Hepatobiliary

Question 1

How to classify liver lesions on imaging?

Answer 1

Cystic - Benign

Congenital cysts

Autosomal dominant polycystic liver

Caroli disease

(Type V Todani - choledochal cysts)

Cystadenoma

Hydatid cyst

Amoebic abscess

Pyogenic Abscess

Other, biloma, haematoma, pseudocysts

Cystic - Malignant

Cystadenocarcinoma

Cystic HCC

Cystic metastasis (rare)

Solid - Benign

Haemangioma

Focal Nodular Hyperplasia

(arterial supply is hepatic artery and venous drainage hepatic veins, No PV supply, poor biliary drainage)

Hepatocellular Adenoma

Biliary Hamartoma

Regenerative nodule (non dysplastic)

Regenerative nodule

(dysplastic) retain PV blood supply

Solid - Malignant

HCC

(lose PV, gain HA flow)

Metastases

Question 2

Liver cyst

Answer 2

• Definition:
  
  • Benign fluid filled cavity within the liver lined by cuboidal epithelium – not usually in continuity with the biliary tree
• Incidence/epidemiology:
  
  • ~5% of the population
  • F>M
• Aetiology & risk factors:
  
  • Polycystic liver disease
  • Autosomal dominant polycystic kidney disease (ADPKD): hepatic cysts may be seen in ~40% of those with ADPKD - usually more than 10 cysts – cerebrovascular aneurysms
  • Von Hippel Lindau disease
• Pathophysiology:
  
  • Simple hepatic cysts are benign developmental lesions that do not communicate with the biliary tree
  • The current theory regarding the origin of true hepatic cysts is that they originate from hamartomatous tissue
  • Complications are torsion, hemorrhage, rupture, compression of adjacent biliary tree
  • Malignant transformation rare
• Clinical manifestations:
  
  • GOO
  • Abdominal or chest pain
• Macroscopic features:
  
  • Simple hepatic cysts may be isolated or multiple
  • May vary from a few millimetres to several centimetres in diameter
• Microscopic features:
  
  • True hepatic cysts contain serous fluid and are lined by a nearly imperceptible wall consisting of cuboidal epithelium, identical to that of bile ducts, and a thin underlying rim of fibrous stroma
• Investigations:
  
  • USS (can be diagnostic on it’s own)
    
    • Round, smooth regular borders
    • Hypoechoic
    • Posterior acoustic enhancement
    • No septae or nodularity
• CT
  
  • Hypoattenuating, smooth, round, non enhancing (avascular)
• MRI
  
  • T1 - low
  • T2 - high
• Treatment:
  
  • Depends if symptomatic or asymptomatic
    
    • If asymptomatic then no further imaging required
    • If symptomatic (must be >4cm or look for other cause) then either NOM or operative
  • Non operative
    
    • Needle aspiration +/- sclerosant injection
  • Operative
    
    • Laparoscopic deroofing/fenestration
      
      • Lower recurrence rate (<15%)
      • Unable to be do done in superiorly located cysts
      • Risks
        
        • Wound infection
        • Chest infection
        • Bile leak
        • Subphrenic hematoma
        • Prolonged postoperative drainage through abdominal drain (more than three days
• Prognosis:
  
  • Excellent
  • High recurrence with needle aspiration 30%

Question 3

Liver cystadenoma

Answer 3

• Definition
  
  • Fluid filled liver lesion lined by biliary epithelium, not in continuity with the biliary tract
  • Also called a mucinous cystic neoplasm (like the pancreatic lesion MCN, which is similar and is also called a pancreatic cystadenoma)
  • Malignant potential
• Epidemiology/incidence
  
  • Rare
• Aetiology & risk factors
  
  • F>M
  • Middle age
• Pathophysiology
  
  • 15% undergo malignant transformation into cystadenocarcinoma
• Macroscopic
  
  • Usually no communication with the bile ducts
  • Range in size from 3 to 40 cm and can be either unilocular or multilocular
• Microscopic
  
  • Cysts lined by cuboidal or columnar epithelium that resembles normal biliary epithelium
  • Variable amount of mucin-producing epithelium
  • Associated with ovarian-type subepithelial stroma
• Clinical manifestations
  
  • Asymptomatic/incidental
  • Symptomatic
    
    • Mass effect
    • GOO
    • RUQ pain or fullness
    • Biliary obstruction
• Investigations
  
  • Serology
    
    • Hydatid serology
    • LFTs
  • Imaging
    
    • USS
      
      • Hypoechoic lesion with thickened, irregular walls and occasional internal echoes representing debris and wall nodularity
• CT
  
  • Thick fibrous wall, mural nodules, internal septae, capsular calcifications, papillary projections, contrast enhancement of the cystic walls
• MRI
  
  • The MR signal intensity of biliary cystadenoma is variable depending on the content of the cyst fluid
• Management
  
  • Requires resection due to malignant potential and for diagnosis
  • Differential diagnosis:
    
    • MCN with an associated invasive carcinoma (cystadenocarcinoma)
    • Echinococcal cyst (frequently associated with calcifications, and patients will have positive serology)
    • Simple cysts (distinguished because of the absence of septations and papillary projections and the presence of serous cystic fluid)
• Prognosis

Question 4

Biliary harmatoma

Answer 4

• Definition:
  
  • A benign neoplasm of the liver more commonly seen in children, characterised by dilated and disorganised bile ducts floating in myxomatous stromal tissues
• Incidence/epidemiology:
  
  • Third most common tumour of liver in paediatric age group (after hepatoblastoma and infantile haemangioma)
• Aetiology & risk factors:
• Pathophysiology:
  
  • No communication with the bile ducts – in contrast to Caroli’s disease
• Clinical manifestations:
• Macroscopic features:
  
  • Can be multiple in von Meyenburg complexes
• Microscopic features:
• Investigations:
  
  • CT
    
    • Hypoattenuating and often show no enhancement
    • Occasionally an enhancing nodule or rim may be identified in a small number of lesions
• MRI
  
  • High SI on T2
• Treatment:
  
  • No treatment required unless. .
• Prognosis:

Question 5

Haemoangioma

Answer 5

• Definition:
  
  • Benign vascular tumour composed of a proliferation of vascular endothelial cells
• Incidence/epidemiology:
  
  • Most common benign liver tumour
• Aetiology & risk factors:
  
  • Grows in exposure to oestrogens
• Pathophysiology:
  
  • Congenital origin
  • Can increase in size with pregnancy
  • Can haemorrhage or rupture
  • Consumptive coagulopathy from lysis of platelets and fibrinogen levels (Kasabach–Merritt syndrome) usually seen in children/infants
  • No malignant potential
• Clinical manifestations:
  
  • Incidental/asymptomatic
  • Local mass effect
    
    • Pain
    • Nausea
    • Vomiting
    • Early satiety
    • Abdominal pain
    • Obstructive jaundice
  • Spontaneous rupture (rare)
• Macroscopic features:
  
  • Can be single or multiple
  • Can be very large
  • Well circumscribed
  • Reddish, hypervascular lesion
  • Lumpy/lobules
  • Commonly peripheral location
• Microscopic features:
  
  • Cavernous vascular spaces lined by flattened endothelium underlying fibrous septa of various widths. The vascular spaces are filled with red blood cells.
• Investigations:
  
  • Imaging
    
    • Generally do not need any follow up imaging
    • US
      
      • Homogenous hyperechoic mass with sharp margins, measuring less than 3 cm in diameter and associated with acoustic enhancement
      • Small proportion (10%) are hypoechoic, which may be due to a background of hepatic steatosis, where the liver parenchyma itself is of increased echogenicity
• CT
  
  • Non con:
    
    • Hypoattenuated
  • Arterial
    
    • Nodular peripheral enhancement
  • PV
    
    • Enhancement fills inwards (centripedal)
    • Ongoing enhancement of the lesion relative to the surrounding parenchyma
• MRI
  
  • Typical
    
    • T1 low SI
    • T1Gd nodular peripheral and centripetal filling
    • T2 high SI (light bulb sign)
• No biopsy due to bleeding
• Treatment:
  
  • Generally non operative/conservative management
  • Non operative
    
    • Monitor large haemangioma during pregnancy
  • Operative
    
    • Relative indication for intervention
      
      • Symptoms (consistent with the size of the lesion)
      • Growth
      • >10cm
      • Contact sports
    • Enucleation or anatomical resection
• Prognosis:

Question 6

Focal Nodular Hyperplasia

Answer 6

• Definition:
  
  • Benign liver lesion that is composed of a proliferation of hyperplastic hepatocytes surrounding a central stellate scar
• Incidence/epidemiology:
  
  • 2^nd most common benign solid liver lesion
• Aetiology & risk factors:
  
  • F>M
  • No connection to OCP
• Pathophysiology:
  
  • Proliferation of hepatocytes
  • Hyperplastic process resulting from an arterial malformation
    
    • Vascular endothelial growth factor is increased due to arterial hyperperfusion, which leads to activated hepatic stellate cells, which are responsible for fibrosis and characteristic central scar formation
    • • It is hyperplasia (response of normal cells to abnormal environment) which is non neoplastic (which results from cell genetic mutation)
• Clinical manifestations:
  
  • Asymptomatic/incidental
  • Local symptoms
• Macroscopic features:
  
  • 20% will have multiple FNH
  • Well circumscribed, non encapsulated, solid, central fibrose scar with fibrose septae
• ​Microscopic features:
  
  • Benign hyperplastic hepatocytes surrounding a central stellate scar
  • Normal-appearing hepatocytes grouped in nodules that are usually divided by fibrous septa radiating from the central scar. The fibrous septa are composed of varying degrees of enlarged portal tracts including feeding arteries, portal veins, and bile ductules
  • Kupffer cells are typically present, a feature that distinguishes FNH from hepatocellular adenoma, which usually lacks bile ducts and Kupffer cells
• Investigations:
  
  • CT
    
    • Non contrast hypodense/isodense with central scar hypodense
    • Arterial phase homogenous enhancement with centrifugal/outward filling (except for scar)
    • PV phase, enhancement of the lesion
    • Delayed phase, isodense with enhancement of the scar
  • MRI
    
    • 80% “typical” central scar with central hepatic artery
    • Low-iso SI T1
    • Iso-high SI T2 (scar bright too)
    • T1c Gd
      
      • Arterial nonenhancement centrally
      • Iso SI PV phase
      • Central artery with wheel spoke flow lights up in equilibrium phase
    • Primovist (HSC)
      
      • Early arterial enhancement
      • Retains contrast due to abnormal biliary excretion
      • Central scar doesn’t enhance
    • DWI low ADC similar to malignancy
• Treatment:
  
  • Resect only if symptomatic
• Prognosis:
  
  • No malignant transformation risk

Question 7

Hepatocellular adenoma

Answer 7

• Definition:
  
  • Monoclonal proliferation of hepatocytes
• Incidence/epidemiology:
  
  • Uncommon – 3 per 100,000 OCP users and lower in general population
  • Increased since anabolic steroids and OCP
• Aetiology & risk factors:
  
  • Women of child-bearing age and are associated with the prolonged use of oral contraceptives and oestrogen treatments
  • 3-5^th decade of life
  • Glycogen storage disorders
  • Obesity
  • Diabetes
  • Iron overload
  • Malignancy more common in
    
    • Teleangectasia and atypical HCAs
    • B catenin mutation
    • Men
    • Size
    • Anabolic steroids
    • Fanconi disease
• Pathophysiology:
  
  • Women
    
    • Risk of malignant transformation ~5%
    • Malignancy within HCAs < 5 cm in this context is exceptional
  • Men
    
    • Risk of malignant transformation %50
    • Malignancy can occur in <1cm tumours
  • Dysplasia is the intermediate step between HCAs and HCC
  • Risk of spontaneous haemorrhage
• Clinical manifestations:
  
  • Abnormal LFTs
  • Abdominal pain
• Macroscopic features:
  
  • Solitary
  • Round
  • Capsule sometimes
  • Pale yellow with central haemorrhage/necrosis or bile staining
• Microscopic features:
  
  • Uniform mass of benign appearing hepatocytes, intracellular fat or beta catenin mutation
• Investigations:
  
  • USS
    
    • Hyperechoic (but variable)
    • Heterogenous
    • Well demarcated
  • CT
    
    • Hypoattenuated
    • Heterogenous
    • Arterial enhancement
    • Isoattenuation on PV
    • Fat containing
    • Can haemorrhage
  • MRI
    
    • Heterogenous SI T1/2 due to haemorrhage/steatosis/necrosis
    • T1c (Gd) high SI arterial and low/iso on hepatobiliary phase
    • T1c (HSC) low SI on hepatobiliary phase (compared to high on FNH)
    • DWI unreliable
• Treatment:
  
  • Non operative
    
    • Female cease OCP and annual MRI
    • Monitor AFP
  • Operative
    
    • Indications
      
      • Haemorrhage
      • B catenin mutation
      • Size
        
        • Women
          
          • >5cm resect
        • Men
          
          • All need resection or ablated
• Prognosis:

Question 8

Choledochal cysts

Answer 8

• Definition:
  
  • Rare congenital cystic dilatation of bile duct
• Incidence/epidemiology:
  
  • 1:200,000
  • More common in Asia & Japan
  • 3:1 female:male
• Aetiology & risk factors:
  
  • Anomalous pancreaticobiliary junction.
  • Babbitt-Hypothesis: reflux of pancreatic secretions via a common channel into the biliary ducts causing chronic epithelial injury, mural weakening and consequent dilatation.
  • Congenital distal stenotic segment of the CBD causing obstruction and secondary dilatation.
• Pathophysiology:
  
  • Related to an aberrant pancreaticobiliary duct junction that allows reflux of pancreatic secretions into the bile duct -> development of cystic dilatation
  • Complications
    
    • Ductal strictures
    • Stone formation
    • Cholangitis
    • Pancreatitis
    • Rupture
    • Secondary biliary cirrhosis
    • Cholangiocarcinoma
• Clinical manifestations:
  
  • Most present before age 10
  • Triad
    
    • Abdominal pain,
    • Jaundice
    • Mass
• Can be diagnosed in adults (30% asymptomatic)
  
  • Seen on MRCP/ERCP
  • Most common symptom in adults is pain
  • Cancer prior to age 18 rare
• Non malignant complications
  
  • Cholangitis
  • Cystolithiasis (stone formation within cyst), cholelithiasis, choledocholithiasis, hepatolithiasis
  • Pancreatitis (acute and chronic)
  • Intraperitoneal cyst rupture
  • Secondary biliary cirrhosis
  • Bleeding due to erosion of cyst into adjacent vessels or due to portal HTN
  • Gastric outlet obstruction due to duodenal obstruction
  • Gallbladder volvulus
  • Intussusception
• Macroscopic features:
  
  • Todani classification
    
    • Type 1:
      
      • The most common (>80%)
      • Solitary fusiform cystic dilatation of a portion extrahepatic biliary tree
    • Type 2:
      
      • An isolated diverticulum of the CBD
    • Type 3:
      
      • Choledochocele (cystic dilatation of the intraduodenal CBD)
    • Type 4: multiple dilatations (2^nd most common)
      
      • A: Extra & intrahepatic
      • B: Extrahepatic
    • Type 5: Intrahepatic dilations (Carolis)
• Microscopic features:
• Investigations:
  
  • LFTs often normal
  • USS
    
    • Frequently misses type III cysts
    • Echogenic foci or bundles (depending on the imaging plane) surrounded by the hypoechoic cystic bile duct dilatations
  • MRCP/MRI
    
    • T1 hypodense with dilatation of intrahepatic bile ducts
    • T2 hyperintense
    • T1c T1 C+ (Gd): enhancement of the central portal radicles within the dilated IHBD
    • MRCP shows continuity of the bile duct with the cystic lesions
  • ERCP
    
    • 100% specificity and sensitivity
  • CT
    
    • Multiple hypodense rounded areas which are inseparable from the dilated intrahepatic bile ducts
    • “Central dot” sign: enhancing dots within the dilated intrahepatic bile ducts, representing portal radicles
• Treatment:
  
  • Aim to prevent complications
  • Operative
    
    • Treat complications first (pancreatitis, cholangitis)
    • Then image to define anatomy
    • Then definitive surgery
      
      • Surgical excision is recommended treatment due to risk of malignancy and sepsis
      • Previously cystenterostomy (drainage of cyst into duodenum) - now no longer recommended as risk of malignancy
      • Hepaticojejunostomy is recommended reconstruction
      • Caroli’s disease requires lobectomy if confined to one lobe, liver transplant if widespread
    • Type
      
      • 1
        
        • Resection of the extrahepatic tree and hepaticojejunostomy
      • 2
        
        • Cholecystectomy and simple excision of the cyst with primary repair over t tube (or the same as type 1/4b)
      • 3
        
        • Rare to have malignant transformation
        • ERCP sphincterotomy will suffice
      • 4a
        
        • Resection of the extrahepatic tree and hepaticojejunostomy
      • 4b
        
        • Resection of the extrahepatic tree and hepaticojejunostomy
      • 5
        
        • Supportive care, then transplant
• Prognosis:
  
  • Cholangiocarcinoma (3/4)
  • GB cancer (1/4) 16% risk

Question 9

Gallbladder adenomyomatosis

Answer 9

• Definition:
  
  • Benign thickening of the gallbladder wall from hyperplasia of the mucosa and muscularis propria
• Incidence/epidemiology:
  
  • Uncommon – 1-9% gallbladder specimen
• Aetiology & risk factors:
  
  • Gallstones
  • Inflammation
• Pathophysiology:
  
  • From hyperplasia of the mucosa and muscularis propria
  • No malignant progression but segmental adenomyomatosis is a risk factor for gallbladder cancer (as it is the result of gallbladder inflammation)
• Clinical manifestations:
  
  • Incidental – histology or USS
  • Differential diagnosis
    
    • Cholecystitis
    • Cholesterol polyps
    • GB cancer
• Macroscopic features:
  
  • Intramural diverticula are called Rokitansky-Aschoff sinuses (RAS), which trap bile that accumulates cholesterol crystals appearing as cystic spaces in a thickened gallbladder wall with a characteristic comet tail artifact
  • 4 main patterns of thickening in adenomyomatosis
    
    • Diffuse
    • Fundal/focal
    • Segmental/Annular
• Microscopic:
  
  • ​Rokitansky Aschoff sinuses (diverticulum)
  • Hyperplasia of the muscular layer
  • epithelial proliferation, epithelial lined cystic spaces
  • Biliary stones within the RAS
• Investigations:
  
  • Malignancy
    
    • Invasion through GB wall
    • Focal thickening that doesn’t have RAS
    • USS 91% accuracy to differentiate GB cancer from GA
    • MRI 93% accuracy to differentiate GB cancer from GA
  • USS
    
    • Gallbladder wall thickening
    • Clean interface between GB and liver parenchyma
    • Small anechoic spaces (RAS) within gallbladder wall with comet tail artifact from cholesterol crystals
  • PET
    
    • Non FDG avid (compared to liver or cancer)
• Treatment:
  
  • Non operative
    
    • If certain of the diagnosis then no further investigation required
    • If not certain consider further imaging or HPB specialist for resection
  • Operative
    
    • Cholecystectomy

Question 10

Gallbladder polyps

Answer 10

Protrusion arising from the gallbladder mucosa

Benign

• Neoplastic
  
  • Adenoma
• Non neoplastic
  
  • Inflammatory
  • Cholesterol
  • Adenomyomatosis

Malignant

Risk of cancer

• >1cm
• Older than 50 years
• Sessile
• Multiple polyps
• Primary sclerosing cholangitis
• Indian
• USS
• If 1cm then consider MRI or MDT review for underlying malignancy
• If +2cm then needs staging
  
  • CT CAP
  • MRI liver
  • Cholecystectomy with local resection 2cm margin + lymphadenectomy

Question 11

ERCP perforation

Answer 11

Stapfer classification

Type I: duodenal wall - endoscope - clip or emergency operation

Type II: periampulla - sphinctertome - CT, if fluid then OT, if not then observe

Type III: bile duct - basket or wire - conservative

Type IV: retroperitoneal air alone - compressed air - conservative

No idea how to remember the name Stepfer.. To remember 1→4

E = endoscope

R = round (sphincter)

C = choledochal

P = pneumo

Question 12

ERCP complications

Answer 12

Serious complication:

• 2% (1:50)

Failure to cannulate

• 8% Taranaki

Failure to clear duct

• 11% Taranaki

Pancreatitis

• 5% Taranaki
• Rectal diclofenac to prevent

Bleeding

• 1%

Perforation

• 0.5%(1:200)

Death

• 0.2%(1:500)

Question 13

Sphincter of Oddi Dysfunction

Answer 13

• Type 1 - Abdominal pain, obstructive liver function tests, biliary dilatation and delayed emptying of contrast at ERCP - no manometry needed, do sphincterotomy
• Type 2 - Pain with only one or two of the above-mentioned criteria - if abnormal manometry then do sphincterotomy
• Type 3 - Recurrent biliary pain only. Mandatory manometry

Question 14

Amoebic liver abscess

Answer 14

• Definition:
  
  • Amebiasis is caused by the protozoan Entamoeba histolytica
  • Parasite  protozoa (single cell) - Entamoeba histolytica
• Incidence/epidemiology:
  
  • 10% of abscess
• Aetiology & risk factors:
  
  • Male predominance
  • 30-40 years old
  • Migrants and travellers from endemic areas
  • Sexual oral-anal contact
  • Immunosuppression
• Pathophysiology:
  
  • Contaminated food or drink  amoebic colitis  migration of trophozoites through the mucosa into the portal vein and onto the liver
  • Provoke enzymatic focal necrosis of hepatocytes and multiple microabscesses that eventually coalesce to form one lesion
  • The anchovy paste is nearly always sterile

• Clinical manifestations:
  
  • Usually ~3 months after infection (but can be years-decades later)
  • 1-2 weeks of RUQ pain and fever
  • Anorexia, malaise, hiccough
  • Diarrhoea or recent desentry
  • Jaundice
  • RUQ tenderness and hepatomegly
  • Complicated disease; rupture into pleural or peritoneal cavity, IVC thrombus, cardiopulmonary complications
  • High WCC but normal eosinophil
  • ALP (80)
  • Colonic ameboma mimicking colon cancer
  • Differential diagnosis
    
    • Pyogenic abscess
    • Hydatid disease (but these are usually symptomatic <10cm)
    • Malignancy
• Macroscopic features:
  
  • Cystic lesion filled with “anchovy paste” consisting of necrotic hepatocytes

(amoebic colitis)

• Microscopic features:
  
  • Trophozoites are seen on microscopy of the aspirate in fewer than 20 percent of cases and are often present only in the peripheral parts of the abscess, invading and destroying adjacent tissue. This is in contrast to aspirates from pyogenic liver abscesses in which bacterial organisms and polymorphonuclear cells are usually readily apparent by Gram stain.
• Investigations:
  
  • USS
    
    • Well defined cystic lesion
  • CT
    
    • Low-density mass with a peripheral enhancing rim, oedema (hypodense) beyond the capsule
    • Treated lesions may become anechoic, calcified, or may persist as cystic-appearing lesions
  • MRI
    
    • Low-signal intensity on T1-weighted images and high-signal intensity on T2-weighted images. After healing, the periphery of the abscess may calcify as a thin, round ring
  • Radionucleotide scan
    
    • Cold (in comparison to hot pyogenic abscess)
  • Serology for antibodies
  • Stool OCP – 1/3 will be positive
  • PCR on aspirated material
• Treatment:
  
  • Non operative
    
    • Metronidazole 500mg TDS for 10 days
    • Paromomycin for luminal cysts
    • Needle aspiration or pigtail if >10cm (anchovy paste appearance)
  • Operative
• Prognosis:
  
  • Uncomplicated disease <1% mortality
  • In india 17% mortality

Question 15

Hydatid Disease

Answer 15

• Definition:
  
  • Hydatid disease is characterized by Echinococcus tapeworm infection
  • Zoonotic disease (disease that can be contracted from animals)
  • Parasitic infection  Helminth (multicellular)Platyhelminth (Flatworms)Cestode (tapeworm) - Echinococcus
• Incidence/epidemiology:
  
  • Endemic
    
    • around Mediterranean, middle East, Central Asia and South America
  • Eliminated
    
    • in NZ / Australia through control programs.
  • Some residual disease in older people and travellers
• Aetiology & risk factors:
  
  • Farmers
  • Migrants
• Pathophysiology:
  
  • Two species of tape worm
    
    • Echinococcus granulosis
    • Echinococcus multilocularis
  • Reproductive cycle involves definitive host and intermediate hosts, human are accidental hosts (or abberant intermediate hosts)
    
    • The dogs have the adult attached to the SB, releasing eggs in faeces
    • The sheep and humans have cysts form around the oncospheres which traverse the SB
  • 1. Definitive hosts are canines, where the adult breeding form of the tapeworm is attached to the small intestine and shed eggs into faeces
  • 2. Intermediate host are sheep or humans, ingest the faeces and the egg releases oncospheres which hook onto the intestinal wall
  • 3. Oncospheres migrate through circulatory system to organs, usually liver and lung
  • 4. The oncospheres become fluid filled cysts called hydatid cysts
  • 5. the intermediate host i.e. sheep, the organs are consumed by the definitive host and the cysts release protoscolices that attach to the intestinal wall and mature into adult tapeworms (completing the life cycle)
  • 6. In humans the hydatid cysts slowly enlarge and are encapsulated by a granulomatous inflammatory reaction, the cysts can divide into multiple smaller daughter cells
  • Echinococcus granulosis is usually asymptomatic but can cause symptoms by mass effect
  • Echinococcus multilocularis is more invasive and can cause severe infection and metastasis of infection

• Clinical manifestations:
  
  • E granulosis
    
    • 2/3 liver
      
      • (right lobe 80%)
      • Usually not a problem until 10cm
      • Mass effect  biliary, venous obstruction and sequelae
      • Secondary bacterial infection
      • Cystobiliary communication – obstruction and jaundice
      • Rupture and peritonitis +/- anaphylaxis +/- seeding for secondary infection
    • ¼ lung
      
      • Rupture and infection
    • Frequently asymptomatic and lay unnoticed for many decades
    • Cysts can develop anywhere
  • E multilocularis
    
    • RUQ pain, jaundice, fevers
    • 100% mortality within 15 years unless treated
• Macroscopic features:
  
  • Pericyst/adventitial layer, host derived tissue
  • Laminated layer – acellular, permeable to electrolytes and water but resistant to immune cells, bile
  • Geminal layer – the living layer of the parasite – produces protoscolices and fluid, daughter cells
  • Hydatid cysts are round in shape and are usually filled with a clear fluid
• Microscopic features:

• Investigations:
  
  • Biochemistry
    
    • Transaminases may be normal, even in very large cysts
• cholestatic mildly elevated in 1/3
  
  • Haematology
    
    • Nonspecific eosinophilia in 25% only
    • WCC only elevated if cyst secondarily infected
  • Microbiology
    
    • 3 tests of serologic tests are available
      
      1. ELISA - sensitivity 64-100%
         2, Immunoelectrophoresis; very accurate for hepatic cysts.
      2. Hydatid antigen blotting
  • Imaging
    
    • US
      
      • Preferred first option
      • Specificity ranges around 90%
      • Standardized US criteria from a WHO working group.
        
        • Cyst wall, hydatid sand (protoscolices), multivesicular cysts.
• if starting to degenerate, see decreased intracystic pressure, no daughter cysts, ultimately a thick calcified wall (inactive cyst)
• if cyst has inactive old burnt out features, usually no living protoscolices.

• CT
  
  • Structural detail
  • Show depth and position of cyst
  • Unilocular or complex, thick walled, often with calcification, presence of daughter cysts
  • Calcification generally is inactive disease
• MRI
  
  • Can compliment CT but not a first line investigation.
  • Cysto-biliary fistulae
• Cyst aspiration or biopsy
  
  • If negative serologic test, percutaneous aspiration or biopsy may be required to confirm the diagnosis by demonstrating the presence of protoscolices, hooklets, or hydatid membranes – but can result in anaphylaxis
• Treatment:
  
  • Depends on underlying organism, cyst factors and patient factors

• E granulosis less aggressive approach
  
  • Small cysts <5cm without daughter cysts or septations = medical treatment (albendazole)
    
    • 3 months albendazole
      
      • Monitor LFTs and CBE for bone marrow suppression
  • Larger cysts without daughter cysts or septations PAIR – puncture aspirate injection reaspiration - protoscolicidal agent (e.g. hypertonic saline or 95% ethanol). Don’t use if eroding into the CBD as will cause sclerosing cholangitis
  • Larger complicated cysts – under cover with albendazole –
    
    • Options include
      
      • Simple cyst drainage, partial cystectomy
      • Radical procedures i.e. pericystectomy, liver resection and rarely transplantation
      • Principles
        
        • Protection of the peritoneal cavity with hypertonic saline packs
        • Suction of the contents and removal of all viable elements
        • Inspection of the cavity to ensure no biliary communication
        • Injection of scolicial agent
        • Obliteration of the cavity
        • Increased morbidity if pericyst not removed
    • Conservative surgery
      
      • Best for cysts on periphery of liver
      • Before entering cyst, pack operative field with scolicidals to minimize risk of peritoneal soilage and contamination.
      • Cyst contents are then aspirated; system infused with scolicidals.
        
        • Note: if cyst fluid bile stained, avoid scolicidals in the cavity.
      • Then unroof cyst and fully explore cavity; clear debris and fill with an omental pedicle.
    • Radical surgery
      
      • Complete removal of cyst and pericyst
      • Including any exocyst and adjacent parenchyma.
      • Is really the best treatment for all forms of hydatid but especially large biliary-cyst fistulae.
      • Either open or closed technique
        
        • if open, cyst contents removed and scolicidals infused; then excision, - contents must not be spilled, Pericyst wall removed by electrocautery and dissector –> recommended for large cysts, thin wall and high risk of rupture.
        • • if closed, whole cyst removed en-bloc; no healthy liver tissue; plane outside pericyst –> preferred when cysts peripheral with thick wall and not involving major structures. Control vessels / biliary structures with clips and sutures, can use intraop USS useful to define relationship with vascular and biliary structures.
        • Closed is more demanding as parenchymal resection.
      • Resection and Transplantation.
        
        • Nonanatomic wedge resection, if less cut liver surface than pericystectomy.
        • No ischaemic pedicle.
        • If large multilocular cysts, formal liver resection.
        • Remnant should be clear.
      • Liver Transplantation
        
        • Unusual circumstances, transplantation may offer only curative approach.
        • E. multilocularis (multilocular by name) –> more likely reqd.
    • Biliary-cyst communication.
      
      • Investigate.
      • Pre-op ERCP can help identify; or cholangitis or numerous segments involved = high risk.
      • Finding of bile-stained fluid in cyst cavity should alert.
      • Leave a dry pad on inner aspect of cyst while applying pressure on gallbladder –> if stains, highly suggestive.
        
        • <5mm communication –> close with sutures.
        • • transcystic dye study after excision.
        • >5mm = more difficult.
        • • can close over a T-tube to decompress the biliary tree
• Prognosis:
  
  • Shock due to protoscolice spillage is rare.
  • Morbidity in range of 20%; mortality 1%.

Question 16

Liver flukes

Answer 16

• Definition:
  
  • Parasitic infection  helminths (multicellular)  platyhelminths (flat worms)  Liver fluke (trematodes - so named because of their conspicuous suckers, the organs of attachment trematos means “pierced with holes”)
• Incidence/epidemiology:
  
  • Clonorchiasis – east asia/russia – 35 million people world wide infected
  • Opisthorchiasis – SE asia/east Europe – 23 million people world wide infected
• Aetiology & risk factors:
  
  • Chlonochiasis – raw/undercooked/pickled/salted fresh water fish
• Pathophysiology:
  
  • The life cycles of Clonorchis and Opisthorchis flukes are similar
  • Begin within Humans release of embryonated eggs into the biliary ducts and subsequently the stool (into the lake/fresh water)
  • Eggs are ingested by a snail (first intermediate host), where miracidia are released and go through several developmental stages (sporocysts, rediae, and cercariae)
  • The cercariae are released from the snail into fresh water and subsequently penetrate the flesh of freshwater fish (second intermediate host), where they encyst as metacercariae
  • Animals or humans (definitive host) acquire infection via ingestion of raw, undercooked, salted, pickled, or smoked freshwater fish. The metacercariae excyst in the duodenum and ascend the biliary tract
  • Maturation to adult flukes takes approximately one month. The adults generally reside in small- and medium-sized biliary ducts; occasionally, they reside in the gallbladder or pancreatic duct
  • Specific immune suppressive mechanisms may promote parasite persistence, therefore allowing continued secretion of parasite products that damage the biliary epithelium, both directly (via mechanical damage) and via inflammation
• Clinical manifestations:
  
  • Most infected individuals are asymptomatic and have a benign course
    
    • The risk of symptomatic infection and complications rises as the intensity and duration of infection increase
    • “Light” infections (<100 flukes or up to 1000 eggs per gram of stool) rarely cause symptoms
    • Peripheral eosinophilia may be present (usually up to 10 to 20 percent), and serum IgE raised
  • 10% develop acute symptoms
    
    • RUQ pain, fatigue, flatulence, diarrhoea, arthalgia, rash, lymphadenopathy, hepatomegly
    • Symptoms persist for 2-3 weeks
  • Chronic symptoms
    
    • Due to mechanical obstruction from worm load or size or HEPATOLITHIASIS
    • Anorexia
    • Raised ALP
    • Liver abscess, jaundice, cholangitis
  • Cholangiocarcinoma
    
    • Chronic irritation to epithelial cells, which desquamate and proliferate, eventually leading to hyperplasia, dysplasia, and fibrosis
• Macroscopic features:
• Microscopic features:
• Investigations:
  
  • Stool or bile microscopy
  • USS echogenic periductal foci with ductal obstruction
  • Serology doesn’t distinguish between current and previous infection
  • Imaging may show slender filling defects in CBD + fibrosis and calculi
  • Differentials
    
    • Acute viral hepatitis – distinguished from liver fluke infection by the absence of eosinophilia and positive hepatitis serology
    • Schistosomiasis – Clinical manifestations of chronic schistosomiasis include signs of portal hypertension, abnormal liver function tests, and eosinophilia. The diagnosis is established by serology and/or microscopy
    • Strongyloidiasis – The diagnosis is established by serology and/or microscopy
    • Ascariasis – Ectopic ascariasis can be a cause of extrahepatic biliary obstruction, with clinical manifestations of abdominal pain and jaundice. The diagnosis is established by serology, microscopy, and/or visualization ERCP
    • Choledocholithiasis
    • Cholangiocarcinoma – MRCP and tumor markers
    • Primary sclerosing cholangitis – MRCP
• Treatment:
  
  • Non operative
    
    • Praziquantel
    • Prevention, freezing/cooking fish, population antihelminth treatment, septic sanitation
• Operative
  
  • May require ERCP or drainage of obstructed ducts
• Prognosis:

Question 17

Cholangiocarcinoma

Answer 17

• Definition:
  
  • Malignancy of the intra or extra hepatic biliary tract epithelium excluding the gallbladder/ampulla, 95% are adenocarcinoma (of cholangiocytes)
• Incidence/epidemiology:
  
  • Rare but increasing incidence, 15% of primary liver cancers turn out to be cholangiocarcinoma
  • M>F 1.3>1
  • >60 usually
  • Geography; SE Asia more commonly
  • 2.5:100,000 mortalities per year in Australasia
• Aetiology & risk factors:
  
  • Majority do not have any identifiable cause
  • Primary Sclerosing Cholangitis (8-40% of PSC patients)
  • Recurrent cholangitis
  • Choledochal cysts – 5 types (type 5 is Caroli disease) (7-28% of cyst patients)
  • Hepatolithiasis (chronic portal bacteraemia conguation of pigments and pigment stones – 10% of these develop cancer)
  • Viral hepatitis
  • Cirrhosis
  • Chemical exposure
    
    • Thorotrast - radiological agent used in the 1960s
    • Dioxin
    • Vinyl chloride
    • Heavy alcohol use
• Pathophysiology:
  
  • Chronic inflammation of the intrahepatic bile ducts is a known risk factor in cholangiocarcinogenesis
    
    • Proinflammatory cytokines activate inducible nitric oxide synthase resulting in oxidative DNA damage, inhibition of DNA repair enzymes and expression of cyclooxygenase 2 (COX2)
    • These pathways also downregulate hepatobiliary transporters and cause cholestasis (Semin Liver Dis 2010;30:186)
    • Bile acids and oxysterols activate epidermal growth factor receptor (EGFR) and enhance COX2 expression (Gastroenterology 2002;122:985)
    • COX2 dysregulates cholangiocarcinoma growth and promotes apoptosis resistance and positively regulates pro-oncogenic signaling pathways such as hepatocyte growth factor (HGF), IL6 and EGFR (Semin Liver Dis 2010;30:186)
    • TP53 and SMAD4 mutations are more frequent in liver fluke associated cholangiocarcinoma
    • BAP1 and IDH1 / 2 mutations are more frequent in non liver fluke associated cholangiocarcinoma (Medicine (Baltimore) 2016;95:e2491)
    • In specimens of bile ducts from patients with hepatolithiasis, biliary intraepithelial neoplasia (BilIN) is a common finding and is considered to be a precursor lesion of cholangiocarcinoma. It is typically a microscopic lesion with a flat or micropapillary dysplastic epithelium. It is synonymous with carcinoma in situ
  • Obstruction of biliary drainage
  • Metastasis
    
    • Intrahepatic metastases – common
    • 50% will have lymph node metastasis
    • Lungs
    • Bone (vertebrae)
    • Adrenals
    • Brain
• Clinical manifestations:
  
  • Depends on location & stage
  • Extrahepatic
    
    • Biliary obstruction
    • Jaundice in 70-90%, can be intermittent due to ball-valve effect of papillary
  • Intrahepatic
    
    • Usually asymptomatic until late stage, picked up by imaging after deranged LFTs, symptoms may include abdominal pain, anorexia, weight loss
  • Cholangitis rare without previous biliary intervention
  • Portal hypertension
• Macroscopic features:
  
  • Usually single, large, homogeneous mass with irregular margins and intratumoral calcification is common, obstructed duct proximally with parenchymal atrophy
  • Focal, multifocal or diffuse
  • Classification by site
    
    • Intrahepatic 10%
    • Extrahepatic 90%
      
      • Perihilar (Klatskin) 60%
      • Distal (to cystic duct) 30%
  • Bismuth-Corlette classification
    
    • Type 1: CHD below confluence
    • Type 2: at the confluence
    • Type 3: Into a hepatic duct R=A L=B (stupid)
    • Type 4: Confluence into both hepatic ducts
• Morphology (Japanese)
  
  • Type 1: Mass forming (exophytic nodule outwards)
  • Type 2: Periductal infiltrating (most common)
  • Type 3: Intraductal (papillary within the duct)
• Microscopic features:
  
  • 95% adenocarcinoma
    
    • 75% well to moderate differentiated
  • 5% other including papillary (better prognosis), signet ring, squamous
  • Fibrosis of periductal tissues and annular bile duct thickening
• Investigations:
  
  • USS
    
    • Good for assessing level and longitudinal involvement of the ducts
    • Great for assessing portal venous involvement
  • CT multiphase
    
    • Prior to biliary stenting
    • Contrast-enhanced CT
    • Heterogenous, variable rim-like enhancement can be observed, predominantly on the arterial phase images with gradual centripetal enhancement on delayed imaging
    • Note
      
      • Level
      • Relationship to surrounding structures
      • State of liver parenchyma
    • Not great for assessing longitudinal involvement of the ducts or LNs
    • CAP staging
  • MRI
    
    • Hypointense on T1-weighted images and hyperintense on T2-weighted imaging
    • Initial rim enhancement characterised by progressive and concentric enhancement post-administration of
    • Lesions do not completely enhance post-contrast
    • In the absence of a separate primary source of disease, a lesion in the liver with this morphology on MRI evaluation can be considered virtually diagnostic of cholangiocarcinoma without a tissue diagnosis
    • Capsular retraction may also be seen
    • MRCP can not great with stents due to artifact
  • PET – Positron Emission Tomography
    
    • Alter management in 30% due to distant disease (not seen on CT)
    • Funded in NZ, not sure AUS
    • False positives can occur in patients with stents
  • Endoscopic
    
    • Cytology sensitivity less than 60% due to fibroplastic reaction
    • Good for stenting and assessing lesions difficult to assess on imaging
    • Spyglass cholangioscopy can be used for direct visualization and targeted biopsy
  • Tumour markers
    
    • CEA
    • Ca19-9; >100 in absence of PSC 50% sensitive
    • AFP for HCC
  • Staging laparoscopy
    
    • 30-40% of “resectable” patients will be found to be unresectable
    • Intrahepatic metastasis (35%), peritoneal mets (30%), coeliac LN mets (25%), portal vein involvement (10%)

Treatment:

• Depends on resectability
  
  • 3 factors; patient, tumour, systemic oncology
  • Intrahepatic
    
    • Sufficient future functional liver remnant
    • i.e.
      
      • Multiple bilobar liver tumours
      • Obvious extensive lymph node metastases
      • Hepatic metastatic disease
  • Hilar - see criteria below
    
    • Consider the bilateral nature of portal vein, hepatic artery, hepatic duct and hepatic lobe atrophy
    • Think, What does the remnant liver look like, does it have all its plumbing?
  • Distal CBD cholangiocarcinoma
    
    • Contraindications
      
      • Presence of tumour in the portal vein >2cm
      • SMA or common hepatic artery involvement
      • Distant metastasis absolute contraindication
      • Regional LN involvement relative contraindication
• Preoperative biliary drainage?
  
  • Pro’s and con’s – improved bilirubin and hepatic function vs sepsis and seeding
  • Stenting doesn’t improve synthetic function in atrophic lobes, will improve sepsis though
  • ?Improve nutrition
  • Palliative stenting
    
    • Perihilar metal stent median patency 6 months
    • Distal CBD metal stent 90% patent at 1 year
• Preoperative portal vein embolization
  
  • Can theoretically reduce the risk of postoperative hepatic dysfunction by inducing preoperative compensatory hypertrophy of the non-embolised lobe
  • If predicted functional liver residual <30% consider PVE
• Type of curative resection depends on location
  
  • Need R0 margins and enough functional liver remaining, arterial reconstruction controversial
    
    • About 50% are thought to have achievable R0 resection on staging – but R1+ resection on pathology
  • Goals (for perihilar and intrahepatic)
    
    • Excision of Supraduodenal bile duct
    • Routine hepatectomy
    • Resection of the caudate lobe
    • Portal lymphadenectomy
    • Routine PV resection? No touch technique is where the PV isn’t dissected – just resected enbloc
  • Intrahepatic
    
    • Hepatic resection
    • Lymphadenectomy for central tumours
  • Perihilar
    
    • Type I-II
      
      • En bloc resection of the extrahepatic bile ducts and gallbladder, left or extended right is usually required to achieve adequate negative bile duct margins
      • 5 to 10 mm bile duct margins
      • Regional lymphadenectomy
      • Roux-en-Y hepaticojejunostomy reconstruction
    • Type III
      
      • In addition to the above operations, type III tumors usually require hepatic lobectomy or trisectionectomy
    • Type IV
      
      • Will also need portal vein resection & reconstruction
  • Distal CBD
    
    • Pancreaticoduodenectomy
  • Transplant
    
    • Overall survival for ALL adult liver transplants is 73% at 10 years
    • Cholangiocarcinoma though
      
      • Indication
        
        • ICC and perihilar if <2cm in size but liver cirrhosis
      • Outcome
        
        • ..
• Adjuvant for resectable
  
  • Capecitabine for 6 months
• Unresectable
  
  • Intrahepatic biliary-enteric bypass
    
    • Either segment III or Right sectoral ducts
    • Only need to decompress a third of the liver to relieve jaundice
    • No point in bypassing atrophic lobes
  • Chemotherapy
    
    • Gemcitabine + cisplatin based on the ABC02 trial
  • Novel agents
    
    • In essence, although novel, the addition of targeted agents in advanced biliary malignancy remains investigational (EGFR, VEGFR, MEK inhibitors)
  • Regional Radiotherapy/hepatic artery infusion
  • Y90 radioembolisation

• Prognosis:
  
  • Survival
    
    • 5 year survival (without treatment?) <20%
    • Post R0 resection (5 year survival)
      
      • Intrahepatic 20-40%
      • Perihilar 30-40%
      • Distal CBD 50%
    • Post transplant
      
      • ? after neoadjuvant - 65% 5 year survival
  • Prognostic factors
    
    • Clinical
      
      • Good
      • Bad
        
        • Jaundice
    • Radiological
      
      • Good
      • Bad
        
        • Main PV involvement
    • Histological
      
      • Good
        
        • R0 resection margins is the most predictive factor of oncologic outcome
        • R0 resection, concomitant hepatectomy, well-differentiated histology and papillary tumour phenotype were all independent predictors of long-term survival
      • Bad
        
        • Perineural and vascular invasion, lymphovascular invasion
        • R1 margin
        • N1
        • 5cm in size

Question 18

• Curriculum - technical expertise specifically for liver (not including trauma):
  
  • Knows
    
    • Liver resection
    • Intraoperative ultrasound
    • Laparoscopic liver biopsy in cirrhosis
    • Principles of resection
  • Does
    
    • Staging laparoscopy
    • Laparoscopic liver biopsy (non cirrhotic)

Answer 18

• Principles of liver surgery:
  
  • Principles of liver surgery:
    
    • Liver mobilisation
    • Inflow control
    • Outflow control
    • Low CVP
    • Parenchymal dissection
  • Liver mobilisation
    
    • Falciform/teres ligament & coronary ligament
      
      • Taken down, ligamentum teres used as a retractor inferior/posteriorly
      • Extended cephalad to exposure the subdiaphragmatic IVC through the coronary ligament
      • The ligamentum teres is anchored to the left portal vein
    • Right triangular ligament
      
      • Exposes the bare area of the liver
      • The vena caval ligament covers the IVC
    • Left triangular ligament
      
      • Care to avoid the left phrenic vein
  • Inflow control
    
    • Pringle maneuverer: compression of the portal vein and hepatic artery at the free edge of the lesser omentum
      
      • Create opening in the pars flaccida medial to the portal triad, umbilical tape through this opening and the foramen of winslow encircling the portal triad, create a rummel tourniquet
      • Vessel loops
      • 10-15 minutes on, 5 minutes off..
    • Dissect out the hilar plate (fibrous connection of the hilar bifurcation to the liver) to control gain selective inflow control or glissonian pedicle approach
    • TVE includes control of liver inflow and outflow
• Outflow control
  
  • Hepatic veins
    
    • Need to have mobilised the liver
    • Caudate lobe has a number of small direct branches
  • Infrahepatic IVC encircled
  • Suprahepatic IVC
• Low CVP
  
  • Hepatic veins are valveless, thus a high CVP causes back bleeding
  • Anaesthetists:
    
    • Low fluid
    • Diuretic
    • Minimal PEEP
    • GTN or epidural
• Parenchymal dissection
  
  • Soft liver parenchyma off the vascular and ductal structures
    
    • Methods
      
      • Finger fracture
      • Diathermy
      • Crushing clamp
      • CUSA – cavitating ultrasonic surgical aspirator
      • Harmonic
      • RFA probe
      • Vascular Stapler (after crushing clamp) – Mem sloan kettering HPB 2008
    • 2 general rules
      
      • 1. The portal vein tends to lie posterior to the bile duct and artery
      • 2. The duct lies superior to the artery and is always close to it
• Postoperative complications
  
  • Bile leak, bleeding, post hepatectomy liver failure

Question 19

Spleen Anatomy

Answer 19

• Definition:
  
  • The spleen is a solid organ in the left upper quadrant posteriorly
  • The largest lymphoid organ, has haematopoietic & immune functions
  • Odd numbers
    
    • 1 x 3 x 5 inches
    • 7oz ~200g
    • 9-11 ribs
• Embryology:
  
  • 6^th week, mesodermal cells in the dorsal mesogastrium
  • Functions as a haemopoietic organ, but 15-18^th week becomes lymphoid
  • Dorsal mesogastrium called gastrosplenic ventrally and splenorenal dorsally
  • Forms the left wall of the lesser sac
  • Multiple condensations of cells fuse to form a single organ, accessory spleens are due to a failure of fusion
• Surface anatomy:
  
  • 9-11 ribs
  • Lower pole doesn’t usually extend past mid-axillary line
• Surrounding structures and relations:
  
  • Intraperitoneal
  • Hilum is the left margin of the lesser sac
  • Gastrosplenic ligament
  • Splenorenal ligament with the splenic vessels and tail of pancreas
  • Splenocolic ligament
  • Phrenosplenic ligament
• Arterial supply:
  
  • Splenic artery (
    
    • Branch of coeliac axis
    • Patterns
      
      • Distributive
        
        • Multiple branches 2-3cm before hilum
      • Majestical
        
        • 1 artery, branches off in the hilum
    • Runs along the superior portion of the pancreas
    • Tortuous
    • Branches
      
      • L gastroepiploic
      • Short gastrics
      • Branches to pancreas
  • Short gastric arteries (from gastroepiploic artery)
• Venous drainage:
  
  • Splenic vein
    
    • Fibrous groove on the posterior aspect of the pancreas
    • Combines with the SMV behind the neck of the pancreas (to form PV)
    • Often has IMV joining it behind the body of the pancreas
  • Short gastric veins
• Innervation:
  
  • Coeliac plexus (sympathetic only)
• Lymphatics:
  
  • Several nodes at the hilum
  • Pancreaticosplenic nodes
  • Coeliac nodes
• Structure within the organ and cell types:
  
  • Function (FISH)
    
    • Filtration
      
      • RBCs (old, damaged)
      • Microbes
      • Antigens
      • Reticuloendothelial system
    • Immune
      
      • Macrophages and dendritic cells – trapping antigens and acting as APC cells
      • Phagocytosis of immunoglobulin labelled antigens
    • Storage
      
      • Reservior for extra cells (normally 50mL) in the venous sinuses
    • Haematopoiesis
      
      • Embryo
      • Myelofibrosis
  • Blood reaches the spleen via the splenic artery, which then divides into many small branches, the central arterioles
    
    • The lymphocyte-rich regions of the spleen are known as the white pulp. The T cell areas encircle the central arterioles, and are thus referred to as the peri-arteriolar lymphoid sheaths (PALS), they interact with APC cells. B cells are found in follicles, analogous to LN follicles, ready to interact with the B cells
      
      • Segregation of T and B cells within the white pulp is maintained by chemokine gradients.
      • Blood traversing the white pulp drains into the marginal sinus.
    • Marginal zone
      
      • Between red and white cells
      • Dendritic cells
    • The red pulp is rich in rbc, mf, DC and plasma cells. It is the major site for phagocytosis of opsonised microbes.
• Relevance to operations:
  
  • Splenuculi – usually in the hilum, gastrosplenic, splenorenal/tail of pancreas, greater omentum, pelvis

Question 20

Splenic lesion

Answer 20

• Definition:
  
  • Space occupying lesion within the spleen and its capsule
  • Benign (mechanism) or malignant (primary or secondary – tissue types)
    
    • Benign
      
      • Trauma
        
        • Haematoma
        • Pseudocyst
      • Inflammatory
        
        • Pseudocyst secondary to pancreatitis
      • Infectious
        
        • Bacterial
        • Parasitic
        • Fungal
      • Neoplastic
        
        • Haemangioma (most common primary benign lesion)
        • Lymphangioma
      • Congenital
        
        • Simple cyst
    • Malignant
      
      • Primary
        
        • Angiosarcoma (most common primary malignant lesion)
        • Haematological
          
          • Lymphoma
      • Secondary
        
        • Breast
        • Lung
        • Melanoma
        • Ovarian
• Incidence/epidemiology:
  
  • • Aetiology & risk factors:
  • Abscess
    
    • Origin
      
      • Haematogenous spread most common
        
        • Endocarditis
        • UTI
        • GI infections
      • Contiguous spread (pancreas, colon, kidney)
    • Organism
      
      • Gram positive cocci
        
        • Staph, strep, enterococcus
      • Gram negative enteric
      • MAC
      • Actinomyces
      • Fungal infections
  • Cyst
    
    • Congenital
    • Pseudocysts
      
      • Pancreatitis
      • Trauma
    • Infectious
      
      • Echinococcus (hydatid)
• Pathophysiology:
• Clinical manifestations:
  
  • Incidental
  • Mass
  • Symptomatic
    
    • Pain
    • Rupture/peritonitis/haemorrhage
    • Anaphylaxis (hydatid)
• Macroscopic features:
  
  • Pseudocysts
    
    • Smooth, uniloculated thick walled lesion, focal calcifications
• Microscopic features:
  
  • True cyst
    
    • Lined by squamous epithelium
• Investigations:
  
  • Bloods
    
    • Serology
      
      • Echinococcus
  • Imaging
    
    • CT
      
      • Hydatid
        
        • Calcifications
        • Daughter cysts
      • Haemangioma
        
        • Punctate peripheral calcifications
      • Lymphangioma
        
        • Hypodense
        • Usually subcapsular
        • Enhancing septa and peripheral rim calcification
      • Haemangiosarcoma
        
        • Multiple complex heterogeneous and hypervascular masses, rare calcifications
• Treatment:
  
  • Treat the underlying cause
  • Post splenectomy OPSI prophylaxis (if required)
  • Non operative
    
    • Primary splenic lymphoma
      
      • Usually associate with HCV
      • Rituximab monotherapy
    • Cyst/pseudocyst
      
      • Percutaneous drain if symptomatic
    • Abscess
      
      • IVABx
      • Percutaneous drain if simple
  • Operative
    
    • Abscess
      
      • Splenectomy
        
        • Indications
          
          • Septic
          • Failure of NOM
          • Multiloculated
    • Haemangioma
      
      • Splenectomy
        
        • Indications
          
          • >2cm due to risk of bleeding
    • Angiosarcoma
      
      • Splenectomy only cancer of cure
    • Metastatic disease
      
      • Splenectomy considered in oligometastatic disease
• Prognosis:
  
  • Angiosarcoma
    
    • Poor prognosis
    • Common liver metastasis

Question 21

Splenomegly

Answer 21

• Definition:
  
  • Splenic enlargement 400-500g
  • Massive splenomegaly 1000g+
• Incidence/epidemiology:
• Aetiology & risk factors:
  
  • Mnemonic - CHAIIIN:
    
    • Congestive (portal venous & cardiac)
    • Haematological
    • Anatomical
    • Infectious
    • Immune
    • Infiltrative
    • Neoplastic
  • Causes of massive splenomegaly (CML)
    
    • CML
    • Myelofibrosis
    • Malaria
    • Leishmaniasis
  • Haematological disorders which might need splenectomy (23 of them…)
    
    • Class by cell type affected
      
      • RBC
        
        • Autoimmune disorders
          
          • Haemolytic anaemia
        • Structural abnormalities
          
          • Spherocytosis
        • Haemoglobinopathies
          
          • Thalasaemia
          • Sickle cell
        • Enzymopathies
          
          • Pyruvate kinase deficiency
          • G6PD
      • Platelet disorders
        
        • ITP
        • TTP
      • Myelo/Lympho-proliferative disorders
      • Miscellaneous diseases
        
        • Gauchers
        • Amyloidosis
        • Sarcoidosis
        • Felty’s syndrome (RA + splenomegly + agranulocytosis)
• Pathophysiology:
  
  • CML
    
    • Normal bone marrow replaced by neoplastic myeloid cells
    • Philadelphia chromosome 9:22 translocation
  • Complications
    
    • Hypersplenism
    • Rupture
• Clinical manifestations:
  
  • Symptoms associated with splenomegaly include abdominal pain, early satiety, weight loss, and abdominal distension
  • CML
    
    • Fevers
    • Splenomegly
    • Blast crisis
      
      • Anaemia
      • Infections
      • Bleeding
• Macroscopic features:
• Microscopic features:
• Investigations:
• Treatment:
  
  • Non operative
    
    • CML
      
      • Hydroxychloroquine
      • Interferon alpha
      • Chemotherapy
    • • Operative
    • Splenectomy
      
      • Indications
        
        • Symptomatic
          
          • Pain
          • Rupture
        • Hypersplenism
          
          • Anaemia
          • Thrombocytopaenia
      • Consider angioembolisation on the day to shrink size and improve bleeding
• Prognosis:
  
  • NHL 75% thrombocytopaenia will improve with splenectomy

Question 22

Acute pancreatitis pathophysiology

Answer 22

• Structure of response:
  
  • Causative factors/aetiology IGETSMASHED
  • Mechanism of acinar injury
  • Local effects (pathophysiology)
  • Systemic effects (pathophysiology)
  • Complications (local & systemic)
• Mechanism of local acinar injury
  
  • Ductal obstruction (benign/malignant) accumulation of pancreatic secretions
  • Direct acinar cell damage (trauma, toxins, viral, ischaemia, metabolic)
  • Defective intracellular transport of trypsinogen and cathepsin B leading to apoptosis
• Local effects
  
  • Enzymes
    
    • Elastase - haemorrhage
    • Lipase & phospholipids - fat necrosis
    • Proteases - proteolysis
  • Pseudocyst: results from disruption of the pancreatic duct or a side branch
• Systemic effects:
  
  • Macrophages are activated by DAMPS (signal 1 & 2) and cathepsin B/trypsinogen interaction (part of Signal 2)
  • • activated macrophages release TNFa, IL 6 and IL 1b
  • Marked decrease in response to endothelin and angiotensin II contributes to hypotension
  • Organ dysfunction from hypotension and cellular hypoxia (from mitochondrial dysfunction)
  • Injury to endothelium causing fluid third spacing
  • Injury to epithelium leading to GI bacteria translocation
  • Abnormal clotting
    
    • A: DAMPS activate coagulation system
    • B: Activation of platelets, endothelium (and loss of thrombomodulin) and immune cells
    • C: Thrombin generation
    • D: Cascade inhibitors are diminished

Question 23

Pancreatitis complications

Answer 23

Local

• Peripancreatic fluid collection
• Pseudocyst
• Acute necrotic collection
• Walled off necrosis
• Pseudoaneurym (splenic artery)
• Splenic vein thrombosis with sinistrial portal HTN
• Ileus
• Pancreatic insufficiency
• Chronic pancreatitis
• Biliary and gastric obstruction

Systemic

• ARDS
• Pneumonia
• MI
• AKI
• Ileus
• VTE
• Abdominal compartment syndrome
• UTI and line infection

Question 24

Severity of pancreatitis

Answer 24

Revised Atlanta classification:

Mild

• No local or systemic complications
• No organ failure

Moderate

• Either local or systemic complication &/or
• Transient organ failure (<48hrs)

Severe

• Either local or systemic complication &
• Persistent organ failure (>48hrs)

Question 25

Modified glasgow criteria

Answer 25

• Modified Glasgow criteria
  
  • > or = 3 is higher risk of M&M
  • measured at 48hours
  • PANCREAS
    
    • Pa02 <60mmHg
    • Age >55
    • Neutrophils >15
    • Calcium <2mmol/L
    • Renal function – urea >16mmol/l
    • Liver enzymes – AST or ALT >200 or LDH >600
    • Albumin <32
    • Sugar >10 BGL

Question 26

CT severity score

Answer 26

• Combination of 2 scoring systems
  
  • Balthazar CT score A->E
    
    • A normal
    • B enlargement
    • C inflammatory changes in the pancreas and peripancreatic fat
    • D ill defined single peripancreatic fluid collection
    • E 2 or more peripancreatic fluid collection
  • Pancreatic necrosis score as a %
    
    • None
    • <30
    • 30-50
    • 50+

Question 27

Pathophysiology pancreatic cancer (rfs, pathophys)

Answer 27

Aetiology & risk factors:

• Adenocarcinoma
  
  • Modifiable & non modifiable (genetic & other)
  • Modifiable
    
    • Smoking (2-3x, ~70% increased risk)
    • Obesity (2-3x)
    • Alcohol abuse (unclear)
    • Occupational exposure (asbestos, pesticides, dry cleaning agents, radiation) 3-5x
  • Non modifiable
    
    • Genetic germline mutation (5% hereditary)
      
      • Family history – two 1st degree relatives (x15 RR)
      • BRCA (1 = 8x RR, 2 = 3.5-10x)
      • Hereditary pancreatitis, PRSS1 mutation (leads to chronic pancreatitis) 40-70% lifetime risk
      • Lynch syndrome (HNPCC)
      • Peutz jagher syndrome STK11(75-130x RR)
      • Familial multiple mole melanoma FAMM (p16 gene mutation) 20-30x RR
    • Other
      
      • Age, 7-8^th decades
      • Diabetes (2-3x)
      • Male
      • Chronic pancreatitis (2-10x)
      • Hepatitis B/C
      • Non O blood type
      • Cystic fibrosis
    • NOT COFFEE
• Neuroendocrine
  
  • MEN 1 (30-70% enteropancreatic)
• Other pancreatic origin types
  
  • Acinar cell
  • Adenosquamous
  • Anaplastic
  • Cystadenocarcinoma
  • Pancreaticoblastoma
  • Small cell
• Metastasis to pancreas
• Pathophysiology:
  
  • 3 pathways
    
    • 1. Stepwise progression from pancreatic ductal intraepithelial neoplasm through to pancreatic cancer
         * PanIN type 1a: columnar & mucin producing ductal epithelium
         * PanIN type 1b – papillary architecture
         
         • KRAS
           * PanIN type 2: nuclear atypia
         • Tumour suppressor genes P53, p16 and CDKN2A
         • Results in increasing accululation of genetic mutations
           * PanIN type 3 – (carcinoma in-situ) marked cytological atypia and loss of polarity
    • 2. Conversion of IPMN into cancer
    • 3. Conversion of mucinous cystic adenoma into cancer
  • Common genes affected
    
    • KRAS
      
      • Proto-oncogene
      • GTP-binding molecule that results in activation of downstream pathways (such as the MAPK pathway) that increase tyrosine kinase activity
    • CDKN2A
      
      • Tumour suppressor gene normally encodes for p16-INK4a to inhibit cell cycle progression
    • SMAD4
      
      • Mediates TGF-β signal transduction which negatively regulates ECM and epithelial cell growth
    • TP53
      
      • Suppression of the p53 protein which is integral to arresting damaged cell cycle progression, apoptosis and cellular senescence
  • Most commonly presents with symptoms of local complications or metastatic disease (50%)
  • Local complications include:
    
    • Biliary obstruction à jaundice and steatorrhea
    • Invasion of local vessels (superior mesenteric or portal vein) and surrounding organs (stomach and colon)
  • Metastasis
    
    • Regional lymph nodes
    • Liver is the most common site of metastasis (60%)
    • Lung and peritoneum metastasis (around 30%)
    • Bone and adrenal (10%)

Question 28

Work up pancreatic mass

Answer 28

History

• Differentials
  
  • Metastatic disease
    
    • RRC
    • Melanoma
  • Pseudopapillary neoplasm
  • Focal chronic pancreatitis
  • IgG4 focal pancreatitis
  • Lymphoma
• Asymptomatic
  
  • Incidental/surveillance
  • No screening?
• Symptomatic
  
  • Weight loss, fatigue, night sweats
  • Pain, epigastric/back
  • GOO – nausea, vomiting
  • Painless jaundice
  • Pruritis
  • GI bleeding
  • New onset diabetes (15% new diabetes in 6 months prior)
  • Pancreatitis
  • Paraneoplastic

Physical examination

• Cachexia
• Jaundice
• Palpable hepatomegly in metastasis
• Epigastric mass
• Palpate distended gallbladder (Couvisers sign)
• Virchows node (L supraclavicular)
• Periumbilical lymph adenopathy (St mary joseph nodule)
• Peritoneal disease with perirectal deposits (palpable blummers shelf on DRE)
• Ascites

Bloods

• Ca 19-9 [carbohydrate antigen] (prognostic, monitoring response biomarker)
  
  • Elevated with biliary obstruction – check after decompressed
  • Normal in 10% of cancer (lack lewis antigen to make the enzyme)
  • Levels (in the absence of jaundice)
    
    • ~ < 100-200 may be curative
    • >500 is bad
    • >1000 is significant
• HbA1c
• LFTs
• Coags
• IgG4 if autoimmune pancreatitis suspected

Imaging

• Stage the primary cancer and stage the patient
• CT
  
  • Pancreatic protocol
    
    • Triple phase (precontrast, early & late arterial, portal venous)
      
      • Early arterial: high resolution of arterial structures
      • Late arterial: adenocarcinoma hypodense to pancreas
      • PV: cancer becomes isodense
    • 1mm thin slices
    • Chest, abdomen and pelvis
  • Findings of cancer
    
    • Ill-defined hypoattenuating mass within the pancreas, although smaller lesions may be isoattenuating, making their identification difficult, particularly on non contrast CT
    • Non enhancing lesion, isodense on delayed imaging
    • Surrounding desmoplastic reaction
    • Secondary signs of a pancreatic cancer
      
      • Parenchymal atrophy
      • Contour abnormalities
      • Pancreatic duct cut off
      • Dilatation of the pancreatic duct &/or common bile duct (double duct)
      • “double duct sign” is present in approximately 62 to 77 percent of cases of pancreatic cancer, but is not diagnostic for a pancreatic head malignancy Approximately 50 percent of ampullary carcinomas have a double duct sign and it can also occasionally be seen with benign adenomas and autoimmune pancreatitis
  • Relationship to:
    
    • Arteries
      
      • SMA
      • Coeliac axis
      • Hepatic
    • Veins
      
      • SMV
      • Portal vein
      • Portal vein confluence
    • Lymph nodes
    • Surrounding structures
  • Anatomical variation
  • Distant metastatic disease
• MRI pancreas
  
  • Not funded in Australia
  • Hypointense on gadolinium-enhanced T1-weighted images in the pancreatic and venous phases. Because it is hypo vascular with abundant fibrous stroma compared to the pancreatic parenchyma. Tumours appear isointense on delayed imaging
  • Better detection of subcentremetre metastasis
• PET
  
  • Not funded in ANZ but still used selectively
  • Recommended in NCCN for high risk patients
  • Recommended in NICE guidelines
  • 75% of pancreatic cancers are FDG avid
  • Can change management in 10-15% of cases – occult metastatic disease
• Endoscopic US
  
  • Assessment of local invasion
  • For tissue biopsy (is better than percutaneous)
    
    • If indeterminate or if neoadjuvant
    • High sensitivity/specificity ,especially with additional molecular genetic analysis (KRAS, p53)
    • FNA more likely to have false negative
    • Unlikely to cause tumour seeding as performed via duodenum that will be resected

Other

• ERCP +/- stenting
  
  • Indication
    
    • Cholangitis
    • Itch
    • Coagulopathy
    • Jaundice prior to neoadjuvant
• NEJM 2010
• Staging laparoscopy
  
  • Performed selectively
    
    • High Ca 19-9 (>1000) (or not <150?)
    • Suspicious radiology
      
      • Ascites
      • Indeterminate peritoneal or hepatic lesions
      • Suspicious lymph nodes
    • Large tumours
  • Purpose
    
    • Small volume metastatic disease
  • Changed management in 20% of patients (avoiding non curative laparotomy)
  • Can be combined with intraoperative USS for vascular invasion
  • Can convert to a laparoscopic palliative bypass (gastrojejunostomy)
  • Steps in diagnostic lap
    
    • Small volume peritoneal and liver metastasis
    • Frozen section of suspected lesions
    • Peritoneal surfaces
    • Liver systemically (can see all except seg 7)
    • Hepatoduodenal ligament (for nodal disease)
    • Lesser sac opened (via gastrocolic omentum)
    • ?Cytology - ?no evidence

Question 29

Management of pancreatic adenocarcinoma

Answer 29

• Multimodality approach
• Treatment depends on clinical stage of disease (resectable, borderline resectable, locally advanced or metastatic) Borderline = no fat plane around vessels, abutment of arteries or involvement of the veins that is reconstructable
• Depends on patient, oncological and anatomical factors
  
  • Patient factors
    
    • Fitness, other comorbidities
    • Preference/consent
  • Oncological
    
    • Presence of metastatic disease and regional lymphadenopathy
    • Ca 19-9 levels (cut off variable)
  • Anatomical
    
    • Invasion of surrounding structures
      
      • Resectable
        
        • Stomach, colon, kidney
    • Classified; resectable, borderline resectable, locally advanced
    • Resectability (brief overview – it is more complicated than this)
      
      • Want 1mm R0 margin
      • NCCN
        
        • No distant metastasis inclusive of regional lymph nodes or any contact with local arteries and/or aortic or venous drainage that cannot be reconstructed or anastomosed surgically
        • Arterial (CA, CHA, SMA)* only some centres will do arterial reconstruction and unclear benefit
          
          • Resectable
            
            • No arterial contact
          • Borderline
            
            • <180 degree contact
          • Advanced*
            
            • >180 degree contact
        • Venous (PV or SMV)
          
          • Resectable
            
            • <180 degree with no contour irregularity or thrombosis
          • Borderline
            
            • >180 degree contact
            • <180 degree contact with contour irregularity or thrombosis
            • Must have reconstruction option proximal and distal
            • IVC contact
          • Advanced
            
            • Unreconstructable due to tumour or thrombosis involvement

(DP-CAR need to preserve hepatic blood flow through collaterals from SMA)

• Preoperative ERCP & stent
  
  • Purpose
    
    • Decompression
    • Cytology brushings
  • Indications
    
    • Bilirubin >100-150
    • Cholangitis
    • Itch
    • Neoadjuvant
    • Palliative
  • Alternative is PTC or surgical decompression
  • Risks
    
    • Perioperative infection
      
      • Cholangitis
      • Fistula
      • Wound infection
    • Procedural risks (perforation, pancreatitis, bleeding etc)
• Systemic treatment
  
  • Cytotoxic chemotherapy
    
    • Neoadjuvant chemotherapy
      
      • Indications
        
        • Borderline resectability – clear indication
        • ?Instead of upfront surgery in resectable patients
      • Theory of neoadjuvant
        
        • Treat early micrometastatic disease
        • Downstage disease
        • Help select patients that will have favourable outcome with surgery
        • Select out the chemosensitive disease
        • Well vascularised tissues prior to ischaemia induced by surgery, thus can get to target
        • Can measure response to treatment
        • Avoid risk of not being about to receive adjuvant due to surgical complications
      • Risks
        
        • Not strong evidence for this in resectable disease but improved overall survival in borderline
        • 10% will progress and become unresectable, maybe this just saved them the morbidity of the surgery
        • Need tissue biopsy prior
        • Need biliary drainage
    • Adjuvant
      
      • Indications
        
        • All resected disease CONKO1 trial
    • Protocols
      
      • FOL-F-IRIN-OX
        
        • Agents
          
          • Folininic acid (leucovorin) FOL
          • Fluouracil
          • Irinotecan
          • Oxaliplatin
        • 4 months if tolerated
        • Restage after treatment
          
          • Ca 19-9
          • CT pancreatic protocol
      • Gemcitabine (better tolerated but less response)
      • Capecitabine + gemcitabine
      • Gemcitabine + nab-paclitaxcel (abraxane)
  • Molecular targeted therapy (US only)
    
    • Pembrolizumab (immune checkpoint inhibitor)
      
      • Indication
        
        • Metastatic disease MSI-H
    • Olaparib (PARP inhibitor)
      
      • Indication
        
        • Metastatic disease BRCA 1/2
• Radiotherapy
  
  • Indications
    
    • Neoadjuvant/adjuvant/palliative
      
      • Borderline or locally advanced disease (neoadjuvant MD Anderson 20-40% may progress to R0 resection)
      • No metastatic disease
      • Considered for local control in R1-R2 resection
      • Symptomatic control (pain/weight/overall function/bleeding)
  • Protocol
    
    • Concurrent fluorouracil or gemcitabine
• Surgery
  
  • Type of procedure
    
    • Head/uncinate/neck (to the right/overlying SMV)
      
      • Whipples (pancreaticoduodenectomy)
        
        • 15-20% 5 year survival (6% in NSW)
        • 30% 5 year survival in node negative disease
    • Body/tail (left of the SMV)
      
      • Distal pancreatectomy
  • Regional lymph node dissection
    
    • 15 LNs should be removed
    • LNs removed
      
      • Pancreatic head
      • Porta hepatis
      • GDA
      • Common hepatic artery
      • SMA
    • No survival benefit, but important prognostic information
      
      • 80% will have positive lymph nodes
  • Morbidity/complication
    
    • General or specific
    • Specific to whipples (below)
    • Pancreatic leak/fistula (5-10% of patients B/C)
      
      • Risk factors:
        
        • Soft pancreas
        • Narrow pancreatic duct
        • Significant blood loss
        • Obesity
        • Jaundice
        • No difference in number of layers, stent, duct to mucosa
      • Diagnosis
        
        • 3x upper limit of serum amylase after day 3 post op
        • Can lead to sepsis and bleeding, increased mortality and LOS
      • Classification ISGPF 2016
        
        • A: biochemical only (not clinically relevant)
        • B: Requires an intervention
        • C: Requires an operation, organ failure, death
      • Management
        
        • 90% closure within 4 weeks
        • TPN and octreotide
        • May require percutaneous drain or return to theatre
    • Bleeding/pseudoaneurysm
      
      • Risk factors
        
        • Pancreatic leak
      • Classification
        
        • Time of onset
          
          • Early <24 hours
          • Late >24 hours
      • Management
        
        • Early
          
          • Return to OT
        • Late
          
          • Angioembolisation or endoscopic control
    • Bile leak
      
      • Risk factors
      • Diagnosis
        
        • Bile in drain
      • Management
        
        • Leave drain in
    • Delayed gastric emptying (~20%)
      
      • Risk factors
        
        • Prior abdominal surgery
        • Cholangitis
        • Diabetes
        • Intraabdominal collection
        • (Pylorus preserving no difference in Cochrane review)
        • (Antecolic vs retro colic no difference in Cochrane review)
      • Diagnosis
        
        • Functional gastroparesis after exclusion of mechanical obstruction by UGI contrast series and endoscopy
        • CT to exclude collection
      • Management
        
        • Supportive care
        • NGT
        • Prokinetics
    • Gastric dumping
      
      • Risk factors
      • Diagnosis
      • Management
    • Diabetes
      
      • Risk factors
        
        • HbA1c >5.4 (3xRR)
      • Diagnosis
      • Management
    • Exocrine dysfunction
      
      • Risk factors
      • Diagnosis
      • Management
    • Chronic pancreatitis
      
      • Risk factors
      • Diagnosis
      • Management
    • Mortality
      
      • 1-2%

Consider that surgical gastrojejunostomy may be more definitive than an endoscopic stent if they are receiving chemotherapy for palliative patients

Question 30

Pancreatic leak/fistula

Answer 30

• Pancreatic leak/fistula (5-10% of patients B/C)
  
  • Risk factors:
    
    • Soft pancreas
    • Narrow pancreatic duct
    • Significant blood loss
    • Obesity
    • Jaundice
    • No difference in number of layers, stent, duct to mucosa
  • Diagnosis
    
    • 3x upper limit of serum amylase after day 3 post op
    • Can lead to sepsis and bleeding, increased mortality and LOS
  • Classification ISGPF 2016
    
    • A: biochemical only (not clinically relevant)
    • B: Requires an intervention
    • C: Requires an operation, organ failure, death
  • Management
    
    • 90% closure within 4 weeks
    • TPN and octreotide
    • May require percutaneous drain or return to theatre

Question 31

TNM Pancreatic adenocarcinoma

Answer 31

T

• Tis: high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and mucinous cystic neoplasm with high-grade dysplasia.
• T1 <2cm
• T2 2-4cm
• T3 >4cm
• T4 involving CHA, Coeliac or SMA

N

• N0
• N1 1-3
• N2 4 or more

M

• M0
• M1 distant metastasis
• Stage
  
  • 1a: T1
  • 1b: T2
  • 2a: T3 (+4cm)
  • 2b: N1 (nodes)
  • 3: N2 or T4
  • 4: Metastatic disease
• 7 out of 10 patients do not receive any time of active treatment, 1 in 10 will have potentially curative surgery
• Majority present at late stage – unresectable – 5 year survival 7%
• Resectable disease (<20% of patients)
  
  • Overall, median survival 12-24 months, 10-25% 5 year overall survival
  • R0 resection with >1mm margin – median 35 months
  • R0 resection with <1mm margin – median 16 months
  • R1 resection – median 14 months
• Metastatic disease
  
  • 6 months median without treatment
  • 11 months median with treatment

Question 32

Pancreatic cystic lesion

Answer 32

Pancreatic Cystic lesions - OVERVIEW

• General
  
  • Mostly incidental and asymptomatic
  • Risk of malignant potential
  • 2.5% of abdominal CT will have a pancreatic cyst
• Classification:
  
  • 1. Inflammatory vs non inflammatory
       * ( i.e. is it related to pancreatitis pseudocyst, ANC etc)
       
       • Inflammatory = pseudocyst
  • 2. Non inflammatory further divided into neoplastic & non-neoplastic
       * Non-neoplastic = true cysts
• 3.Neoplastic further divided into mucinous, non-mucinous and other
  
  • Non mucinous
    
    • Serous cystadenoma
    • Solid pseudopapillary
  • Mucinous
    
    • Mucinous cystic neoplasm
    • Intraductal Papillary Mucinous Neoplasm(MD or BD)
  • Other
    
    • Neuroendocrine (usually solid but can be cystic)
    • Cystic degeneration of pancreatic adenocarcinoma
• Patient demographic (age & gender)
• Bloods
  
  • Serum Ca 19.9, lipase, LFTs
• Macroscopic appearance on imaging
  
  • MR is best for delineation of the ducts and fluid components
• EUS findings important in indeterminate or suspicious lesion
  
  • Fluid CEA
  • Cytology
  • Amylase
  • KRAS molecular testing

Name

Pathology

Population

Malignant

Imaging

EUSfluid

Management

Pseudocyst

No epithelial lining, disrupted PD

Anyone

Most common cystic lesion

High lipase

+4cm or symptomatic drain

Solid pseudopapillary neoplasm (SPN)

Rare

Rare communication with duct

Daughter 20-40 y.o

F 80%

Potentially

15% cancer

Anywhere, large mixed cystic solid, heterogenous

Low CEA, lipase.

Positive for periodic acid schiff

Resect

Serous cystoadenoma (SCN)

Rare communication with duct

VHL associated

75% F

60-70 y.o

Grandma

Benign

.2% malignant

Lobulated

Microcytic Honeycomb

Central Ca2+ scar 18%

Anywhere

D/C if incidental

Mucinous cystic neoplasm (MCN)

No/occasional

communication with duct

Ovarian type stroma

99%

40-60 y.o

Mother

Potentially

10-17%

Macrocystic

Peripheral Ca2+ 25%

95% in tail/body

CEA>192 or mucin

+4cm, mural nodule or Symptomatic (Euro 2018 guidelines)

Intraductal papillary mucinous neoplasm (IPMN)

Mucin producing epithelial tumour

In communication with duct, MD or BD or mixed

M>F

60-80 y.o

STK11, FAP, Hx of pancreatitis

Potentially

Mainly head

CEA>192 or mucin

Cystic PNEN

Usually non functional

Less likely to metastasis

MEN1

NETs larger is cystic and smaller if solid

Potentially

Cystic degeneration

RCC, adenocarcinoma

Yes

Question 33

IPMN

Answer 33

• Definition:
  
  • Mucin producing epithelial neoplasm of the pancreas that have a papillary architecture
  • Absence of ovarian type stroma
• Incidence/epidemiology:
  
  • 2:100,000
  • Roughly equal
• Aetiology & risk factors:
  
  • Cigarette smoking
  • Diabetes
  • Family history of pancreatic adenocarcinoma
  • Peutz-Jegher syndrome (STK 11 gene, hamartomas, autosomal dominant)
  • FAP (APC gene, tumour suppressor, multiple polyps, autosomal dominant)
  • Previous pancreatitis
  • Colon, breast and prostate cancer association
• Pathophysiology:
  
  • Premalignant lesion of pancreatic adenocarcinoma (adenoma – dysplasia – carcinoma sequence)
  • A cause of obstructive pancreatitis
  • The mucin content of IPMN is frequently highly viscous and therefore likely to be retained in the duct system, causing dilation. Patients with IPMN can present with repeated episodes of acute pancreatitis, presumably triggered by intermittent duct obstruction caused by mucus plugs.
  • MD IPMN 50-60% malignant
  • BD IPMN 20-30% malignant
• Clinical manifestations:
• Macroscopic features:
  
  • Subtypes
    
    • Branch duct
    • Mixed
    • Main duct
  • Fish eye side – mucin coming from the ampulla
• Microscopic​
  
  • Absence of ovarian type stroma
• Investigations:
  
  • EUS
    
    • Cyst fluid CEA >200ng/ml consistent with mucinous neoplasm
    • Mucin containing columnar cells of varying atypia
  • MR
    
    • Fukuoka guidelines
    • High risk stigmata à resect
      
      • Obstructive jaundice (if a HOP lesion)
      • Enhancing solid component/nodule (+5mm within cyst)
      • Main PD +10mm
    • Worrisome stigmata à EUS imaging and aspiration/cytology à consider resection
      
      • Enhancing mural nodule <5mm size
      • Main PD 5-9mm
      • Abrupt change in PD calibre with distal pancreatic atrophy
      • Pancreatitis clinically
      • +3cm cyst size or 5mm growth over 2 years
      • Thickened enhancing cyst walls
      • Lymphadenopathy
      • Serum Ca 19.9
    • If no worrying stigamata then consider the largest cyst size
      
      • <1cm
      • 1-2cm
      • 2-3cm
      • >3cm
      • Alternating EUS and MRI every 3 months…. Consider surgery in young fit

Standard oncological resection, whipples/distal/total depending on location

Question 34

SPN pancreas

Answer 34

Solid Pseudopapillary Neoplasm (SPN)

• Definition:
  
  • Mixed solid and cystic lesion
• Incidence/epidemiology:
  
  • Rare <2% of pancreatic cystic tumours
  • Young women
  • Non white
  • 20-30’s
  • The Daughter tumour
• Aetiology & risk factors:
• Pathophysiology:
  
  • 15% malignant, 75% benign
  • Associated with a B-catenin mutation
• Clinical manifestations:
  
  • 80 percent of patients with SPNs were symptomatic
  • Incidental detection of SPNs 50%
  • Symptoms
    
    • Abdominal pain, followed by nausea, vomiting, and weight loss
    • Other symptoms that occur less frequently include gastrointestinal obstruction, anemia, jaundice, and pancreatitis. Patients may also have a palpable mass, which is the most common presentation in children.
• Macroscopic features:
  
  • Usually large – 8cm
  • Capsule
  • Usually pancreatic tail

• Microscopic features:
  
  • EUS-FNA cytologic
    
    • Branching papillae with myxoid stroma
    • Cytology is diagnostic in 75 percent of cases
    • Special stains
      
      • Vimentin,
      • CD10,
      • beta-catenin,
      • may be required to differentiate an SPN from a pancreatic neuroendocrine tumor (eg, insulinoma)
  • Histology
    
    • Solid nests of poorly cohesive cells forming a cuff surrounding blood vessels, resulting in a pseudopapillary architecture
    • Stroma usually shows various degrees of hyalinization or evidence of degeneration such as hemorrhage, foamy macrophages, calcification and cholesterol clefts
    • Tumor cells usually have a moderate amount of eosinophilic cytoplasm with large intracytoplasmic hyaline globules and perinuclear vacuoles
    • Relatively uniform nuclei with finely textured chromatin, inconspicuous nucleoli and characteristic longitudinal grooves
    • Oncocytic or clear cell changes may occur
    • Rare mitotic figures
    • Although grossly well circumscribed, microscopic finding of infiltration to the surrounding pancreatic tissue is not uncommon
• Investigations:
  
  • CT
• EUS
  
  • Well-demarcated
  • Echo-poor but solid-appearing mass, (can also appear as a mixed solid and cystic lesion or a purely cystic lesion)
  • Irregular calcifications are present in up to 20 percent of cases
• MRI
  
  • Well-demarcated solid tumors
  • MRI
    
    • Lower SI T1
    • High SI on T2-
    • Early heterogeneous and progressive enhancement on MRI compared with adenocarcinomas and endocrine tumor
• Treatment:
  
  • Non operative
  • Operative
    
    • Resect
• Prognosis:
  
  • Favourable prognosis if resected

Question 35

MCN

Answer 35

• Definition:
  
  • Mucinous cystadenoma is another name
  • Neoplasm that have malignant potential
• Incidence/epidemiology:
  
  • Occurs in the Mother (as opposed to the grandmother SCN)
  • 1/3 of the cystic lesions of the pancreas
• Aetiology & risk factors:
• Pathophysiology:
  
  • DO NOT communicate with the ducts
  • 15% risk of malignancy overall
• Clinical manifestations:
  
  • Female predominance 99%
• Macroscopic features:
  
  • Can be very large
  • More common in the body/tail

• Microscopic features:
  
  • Columnar epithelium and presence of ovarian like stroma (distinguishes from IPMN) which stain positive for ER/PR
• Investigations:
  
  • CT
    
    • Well circumscribed lesion
    • Peripheral calcification “eggshell sign”

( Large multilocular cysitc lesion arises from the pancreatic tail and shows multiple cystic areas with enhanced septae, contents of variable density and foci of calcification within the wall. It displaces the surrounding bowel loops)

• Treatment:
  
  • Non operative
    
    • <3cm and no mural nodule can be observed
  • Operative
    
    • MCN ≥40mm should undergo surgical resection. Resection is also recommended for MCN which are symptomatic or have risk factors (ie, mural nodule) irrespective of their size (European 2018 guidelines)
• Prognosis:
  
  • Does undergo malignant transformation
  • If invasive 5 year survival 26% vs non invasive 100% 5 year

Question 36

SCN

Answer 36

Serous cystadenoma neoplasm (SCN)

• Definition:
  
  • Benign
• Incidence/epidemiology:
  
  • These happen in the grandmother 7^th decade female
  • About a 25% of pancreatic cystic lesions
• Aetiology & risk factors:
  
  • Associated with von Hippel-Lindau tumor suppressor gene on chromosome 3p25.3) ?polycystic kidney disease
• Pathophysiology:
  
  • Doesn’t usually cause obstructive or compressive symptoms
• Clinical manifestations:
  
  • Asympatomatic
• Macroscopic features:

• Multiple microcysts (6+, smaller than 2cm) with central calcification
• The solid type can confuse people for neuroendocrine tumour
• Most common in the head
• Microcytic type most common

• Microscopic features:
• Investigations:
  
  • EUS
• Treatment:
  
  • Non operative
    
    • Conservative approach
  • Operative
    
    • Resect rarely
• Prognosis:
  
  • 0.2% malignant change (vs 1.5% death from whipples)

Question 37

Cystic neuroendocrine tumour of the pancreas

Answer 37

• Definition:
• Incidence/epidemiology:
  
  • Pancreatic neuroendocrine tumours ~5% of pancreatic malignancies
  • 10% of PNEN are cystic i.e. 0.5% of pancreatic malignancies (rare)
• Aetiology & risk factors:
• Pathophysiology:
  
  • Not clear why cystic
• Clinical manifestations:
  
  • Less likely functional (than solid PNEN)
• Macroscopic features:
  
  • More common in body or tail
• Microscopic features:
• Investigations:
  
  • Difficult to assess even via EUS
  • CT
    
    • Hypervascular or hyperdense lesion
    • Can also appear cystic or contain calcifications.
    • The presence of a large incidental mass within the pancreas, particularly without vascular encasement or desmoplastic reaction, should also alert the clinician to the possibility of a PNET
  • MRI
  • Low signal intensity on T1-weighted images and they are particularly well seen on fat-suppressed (T1- and T2-weighted) images
• Treatment:
  
  • Non operative
    
    • Observation for cystic PNEN if under 2cm
  • Operative
• Prognosis:
  
  • Less aggressive than solid PNEN

Question 38

Describe Whipples procedure

Answer 38

• Goals:
  
  • Pancreaticoduodenectomy can be described in 3 phases, being assessment for metastatic or irresectable disease, oncological resection and reconstruction
  • The resection includes the head & neck of the pancreas with en-bloc resection of the duodenum and bile duct, with the R0 margin and removal of 15 regional lymph nodes
  • The reconstruction typically includes
    
    • Pancreatojejunostomy
    • Hepaticojejunostomy
    • Gastrojejunostomy
• Indications
  
  • Neoplasm
    
    • Malignant or suspected malignancy
      
      • Ampulla
      • Distal CBD
      • HOP
      • Duodenum
    • Benign
      
      • Trauma (combined duodenal/pancreatic injury)
      • Inflammation (chronic pancreatitis)
• Investigations:
  
  • CT C/A/P and pancreatic protocol (minimum)
• Preparation:
  
  • Vitamin K if jaundiced
  • GA/ETT
  • NGT
  • IDUC
  • Thromboprophylaxis
  • Cephazolin
• Steps:
  
  • Access
    
    • +/- diagnostic laparoscopy
    • Bilateral subcostal incision
    • Retractor ?Omnitract
  • Abdominal exploration (assess curability)
    
    • Peritoneal cavity
    • Mesocolon
    • DJ flexure/root of mesentery and proximal jejunum
    • Liver
    • Hepatoduodenal ligament
  • Resection
    
    • Mobilisation of the duodenum and HOP to the aorta (assess resectability)
      
      • R colon mobilised
      • Kocher incision
        
        • Use finger to develop plane between posterior pancreas and IVC/R kidney
        • Identify IVC & L renal vein
        • Aorta and IMA
      • Some resect the aortocaval nodes
    • Expose root of SMV
      
      • Reflect back the greater omentum off the transverse colon and mesocolon entering the lesser sac or
      • The lesser sac is entered through the gastrocolic ligament staying below the gastroepiploic arcade and the transverse mesocolon is separated from the bare area of the duodenum and pancreatic head
      • The middle colic vein is traced down to its union with the right gastroepiploic vein, which classically forms a common trunk (i.e., gastrocolic trunk or trunk of Henle) draining into the SMV. The gastroepiploic vein is ligated and anterior exposure of the SMV is obtained.
    • Porta hepatitis dissected out
      
      • En bloc cholecystectomy and CA divided
        
        • [Beware of abberant/replaced/low bifurcation of R hepatic artery]
      • GDA identified - patency of hepatic arteries confirmed when GDA clamped
        
        • [Some patients with celiac stenosis become reliant on retrograde flow from the GDA to supply the liver, therefore ligating the GDA in these patients can be catastrophic. Celiac stenosis identified from preoperative imaging should be addressed prior to proceeding with the PD.]
      • GDA ligated, clipped and divided
        
        • Portal vein lies deep to hepatic artery
      • Hepatic duct divided above the CD
    • Retropancreatic tunnel completed and looped with umbilical tape
    • Division of the proximal duodenum or antrum
    • Mobilisation and transection of jejunum
      
      • 40cm from DJ flexure divide with stapler
      • Dissect off the mesentery along the bowel wall
      • Proximal jejunum and mesentery passed back under the ligament of Treitz/SMV to the right side
    • Transection of pancreatic neck
      
      • Ligation of the marginal pancreatic vessels for haemostasis
      • Neck divided over the SMV
      • Uncinate process dissected off the SMV
      • Specimen sent for frozen section
  • Reconstruction
    
    • Pancreaticojejunostomy
      
      • 2 layered, duct to mucosa anastomosis of 5mm duct in a soft pancreas. 3/0 maxon continuous for capsule, 6/0 interrupted for duct.
    • Hepatojejunostomy:
      
      • End to side, single layered continuous with 4/0 PDS. White gauze test negative.
    • Duodenojejunostomy:
      
      • End to side, single layered, continuous with 3/0 Maxon
  • Closure
    
    • 15Fr blakes drains along anastomosis
• Pitfalls:
• Bail out options:
• Post op care & Follow up:

Question 39

Buzz words for liver lesions on radiology

Answer 39

• Caroli disease = central dot sign
• Hydatid cyst = Gharbi classification
• Haemangioma = bright dot sign (T2), centripetal filling in
• FNH = central scar, centrifugal filling/bike spokes, retains HSC
• Adenoma = doesnt retain HSC
• HCC = washout, LIRADS
• Mets = holes in liver on HSC

Question 40

Descibe the liver

Answer 40

• Gland in the RUQ
  
  • Divisions
  • Peritoneum
  • Ligaments
  • Capital H of the visceral surface
• Divisions
  
  • Divided into left & right anatomical lobes by the falciform ligament
  • Divided into left & right functional lobes by Cantlies line (GB to IVC, mid cystic plate, middle hepatic vein)
  • Divided in the sagital plane by the three hepatic veins into sectors (quaters)
  • Divided in the axial/transverse plane at the level of the primary portal division into Couinauds segments
  • Named 1-8 each of the segments is independent and has its own vascular inflow, outflow, and biliary drainage
  • Segment 1 is the caudate lobes and segment 4 is divided into 4A/4B
• Invested in peritoneum, except
  
  • The posterior surface (the bare area),
  • The GB bed
  • The porta hepatis
• The peritoneum reflected on the surface of the liver – called ligaments
  
  • Falciform ligament
    
    • Attaches the anterior liver to the anterior abdominal wall
    • Contains ligamentum teres (left umbilical vein) in its free edge
  • Coronary ligament with its anterior and posterior leafs
    
    • Borders the bare area of the liver
    • Close proximity to the hepatic veins and IVC
  • Left and right triangular ligaments
    
    • Formed by the junction of the anterior and posterior leaves of the coronary ligament
  • Capital H shape arrangement when looking at the posterior surface of the liver
    
    • R lateral vertical component
      
      • IVC posteriorly
      • GB anteriorly
      • Separated by the caudate process
    • Medial vertical component
      
      • Fissure for ligamentum teres anteriorly wraps around like giant C
      • Fissure for ligamentum venosum posteriorly, medial border of caudate lobe and attaches to the lesser omentum
    • Horizontal cross beam is the transverse fissure/portal hepatis

Question 41

Liver embryology

Answer 41

• Key words:
  
  • 4-12 weeks
  • Ventral diverticulum
  • Hepatic bud
  • Septum transversum
  • Ventral mesogastrium
  • Vitelline veins
• The hepatic diverticulum grows into the septum transversum from the ventral aspect of the distal foregut
• The cranial portion of the septum transverum forms the pericardium & diaphragm, the caudal portion forms the ventral mesogastrium which is later the falciform ligament, liver capsule and lesser omentum, also the endothelial cells/Kuppfer cells of the sinusoids
• Liver grows as a proliferation of endodermal cells called the hepatic bud from the diverticulum into the ventral mesogastrium of the foregut, the hepatoblasts anastomose around the vitelline veins breaking the continuity of these veins resulting in sinusoids
• The hepatoblasts form the hepatocytes and biliary epithelial cells
• The original diverticulum from the endoderm of the foregut becomes the bile duct; its Y-shaped bifurcation produces the right and left hepatic ducts. A blind diverticulum from the bile duct becomes the cystic duct and gallbladder. The hepatic ducts divide and redivide to become the interlobular and intralobular bile ductules.
• Although the hepatic diverticulum arose initially from the ventral aspect of the foregut, growth and rotation of the duodenum causes the entrance of the bile duct and the developing ventral pancreas both to become dorsally placed, entering the posterior wall of the duodenum, and lying within the dorsal mesentery
• Circulation
  
  • The vitelline veins:
    
    • Carry blood from the yolk sac to sinus venosus.
    • Form a plexus around the future duodenal portion of the foregut.
    • Fuse to form the SMV, portal and splenic veins.
  • The L umbilical vein → Drains into the hepatocardiac channel bypassing the hepatic sinusoids via ductus venosus (eventually becoming the ligamentum venosum) LUV->L portal V->Ductus venosus -> L hepatic V
  • The R umbilical vein → ?obliterates

Question 42

Which segments are resected in each type of hepatectomy?

Answer 42

• (left) lateral sectionectomy - s2+3
• (right) posterior sectionectomy - s6+7
• left hepatectomy - s2+3+4
• right hepatectomy - s5+6+7+8
• extended left hepatectomy - s2+3+4+5+8
• extended right hepatectomy - s5+6+7+8+4

Question 43

What is the transpyloric plane and what structures lie on it?

Answer 43

Imaginary axial plane located

• Midway between the jugular notch and superior border of pubic symphysis
• At approximately the level of L1 vertebral body

Pylorus of the stomach

D1 part of the duodenum

Duodeno-jejunal flexure

Root of the transverse mesocolon

Hepatic flexure of the colon

Splenic flexure of the colon

Fundus of the gallbladder

Neck of the pancreas

Hila of the kidneys

Hilum of the spleen

Ninth costal cartilage

End of spinal cord and superior portion of conus medullaris

Origin of superior mesenteric artery

Splenic vein joins superior mesenteric vein to form portal vein

Cisterna chyli

Question 44

What is the cambridge twist?

Answer 44

https://www.youtube.com/watch?v=tb7nRIipLOo

Question 45

Relationship to surrounding structures - bile duct

Answer 45

• Posterior
  
  • Supraduodenal – Portal Vein
  • Retroduodenal – IVC
  • Paraduodenal – R renal vein
• Anterior
  
  • Supraduodenal – R lobe liver in peritoneal cavity
  • Retroduodenal – D1 & pancreatic branches of the GDA
  • Paraduodenal – HOP
• Right
  
  • Supraduodenal – Free edge of lesser omentum
  • Retroduodenal – D1
  • Paraduodenal – HOP & D2 – Ampulla of Vater
• Left
  
  • Supraduodenal – hepatic artery
  • Retroduodenal – Portal vein and GDA
  • Paraduodenal – Pancreatic duct

Question 46

Give an overview of anatomical variants of bile duct drainage

Answer 46

• Hepatic duct confluence
  
  • Blumgart’s classification [A-F]
• Right posterior sectoral duct insertions
  
  • Hisatsugu classification [1-5]
• Subvesicle (gallbladder)/Luschka duct classification
  
  • Schnelldorfer et al J gastrosurg 2012 [1-4]
• Cyst duct variation
  
  • R posterior sectoral duct confluence with CD (Hisatsugu 1 & 5)
  • Angular (most common)
  • Spiral
  • Parallel

Important/dangerous biliary variations for cholecystectomy:

• Any accessory or aberrant hepatic duct (usually right posterior sectoral) that has..
  
  • Low insertion to CHD
  • Drains into the CD
  • Drains into the gallbladder
• Parallel cystic duct

All of the intrahepatic duct confluence variations are important for liver surgery, also note the common arrangement of Hjortsjo’s crook formed by the medial insertion of the right posterior/lateral sectoral duct into the right anterior/medial duct

Question 47

Sphincter of Oddi

Answer 47

• The muscle fibers of the sphincter of Oddi surround the intraduodenal segment of the common bile duct and the ampulla of Vater
• A circular aggregate of muscle fibers, known as the sphincter choledochus (or sphincter of Boyden), keeps resistance to bile flow high, and thereby permits filling of the gallbladder during fasting and prevents retrograde reflux of duodenal contents into the biliary tree
• A separate structure, called the sphincter pancreaticus, encircles the distal pancreatic duct.
• The muscle fibers of the sphincter pancreaticus are interlocked with those of the sphincter choledochus in a figure eight pattern.

Question 48

Ingredients in bile

Answer 48

• Water
• Electrolytes
• Bile salts
• Cholesterol
• Lecithin (phospholipids)
• Bilirubin

Question 49

Enterohepatic circulation of bile

Answer 49

• The major pigment of bile, is an end product of heme catabolism
• Travels to the liver bound to albumin
• Once inside the liver, the enzyme uridine diphosphate glucuronyltransferase (UDPGT) conjugates bilirubin to form bilirubin glucuronide.
• The water-soluble conjugated bilirubin is then secreted into bile, providing its characteristic yellow colour.

Question 50

5 functions of bile

Answer 50

• Aids in the digestion of fat via fat emulsification
• Absorption fat-soluble vitamins
• Excretion of bilirubin and excess cholesterol
• Provides an alkaline fluid in the duodenum to neutralize the acidic pH of the chyme that comes from the stomach
• It provides bactericidal activity against microorganisms present in the ingested food

Question 51

Explain how bile salts help fat absorption

Answer 51

Dietary lipids (mostly triglycerides), upon their entry into the small intestine, are emulsified by bile salt (also called bile acid) released from the gall bladder. Bile salt functions as a detergent (due to their OH and COOH groups), and large lipid molecules form smaller lipid droplets surrounded by a layer of bile. Emulsified lipids are acted upon by enzyme pancreatic lipase and converted into fatty acids, monoglycerides and glycerol.

The lipid digestion products are assembled into micelles. These are temporary combinations of bile salt, fatty acids, monoglycerides, and other fat-soluble substances such as vitamins and cholesterol. The micelles are water soluble and enable the lipid digestion products to be transported to the small intestinal surface for absorption. At the site of absorption, the micelle breaks down and the bile salt returns to the intestine for continuing emulsification processes (bile salt recycling). The components are absorbed into the small intestine by passive diffusion.

Question 52

Why use medium chain fatty acids in chyle leak?

Answer 52

Short and medium chain triglycerides are directly absorbed into the capillaries and to the liver via the portal vein, in contrast to larger long chain fatty acids which are transported by chylomicrons in the intestinal lacteals

Question 53

Describe enterohepatic circulation of bilirubin

Answer 53

Question 54

Variceal bleed

Answer 54

• CCrISP algorithm A-E approach with simultaneous assessment and resuscitation
  
  • Low threshold for intubation to protect the airway, high flow oxygen
  • Poor outcomes with over transfusion therefore transfuse if Hb<70, aim for up to 90
  • Coagulopathy from poor synthetic function and thrombocytopaenia from hypersplenism
  • Platelets when <50, FFP if INR >1.5, massive transfusion protocol
  • Investigations: FBC, Urea, Cr, Electrolytes, LFTs, Coag screen, Cross Match, Lactate, CXR and ECG
  • PPI given because it may not be a variceal cause of bleeding (1/3 of patients will have alternative cause of UGI bleed)
  • Antibiotics reduce incidence of rebleeding, bacteria infections and improve survival
  • Teripressin (vasopressin analogue) lowers portal pressures by splanchnic arteriolar vasoconstriction shifting of blood from splanchnic to systemic circulation – shown to reduce transfusion requirement

Question 55

Grade oesophageal varices

Answer 55

Grade 1-3

Small, collapse on insufflation with air

Moderate, don’t collapse on insufflation

Large, occluding lumen

Question 56

Varices oesophageal management

Answer 56

When do you consider giving non-selective beta blockers?

As secondary prophylaxis of rebleed in combination with EBL or

Primary prophylaxis in grade 2-3 or any with red colour signs

What are the endoscopic treatment options of oesophageal varices?

Variceal band ligation first line, start distal and work proximal, up to 6 bands in lower 8cm of oesophagus (2 bands on each varix 2cm apart, band the varix)

Others; sclerotherapy, glue, thrombin, haemospray (cant imagine that would be good), covered metal stent, balloon tamponade

Question 57

How to use balloon tamponade in variceal bleed

Answer 57

Sengstaken-Blakemore tube:

A 250ml gastric balloon, an oesophageal balloon, and a single gastric suction port

The Minnesota tube has 500ml gastric balloon, oesophageal balloon and suction ports for the oesophagus and the stomach

Check that the balloons inflate and don’t leak (can check under water)

Well lubricated

Patient is intubated

Insert orogastrically with laryngoscope and McGill’s forceps to 50cm

Suction the stomach

Inflate the gastric balloon with 50ml of air and obtain CXR to ensure below the diaphragm

Fill remaining 200ml air into balloon, soft clamp the port to prevent accidental leakage

Place under gentle traction, secure to 0.5-1L fluid bag over IV pole

Irrigate and aspirate the gastric port

If ongoing bleeding inflate the oesophageal balloon to 35mmHg

Can leave in place for 48hrs, need to periodically deflate oesophageal balloon 12 hourly

Monitor for pressure areas

Question 58

Portal hypertension diagnosis

Answer 58

Portal hypertension definition

Portal hypertension is a hepatic venous pressure gradient (HVPG) greater than 5mmHg

Complications of portal hypertension start to occur once the HPVG is >10 mmHg

Diagnosis

Pressure gradient = Wedged pressure – free pressure. The hepatic venous pressure gradient is measured invasively by cannulating the right hepatic vein and recording a free pressure, then inflating a balloon and recording a wedged hepatic pressure which represents the pressure at the level of the sinusoids. This method is not reliable in pre and post sinusoidal causes of portal hypertension.

Although HVPG is the gold standard it is invasive, non-invasive modalities can be used. A high Fibroscan reading of 25kPA or a moderate reading of 15-24 in combination with platelets <150 is indicative of portal hypertension (from cirrhosis) and those patients should be screened for varices with endoscopy.

USS:

• Enlarged portal vein: >13 mm
• Slow portal venous flow <15 cm/sec
• Reversal or hepatofugal portal venous flow
• Splenomegly
• Varices
• Ascites
• Aetiology i.e. cirrhotic liver, fatty liver, thrombosis etc

Aetiology

Classified anatomically

Presinusoidal , sinusoidal and post sinusoidal

These are further broken down into prehepatic, intrahepatic and post hepatic

In the developed world the cirrhotic causes are much more common mainly alcohol/viral/NAFLD(cryptogenic), in the developing world schistosomiasis and portal vein thrombosis are leading causes

Question 59

Pathophysiology of portal hypertension in cirrhosis

Answer 59

Portal hypertension develops when there is resistance to portal blood flow, and it is aggravated by increased portal blood flow

There are two components to the increased resistance, architectural/structural changes and functional/dynamic changes

Architectural changes occur when there is distortion of the liver microcirculation by fibrosis and nodules.

Functional changes occur when there is contraction of myo-fibroblasts that surround the sinusoids in fibrous bands and vascular smooth muscle cells of the hepatic vasculature. The dynamic changes are due to increased production of vasoconstrictors and reduced release of endothelial vasodilators.

As portal hypertension worsens, splanchnic blood flow is increased because of local release of nitric oxide, and other splanchnic vasodilators that cause splanchnic arteriolar vasodilation and angiogenesis. These changes also lead to systemic hypotension, vascular underfilling, stimulation of renin-angiotensin and sympathetic nervous systems, plasma volume expansion, and increased cardiac output and therefore increased portal inflow

Varices: Decompression of the increased pressure in the portal vein results in shunting of up to 90% of portal blood flow back to the heart through existing portosystemic collaterals. These veins enlarge and place tension across a thin wall predisposing them to rupture under pressure and continue to bleed due to coagulopathy.

Encephalopathy: results from shunting of absorbed ammonia from the gut into the systemic circulation

Ascites: from increased formation of splanchnic lymph, low albumin, salt and water retention from RAAS activation

SBP: the infection of that ascitic fluid due to a combination of immunocompromise and bacterial translocation from the gut

Hepatorenal syndrome: acute on chronic kidney injury from repeated bouts of sepsis and hypovoluaemia in the setting of chronic renal vasoconstriction

Question 60

Classification of gastric varices

Answer 60

Sarin classification

• GOV1:
  
  • Extending <5 cm from GOJ into stomach
  • Treated with EBL
• GOV2:
  
  • Extending from GOJ into fundus
• IGV1:
  
  • Isolated varices in gastric fundus
• IGV2:
  
  • Isolated non-fundic gastric varices
• GOV2 and IGV1-2 treated with Injection of cyanoacrylate or thrombin

All respond well TIPS

IGV 1 associated with splenic vein thrombosis, consider splenectomy or SAE

• The splenic artery remains intact and thus enables continued high pressure in the spleen, which forces an abnormal outlet through collaterals.
• Increased blood flow through the short gastric veins to the coronary vein or through the gastroepiploic vein to the pancreaticoduodenal vein creates a localized form of “left-sided” portal hypertension with dilatation of the submucosal veins within the stomach wall, producing the formation of gastric varices along the greater curvature and the fundus of the stomach.
• The oesophageal veins can usually drain through the patent coronary vein, so the development of associated oesophageal varices is prevented

Question 61

Liver (dys)functions

Answer 61

• Function and malfunction
  
  • Carbohydrate metabolism
    
    • Muscle (under anaerobic conditions) converts glucose to lactate
    • Liver converts lactate to glucose (Cori cycle) – providing glucose and preventing lactic acidosis
    • In liver failure, this process is impaired -> lactic acidosis and hypoglycaemia
  • Protein metabolism
    
    • Liver breaks down proteins and amino acids and clears nitrogen
    • GIT uses amino acids for fuel for enterocytes, this produces ammonia, this ammonia is usually detoxified by the liver into urea and excreted in the urine
    • In liver failure the ammonia builds up and causes hepatic encephalopathy
    • Hepatic encephalopathy is a reversible neuropsychiatric syndrome, characterised by cerebral oedema, raised ICP, risk of brain herniation and death – treatment is clearance of ammonia in GIT by giving lactulose to stop ammonia from getting into the portal and thus systemic circulation
  • Coagulation
    
    • Liver synthesises clotting factors, anticlotting factors, fibrinolytic proteins
    • In liver failure there is an increased risk of bleeding AND thrombosis
    • Bleeding: impaired bile salt excretion –> impaired vitamin K absorption –> vitamin K dependent factors (2, 7, 9, 10) are reduced
    • Thrombosis: Loss of protein C and S synthesis -> these anticoagulant factors are needed to prevent thrombosis. So despite high INR they may also have increased risk of clotting
    • Unable to remove circulating clotting and anticlotting factors
  • Immune function
    
    • Phagocytosis of bacteria by producing opsonins that facilitates this
    • Acute phase proteins such as CRP, which plays a role in inflammatory reaction to infections
    • Innate immune system as Kupffer cells that are part of the reticuloendothelial system of the body, loss of this function interrupts the innate immune response to infection
  • Medication metabolism
    
    • Opioids and benzodiazepines will have prolonged half life
  • Plasma Protein synthesis
    
    • Albumin
      
      • Regulating blood volume and distribution of fluids
      • Low albumin -> third spacing, oedema, ascites
  • Bile salts
    
    • Bilirubin used to make bile salts
    • In liver failure -> jaundice
  • Hyperdynamic circulation
    
    • Increased intrahepatic vascular resistance and portal hypertension  vasodilation of the splanchnic vascular system  reduction of effective arterial blood volume
    •  Compensatory cardiac output and neuroendocrine (RAS) mediators that leads to salt and fluid retention to increase plasma volume. In decompensation the increased cardiac output and plasma volume is inadequate, further activation of the RAS and increased vasoconstriction, sodium and water retention  ascites and renal failure due to decreased renal perfusion (hepatorenal syndrome develops)
  • Varices and portosystemic shunts

Question 62

Sites of portosystemic shunts

Answer 62

Question 63

Childs pugh score

Answer 63

• Childs Pugh
  
  • 5 factors (2 clinical and 3 biochemical)
  • 2 clinical
    
    • Ascites
      
      • 1: absent
      • 2: managed with medication
      • 3: refractory
    • Encephalopathy
      
      • Agitation, reverse sleep wake, lethargy, confusion/coma
      • 1: None
      • 2: grade 1-2 or supressed with medications
      • 3: 3+ or refractory
  • 3 biochemical
    
    • Bilirubin
      
      • 1: <34
      • 2: 34-50
      • 3: 50+
    • Albumin
      
      • 1: 35+
      • 2: 28-35
      • 3: <28
    • INR
      
      • 1: <1.7
      • 2: 1.7-2.2
      • 3: 2.2+
  • Total score:
    
    • Class A
      
      • 5-6 points
      • 100% survival
      • Elective laparotomy 90 day mortality <10%
      • Emergency laparotomy 90 day mortality 20%
    • Class B
      
      • 7-9 points
      • 80% survival
      • Elective laparotomy 90 day mortality 20%
      • Emergency laparotomy 90 day mortality 30%
    • Class C
      
      • 10-15 points
      • 45% survival
      • Elective laparotomy 90 day mortality 50%
      • Emergency laparotomy 90 day mortality 80%
  • Limitations
    
    • Subjective
    • Decompensation can occur in CP A
    • Doesn’t predict mortality
    • B is very broad!

Question 64

TNM gallbladder carcinoma

Answer 64

Gallbladder has no submucosa

T1a: invades lamina propria

T1b: invades muscularis propria

T2a: invades perimuscular tissues on peritoneal side

T2b: invades perimuscular tissues on liver side

T3: penetrates the visceral peritoneum (serosa on peritoneal side), or invades the liver +/- 1 adjacent extrahepatic structure

T4: invades main portal vein, hepatic artery, or 2 extrahepatic structures

Question 65

congenital biliary atresia

Answer 65

• Definition:
  
  • Congenital abnormality where one or more bile ducts are abnormally narrow, blocked or absent
  • Progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that presents with biliary obstruction exclusively in the neonatal period
• Incidence/epidemiology:
  
  • 1:10,000 live births
  • Most common cause of paediatric transplant
• Aetiology & risk factors:
• Pathophysiology:
  
  • Unclear
    
    • Viral
    • Toxins
    • Genetic
    • Immunological
• Clinical manifestations:
  
  • Atresia without other abnormalities (80%)
    
    • Born without jaundice
    • <2 months progressively more jaundiced and stools acholic
  • Atresia with laterality malformations (15%)
    
    • Also known as biliary atresia splenic malformation (BASM) or “embryonal” biliary atresia
    • Laterality malformations include situs inversus, asplenia or polysplenia, malrotation, interrupted inferior vena cava, and cardiac anomalies
  • Atresia with other congenital malformations (5%)
    
    • Associated congenital malformations include intestinal atresia, imperforate anus, kidney anomalies, and/or cardiac malformations
  • Jaundice
  • Note that urine will stain the nappy yellow..
  • Hepatosplenomegly
• Macroscopic features:
• Microscopic features:
  
  • The histology typically shows inflammation, portal tract fibrosis, cholestasis, and bile duct proliferation
• Investigations:
  
  • Prenatal imaging usually normal but if hilar cyst or laterality malformation then monitor
  • Intraoperative cholangiography done at time of exploration; loss of patency of the extrahepatic bile ducts
  • Fibrous cord above the porta hepatis
  • Liver biopsy:
    
    • Confirm obstruction
    • Rule out intrahepatic cholestasis
• Treatment/Prognosis:
  
  • Managed in the neonate by portoenterostomy (Kasai’s operation)
  • Cystic plate cleared of all fibrosis tissue
  • Anastomosis of a Roux-loop of jejunum to the liver hilum. With restoration of bile flow reported in 86% if performed before 8 weeks of age (only 36% if performed in older infants).
  • Of these 60% require future liver transplantation as an adult
  • Long term issues with poor nutrition, fat soluble vitamins, ascending cholangitis, portal hypertension, variceal bleeding and cirrhosis

Question 66

Primary Sclerosing Cholangitis

Answer 66

• Definition:
  
  • An autoimmune inflammatory disease of the intra & extrahepatic bile tracts leading complications of cholestasis and liver failure, often associated with IBD
• Incidence/epidemiology:
  
  • Rare 6:100,000
• Aetiology & risk factors:
  
  • Inflammatory bowel disease 90% of patients
    
    • UC 80%
    • Crohns 7%
    • Note only 5% of IBD patients have PSC, only investigate for PSC in IBD patients if abnormal LFTs
• Pathophysiology:
  
  • High risk of cholangiocarcinoma, liver failure and cholangitis
  • Progressive, obliterative, fibrosis of the intrahepatic and extrahepatic biliary tree
  • Multifocal diffuse strictures throughout the biliary tree
    
    • Intrahepatic and extrahepatic bile ducts – 87 percent
    • Intrahepatic bile ducts alone – 11 percent
    • Extrahepatic bile ducts alone – 2 percent
• Clinical manifestations:
  
  • Initially asymptomatic (half at diagnosis)
  • Cholestasis
    
    • Jaundice
    • Ill-defined pain
    • Fevers and cholangitis
    • Fatigue and pruritis
    • Cirrhosis
  • Liver failure
• Macroscopic features:
  
  • Beads with associated dilations between the strictures
• Microscopic features:
• Investigations:
  
  • Physical examination
    
    • Scratch marks
    • Hepatosplenomegly
  • Imaging
    
    • MRCP
      
      • Multiple intra-hepatic bile duct strictures and beading
    • CT IVC cholangiogram
    • ERCP
      
      • Beware of contaminating undrained segments
    • Patients with variant small duct disease require a liver biopsy for diagnosis
    • In a dominant stricture brushing for cytology need to be taken to detect cancer
  • Bloods
    
    • LFTs
      
      • Cholestatic
    • Autoantibodies:
      
      • Anti Neutrophil Cytoplasmic Antibodies (ANCA)
      • Antimitochondrial antibodies are normally negative (positive in primary biliary cholangitis)
  • Liver biopsy not usually performed unless isolated small duct disease(atypical)

(stricturing)

• Treatment:
  
  • “As will be seen, there is no proven treatment that slows progression of the disease. However, excellent outcomes may be achieved after liver transplantation for advanced disease” - uptodate
  • Medical, endoscopic, and surgical
    
    • Medical
      
      • Cholangitis
        
        • Broad spectrum Abx
      • Immunosuppression
    • Endoscopic
      
      • Investigate for IBD if not already a known patient
      • Dilatation or stenting – only for dominant strictures that are causing obstruction
    • Operative
      
      • Drainage of dominant stricture
      • Transplant due to cirrhosis or liver failure
        
        • Need to exclude cholangiocarcinoma
      • “Thus, surgical therapies other than transplantation should generally be avoided in patients with PSC. The only exception may be in patients with isolated focal extrahepatic strictures and early histologic stage disease” Uptodate
  • Screen for:
    
    • Fat soluble vitamin deficiency
    • Metabolic bone disease
    • Cholangiocarcinoma
    • GB carcinoma
    • HCC (in those with cirrhosis)
    • CRC (in IBD patients)
• Prognosis:
  
  • 5-20% risk of cholangiocarcinoma
    
    • 1-2% incidence per year in PSC
  • Median survival without liver transplantation after diagnosis is 10 to 12 years

Question 67

Primary Biliary Cirrhosis (cholangitis)

Answer 67

• Definition:
  
  • Autoimmune condition of the small bile ducts of the liver causing cholestasis
• Incidence/epidemiology:
  
  • Rare, 2.7:100,000
  • 90% female
  • 30-65 years, usually 40-50s
• Aetiology & risk factors:
  
  • Female
  • Family history
  • Smoking
  • NOT ASSOCIATED WITH IBD
  • NOT associated with alcohol
• Pathophysiology:
  
  • T-lymphocyte-mediated attack on small intralobular bile ducts.
  • A continuous assault on the bile duct epithelial cells leads to their gradual destruction and eventual disappearance
  • The sustained loss of intralobular bile ducts causes the signs and symptoms of cholestasis and eventually may result in cirrhosis and liver failure
  • HCC if cirrhosis
  • Not associated with cholangiocarcinoma or CRC
• Clinical manifestations:
  
  • Symptoms
    
    • Itching, fatigue, dry eyes and mouth, abdominal pain
  • Associated autoimmune conditions
    
    • Sjogrens (50%)
    • Thyroid disease
    • Scleroderma
    • Rheumatoid arthritis
    • Raynauds
  • Portal hypertension, cirrhosis and liver failure
• Macroscopic features:
  
  • Hepatomegly or nodular cirrhosis
  • Green discolouration of cholestasis
• Microscopic features:
  
  • Dense lymphocytic infiltrate in portal tracts with granulomatous destruction and loss of medium sized interlobular bile ducts, focal and variable within the liver
  • Key finding is the florid duct lesion: interlobular bile ducts (within small portal tracts) are destroyed by poorly formed portal epithelioid granulomas
• Investigations:
  
  • Two of the following:
    
    • Raised ALP
    • Positive disease specific antibodies (AMA)
    • Diagnostic liver biopsy.
  • Normal MRCP/ERCP imaging (compared to PSC)
• Treatment:
  
  • Ursodeoxycholic acid
  • Transplant
• Prognosis:
  
  • Good prognosis with UDCA response

Question 68

Differences between PSC and PBC

Answer 68

Question 69

Cholangitis Toyko guidelines 2018

Answer 69

• Make diagnosis
  
  • A: Inflammation (systemic)
    
    • Fever >38C
    • Bloods
      
      • <4 WCC 10<
      • 1< CRP
  • B: Cholestasis
    
    • Bilirubin >20
    • Raised liver enzymes >1.5
  • C: Radiological
    
    • Biliary dilatation
    • Aetiology of obstruction
  • Degree of certainty
    
    • Suspected
      
      • One in A plus
      • One in B or C
    • Definite
      
      • One in A, B and C
• Assess severity
  
  • Mild, moderate or severe
  • Mild
    
    • Not moderate or severe
  • Moderate (no organ markers here)
    
    • WCC >12 or <4
    • High fever >39
    • Age >75
    • Bili >50
    • Albumin low
  • Severe
    
    • Cardiovascular (inotropes)
    • Respiratory(PaO2/FiO2 ratio <300)
    • Neurological disturbance
    • Renal (oligouria or creatinine >200)
    • Hepatic dysfunction (INR>1.5)
    • Haematological dysfunction (platelets <100)

Question 70

Gallstones in pregnancy

Answer 70

After discussion with the family, obstetrics, anaesthetics and surgical colleagues

• If asymptomatic, do nothing
• If symptomatic (i.e. biliary colic, maybe even just once especially in first trimester) then consider cholecystectomy after short trial on conservative management
• If complicated disease (cholecystitis, pancreatitis) then advocate lap cholecystectomy regardless of trimester

Question 71

Mirizzi syndrome

Answer 71

• Csendes (pronounce ~sen dez) classification
  
  • Cholecystobiliary fistula
    
    • Type I: No fistula (compression)
    • Type II: 1/3 CHD
    • Type III: 2/3 CHD
    • Type IV: 3/3 CHD
  • Cholecystoenteric fistula
    
    • Type V
• Treatment:
  
  • Treat the sepsis, CrRISP principles, IVABx, biliary drainage ERCP/PTC preoperatively
  • Depends on type
    
    • Type I:
      
      • Partial or total cholecystectomy, either laparoscopic or open. Common bile duct exploration is typically not required.
    • Type II:
      
      • Cholecystectomy plus closure of the fistula,
        
        • Either by suture repair with absorbable material
        • T tube placement
        • Or choledochoplasty with the remnant gallbladder
    • Type III:
      
      • Will need some degree of reconstruction
      • Choledochoplasty or bilioenteric anastomosis (choledochoduodenostomy, cholecystoduodenostomy, or choledochojejunostomy) depending on the size of the fistula. Suture of the fistula is not indicated.
    • Type IV:
      
      • Bilioenteric anastomosis, typically choledochojejunostomy, is preferred because the entire wall of the common bile duct has been destroyed.

Question 72

Gallstone ileus

Answer 72

• AXR
  
  • Rigler’s triad: small bowel obstruction, gas within biliary tree and gallstone (usually in right iliac fossa)
• Treatment:
  
  • Non operative
    
    • Manage SB obstruction – IV fluid, NGT, analgesia. Catheter, NBM, VTE prophylaxis
    • Laparotomy, enterotomy (longitudinal closed transverse), assess viability, if needed then SB resection
    • Delayed cholecystectomy unless fit patient
    • A one-stage procedure includes enterolithotomy, cholecystectomy, and biliary-enteric fistula closure, with an optional common bile duct exploration.
    • Compared with enterolithotomy alone, the one-stage procedure reduces recurrences of gallstone ileus; prevents malabsorption and weight loss from a persistent biliary-enteric fistula; and prevents cholecystitis, cholangitis, and gallbladder carcinoma, but at the risk of higher surgical morbidity and mortality
  • Operative
    
    • Open procedure
    • Removal of stone (enterolithomy with enterotomy through healthy bowel)
      
      • If proximal stones:
        
        • ” Milk through SB
        • Don’t attempt repair of choledochoenteric fistula - some debate as to whether to treat the fistula and perform cholecystectomy at the initial operation - depends on surgeon experience
        • Duodenum
          
          • Milk into stomach and perform gastrotomy
          • Can lead to gastric outlet obstruction (Bouveret’s syndrome)
    • DJ flexure
    • Isthmus (~where Meckel’s is in SB)
    • SB resection as needed - bowel wall may be necrotic
    • Complete SB run as 10% have multiple stones
• Prognosis:
  
  • High mortality (10- 20%) is attributed either to delayed medical attention or to accompanying medical diseases
  • Mortality 5-10x higher than other causes of mechanical bowel obstruction

Question 73

Bile duct injury classification

Answer 73

Question 74

Risk factors for cancer in gallbladder polyp

Answer 74

• Risk factors
  
  • >1cm
  • Older than 50 years
  • Sessile
  • Multiple polyps
  • Primary sclerosing cholangitis
• If over 2cm then do staging
  
  • CT CAP
  • MRI liver
• Depends on European Guidelines 2017 (Eur Radiol; 2017)
  
  • Size
  • Symptoms
  • Suspicious risk factors
    
    • Age >50
    • PSC
    • Sessile polyp, GB wall thickening +4mm
  • If +10mm then cholecystectomy
  • If symptomatic then cholecystectomy
  • If risk factors then cholecystectomy unless under 6mm (then intensive USS surveillance)
  • If asymptomatic, no risk factors and <10mm then can do USS surveillance

Question 75

Gallbladder dyskinesis

Answer 75

• Definition:
  
  • Functional gallbladder disorder (FGBD) to describe patients with biliary pain and an intact GB without stones or sludge
  • Rome IV definition
    
    • Mandatory
      
      • Biliary pain
      • No gallstones or other structural pathology
    • Supportive
      
      • Ejection fraction low
      • Normal LFTs and lipase
• USS
  
  • Exclude stones or structural abnormality
• Nuclear-CCK stimulated cholescintigraphy
  
  • GBEF of less than 35 to 40 percent = abnormal gallbladder motility and are more likely to respond to cholecystectomy
  • CCK-stimulated cholescintigraphy should only be performed in patients with typical biliary symptoms
  • NOT ordered for atypical symptoms as unlikely to respond to surgery even in the presence of a low GBEF

Question 76

Perioperative optomisation of cirrhotic patient

Answer 76

Preoperative

• Treat any decompensation (in conjunction with a gastroenterologist/ liver unit)
  
  • Ascites
    
    • Paracentesis with albumin
    • Diuretic therapy
  • Correction of coagulopathy
    
    • IV Vit K, FFP and prothrombinex
  • Portal hypertension
    
    • β blocker – e.g. propranolol or TIPPS
  • Lactulose to improve encephalopathy
• Control of the potential complications of cirrhosis
• Treatment of infection
• Treatment of renal impairment
• Optimization of nutrition (in conjunction with gastroenterologist and dietician)
  
  • Increased infection, wound healing problems etc if malnourished
  • Management of glucose intolerance,
  • Deficiencies of vit A, C, E, folic acid and zinc are common and should be treated
  • Deficiencies of branch chained amino acids
• If uncontrolled cirrhosis, acute decompensation, excessive peri operative risk
  
  • Discuss with patient and consider delaying/ cancelling surgery if risk > benefit from symptom management
  • Childs & MELD score
    
    • A = OK
    • 10-14, B = evaluation and optimisation
    • 15, C = avoid

Intraoperative

• Theatre
  
  • Hep B/ Hep C positive patients - Inform theatre staff
  • Start lap (even with ascites) but consider starting away from umbilicus (hernia, portal hypertension) - Eg LUQ visiport
  • Arterial line/ IDC/ CVC for close monitoring
  • Pre op antibiotic prophylaxis
  • Intraop Hb and BSL checks for prolonged procedures
• Operative technique
  
  • Low threshold for open
  • Meticulous attention to haemostasis
    
    • Meticulous attention to avoiding the multiple, large vascular structures seen with portal hypertension
    • Cirrhotics can bleed because of (3 fold causes)
      
      • Thrombocytopaenia – Consider peri-operative platelet transfusion
      • Lack of/ poor synthesis of Vit K dependent coag. Factors
      • Portal hypertension

Post operative

• Manage on liver unit or at least in conjunction with a gastroenterologist) – Not Day Case
• Daily UEC (Na), LFT (bili), and INR
• Daily assessment of weight (fluid balance), ascites, oedema, pyrexia
  
  • Problems with fluid and sodium balance common
  • ADH/ aldosterone and ANP oversecretion
• Early treatment of Infection
• Low urine output
• Coagulopathy (FFP may be needed and more useful than vit K)
• Hypoalbuminaemia/ ascites
• Consider PPI if not already given
• Regular iv vit K supplementation
• Chest physio extremely important for avoidance of infection
• Cautious analgesia using low dosages of paracetamol, morphine, tramadol, benzodiazepines, saline
  
  • Anaesthetic implications, an anaesthetist experienced with these patients is essential
  • Drug metabolism
  • Patients with cirrhosis show variable degrees of alteration in drug metabolism (particularly those drugs requiring oxidation/ reduction or hydroxylation)
  • Narcotics and benzodiazepines show particularly increased durations of action
  • Alterations in the metabolism of anaesthetic agents modifies which agents should be selected (e.g. isoflurane is the gas of choice) but this is not the domain of the surgeon
  • IM injections should be avoided
  • Morphine use must be judicious if at all
• Cardiorespiratory status
  
  • Cirrhotics may have
    
    • Reduced systemic vascular resistance and increased cardiac output
    • Systemic and pulmonary shunting of blood
    • Hepatomegaly and ascites may cause volume effects on the lung
    • Hepatic blood flow
      
      • Liver blood flow is an important consideration in these patients and anaesthetist should take precautions to ensure it is maintained to a great a degree as possible. Periods of hypotension and hypoxia can affect liver function markedly in these patients.
• Renal status
  
  • Cirrhotics are likely to develop hepatorenal syndrome in the post operative period
  • Strict fluid and sodium balance, avoidance of nephrotoxins and aggressive treatment of infection is crucial
• Haemostatic status
  
  • Coagulopathic due to
    
    • Poor liver function
    • Fluid replacement

Additionally for hernias elective repair after ascites has been reduced to a minimum preoperatively. Sponatenous rupture of umbi hernia in setting of ascites is associated with increased mortality. Electively as optimal ascites control mortality rate as high as 14%.

With Laparoscopic procedures, especially lap vs open chole – lower morbidity in term of blood loss and wound infection.

Question 77

Resectability of cholangiocarcinoma

Answer 77

• Intrahepatic
  
  • Sufficient future functional liver remnant
  • i.e.
    
    • Multiple bilobar liver tumours
    • Obvious extensive lymph node metastases
    • Hepatic metastatic disease
• Hilar - see criteria below
  
  • Consider the bilateral nature of portal vein, hepatic artery, hepatic duct and hepatic lobe atrophy
  • Think, What does the remnant liver look like, does it have all its plumbing?
• Distal CBD cholangiocarcinoma
  
  • Contraindications
    
    • Presence of tumour in the portal vein >2cm
    • SMA or common hepatic artery involvement
    • Distant metastasis absolute contraindication
    • Regional LN involvement relative contraindication

Question 78

Pathophysiology of HCC development

Answer 78

• Progression from macroregenerative nodule to low-grade DN, high-grade DN and frank HCC is characterised by loss of visualisation of portal tracts and development of new non-triadal arterial vessels which become the dominant blood supply in overt HCC lesions (and targeted by TACE)

Question 79

Microscopic appearance HCC

Answer 79

• Well vascularised from hepatic artery* hallmark
• Loss of portal tracts
• Preponderance for portal venous invasion
• Wide trabecular
• Acinar pattern
• Small cells
• Cytological atypia and mitotic activity
• Intrahepatic metastasis
• Loss of Kupffer cells
• Edmondson grades 1–4,
  
  • Well-differentiated
  • Moderately differentiated
  • Poorly differentiated
  • Undifferentiated types
    
    • IHC staining (to differentiate from dysplastic nodules)
      
      • Glypican 3 (GPC3)
      • Heat Shock Protein 70 (HSP70)
      • Glutamine Synthetase (GS)
      • Any 2 positive then 73% sensitivity and 100% specificity on resected specimens
  • WHO classification subtypes
    
    • Fibrolamellar
      
      • Younger patients
      • Non cirrhotics
      • Can have central scar and mistaken for FNH
      • Don’t make AFP, might have oestrogen
      • Better prognosis if resected compared to others

Question 80

Ideal conditions for transcystic CBDE

Answer 80

Question 81

Principles of liver surgery

Answer 81

• Principles of liver surgery:
  
  • Principles of liver surgery:
    
    • Liver mobilisation
    • Inflow control
    • Outflow control
    • Low CVP
    • Parenchymal dissection
  • Liver mobilisation
    
    • Falciform/teres ligament & coronary ligament
      
      • Taken down, ligamentum teres used as a retractor inferior/posteriorly
      • Extended cephalad to exposure the subdiaphragmatic IVC through the coronary ligament
      • The ligamentum teres is anchored to the left portal vein
    • Right triangular ligament
      
      • Exposes the bare area of the liver
      • The vena caval ligament (hepatocaval ligament) covers the IVC
    • Left triangular ligament
    • Care to avoid the left phrenic vein
  • Inflow control
    
    • Pringle maneuverer: compression of the portal vein and hepatic artery at the free edge of the lesser omentum
      
      • Create opening in the pars flaccida medial to the portal triad, umbilical tape through this opening and the foramen of winslow encircling the portal triad, create a rummel tourniquet
      • Vessel loops
      • 10-15 minutes on, 5 minutes off..
      • Dissect out the hilar plate (fibrous connection of the hilar bifurcation to the liver) to control gain selective inflow control or glissonian pedicle approach
      • TVE includes control of liver inflow and outflow
    • Outflow control
      
      • Hepatic veins
        
        • Need to have mobilised the liver
        • Caudate lobe has a number of small direct branches
      • Infrahepatic IVC encircled
      • Suprahepatic IVC
    • Low CVP
      
      • Hepatic veins are valveless, thus a high CVP causes back bleeding
      • Anaesthetists:
        
        • Low fluid
        • Diuretic
        • Minimal PEEP
        • GTN or epidural
    • Parenchymal dissection
      
      • Soft liver parenchyma off the vascular and ductal structures
        
        • Methods
          
          • Finger fracture
          • Diathermy
          • Crushing clamp
          • CUSA – cavitating ultrasonic surgical aspirator
          • Harmonic
          • RFA probe
          • Vascular Stapler (after crushing clamp) – Mem sloan kettering HPB 2008
        • 2 general rules
          
          • 1. The portal vein tends to lie posterior to the bile duct and artery
          • 2. The duct lies superior to the artery and is always close to it
    • Postoperative complications
      
      • Bile leak, bleeding, post hepatectomy liver failure

Question 82

Definition and embryology spleen

Answer 82

• Definition:
  
  • The spleen is a solid organ in the left upper quadrant posteriorly
  • The largest lymphoid organ, has haematopoietic & immune functions
  • Odd numbers
    
    • 1 x 3 x 5 inches
    • 7oz ~200g
    • 9-11 ribs
• Embryology:
  
  • 6^th week, mesodermal cells in the dorsal mesogastrium
  • Functions as a haemopoietic organ, but 15-18^th week becomes lymphoid
  • Dorsal mesogastrium called gastrosplenic ventrally and splenorenal dorsally
  • Forms the left wall of the lesser sac
  • Multiple condensations of cells fuse to form a single organ, accessory spleens are due to a failure of fusion

Question 83

ITP

Answer 83

Immune Thrombocytopaenia (ITP)

• Definition:
  
  • Also known as Idiopathic Thrombocytopenic Purpura
  • Isolated thrombocytopaenia
    
    • Normal bone marrow
    • Absence of other causes
• Incidence/epidemiology:
  
  • Most common cause of splenectomy for haematological disease
• Aetiology & risk factors:
  
  • Causes of secondary ITP
    
    • CLL
    • SLE
    • Antiphospholipid syndrome
    • Common variable immune deficiency
    • MMR
    • H Pylori
    • HIV
    • HCV
    • CMV
    • COVID-19
• Pathophysiology:
  
  • Combination of increased platelet destruction and impaired platelet production caused principally by antiplatelet autoantibodies (GPIIb/IIIa)
  • Can be primary (cause unknown or secondary)
    
    • Autoantibodies to platelet membrane glycoproteins  over active phagocytosis by macrophages in the spleen
  • Can be acute or chronic
    
    • Acute more common in children after viral illness, is rapid onset and more severe but resolves
    • Chronic more common in adults, older females, persists for more than 6 months
• Clinical manifestations:
  
  • Bleeding
    
    • Petechiae
    • Purpura
    • Epistaxis
    • Gingival bleeding
    • Severe haemorrhage (ICH, GI) platelets <20,000
• Macroscopic features:
• Microscopic features:
• Investigations:
  
  • History & Examination
    
    • Spleen is nearly normal in size
  • Bloods
    
    • CBE
      
      • Low platelets
    • Coags
      
      • Normal
  • Bone marrow
    
    • Normal
• Treatment:
  
  • Non operative
    
    • Treat the underlying cause
    • Bleeding
      
      • Minor
        
        • Minor bleeding or platelets <20,000
          
          • IV glucocorticoids
      • Severe
        
        • IV glucocorticoids
      • Critical
        
        • Platelet transfusion
        • IV dexamethasone
        • IVIG
    • Not bleeding
      
      • If platelets >30,000-50,000 then observe
    • Second line treatments
      
      • Rituximab
      • TPO receptor agonist
  • Operative
    
    • Splenectomy
      
      • Failed medical management
      • >12 months without spontaneous remission
    • Elective surgery
      
      • If planned major surgery (not neurosurg) then need platelets >50,000
    • Perioperative notes
• Prognosis:
  
  • Splenectomy
    
    • 80% cured
    • 15% partial
    • 5% no response
    • Missing accessory spleen or seeding from the procedure

Question 84

Steps in splenectomy

Answer 84

Access abdomen

4 quadrant packing for haemostasis

Mobilise spleen by dividing its attachments

Ligate short gastrics with care to avoid the stomach

Ligate splenic vessels individually protecting pancreatic tail

Systematic inspection for associated injuries

Close

Question 85

Describe the pancreas (definition and embryology)

Answer 85

• Definition:
  
  • Composite gland having exocrine acini that aid digestion and endocrine islets that regulate carbohydrate metabolism
  • Shaped like the upper end of a thick walking stick with the hooked handle on the right and pointing downwards, approximately 15cm long
  • Firm consistency and finely lobulated surface
  • Big head on the right, connected by a short neck to the body, this crosses midline and tapers to a narrow tail on the left
  • The head and tail incline along the R & L paravertebral gutters
  • The neck and body are curved forwards by the IVC and aorta over L1
  • Organ is mostly retroperitoneal except the tail which runs in the splenorenal ligament with the splenic vessels
• Embryology:
  
  • 5^th week gestation
  • Pancreas develops as two separate buds, each an outgrowth of the endoderm of the distal foregut
  • Dorsal bud grows into the dorsal mesogastrium
  • Ventral bud growth into the ventral mesogastrium
  • Both buds have openings into the duodenum, the ventral pancreatic duct shares a common opening with the bile duct
  • As the duodenum rotates and becomes adherent to the posterior abdominal wall, the pancreatic buds also become retroperitoneal, the ventral bud travels clockwise to the right and fuses with the dorsal bud to form a single organ
  • The two pancreatic ducts merge to form the main pancreatic duct, the duodenal end drains via the major duodenal papilla with the common bile duct
  • The duodenal end of the dorsal duct drains into the duodenum by the minor duodenal papilla as the accessory pancreatic duct
  • Failure to rotate can cause annular pancreas → GOO
  • Failure of the two ducts to fuse results in divisum, with the majority of drainage via the minor papilla → pancreatitis
  • Accessory duct can atrophy and minor duodenal papilla located 1-2cm proximal to the major, is absent

Question 86

Surrounding structures and relations of pancreas

Answer 86

• Surrounding structures and relations:
  
  • Head; sits in the C shaped curve of the duodenum, overlying the IVC at the level of the renal veins and the bile duct
  • Uncinate, projection of the head that passes forward and to the left, behind the SMV/A and in front of the aorta
  • Neck; overlying the confluence of the SMV and the splenic vein
  • Body;
    
    • Triangular in cross section
    • overlying
      
      • L renal vein
      • Aorta
      • L crus of the diaphragm
      • L psoas
      • Lower part of left adrenal gland
      • Hilum of left kidney
      • Splenic vein
    • Inferiorly SMA, DJ flexure
    • Anteriorly is the transverse mesocolon and the lesser sac
  • Tail:
    
    • Passes anteriorly over the kidney
    • Accompanies the splenic vessels and lymphatics in the splenorenal ligament
    • Extends to the hilum of the spleen
  • Splenic artery has peaks and troughs which arise above the upper border of the pancreas
  • The distal 2-10mm the pancreatic duct may run parallel with the distal CBD, or may fuse creating a common channel called the
  • The pancreatic duct is posteromedial to the bile duct (rarely anterior, which would put it at risk when doing sphincterotomy)

Question 87

Pancreas arterial, venous, nervous and lymphatic supply

Answer 87

• Arterial supply:
  
  • Sequential
    
    • Head and uncinate
      
      • SPDA and IPDA running along the inner aspect of the C shape of the duodenum (pancreaticoduodenal arcade)
    • Neck/Body/Tail
      
      • Branches of the splenic artery
      • Largest – arteria pancreatica magna
• Venous drainage:
  
  • Multiple small veins
    
    • Neck/body/tail → splenic vein
    • Head → SPDV (into portal vein) and IPDV (SMV)
• Innervation:
  
  • Predominately under hormonal control
  • Parasympathetic
    
    • Fibres from the (right) posterior vagal trunk via the coeliac plexus
  • Sympathetic
    
    • T6-10 spinal segments via splanchnic nerves and the coeliac plexus, the post ganglionic fibres running with the blood vessels
  • Pain
    
    • Pain fibres accompany sympathetic supply
• Lymphatics:
  
  • Follows the arteries, along the splenic hilum, splenic artery, CHA and coeliac and superior mesenteric nodes

Question 88

Pancreatic exocrine cells

Answer 88

• Endocrine cells within the pancreatic parenchyma in clusters called islets of langerhans (2% of the whole gland)
  
  • Stain light compared to surrounding acinar cells which are dark purple
  • 4 cell types
    
    • Alpha cells = glucagon
    • Beta cells = insulin
    • D cells = somatostatin
    • D2 cells = vasoactive intestinal peptide
    • All related to glucose homeostasis

Question 89

6 gateways in hepatobiliary surgery (toronto atlas)

Answer 89

• Right gastroepiploic vein (which runs along the greater curve joins the middle colic to form confluence of henle at the SMV)
  
  • Gateway to inferior part of tunnel behind the neck of the pancreas
• GDA (off the hepatic artery diving behind D1
  
  • Gateway to superior part of tunnel behind neck of pancreas
• Left gastric vein (coronary)
  
  • Gateway to origin of splenic and proximal common hepatic arteries (coeliac axis)
• Cystic artery & duct
  
  • Gateway to right hepatic artery and portal vein
• Hepatocaval ligament
  
  • Gateway to right hepatic vein
• Ligamentum venosum
  
  • Gateway to left hepatic vein, hanging maneuvere

Question 90

Indications for ERCP in pancreatic cancer

Answer 90

• Preoperative ERCP & stent
  
  • Purpose
    
    • Decompression
    • Cytology brushings
  • Indications
    
    • Bilirubin >100-150
    • Cholangitis
    • Itch
    • Neoadjuvant
    • Palliative
  • Alternative is PTC or surgical decompression
  • Risks
    
    • Perioperative infection
      
      • Cholangitis
      • Fistula
      • Wound infection
    • Procedural risks (perforation, pancreatitis, bleeding etc)

Question 91

IPMN indications for surgery

Answer 91

• Fukuoka (Foo-kew-0-kah) guidelines
• High risk stigmata = resect
  
  • Obstructive jaundice (if a HOP lesion)
  • Enhancing solid component/nodule (+5mm within cyst)
  • Main PD +10mm
    
    • Worrisome stigmata → EUS imaging and aspiration/cytology & consider resection
      
      • Enhancing mural nodule <5mm size
      • Main PD 5-9mm
      • Abrupt change in PD calibre with distal pancreatic atrophy
      • Pancreatitis clinically
      • +3cm cyst size or 5mm growth over 2 years
      • Thickened enhancing cyst walls
      • Lymphadenopathy
      • Serum Ca 19.9
    • If no worrying stigamata then consider the largest cyst size
      
      • <1cm
      • 1-2cm
      • 2-3cm
      • >3cm
        
        • Alternating EUS and MRI every 3 months…. Consider surgery in young fit

Intensive!

Falconi et al 2015 see picture

Question 92

IPMN risk

Answer 92

Fukuoka (Foo-kew-0-kah) guidelines High risk stigmata -> resect • Obstructive jaundice (if a HOP lesion) • Enhancing solid component/nodule (+5mm within cyst) 21 • • Main PD +10mm Worrisome stigmata -> EUS imaging and aspiration/cytology -> consider resection • Enhancing mural nodule <5mm size • Main PD 5-9mm Abrupt change in PD calibre with distal pancreatic atrophy • • • Pancreatitis clinically +3cm cyst size or 5mm growth over 2 years Thickened enhancing cyst walls Lymphadenopathy • Serum Ca 19.9 If no worrying stigmata then consider the largest cyst size • <1cm • 1-2cm • 2-3cm • >3cm о Alternating EUS and MRI every 3 months….