on day 6
Dyssingergistic defecation =
≥6 markers in rectosigmoid
588
Fill in the blanks
589
From which artery does the hepatic artery arise?
Coeliac axis
590
Which liver segments are supplied by the right hepatic artery?
I, V, VI, VII and VIII
591
Which liver segments are supplied by the left hepatic artery?
II, III, IV
592
What segments are resected in right and extended right hepatectomy?
Right hemi-hepatectomy: resection V-VIII
Extended right hepatectomy sometimes extended to include caudate (segment I)
593
What segments are resected in left hepatectomy?
II, III, IV
594
From where does the portal vein arise?
Confluence of superior mesenteric and splenic veins
595
List the types of potential varices and their anatomical basis
Oesophageal: anterior and posterior oesophageal venous tributaries of the left gastric vein
Gastric: peripheral venous tributaries of the left gastric, short gastric and gastro-epiploic veins
Rectum: superior haemorrhoidal vein
Retroperitoneum: gonadal, lumbar and paraduodenal veins
Surgical stoma: communication between relocated mesenteric & cutaneous veins
596
Fill in the blanks
597
Fill in the blanks.
What do the green and red arrows represent?
Green: flow of bile
Red: blood flow
598
What cell types are there in the liver?
Hepatocytes
Kupffer cells - phagocytic cell which lines the sinusoids
Stellate cell - lipid storage cell which store vitamin A and respond to cellular injury producing extracellular matrix proteins. Key role in liver fibrosis development
Endothelial cell
599
Fill in the blanks
600
Detail the child-pugh score and its prognostic significance
Bilirubin
1 point: <35
2 points: 35-50
3 points: >50
Albumin
1 point: >35
2 points: 28-35
3 points: <28
INR
1 point: ≤1.7
2 points: 1.71-2.3
3 points: >2.3
Ascites
1 point: none
2 points: mild
3 points: moderate-severe
Encephalopathy
1 point: none
2 points: grade I-II (or suppressed with medication)
3 points: grade III or IV (or refractory)
CLASS A: score 5-6, 1 year survival 100%
CLASS B: score 7-9, 1 year survival 80%
CLASS C: socre 10-15, 1 year survival 45%
601
List the blood tests / scores for fibrosis and their cutoffs or components
Fib4 ≥3.25 (age, ALT, AST, plt)
ELF ≥ 9.8
- Blood test of three extracellular matrix turnover proteins (hyaluronic acid, tissue inhibitor of metalloproteases-1 and amino terminal propeptide of type III procollagen)
APRI (equation using AST and platelet count) ≥1
AST:ALT ratio ≥1 (noting that usually in NAFLD ALT > AST
BARD score ≥2 (BMI, AST:ALT, DM)
NAFLD fibrosis score (age, albumin, ALT, AST, BMI, DM, platelet count) >0.675
602
Fill in the blanks
603
Fill in the blanks
What does F1-4 mean?
F0-1: minimal fibrosis
F2: advanced fibrosis
F3: severe fibrosis
F4: cirrhosis
604
Fill in the blanks
605
On the basis of ascitic fluid analysis, how can heart failure and portal hypertension aetiologies be told apart?
When SAAG >11g/L, an ascitic fluid protein <25g/L suggests cirrhosis more likely; ≥ 25g/L suggests heart failure
606
How often should decompensated cirrhotics have oesophageal variceal screening?
Annual
607
What dietary advice is given to liver cirrhosis patients?
1.5-2g/kg protein per day
30-35kcal/kg per day
Carbs every 2-3 hours
Bedtime snack
No added salt
608
Detail the west haven hepatic encephalopathy score
1) Trivial lack of awareness, shortened attention span, euphoria or anxiety, impaired addition
2) Lethargy, minimal disorientation, inappropriate behaviour, personality change, impaired subtraction
3) Somnolence-semi stupor, gross disorientation, asterixis
4) Coma
609
What is the driving advice after an episode of HE?
No driving for 3 months after overt episode
610
What is the driving advice in alcohol use disorder?
Alcohol free 12 months
611
If the lab delays ammonia processing, is a false negative or positive more likely?
False positive
612
What is the prognostic benefit of ammonia?
Predicts cerebral oedema in acute liver failure
613
What is HVPG? What is the relevance of different values?
HVPG = hepatic venous pressure gradient
Difference between wedged and free hepatic venous pressures
Catheter goes into hepatic vein usually via jugular vein
HVPG 1-5 mmHg = normal
HVPG 6-9 mmHg = preclinical sinusoidal portal hypertension
HVPG ≥10mmHg is clinically significant portal hypertension (and pre requisite for developing varices)
-- Independent risk factor for HCC development in cirrhosis
-- Increased the risk of decompensation after hCC resection - thus only resect those with HVPG <10mmHg
Reducing HVPG <12 mmHg is associated with reduced risk of variceal bleeding, ascites and mortality
614
What are the indications for SBP prophylaxis?
What are the drug options?
Indications
If previous episode of SBP
If ascitic fluid protein <15g/L
Drugs
960mg co-trimoxazole OD
ciprofloxacin 500mg OD
norfloxacin 400mg OD
615
Define AKI in cirrhosis and the stages
AKI in cirrhosis is defined as a rise in serum creatinine ≥26.5umol/L in <48 hours or a rise of 1.5x from baseline in <7 days
Stage 1 ≥1.5x baseline
Stage 2 ≥2x baseline
Stage 3 ≥3x baseline
616
Which urinary tests suggest pre-renal or HRS AKI?
Urinary sodium <20
FeNa <0.1% (usually <1%, however, cirrhosis already has a state of sodium retention therefore some suggest stricter cutoffs)
FeUrea <21%
617
Which urinary tests suggest parenchymal renal disease in AKI?
Proteinureia >500mg/day
Microscopic haematuria (>50 RBCs per HPF)
Muddy brown casts on microscopy suggests ATN
High FeNa (>2-3%) and high FeUrea also suggests ATN
ATN does not affect glomerulus and should not cause significant proteinuria
618
What is the fluid regimen recommended in the first 48 hours in decompensated cirrhotic patients presenting with AKI?
Intravascular depletion
- crystalloid solutions
Equivocal volume status
- 1g/kg/day albumin (in 20% solutions)
619
What is the role of albumin and terlipressin in HRS?
First 48 hours (when suspected but not confirmed HRS)
- 1g/kg/day HAS 20%
Thereafter (when HRS confirmed)
- HAS 20% 1-2 bottles / day
+ terlipressin 1mg QDS
Reassess after starting treatment
- if creatinine level decreases <30% then increase to 2mg QDS
Continue terli max 14 days + discontinue if creatinine <1.5mg/dL (132umol/L)
620
What is hepatopulmonary syndrome? What is the diagnostic criteria? What are the key clinical features?
Syndrome from increased NO + endothelin production
Diagnosis
- liver disease and / or portal hypertension
- positive contrast enhanced (bubble) echocardiography or >6% updake in the brain with radionucleotide lung perfusion
- PaO2 < 10.7 kPa on room air OR < 9.3 kPa if >64 years
Orthodexia = lying and standing blood gas drop 0.5kPa
621
What is the treatment of hepatopulmonary syndrome?
Liver transplant
- may take months
- may be too sick to undergo
Supplemental oxygen in the interim
622
What is portopulmonary hypertension? How is the diagnosis made?
Pulmonary hypertension with vasoconstriction secondary to portal hypertension
Severity does not correlate with severity of liver disease
Screening: echo RVSP ≥50mmHg or RV hypertrophy
Diagnosis
1) portal hypertension
2) right heart cath
- mean pulmonary artery pressure >25mmHg
- mean pulmonary capillary wedge pressure <15mmHg
- pulmonary vascular resistance >240dyn/s/cm^5 or 3 wood units
Severity defined by MPAP
Mild 25-34
Moderate 35-44
Severe ≥45
623
What is the relevance of portopulmonary hypertension? What is the treatment?
Does not resolve portopulmonary hypertension reliably, so not an indication for transplant
High mortality from LT in severe portopulmonary hypertension
Mx
- Sildenafil
- prostoglandin analogues (iloprost, epoprostenol)
- endothelin receptor antagonists (bosentan… some data that it worsens liver function so generally avoided)
- Improves 5 year survival to 45% from around 15%
624
What HVPG values are required for variceal bleeding?
≥10 mmHg
625
Detail the grading of oesophageal varices
Grade I: completely flatten on insufflation
Grade II: <30% of oesophageal lumen
Grade III >30% of oesophageal lumen
626
How common are oesophageal varices?
In compensated disease, 10-15% have varices requiring primary prophylaxis
Overall 50% of cirrhotics have GOVs of any type
- 40% in child-pugh A
- 86% in child-pugh B
627
What is the approach to primary prophylaxis for oesophageal varices in liver cirrhosis? Who should be screened for varices?
Baveno VI criteria regarding who to test:
If plt >150 and fibroscan <20kPa then no variceal screening needed
Should be remeasured annually to reassess
Also HVPG <10 mmHg can avoid, but this is rarely measured
Grade I varices
If on index endoscopy + child Pugh A + no red signs - no therapy and repeat in 1 year
If red signs - NSBB
If child pugh B/C - NSBB
≥ grade II
If red signs - band + NSBB
If no red signs - NSBB
If patients decompensate then urgent OGD for varices assessment
628
What is the rate of varices development and the chance of variceal bleeding?
Those cirrhosis but without varices develop them at a rate of 8% per annum + those with small varices develop large varices at a rate of 8% per annum
15% chance of variceal haemorrhage per annum in those with large varices, vs 5% chance in those with small varices
629
What is the approach to correcting coagulopathies in acute GI bleeding?
PLT >50
FFP 3-4 units (15ml/kg) if INR >1.5
Cryo if fibrinogen <1
630
What IR procedures are available for gastric varices? What are their indications?
(Modified) balloon-occluded retrograde transvenous obliteration
For prominent infra-diaphgragmatic portosystemic shunts e.g. gastrorenal, gastrocaval
Indications
- active haemorrhage
- failed endoscopic treatment
- contraindications to TIPSS
- prophylaxis against rebleeding (after primary endoscopic therapy)
631
What are the indications for rescue TIPSS?
Definite:
CP C ≤13
No RV/LV failure
No HE
Possible:
CP C ≥14
HE or previous HE
632
What is the management of rectal varices
Consider endoscopic glue injection
Sengstaken and inflate to 100-150ml
633
What electrolyte abnormalities can occur with terlipressin?
Hyponatraemia
634
What is the management of different GOVs and IGVs?
IGV1-2
- glue
- TIPSS
- BRTO
GOV1
- usually just banding
- sengstaken
GOV2
- glue
- sengstaken
635
What is the definition of acute liver failure?
Jaundice
AND INR >1.5 AND encephalopathy
WITHOUT pre-existing cirrhosis
AND <26 weeks duration
Specific exceptions to ‘without pre-existing cirrhosis’ rule
- Acute presentation of autoimmune liver disease
- Budd chiari
- Wilson’s disease
- Reactivation of hepatitis B
636
What is the mortality of ALF?
40%
637
What ALF aetiologies carry a favourable prognosis?
Paracetamol
Ischaemia
Pregnancy
Hepatitis A
638
What ALF aetiologies carry an unfavourable prognosis?
DILI
Cryptogenic
Autoimmune
Hepatitis B
Wilson disease
639
What is the O'Grady classification of ALF? What are the aetiologies of each?
Hyperacute (<7days)
Paracetamol
Ischaemia
MDMA
Pregnancy
Very high transaminases
Highest chance of cerebral oedema
Chance of survival even with severe hepatic encephalopathy
Acute/subacute (day 8-28 onwards)
Viral hepatitis, budd-chiari
Mod-high transiminases
Encephalopathy is associated with very poor outcome
Subacute (5-12 weeks)
Bilirubin more pronounced, transaminases less pronounced
DILI
AIH
Cryptogenic causes
640
What are some difficulties with imaging in ALF?
Parenchymal collapse can mimic liver cirrhosis in imaging
Liver cirrhosis is not detectable in 20% cross sectional imaging
641
What imaging feature is classic for subacute liver failure?
Shrinking liver size?
642
In ALF, what is the indication for liver biopsy?
AIH features
Cirrhosis, alcoholic hepatitis features?
Exclusion of malignancy, lymphoma, HLH
643
What is the dosing of NAC?
150mg/kg over 1 hour, then 50mg/kg over 4 hours, then 100mg/kg over 16 hours, followed by 100mg/kg/day, should be continued for minimum 3 days, but up to 7 days
644
What intracranial hypertension monitoring can be used in ALF?
Cerebral pulsality index by transcranial doppler sonography
Optic nerve sheath diameter by ultrasound
645
What options are there for reducing intracranial hypertension in patients with ALF?
Prophylaxis
- elevate head to 30 degrees
- induce hypernatraemia 145-155
- Early CRRT (lowers ammonia, corrects hypo-osmolality)
- prophylactic hypothermia (35-36C)
- induce mild respiratory alkalosis
Treatments
- mannitol boluses
- hypertonic saline boluses
- vasopressors aim MAP >65mmHg
- therapeutic hypothermia (32-34C)
- deeper sedation
646
In ALF what is the general split in terms of functional coagulability in patients?
20% hypocoag
45% normal
35% hypercoagulable
647
What is the approach to VTE prophylaxis in ALF?
Whilst INR is still climbing (acute phase) generally avoid, but then as it stabilises/improves (recovery phase) definitely give
648
What is the role of antibiotics in acute liver failure?
Start abx if progression of hepatic encephalopathy due to risk of worsening intracranial hypertension with infection
Temperature + wcc unreliable in ALF
Consider co-trimoxazole prophylaxis for all
Consider aciclovir prophylaxis according to CMV status
649
What liver biochemical patterns give clues to particular liver aetiologies?
Transaminases in the thousands
- Ischaemia
-> AST:ALT often 2:1
- Viral (less so for CMV/EBV)
- Paracetamol
-> renal failure particularly prominent
Fever
HAV, EBV, CMV
AIH
High hundreds AST
IgG may be normal
Wilson's
Haemolysis
Low level transaminitis
Low ALP
Renal failure
Acidosis
Caeruloplasmin and 24 hour urine copper not sensitive in ALF
650
What can be given for mushroom liver toxicity/ALF?
silymarin/milk thistle
651
What can be given for HSV liver toxicity / ALF?
Aciclovir
652
What are the King’s college criteria (paracetamol) for transplant in ALF? What are the other markers of poor prognosis?
Arterial ph <7.3 after resuscitation and >24 hours since ingestion
OR all of
- Grade 3 HE
- Serum creatinine >300
- INR >6.5
Other markers of poor prognosis
- Lactate >3mmol/L after 12 hours of fluid resuscitation OR >3.5 after <4 hours resuscitation
- Phosphate >1.2 mmol/L at 48-96 hours
653
What are the King’s college criteria (non-paracetamol) for transplant in ALF?
INR >6.5
OR 3 / 5 following
- Indeterminate or drug-induced aetiology
- Age ≤10 or >40
- Jaundice-encephalopathy interval >7 days
- Bilirubin >300
- INR >3.5
654
What is the definition of ACLF?
ACLF = acute decompensation of chronic liver disease (e.g. ascites, jaundice, GI haemorrhage, encephalopathy) which involves 1+ organ failure (liver, kidney, brain, coagulation, circulation, respiration) and systemic inflammation
655
What are the ACLF transplant criteria in the UK? What are the individual definitions of organ failure in ACLF?
Inclusion criteria
- Cirrhosis AND
- Severe organ dysfunction / failure requiring ITU support and 28 day survival <50% - usually signified by ACLF 3
Exclusion criteria
- Alcoholic hepatitis
- Patients > 60
- Severe chronic comorbidity which would preclude LT
- Gross frailty
- Previous LT
- Active bacterial or fungal sepsis
- CMV viraemia
- Severe irreversible brain injury
- Multi-organ failure severity or trajectory which would preclude successful LT
- Use of ECMO
- Active malignancy
- Acute severe pancreatitis or intestinal ischaemia
Definitions of organ failures in ACLF
- INR ≥ 2.5
- Bilirubin ≥ 205 (12mg/dL)
- Encephalopathy III-IV
- Creatinine ≥ 175 (2mg/dL) OR RRT need
- Vasopressors
- PaO2/FiO2 ≤200
656
What is the prevalence of NAFLD?
25%
657
What are the extrahepatic manifestations of chronic hepatitis B?
Vasculitis, skin manifestations (purpura), polyarteritis nodosa, arthralgias, peripheral neuropathy, glomerulonephritis, mixed cryoglobulinemias
658
What are the indications for treatment in chronic hepatitis B?
1) HBV DNA >2000, ALT >ULN, moderate necroinflammation or fibrosis
2) any HBsAg positivity with cirrhosis
3) HBV DNA >20000, ALT >2x ULN, any liver disease state
4) High HBV DNA, persistently normal ALT, HBeAg positive, aged >30
5) FHx of HCC or cirrhosis with extrahepatic manifestations of chronic hepatitis B
6) Pregnancy, HBV DNA >200000 or eAg positive (start TDF at 24-28 weeks and continue at least 12 weeks after pregnancy)
659
How would you determine the state of fibrosis in a patient with chronic hepatitis B?
Without inflammation
>9kPa suggests advanced fibrosis/cirrhosis
6-9kPa is intermediate fibrosis
With inflammation (ALT rise but <5x ULN)
>12kPa suggests advanced fibrosis/cirrhosis
6-12kPa suggests intermediate fibrosis
Patients with intermediate fibrosis may require liver biopsy
(APRI score ≥ 1)
660
What is the approach to prophylaxis for hepatitis B in patients receiving immunosuppressant medications?
Vaccinate sAg-cAb- patients
Treat all sAg positive patients with tenofovir
+ continue 12 months
+ continue 18 months post in rituximab / stem cell transplant regimens
sAg-cAb+ patients
- Treat all on rituximab / receiving stem cell transplants
- Observe all others + treat only if detectable HBV DNA / HBsAg (measure every 1-3 months)
661
What is the approach to hepatitis B prophylaxis in renal transplant and dialysis patients?
TDF to all renal transplant patients if sAg positive
Close monitoring of renal transplant patients sAg-cAb+
Standard for dialysis patients
662
What is the management of chronic hepatitis B post transplant?
TDF + hepatitis B immunoglobulin (can stop the immunoglobulin eventually, usually after 1-2 years)
663
What is the risk of acute HBV/HDV co-infection and acute HDV superinfection progressing to chronicity? How would you tell them apart?
Co-infection <5%
Superinfection >90%
Use HBcAb IgM to distinguish
664
Does HDV have an HCC risk?
Not established, but cirrhosis obviously does
665
What is the most severe form of viral hepatitis?
Delta
666
What other liver condition is associated with hepatitis delta?
Autoimmune hepatitis
667
What is the treatment of hepatitis delta? What is the treatment of chronic hep b in these patients?
Treat all patients with chronic hepatitis D
Peg-IFNa for 48 weeks
- Monitor HDV 6, 12 months + yearly after treatment
Bulevirtide 2mg OD should be considered for all patients if available
- Monitor HDV 1, 3, 6, 12 months + yearly after treatment
What to do about chronic hepatitis B / tenofovir?
- All decompensated cirrhotics
- Compensated cirrhotics with detectable HBV
- All patients with HBV >2000
Transplant is only cure
- Post transplant will need to be maintained on tenofovir / entecavir + HBV immunoglobulin
668
What is bulevirtide?
Entry inhibitor for hepatitis delta (NCTP receptor antagonist)
669
What is hepatitis E
Faeco-orally transmitted single stranded RNA virus which usually runs a course similar to hepatitis A, but can cause liver failure
Can cause chronic infection in immunocompromised patients
670
What is the management of hepatitis E?
Usually just supportive
Reduce the dose of immunosuppression if chronic HEV
Consider ribavirin
- severe hepatitis
- pre-existing chronic liver disease
- chronic HEV not responding to decrease in immunosuppression
671
What is the sustained virological response rate in hepatitis C?
>95%
672
What are the treatment options for hepatitis C?
Sofosbuvir/velpatasvir (epclusa)
- 12 week course for non-cirrhotics or child pugh A cirrhosis, whether treatment naive or experienced
- Child pugh b/c cirrhosis or previous decompensations
---> 12 week course + ribavirin (1g OD if <75kg, 1.2g OD if ≥75kg)
---> If ribavarin intolerant or contraindicated then 24 week course of epclusa
Glecaprevir/pibrentasvir
- 8 week course for non-cirrhotics, or child pugh A cirrhotics who are treatment naive
- 12 week course for child pugh A cirrhotics who are treatment experienced
673
What are the contraindications to Hep C treatment?
cP450 inducing agents e.g. carbamazepine, phenytoin and phenobarb due to significantly reduced concentration of HCV DAAs
HCV protease inhibitors e.g. grazoprevir, glecaprevir or voxilaprevir are contraindicated in child pugh b/c cirrhosis or previous decompensations
674
What factors decide whether HCV patients should be treated pre or post transplant? What is the post transplant treatment regimen?
Indications for post LT transplant
- Child pugh B/C cirrhosis with MELD ≥18-20 and without HCC, unless waiting time for LT is likely to exceed 6 months
OTHERWISE, treat pre-LT
Post transplant treatment
- Usually 12 weeks of epclusa once patient stabilised post LT (usually 3 months)
UNLESS they develop cirrhosis again and then as per cirrhosis guidelines
675
What factors decide timing on HCV treatment in HCC?
No cirrhosis or child pugh A
- If undergoing RFA or resection with curative intent, then delay treatment until AFTER HCC procedure
- If awaiting transplant, then treat pre-transplant
If awaiting transplant with a longer waiting list where locoregional therapies would be required, then pre-transplant treatment is advised to facilitate bridging locoregional therapies
Patients with palliative HCCs can still be treated with antivirals if - liver function / survival benefit anticipated OR to reduce onwards transmission
Post HCC treatment + antiviral treatment, due to ongoing HCC risk, perform 6 monthly screening USS
676
What about HCV treatment in pregnancy?
Epclusa is probably safe but trial to determine this is ongoing?
Children should be tested at 18 months and treatment can begin at age 3
Breastfeeding not contraindicated unless cracked/bleeding nipples
677
What is the management of HCV/HBV co-infection?
HBV guidelines trump all
Otherwise, if HBsAg positive then start TDF and HCV treatment simultaneously and continue until at least 12 weeks post HCV treatment complete
678
What proportion of patients with PBC are AMA positive?
>90%
679
What biochemical features can diagnose PBC?
Diagnosis if any 2+ of
Biochemical
Persistently elevated ALP 1.5x ULN
Serological
AMA titre ≥1:40
OR if AMA negative
specific ANA immunofluorescence
- nuclear dots (anti-sp100)
- or perinuclear rims (anti gp210)
Liver biopsy
suggestive of non-suppurative cholangitis and destruction of interlobular bile ducts (not usually required)
680
What immunoglobulin pattern might be seen in PBC?
Raised IgM
681
What conditions are associated with PBC?
High cholesterol, psoriasis, depression, restless legs
682
How is the histological severity of PBC staged?
Stage 0: Normal liver
Stage 1: Inflammation and/or abnormal connective tissue confined to the portal areas
Stage 2: Inflammation and/or fibrosis confined to portal and periportal areas
Stage 3: Bridging fibrosis
Stage 4: Cirrhosis
683
List the poor prognostic factors in PBC
Male gender + age <45 associated with UDCA failure
ALP >2x ULN
Elevated bilirubin
684
What is the management of PBC LFTs?
UDCA 12-15mg/kg
Reassess at 1 year
- if no normalisation of bilirubin or ALP <1.5x ULN then add additional agent
EITHER
- obeticholic acid (<10% increase in pruritus)
- bezafibrate (beneficial for pruritus)
685
How can pruritus be managed in PBC?
Emollients / oatmeal extract for dry / inflamed skin
Cold water baths / showers if exacerbated by heat
Bile acid sequestrants
Rifampicin 150-300mg BD
- Beware hepatotoxicity
- Drug induced hepatitis occurs in 12% of cholestatic patients, typically at 2-3 months
Bezafibrate - actually helps pruritis and PBC vs obeticholic acid which worsens pruritis in many
Naltrexone titrated to 50mg daily - poorly tolerated
Sertraline titrated to 75-100mg OD
686
How can fatigue be managed in PBC?
Treat depression
Modafinil
687
How should bone density be approached in PBC?
DEXA at diagnosis and then every few years if osteopenic
688
What is the prognosis of PBC? What is the pattern of portal hypertension development in this condition?
8/10 patients never develop cirrhosis
Portal hypertension & oesophageal varices can develop before the development of cirrhosis
689
What disease associations exist with PSC?
60-70% have IBD
- 75% UC (more right sided though)
- 15% crohn’s
- 10% unclassified
- 2% with IBD have PSC
AIH (10% overlap syndrome of those with PSC)
IgG4-RD
Coeliac
DM1
Psoriasis
Sarcoidosis
Thyroid disease
690
Detail the differences between small vs large duct PSC. What PSC overlap syndromes exist?
Small duct PSC
- 10% of cases
- Low malignant potential
- Low progression to advanced liver disease
- 25% will progress to classical PSC
- Crohn’s patients with PSC tend to have small duct PSC
Large duct PSC
Overlap syndromes
- IgG4
- AIH
691
What is the histology of small duct PSC?
Concentric biliary fibrosis (onion skinning) surrounding the hepatic bile duct and portal inflammatory infiltrate
692
What serological/biochemical patterns are seen in PSC?
IgG & IgM are often elevated
pANCA often positive (50-80%),
ANA often positive
Transaminases frequently raised, but if AST 5x ULN then should investigate for AIH
693
What are the secondary causes of cholangitis?
Chronic obstruction
- choledocholithiasis
- choledochal varices
- surgical trauma
- obstructing tumour
- anastomotic stricture
- chronic pancreatitis
Immune
- IgG4-RD
- hepatic sarcoidosis
- liver rejection
Infectious
- recurrent cholantitis
- liver fluke
- histiocytosis x
- cryptosporidiosis, microsporidiosis
- CMV
- AIDS cholangiopathy (usually fungal infections)
Ischaemic
- hepatic artery thrombosis / stenosis
- critically ill patient
- systemic vasculitis
Hereditary
- CF associated cholangiopathy
- ABCD4 mutation (with intrahepatic choledocholithiasis)
Ketamine
694
What is the management of PSC?
15-20mg/kg UDCA - may improve LFTs, but limited survival benefit. 12 month trial, if no effect then stop
Treat dominant bile strictures - dilatations superior to stenting
- High grade stricture is >75% diameter reduction (≤1.5mm diameter in CBD or ≤1mm diameter in main hepatic ducts within 2cm of hilum)
- Relevant stricture is a high grade stricture with signs or symptoms of obstructive cholestasis or bacterial cholangitis
695
What is the approach to monitoring in PSC?
Yearly abdominal imaging in the absence of cirrhosis (otherwise 6 monthly)
Every other year - MRCP/MRI liver, or consider if uptrending ca199/lfts
MRCP every 3 years for small duct PSC
ERCP + brushings for every new stricture
DEXA every 2-4 years
Fibroscan every 2-3 years
696
What is the recurrence of PSC after transplant? How is it diagnosed?
20% recurrence after transplant over 10 years
Recurrence leads to graft failure in 50% of patients
To confirm recurrence of PSC post transplant
- MRCP - cholangiographic findings
- CT liver triple phase - exclude hepatic artery thrombosis or stenosis
- Histology (occurring >90 days after transplant)
---> Confirm PSC features
---> Exclude chronic rejection
- Exclude CMV infection
697
What are the risk factors for PSC recurrence?
Male gender
CMV mismatch
Living-related donation
Active IBD
Early post-LT cholestasis
Some HLA genotypes
698
What is the typical AIH demographic?
Female predominance
All ages but peaks in 2nd decade and 5-6th decades
Strong association with autoimmune disorders e.g. autoimmune thyroiditis, rheumatoid arthritis, type 1 diabetes mellitus, ulcerative colitis, celiac disease, sjogren’s syndrome and SLE
699
What are the extrahepatic features of AIH?
Skin rashes are very common (8-17%) - typically transient, nonspecific maculopapular rash
Other associated skin lesions also include psoriasis, vitiligo, urticaria, acne, lichen planus, erythema nodosum, and pyoderma gangrenosum
700
What is the typical LFT pattern in AIH?
Transaminases may exceed 10x ULN
ALP:ALT/AST <1:5 to <1:10, but may be lower in cases of cirrhosis where transaminitis is less severe
701
Detail the simplified diagnostic criteria for AIH
Simplified diagnostic criteria (max 8)
≥7 definite AIH
≥6 probable AIH
Autoantibodies (max 2 points per patient)
1: ANA or SMA ≥1:40
2: ANA or SMA ≥1:80
2: LKM ≥1:40
2: SLA/LP any titre
IgG or gamma globulins
1: >ULN
2: >1.1x ULN
Liver histology
1: compatible
2: typical
Absence of viral hepatitis
2: yes
702
What are the typical and compatible histologies with AIH?
Typical
- Interface hepatitis
- Lymphoplasmocytic infiltrates in portal tracts extending into the lobule
- Emperipolesis (penetration by one cell into another)
- Rosette formation
Compatible histology
- Chronic hepatitis with lymphocytic infiltration
- Without other features above
703
How is AIH subclassified?
Type 1
ANA, anti-smooth +/- anti mitochondrial
1/3 soluble liver antigen/liver pancrease (SLA/LP)
25% and dsDNA
Atypical pANCA
Type 2
Classically anti-liver/kidney microsomal-1 antibody +/- anti-liver cytosolic 1
+/- ANA
+/- soluble liver antigen / liver pancreas
Seronegative AIH
Globulins usually significantly raised
704
What are the aims of AIH treatment to define sufficient response?
Normalisation of serology (AST, IgG) within 6 months (otherwise classified as insufficient responders)
Histological remission (HAI <4/18) - on biopsy at 1-2 years
705
What is the treatment of mild-moderate AIH?
0.5-1mg/kg/day prednisolone
Add azathioprine 1mg/kg/day 2 weeks after starting pred providing response to treatment seen
Taper pred every 1-2 weeks by 5-10mg until 10mg + hold until complete normalisation of biochemistry/serology
After normalisation of biochemistry, downtitrate pred to stop
NB: avoid azathioprine in decompensated cirrhosis
706
What is the treatment of acute severe AIH? How can you prognosticate severe AIH?
1mg/kg/day IV methyl pred
Avoid azathioprine acutely
Prognostic features
- D0 MELD >27 - poor response to steroids
- F3/4 (severe necrosis) on liver biopsy
- 3 day response of INR and bilirubin is indicative
If no improvement after 7 days of steroids then consider LT
707
What is the role of budesonide in AIH? How is it dosed?
Older patients / at risk of osteoporosis
Mild disease
No portal hypertension / cirrhosis
Budesonide 3mg TDS until biochemical response achieved, then reduce to 3mg BD
708
What is the approach to drug withdrawal in AIH?
Generally avoided due to high relapse rates (81% at 3 years)
Minimum treatment duration 2 years, 18 months in complete biochemical remission.
Then can consider withdrawal if
- Anti-LKM1 negative
- Anti-SLA/LP negative
- Age >16
- No interface hepatitis on liver biopsy
Process
- Down-titrate steroids by 2.5mg every 2 weeks
- Down-titrate azathioprine to 50mg for 1 month, then stop
709
What drug options exist for insufficient response to standard therapy in AIH?
Check TGN levels (>220)
Consider 2mg/kg aza
OR consider alternative therapies
MMF - 500mg BD and then uptitrated to target 1g BD (CI pregnancy) --- some evidence that this may be better than aza?
3rd line therapies
Tacrolimus
Ciclosporin
IFX
710
How is AIH-PSC variant syndrome managed?
Combination steroids + azathioprine may be beneficial - a controversial area.
More likely to be effective the higher the IgG is
711
How is AIH-PBC variant syndrome managed?
According to which subtype
Histological AIH but serological PBC (i.e. anti-mitochondrial antibody)
- Essentially behave and managed identically to type 1 AIH
Histological features of PBC but serological features of AIH (typically ANA, anti smooth muscle)
- NB: others consider this AMA negative PBC
- Mx
- trial 0.5mg/kg/day prednisolone
- If no effect then start UDCA 12-15mg/kg/day
- If there is effect then start UDCA and steroid sparing agent (azathioprine) + perform liver biopsy after 1-2 years to ensure histological improvement
712
Name some agents that cause intrinsic DILI
Paracetamol
Amiodarone
Anabolic steroids
Ciclosporin
Sodium valproate
HAART drugs
Statins
713
Name some drugs that cause idiosyncratic DILI
Allopurinol
Amiodarone
Penicillins: co-amox, fluclox
Bosentan
Dnatrolene
Diclofenac
Fenofibrate
Halothane
Isoniazid
Ketoconazole
Lisinopril
Methyldopa
Minocycline
Nitrofurantoin
Phenytoin
Statins
Tolvaptan
714
What are the risk factors for DILI severity and pattern?
More severe in older age
Women more likely to have DILI leading to ALF
Older patients more cholestatic
HLA-A*33:01 cholestatic DILI linkage
Women more likely to have nitro DILI
715
What is DRESS and what agents cause it?
Drug induced hypersensitivity involving eosinophilia, fever, skin rash, DILI +/- other organ involvement
Causes: carbamazepine, phenytoin, phenobarbitone, allopurinol
716
What are the causes of DI-AIH?
Diclofenac, halothane, metyldopa, minocycline, infliximab, nitrofurantoin, statins
717
What are the drug causes of secondary sclerosing cholangitis?
Amiodarone, atorvastatin, co-amoxiclav, gabapentin, IFX, 6-MP, sevoflurane, venlafaxine, (ketamine)
718
What are the drug causes of granulomatous hepatitis?
Allopurinol, carbamazepine, methyldopa, phenytoin, quinidine, sulphonamides
719
What are the drug causes of acute fatty liver?
Amiodarone, valproate
720
What are the causes of drug-associated fatty liver disease?
MTX, 5-FU, tamoxifen, corticosteroids
721
What are the drug causes of nodular regenerative hyperplasia?
Azathioprine, bleomycin, cyclophosphamide, doxorubicin, 6-thioguanine, oxaliplatin
722
What are the drug causes of vanishing bile duct syndrome?
Azathioprine, androgens, co-amox, carbemazepine, chlorpromazine, erythromycin, estradiol, flucloxacillin, phenytoin, terbinafine, co-trimoxazole
723
What are the drug causes of hepatic adenomas?
Oral contraceptives and anabolic steroids
724
What is the treatment of DRESS?
Stop drug + pred 40mg OD
725
What specific treatments for DILI exist?
Paracetamol - NAC
Leflunomide and terbinafine - cholestyramine
Valproate - carnitine
?ursodeoxycholic acid
726
What is AIH-like DILI? What is the treatment? What are the typical causes?
AIH serology + histology in response to drug trigger
Responds to steroids
Very low chance of relapse if offending agent is discontinued
Classical drug causes: minocycline, nitrofurantoin, hydralazine, methyldopa, interferon, imatinib, adalimumab and infliximab
727
List the CYP450 inducers
Rifampicin
Anticonvulsants e.g. carbemazepine, phenobarbital, phenytoin
ARTs - efavirenz, nevirapine
St John’s wort
Chronic alcohol intake
728
List the CYP450 inhibitors
CCBs
Azole antifungals
Macrolides
Protease inhibitors
Grapefruit juice
729
What are the risk factors and associated conditions with PV thrombosis?
Myeloproliferative disorders
Thrombophilias
- protein C deficiency
- factor V leiden
- protein S deficiency
- JAK2 mutation
- antiphospholipid syndrome
- antithrombin III deficiency
Anatomical reasons
- Pregnancy
- Previous abdominal surgery
- Cirrhosis
Inflammatory reasons
- Cancer
- Pancreatitis
- IBD
- Abdominal infections
- Ascites
- Paroxysmal nocturnal haemoglobinuria
730
What is the prevalence of PVT in cirrhosis and HCC?
35%
731
In which situations might PV thrombosis lead to gastric varices?
If there is splenic vein involvement
732
What is the management of portal vein thrombosis in cirrhosis?
Anticoagulation indications
- Recent (<6 months onset)
- Completely or >50% occlusion
- Absence of cavernoma
- Symptomatic PV irrespective of extension
- Involvement of SMV
- In potential LTx candidates regardless of extension/size (as PVT significantly negatively impacts LTx outcomes)
- If PVT <50% progresses over 1-3 months
Choice of anticoagulation
- LMWH 1st line
- Vit K antagonists - harder to monitor given baseline INR dysfunction
- DOACs
---> Caution in childs-pugh B
---> Contraindicated in childs-pugh C
TIPSS indications
- significant symptoms related to portal hypertension (recurrent bleeding or refractory ascites)
- failure of PVT recanalisation with anticoagulation
Thrombolysis
- highly selective including gut ischaemia
733
What is budd-chiari syndrome? What would the liver histology show?
Hepatic vein obstruction -> sinusoidal congestion, ischemia, and finally hepatocellular necrosis.
Centrilobular fibrosis, nodular regenerative hyperplasia and/or cirrhosis
734
What is the presentation of budd-chiari syndrome?
Asymptomatic -> liver failure
Ascites, hepatomegaly, abdo pain, oesophageal varices, GI bleeding
ALT often high
735
What is the prognosis of budd-chiari syndrome?
ALT 5x ULN which does not rapidly improve in coming days = poor prognosis
Prognosis overall poor (80% mortality 3 years)
But if managed ‘appropriately’ then survival can exceed 80%
(above is NEJM data)
Chronic budd chiari - 50% ??
(above is BMJ onexamination data)
736
What is the treatment of budd-chiari? What effect will transplant have on heritable coagulopathies?
Anticoagulate
Treat the cause
Consider catheter directed thrombolysis
TIPSS or surgical shunt
Transplant - cures thrombophilias as new liver will produce correct factors
737
What congenital causes of portal hypertension exist?
Abernethy malformation
Congenital absence of a portal vein, with portal blood draining into systemic venous circulation
Have all features of portal hypertension including hepatic encephalopathy (portosystemic shunting)
Type 1: complete absence of portal vein, only females
Type 2: hypoplastic portal vein, male predominance
738
Describe the genetics of alpha 1 antitrypsin deficiency
Mutations in SERPINA1 gene
Autosomal co-dominant pattern
PI*M is normal gene
Pi*S produces 50-60% of normal A1AT
and Pi*Z produces 10-20% of normal A1AT
739
Detail the different phenotypes that result from different A1AT genotypes
Pi*ZZ most severe
<15% A1AT level
20-45mg/dL A1AT
40% of adults will have cirrhosis
Pi*SZ
35% A1AT level
75-120mg/dL A1AT
Moderate increased risk of lung disease + liver cirrhosis
Increased risk of HCC
PI*MZ
90-210mg/dL A1AT
genetic modifier for liver disorders and COPD (in smokers)
Pi*SS
No clinically relevant risk of liver disease
Increased COPD risk in smokers
Pi*MS
No liver disease risk
Possible increased COPD risk in smokers
740
What histology might one find in A1AT?
Fibrosis
PAS staining (see image)
Immunohistochemistry positive for Pi*Z variant of SERPINA1
741
What is the management of A1AT? What is the role of HCC screening?
There is sometimes poor correlation with liver stiffness measurements and presence of fibrosis - important role for biopsy
HCC screening USS regularly for
- Pi*ZZ patients
- Pi*SZ patients with liver fibrosis
Augmentation therapy (infusion of human plasma-derived A1AT) has a role in lung disease, but not liver disease
LT is only treatment for liver disease
742
What is Wilson's disease?
AR ATP7B gene mutations on xsome 13 -> defective biliary excretion of copper + accumulation in brain and liver
743
What are the clinical features of Wilson's disease? When does it present?
Cirrhosis
Neuropsych
Corneal kayser-fleischer rings
Acute episodes of haemolysis (often in association with ALF)
Young patients - most present 5-35 years old
3% present beyond 4th decade
10% of ALF
744
What are the biochemical patterns in Wilson's disease?
Low ALP, mild transaminitis, haemolytic anaemia, renal failure common
745
How is a diangosis of Wilson's disease established?
Low serum caeruloplasmin <0.1g/L
- but may be falsely elevated because it is an acute phase protein
- Other causes low serum caeruloplasmin - AIH, advanced liver disease, familial acaeruloplasminaemia
Confirmatory tests
- 24 hour urinary copper (not reliable in ALF), serum free copper
- liver biopsy for hepatic copper content
746
What is the management of Wilson's disease?
D-penicillamine - high side effects
Trientine - second line
Zinc - good for neuropsych (+ asymptomatic siblings)
Liver transplant
747
What are the genetics and pathophysiology of classical haemochromatosis?
Heritable condition of iron overload
Most are AR HFE gene mutations - homeostatic iron regulator gene, which encodes HFE transmembrane protein, where its binding to other receptors and proteins in the liver regulates hepcidin production i.e. mutations reduce HFE transmembrane trafficking/expression and thus reduce hepatic hepcidin production and thereby iron elimination in the gut
Examples
- C282Y homozygosity (80%) of cases
---> 1:83 in Ireland are carriers
---> 50% get clinically significant iron overload
- H63D homozygosity affects iron handling but will rarely cause symptoms
- H63D/C282Y heterozygosity can lead to liver disease with another risk factor
748
What are the non-HFE causes of hepatic iron overload?
Iron loading anaemias
Beta thalassaemia
Sickle cell disease
Ferroportin disease (SLC40A1 gene mutation)
Other rare iron storage diseases
- Acaeruoplasminaemia
- Atransferrinaemia
Iron overload biochemically may also be seen in fatty liver disease, liver failure, advanced cirrhosis, acute liver injury
749
What are the clinical features of haemochromatosis?
Early: fatigue, joint pain
Later: diabetes, liver disease, skin pigmentation, impotence, cardiac arrhythmias, heart failure
750
What are the biochemical features of haemochromatosis?
Elevated transaminases
TSAT >50% men, >45% women
Ferritin >300ug/L men, >200ug/L women
751
Who should be genetically tested for C282Y and H63D mutations (HFE test)?
Symptomatic or asymptomatic patients with following biochemistry with or without transaminitis
- Men: TSAT >50%, ferritin >300mcg/L
- Women: TSAT >45%, ferritin >200mcg/L
Patients with persistently elevated TSAT not meeting the above criteria without other explanation
Adult 1st degree relatives of patient with confirmed diagnosis
752
What rarer HFE and non-HFE haemochromatosis genes should be screened for in suspected cases?
HAMP - hepcidin (antimicrobial peptide) gene
HJV - haemojuvelin which regulates hepcidin
TFR2 - transferrin receptor 2 gene
TF - transferrin gene
CP - homozygous mutations cause acaeuroplasminaemia
BMP6 (bone morphogenetic protein) - non-HFE haemochromatosis
SCL40A1 - ferroportin disease
753
How can iron deposition be assessed/quantified?
Liver MRI R2* sequences
- primarily used in non C282Y homozygous cases of hyperferritinaemia
Liver biopsy with Prussian blue stain (see picture)
754
Describe the pattern of iron deposition in early haemochromatosis, acaeruloplasminaemia, ferroportin disease and transfusion related iron deposition
Liver predominant: haemochromatosis and acaeruloplasminaemia
Spleen predominant: transfusion related and ferroportin disease
755
How is fibrosis best assessed in haemochromatosis?
Fibroscan excludes advanced fibrosis if ≤6.4kPa
Biopsy can be performed for liver stiffness 6.4-12kPa in absence of clinical cirrhosis to determine role for HCC screening
756
What is the approach to phlebotomy in haemochromatosis?
Induction phase (weekly or biweekly)
- check Hb, if <11 then pause, if <12 the reduce rate
- check ferritin after 4 phlebotomies until 200 is reached, then every 1-2 sessions
- target ferritin 50
Maintenance phase:
- target ferritin 50-100
- check ferritin + TSAT 6 monthly
- variable frequency but usually 2-6 phlebotomies per year
757
What are alternatives to phlebotomy in treating haemochromatosis
Erythrocytapheresis
- fewer haemodynamic changes
Iron chelating
- oral deferasirox 10mg/kg start
- CI in pregnancy
758
What are the diet / lifestyle recommendations in haemochromatosis
Avoid vitamin C supplementation
Avoid iron rich foods e.g. red meat
Avoid raw/undercooked seafood (may contain bacteria that grow well in iron rich environment)
Minimal/no alcohol
759
What is the rate of HCC development in cirrhotics?
1/3 will develop at some point
1-8% development per year
760
How does SVR in hep C affect HCC risk?
Risk of HCC remains in patients with HCV cirrhosis obtaining SVR, but risk is reduced
High rate of HCC recurrence post treatment with curative intent in HCV cirrhosis with SVR
761
What are the risk factors for HCC in chronic hepatitis B?
E antigen positivity
High viral load
Genotype C
762
What is the pattern of HCC in NASH patients?
Half of HCC in NASH patients occur without cirrhosis
763
How is HCC diagnosed in patients with cirrhosis?
Biopsy is not required
Mass <1cm?
- Repeat USS every 4 months if stable
- if growing / changing perform CT triple phase or MRI liver with contrast (GAD or PRIMOVIST)
----> if 1 positive hallmark for HCC e.g. rapid filling/washout then HCC diagnosed
---.> biopsy if no imaging findings
Mass >1cm?
- go straight to cross-sectional imaging
764
How is HCC diagnosed outside of cirrhosis?
Liver biopsy
765
Detail the BCLC staging and the treatment implications
0: very early stage
Single lesion <2cm
Preserved liver function
PS0
Mx: resection or ablation
A: early stage
Single or 2-3 nodules <3cm
Preserved liver function
PS0
Mx
- solitary: resect if good surgical candidate otherwise consider transplant or ablation
- 2-3 nodules: transplant if candidate, otherwise ablate
B: intermediate stage
Single >5cm, multinodular, unresectable
Preserved liver function
PS0
Mx: chemoembolisation
C: advanced stage
Portal invasion/extrahepatic spread
Preserved liver function
PS 1-2
Mx: systemic therapy
- atezo/bev preferred
- OR sorafenib
D: terminal stage
non-transplantable
End stage liver function (CP C)
PS 3-4
Mx: supportive
766
Detail the treatment considerations for systemic therapy in HCC
Preferred systemic therapy = atezo/bev over sorafenib now
Bevacizumab increases bleeding - e.g. varices --- contraindication
Atezolizumab not suitable for patients with autoimmune disease --- contraindication
Sorafenib used as 1st line if any of the above present as a result
767
Detail the risk stratification for lobectomies in HCC in the context of cirrhosis
Considerations
- portal hypertension
- MELD >9
- ≥3 segment resection
Low risk (5% risk liver decompensation)
- <3 segment resection in patient with MELD ≤9 and no portal hypertension
Intermediate risk (<30% risk of liver decompensation)
- <3 segment resection in patient with MELD >9 and no portal hypertension
- <3 segment resection in patient with portal hypertension
- ≥3 segment resection in patient without portal hypertension
High risk (>30% risk of liver decompensation)
- ≥3 segment resection in patient with portal hypertension
768
What are the UK selection criteria for HCC transplant listing?
1st line for decompensated cirrhosis and the below…
2nd line for compensated cirrhosis with tumor <2cm
Single HCC ≤5cm diameter
5 HCCs all ≤3cm diameter
Single HCC >5cm and ≤7cm
- Where there has been <20% tumour progression in 6 months, no new nodules, no extra-hepatic spread
- Locoregional therapy +/- systemic therapy can be given in that time whilst listing occurs
AFP <1000
769
What is the role of AFP with regards to LT in HCC
AFP >1000 is a poor prognostic marker and considered contraindication to transplant
770
What are the common aetiologies of hepatic adenoma?
Women taking OCP
Males using anabolic steroids
Obesity/metabolic syndrome
771
What is the prognosis of hepatic adenoma?
25% risk of haemorrhage
5% risk of malignant transformation
772
What are the US/CT/MRI findings of hepatic adenoma?
US - variable appearance
CT
Well-demarcated and low attenuation or isodense.
Peripheral enhancement during the early phase with subsequent centripetal flow during the portal venous phase, which is characteristic of HCA
Subsequent washout
Often have areas of haemorrhage, necrosis, or fibrosis, giving them a heterogeneous appearance
MRI
Usually well-demarcated on contrast-enhanced MRI
show arterial phase enhancement on MRI, while enhancement patterns in the subsequent phases vary depending upon the lesion subtype
MRI with primovist retention suggests FNH over hepatic adenoma
773
What is the management of hepatic adenoma?
Men: surgical resection due to increased risk of malignant transformation
Women: 6-month observation with lifestyle advice (e.g. stopping OCP and weight loss)
- Resect if persistently >5cm in size OR growing ≥20% OR symptomatic
- If no risk factors identified for the woman - resect
- Ongoing surveillance intervals - annually after initial 6 month interval
Alternatives to resection
- Transarterial embolisation
- RFA (if <3cm)
774
What is the prognosis after LT?
>90% 1 year survival
70% 10 year survival
775
What is the UKELD criteria for LT in chronic liver failure? What is the prognosis of patients with this score?
UKELD >49 (representing <50% 5 year survival)
776
Detail the variant syndromes for which LT can be considered
Hepatopulmonary syndrome
Persistent/intractable pruritis
Polycystic liver disease
Familial hyperlipidaemia
Recurrent cholangitis
Familial amyloidosis
Hepatic epithelioid haemangioendothelioma
Nodular regenerative hyperplasia
Hereditary haemorrhagic telangiectasia
Ornithine transcarbamylase deficiency
Glycogen storage disease: symptomatic or with hepatic adenoma
Primary hyperoxaluria with renal impairment
Maple syrup urine disease
+/- portopulmonary hypertension (if clinical response to medical therapy)
777
Detail the contraindications to LT
Absolute
- untreated HIV
- severe extrahepatic disease with >50% 5 year mortality (including psychiatric disorder)
- severe irreversible pulmonary diseases
- ongoing alcohol misuse
- active illicit drug use
- certain anatomic variants
- ongoing extrahepatic sepsis
- active or previous extra-hepatic malignancy
Relative
- inadequate social support
- smoking
- certain anatomical variants
- extensive previous abdominal surgery
- BMI >40
- poor clinic attendance/adherence
778
What period of time does urine ETG/ETS assess alcohol metabolites?
3 days
779
What scoring systems aid organ allocation decision making in liver transplantation?
Transplant benefit score (for DBD)
Data inputs for recipient to predict survival with and without transplant (and also donor factors to predict donor-recipient combination outcomes)
780
Detail the different kinds of LT grafts
DBD - donation after brain death (the best)
DCD - donation after circulatory death
Living donor transplantation (usually paediatric)
Hep C and Hep B organs can be considered
Splitting
- This can be done for some grafts so that one donation can be used in both an adult and paediatric transplant
- There are additional risks associated with this
781
Detail the different biliary anastomoses in LT
Duct-to-duct anastamoses are generally preferred
Hepaticojejunostomy may be preferred in cases of diseased bile ducts e.g. PSC
782
What are the early complications of LT?
Primary non-function
- related to donor age, ICU time, cold ischaemic time
Biliary complications
- bile leak (esp split grafts)
- ischaemic duct injury (hepatic artery thrombosis/stenosis or ischaemic cholangiopathy)
- DCD cholangiopathy (ischaemic cholangiopathy)
- anastomotic stricture
Vascular
- HAT/stenosis presenting as graft dysfunction
- PV thrombosis or outflow obstruction from IVC anastomosis/obstruction
Infection: CMV, fungal, other
Rejection (acute, cellular)
783
What is the difference in early vs late hepatic artery thrombosis presentations
Early: ischaemic level transaminitis
Late: bile duct strictures
784
What is the management of hepatic artery thrombosis post LT?
Surgical revascularisation if possible
Otherwise retransplant (>50% of cases)
785
What is the typical approach to post LT immunosuppression?
Usually steroids + tacrolimus induction
Maintenance tacrolimus (usually trough 3-8ng/L)
Some may have immunosuppression discontinued fully
Pre-existing AIH - may remain on steroids
786
What is the renal prognosis in LT patients? What is their frequency? What is the aetiology?
20% CKD and 5-9% ESRF, usually CNI related
787
What histology may be seen in acute cellular rejection?
Portal inflammation with mixed inflammatory infiltrate, but predominantly mononuclear cells
Bile duct inflammation with non suppurative cholangitis
Venous endothelial inflammation (endotheliitis) involving portal vein and hepatic venule
788
What is the management of acute cellular rejection in LT?
Mild cases: maximise immunosuppression
Mod-severe IVMP pulsed 1g 3 days
789
What is chronic cellular rejection in LT?
Rare (acute much more common)
Cellular process with similar histology and may respond to maximising immunosuppression
790
What are the late complications with LT?
Chronic rejection
Disease recurrence
Cholangiopathy: DCD and late HAT
Metabolic syndroome
- NAFLD +/- new onset diabetes occurring de novo (CNIs are RF for diabetes)
Malignancy
- skin, haematological, solid organ
- PTLD
791
What is the time frame and aetiology of PTLD?
6-10 month post transplant
EBV mismatch with reactivation or infection
792
Which conditions may recur in post LT?
PBC 12-30% first 5 years (rarely leads to graft failure)
PSC 12-60% ---- hard to diagnose cholangiopathy
AIH 17-42% --- hard to distinguish rejection vs AIH recurrence on biopsy ‘immune mediated graft dysfunction’
NASH
ArLD
Hepatitis B - lifelong therapy
793
What is the use of UDCA post LT?
DCD and PSC cholangiopathy
794
Detail the normal LFT changes in pregnancy
ALP, AFP and clotting factors (I, II, V, VII, X and XII) increase
ALP in third trimester - placental + foetal bone
AFP 4x due to foetal liver production
Bilirubin, transaminases and INR remain unchanged
Other increases
WCC
Caeruloplasmin
alpha and beta globulins
Cholesterol and triglycerides
Decreases
Gammaglobulin
Mild thrombocytopenia but 90% remain >100
Hb (later in pregnancy)
Small clinically insignificant GOVs in 50% of pregnancies due to gravid uterus pressure
795
Define HELLP syndrome
Pre-eclampsia subtype which is defined as:
SBP ≥140 or DBP ≥90 on ≥1 occasion at least 4 hours apart in previously normotensive woman, with onset ≥20 weeks gestation (3rd trimester)
AND
Proteinuria (i.e.,≥30mg/mol protein:creatinine ratio; ≥300 mg/24hour; or ≥2+ protein dipstick)
Other maternal end organ dysfunction (headaches, decreased GCS, seizures, PLT <150)
Uteroplacental dysfunction
May be full or partial
Typically 3rd trimester but can present post partum
HELLP diagnostic criteria (Tennessee)
- haemolysing evidence by 2 of
—> blood film with schistocytes and burr cells
—> serum bilirubin >20.5
—> low serum haptoglobin <25mg/dL or LDH >2x ULN
—> severe anaemia unrelated to blood loss
- transaminitis >2x ULN
- low platelets <100
796
What are the risk factors for pre-eclampsia?
PMHx of the same or gestational hypertension
Nulliparity
CKD
797
Detail the differences in HELLP vs acute fatty liver of pregnancy
798
What are the typical investigations for HELLP syndrome?
Microangiopathic haemolytic anaemia (schistocytes on blood film and elevated LDH)
Raised transaminases 2x ULN
Thrombocytopenia
799
What are the severe hepatic complications of HELLP?
Liver haemorrhage or rupture
800
What is the management of HELLP / pre eclampsia?
Pre- eclampsia
- Control blood pressure (Mag sulf if ≥160/110)
- All pre-eclampsia high risk women should be given asprin 150mg OD until 36 weeks gestation
HELLP drugs
- GA<34 weeks - steroids for foetal lung maturity
- AND if GA<32 weeks - also mag sulf
HELLP delivery
- ≥34 weeks - prompt
- <34 weeks - consider delivery
801
When does acute fatty liver of pregnancy occur?
Third trimester, typically after 30 weeks
802
What are the risk factors for acute fatty liver of pregnancy?
Extremes of maternal age
low BMI
pregnancy-induced hypertension
multifetal pregnancy
FGR
male foetus
803
What are the symptoms of acute fatty liver of pregnancy?
Fatigue
Nausea, vomiting
Abdo pain, anorexia
Liver decompensation
804
What are the diagnostic criteria for acute fatty liver of pregnancy?
805
What is the role of US in acute fatty liver of pregnancy?
Supportive of the diagnosis if the liver appears bright, but usually normal
806
What is the management of acute fatty liver of pregnancy? What is the post partum outcome for mothers?
Delivery - most features including LFTs and renal failure normalise quickly
LT required for some
807
What is intrahepatic cholestasis of pregnancy? When does it occur? how common is it?
Most common liver disease of pregnancy affecting 5% of pregnancies
Features
- Third trimester pruritis (typically palms and soles)
Moderate ALT rise, jaundice and elevated bile acids
- Sometimes profound cholestasis can cause steatorrhoea and malabsorption of fat soluble vitamins (A, D, E, K)
- Increased risk of pre-term labour and intrauterine death
808
What are the risk factors for intrahepatic cholestasis of pregnancy?
FHx of the same
Previous cholestasis after OCP
809
What are the key investigations / biochemistry in intrahepatic cholestasis of pregnancy?
Elevated serum bile acids (usually 0-10 umol/L)
- >40 umol/L associated with adverse pregnancy outcomes
- Serum bile acids ≥100 - risk of stillbirth increases after 35 week gestation so planned C-section should be planned
60% have deranged ALT (usually 2x ULN)
25% will develop jaundice
May have elevated INR if profound cholestasis leads to fat soluble vitamin malabsorption
810
What is the management and monitoring approach to intrahepatic cholestasis of pregnancy?
Exclude other causes
2 weekly LFTs and serum bile acids until 32/40, then weekly
UCDA used 1st line to relieve symptoms 10-15mg/kg/day AND should be recommended if raised serum bile acids
Rifampicin can be used second line for pruritis
Induce women at 39 weeks in general if raised serum bile acids (certainly >40)
If serum bile acids ≥100 then deliver at 35 weeks
811
Detail the MUST score
Acutely unwell (and likely to be / has had no nutritional intake for >5 days) +2
BMI
<18.5 +2
18.5-20 +1
>20 +0
Weight loss in last 6 months
>10% +2
5-10% +1
<5% +0
≥2 is high risk
812
What could be the aetiology of diarrhoea and dypsepsia in someone taking an ACEi?
Drug induced villous atrophy
Microscopic colitis
Lymphocytic gastritis
813
What are the aetiologies of gastroparesis?
Idiopathic
Post-surgical
- Usually vagus nerve injury
Diabetic
Drug causes of delayed gastric emptying
- GLP-1s e.g. exenatide, semaglutide, liraglutide
- TCAs
- Octreotide
- opioids
814
What is the diagnostic test for gastroparesis?
Gastric emptying study with scintigraphy, measuring emptying at 1, 2 and 4 hours, with 4 hour retention providing diagnosis
- 10-15% = mild
- 15-35% = moderate
- >35% = severe
815
What is the role of gastroduodenal manometry?
Can help differentiate from myopathic vs neuropathic gastroparesis
Myopathic - reduced amplitudes of contractions
E.g. amyloid, scleroderma
Neuropathic - normal amplitude of contractions but disorganised activity
816
For which subgroups in gastroparesis is G-POEM most effective? What is their relative success? (Data based on one Czech study)
89% success diabetic
67% success idiopathic
50% success post surgical
FLIP manometry may also help to guide
817
What is the pre and post PEG insertion management?
Prophylactic abx
Don’t move PEG for 7 days
Thereafter daily advancement 5-10cm and rotation (avoid rotation if jejunal extension) to avoid buried bumper + avoid pulling/fixing too tight
818
What is the management of a buried bumper?
Endoscopic mx
- Needle knife, balloon push, balloon pull, snare, external extraction
Surgical removal
In high risk patients a jejunal extender can simply be passed for ongoing feeding??
819
What is the cause of symptoms in the following patient with short bowel syndrome?
Delirium, slurred speech, ataxia
Bloods: acidosis, normal lactate
What is the pathophysiology and management?
D-lactic acidosis
D-lactate is produced in the gut because of
- Absence /reduced length of small intestine, the site of normal simple carb absorption
- Presence of colon where unabsorbed carbs are made available for fermentation by colonic microbiota
High anion gap metabolic acidosis results
Normal L-lactate (conventional type measured in machines)
Management
Correct acidosis + hydrate with sodium bicarbonate
Decrease substrate for D-lactate e.g. carbs in meals
820
Define intestinal failure and insufficiency
Failure: reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth
Insufficiency: the reduction of gut absorptive function that does not require any intravenous supplementation to maintain health and/or growth
821
How is intestinal failure classified?
Type I acute IF; acute short-term and often self-limiting condition
Type II prolonged acute IF: prolonged acute condition, typically in metabolically unstable patients, requiring complex multidisciplinary care and intravenous supplementation over periods of weeks or months
Type III chronic IF: a chronic condition, in metabolically stable patients, requiring intravenous supplementation over months or years. It may be reversible or irreversible.
822
What are the aetiologies of IF?
Short bowel syndrome (usually SB <200cm)
intestinal fistula
intestinal dysmotility
mechanical obstruction
extensive small bowel mucosal disease
823
What are the complications of IF?
Diarrhoea
Hepatic steatosis and cholestasis (PN related)
Cholelithiasis
Electrolyte, vitamin and mineral deficiencies
Metabolic bone disease
Oxalate renal stones
D-lactic acidosis
Line sepsis
Access issues
Line related thromboses
824
What can be used for the management of diarrhoea in short bowel syndrome?
Limiting hypotonic fluid
St Mark's solution (high sodium isotonic fluid)
Drugs: Codeine, loperamide, teduglutide (GLP-2)
825
What are the risk factors for cholelithiasis in IF?
PN
TI resection
SB <120cm
826
What are the typical electrolyte, vitamin and mineral deficiencies in IF?
Fat soluble vitamin (A, D, E, K) deficiencies and essential fatty acids
B12 (especially if >50-60cm of TI resected)
Zinc, copper, selenium deficiencies
Magnesium, potassium, calcium and bicarbonate losses
827
What lifestyle advice and medications can reduce the risk of oxalate renal stones in IF?
Reduction in oxalate rich foods e.g. beetroot, chocolate, spinach, kiwi, rhubarb, blackberries, blueberries, raspberries, aubergine, okra, wheat bran, black tea, chocolate, almonds, peanuts, tofu, soybeans, tomatoes
Low fat diet
Ensure adequate hydration and thus good urinary flow
Increasing dietary calcium (to increase availability for oxalate binding)
Cholestyramine
Pyridoxine can help reduce hyperoxaluria
828
What is the SNAP protocol in intestinal failure?
Sepsis
Antibiotics
Radiological / surgical drainage of collections
Nutrition
Optimise in the interim
Anatomy
Define this prior to next intervention
Plan
IF patients post emergency surgery / recovering intra-abdominal sepsis should have next surgical procedure delayed by 4-6 months??
829
What are the indications for bariatric surgery?
BMI ≥40
BMI 35-40 with other co-morbidity which would improve with weight loss
+ failed to lose weight with other strategies (diet, exercise, medication)
830
What are the general complications of bariatric surgery?
Iron deficiency
SIBO (bypasses)
Early dumping syndrome (vasomotor + GI symptoms <1 hour)
Late dumping syndrome (reactive hypoglycaemia)
Vitamin deficiencies
831
What is the post polypectomy syndrome? What are its features? How is it managed?
Inflammatory reaction from thermal injury without perforation
Results from diathermy
Causes abdo pain, tachycardia, leukocytosis
More common for polyps >2cm OR if normal mucosa also caught in snare
SC injection of fluid reduces risk
Occurs in 0.5-1% of polypectomies, 7-8% of ESDs
Presentation 12 hours to 5 days post
Mx
Must rule out perforation
Fluids, analgesia, antibiotics
832
In which ERCP procedures should prophylactic antibiotics be given? Which?
Biliary obstruction / CBD stones
Only if biliary decompression not achieved in which case a full course of antibiotics should be given
Biliary drainage unlikely to be achieved
Cipro 750mg PO 60-90 mins pre-procedure
OR Gent 1.5m/kg IV over 2-3 mins
Communicating pancreatic cyst / pseudocyst
As above
Biliary complications following liver transplant
As above + either 1g IV amoxicillin or 20mg/kg vancomycin
833
What is the approach to prophylactic antibiotics in EUS?
FNA solid lesions
Not indicated
FNA cystic lesions in or near pancreas or drainage of cyst
Co-amox 1.2g IV
Cipro PO 750mg
834
When should OGDs be performed post oesophageal caustic injury? What are the indications and contraindicatins?
12-48 hours post ingestion, beyond this risks perforation
Contraindications
haemodynamic instability, severe respiratory compromise and suspected perforations
To risk stratify extent of injury
835
How would your risk stratify caustic oesophageal injury? What is the prognosis based on these stages?
Zargar's classification
OGD at 12-48 hours
9x increase in morbidity and mortality with every increased injury grade
Grades 0-IIA generally recover without sequelae
Grades I often heal without
Grade IIA may develop strictures
Grade IIB 70-100% stricture risk
Grade IV 65% mortality
Grade IIB-III eventually develop oesophageal / gastric scarring +/- strictures
Grade 0 - normal
Grade I - oedema / erythema
Grade IIA - haemorrhage, erosions, blisters, superficial ulcers
Grade IIB - circumferential lesions
Grade IIIA - focal deep grey or brownish black ulcers
Grade IIIB - extensive deep grey or brownish-black ulcers
Grade IV - perforation
836
What are the EUS and ERCP KPIs?
EUS
Antibiotic prophylaxis pre EUS-puncture cystic lesions >95%
Tissue sampling during EUS >85%
Minor KPI EUS
Adequate EUS landmark documentation >90%
ERCP
Adequate antibiotic prophylaxis pre ERCP >90%
Bile duct cannulation >90%
Appropriate stent placement in patients with biliary obstruction below the hilum >95%
Bile duct stone extraction >90%
Post ERCP pancreatitis <10%
837
What are the main causes of intussusception in adults? What is the main site?
90% structural lesions, 67% of which neoplastic
Other causes: infections, adhesions, intestinal ulcers, congenital abnormalities and Meckel’s diverticulum
Main site: small bowel
838
What are the grades of internal haemorrhoids?
1) bleeding, no prolapse
2) prolapse, reduces spontaneously
3) prolapse requires manual reduction
4) prolapse cannot be reduced
839
What defines internal vs external haemorrhoids?
Origin above or below dentate line
840
What is the management of symptomatic haemorrhoids?
External haemorrhoids do not respond well to conservative measures
Lifestyle
- Exercise
- Increase fibre + stay hydrated (avoid constipation)
Medication
- Laxatives if constipated
--- Stool softeners - docusate
--- Bulk forming laxatives - fybogel
Topical therapies
- Local anaethetic creams
- Astringents and protectants e.g. zinc oxide paste - in anusol
- Hydrocortisone cream 1-2.5% (up to 7 days)
- GTN 0.2-0.5% ointment - bleeding
- Warm sitz baths
Endoscopic
- Rubber band ligation - for refractory haemorrhoids grade I-III
--- Long-term success of >80%
--- NB: avoid in rectal varices due to risk of delayed bleeding
- Sclerotheray and heater probe (grades I-II) but have higher complication rates
Surgical
Indications
- Grade IV internals
- External symptomatic haemorrhoids, usually thrombosed
Procedures
- External haemorrhoidectomy
- Internal haemorrhoid surgery
--- Conventional hemorrhoidectomy has the highest rate of postoperative complications but the lowest rate of recurrence.
--- Hemorrhoidal artery ligation (HAL) has the lowest rate of postoperative complications but the highest rate of recurrence
--- Stapled hemorrhoidectomy has both a modest postoperative complication rate and a modest recurrence rate
841
What is the management of anal fissures?
Treat constipation
Topical creams
- Local anaesthetic
- Diltiazem - superior side effect profile
- GTN
Warm sitz bath (relaxes sphincter)
Botox injection
Surgical
-Sphincterotomy
842
What is single rectal ulcer syndrome? Who gets it? What are the symptoms?
Chronic, benign, rare (1:100,000) disorder in young adults (3rd-4th decade), M=F
Clinical features
- Rectal bleeding during defacation, mucus discharge
- Associated with excessive straining or abnormal defecation
- 25% are asymptomatic with incidental diagnosis
843
What are the endoscopic and histological features of single rectal ulcer syndrome?
Endoscopic features
- Single/multiple ulcerations of rectal mucosa, covered by white/yellow slough
- Only 20% of patients have a solitary ulcer
Histological features
- Fibromuscular obliteration of the lamina propria
- Hypertrophied muscularis mucosa
- Glandular crypt abnormalities
844
What are the associations with single rectal ulcer syndrome? What other tests may be useful to investigate this?
Dyssynergic defecation is associated with SRUS in 25-82% of patients
Defecatory proctogram and/or anorectal manometry are useful for determining the presence of intussusception, rectal prolapse, or dyssynergic defecation
845
What is the managaement of single rectal ulcer syndrome?
Conservative ---- mainstay
- High fibre diet
- Biofeedback
Medical therapy
- Topical sucralfate
- Topical mesalazine
Surgery - in presence of prolapse
846
What may chlamydia lymphogranuloma venereum proctitis mimic?
Rectal crohn's
847
What are the symptoms of LGV proctitis?
Proctitis symptoms within a few weeks of sexual contact
- Anorectal pain, mucopurulent discharge, PR bleeding, tenesmus, constipation
May have tumorous masses on examination
848
What is the diagnostic test for LGV proctitis? What is the management?
C trachomatis DNA in rectal specimens from anorectal swabs
Mx: doxycycline or erythromycin
849
What are the causes of sexually transmitted proctitis and proctocolitis?
Proctitis
Neisseria gonorrhoeae
LGV
Chlamydia trachomatis: genotypes D-K, L1-3
Treponema pallidum
HSV
Proctocolitis
Shigella
Campylobacter
E Coli
Entamoeba histolytica
Cryptosporidium
CMV (only in immunocompromised)
850
What is AIN? What is the prognosis? What are the symptoms?
Precursor lesion to anal SCC
10% progress to invasive anal cancer at 5 years
Symptoms
Pruritus
Discharge
Abnormal perianal skin: flat, white/grey/purple/brown
- Presence of ulcers suggests invasion
851
What are the RFs for AIN?
HPV
HIV+ve and immunosuppressed individuals
Long-term corticosteroid users
852
What is the management of AIN?
Topicals
- Cidofovir
- Imiquimod
Local ablative therapies
Local excision for lesions involving <30% anal circumference - preferable to ablative therapies
Close follow up
853
What are the causes of faecal incontinence?
Obstetric/surgical trauma
Idiopathic sphincter degeneration - most common arising some time post births
Neuropathy e.g. DM
Pelvic floor disturbance e.g. rectal prolapse
Inflammatory conditions e.g. radiation proctitis, IBD
CNS disorders
854
What are the risk factors for delayed (i.e. not immediately post delivery) idiopathic faecal incontinence?
Strongest risk factors in middle aged women:
- IBS
- diarrhoea
- prior cholecystectomy
Less strong risk factors
- high BMI
- current smoking
- rectocoele
- urinary stress incontinence
855
What is hereditary diffuse gastric cancer? What is the management?
Mutation in the CDH1 gene.
AD inheritance
HDGC is an inherited cancer syndrome that leads to an increased risk for both diffuse stomach cancer and lobular breast cancer.
Mx: prophylactic gastrectomy as it arises in signet ring cells below normal epithelium and thus becomes mucosally apparent only late in the disease process
856
Which drug classically causes villous atrophy? What are the symptoms? What serology might be present? What is the treatment?
ARB - olmesartan
Diarrhoea, weight loss, malabsorption
HLA DQ2/8 may be positive, usually TTG negative
Stop the drug
857
What are the indications for intestinal transplant (+/- liver transplant)?
Permanent/irreversible or life-limiting chronic intestinal failure WITH ONE of the following:
- Evidence of advanced or progressive IFALD
---> Hyperbilirubinemia >75 mmol/L (4.5 mg/dL) despite intravenous lipid modification strategies that persists for >2 months)
---> OR Any combination of elevated serum bilirubin, reduced synthetic function and laboratory indications of portal hypertension and hypersplenism, especially low platelet count, persisting for >1 month in the absence of a confounding infectious event(s)
- Thrombosis of three out of four discrete upper body central veins (left subclavian and internal jugular, right subclavian and internal jugular)
- Invasive intra-abdominal desmoids
- Acute diffuse intestinal infarction with hepatic failure
- Failure of first intestinal transplant
(- Any other potential life-threatening morbidity)
858
What steps can help the prevention of intestinal failure associated liver disease?
Treat/prevent sepsis
Preservation of small intestinal length and retainment/restoration of the colon in continuity with small bowel
maintenance of oral/enteral intake and, where feasible, considering distal EN/chyme reinfusion in patients with non in continuity small intestine
cycling PN infusion (ie PN free time in a day)
avoiding PN overfeeding
limiting the dose of soybean-oil based lipid to less than 1 g/kg/d (medium chain triglycerides, olive oil, fish oil) to reduce polyunsaturated fat content
avoiding any hepatoxic insults wherever possible (e.g. alcohol)
859
How can IFALD be treated?
revising the lipid component of the PN admixture, in order to decrease the total amount and/or to decrease the u-6/u-3 PUFA ratio
treat any inflammation/infections
exclude and treat other causes of liver dysfunction
860
How can PN associated cholestasis be managed?
Resume oral intake if possible
Cholecystectomy
861
How can renal failure be prevented in intestinal failure?
Dietary steps to reduce oxalate stones (low fat, low oxalate)
Calcium supplementation to reduce oxalate stones
Monitor for stones
Avoid dehydration / monitor for this
862
What is the role and indication for teduglutide in short bowel syndrome?
Teduglutide is a GLP-2 drug with intestinal growth factor action
Used for patients who remain on PN despite a period of 12-24 month stability since last bowel resection, with the aim of improving intestinal adaptation and length
Can aid in weaning patients off PN
863
What are the potential risks of teduglutide in short bowel syndrome? How should these be addressed?
Increases risk of intestinal cancer
Colonoscopy, abdominal ultrasound, and gastroscopy to screen for polyps / neoplasia before starting
Repeat the above after 1 year and then every 3-5 years following treatment
864
What bowel lengthening procedures exist?
Bianchi LILT (longitudinal intestinal lengthening and tailoring) procedure
Serial transverse enteroplasty - technically easier and can be done serially
865
What surgery can address rapid transit in short gut syndrome?
Segmental reversal of the small bowel procedure
10-12cm small bowel segment is turned around to antiperistaltic direction
Done 10cm from end ileostomy or ileocolonic anastamosis
866
In what prognostic cases should home PN be contraindicated
Cancer cases with <3 months prognosis
867
What is the role of enteral nutrition in patients with intestinal failure with enterocutaneous fistulae?
Should not be withheld in situation of enterocutaneous fistula, as it does not promote fistula healing, and enteral feeding can actually improve immune barrier function in these areas
868
What is the management of chronic IF secondary to intestinal dysmotility?
PN is mainstay, but continue oral/enteral as able
Can try prokinetics
Treat any SIBO
AVOID surgery due to high complication rate
869
What are the indications for antibiotic prophylaxis in ERCP? What antibiotics should be given?
Biliary obstruction / CBD stones
- Only if biliary decompression not achieved in which case a full course of antibiotics should be given
Complete biliary drainage unlikely to be achieved e.g. malignancy, PSC
- Cipro 750mg PO 60-90 mins pre-procedure
- OR Gent 1.5m/kg IV over 2-3 mins
Communicating pancreatic cyst / pseudocyst
- As above
Biliary complications following liver transplant
- As above + either 1g IV amoxicillin or 20mg/kg vancomycin
870
What are the indications for antibiotic prophylaxis in EUS?
FNA solid lesions
- Not indicated
FNA cystic lesions in or near pancreas or drainage of cyst
- Co-amox 1.2g IV
- OR Cipro PO 750mg
871
What is the approach to antibiotic prophylaxis in PEG insertion cases?
Give to all
Co-amox 1.2g IV
OR cefuroxime 750mg IV
OR teicoplanin 400mg IV
872
What is the approach to antibiotic prophylaxis for severely immuncompromised patients undergoing endoscopy? What cases would this include?
Cases
- neutrophils <0.5
- advanced haematological malignancy
Antibiotic prophylaxis guided by haematology
873
What is the management of intussusception in adults? How does this differ to management in children?
Adults: surgical
Children: US or fluoroscopy guided pneumatic/hydrostatic enema
874
What are the indications for endoscopic therapy in haemorrhoids? What is their success?
Endoscopic band ligation if grade I-III haemorrhoids resistant to medical therapy
>80% long-term success
875
What are the indications for surgery in haemorrhoids?
Grade IV internals
External symptomatic haemorrhoids, usually thrombosed
876
What is the management and investigational approach to patients with faecal incontinence?
Initially conservative measures
- Dietary modification
- Loperamide
Then anorectal manometry = first line investigation
- Measures rectal sensation, rectal balloon expulsion and anal sphincter resting and squeeze pressures
- Urge incontinence: Reduced squeeze pressures
- Passive incontinence: Lower resting sphincter pressures
- Nocturnal incontinence: Rare, but can occur in DM and scleroderma
In patients with weak sphincter pressures, further workup required
- Assessment of sphincter integrity with endoanal US and pelvic MRI, which may guide surgical intervention
When neurogenic causes suspected
electromyography can be used as work-up for sacral nerve stimulator
Biofeedback can be helpful for all causes
876
What are the different surgical procedures available for haemorrhoids? What are their relative benefits?
External haemorrhoidectomy
Internal haemorrhoid surgery
- Conventional hemorrhoidectomy has the highest rate of postoperative complications but the lowest rate of recurrence.
- Hemorrhoidal artery ligation (HAL) has the lowest rate of postoperative complications but the highest rate of recurrence
- Stapled hemorrhoidectomy has both a modest postoperative complication rate and a modest recurrence rate
877
What are the different gland structures of the stomach? What are their respective functions?
Cardiac
- Mainly mucus production
Fundic / oxyntic
- Secrete HCl, mucus, intrinsic factor, pepsinogen, gastric lipase, ghrelin
Pyloric
- Mainly gastrin release, very little HCl release
878
What are the different cell types of the stomach? What are their functions? Where are they found
Parietal (fundic) - hydrochloric acid and intrinsic factor
Chief (fundic) - pepsinogen (which is converted to pepsin in acidic environment and is a protease) and gastric lipase
G cells (antrum) - gastrin release. Released in response to protein/amino acid detection. Increases HCl production by gastric parietal cells
D (antrum, body, stomach) - somatostatin (also produced in delta cells of pancreas)
Enterochromaffin-like (gastric body) - Secrete histamine in response to gastrin, which acts on gastric parietal cells to secrete acid
Enterochromaffin cells - serotonin secreting, and have mechanosensory function, mainly paracrine signalling to aid in peristalsis
Foveolar cells - mucin producing cells which line the stomach, particularly in gastric antrum
A cells - produce glucagon
Ghrelin cells - fundic / oxyntic glands
879
What are intestinal crypts? What cell types do they contain? What are their roles?
Structures between villi at the base
Paneth cells - sense microbes and secrete antimicrobial peptides
Stem cells - basis for intestinal regeneration
Goblet cells - mucus secretion (also found in villi)
880
What are Brunner's glands?
Duodenal glands immediately proximal to the sphincter of Oddi
Secrete bicarbonate rich juice
Open at the base of duodenal villi
881
What are the functional subtypes of cells in the small intestine? What cells are in each category? What are their basic roles?
Absorptive
- enterocyte
Secretory
- Goblet: secrete mucins to create mucus
- Paneth: antimicrobial sensing and peptide secretion
Enteroendocrine
- Enterochromaffin cells. Secrete serotonin which modulates ENS including peristalsis in response to mechanoreceptor function of these cells
- Enterochromaffin like cells. Secrete histamine in response to gastrin, which acts on gastric parietal cells to secrete acid
- D cells. Stomach (antrum), duodenum and pancreatic locations. Release somatostatin in response to low pH, gastrin, VIP, low-grade gastric distention, acetycholine, inhibited by catecholamines
Decreases stomach acid production, pancreatic endocrine and exocrine function, and most gut hormone production, decreases gastric emptying and peristalsis
- I cells (sometimes called enteroendocrine cells?): Duodenum. Secrete cholecystokinin post prandially in response to fatty acids and protein
- K cells: mostly duodenum: Secrete gastric inhibitory peptide (GIP) in response to glucose
- L cells: Distal ileum, colon, (jejunum, duodenum).
Secretes GLP1 in response to glucose. Co-secretes GLP2. Also secretes Peptide YY
- Mo cells: Crypts of the duodenum and jejunum. Secrete motilin which increases peristalsis and gastric emptying
- N cells. Ileal. Release neurotensin which regulates peristalsis
- S cells. Mainly duodenal, but also ileal
Secrete secretin in response to low duodenal pH
Tuft cells
- Chemoreceptive cells
- May play a role in type 2 immunity
Others
- Cup cell - unknown function
- M cell - overlie peyer’s patches and perform microbial trafficking and presentation to IELs
882
What is the role of gastric inhibitory peptide (GIP) aka glucose-dependent insulinotrophic polypeptide? What cell secretes it? In response to what?
Stimulates insulin secretion in response to hyperosmolarity of glucose
Secreted by K cells of the duodenum (mostly)
883
What is the role of GLP1? What cell secretes it? In response to what?
Secreted by L cells of the distal ileum, colon, (jejunum, duodenum) in response to glucose
Promotes insulin secretion
Inhibits gastric emptying, acid secretion and glucagon release
Stimulates glucose-dependent insulin release
Decreases appetite
884
What is the role of GLP2? What cell secretes it? In response to what?
Co-secreted with GLP1 by L cells of the distal ileum, colon, (jejunum, duodenum) in response to glucose
inhibits gastric emptying and gastric acid production
induces small bowel mucosal growth and stimulates mesenteric blood flow
885
What is the role of peptide YY? What cell secretes it? In response to what? Does bariatric surgery affect it?
Post-prandial secretion by L cells of the distal ileum, colon, (jejunum, duodenum)
Inhibits gastric emptying and suppresses appetite
Its release is increased post Roux-en-Y contributing to mechanism of weight loss
886
What is the role of cholecystokinin? What cell secretes it? In response to what? In what functional imaging test can it be used?
Secreted by I cells of the duodenum post prandially in response to fatty acids and protein
Stimulates CNS to signal satiety
Stimulates release of bicarbonate rich pancreatic juice through mechanisms including relaxation of sphincter of Oddi and gallbladder contraction
CCK-stimulated cholescintigraphy can be used to investigate functional gallbladder disorders (CKK infusion followed by radiolabelled tracer to view gallbladder contractility and emptying)
887
What is the role of neurotensin? What cell secretes it?
Secreted by N cells of the ileum. Regulates peristalsis
888
What is the role of secretin? What cell secretes it? In response to what? In what functional imaging test can it be used? In what other endocrine stimulation test can it be used?
Secreted by duodenal (but also ileal) S cells in response to low duodenal pH
Leads to decreased gastrin production and increased pancreatic bicarbonate production + bicarbonate production in duodenal Brunner’s glands to optimally control duodenal pH
IV secretin stimulated MRCP can aid detection of pancreatic duct abnormalities e.g. fistulae +/- sphincter of oddi dysfunction
Secretin provocation test (failure to suppress gastrin <200pg/ml) - diagnosis of Zollinger Ellison syndrome
889
What is the role of somatostatin? What cell secretes it? In response to what?
Secreted by D cells of the stomach (antrum), duodenum and pancreas
Release somatostatin in response to low pH, gastrin, VIP, low-grade gastric distention, acetycholine, inhibited by catecholamines
Decreases stomach acid production
Suppresses pancreatic endocrine and exocrine function
Suppresses most gut hormone production
Decreases gastric emptying and peristalsis
890
What are the cell types of the colon?
Absorptive - colonocyte
Secretory - goblet cells
No paneth cells
Cup cell - unknown function
M cell - immune sensing of luminal bacteria
891
Describe the cellular arrangement and function of the exocrine pancreas
Arrangement of acinar cells around branching ducts
1.5-2L bicarbonate rich fluid containing digestive enzymes and proenzymes secreted each day
Enzymes + proenzyme secretion: trypsinogen, chymotrypsinogen, elastase, (pro-)carboxypeptidase, pancreatic lipase, nucleases, amylase
892
Describe the cellular arrangement and function of the endocrine pancreas
Islets of Langerhans
Alpha cells - secrete glucagon
Beta cells - secrete insulin, amylin (slowing gastric emptying and promoting satiety), C-peptide and GABA
Delta cells - secrete somatostatin
- Decreases stomach acid production
- Suppresses pancreatic endocrine and exocrine function (both insulin and glucagon)
- Decreases gastric emptying and peristalsis
Epsilon cells - secrete ghrelin (lesser than in fundic glands)
- Also other complex endocrine functions affecting somatostatin release
F/PP cells - secrete pancreatic polypeptide in response to fasting, exercise, hypoglycaemia, (and protein meals?). Has antagonistic effects to cholecystokinin, reducing pancreatic fluid, bicarbonate, and enzyme secretion
893
What are the constituents of bile?
Bile acids/salts, cholesterol, phospholipids, bile pigments (such as bilirubin and biliverdin), electrolytes and water
894
What are the differences between primary bile acids, bile salts and secondary bile acids?
Primary bile acids are produced by the liver
They are conjugated by hepatocytes to form water soluble bile salts which act as detergents to emulsify dietary lipids in the gut
Primary bile acids are metabolised into secondary bile acids by the action of colonic bacteria
895
Describe the enterohepatic cycling of bile acids
Bile salts are actively reabsorbed in the TI
Primary and secondary bile acids are passively reabsorbed throughout the GI tract
These all re-enter the liver via the portal circulation and are used as building blocks for the re-synthesis of primary bile acids/salts
Single bile molecule re-used 20x
896
What is the mechanism of b12 absorption?
Cobalamin (b12) is usually protein bound in the foods we consume
Pepsin (a protease) + stomach acid release cobalamin
Salivary glands produce R-protein which binds cobalamin to protect it from acid-mediated degradation
Pancreatic enzymes hydrolyse the R-protein in the duodenum which releases cobalamin again, and then binds to intrinsic factor produced by gastric parietal cells
Intrinsic factor-bound cobalamin can then be absorbed in the distal ileum
897
Detail the histological findings in someone with alcohol related liver disease
Steatosis
- Macrovesicular steatosis: fat droplet accumulation in hepatocytes
- First begins in zone 3 (perivenular)
Steatohepatitis
- Steatosis + inflammatory cell infiltrate
- Ballooning degeneration: cellular swelling, rarefaction of the hepatocytic cytoplasm and clumped strands of intermediate filaments
- Satellitosis: ballooned hepatocyte surrounded by neutrophils
- Mallory-Denk body: a deeply eosinophilic, ropy intracytoplasmic inclusion that represents aggregates of misfolded proteins
---> Often but not necessarily found in ballooned hepatocytes
---> Persists for several months after cessation of drinking
---> Associated with increased risk of progression to cirrhosis
Fibrosis
- Begins perivenular and progresses to portal/periportal, bridging fibrosis and cirrhosis
- Pericellular pattern
- With progressive cirrhosis, steatosis and ballooning may burn out
Other features
- Lipogranuloma
- Giant mitochondria: associated with recent heavy alcohol intake and disease progression
- Acute foamy degeneration: rare, extensive microvesicular steatosis with no / minimal inflammatory activity; clinically presents with jaundice, abdominal pain and hepatomegaly
- Sclerosing hyaline necrosis: fibrous obliteration of terminal hepatic venule (phlebosclerosis) due to perivenular fibrosis; severe form of alcoholic hepatitis associated with noncirrhotic portal hypertension
- Iron deposition: usually mild; mainly in hepatocytes (grade 1 - 2) and occasionally in Kupffer cells
898
What are the histological findings that might be found in someone with MAFLD?
Steatosis
- Macrovesicular steatosis: fat droplet accumulation in hepatocytes
- First begins in zone 3 (perivenular)
Steatohepatitis
- Steatosis + inflammatory cell infiltrate
- Ballooning degeneration: cellular swelling, rarefaction of the hepatocytic cytoplasm and clumped strands of intermediate filaments
- Satellitosis: ballooned hepatocyte surrounded by neutrophils
- Mallory-Denk body: a deeply eosinophilic, ropy intracytoplasmic inclusion that represents aggregates of misfolded proteins
---> Often but not necessarily found in ballooned hepatocytes
Fibrosis
- Begins perivenular and progresses to portal/periportal, bridging fibrosis and cirrhosis
- Pericellular pattern
- With progressive cirrhosis, steatosis and ballooning may burn out
Other features
- Lipogranuloma
- Giant mitochondria: associated with recent heavy alcohol intake and disease progression
- Glycogenated nuclei
- Iron deposition: usually mild; mainly in hepatocytes (grade 1 - 2) and occasionally in Kupffer cells
899
What is the cellular origin of GIST?
Interstitial cells of cajal within Auerbach's plexus aka myenteric plexus
900
What is the approach to endoscopic investigation / surveillance of an incidental subepithelial lesion?
<1cm
- OGD +/- EUS in 6-12 months + get tissue if possible
- 3 yearly surveillance if no growth and no high risk factors (or consider discharge)
1-2cm
- OGD +/- EUS + get tissue if possible
- 2 yearly surveillance if no high risk factors
>2cm or high risk feature
- OGD +/- EUS + CT + get tissue
- discuss resection
901
What types of DILI are caused by thiopurines? What are their features? How common are they?
Transient transaminitis
- 10% of patients
- Resolves with dose reduction/discontinuation
- Associated with higher methyl mercaptopurine (metabolite)
Cholestatic hepatitis
- 1/1000 develop this idiosyncratic drug reaction
- Modest transaminitis and ALP + moderate-severe jaundice
Sinusoidal obstruction syndrome
- Veno-occlusive disease
- Usually occurs after presents after haematopoietic stem cell transplantation (days/weeks, related to pre transplant chemo) - 15% of transplants
- Also some chemotherapeutics
- Injury to sinusoidal endothelial cells -> inflammation + narrowing and coagulation of liver sinusoids
- Signs/symptoms
---> Thrombocytopenia
---> Hepatomegaly
---> Ascites
---> Jaundice
---> Can progress to multi organ failure and death
- Biopsy
---> Liver sinusoids dilated and congested by erythrocytes
---> Nonthrombotic fibrous occlusion of the central veins and small venules
---> +/- widespread zonal disruption and centrilobular haemorrhagic necrosis
---> Later: collagen in sinusoids, sclerosis of venular walls, fibrosis of venular lumens and occlusion of terminal hepatic venules
- DDx: Acute graft versus host - Similar liver appearances, but usually also have skin and GI manifestations
NRH
- 1% of IBD patients treated with azathioprine for 10 years
- Diffuse nodularity without annular fibrosis
- A cause of non-cirrhotic portal hypertension
902
What is the approach to oral fluid management in short gut syndrome?
Limit hypotonic fluid to 500ml/day
AND EITHER
1L St Mark’s solution (20g glucose, 3.5g salt, 2.5g sodium bicarbonate)
- To achieve sodium concentration >90mmol/L in fluid
OR
10 sachets of dioralyte in 1L
- Beware this has higher K load
- Beware in renal failure
903
Is there a situation in which liver transplant is preferable for the management of cholangiocarcinoma?
Perihilar tumours <3cm in patients with chronic liver disease (usually PSC) if there is no evidence of extrahepatic disease
904
What is the staging system for perihilar cholangiocarcinoma?
AJCC 8th edition
T1 - confined to bile duct up to muscle layer
T2a - invades through bile duct into surrounding adipose tissue
T2b - invades through bile duct into surround liver parenchyma
T3 - invades unilateral branches of the hepatic artery or portal vein
T4
tumour invades the main portal vein or its branches bilaterally, or
unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement
bilateral second order bile duct invasion
N1: 1-3 positive regional lymph nodes
N2: 4 or more positive regional lymph nodes
M1 distant mets
905
What is the staging system for intrahepatic cholangiocarcinoma?
AJCC 8th edition
T1 - solitary tumour without vascular invasion
T1a ≤5cm
T1b >5cm
T2 - solitary tumour with vascular invasion or multiple tumours
T3 - invades visceral peritoneum
T4 local invasion of extrahepatic structures
N1 - regional LNs
M1 distant mets
906
What is the role of radiotherapy in cholangiocarcinoma management?
Unresectable disease
- Symptomatic metastatic disease should be considered for palliative radiotherapy
- Consider SBRT (stereotactic radiotherapy) for oligometastatic disease
Pre-liver transplant in select pCCA cases (PSC + <3cm tumour with no extrahepatic spread)
907
What are the features of hEDS?
Generalised joint hypermobility
- e.g. Beighton score formalises this
--- >5 positive in adults
--- >4 positive in people over age of 50
- chronic pain
- Association with functional GI disorders
- Association with autonomic disorders
--- POTS
--- Irritable bladder
No genetic basis known
908
What is the basis for slow wave contractions in the GI tract
Pacemaker activity of the interstitial cells of cajal
909
What is the migrating motor complex
Hormonal controlled (e.g. motilin) migrating waves of electrical activity in the bowel that initiate peristaltic movements and vary with fasting-eating (via hormonal control)
Not stretch activated
910
What are the high risk features of patients with eating disorders
High risk features for eating disorder patients - one or more red (listed below) or 2 or more amber (not listed)
Weight loss
- Recent weight loss ≥ 1kg / week for 2 consecutive weeks in undernourished patient
- Rapid weight loss in any other patient
- BMI <13
Eating disorder behaviour
- Acute food refusal
- <500kcal/day 2+ days
- Multiple daily purging
- Multiple daily laxative abuse
- >2h daily exercise + malnourished
Management plan engagement
- Poor engagement
- Poor insight/motivation
- Fear of weight gain
Suicidal/self harm behaviours
- Self poisoning
- High risk suicidal ideation
Heart rate <40
Blood pressure <90SBP + 20mmHg postural drop with recurrent syncope
ECG
- QTc >450ms females
- QTc >430ms men
Biochemical abnormalities
- Hypophosphataemia and falling phosphate
- Hypokalaemia (<2.5mmol/L)
- Hypoalbuminaemia
- Hyponatraemia
- Hypocalcaemia
- Transaminases >3x normal range
- Inpatients with diabetes mellitus: HbA1C >10% (86mmol/mol)
- Blood glucose <3
Haematological abnormalities
- Low WCC
- Hb <10
Hydration status - fluid refusal or severe dehydration
Temperature <35.5C
Muscular function
- Unable to sit up from lying
- Unable to stand from squat without upper limbs
Other associated clinical conditions
- Severe haematemesis
- DKA
- GI perforation
- Acute confusion
- Significant alcohol consumption
911
For pancreatic cancer, what vascular involvement would be unresectable vs borderline unresectable? What is the clinical implication?
Borderline unresectable cancers can be considered for neoadjuvant chemoradiotherapy as a bridge to surgery
Unresectable
- Involvement of the SMA or celiac axis to the extent where the tumour would theoretically lead to arterial resection and reconstruction (>180 degrees or with deformity/stenosis)
- Any involvement of the aorta (even if just abutting)
- Venous involvement exceeding the inferior border of the duodenum
Borderline unresectable
- Venous involvement alone not exceeding the inferior border of the duodenum
- Arterial involvement <180 degrees of SMA/coeliac axis without deformity or stenosis
- Common hepatic artery contact alone
912
How does Forrest classification affect DAPT restarting decisions?
Restart DAPT immediately for IIc / III lesions
913
What are the causes of pruritis ani?
Pinworm most common cause in children. Mx albendazole
Threadworm (enterobius vermicularis) is another cause in children/institutions. Mx mebendazole
Idiopathic most common in adults
Secondary causes
- Perianal neoplasia
- Other derm conditions
- Faecal leakage
- Excessive sweating
- Anal fissures
- Fistulae
- Skin tags
- Candida (10% adults): obese, elderly, immunocompromised
- Herpes (sexually transmitted)
- Dietary causes: caffeine, alcohol, tomatoes, spicy foods
- Itch-scratch-itch cycle
914
What is the general management of pruritis ani?
Treat any secondary causes
Topical
- Anusol/zinc oxide ointment
- Berwick’s solution
- (capsaicin)
Avoid excessive cleaning/rubbing of perianal area; Warm water only
915
How does UC in the elderly differ in presentation than in the young?
- Higher risk of hospitalisation
- More atypical presentations with abdo pain and fever more common
- Left sided disease more common
- Proctitis less common
916
How does crohn's present in the elderly compared to how it presents in the young?
Colonic disease more common
917
What is the approach in the days leading up to colonscopy for bowel preparation?
4 days prior
- Stop taking iron tablets
3 days prior
- Stop taking codeine / loperamide
2 days prior
- Stop eating fibre
- Reduce meal size
- Increase fluid intake
1 day prior
- Stop bulk forming laxatives
- Light breakfast 9am or earlier, then no more food until after test
- You can have drinks including light stock & squash & tea/coffee
- Start bowel prep
Day of procedure
- Drink clear fluid up until 3 hours pre-procedure
- Do not eat anything
For morning procedures
- 6am take bowel prep
PM procedures
- 10am take bowel prep
918
What is the preferred type of bowel prep for IBD patients
PEG
919
What is the preferred type of bowel prep for elderly patients?
Osmotically balanced PEG
920
Define the severity of alcohol withdrawal based on the CIWA score
Mild ≤ 8
Moderate >8
Severe ≥15-20 (different info)
921
What may be found on aspiration of a pancreatic pseudocyst?
High amylase
922
What types of collections are uniquely found in necrotising pancreatitis?
Acute necrotic collections
Walled off necrosis
- maturation after >4 weeks of acute necrotic collection
Both heterogenous collections vs homegenous pancreatic pseudocysts
923
What is the approach to pain management in chronic pancreatitis?
Alcohol cessation
Pancreatic enzyme supplementation does not improve pain
Oral analgesia
- Tramadol preferred over morphine due to fewer GI side effects
- Adjuvants include neuropathic agents
Management of structural lesions
- Pseudocysts - EUS guided gastric drainage with LAMS or surgical cystogastrostomy
- Ductal calculi: Main pancreatic duct stones >5mm - extracorporeal shockwave lithotripsy
- Strictures: Painful dominant main pancreatic duct strictures - plastic stenting
EUS guided coeliac plexus block - however often short lived (<10% experience pain relief for >24 weeks)
Surgical
- Drainage procedures (pancreatico-jejunostomy)
- Partial/total pancreatectomy
924
Describe the process of giardiasis spread and how it causes disease
Faeco-oral spread
Cysts ingested and stomach acid degrades cyst, releasing trophozoites
Trophozoites undergo asexual reproduction in the gut and colonize the upper small bowel by adherence, not invasion
Cause cytokine release -> electrolyte and water loss
925
Where is giardiasis found? What is the incubation period? How is it diagnosed?
Worldwide
Days to months
Stool showing cysts - double nuclei
926
What are the symptoms and management of giardiasis?
Symptoms
- Bloating, flatulence
- Abdo pain
- Non-bloody diarrhoea
- Malabsorption and weight loss
Mx
- Tinidazole single dose
- Short course metronidazole
927
What is a granular cell tumour? What are the main features that define it in terms of investigations? How is it managed?
Rare, usually benign, lesion of schwann cell origin
Some may recur locally
Second most common stromal tumour of the oesophagus
Can be found anywhere in the GI tract but the lower oesophagus is most common
Endoscopy: sessile, yellowish white, firm, intact epithelium (submucosal)
Histology
- Sheets/packets of polygonal epithelioid cells
- Granular eosinophilic cytoplasm
Mx
- Endoscopic resection (ESD)
- Vs conservative
- Some do not grow much, mitotic figures may guide this
928
What is a leiomyoma? What are the main features that define it in terms of investigations? How is it managed?
Most common benign tumour of the oesophagus
Arise from muscularis layers (propria or mucosae)
Endoscopy
- 2-5cm well circumscribed, submucosal, solitary mass
- Usually sessile but may be polypoid
- Pinkish gray white with whorled cut surface; mucosal surface is only rarely ulcerated
Histology: Whorls of long spindle-like smooth muscle cells with eosinophilic cytoplasm
Mx: resection vs conservative (based on symptoms)
929
What is a fibrovascular polyp? What are the main features that define it in terms of investigations? How is it managed?
Polyp of fibroadipose tissue which typically affects the upper oesophagus
Previously thought to be benign but now considered to be well-differentiated or de-differentiated liposarcomas based on immunohistochemistry
Typically present in older men
Endoscopy
Can become very large (up to 20cm)
Pedunculated polyps
Typically present in proximal oesophagus
Histology
folds of normal squamous mucosa containing blood vessels, adipose cells, and stroma
Mx
Well differentiated types are benign but can still grow
De-differentiated types can recur and metastasize
Endoscopic or surgical resection
930
What is the UCEIS score? What are its components and its interpretation?
Endoscopic score of severity in UC
Vascular pattern
0: normal
1: patchy obliteration of vascular pattern
2: complete obliteration
Bleeding
0: none
1: mucosal surface bleeding only
2: mild luminal bleeding
3: frank blood in the lumen which oozes after washing
Ulceration
0: normal
1: tiny <5mm erosions
2: >5mm superficial ulcers
3: deep ulcers
Interpretation
0-1: remission
2-4: mild
5-6: moderate
7-8: severe
931
What is the mayo score? What are its components and its interpretation?
Simple endoscopic score of UC severity
1: mild disease. Erythema, decreased vascular pattern, mild friability
2: moderate disease. Marked erythema, obliterated vascular pattern, erosions, friability
3: severe disease. Spontaneous bleeding, ulcerations
932
What is the management of oesophageal perforation?
General
- NBM
- IV fluids
- Antibiotics and antifungals
- Imaging: CT chest/abdo
Endoscopy related perforation
- Endoscopic closure of small/non-inflamed defects
- Covered metal stent insertion for larger/inflamed defects
- Contrast enhanced CT to assess leak after management + guide resuming PO intake vs need for surgical or surgical-endoscopic hybrid repair
Non-endoscopy related
- If patient presents <24 hours, is not septic, has a cervical or thoracic perforation, has a small and contained perforation and no other oesophageal disease
---> Non-operative management with PPI + PN or NGT feeding
Reassess with contrast enhanced CT chest after 5-7 days
- Otherwise surgical or surgical-endoscopic hybrid repair
933
What is katayama syndrome?
Hypersensitivity reaction to shistosomiasis in niaive patients with systemic symptoms including fever, cough, myalgia, headache, diarrhoea
May occur after typical 'swimmer's itch' at site of entry
934
Wat is the kato katz thick film?
5mg of stool examined for schistosomiasis with low power microscopy
935
What is the stroop test?
Used for diagnosis of covert HE (not developed for this)
Psychomotor speed and flexibility - words of colours in incongruent font colour - time to name them
936
What percentage of thiopurine induced leucopenia is accounted for by TPMT variants?
Up to 25%
937
What is the prevalence of different TPMT genotype/phenotypes?
Data in caucasians only
0.3% homozygous variant - absent TPMT
10% heterozygous - low TPMT
90% homozygous wild type - high/normal
938
What investigations should be used as part of the staging and workup of gastric cancer?
- Bloods
- Endoscopy
- CT CAP
- EUS can be used for accurate T and N staging in potentially resectable disease
- Diagnostic laparoscopy and peritoneal washings to exclude peritoneal disease in patients with advanced but potentially resectable disease
- FDG PET not routinely recommended as mucinous and diffuse gastric cancer types do not show uptake
939
Detail the functional biliary / gallbladder disorders and their management
SOD1
Persistent biliary type pain (episodes that last 30+ mins, recurring at different intervals, pain that builds to a steady level, moderate-severe pain type, not related to bowels/postural change/antacids)
Abnormal LFTs AND dilated bile ducts
Now thought to be organic sphincter of oddi stenosis
Mx: sphincterotomy
SOD2
Persistent biliary type pain
Abnormal LFTs OR dilated bile ducts
Now called functional biliary sphincter disorder
Approach
EUS to exclude microlithiasis
Consider ERCP + sphincter manometry OR hepatobiliary scintigraphy for supportive information
Options
- May depend on sphincter manometry / scintigraphy
- Conservative (consider CCBs, amitriptyline, duloxetine) + analgesia
- Sphincterotomy
- Sphincter botox
SOD3
Persistent biliary pain
Normal LFTs and ducts
Now called functional gallbladder disorder
Options
- Conservative + analgesia; consider CCBs, amitriptyline, duloxetine
- Cholecystectomy if very typical symptoms
940
What is the perforation rate for benign oesophageal strictures?
1%
941
Is balloon or bougie dilatation of benign oesophageal strictures better?
Equivocal
942
When should barium swallow be considered in benign oesophageal strictures?
For suspected long/complex strictures
943
What is pharyngeal pouch? What are the symptoms? How is it managed?
Also called zenker’s diverticulum
Prolapse of mucosal and submucosal layers of the oesophagus through Killian’s triangle
More common in older individuals
Symptoms
Dysphagia +/- aspiration pneumonia
Halitosis
Gurgling sensation
Regurgitation
Mx
Endoscopic diverticulotomy - safer
Cricopharyngeal myotomy - surgical approach reduced risk of symptom recurrence
944
In what liver disease do symptom severity not correlate well disease stage?
PBC
945
What are the Baveno VI criteria?
If plt >150 and fibroscan <20kPa then no variceal screening needed
946
What is the approach to CMV prophylaxis post LT?
Donor positive/recipient negative CMV status (CMV mismatch) is the highest risk for developing CMV disease and require 3 months valganciclovir prophylaxis post LT
Donor/recipient positive and donor negative/recipient positive should just have CMV monitored and valganciclovir only for persistent viraemia
Donor/recipient negative are at lowest risk and do not need routine screening
947
What are the direct and indirect effects of CMV infection post LT?
Direct effects of CMV infection
- Colitis, hepatitis, retinitis
Indirect effects of CMV infection
- Increased risk of organ rejection
- Increased risk of vanishing bile duct syndrome
- Increased risk of PTLD
- Increased risk of hep C recurrence
948
What is the management approach to someone who has ingested a large volume of drugs packed in plastic bags?
Avoid retrieval attempts as plastic bag rupture could risk systemic intoxication
If bowel obstruction or intoxication occur then surgery may be required
Otherwise whole bowel irrigation and laxatives and monitoring are required
949
Which IBD drugs work in psoriatic arthritis?
Anti-TNFs
- IFX
- ADA
- Golimumab
Ustekinumab
JAK inhibitors
- Tofacitinib
- Upadacitinib
950
Which IBD drugs work in plaque psoriasis?
ADA
IFX
Ustekinumab
951
Which IBD drugs work in axial spondyloarthritis?
Anti-TNFs
- IFX
- ADA
- Golimumab
Upadacitinib
952
Which IBD drugs work in ankylosing spondylitis?
Anti-TNFs
- IFX
- ADA
- Golimumab
JAK inhibitors
- Tofacitinib
- Upadacitinib
953
Which IBD drugs work in rheumatoid arthritis?
Anti-TNFs
- IFX
- ADA
JAK inhibitors
- Tofacitinib
- Upadacitinib
- Filgotinib
954
Which IBD drugs work in juvenile idiopathic arthritis?
Anti-TNFs
- IFX
- ADA
- Golimumab
JAK inhibitors
- Tofacitinib
- Upadacitinib
955
Which IBD drugs work in MS?
Ozanimod
956
Which IBD drugs work in hydradenitis suppurativa?
ADA
957
In what percentage of upper GI bleeding is no case found at index endoscopy?
17%
958
What are the different types of gallstones
90% cholesterol
10% pigment (excess unconjugated bilirubin)
- brown pigment: conditions of biliary obstruction and infection, stones form in ducts
- black pigment: conditions of hyperbilirubinaemia, stones form in gallbladder
959
What is the management of upper GI bleeding secondary to aorto-enteric fistulae?
Surgical
- graft excision + graft reconstruction or bypass
Endovascular
- stenting
- balloon occlusion
- coil embolisation
960
What is hydatid disease? What are the symptoms? How is it diagnosed? How is it treated?
Echinococcus granulosus
Eggs ingested -> cystic lesions in liver and lungs
Dogs are main definitive host
Globally distributed but most present in South America, East Africa, Central Asia, China
Asymptomatic incubation period can last years until cysts reach a sufficient size -> abdominal pain, nausea
Chronic cough and chest pain may also be present
Ix
Eosinophilia is common
Radiology: US/CT show fluid density cysts with peripheral focal calcification
+/- aspiration
Hydatid serology
Mx
Drugs: albendazole
PAIR treatment - puncture, aspiration, instillation and reaspiration of scolicidal agent
Surgical cystectomy
Depends on size and complexity of cyst
961
According to JAG standards, is there a target for proportion of ERCPs carried out in a unit with therapeutic intent?
90%
962
Describe common genetic changes leading to the development of sporadic colorectal cancer
Tumour suppressor gene inactivation
APC -> polyp formation
P53
P27
Activation of oncogenes
KRAS
B-catenin -> polyp formation
Through mutations
963
Detail the main risks in ERCP and their relative occurences
Pancreatitis is most common - incidence 1.3-6.7%
3% mortality of these cases
Cholangitis 1%
GI haemorrhage 0.7-2%
Duodenal perforation 0.3-1%
Cardiorespiratory complications 0.5-2.3%
964
What is the rate of perforation in diagnostic OGD?
1:5000
965
What is the rate of perforation and haemorrhage in diagnostic colonoscopy?
Perforation 1:1500
Haemorrhage 1:500
966
What is the rate of perforation and haemorrhage in colonoscopic polypectomy?
Perforation 1:500
Haemorrhage 1:100
967
What is the rate of perforation in oesophageal balloon dilatation in benign strictures, malignant strictures and achalasia?
Benign: 1:100-200 (0.5-1%)
Malignant 1:25 (4%)
Achalasia 1:20-100 (1-5%)
968
Describe the genetics and pathophysiology of Gilbert's. What makes jaundice better or worse?
AR inheritance, but with incomplete penetrance
Missense mutation in UDPGT gene can lead to AD causes - less common
Effects 2-5% of the population
UDP glucoronyl transferase levels are reduced leading to unconjugated hyperbilirubinaemia
Jaundice occurs when unwell and reduced by enzyme inducers e.g. phenobarb/phenytoin/carbemazepine
Unconjugated bilirubin does not pass into the kidneys
969
In what liver conditions is skin pigmentation seen in addition to jaundice?
PBC
Haemochromatosis
970
Is budd-chiari or PV thrombosis more likely in a presentation with ascites, abdominal pain and hepatosplenomegaly?
Budd-chiari
In PV thrombosis, portal hypertension can develop with chronic disease. Mesenteric infarction more likely here through thrombus extension into the SMA
971
What is the approach to stone management in gallstone pancreatitis?
Lap chole
- Same admission for mild pancreatitis, ideally within 2 weeks
- Early lap chole when safe to do so for others
ERCP acutely
- Co-existent cholangitis or persistent biliary obstruction - urgent ERCP <72 hours - sphincterotomy and stone extraction
---> <24 hours if septic shock
Outpatient ERCP
- If persistent CBD stone but did not require inpatient ERCP - sphincterotomy and stone clearance
972
What is Kikuchi staging? What is it's clinical relevance?
Kikuchi staging: extent of invasion of cancer into flat polyps
1: invasion of superficial third of submucosa - 0% metastasis chance
2: invasion up to intermediate third of submucosa - 10% metastasis chance
3: invasion extending to the inner surface of muscularis propria - 25% metastasis chance (including LN spread)
Recurrence rates for lesions with clear margins are thus
SM1: 0%
SM2: 10%
SM3: 25%
973
What pre-dilatation investigations should be done for oesophageal strictures?
Always biopsy strictures to exclude malignancy
Biopsy when concerned re EoE - young patients and food bolus obstruction presentation
CT/EUS for strictures concerning for malignancy
Barium swallow for suspected complex strictures to detail anatomy
974
What form of oesophageal dilatation is more uncomfortable?
Bougie
975
What considerations are there for choosing size dilator for oesophageal strictures/achalasia?
Limit initial dilatation to 10-12mm for impassable strictures
Aim dilatation every 2 weeks until at least >15mm and then according to symptoms
Achalasia
- Start at 30mm
- 2-28 days later 35mm
- Consider going up to 40mm
Shatzki ring: Single session of graded 16-20mm dilatation
EoE: consider balloon pull through to guide
Post surgical
- post nissen: 30-40mm balloon
- anastamotic: triamcinolone and bougie dilatation
976
What imaging should be done post oesophageal dilatation?
None routinely
If perforation suspected (persistent pain, tachycardia, fever) then CT chest with PO contrast
977
What therapies can be given to reduce oesophageal stricture recurrence?
PPIs
Consider intralesional steroid injection or PO steroid in refractory cases
978
In what endoscopic procedures is oesophageal stricture formation likely?
50% chance of stricture requiring dilatation after EMR/ESD of >75% circumference and 4cm long lesion
High energy RFA
979
What is the approach to stricture management post caustic oesophageal injury?
Avoid dilatation within 3 weeks of ingestion
Consider time interval between dilatations of <2weeks
980
What is porphyria cutanea tarda? How does it present?
Deficient activity of uroporphyrinogen decarboxylase in the liver
Type 1: sporadic
Absence of UROD gene variant
80% of individuals
Type 2 (familial)
Heterozygous UROD gene variant
20% of individuals
NB: most individuals with this variant do not get PCT
Type 3
Familial but no UROD gene variant
Presentation
Photosensitive sink rash
Liver injury - transaminitis
Increased risk of cirrhosis and HCC
NO neurovisceral symptoms
981
How is porphyria cutanea tarda diagnosed? How is it treated?
Ix
Total serum porphyrins - elevated
OR urine porphyrins - elevated
Specifically increased uroporphyrin, hepta/hexa/penta-carboxyl porphyrins
UROD (AND HFE, which may be contributing) gene analysis
Liver biopsy will show porphyria loading +/- iron loading
Mx
Phlebotomy if iron overload present
Otherwise consider low dose hydroxychloroquine
Treat any other contributing liver disease
982
What is Goodsall's rule?
Relating to internal openings of fistulas
Posterior fistulas always have their internal opening at 6 o’clock
Anterior fistulas have their internal opening at the same clock face as the external opening
983
What serology is suggestive of pernicious anaemia? What are their relative merits?
Anti-intrinsic factor antibodies are diagnostic, but absent in 50% of cases (most specific)
Anti gastric parietal cell antibodies are present in 85% of cases, but also in 10% of healthy individuals (most sensitive)
984
What is the approach to colonoscopic screening and surveillance in acromegaly? What is the basis of this?
Offer colonoscopy at diagnosis or age 40
If IGF1 levels high or adenoma detected last endoscopy - every 3 years
If initial colonoscopy negative, or hyperplastic polyps found, or IGF1 normal range, screen every 5-10 years, or participate in bowel cancer screening
985
What are the grades of hypovolaemic shock?
Total blood volume is 70ml/kg = 5L for 70kg
1) 15% blood volume (750ml average). Mild resting tachycardia
2) 15-30% blood volume (750ml-1.5L). Moderate tachycardia, narrow pulse pressure, increased CRT
3) 30-40% blood volume (1.5-2L). Hypotension, tachycardia, low urine output
4) 40-50% blood volume (2-2.5L). Profound hypotension with end organ failure
986
What is scombroid poisoning?
Symptoms of rapid onset
- facial flushing
- urticarial rash
- diarrhoea
- headache
- rarely severe bronchosmasm
Occurs soon after eating contaminated fish (or Swiss cheese)
Results from spoiled fish which are improperly stored and thus bacterial overgrowth occurs and bacterial enzyme histidine carboxylase leads to histamine production
Management
- supportive
- antihistamines
- treat as anaphylaxis if shock occurs
987
What are the extrahepatic features of hepatitis C?
Haematological
- Vasculitis associated with mixed-cryoglobulinaemia: cutaneous, neuropathic and renal complications
- Non-hodgkin B cell lymphoma
- Monoclonal gammopathies
Autoimmune
- Sjogren’s syndrome
- Autoimmune hepatitis
- Thyroid disease
- ITP / autoimmune haemolytic anaemias
Dermatological
- Porphyria cutanea tarda
- Lichen planus
Renal disease
- Cryoglobulinaemia
- HCV immune complex nephropathy
988
How is iron absorbed enterally?
Ferrous -> ferric iron by action of acid in the stomach
Ferric acid is absorbed in the duodenum
Absorption of iron is improved by ascorbic acid / vitamin C
989
What are the 2ww and non-urgent referral criteria for OGD?
2ww for OGD
Dysphagia
≥55 years + weight loss +
- Upper abdominal pain
- Dyspepsia
- Reflux
Other less urgent criteria for referral (routine OGD)
Haematemesis
OR
≥55 years +
- Treatment resistant dyspepsia
- Upper abdominal pain + anaemia
- Nausea / vomiting +
---> Weight loss
---> Reflux
---> Dyspepsia
---> Upper abdo pain
- Raised platelets +
---> Nausea / vomiting
---> Weight loss
---> Reflux
---> Dyspepsia
---> Upper abdo pain
990
What are the features of glucagonoma?
Weight loss
Necrolytic migratory erythema
- 70-80% of patients
- erythematous papules involving face, perineum and extremeties, which coalesce, before clearing to leave bronze coloursed indurated areas with blistering and scaling at the borders
- process also affects mucous membranes: glossitis, angular cheilitis, stomatitis, blepharitis
Diabetes/impaired glucose tolerance
Chronic diarrhoea
Venous thrombosis
Normocytic normochromic anaemia
991
What is necrolytic migratory erythema? What is the diagnostic test? In what other conditions can it be found?
Skin rash which classically occurs in 70-80% of patients with glucagonoma
Erythematous papules involving face, perineum and extremeties, which coalesce, before clearing to leave bronze coloursed indurated areas with blistering and scaling at the borders
Process also affects mucous membranes: glossitis, angular cheilitis, stomatitis, blepharitis
Diagnosis: skin biopsies showing superficial necrolysis with separation of the outer layers of the epidermis and perivascular infiltration with lymphocytes and histiocytes
NB: not specific for glucagonoma -- hepatitis B, cirrhosis, jejunal and rectal adenocarcinoma, MDS
992
Where can GISTs be found?
Classically in the body of the stomach
Also found in descending frequency
- small bowel
- oesophagus
- rectum
993
What is the management of reflux in pregnancy?
1) Antacids - proven to be safe
2) H2 antagonists - also found to be safe from observational studies
3) PPIs should be used with caution - conflicting evidence on safety? Not known to be harmful
994
How should hepatitis C sustained virilogical response (SVR) be measured?
Undetectable viral load 12 and 24 weeks after treatment
995
How should recently acquired hepatitis C be defined and treated?
New HCV positivity in a patient with negative samples <12 months ago
OR
HCV positivity + 3x ULN ALT + high risk behaviour in the last 6 months with exclusion of other causes of liver disease
Management
- sofosbuvir/velpatasvir 8 weeks
OR
- glecapravir/pibrentasvir 8 weeks
996
What is the management of typhoid/enteric fever?
Preventative
- hygiene
- typhoid vaccine
Abx
- ceftriaxone or cefotaxime if severe
997
What blood markers and patient characteristics suggest poor prognosis in acute pancreatitis?
Glasgow imrie features (no longer used routinely in 1st 48 hours)
Age>55
WCC >15
Urea > 16
Calcium <2
Glucose >10
Albumin <32
LDH >600
PaO2 <8kPa
Others
CRP >150
998
Which is the most sensitive method of H pylori testing? How does it compare with other methods?
Carbon-13 urea breath testing
- most sensitive 95%
- 98-100% specific
- licenced for retesting
Rapid urease test on biopsy (CLO)
- 80-95% sensitive
- 95-100% specific
Histology
- 80-90% sensitive
- 95% specific
Serology only has IgG
Stool antigen?
999
What peripheral clinical signs might be seen in PBC?
Palmar xanthomas
Tuberous xanthomas (particularly extensor surfaces)
1000
What is acute and chronic graft versus host disease? What are their features? How is it diagnosed?
General: Multisystem disorders common following allogeneic haematopoietic stem cell transplant
Acute
Onset <100 days (although rarely can occur later)
Skin
- Maculopapular rash
GI
- Nausea
- Vomiting
- Abdominal cramps
- Large volume diarrhoea
- Histology: crypt cell necrosis with accumulation of degenerative material in the dead crypts - rectal biopsy most commonly performed
- Severity of disease is based on volume of diarrhoea
Liver
- Rising bilirubin and ALP occur first
- Liver biopsy: extensive bile duct damage with lymphocytic infiltration
Chronic
Onset after day 100 (but usually within 1 year)
Can occur with or without prior acute graft versus host disease
Mucocutaneous
- Skin resembles lichen planus or cutaneous manifestations of scleroderma e.g. erythematous plaques, desquamation, photosensivitiy, slerosis
- Dry oral mucosa with ulcerations and sclerosis of the GI tract
- Nail dystrophy / other changes
- Alopecia, scarring/scaling of scalp, brittle hair/hair change
GI
- Oesophageal strictures
- Oesophageal webs
- Gastritis/colitis
- Histology: crypt apoptosis, crypt abscesses, crypt necrosis
Liver
- Acute hepatitis
- OR slowly progressive cholestasis
Lungs
- Obstructive or restrictive lung disease
- Dry, non-productive cough
- Bronchiolitis obliterans
But essentially any organ can be affected including eyes, joints, genitalia
1001
What is the treatment of acute and chronic graft versus host disesae?
Acute
- Ensure adequate tacrolimus levels
- Topical steroids for mild disease
- Systemic glucocorticoids for more severe disease - IVMP 2mg/kg/day + tapered according to response
---> You would want to see improvement by day 5-7
---> For GI disease IV steroids + budesonide have been suggested
- Ruxolitinib is second line for non-response to glucocorticoids
- Supportive
Chronic
- Topical treatments for mild disease
---> Calcineurin inhibitors
---> Steroids
---> Steroid mouth washes
- Systemic glucocorticoids for more severe disease
---> 1mg/kg/day prednisolone
- Endoscopic therapy
---> Dilatations
---> UGI endoscopy to assess
- Consider pancreatic exocrine insufficiency
- Ruxolitinib is second line for steroid refractory
1002
What is Cowden syndrome? What are its features?
PTEN mutations leading to a variety of hamartoma tumour syndromes, of which Cowden syndrome is one
AD inheritance
Mucocutaneous
- Trichilemmomas
- Keratosis
Breast
- Breast cancer risk
- Thyroid
- Multinodular goitre
- Hashimoto’s thyroiditis
- Adenomas
GI
- Glycogenic acanthosis
- Gastric and duodenal polyps e.g. hamartomas, hyperplastic polyps, adenomas, inflammatory polyps
- Colonic polyps - typically hamartomatous and inflammatory polyps
- Increased risk of cancer: Colonoscopic surveillance recommended
Neuro
Bone
1003
What are the bowel cancer screening programme minimum requirements for colonoscopy performance?
Unadjusted colonoscopy completion rate >90%
<3 serious complications / 1000 colonoscopies
<1/500 post polypectomy perforation
<1/1000 overall perforation rate
Adenoma detection rate >35% (>0.6% of screened patients)
Colorectal cancer detection rate >11% (>0.2% of screened patients)
Identification of correct colonic segment >90% accuracy
Tattooing of suspected malignant polyps >100%
Polyp recovery rate >90%
1004
Following which GI infections can reactive arthritis develop?
Campylobacter
Shigella
Salmonella
Yersinia
1005
What are the most common routes for Hepatitis B transmission? What is the likelihood that a patient who contracts hepatitis B develops a chronic infection?
Most cases are perinatal transmission - 90% of eAg mothers will pass on hepatitis B
30% cases are from sexual transmission
10% of acute infections will go on to chronic hepatitis B
1006
What group of bacteria most commonly cause spontaneous bacterial peritonitis?
Aerobic/facultative anaerobic bacteria e.g. e coli and klebsiella
1007
What is actinomycosis? What are its clinical features? How is it diagnosed? How is it treated?
Chronic granulomatous disease caused by filamentous, gram positive, anaerobic bacteria, usually actinomyces israelii
Worldwide distribution, affects mostly middle aged men
Pathogenesis
- Actinomycetes are commensals of the oral cavity and GI tract
- If they breach the lining they become pathogenic with formation of granulomas, reactive fibrosis, necrosis, abscesses and fistulae
Presentation
- Cervicofacial disease is most common
- GI involvement is next most common and usually involves appendix / ileocaecal region
- May present following surgical interventions in that localised area
- Slow growing disease
- Subacute fevers
Histology of surgical specimens
- Actinomycotic sulfur granules
- Zone of granulation tissue surrounding one or more oval eosinophilic granules
- Beaded of filamentous, non-acid-fast, gram positive bacilli radiate from these granules
Management
Benzylpenicillin
+/- surgical resection/drainage
1008
How soon after H Pylori eradication should stool antigen testing be performed?
4-8 weeks
1009
Where might lymphadenopathy be palpated in anal cancer that has spread to the lymph nodes?
Inguinal region (as with any lesion below the dentate line)
1010
What is gardner syndrome?
Variant of FAP which also shows AD APC mutation as underlying cause
Extra-intestinal manifestations define it
- Osteomas and dental abnormalities
- Cutaneous lesions
- Desmoid tumours
- Congenital hypertrophy of the retinal pigment epithelium
- Adrenal adenomas
- Nasal angiofibromas
1011
In acute liver failure, what are the criteria for referral to a transplant unit?
Paracetamol
- pH <7.3 or bicarbonate <18
- INR >3 D2 or >4 thereafter
- oliguria and/or AKI
- altered GCS
- hypoglycaemia
- lactate >4 unresponsive to fluid resuscitation
Non-paracetamol
- pH <7.3 or bicarbonate <18
- INR >1.8
- oliguria/renal failure/Na <130
- encephalopathy
- hypoglycaemia
- bilirubin >300
1012
What vitamin absorption can be affected by cholestyramine?
Fat soluble vitamins: A, D, E, K
1013
What HLA linkages are seen in AIH?
B8, DR3, Dw3
1014
What are the rome IV criteria for functional constipation?
Symptoms present for the last 3 months, with symptom onset at least 6 months ago
Must include two or more of the following:
- Straining during more than ¼ (25%) of defecations
- Lumpy or hard stools (Bristol Stool Form Scale 1-2) more than ¼ (25%) of defecations
- Sensation of incomplete evacuation more than ¼ (25%) of defecations
- Sensation of anorectal obstruction/blockage more than ¼ (25%) of defecations
- Manual maneuvers to facilitate more than ¼ (25%) of defecations (e.g., digital evacuation, support of the pelvic floor)
- Fewer than three spontaneous bowel motions per week
- Loose stools are rarely present without the use of laxatives
- Insufficient criteria for irritable bowel syndrome
1015
What is the cause of angular stomatitis?
Iron deficiency
1016
How is Zieve's syndrome defined?
Jaundice
Alcoholic hepatitis
Hyperlipidaemia
Haemolysis
1017
What pH is safe for NG feeding?
<5.5
1018
What is the 2 year mortality of SBP?
50%
1019
In terms of adjunctive medications in IBS, what considerations might you have for TCAs and SSRIs?
TCAs - increase orocaecal time therefore may worsen IBS-C
SSRIs - reduce orocaecal transit time therefore may worsen IBS-D
1020
What drugs may cause dyspepsia?
Steroids
CCBs
Theophyllines
Nitrates
Bisphosphonates
NSAIDs
1021
Describe the aetiology, prevalence, and symptoms of somatostatinomas
Extremely rare
Associated with NF1, VHL, MEN1
Least likely functional NET
Usual symptoms: abdominal pain and weight loss
Classical pentad - not the most common presentation
- Diabetes
- Steatorrhoea
- Gallstones
- Weight loss
- Achlorhydia
1022
Detail the inherited conditions of isolated hyperbilirubinaemias by type
Conjugated
- Dubin Johnson
- Rotor syndrome
Unconjugated
- Crigler Najjar
- Gilbert's
1023
What is Dubin Johnson syndrome? How is it diagnosed? How is it treated?
AR
Impaired excretion of conjugated bilirubin from the hepatocyte
Mild jaundice worsened by intercurrent illness etc
Isolated raised conjugated bilirubin
Dense pigmentation on biopsy but otherwise normal
Normal urinary coproporphyrin excretion
Benign condition not requiring treatment
1024
What is Rotor syndrome? How is it diagnosed? How is it treated?
AR
Impaired reuptake of conjugated bilirubin secreted by hepatocytes, leading to increased conjugated bilirubin
Isolated raised conjugated bilirubin
Normal liver histology
Increased urinary coproporphyrin
Benign condition not requiring treatment
1025
What is Crigler Najjar syndrome? How is it diagnosed? How is it treated?
AR condition
Severe unconjugated hyperbilirubinaemia which can cause bilirubin induced neurologic dysfunction, encephalopathy and death aka kernicterus in neonates
Type 1: undetectable-extremely low UDP glucoronosyltransferase
- Daily phototherapy required to avoid kernicterus
- At risk of bilirubin induced neurologic dyfunction outside of neonatal period
Type 2: very low UDP glucoronosyltransferase
- Usually avoid regular phototherapy
- Phenobarbital may be required to control jaundice (enzyme inducer)
Liver transplant is curative for both and should be referred for at an early age
1026
What is Gilbert's syndrome? How is it diagnosed? How is it treated?
AR inheritance, with heterozygotes having a higher average bilirubin as well
Less significantly low UDP glucoronosyltransferase levels
Recurrent isolated unconjugated hyperbilirubinaemia e.g. during infections
Benign condition not requiring treatment
1027
What are the biochemical features of refeeding syndrome?
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
B1 deficiency
Salt/water deficiency
1028
What are the BSG guidelines re OCP and bowel prep?
Take extra precautions for 1 week after bowel prep
1029
What is the 1st line oral opioid analgesic in advanced liver cirrhosis?
Morphine 2.5mg 4-6 hourly PRN and uptitrate
1030
In advanced liver cirrhosis what are the first line antiemetics for GI, opioid or central causes of nausea?
GI causes
- domperidone or metoclopramide 5-10mg TDS
Opioid/central causes
- haloperidol 0.5-1mg BD PO or 0.25-0.5mg TDS SC
1031
What are the GI manifestations of CF? How are they manged?
GORD: same approach
Meconium ileus
Distal intestinal obstruction syndrome: meconium ileus of the adult
- Osmotic laxatives and ORS; Gastrografin can be used
- Laparotomy may be required if does not respond / develop complications e.g. intestinal ischaemia
Fibrosing colonopathy: Stricture formation which occurred in 1990s ?linked to pancreatic enzyme supplementation
Constipation
Less acute onset than distal intestinal obstruction syndrome, and AXR shows more widespread faecal impaction
- Osmotic laxatives are first line
- Prucalopride is a good second line
Intussusception: Inspissated intestinal contents as lead point
SIBO
Pancreatic insufficiency
- PPIs can help to avoid acid related degradation of pancreatic enzymes
Pancreatitis
T3c diabetes
CF related liver disease - 40% by adolescence
- Focal biliary cirrhosis, can progress to multilobular cirrhosis (with or without portal hypertension)
---> Histology: Proliferation of bile ducts, Portal fibrosis, Accumulation of period ascid schiff staining material within bile ducts
- Non cirrhotic portal hypertension: Usually shows nodular regenerative hyperplasia with portal venopathy on biopsy
- Hepatic steatosis - up to 60% of patients with CF
- Management
---> Optimise nutrition in cases of cirrhosis
--->Standard cirrhosis HCC / variceal screening but Beta blocker prophylaxis is not recommended due to bronchoconstriction risk
---> Ursodeoxycholic acid 10-20mg/kg/day may be beneficial in cholestatic disease
---> Liver transplantation is ultimate solution
Microgallbladder: <35mm gallbladder
Gallstones: 12% of patients
- Usually cholesterol stones, do not respond to UDCA
Cholecystitis
- Due to biliary sludge or gallstones
Sclerosing cholangitis & hepatolithiasis
- UCDA may help
1032
What are the different types of gastric volvulus?
Complete (>180 degrees) or partial
Primary (ligament fixation issues) or secondary (other anatomical issues with the stomach or diaphragm, e.g. paraoesophageal hernia)
Organoaxial (along line through GOJ and pylorus, more often cause and more complete obstruction) or mesenteroaxial (along line through mid body of the stomach)
1033
What is the treatment of gastric volvulus?
Initial attempts at decompression
- NG tube
- endoscopy
Immediate surgery
- if failure to decompress or complications e.g. perforation
- detorsion +/- partial gastrectomy
Definitive treatment
- surgical repair of any anatomical defects
1034
What is immunoproliferative small intestinal disease? How does it present? How is it diagnosed? How is it treated?
B cell lymphoma with IgA heavy chain synthesis which occurs on a background of extensive chronic diffuse mucosal plasmacytosis
Often caused by Campylobacter jejuni
Called Mediterranean lymphoma due to geographic distribution
Symptoms: malabsorption
Endoscopic findings
- Nodular appearance of distal duodenum/proximal jejunum with thickened folds
Histology
- Low grade: Heavy lymphoplasmacytic infiltrate by mature cells
- High grade:
---> Resembles diffuse large cell lymphoma with plasmacytoid features
--->May have starry sky pattern, follicular hyperplasia
Management
- Early stage: antibiotics (tetracycline based)
- Late stage: chemotherapy
1035
What types of infections are patients with coeliac at risk of? What is recommended to prevent this?
Encapsulated bacteria
Pneumococcal vaccine
1036
What is the most common type of small bowel tumour?
NET
1037
What is the aetiology of acute pseudoobstruction? How is it treated?
Causes
- Post surgical
- Drugs: opioids, anticholinergics
CNS disorders: parkinsons, stroke, dementia
- Metabolic disturbance: K, Ca, Mg
Management
- If mild abdo pain, or caecal diameter <12cm
---> Correct electrolytes
---> Laxatives
---> Avoid lots of enemas due to risk of aspiration
---> Stop contributing drugs
---> NG decompression
---> Ambulate if possible
--->Monitor for 72 hours (AXR, bloods) and progress to next section if unsuccessful
- If moderate-severe abdo pain or caecal diameter >12cm
---> Neostigmine 2-5mg with slow IV injection
---> Beware bradycardia, keep atropine around
---> Can give a second dose if the initial one fails
---> Colonoscopic decompression
---> Water and no air
---> Avoid opioid analgesics for induction
---> Aim to reach distal transverse colon and then suction all air
---> Place flatus tube + colonic administration of PEG
- Surgical
---> If complications e.g. perforation
---> OR if failure of the above
---> Stoma formation +/- resection
- Others
---> Consider erythromycin
---> Consider percutaneous colostomy
- Ongoing therapy
---> After resolution, daily PEG laxative
1038
What is the aetiology of chronic pseudoobstruction? How is it treated?
Aetiology
- CNS: CVA, parkinsons, dementia
- Immune: associations with scleroderma, dermatomyositis, SLE through alteration of enteric nerves and smooth muscle
- Infection: trypanosoma cruzii (Chagas)
Management
- Enteral/liquid nutrition
- Treat underlying disease
- Prokinetics
---> Prucalopride
---> Pyridostigmine
---> Erythromycin acutely
---> Neostigmine acutely
- PN (if intestinal failure)
- ?intestinal transplantation
1039
Detail the mechanism of action of different anti-emetics and their respective indications
Domperidone
- does not cross BBB (acts peripherally on GI receptors and in CTZ which is outside of true BBB)
- safe in Parkinson’s and as PD has impaired gastric emptying, a prokinetic is preferred
CTZ
- 5HT3 receptors
---> Ondansetron
---> Massive stimulation of these receptors triggered by gastric irritation and distension
- H1 receptors
---> Cyclizine - indicated for vestibular causes
- Muscarinic receptors
---> Hyoscine hydrobromide - indicated for vestibular causes
- D2 receptors - cross BBB + recommended first line for opioid induced nausea
---> Metoclopramide
---> Prochlorperazine
---> Haloperidol
- Substance P / Neurokinin-1 neuropeptide
1040
What is the management of post cholecystectomy bile leak?
ERCP and plastic stent insertion
1041
What are the rates of TACE side effects?
Post-embolisataion syndrome: self-limiting nausea, abdominal pain, and fever 2-7%
Transient hepatic decompensation <20%
Minority of patients develop irreversible liver failure
1042
Which drugs can cause paradoxical worsening of pruritis in cholestatic liver disease?
UDCA (except in intrahepatic cholestasis of pregnancy)
Obeticholic acid (<10%)
1043
What drugs classically cause cholestatic DILI?
Co-amoxiclav, flucloxacillin, macrolides (e.g. clari/azithro/erythro), co-trimoxazole, chlorpromazine, terbinafine
1044
What is the definition of high output stoma?
>1.5-2L/24 hours
1045
What are the relative benefits / drawbacks to different bariatric surgeries?
Laparascopic gastric band
- lowest post operative mortality
- highest rate of long-term complications (25%) e.g. band slippage, band erosion, gastric necrosis, GORD
- highest long-term re-operation rate (12% e.g. band slipping, band erosions)
- no bypass side effects
less robust weight loss and T2DM remission
Sleeve gastrectomy
- robust weight loss and T2DM remission
- no bypass side effects (SIBO)
Roux-en-Y
- robust weight loss and T2DM remission
- risks bypass side effects (SIBO)
Biliopancreatic diversion (with duodenal switch)
- most robust weight loss and T2DM remission
- highest major complication rate
- more nutrient malabsorption
Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S)
- less malabsorption vs duodenal switch
1046
Define the exclusion anatomical criteria for surgical resection in perihilar cholangiocarcinoma
- bilateral involvement of the second order bile ducts
- bilateral or contralateral vascular involvement
- presence of metastatic disease
- underlying PSC (LT should be offered if <3cm)
NB:
- locoregional nodal disease is not a contraindication but predicts poorer surgical outcome
- abutment of vasculature is not a contraindication
1047
What percentage of PSC patients have co-existent IBD?
60-70%
1048
What percentage of IBD patients have PSC?
2%
1049
What is the increased colorectal cancer risk in PSC/IBD over IBD alone?R
4x
1050
In which inflammatory diseases can infliximab be used?
UC
Crohn's
Psoriatic arthritis
Psoriasis
Non-radiographic spondyloarthritis
Ankylosing spondylitis
Rheumatoid arthritis
JIA
1051
In which inflammatory diseases can adalimumab be used?
UC
Crohn's
Psoriatic arthritis
Psoriasis
Non-radiographic spondyloarthritis
Ankylosing spondylitis
Rheumatoid arthritis
JIA
Hidradenitis suppurativa
1052
In which inflammatory diseases can golimumab be used?
UC
Psoriatic arthritis
Non-radiographic spondyloarthritis
Ankylosing spondylitis
JIA
1053
In which inflammatory diseases can vedolizumab be used?
Ulcerative colitis
Crohn's
1054
In which inflammatory diseases can ustekinumab be used?
Ulcerative colitis
Crohn's
Psoriatic arthritis
Psoriasis
1055
In which inflammatory diseases can tofacitinib be used?
Ulcerative colitis
Psoriatic arthritis
Ankylosing spondylitis
Rheumatoid arthritis
JIA
1056
In which inflammatory diseases can upadacitinib be used?
Ulcerative colitis
Crohn's
Psoriatic arthritis
Non-radiographic spondyloarthritis
Ankylosing spondylitis
Rheumatoid arthritis
JIA
Atopic dermatitis
1057
In which inflammatory diseases can filgotinib be used?
Ulcerative colitis
Rheumatoid arthritis
1058
In which inflammatory diseases can ozanimod be used?
Ulcerative colitis
MS
1059
What is this?
Granular cell tumour
1060
What is this?
Leiomyoma
1061
What is this?
Gastric MALT lymphoma
1062
Name these bariatric procedures
1063
Describe the cancer referral pathway for colorectal cancer
Offer FIT test initially if
- abdominal mass
- change in bowel habit
- iron deficiency anaemia
- aged 40+ with unexplained weight loss and abdo pain
- <50 with rectal bleeding AND EITHER
---> abdo pain
---> OR weight loss
- >50 with EITHER
---> rectal bleeding
---> OR abdo pain
---> OR weight loss
- age 60+ with any anaemia
2ww referral if >10mcg/g
Can still refer if negative FIT if strong suspicion
1064
What is Gorlin syndrome?
AD condition
Gastric hamartomas
Basal cell carcinomas
Mandibular bone cysts
Intracranial calcification
Pits on the palms and soles
Ophthal issues
Developmental issues
1065
What is the Eckhardt score? Detail its components and interpretation
Achalasia symptoms score
Weight loss
0: no weight loss
1: <5kg
2: 5-10kg
3: >10kg
Dysphagia
0: none
1: occasional
2: daily
3: each meal
Retrosternal discomfort
0: none
1: occasional
2: daily
3: each meal
Regurgitation
0: none
1: occasional
2: daily
3: each meal
<4 total suggests treatment success
1066
What are the general TPN requirements for patients? In what disease states would this be different?
Energy
- 30kcal/kg/day in mobile patients
- 25kcal/kg/day in bedridden patients
- for critically unwell start at 75% of this
Protein
- 0.8-1.2g/kg/day in healthy patients
- 1.2-1.5g/kg/day in acutely ill patients or post surgical patients who are well nourished
- 1.5-2g/kg/day to burns or multiple trauma patients
- Lower amounts in liver failure or renal failure
- 1g protein = 4 kcal
- 10-16% of kcal from protein
Nitrogen
- from essential and non-essential amino acids mixtures for TPN (16% of protein weight)
- 0.1-0.15g/kg/day in general
- 0.15-0.2g/kg/day in inflammatory/hypermetabolic states
Glucose
- 125-200g per day???
- sometimes more like 260-315g (70kg person) = 3.7-4.5 g/kg/day to represent 50-60% of kcal
- the more glucose the less protein required etc
- 1g glucose = 4kcal
- max glucose infusion rate 5-7 mg/kg/min
Lipids
- 200g lipid emulsion / week??
- 1g fat = 9kcal
- = 12% kcal for 70kg
- ? Maybe more - 20-25% kcal = 0.67-0.83 g/kg/day
- lower ratio n6-n3 polyunsaturated fats prevents hepatobiliary complications from TPN
Fat/water soluble vitamins and trace elements
1067
What is the pharmacological management of cyclical vomiting syndrome?
Prophylaxis
1) amitriptyline or nortriptyline (25mg ON -> 100mg ON max)
2) topiramate (25mg OD -> 150mg max in 25mg increments)
3) aprepitant 25mg twice weekly
Abortives
1) Ondansetron SL / rectal
2) Sumitriptan 20mg intranasal and repeat after 2 hours
3) aprepitant 125mg during prodrome, then 80mg OD for 2/7
1068
What is the pharmacological management of cyclical vomiting syndrome?
Prophylaxis
1) amitriptyline or nortriptyline (25mg ON -> 100mg ON max)
2) topiramate (25mg OD -> 150mg max in 25mg increments)
3) aprepitant 25mg twice weekly
Abortives
1) Ondansetron SL / rectal +/- benzo
2) Sumitriptan 20mg intranasal and repeat after 2 hours
3) aprepitant 125mg during prodrome, then 80mg OD for 2/7
1069
What are the signs and symptoms of manganese deficiency and toxicity. What are their causes? What are their investigations and direct directory sources?
Deficiency symptoms: animal models show, poor growth, decreased fertility, ataxia, skeletal, deformities, abnormal, carbohydrate, and fat metabolism. Others: scaly dermatitis, dyslipidemia.
Toxicity symptoms: extra pyramidal, neurotoxicity similar to parkinsonism
Causes: parental nutrition may lead to toxicity, particularly in the setting of cholestasis where manganese excretion is impaired. Only a small proportion of ental manganese is absorbed, whereas all IV administered remains.
Ix: serum/whole blood manganese level
Dietary sources: grains, dried fruit, vegetables, and nuts
1070
What are the signs and symptoms of manganese deficiency and toxicity. What are their causes? What are their investigations and direct directory sources?
Deficiency symptoms: animal models show, poor growth, decreased fertility, ataxia, skeletal, deformities, abnormal, carbohydrate, and fat metabolism. Others: scaly dermatitis, dyslipidemia.
Toxicity symptoms: extra pyramidal, neurotoxicity similar to parkinsonism
Causes: parental nutrition may lead to toxicity, particularly in the setting of cholestasis where manganese excretion is impaired. Only a small proportion of ental manganese is absorbed, whereas all IV administered remains.
Ix: serum/whole blood manganese level
Dietary sources: grains, dried fruit, vegetables, and nuts
1071
What is the fluid requirement for TPN?
1500ml + 20ml/kg for every kg >20kg
1072
What is the fluid requirement for TPN?
1500ml + 20ml/kg for every kg >20kg
1073
What are the total daily PN vitamin doses?
- A: 800-1100 mcg
- D: 200 IU or 5mcg
- E: 9-10 mg
- K: 150 mcg (usually in lipid emulsion)
- B1: 2.5mg
- B2: 3.6mg
- B3: 40mg
- B5: 15mg
- B6: 4mg
- B7: 60 mcg
- B9: 400 mcg
- B12: 5 mcg
- C: 100-200 mcg
1074
What are the daily doses of trace minerals required in PN?
Chromium: 10-15 mcg
Copper: 0.3-0.5 mg
Fluoride: 0-1 mg
Iodine: 130 mcg
Iron: 1.1 mg
Manganese: 55 mcg
Molybdenum: 19-25 mcg
Selenium: 60-100 mcg
Zinc: 3-5 mg
1075
What are the daily doses of trace minerals required in PN?
Chromium: 10-15 mcg
Copper: 0.3-0.5 mg
Fluoride: 0-1 mg
Iodine: 130 mcg
Iron: 1.1 mg
Manganese: 55 mcg
Molybdenum: 19-25 mcg
Selenium: 60-100 mcg
Zinc: 3-5 mg
1076
What endoscopic screening should be offered to patient with pernicious anaemia?
Defined as b12 deficiency plus anti gastric parietal cell or intrinsic factor antibodies
Screening OGD aged 50
