Hepatopancreaticobiliary Flashcards
1
Q
Embryology of the liver
A
Endodermal origin
Blind tube (hepatic diverticulum) forms from foregut into ventral mesogastrium
Left and right buds form and become lobes
Enclosed within layers of the ventral mesogastrium
Umbilical vein (oxygenated) runs along caudal margin of ventral mesogastrium
2
Q
Caudal surface anatomy of the liver
A
3
Q
Anterior surface anatomy of the liver
A
4
Q
Cuinaud segments
A
5
Q
Venous supply and drainage of the liver
A
Liver receives 25% of cardiac output
portal vein provides 75% of hepatic inflow
50-70% of the overall oxygen requirement of the liver provided by portal vein
Drainage via the 3 (left, middle,right hepatic veins)
- caudate drains directly into IVC via several perforators
6
Q
Relationship of the portal structures
A
Bile duct anterior right
Hepatic artery anterior left
Portal vein posterior
7
Q
Aberrant anatomy of the hepatic artery
A
Normal is only present 60%
8
Q
Biliary drainage of the caudate lobe
A
80% left and right
15% left only
5% right only
9
Q
Variations in the cystic artery
A
10
Q
Blood supply of the bile duct
A
From sup. pancreaticoduodenal and gastroduodenal arteries
Run on either side at the 3 and 9 o’clock positions
Poor segmental supply until close proximity to the liver where it is well supplied from hepatic supply
11
Q
Innervation of the liver
A
Sympathetics
- T7-10
- through coeliac ganglia
Parasympathetic
- both vagal nerves
12
Q
Describe the structure of a liver lobule
A
Central venule surrounded by 4-6 portal triads
Venous sinusoids
3 cell zones with enzymatic/functional differences between hepatocytes- depending on proximity to arterial/portal supply (and nutrients and oxygen)
13
Q
Role of hepatic stellate cells in cirrhosis
A
Stellate cells located in the space of Disse
- store Vitamin A
- synthesise extracellular collagen and other ECM proteins
In acute and chronic injury stellate cells become activated to a myofibroblastic state
- abnormal deposition of ECM and collagen leads to loss of architecture of liver with fibrosis and ultimately cirrhosis
14
Q
Substrates for gluconeogenesis
A
Lactate
Pyruvate
Glycerol
Propionate
Alanine
15
Q
Basic physiologic functions of bile
A
- Excretion of waste products of metabolism
- Provide enteric bile salts to aid fat absorption
16
Q
What are major organic solutes in bile
A
Bile acids
Bile pigments
Cholesterol
Phospholipids
17
Q
Bile volume
A
1500ml/day although some texts also suggest more like 600ml/day
97% Water
18
Q
Bile solutes and concentrations
A
19
Q
Bile Salts
A
3 Salts
- Cholic acid 40%
- Chenodeoxycholic acid 40%
- Deoxycholic acid 20%
Produced in liver from cholesterol
Conjugated within hepatocytes with glycine or taurine
Secreted into bile
90% reabsorbed by hepatocytes and resecreted
This cycle constitutes the enterohepatic circulation
20
Q
Excretion of bilirubin
A
- Breakdown product of heme
- Unconjugated binds to albumin
- Dissociates within space of Disse
- Uptake by hepatocytes
- Conjugated with Glucuronic acid
- Secreted into bile
- Deconjugated by bacteria to urobilinogens
21
Q
Substrates for gluconeogenesis
A
Mostly from alanine from muscle breakdown
Some from glycerol from adipose
22
Q
Ketogenesis
A
From fatty acids from adipose tissue
Beta oxidised in liver to form ketones
23
Q
Lipid Metabolism
A
Balance of esterification vs oxidisation
Esterification with glycerol yeilds triglycerides for storage in adipocytes
Beta oxidation yeilds ATP and Ketone bodies
24
Q
Protein metabolism
A
- Liver metabolises to any of glucose, ketones or lipids or oxidised for energy
- Oxidation yeilds nitrogenous waste products
- Nitrogenous waste converted to urea in urea cycle
- Excreted largely in urine
- Nitrogenous waste converted to urea in urea cycle
- Oxidation yeilds nitrogenous waste products
25
What pathway is primarily responsible for metabolism of drugs and toxins
Cytochrome p450
26
Histological findings of cirrhosis
Regenerating liver nodules surrounded by fibrous septae
27
Define portal hypertension
Portal pressure \>5mmHg
Pressures of 8-10mmHg are generally required to cause collateralisation and portosystemic shunting
Pressures are measured by hepatic wedge pressure
28
Sites of portosystemic shunting
Oesophageal Varices
* flow predominantly from left gastric and coronary veins through distal oesophageal plexus to the azygous
Caput medusae
* recanalisation of umbilical vein
Retroperitoneal collaterals (of Retzius)
Rectal Varices
* Superior rectal (IMV) to inf. rectal (int. iliac)
Intrahepatic
29
Sinestral hypertension
Isolated splenic vein thrombosis
High splenic with normal SMV and portal pressures
Usually from mass or pancreatitis
Resultant portoportal collateral flow through gastroepiploic veins
* Predominantly left gastroepiploic
Isolated gastric varices without oesophageal varices
Curable with splenectomy
30
Pyogenic liver abscess epidemiology and risks
Uncommon (10 per 100000 admissions)
Male 1.5 : 1 female
Cirrhosis
Malignancy
Diabetes
CRF
Sphnicterotomy/hepaticoenterostomy
Biliary sepsis
31
Caroli disease
Rare
Autosomal dominant and recessive form exist (recessive is more severe)
Cystic dilatation of intrahepatic ducts
100 fold risk of cholangiocarcinoma vs gen. pop.
32
Colorectal cancer and pyogenic abscess
4 fold risk of colorectal cancer in liver abscess
33
Sources of pyogenic liver abscess
Portal vein
Biliary tree
Direct extension
Trauma
systemic (arterial)
Most commonly the exact cause is not identified
34
Distribution of hepatic abscesses
Right 75%
left 20%
Caudate 5%
Multiple abscesses are uncommon
35
Bacteriology of liver abscess
Portal/biliary source
* poly microbial
* high rate of gram negatives (E.coli, Klebsiella pneumoniae)
* Assume anaerobes (Bacteroides)
* Enterococci
Systemic (endocarditis, IVDU etc)
* Staph. aureaus, Strep. species
36
What microbial kingdoms may be implicated in liver abscesses
Bacterial- most common
Fungal
Mycobacterial
Amoebic
Parasitic (helminthic)
37
What is a rare complication of Klebsiella liver abscess
Endogenous endopthalmitis
esp. in diabetics
38
CT findings consistent with liver abscess
Hypodense central lesion with peripheral enhancement
39
Differentiating amoebic from pyogenic abscess
Entamoeba histolytica serology
Otherwise it can be difficult in an endemic area
Even aspiration unlikely to yeild the answer (may be culture negative)
40
Entamoeba histolytica and liver abscess
Amoebic
* Endemic in tropics and developing world
* Exists as cyst or trophozoite
* faeco-oral transmission
* Migrates through portal circulation
Causes liquefactive necrosis and subsequent abscess
* Glissons capsule is resistant to degradation
* Abscesses classically abut the capsule
Detectable by serology
Treatment is with metronidazole drainage is not needed
* classic appearance is of anchovy sauce (but odorless) if aspirated
41
Life cycle of Echinococci
42
Treatment of hydatid disease
* Treatment with Albendazole or albendazole induces cyst regression but resolution in \<50%
* PAIR (puncture, aspiration, injection, reaspiration) is as good as surgery if single cyst with no daughter cysts
* Treat with Albendazole for 1 month afterward
* Surgery is still the treatment of choice for multiple cysts
* technique
* be prepared for anaphylaxis
* pack off the rest of the abdomen to reduce contamination
* expose the cyst, closed aspiration and scolicidal injection (hypertonic saline)
* leave the cyst open or excise it seem equivalent
43
Recurrent pyogenic cholangitis
Asian peoples, low socioeconomic status
young (age 20-40)
strictures and stones develope in the biliary tree
recurrent segmental cholangitis
Surgical clearance of stones and resection/plasty of strictures is treatment
Probably an increased risk of cholangiocarcinoma
44
Liver Cell Adenoma epidemiology
Rare
Frequently symptomatic (haemorrhage and necrosis)
Female 11 : 1 Male
Age 20-40
Associated with:
* steroid hormone use- esp OCP (30 fold)
* Obesity
*
Usually singular lesion, occasionally multiple (~20%)
Multiple lesions less associate with OCP and female sex
If it's a man it should probably be resected
45
Risks of liver cell adenoma
* Rupture and haemorrhage
* ~ 30% risk
* All over 5cm when bleeding occurs
* Can be major haemorrhage with capsular rupture
* Manage with embolisation, stabilisation then resection
* Malignant transformation
* Low risk
* LCA with beta catenin activation are highest risk for transformation
* Develop into HCC
46
Liver cell adenoma imaging
CT Peripheral uptake with centripetal filling
MRI- well demarkated mass with fat and haemorhage
47
What is a liver cell adenoma
Benign proliferation of hepatocytes
Loss of normal architecture with no ducts seen on histology
Cords of hepatocytes with increased glycogen and fat
48
Liver cell adenoma management
In a man: probably resect any size
In a woman:
* If OCP associated- consider stop OCP and observe
* 5cm is a reasonable guideline
* \<5cm observe
* \>5cm Resect
Balance is of risk of rupture and HCC vs resection
49
FNH imaging:
CT
CT- multiphase is ideal
* usually hypoattenuating
* rapid hyperenhancement on arterial phase with central stellate scar
* isodense on portal and delayed phases with delayed enhancement of the central scar
50
FNH epidemiology and histology
Common (2nd most common benign after haemangioma)
Very strong in F:M preponderance
Benign cellular proliferation with fibrous septa around a central scar, often a large central artery within the central scar
If it's a man be dubious thats it's actually an FNH
51
Haemangioma epidemiology and histology
Most common benign liver solid lesion
Female 5 : 1 male
Vascular malformation- enlarge by ectasia rather than proliferation.
Consist of endothelially lined cavernous blood filled spaces
Can bleed
No malignant potential
52
Kasabach Merritt syndrome
Rare complication of giant liver haemangiomas
Thrombocytopaenia and consumptive coagulopathy
53
Haemangioma imaging
Look at the blood pool, haemangiomas are an extension of this
* Non contrast- density of blood- (lower than liver)
* Arterial phase- density of aorta
* peripheral nodular enhancement pattern.
* Portal phase- density of portal vein
54
Liver haemangiomas in children
Large haemangiomas can cause massive haemodynamic demand and CHF from shunting.
High mortality if left untreated
Small lesions can still be observed
Consider embolisation of large lesions
55
name rare benign solid liver lesions
Most are haemangiomas, adenomas or FNH.
Others:
* Macroregenerative nodules (in cirrhotics, have malignant potential)
* Nodular regenerative hyperplasia
* Mesenchymal hamartomas (paeds)
* Lipomas
* AML
* Myelolipomas
* Angiolipomas
56
HCC risk factors
Chronic hepatitis
* Hepatitis B
* Hepatitis C
Metabolic liver diseases
* Haemochromatosis
* Apha 1 antitrypsin defiency
* Wilson's disease
Cirrhosis
* Alcoholic
* PBC
57
HCC characteristics on CT
Blood supply is prodominantly from the hepatic artery
* Rapid contrast enhancement in late arterial phase
* Early washout of contrast
* May leave a capsule like area of enhancement on portal venous phasing
* Occasionally have central scar (which does not then have late enhancement as for FNH)
58
HCC pathology and variants
Metastasises to lung, bone and peritoneum
Classically aggressive
Path/histo variants include:
* hanging (pedunculated)
* pushing type
* infiltrative type
* multifocal type
* fibrolamellar type
* young patients without cirrhosis- better prognosis
* mixed HCC/cholangiocarcinoma
* clear cell
59
Treatment options in HCC
Patients have 2 diseases
* balance of malignancy vs liver function/reserve
* Resection
* many scoring systems but Childs Pugh is important
* A- ok
* B- maybe- individualise
* C- No
* Transplant
* Ablation
* TACE
* Radiotherapy
* Systemic
* TKI
60
Prognostic factors in HCC
Tumour size
Cirrhosis
infiltrative pattern
Lack of capsule
Mets
Multifocal tumours/intrahepatic mets
Margin \<1cm
61
Transplant criteria for HCC and cirrhosis
Milan criteria
* single tumour \<5cm, or
* up to three tumours, each smaller than 3cm, and
* no gross vascular invasion
UCSF (Uni of Cali, San Fran.)
* used by Transplant society of Aus and NZ
* Single tumour \<6.5cm, or
* up to three tumours with
* largest lesion \<4.5cm, and
* sum of tumour diameters \<8cm
62
Intrahepatic cholangiocarcinoma imaging
Dilated ducts peripheral to tumour
hypoattenuating on non contrast
low peripheral enhancement on arterial
gradual centripetal filling on delayed
63
Intrahepatic cholangiocarcinoma risks
viral
* Hep a,b
* HIV
* EBV
PSC
Caroli's
Cholangitis
* recurrent pyogenic
* choledocholithiasis
64
Name rare liver solid primary malignancies
Sarcomas
Lymphomas
Hepatoblastomas
65
Hepatic mets on imaging
hypoattentuating on non contrast
Enhancing less than surrounding liver on contrast
washout on delayed phase
66
Poor predictors of prognosis in liver metastectomy
CEA \>200
size \>5cm
recurrence \<1 year from resection of primary
Multiple tumours
LN positive primary
67
Solid liver lesion malignant differential
Metastasis
* Colorectal
* Neuroendocrine (esp PNETs)
* melanoma, breast, urological, gynaecological, lung
Primary
* HCC
* IHCC
68
Cystic liver lesions
Degenerative
* Simple cysts
Congenital
* Polycystic liver disease
* manifestation of PKD
* Carolis disease
Neoplastic
* Cystadenoma
* Mucin filled cyst
* Malignant potential to progress to cystadenocarcinoma
Infectious
* Hydatid
* Abscess
Trauma
* Biloma
69
Variations of the biliopancreatic ductal confluence
70
Anatomy of the gallbladder
Fibromuscular sac lined by simple columnar epithelium
* 50ml
Three parts
* fundus, body, neck
* mucus glands in the neck only
Undersurface of liver, between segments 4b and 5.
* Fundus touches abdominal wall at tip of 9th costal cartilage
Cystic duct 2-3cm in length
* contains spiral valves of Heister
Blood supply from cystic artery
Venous drainage though cholecystic plate to liver parenchyma
Lymphatic to cystic node (of Lund) then coeliac
71
CHD/CBD normal size and length
CHD 4cm
CBD 8cm
Diameter 5mm until age 50 then 1mm extra per decade thereafter
72
Variations in cystic duct anatomy
73
Pathogenesis of gallstones
Four phases
* super saturation
* concentration
* crystal nucleation
* GB dysmotility
70% cholesterol and calcium
* Gallbladder actively resorbs Na
* Water follows
* Increased cholesterol concentration
* Also increased calcium concentration
* Calcium destabilises phospholipid and cholesterol vesicles
* Cholesterol and calcium precipitates form
10% pure cholesterol
Bile pigment stones more rare
74
What factors stimulate gallbladder contraction
CCK
vagal tone
75
Bacteriology of the biliary tree
E.coli
Klebsiella
Enterobacter
Enterococci
76
Bismuth Strassbourg classification
Bismuth-Strasberg classification of bile duct injury.
* (A) Bile leak from cystic duct or liver bed;
* (B) occlusion of the right segmental duct;
* (C) bile leak from divided right segmental duct;
* (D) lateral injury to the common hepatic duct;
* (E1) main bile duct injury,\>2 cm from the confluence;
* (E2) main bile duct injury,\<2 cm from the confluence;
* (E3) hilar injury with intact confluence;
* E4) confluence involved, right and left hepatic ducts are separated;
* (E5) injury of aberrant right sectoral duct with concomitant injury of main bile duct
77
Reynolds Pentad
Charcots triad
* Fever
* Jaundice
* RUQ pain
Plus:
* Mental status changes
* Hypotension
78
Pathophysiology of recurrent pyogenic cholangitis
colononisation of biliary tree by Clonorchis and Ascaris species
hydrolyse congugated bilirubin to free bilirubin
Brown pigment stones form
Unclear if this is primary or secondary to benign biliary strictures
79
PSC salient points
Associated with IBD esp UC
* Not affected by resection of IBD
Prognosis
* Ultimately fatal due to cirrhosis
* Increased risk of cholangiocarcinoma
Treatment
* no medical treatment options
* Transplant may be necessary but strictures may develop in transplanted liver also
80
Mirizzi Classification
Type I (11%)
* External compression, no fistula
Type II (41%)
* Fistula \<1/3 of CBD circumference
Type III
* Fistula 1/3-2/3 CBD circumference
Type IV
* \> 2/3 (complete destruction) of CBD
81
Classification of choledochal cysts
The Todani classification
82
Choledochal cyst complications
Obstruction
Fibrosis
Cirrhosis
Cyst rupture
Malignancy (10-30% risk) (choledochgal cysts should be considered a premalignant condition)
83
GB Cancer risks
Female sex (3:1)
porcelain GB
Stones esp. large stones \>3cm
GB polyp \>1cm
APBJ
Choledochal cysts
PSC
84
Distrbution of cholangiocarcinoma
2/3 perihilar (Klatskin)
Remainder are usually intrahepatic or periampullary
85
Cholangiocarcinoma risks
recurrent pyogenic cholangitis
Asian liver flukes (Clonorchis and Opistorchis sp.)
PSC
Choledochal cysts
86
How many AJCC staging systems are there for are cholangiocarcinoma
Differs by anatomic location
AJCC has 3 separate staging systems
* Intrahepatic
* Perihilar
* Periampullary
87
Pancreas
gross anatomy
~15cm in length
Divisions
* Head- right of portal vein
* Neck- Anterior to portal and SMV
* Body- to left renal hilum
* Tail- to splenic hilum
Blood supply
* Arterial
* Splenic artery to neck, body, tail
* Superior and inferior pancreaticoduodenals to head
* Venous
* Head- SPDV to portal and IPDV to SMV
* Neck, body and tail to splenic vein
Nerve
* Parasympathetic mainly post. vagus, coeliac plexus
* Sympathetic T6-10 (pain fibres also)
88
Pancreas microscopic structure
Composed of exocrine serous acinii spotted with endocrine islet of Langerhan
beta cells produce insulin
alpha cells produce glucagon
delta cells produce somatostatin
89
Pancreatic development
Endodermal origin
Develops as separate dorsal and ventral buds
Ventral bud arises as a diverticulum from lower bile duct in ventral mesogastrium
* becomes uncinate process
Dorsal bud arises separately from gut tube
Ventral and dorsal ducts fuse and drainage
* Major papilla eventually primarily drains upper head, neck, body, tail and biliary tree
* Accessory duct papilla is found proximal and anterior to the main papilla
* primarily drains the uncinate process
90
Name the main pancreatic proteases.
How are they synthesised and activated?
Trypsin
Chymotrypsin
Carboxypeptidase
Elastase
Synthesised as inactive proenzymes (trypsinogen and chymotrypsinogen, procarboxypeptidase and proelastase)
Stored as zymogen granules in acinar cells
Activated by duodenal Enterokinase
91
Mechanisms for maintaining inactivation of pancreatic enzymes
pH \<7 (ideal is 8-9 for proteases and lipase)
Pancreatic secretory trypsin inhibitor (encoded by SPINK1)
Storage within zymogen granules as inactive precursors
92
Phases of pancreatic secretion
Cephalic
* vagus mediated
* 20-25% or secretion
Gastric
* vagovagal reflex
* 10%
Intestinal phase
* Secretin (S cells) in response to low pH
* fluid and bicarb secretion
* CCK (I cells) in response to nutrient load
* enzyme secretion
* 65-70%
93
Pathophysiology of pancreatitis
Pancreatic acinar cell injury
Colocation of lysosome and zymogen granules
* Mediated by Calcium influx whish is increased by
* NFkB
* Duct HTN
* Ethanol
* Low pH
Activation of pancreatic enzymes
Tissue injury
Inflammatory cascade induced
* TNFa, IL-1
* IL-2, IL-6, IL-8, IL-10, bradykinin, PAF
*
SIRS
MODS
Death
94
Functions of the interleukins
IL-1
* Fever
IL-2
* Activation of NK and cytoxic T-cells
IL-4
* B cell antibody production (plasma cell differentiation)
IL-6
* Hepatic acute phase proteins
IL-8
* Neutrophil chemattractant
* Angiogenesis
IL-10
* Suppression of inflamatory pathway
95
Immunosuppressants used in transplant
Usually triple pathway
* Calcineurin inhibitors
* Tacrolimus
* Inhibit calcineurin-calmodulin pathway
* Prevent nuclear factor of activated T cells
* Antimetabolites
* Mycophenolate mofetil
* Interruption of purine synthesis
* Steroid
* prevents nuclear translocation of NFkB
* prevents T- cell activation
* reduces antigen presentation
96
Somatostatin
Cell, location, functions
Released from D cells in panceatic islets and GI mucosa
Downregulates GI hormones
Antigrowth hormone
97
Pancreatic pseudocyst definition
Wall is composed of collagen and granulation tissue
Not epithelialised
At least 4-8 weeks to develop
98
Genes in congenital pancreatitis
CFTR
* regulation of fluid, chloride and bicarb,
* increases enzyme concentration in ducts
PRSS1
* Encode trypsinogen-
* defects lead to unstable and easily activated trypsin
SPINK1
* Encodes serine proteas inhibitory protein
99
Autoimmune chronic pancreatitis
Type 1
* IgG4 Mediated
* Dense infiltration with plasma cells
Type 2
* Idiopathic duct centric pancreatitis
* Associated with IBD
100
Chronic pancreatitis
Probably a spectrum of disease with acute pancreatitis
Various aetiologies
Often an underlying genetic factor also (SPINK1, CFTR, PRSS1)
Varies in that predominant manifestation is glandular fibrosis
Progression of fibrosis leads to ductal strictures, calcifications and loss of acinar and islet cells
Often culminates in endocrine and exocrine insuffiency
Pain!
101
Peustow procedure
Simple longitudinal pancreaticojejunostomy
Useful if a dilated panc duct present
102
Freys Procedure
Longitudinal pancreaticojejunostomy with resection of the anterior head
103
Name the cystic neoplasms of the pancreas
MCN
* Mucinous cystic neoplasm
SCN
* Serous cystic neoplasm
IPMN
* Intraductal papillary mucinous neoplasm
* Main duct
* Side branch
SPN
* Solid pseudopapillary neoplasms
pNET
* Neuroendocrine tumours will occasionally appear cystic
104
Characteristics increasing suspicion for malignancy in pancreatic cysts
Symptoms
Cyst size \>3 cm (OR 3.0)
Solid component within the cyst (mural nodule) (OR 7.7)
Main pancreatic duct dilated (OR 2.4)
Type of cystic neoplasm
* Serous cystic- very low
* Solid pseudopapillary, mucinous cystic neoplasms, side branch IPMNs- Moderate
* Main duct IPMN- up to 70%
105
Algorythm for cystic pancreatic neoplasms:
Fukuoka guidelines (2017)
106
Serous cystic neoplasms of the pancreas
Female \> male
Negligible malignant potential
CT shows cystic lesion with "honeycomb" or "bunch of grapes" appearance
* central scar or sunburst calcification is pathognomonic
107
Mucinous Cystic Neoplasms (MCN) of the pancreas
Almost exclusively female
CEA \>192
Classically septated cyst with peripheral calcifications
* occasionally unilocular
* Usually occur in body and tail
Moderate malignant potential \>4cm
Low risk \<3cm
108
IPMNs
Female = male
Cystic lesion associated with:
* Main duct diatation (\>5mm) in MD IPMN
* high malignant potential
* Side duct dilatation in SB IPMN
* Low malignant potential
solid component suggests malignancy
CEA \>200
109
Solid pseudopapillary tumour of the pancreas
Females \> males
young age
mixed solid and cystic lesions on imaging
CEA not helpful
Moderate to high malignant potential
Should be resected
110
Genetic syndromes associated with pancreatic adenocarcinoma
CFTR
* Delta F508
Peutz-Jeghers
* STK11
Hereditary pancreatitis
* SPINK1
* PRSS1
Familial atypical mole and multiple melanoma syndrone
* CDKN2A
Hereditary breast and ovarian cancer
* BRCA2
Lynch syndrome
* MMR mutations
* MLH1, MSH2, MSH6
FAP
* APC
Familial pancreatic cancer
* No known gene
Li-Fraumeni
* TP53
111
Tumour suppressor and oncogenes of PDAC
PDX1
KRAS2 oncogene
* Activated in 95% of pancreatic cancers
p53 tumour suppressor
* occurs late in progression to invasive cancer, seen in 90% of PDAC
DPC4 (SMAD4) tumour suppressor
* occurs late in progression to invasive cancer, seen in 80% of PDAC
CDKN2A/p16 tumour suppressor
112
Oncogenetic progression in pancreatic intraepithelial neoplasia to PDAC
113
Signs to assess in advanced or deseminated pancreatic cancer
Courvoisier
Blummer Shelf
Sister Mary Joseph
Virchow Node
114
Laboratory investigations in pancreatic cancer
LFT's
Albumin and prealbumin
CEA
CA 19-9 (most useful)
* Caution as elevated in biliary obstruction anyway
* 10-15% of PDAC do not produce.
Alpha fetoprotein
115
Definition of post operative pancreatic fistula?
Any measurable volume output from an operative or percutaneous drain with amylase \>3x serum
116
Splenic ligaments and their contents
4 Ligaments
* Splenocolic
* Largely avascular
* Splenophrenic
* Largely avascular
* Splenorenal
* Carries the splenic artery and vein and the tail of the pancreas
* Gastro splenic
* Carries the short gastrics
117
Splenic gross anatomy
Arises from dorsal mesogastrium
Mesodermal not endodermal origin
1,3,5,7,9,11
* 1x3x5 inches (2.5x7.5x12.5cm)
* 7 Ounces (200g)
* 9th to 11th ribs
Blood supply from splenic artery
Splenic Vein
Lymphatics follow the artery to coeliac via retropancreatic and hilar nodes
4 ligaments
118
relationships of the spleen
Diaphragm
9-11th ribs
upper pole of left kidney
tail of pancreas
greater omentum, short gastrics, stomach
119
The substance and function of the spleen
Substance comprised of:
* Capsule
* Red pulp
* Sinusoids
* Removal of sinescent erythrocytes
* White pulp
* Periarteriolar lymphatic sheath (PALS)
* T cells
* Folicles
* B cells
* Antibody production
* Opsonisation of encapsulated organisms
Primary site of haematopoesis until 5th month of gestation
* Afterwards just filters and assists humoral immunity
120
OPSI pathogens
Overwhelming Post Splenectomy Infection
* Pneumococcus
* Strep. pneumoniae
* Haemophillus influenzae B
* Nisseria meningitidis
OPSI risk most significant in kids and for haematologic disorders
121
Indications for splenectomy
Haematologic disorders
* ITP (platelet antibodies)
* Failure of steroid or IVIg
* Haemoglobinopathies
* Heriditary spherocytosis
Trauma
Abscess or cyst
Primary or metastatic disease
* Lymphoma
* Leukemia
* CLL, CML
Sinestral hypertension
122
OPSI pathophysiology
Asplenia
Infection with polysaccharide-encapsulated organism
Decreased production of properdin and tuftsin
* Properdin activates alternative compliment cascade
* Tuftsin enhances phagocytosis
Decreased cleavage of tuftsin to functional form
Decreased opsonisation of bacteria
Reduced phagocytosis by splenic macrophages
Overwhelming infection
123
Post splenectomy complications
Pancreatic leak
OPSI
Thrombocytosis causing thrombosis (esp portal)
124
Vaccination in splenectomy
125
Algorythm for cystic pancreatic neoplasms:
European guidelines (2018)
126
European guidelines on pancreatic cystic neoplasms:
Absolute indications for surgery
* Positive cytology
* Solid mass
* Jaundice
* Enhancing mural nodule \>5mm
* MPD dilated 10mm or more
127
European guidelines on pancreatic cystic neoplasms:
Relative indications for surgery
* Growth \>5mm/12 months
* Elevated serum CA 19-9
* MPD 5-10mm
* Diameter 40mm or more
* New DM
* Pancreatitis
* Enhancing mural nodule \<5mm
128
Variations in intrahepatic bile duct anatomy
129
Define the critical view of safety in cholecystectomy
* The hepatocystic triangle is cleared of fat and fibrous tissue.
* The hepatocystic triangle is defined as the triangle formed by:
* the cystic duct
* the common hepatic duct
* inferior edge of the liver.
* The lower one third of the cystic plate.
* Two and only two structures should be seen entering the gallbladder.
130
CT imaging of acute pancreatitis
CT Severity Index (CTSI)
* Graded 0-10
* 2 Subscores
* Balthezar
* 0- Normal
* 1- Enlarged
* 2- Inflamatory changes in pancreas and peripancreatic fat
* 3- single peripancreatic collection
* 4- two or more peripancreatic collections
* Pancreatic necrosis score
* 0- None
* 2- \<30%
* 4- 30-50%
* 6- \>50%
NB "Severe" pancreatitis on imaging is defined by the presence of necrosis and in imaging the terms are synonymous
131
Post cholecystostomy management and decision making
* Leave it for 6 weeks
* Perform a check cholecystostogram
* If the duct is obliterated spiggott for 2/52
* If fine remove and no further management
* If duct patent
* Consider either risk reducing ERCP or cholecystectomy
132
What guidelines can be used for diagnosis and severity scoring in cholangitis?
What are the parameters
The Tokyo guidelines 2018
* Provides
* diagnostic criteria
* (suspected vs definite)
* severity grading
* (mild, moderate, severe)
Parameters
* SIRS
* Temp, WCC/CRP
* Cholestasis
* Jaundice, LFT's
* Imaging
* biliary dilatation, etiology seen
* Grading
* cardio, neuro, resp, renal, hepatic (INR), haematological dysfunction
* WCC\>12, Temp \>39
* age
* bili \>5, hypoalbuminaemia
133
Define cholangitis
Jaundice with stasis leading to bacterial infection and sepsis either suspected or established
134
What is the Atlanta classification
An international, web-based consensus which provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria.
135
What is the Atlanta criteria definition of acute pancreatitis
The diagnosis of acute pancreatitis requires two of the following three features:
(1) abdominal pain consistent with acute pancreatitis
* (acute onset of a persistent, severe, epigastric pain often radiating to the back)
(2) serum lipase activity
* (or amylase activity) at least three times greater than the upper limit of normal
(3) characteristic findings on imaging
* Preferably contrast-enhanced computed tomography (CECT)
* less commonly MRI or USS
136
What two subtypes of pancreatitis does the Atlanta criteria define.
With what relative frequency does each occur
Interstitial oedematous pancreatitis (90-95%)
Necrotizing pancreatitis (5-10%)
137
What are the limitations of amylase when compared to lipase in detecting acute pancreatitis
Shorter half life
Amylase may be falsely normal in hypertriglygeridaemia
138
Pathophysiology of pancreatitis:
Secondary enzyme activations after trypsin activation
139
Complications of pancreatitis:
Local complications
Pancreas
* peripancreatic fluid collections
* necrosis
* infection
Luminal
* GOO
* colonic stricture
* colonic perforation
* biliary obstruction
Vascular
* venous thrombosis
* arterial pseudoaneurysm
* haemorrhage
* direct or DIC
Compartment
* pseudoobstruction/ileus
* abdominal compartment syndrome
140
How does the Atlanta criteria define collections associated with pancreatitis
Fluid alone
* Acute peripancreatic fluid collection
* \<4 weeks
* Pancreatic pseudocyst
* \>4 weeks
With a solid component (and variable fluid content)
* Acute necrotic collection
* \<4 weeks
* Walled off necrosis
* \>4 weeks
141
How is organ dysfunction defined in the Atlanta criteria
By the Marshall criteria
* Graded score 0-4 in 3 organ categories
* Resp by Pa02/FiO2
* Renal by creat
* Cardio by BP
* Score of 2 or more in a system defines organ dysfunction
142
Severity in pancreatitis by Atlanta criteria
Outside Atlanta criteria what is an additional category proposed
Mild
* No organ failure
* No local complications
Moderate
* Transient organ failure \<48H
* and/or
* Local or systemic complications without persistent organ failure
Severe acute pancreatitis
* Persistent organ failure \>48H
Critically severe
* severe pancreatitis with bacterial infection of local complications
143
Fluid resuscitation in pancreatitis
Fluid resuscitation has to be balanced
* Enough to maintain organ perfusion
* Avoid overload and resultant organ dysfunction from intra abdominal hypertension
* Lactated ringers is preferred crystalloid
* About 2500ml to 4000 ml usually is enough in first 24hours
* IAP/APA suggests 5-10ml/kg/h for initial resuscitation with switch to goal directed therapy as able
* Aim for
* UO \>0.5
* MAP 65-85
* HCT 35-44%.
* Pulse \<120
* Advanced/Invasive measures (central venous oxygenation, Echo, serial lactate can all be used also)
144
In what ways does cirrhosis affect perioperative and operative care
Protein synthesis dysfunction
* poor wound healing
Portal HTN
* Bleeding risk
* Splenic sequestration = peripheral thrombocytopenia
* Abnormal secondary haemostasis
* coagulation + fibrinolysis
Abnormal drug metabolism
Poor renal function
145
Contraindications to elective surgery in patients with liver disease
Acute hepatitis
Childs-Pugh C cirrhosis
Fulminant hepatic failure
severe chronic hepatitis
severe coagulopathy
severe extrahepatic complicaations
* ARF
* Cardiomyopathy, CHF
* Hypoxaemia
146
What parameters are included in the Child-Turcott-Pugh score
ABCDE
## Footnote
Albumin
Bilirubin
Coagulation
Distension (ascites)
Encephalopathy
147
FNH imaging:
MRI
T2 hyperintense
T1 hypo
Rapid peripheral, nodular enhancement
Progressive, centripetal filling
Central scar
148
Overview of MRI findings in benign liver lesions
149
What is the role and significance of CEA measurements on pancreatic cyst aspirates by EUS
CEA is a sentitive and specific differentiator for mucinous vs non mucinous neoplasia at a cut off of 192ng/ml
Values \>800ng/ml are seen in malignancy
150
What is an IPMN
A mucin producing epithelial neoplasm of the pancreas which results in dilatation of pancreatic ducts either side branch or main duct
151
lymphoepithelial pancreatic cysts
M\>F
Very rare
Entirely benign
"zero" malignant risk but:
CEA\>800
May be difficult to differentiate from MCN
May require resection to achieve diagnosis
152
How much liver can be resected
Measured in functional liver remnant
Marathon runner level of fitness 20%
Normal fitness 30%
Cirrhosis 40%
153
Strawberry gallbladder
* Gallbladder cholesterolosis
* Typical stippled appearance of the mucosal surface on gross examination
Results from abnormal deposits of cholesterol esters in macrophages within the lamina propria (foam cells) and in mucosal epithelium.
Benign
* Not closely associated with cholelithiasis or cholecystitis
154
What classification system can be used for post ERCP perforations
Stapfer classification.
* Type I: Free bowel wall perforation
* Type II: Retroperitoneal duodenal perforation secondary to periampullary injury
* Type III: Perforation of the pancreatic or bile duct
* Type IV: Retroperitoneal air alone
155
What is a rare complication of giant liver haemangiomas
resulting in thrombocytopaenia and consumptive coagulopathy
Kasabach Merritt syndrome
156
what is the classic ERCP appearance of PSC
Chain of beads
157
Familial hepatic adenomas
Gene: HNF1A
Liver adenomatosis is a rare disease defined by the presence of multiple adenomas within an otherwise normal hepatic parenchyma
* bi-allelic inactivation of TCF1/HNF-1alpha identified in hepatocellular adenomas
* heterozygous germline mutations of TCF1/HNF1a have been linked to the occurrence of MODY3 in humans.
* MODY3 is a rare dominantly inherited subtype of non-insulin-dependent diabetes mellitus characterized by early onset, usually before the age of 25, and a primary defect in insulin secretion.
158
Insulinoma clinical features
Whipples triad
* Symptoms of hypoglycaemia
* Hypoglycaemia
* Symptoms relieved by glucose
159
Insulinoma tumour location
Pancreas (\>99%)
160
Zollinger-Ellison syndrome clinical manifestations
Peptic ulceration
Diarrhoea
161
Gastronoma location
The gastrinoma triangle
* Junction of cystic/CBD
* D2/D3 junction
* Junction of body/neck of pancreas
162
VIPoma clinical syndrome
Diarrhoea
Hypokalaemia
Dehydration
163
Glucagonoma clinical syndrome
Rash
Glucose intolerance
Necrolytic migratory erythema
Weight loss
164
Somatostatinoma clinical syndrome
DM
Cholelithiasis
Diarrhoea
165
What criteria can be used to classify suspected sphincter of oddi dysfunction
The Milwaulkee criteria
166
What are the subtypes of IPMN
Main duct
Mixed
Side branch IPMN
