HPB Flashcards
Describe the divisions of the liver
- The falciform is the anatomical division of the right and left lobe – this does not correspond to the functional lobes of the liver.
- The anatomical division is dictated by the falciform ligament which splits the liver into a large right lobe and a small left – this does not determine the functional lobes of the liver.
- Division of the functional lobes is determined by the inflow and outflow of the liver.
- The portal triad divides into the left and right hepatic veins, duct, and artery which divides the two functional lobes.
- The line of division along a theoretical line which goes from the tip of the GB and just to the left of the IVC (Cantile’s line)
- Further division of the functional liver can be further drawn up.
Caudate lobe
- Segment 1 is the caudate lobe – medially, the ligamentum venosum borders the caudate lobe.
- Inferior to the caudate lobe is the inflow to the liver (portal vein etc) and superiorly to the caudate lobe is the hepatic vein confluence.
- Has mixed inflow (both left and right)
- Has direct venous drainage into the IVC via smaller veins.
Segment 2, 3 and 4
- All supplied by left portal triad.
- Segment 4 is also called the quadrate lobe – demarcated by the falciform ligament medially and the gallbladder laterally
- Segment 4 is split into 4a and 4b.
Segment 5, 6, 7, 8
- Travel in an anticlockwise direction
Supplied by branches of the right portal triad.
What are the branches of the common hepatic artery
- Right gastric – comes off just before the pylorus – runs along lesser curve.
- GDA – occurs just in-front of the portal vein behind D1. GDA courses behind D1. Gives off the right gastro-epiploic artery and terminate as the anterior superior pancreaticoduodenal artery (the posterior superior pancreaticoduodenal artery usually comes directly off the GDA).
- Common hepatic artery then becomes the hepatic artery proper
- Bifurcate in a Y shape into the left and right hepatic arteries.
The cystic artery usually comes off the right hepatic artery
What are the branches of the cystic duct
- Can sometimes be x2 cystic arteries.
- Can come off left hepatic artery, GDA, or hepatic artery proper.
Usually passes behind CBD but can pass infront.
What is Coinaud classification of biliary duct variants
A – typical anatomy confluence.
B – Triple confluence.
C – right sectoral duct drains into common hepatic duct.
D – right sectoral duct drains into left hepatic system
E – absence of the hepatic duct confluence.
F – ectopic drainage of the right posterior sectoral duct into the cystic duct.
What is the embryology of the pancreas
- Develops at 2 separate buds.
- Each of them are an outgrowth of the endoderm at the junction of the foregut and midgut.
- The dorsal bud (larger) grows into the dorsal mesogastrium.
- The ventral bud (smaller) grows into the ventral mesogastrium.
- As the duodenum develops and rotates, both buds rotate clockwise (dorsal 90 degrees and ventral 270 degrees).
- The ventral bud makes up the uncinate process and the inferior part of the pancreatic head.
- Ducts then fuse to create a common duct
- The accessory pancreatic duct which drains into the minor papilla will only drain dorsal bud (head body and tail)
- Pancreatic divisum is where there is no communication between the two ducts (thus ventral bud drains via major papilla and dorsal bud via minor papilla)
Annular pancreas – complete ring of pancreatic tissue around the duodenum. The duct will also circle around the duodenum. Can cause compression of the duodenum requiring surgical intervention.
What is the blood supply of hte pancreas
- Head, uncincate process (posterior projection behind SMA + SMV), neck (narrowest portion), body (slopes gently upwards across L renal vein, aorta, left crus, left psoas muscle, hilum of left kidney, finishes in splenic hilum)
Blood supply to the pancreas - Head – superior and inferior pancreatico-duodenal arteries.
- Neck body and tail – branches of the splenic artery – the largest being named the arteria pancreatica magna.
Describe the anatomy of the gastrocolic trunk of Henle
- Gastro-colic trunk of Henle sits adjacent to the SMV over the head of the pancreas.
- Has very variable anatomy but will often receive a middle colic vein, right colic vein, right superior colic vein, and gastro-epiploic vein.
- The right superior colic vein drains the hepatic flexure and this can be torn when mobilising the hepatic flexure (registrar vein) .
What is the definition of ascites
- Defined as the pathological accumulation of excess fluid in the peritoneal cavity.
- Normally peritoneal cavity contains 25-50mls of ascitic fluid which helps hydrate serosal surfaces.
- The fluid in the peritoneal cavity is constantly being exchanged through the capillary bed under the visceral peritoneum.
Ascites occurs when rate of formation exceeds rate of absorption.
What are the causes of ascites
- Cirrhosis - 85% of cases
- Malignancy
- Heart failure
- TB
- Alcoholic hepatitis
- Budd-Chiari syndrome
Nephrogenic ascites
What is the pathophysiology of ascites
- Triad of portal hypertension, arterial vasodilatation and neurohormonal activation, leading to sodium and water retention.
- Portal hypertension plays a major role - ascites usually develops in patients with a hepatic venous pressure gradient of greater than 12mmHg.
- Portal HTN - increased levels of NO in the gut - splanchnic vasodilatation - decreased renal blood flow - activation of RAAS - salt retention.
- Portal HTN also causes sympathetic over-activity which stimulates Na re-absorption in PT, loop of Henle, distal tubule.
- This excess sodium retention - hypervolemia - increased capillary hydrostatic pressures - fluid leaks into peritoneal cavity.
Contrary to earlier theories, decreased plasma oncotic pressure from low albumin does not cause ascites
What investigations should be done for a patient with ascites?
Lab testing
- Full panel LFTS with albumin
- Coagulation studies.
- FBC looking at platelets.
Imaging
- Abdominal USS - can evaluate liver architecture, dilatation of portal vein (>13mm, dilatation of splenic vein (>11), and recanalization of the umbilical vein.
- To differentiate between RHR and cirrhosis do BNP (high cardiac), look at JVP and consider echo.
Paracentesis
- Should be done to identify cause of ascites
Coags do not really reflect bleeding risk in cirrhosis as there is a balanced deficiency or procoagulants and anti-coagulants.
How is ascitic fluid evaluated and interpreted?
Ascitic fluid analysis report will comment on
- Colour - clear, bloody, pus
- Cell count and differential - will rule out infection (which is very dangerous in ascites). Neutrophil count >250/mm should be treated with antibiotics.
- Culture - should be inoculated into blood culture bottles at the bedside
- Total protein
- Serum-to-asicites albumin gradient (SAAG) - subtract ascitic fluid albumin value from serum albumin value. SAAG > 11 predicts the patient will have portal hypertension. SAAG < 11 will predict they do not (this reflects that ascitic albumin is very low because it is just water leaking)
Other rests include testing for glucose (high in peritoneal carcinomatosis), LDH (bowel perforation and peritoneal carcinomatosis), Gram stain, amylse, TB, cytology, triglyceride concentration, bilirubin (biliary leak)
How is ascites graded?
- Mild ascites only detectable by USS - don’t treat
- Moderate ascites with moderate abdominal distension - salt restriction and diuretics
- Marked ascites with marked abdominal distension - paracentesis then salt restriction with diuretics
What is the treatment of ascites?
- Dietary sodium restriction - no added salt to diet and avoid pre-prepared meals. Can measure compliance by doing a urinary sodium (if higher than 78 - not being compliant).
- Diuretics - spironolactone and Frusemide (spiro is better but you usually need to give both)
- Large volume paracentesis - if removing > 5L need to give an albumin infusion. If remove to quickly or too much can develop hepatorenal syndrome or water retention causing dilutional hyponatremia.
What is the definition of refractory ascites?
- Defined as ascites that is unresponsive to sodium-restricted and high dose diuretics OR ascites which recurs rapidly after paracentesis.
- Median survival of 6 months.
Patients with refractory ascites should be considered for transplantation.
- Median survival of 6 months.
What is TIPS and what is it used for?
- can achieve portal decompression and therefor prevent complications of portal hypertension, ascites and hydrothorax. Reduced portal pressures reduces RAAS activation and thus improves GFR and in turn further reduces salt re-absorption.
- Also makes people sensitive to diuresis again
- TIPS shown to have a surival benefit over serial paracentesis.
- More likely to develop hepatic encephalopathy
- Complications include shunt thrombosis and stenosis.
CI include CHF, pulmonary HTN, recurrent encephalopathy, hepatic abscesses, HCC.
What are the 4 parameters used when grading severe acute liver failure using the Kings Hospital criteria
- Total bilirubin
- Prothrombin time
- Serum lactate
Encephalopathy (West Haven criteria)
How can liver function be assessed pre-operatively
Blood tests
- LFT’s are not a measure of function, but do give an indication of processes going on in the liver.
- AST and ALT are hepatocyte enzymes release in conditions where hepatic damage occurs - ischaemic injury, hepatitis, sepsis.
- ALP - predominately expressed in biliary epithelium - elevated in cholangitis and biliary obstruction.
- GGT is expressed by both hepatocytes and biliary epithelium.
Tests of liver function
Indocyanine green clearance test
- ICG is excreted by hepatocytes rapidly.
- In the normal liver, hepatic blood flow is the rate limiting step.
- In the disease liver, both hepatic flow and hepatocyte function is reduced, thereby impairing the clearance of ICG.
- ICG levels are taken at 5 and 15 minutes.
- Hou can also do a continuous measurement of ICG clearance which is probably more accurate.
Hepatobiliary scintigraphy and single photo emission CT
- Tc99 is combined with SPECT CT to evaluate the uptake of the FLR.
- Amsterdam medical centre did show that implementing this reduced post-op liver failure as it allowed better case selection for PVE
Others
- Lidocaine - rate of disappearance of lidocaine (metabolised by cytochrome P450) correlates with liver function
- Aminopyrine breath test - carbon labelled aminopyrine is taken orally, metabolized by cytochrome p450, liberates C02 which can be measured.
Blood flow
- Can be measured intra-operatively or non-invasive.
- The ratio of hepatic artery to portal vein flow changes with increasing stiffness of the liver (i.e. portal pressures become higher which reduces flow ).
- Doppler USS can be used intra-operatively after dissecting out the vessels.
MRI can be used to measure volume
What is the role of PVE in liver surgery?
What are the limitations?
nvolves embolizing a portal vein on one side to cause contralateral hypertrophy and thus increase the future liver remnant.
- Limitations to PVE include pre-existing hepatic fibrosis, cirrhosis, technically can’t access/occlude PV.
- Perc approach most common
For large right side tumours, you often have to also embolize segment 4 (thus will get as much hypertrophy out of segment 2 and 3 as possible)
What are the risk factors for Cholangiocarcinoma?
Situation that cause chronic inflammations
- PSC
- Recurrent cholangitis and choledocholithiasis
- Choledochal cysts.
- Hepatolithiasis
- Chronic hepatitis, HIV, EBV, Cirrhosis, heavy ETOH use, T2DM, smoking, biliary enteric anastomosis.
PSC is strongly associated with IBD. Unfortunately, patients with PSC associated cholangiocarcinoma’s are not candidates for resection because of the multi-focal nature of the disease and severe underlying hepatic dysfunction
What are 3 locations of cholangiocarcinoma?
- Intrahepatic
- Hilar
- Distal
What are the 3 types of growth patterns in cholangiocarcinoma?
- Mass forming – exophytic mass or nodule
- Peri-ductal infiltrating – tumour which infiltrates along the duct itself. Often associated with a stricture
Intra-ductal – abrupt caliber change with or without a visible mass.
What tumours markers should be performed when working up a patient with possible cholangiocarcinoma?
- AFP level – good for differentiating between an intra-hepatic cholangiocarcinoma and HCC
- CA-19-9 is the most useful marker and very high CA19-9 levels are often associated with unresectable disease.
CEA, CA 125 should also be sent as these are tumour markers but they are NOT specific.
What radiological ix should be done to workup a patient with possible cholangiocarcinoma?
- USS will have often been done – will be able to see a mass or site of narrowing, biliary dilatation.
- Generally you should try and get imaging before stenting, as stenting can cause inflammation making assessment of the primary tumour difficult.
- CT – CAP PV with IV contrast and arterial phase. Provides good assessment of the tumours relationship to vascular and portal structures.
- MRCP – useful for information about the ductal system, especially identifying the burden of ductal disease. May also be able to find evidence of intra-hepatic lymphatic disease, lymph node status.
CT-PET – this should be done when disease looks localized on CT/MRI and resection is being considered. Is good at identifying extra-hepatic disease (but not good at determining resectability)
How does cholangiocarcinoma spread/metastasis
- Lymphatic – 50% of patients
Hematogenous – lungs, vertebra, brain, adrenals.
What is the role of PTC and ERCP when working up a patient with cholangiocarcionoma? What are the downsides?
- You don’t need a tissue biopsy to make diagnosis
- Can be made off radiology
If you do a percutaneous biopsy of an intra-hepatic c
What is the Blumgart staging for hilar cholangiocarcionoma?
T1 - Tumour involving biliary confluence +/- unilateral extension to secondary biliary radicals.
T2 - Tumour involving biliary confluence +/- unliateral extension to secondary biliary radicals and
ispilateral portal vein involvement +/- ipsilateral lobar atrophy.
T3 - Tumour involving biliary confluence + bilateral extension to secondary biliary radicals or
unilateral extension to secondary biliary radicals with contralateral portal vein involvement or
unilateral extension to secondary biliary radicals with contralateral lobar atrophy or
main or bilateral portal vein involvement.
What T stages can be resected for Hilar cholangio?
What is the median survival for each T stage?
Only T1 and T2 can be considered for resection - but the outcomes from resecting a patient with T2 disease is poor (high chance of finding metastatic disease at exploration and poor median survival)
The median survival is 20, 13, and 8 months for T1, T2, T3 respectively.
How is resectability assessed for cholangiocarcinoma?
Patient factors – unfit or cirrhotic.
Tumour factors
- Encasement of occlusion of main portal vein.
- Extension into second order biliary radicals bilaterally.
- Lobar atrophy with contralateral portal vein encasement or occlusion, or contralateral second order biliary radical involvement
- Unilateral secondary biliary radical involvement with contralateral PV encasement or occlusion.
- Any involvement of the hepatic artery.
Metastasis – to distant lymph nodes basins (nodes other than the ones in the liver/biliary tree), liver lung or peritoneal metastasis.
Two answer this in the exam I use “ABC” (like pancreatic cancer)
A - anatomy - looking at portal vein involvement, involvement of second order biliary radical, hepatic artery involvement, and lobar atrophy. Once there is evdience of disease on both sides then a tumour becomes unresectable, and any arterial involvement means tumours is unresectable.
B - tumour biology - if there is evidence of metastasis or very high CA 19-9
C - co-morbidities - is the patient fit for major surgery or a cirrhotic.
What is considered an adequate FLR for patients undergoing a liver resection?
How is do you determine if someone has an adequate FLR?
- If patients are undergoing a hemi-hepatectomy, they need to have an adequate functional liver remnant
- This is done mainly by using CT/MRI 3D modelling to determine what the volume is the liver remnant. This liver remnant will thus be affected by the underlying quality of this liver
- Generally a FLR < 30% is required for people with normal liver.
- For patients with baseline liver dysfunction OR receiving neoadjuvant chemotherapy, a FLR < 40% is used as a cutoff.
For patients with cirrhosis the FLR cutoff is 40-50% (note, you don’t offer resection to cirrhotic’s with cholangiocarcinoma)
What is the expected liver remnant growth after FLR? What liver kinetics are generally deemed adequate?
- Results in liver hypertrophy of the non-embolized segment, secondary to altered portal flow.
- On average, up to a 15% increase in the total volume of the FLR can be expected within 6 weeks.
Want the growth rate to be more than 2% per week – if the liver doesn’t grow quickly after PVE then you can be suspicious of underlying liver disease
What are the pros and cons of biliary decompression prior to hepatic resection for patients with cholangiocarcinoma?
- Pro’s – likely improves patients nutrition pre-operatively, and the function of the liver remnant.
- Con’s – can introduce infection to the biliary tree – increases pre-operative risk of cholangitis. May cause tumour seeding.
- Likely useful if you have a jaundiced patient with a small/borderline FLR.
- Probably of limited benefit in a well patient, not jaundiced with a good FLR.
Thus case by case basis.
What are the indications for transplant for patients with cholangiocarcinoma?
- Tumours < 2cm in size with concomitant cirrhosis
What adjuvant chemotherapy options can be considered for patients with cholangiocarcinoma?
- Due to how rare this tumour is there is limited data.
- For high risk disease – patients should be given adjuvant capecitabine - this is based on the BILCAP 2019 study which showed an improved overall survival.
High risk includes tumours > 5cm, perineural or LVI, lymph node involvement, positive resection margins.
What 4 requirements when considering if a patient with a hepatic metastasis is appropriate for resection
- Tumour can be removed completely
- FLR is adequate to prevent post-operative liver failure.
- Extra-hepatic disease sites are controllable
- Primary can be resected for a cure.
How do you determine resectability for a patient with hepatic metastasis?
Base on technical, oncological, and patient factors.
- Technical - Ro resection, adequate FLR, adequate vascular inflow and outflow, adequate biliary drainage.
- Oncological - Burden of disease, response to neoadjuvant treatment, disease free interval, presence of extra-hepatic metastasis.
Patient factors - patient well enough to undergo liver surgery.
Describe the ALPPS procedure?
- Can be used for bilobar liver metastasis when an extended right hemi-hepatectomy is required.
- Small tumours from one side are resected, liver is then partitioned, and the other side is ligated.
- This allows for rapid growth of the liver remnant
- Formal resection can be done at 2 weeks.
- Is fairly radical and probably only reserved for well-selected healthy patients.
The difference between a two staged hepatectomy and ALPPS is that in ALPPS the liver is partitioned and the patient is brought back to the OR relatively quickly
What pre-op, intra-op, and post-op treatments can be used to reduce the risk of post-op liver failure after hepatic resection?
Pre-op
- Avoid fasting pre-operative.
Intra-op
- Oxidative stress – reduce Pringle time and also intermittently give breaks.
- Minimizing blood loss.
- Minimizing blood transfusions.
Post-op
- Early recognition and treatment of post-operative haemorrhage.
- Early recognition of biliary obstruction of leak.
- Early recognition of intra-abdominal sepsis.
- Maintaining hydration post-operative.
Adequate nutrition and the use of TPN.
What is the definition of post-operative liver failure?
- The definition of post-operative liver failure is an acquired deterioration in the ability of the liver to maintain its synthetic, excretory, and detoxifying functions.
Is found if the INR is increased, or elevated bilirubin on post-operative day 5.
What are the main principles of liver surgery?
Principles of liver surgery
- Mobilization
- Inflow control.
- Maintenance of low CVP
- Parenchymal transection.
Mobilization
- Dividing the peritoneal attachments.
- Depends on what lobe is being operated on – may need to divide triangular ligaments, coronary ligaments, falciform ligament.
- Often need to mobilize the liver of the IVC which will allow outflow control
Inflow control
- Can be controlled with a Pringles Maneuver
- Should only be left on for 10-15 mins at a time with 5 mins off.
Outflow control
- Relates to control of the hepatic vein
- Mobilization of the liver is important to get access.
- Caudate lobe will have a number of small vessels which go directly into Caudate lobe.
- CVP reduction is performed by minimizing fluids, minimizing PEEP, using GTN to increase the total venous volume.
Parenchymal transection
- Finger fracture – push away liver parenchyma
- Crushing clamp
- CUSA
- Ligasure
RFA probes.
What chemotherapy agents are used in treatment of liver metastasis?
- FOLFOX, FOLFIRI and XELOX are used - what to use primarily depends on what regimes the patients has previously had. Studies haven’t shown any difference in OS between the regimes.
- FOLFOXIRI (is FOLFOX and FOLFIRI combined) is often used in younger patients with a significant tumour burden - especially if they have contra-indications to biologic agents.
- Cetuximab can be given for non-mutant KRAS tumours.
Bevacizumab is often used in metastatic colorectal cancer (both wild-type BRAF mutant (BRAF)
What are the risk factors for HCC?
- Environmental – smoking, alcohol, aflatoxins (produced by fungi on maize), obesity.
- Genetic – haemochromatosis, alpha-1-antitrypsin deficiency, PSC
- Viral – Hep B and C
- Auto-immune – autoimmune hepatitis and primary biliary cirrhosis.
Cirrhosis.
What is the aetiology/pathophysiology of HCC?
- 90% of patients with HCC have underlying cirrhosis – repeated cellular injury – chronic inflammation – regeneration – fibrosis – cirrhosis – dysplasia – carcinoma.
- Pathway from microscopic dysplastic foci, nodules with low grade dysplasia, to nodules with high grade dysplasia, to early HCC(<2cm in size) and then HCC.
The aetiology for non-cirrhotic HCC are less well understood - although the risk factors for non-cirrhotic HCC have been identified (and are generally the same risk factors for cirrhosis i.e. viral, autoimmune, genetic, and environmental)
What are the indications for screening for HCC patients?
- Because HCC develops over decades - high risk populations should are screened.
- Screening should be performed in high risk individuals 6 monthly - known cirrhosis, Hep B infection, and Hep C infection.
Screening should be with ultrasound and AFP.
What pre-malignant lesions exist for HCC?
Microscopic dysplastic foci
- <1mm lesions
- Characterized by dysplastic hepatocytes.
-
Low grade macroscopic dysplastic nodules
- Include low grade dysplastic nodules
- 2mm-1cm in size.
- Found in cirrhotic liver.
High grade macroscopic dysplastic nodules
- Usually 1-2cm
- Meet the criteria for a pre-cancerous lesion.
- Will show signs of neoplasia with increased N:C ratio, irregular nuclear borders, mitosis, pseudo-gland formation.
- Can be difficult to differentiated from a well-differentiated HCC.
May harbor foci of invasive HCC.
What are the different patterns of HCC
- Solitary
- Multi-nodular
- Multi-centric (multiple HCCs developing in different segments of the liver)
Diffuse infiltrating type – often poorly defined lesion.
Describe small HCC
- Small HCC is a term used to describe tumours which are less than 2cm in size.
- This is because they have a significantly better prognosis than HCC in general.
- “Vaguely nodular type” – early type HCC. No capsule. These tumours usually don’t have a capsule.
“Distinctly nodular type“ – clearly defined capsule – poorer prognosis. More likely to have PV invasion.
Describe the histopathology of HCC
- Typically are well vascularized tumours with most of the blood supply from the hepatic artery.
- Wide trabecula, prominent acinar pattern, preponderance for vascular invasion.
- As HCC progress, lose normal portal tracts and develop non-triad related vessels – this angiogenesis is the hallmark of an HCC.
- HCC has a surrounding capsule (up to 80% of the time).
- HCC can also cause biliary obstruction
Describe the Edmonson grade of HCC
- Edmonson grades 1-4 are used
- Grade 1 and 2 are well differentiated.
- Grade 3 is moderately differentiated.
Grade 4 is poorly differentiated.
What IHC stains are positive in HCC?
- Glypican-3
- Heatshock protein 70
- Glutamine synthetase
Useful to use these markers to differentiate HCC from pre-malignant nodules
What is fibrolamellar HCC and how does it appear on imaging?
- These tumours are often found in young people who don’t have history of cirrhosis
- Are encapsulated with a central scar thus can be mistaken for focal nodular hypoplasia
- On T2 imaging, the central scar is hypointense.
- Fibrolamaller HCC will not take up Primovist on MRI unlike FNH. This test is used to distinguish between between the two.
- The central scar in fibrolamellar HCC is due to central necrosis (whereas in FNH the central scar is due to fibrosis associated with numerous vascular channels).
- DO NOT MAKE AFP
Do have a better prognosis than a normal HCC if they can be resected.
What is the significance of AFP in HCC?
- Can help with diagnosis
- AFP levels > 20ng/L generally prompt investigation for HCC.
- AFP are high in fetal life but a low as an adult.
- Levels of AFP > 400ng/L are diagnostic of HCC with a greater than 95% confidence.
- Level of the AFP also correlates with the tumour biology – higher AFP levels from tumours which are more likely to be undifferentiated and associated with vascular invasion.
Other tumours which increase AFP levels are seminomas, hepatic gastric tumours and very rarely neuroendocrine tumours.
What are the imaging findings for HCC?
USS
- Appear hypo-echoic compared to normal liver parenchyma.
- Larger HCC’s are often heterogenous in nature.
CT
- Typically hypodense on non-con phase.
- Brisk enhancement on arterial phase due to aberrant blood vessels from hepatic artery.
- Evidence of rapid washout in PV and delayed phase (as has no portal venous inflow).
- Often associated with a capsule - which enhances on portal venous and delayed phase.
- If you see evidence of ‘washout’ then you are saying this is an HCC.
Why do HCC lesions washout? This is due to a lack of portal venous supply to HCC’s (which generally run off the arterial supply)
LIRADS system
- Is used on reporting lesions in a cirrhotic liver
- There is a LIRADS score for MRI, CT and USS
1 – benign
2 – probably benign
3 - intermediate
4 – likely HCC
5 – Definitely HCC
MRI
Similar to CT when given gadolinium i.e. brisk uptake with evidence of washout.
Describe the Barcelona staging system for HCC?
Barcelona Clinic Liver Cancer Staging system
- Stage 0 – Very early stage, means the tumour is less than 2cm, Child-Pugh A
- Stage A – early stage – up to 3 tumours all less than 3cm, Child Pugh A or B.
- Stage B – intermediate stage – many tumours in the liver, Child Pugh A or B
- Stage C – Cancer has spread to blood vessels, lymph nodes, or other body organs. Child-Pugh A or B.
- Stage D – severe liver disease. – Child Pugh C.
What are the 5 factors in the Child-Pugh grade?
- Bilirubin
- Albumin
- PT time.
- Evidence of ascites.
Encephalopathy.
What is the milan criteria for transplant for HCC?
- Criteria which is trying to select patients which have > 70% 5-year survival after liver transplant
- Solitary tumour, less than 5cm in size or £ 3 tumours which are £ 3cm in size, no extrahepatic manifestations, no vascular invasion.
Patients beyond Milan criteria may still be offered surgery if they can downstage into an accepted criteria.
What are the contraindications to resection in HCC?
- Child-Pugh C
Portal hypertension – high rates of post-operative morbidity or mortality.
What ablation techniques can be used for HCC
Ablation techniques
- Percutaneous ethanol injection
- Radiofrequency ablation
- Microwave ablation
Percutaneous ethanol ablation - PEI
- Is effective for tumours < 2cm
- Less successful for tumours > 2cm.
- When compared with RFA is generally inferior.
Radiofrequency ablation
- Uses high frequency alternating currents to generate frictional heat, inducing cell death.
- Heat causes coagulative necrosis
- Is very good for tumours <3cm.
- For large tumours can still be successful if combined with TACE
- RFA competes with surgery for small solitary lesions - having a slightly higher recurrence rate but lower morbidity.
Microwave ablation
- Heating effect of microwaves at high frequency causes tissue necrosis
- Useful for small tumours < 2cm.
- One of the benefits is that large nearby vessels cause less heat sink.
- It also can be performed to multiple lesions at the same time thus reducing procedural time.
- Is comparable to RFA.
- Can get seeding of the tract
Radiofrequency ablation
Radio or energy waves are applied to the tumour – works similar to microwave ablation and the problems are the same
What is TACE and when is it used?
TACE
- Trans-arterial chemo-embolization.
- Causes both and ischaemic hit to the cancer as well as a cytotoxic hit.
- Either the hepatic artery or branch of the hepatic artery is embolized leading to tumour necrosis.
- The most commonly used drugs as doxorubicin and cisplatin.
- Is often combined with iodoised oil (Lipiodol) as this increases there concentration in tumour cells.
- TACE should not be performed in patients with decompensated liver failure or when tumour burden is > 50% of the liver volume.
- Is contraindicated if you have total PV thromboses as this will results in all the of the blood flow to the liver being cut off.
- Doesn’t have great long term outcomes as the tumour just grows a new blood supply.
Is also contraindicated in severe underlying liver disease i.e. Child-Pugh C.
What are the indications for treatment for a liver cyst?
- Symptomatic -can percutaneously drain and inject a sclerosant, deroof, or anatomically resect (if the cyst is very large)
- Concern about nodularity.
- Intra-cystic haemorrhage (shouldn’t occur in a simple cyst).
DDx of a liver cyst
- Infections including Echinoccocus
- Neoplasia
- IPMN of the bile duct
- HCC
- Cystic metastasis to the liver – colorectal, breast etc.
Post-traumatic cysts.
Aeitiology, natural history and histology of FNH
Focal nodular hyperplasia
- Benign condition of the liver with no malignant potential. Risk of rupture is very low (unlike hepatic adenoma)
Aetiology
- Hyperplastic process arising from an arterial malformation causing hyper-perfusion
- Main risk factor is female sex 9:1 preponderance
- Because FNH occurs commonly in woman between the ages of 20-40 a relationship with the OCP has been suggested but not confirmed.
Natural history
- Most don’t change in size.
- 20% of patients will have more than 1 area.
Histology
- Well circumscribed, non-encapsulated, focal area of hepatocytes with a central fibrous scar.
- Central scar consists of collagen, aberrant arteries and veins.
- Proliferation of hepatocytes with cirrhotic like architecture.
- Fibrous septa replace bile ducts. Arteries show intimal fibrosis and media hypertrophy.
What are the imaging findings of FNH?
Imaging findings
CT
- Characterized by a central scar
- Hypo or isodense liver lesions.
- On arterial phase will get homogenous arterial enhancement apart from the central scar.
- The lesion remains enhanced on PV phase
- On the delayed phase the scar can enhance
MRI
- Typically is done with Primivist contrast
- On non-enhanced T1 image will look isointense (same as surrounding liver) with central scar looking hypointense
- On arterial phase FNH will enhance and the scar will remain hypointense.
- On the PV phase you will get an isointense lesion with an enhancing scar.
- On T2 will you have an isointense lesion but the scar will hyperenhance
- When using Primovist, there will be uptake with Primovist contrast on the hepatobiliary phase - this is unlike hepatic adenomas or hepatocellular carcinomas.
The key thing with using Primivist (Gadoxetic acid) is that an FNH lesion will take up Primivist in the T1 hepatobiliary phase (which is the delayed phase) due to the presence of normal hepatocytes and abnormal bile ductules. This is different to a hepatic metastasis, or hepatic adenoma which will not take up primivist contrast during the hepatobiliary phase.
The hepatobiliary phase is a delayed phase thus an HCC will appear to “washout”
How is FNH managed?
Management of FNH
- Benign non-malignant lesion so if asymptomatic then don’t do anything.
- If diagnostic doubt – included in the differential is a fibrolamaller HCC (fibrolamaller HCC also has a central scar) which is an aggressive lesion. Because of this – it may require interval imaging, biopsy and of course discussion in an MDT.
Surgery is limited to patients with a symptomatic lesion or when malignancy cannot be ruled out with imaging and biopsy.
- Treatment of symptomatic lesion can include resection
- TACE and RFA can also be used (in cases where resection poses risk)
NB: The central scar of a fibrolamellar HCC is due to central necrosis which is why it won’t enhanced on a T1 MRI delayed phase with Primovist.
FNH and OCP
- Although the OCP doesn’t cause FNH, they do stimulate growth - thus lesions should be followed with USS.
If not interval growth after 2-3 years can stop.
Risk factors, aetiology and presentation of hepatic adenoma?
Risk factors
- Occurs mainly in young to middle aged woman.
- ARE associated with use of the OCP and anabolic steroid (were relatively uncommon before the advent of the OCP)
- Are associated with obesity, glycogen storage disease, diabetes, galactosaemia, iron overload, occur in woman in the 3rd to 5th decade of life.
- Increased risk in pregnancy.
Aetiology
- Unclear but likely due to a combination of genetic mutations and hepatic vascular abnormalities with porto-systemic shunting.
Presentation
- Asymptomatic.
- Present with abnormal LFTs and pain
- Have a risk of spontaneous haemorrhage thus can present acutely.
- Have a risk of malignant transformation.
What is the Bordeux classification for a hepatic adenoma?
ordeux classification - based on genomic analysis
- Hepatocyte nuclear factor alpha (HNF1a) germline mutated adenomas – 30-35%. Low risk of progression to malignancy
- Inflammatory – 30% of adenomas. more common in obese patients or NAFLD, more likely to be associate with haemorrhage.
- b-catenin mutated adenomas - 10% of adenomas - much higher incidence of malignancy
- Sonic hedgehog adenomas – rare.
What are the imaging findings for hepatic adenoma?
CT
- Due to mixed composition of cells, fat and haemorrhage these lesions often look heterogenous.
- Unenhanced CT – hypodense
- Arterial phase – enhance (centripetal)
- Portal venous phase – isodense
MRI
- T1 imaging – hyperintense and heterogenous
- T2 imaging – hyperintense and heterogenous
- Difference between HCC and adenoma is that an HCC has washout – will become hypointense on portal venous/hepatocellular phase imaging.
What are the indications for resection for a hepatic adenoma?
- Adenomas in men (all adenomas in men should be considered for resection)
- > 5cm in size in woman after cessation of hormonal therapy
B-catenin mutated tumours (although in most cases you will not know this as biopsying hepatic adenomas is relatively risky)
What are the indications for resection for a young woman with a hepatic adenoma?
- If a young woman has a hepatic adenoma while on the pill this should be discontinued as often this will result in shrinkage or resolution of the lesion.
- If the lesion returns to below 5cm – can continue with surveillance.
Woman who are going to get pregnant need to be made aware that the adenoma may increase in size of have hemorrhagic complications.
What is the definition, aetiology, and histopathology of haemangiomas?
- Most common benign liver tumour
- No malignant potential and risk of rupture is very low (unlike hepatic adenoma)
- Big range in size and number (i.e. can grow to +++ large)
- DOES NOT have an association with the OCP
- No evidence that OCP use or pregnancy has a negative impact on growth
- Majority picked up incidentally.
Aetiology
- Exacty pathogenesis unknown. VEGF production plays a role in haemangioma development.
Histopathology
- Dilated vascular channels with fibrous walls layered by flat endothelial cells.
What are the imaging findings for haemangiomas?
CT
- Hypodense on non-contrast phase
- Arterial phage – nodular peripheral enhancement
- PV – enhancement continues towards the centre of the lesion (centripetal filling).
- Delayed phase – ongoing enhancement of the lesion
MRI
- Looks very bright (lightbulb sign) on T2 imaging (because haemangiomas are fluid filled)
- Looks hypointense on T1 imaging compared to surrounding liver.
Haemangiomas can generally be made using the imaging studies.
What are the indications for treatment for a haemangioma?
Indications for intervention
- Symptoms (compressive and pressure symptoms or Kasabach-Merrit syndrome)
- Diagnostic doubt
Relative indications
- Growth on interval imaging
- Tumours which are greater than 10cm (not 5cm like hepatic adenomas)
Patients who play contact sport.
What are the management options for haemangioma?
Management
- Can anatomically resect or enucleate.
- Surgery is generally associated with long procedure times, and significant blood loss due to the vascular nature of these lesions.
- TACE can be attempted but there is no good long-term evidence for this lesion.
TACE or RFA is can also be considered prior to resection (again no good long term evidence)
What is Kasabach-Merrit syndrome
With multiple haemangiomas, a patient can develop a consumptive coagulopathy due to platelets and clotting factors being eaten up in the haemangioma due to turbulent flow.
Whats an angiomyolipoma, biliary hamartoma, bile duct adenoma, and leiomyoma of the liver?
Angiomyolipomas
- Rare tumours which arise from smooth muscle cells, adipose tissue, and proliferating blood vessels (thus mesenchymal origin)
- Can be associated with tuberosclerosis but mostly are sporadic.
- Usually found incidentally.
- Affect woman 30-50 years old
- Only rarely are associated with malignancy.
- Because of 3 different tissue components can have confusing imaging findings and be confused with adenomas and HCC.
- If > 5cm then have a higher risk of malignant transformation thus liver resection should be considered.
Biliary hamartomas
- Also called Von Meyenburn complexes
- Abnormal developmental clusters of small intrahepatic bile ducts which lead to ulcerated areas with inflammatory cells and fibrosis.
- Usually present as multiple lesions which are small scattered throughout the liver (hyperintense on MRI)
Bile duct adenoma
- Proliferation of non-cystic biliary structures within a dense fibrous stroma.
- Generally not believed to be malignant thus left alone.
- Thought to be an exaggerated inflammatory response from an underlying infectious process.
- Difficult to be differentiated from cholangiocarcinoma thus sometimes will be found on a resection specimen.
- Can be treated with steroids and antibiotics.
Leiomyomas
- Benign liver tumour arising from smooth muscle cells of the bile ducts.
- More common in woman.
- Associated with EBV and HIV infection.
Varying enhancement on CT.
