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Liver Tumors

Women are benign, Men are malignant

 Introduction and anatomy of the Liver: 

The liver is the second largest organ after the skin, and the largest
internal organ in the body 
weighing 2% of the body weight in adults (1.5 kg
 in a 70 kg normal person).

The liver receives its blood supply (1.5/min liter of the normal 5 liters of a
70 kg person) from both the portal vein (the joining of the superior
mesenteric veins and splenic vein) and the proper hepatic artery (celiac
trunk division). Then it gives off the blood back through the middle, right

 and left hepatic veins that drain directly into the inferior vena cava.

Imp note: During surgery, and because of the passage of the IVC
between the liver tissue, sometimes it makes it really hard to
perform the surgery
 especially if we are talking about total
 hepatectomy.

The liver has many important functions, that’s why  we cannot replace its
 function by simply using a machine like the kidney.

The classical anatomical classification of the liver was just dividing the liver
into the left lobe and the right lobe, separated by the falciform ligament,
which gives off the coronary ligaments, which then at the end turn into the
left and the right triangular ligaments. The main job of these ligaments is to

attach the liver onto the diaphragm.
The surgical classification classifies the liver into eight different lobes. Also
known as the Couinaud classification.

The Couinaud classification of liver anatomy divides the liver into eight
functionally independent segments. Each segment has its own vascular inflow,
outflow and biliary drainage.

In the centre of each segment there is a branch of the portal vein, hepatic
artery and bile duct. In the periphery of each segment there is vascular outflow
through the hepatic veins.

- Right hepatic vein divides the right lobe into anterior and posterior segments.
- Middle hepatic vein divides the liver into right and left lobes (or right and left
hemiliver). This plane runs from the inferior vena cava to the gallbladder fossa.
- Left hepatic vein divides the left lobe into a medial and lateral part.
- Portal vein divides the liver into upper and lower segments.
The left and right portal veins branch superiorly and inferiorly to project into the
center of each segment.

Because of this division into self-contained units, each segment can be resected
without damaging those remaining. For the liver to remain viable, resections must
proceed along the vessels that define the peripheries of these segments. This means,
that resection-lines parallel the hepatic veins.
The centrally located portal veins, bile ducts, and hepatic arteries are preserved.

In order to understand the classification better revise this:
 Benign liver tumors: = Women 

1) Hemangioma (unknown etiology ”most likely congenital”- no malignancy what
so ever!): A hemangioma is a benign and usually self-involuting tumor (swelling
or growth) of the endothelial cells that line blood vessels, and is characterized
by increased number of normal or abnormal vessels filled with blood.

It is the most
 common benign lesion of the liver, and it could be capillary or
 cavernous.
- Cavernous mean the same malformation of blood vessels, but it results in
forming a cavity. And it is never self involuting, and it could be dangerous
especially if it happened in the brain or the liver (could cause bleeding).

Usually it is asymptomatic and discovered incidentally.
 

It is of an unknown etiology, but what makes it more prominent to occur in
females is the suspected relation with estrogen hormone levels. That is why
it decreases in size for women after menopause.
 

No need for surgery unless it causes a problem.

 Problems that may arise from a hemangioma: 

A) Large size causes stretching of the liver capsule, which causes pain.
B) These abnormal blood vessels could get thrombosed, which in turn
causes pain.
C) Large size could also result in Kassabach- Merrit syndrome ( hemangioma
with thrombocytopenia, leading to bleeding and possibly DIC and death) .

 Could be noticed on both: 

1) CT- with IV contrast- where you can notice the hemangioma starting to
fill from the periphery with patchy infiltrates and with more delayed images
it will fill into the middle.
2) T2 MRI- usually on T2 the fluid that are static will appear as bright, so
because of the presence of a hemangioma, there will be stagnation of blood, and
it will appear as static on T2 MRI.

2) Hepatocellular adenoma: Uniform masses of benign appearing hepatocytes without
ducts or portal triad. So it’s a liver mass made of its own cells.

Basically it is associated
 with high levels of estrogen and the use of
 contraceptive pills.

Asymptomatic, or symptomatic, Diagnosed by the use of MRI imaging. The
most common complication of this benign  lesion is bleeding (either into the
tumor if the surrounding liver tissue).

It has the tendency to turn into malignant, so
resection of asymptomatic or
symptomatic masses is the proper treatment.

3) Focal nodular hyperplasia: Masses of many normal hepatocytes mixed with bile
ducts and divided by fibrous septa, so it’s the same as adenoma except that it has
bile ducts within the masses, and these masses are separated by a fibrous septum
that we call “A scar”. The scar is a very important feature to differentiate FNH.

Again most commonly occurs
 in women. It could be multifocal and it could
 accompany a hemangioma.

It is difficult to diagnose it by imaging, butthe “scar” is a prominent
 feature, but we usually need to take a biopsy.

There is no proof of malignancy in FNH, but because it is difficult to
diagnose, so it is always safe to remove. 
It is also safe to remove when it is
symptomatic or have a really large size.

4) Simple liver cyst: Non-parasitic single or multiple cysts that are lined by single
layer of cuboidal or columnar epithelial cells.

Again and again, it affects females 4 times more than males. 

Usually asymptomatic, but if enlarged it could cause pain like the other benign
 lesions.

Simply on anUS or CT scan you can notice a round water-filled lesion, this is
 diagnostic.

It is removed through what is known as deroofing (laparoscopic
 removal
 of the cyst off the top of the liver) for symptomatic cysts.

 
This is an example of a
large cyst, no nodular
walls or septation.
5) Other benign lesions: What is worth mentioning here is the bile duct
adenoma/hamartoma- Almost always asymptomatic and found incidentally on
laparoscopy or laparotomy where they can be confused with liver mets.

 Malignant liver tumors: = Men! 

Primary liver tumors are uncommon with metastatic carcinomas representing the
most common malignant lesions; hence most common are secondary liver tumors
(mets from the colon from the rectum). Most malignant cases are preceded by
liver cirrhosis. And here, malignant tumors are more prominent in men.

Hepatocellular carcinoma:

Epidemiology : Accounts for 90% of all primary liver tumors, and it is the
th rd
5 most common tumor and the 3 most common cause of cancer related

- male : female ratio = 4:1 , in Europe peak age at presentation is 80 years ,
while in Africa and asia peak presentation is 40 years .
- incidence of HCC parallels the world-wide prevelance of hepatitis B ,
which means as hepatitis B incidence increase , HCC incidence increase also

The pathogenesis of HCC is important to understand the risk factors (in
 order for them to make sense, and for you not to forget in the future).


Hepatocellular carcinoma, like any other cancer, develops when there is a mutation
to the cellular machinery that causes the cell to replicate at a higher rate and/or
results in the cell avoiding Apoptosis. In particular, chronic infections of Hepatitis
B and/or Hepatitis C can aid the development of hepatocellular carcinoma by
repeatedly causing the body's own immune system to attack the Hepatocyte, some
of which are infected by the virus, others merely bystanders. While this constant
cycle of damage followed by repair can lead to mistakes during repair which in turn
lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C.
Chronic hepatitis C causes HCC through the stage of Cirrhosis. In chronic hepatitis
B, however, the integration of the viral genome into infected cells can directly
induce a non-cirrhotic liver to develop HCC.
Alternatively, Alcoholism can have a similar effect. Besides, Cirrhosis is commonly
caused by alcoholism, chronic Hepatitis B and chronic Hepatitis C. The toxin
Aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids
carcinogenesis of hepatocellular cancer by building up in the liver. The combined
high prevalence of rates of aflatoxin and hepatitis B in settings like China and West
Africa has led to relatively high rates of heptatocellular carcinoma in these
regions. Other viral hepatitis such as Hepatitis A has no potential to become a
chronic infection and thus is not related to hepatocellular carcinoma.

The incidence of HCC is related to the risk factors, and we have two simple major

1) Hepatitis C and B, that count for 75% of the cases of HCC, and usually HCC
develops after 20-40 years of the viral contamination. The more the chronicity of
the virus the more likely the HCC will develop. And, that is why Hep C has high
prevalence, while Hep A has zero prevalence. It also depends on the area, in China
there is high prevalence for Hep B, while in the USA the high prevalence goes to
Hep C because of the vaccination programs.

2) Liver cirrhosis, which could be caused by:

A) Alcoholism, most commonly.
B) NASH, non-alcoholic steatohepatitis.
C) Hemochromatosis.
Note: Primary biliary cirrhosis or autoimmune hepatitis could cause cirrhosis
of the liver but rarely do go to the next step of HCC.

3) Diabetes mellitus, aflatoxin exposure, hepatic adenoma, Alpha-antitrypsin

deficiency, Wilson’s disease. All of these are considered risk factors.

When Cirrhosis is present, if it associated with a late stage, old age, male sex
and diabetes it could have a higher risk of HCC (hence combining the many risk

Clinical presentation :

- Suspected in any patient with liver cirrhosis who shows evidence of clinical
deterioration .

- It's often presented with right hypocondrial pain +/- mass .

- Generally presenting like any other malignancy : malaise , weight loss , low grade
pyrexia , loss of appetite , fatigue .
- Jaundice but as a late feature .

- Haemobilia , hemoperitoneum , which are the immediate causes of death .

- With increased size, it could result in abdominal pain, loss of weight

unintentionally and loss of appetite.
 In some cases, there is rupture of the tumor
which results in acute abdomen.

 

Diagnosis : The best way to diagnose HCC is through screening for the tumor in
those patients who have 
risk factors. So, Liver function tests are not specific.
The best two tests are:

A) The tumor marker that is Alpha feto protein (AFP).
B) The cornerstone diagnostic tests are imaging, featuring early uptake (which is
enhancement on the arterial phase) and delayed washout (which is disappearing
on venous phase). HCC is supplied by the hepatic artery.

Other general ways to detect HCC : Ultrasound (transabdominal or laparoscopic) , CT

scan (conventional or lipoidal enhanced) , CT portography .

** Alpha-fetoprotein :

- Alpha : a protein contains alpha chain .

- feto : produced by yolk sac and the liver of the fetus .
so this protein is produced by the yould sac and the liver of the fetus and it's
found in a high level in the fetal life . but when the child is born the level of this
protein will decrease .
Hence , any increase in the level of Alpha-fetoprotein during life indicates a
problem in the liver .
1- Slight increase (fluctuating serum levels) : seen in hepatitis and cirrhosis .
2- Progressive increase in serum level : seen in 70-90% of patients with HCC .

Note that :
Alpha-fetoprotein serum level increase as the size of the tumor increase . Tumor
resection will result in a fall in Alpha-fetoprotein serum level . serial assessment of
Alpha-fetoprotein serum level is useful in measuring response to treatment .


A) Curative treatments:
1) Liver resection: in case of compensated cirrhosis.
2) Liver transplantation: late stage of cirrhosis. It is important to mention
here Milan criteria for Liver transplantation which is:

 
One lesion smaller than 5 cm.
 
Up to 3 lesions smaller than 3 cm.
  
No extra-hepatic manifestations.
 
No vascular invasion.

B) Palliative treatments:

1) TACE: Trans-arterial chemo-embolization is a minimally invasive procedure

performed in interventional radiology to restrict a tumor's blood supply.
Small embolic particles coated with chemotherapeutic agents are injected
selectively into an artery directly supplying a tumor.

2) Ablation: Destroying the tumor while it is in its place, through

A) RFA: radio-frequency ablation, which uses heat.
B) PEI: percutaneous ethanol injection. (High levels of alcohol that kills
the tumor).
C) Microwave.
D) Cryo. The use of freezing.

3) Sorafenib, which is a tyrosine kinase inhibitor, it is found that it improves

the survival period by six months, but it is a very expensive drug.

Peripheral Cholangiocarcinoma: affecting the right and left hepatic ducts, so it

affects intrahepatic bile ducts.

 Used to be known as metastatic carcinoma of unknown origin. 

Risk factors for this tumor are:

A) Chronic choledocholilithiasis.
B) Parasitic biliary infestations.
C) Chronic typhoid.
D) Bile duct adenoma.
E) Choledochal cyst (congenital cyst in the biliary tree).
F) Caroli’s disease (congenital dilatation of intrahepatic ducts).
G) HBC, HBV, Alcoholism and NASH.

Usually discovered atadvanced stage with non specific symptoms like abdominal
pain and weight loss.

 
Tumor markers: CA 19-9 and less commonly CEA may be elevated.

 Staging of peripheral Cholangiocarcinoma is very important here: 
The Liver Cancer Study Group of Japan classified peripheral cholangiocarcinoma into
three types: Mass forming (most common), periductal infiltrating, and intraductal

o Stage I: Single tumor with no vascular invasion o Stage II:
Single tumor with vascular invasion
o Stage IIIA: Multiple tumors
o Stage IIIB: Tumor with regional lymph node
o Stage IV: With distant metastasis

Treatment: is similar to HCC, but liver  transplantation is not approved yet. Some
centers do it under very strict criteria.

Other malignant tumors:

Fibrolamellar carcinoma. 

Epithelioid Hemangioedothelioma. 

Angiosarcoma. 

Primary Hepatic lymphoma.

Liver metastases :

The most common malignant tumors in the liver are "liver metastases" which are
Secondary tumors .
Be aware that HCC is the most common primary malignant liver tumor …

- the most common organ that causes liver metastases is the Colon , about 50% of
patients with colorectal carcinoma develop liver metastases .
- 20% have metastases at time if initial surgery.
- 25% develop metastases within 5 years of 'curative' resection .
-Median survival with metastases is about one year .

Detection of metastases :

* Value of intensive follow-up after curative resection for colorectal cancer is

controversial .
* Lesions more than 0.5 cm in diameter are detected by ultrasound .
* Lesions less than 0.5 cm in diameter are detected by CT scan .
So CT scan is the diagnostic modality of choice to detect liver metastases on follow
up of a patient with colorectal cancer .
* we can find elevated tumor markers ( CEA , CA19.9 , CA 242)
Liver resection for metastatic disease :
Resectional surgery is the only chance of cure for patients with liver metastases . only
10% of these patients are suitable for curative hepatic resection .

If the metastases found in a certain segment then we do segmedectomy , if it's found

in a certain lobe we do hemi-hepatectomy , we do them by 1 cm safety margins , but if
the metastases is diffuse ,we do nothing .

Liver abscesses :

Pyogenic liver abscess :

It's an inection within the liver parenchyma . usually seen in elderly patients , can
be multiple or solitary . it arises as a result of biliary sepsis (specially cholengitis) : in
biliary sepsis there is an obstruction of the common bile duct which lead to
accumulation of the bile and growth of bacteria in this bile which causes infection .
Mortality is high as diagnosis is often delayed . commonest organisms involved are
E.coli , klebsilla , proteus and bacteroides species .

Etiology :
1- The most common is biliary diseases : cholecystitis , ascending cholengitis , or
pancreatitis .
2- Portal pylophlebitis : appendicitis , diverticulitis or pelvic infections .** how can
appendicitis cause liver abscess ? by venous drainage ilio-colic vein at appendix
 superior mesenteric vein  potal vein which transfers the infection to the
liver) .
3- Trauma : blunt or penetrating .
4- Direct extension : empyema of the gallbladder , subphrenic or perinephric
abscess .
5- Septicemia
6- Infected liver cysts or tumors .

Clinical features :
Patients are generally systemically unwell suffer from severe abdominal pain usually
localized to right hypocondrial region with swinging pyrexia (can be as high as 39.5
then become very low) , rigors , chills , weight loss , anorexia , 25% with jaundice , and
30% right sided pleural effusion .

On examination : hypochondrial or epigastric mass which causes tenderness .

Investigations :

* Serology shows a raised WBC , increased ESR and deranged liver function test .
* Chest X-ray often shows a raised right hemi-diaphragm and pleural effusion .
* Ultrasound will localize the abscess and will guide drainage .
* CT scan is useful if diagnosis in doubt or if there are multiple abscesses .

Management :
Non-surgical management .

- Like any other infection , patients with liver abcesses should be started with
appropriate antibiotics (metronidazole , cephalosporin) evacuate the pus , and
eliminate the source of infection ,
- Percutaneous drainage under ultrasound guidance is the initial treatment of choice ,
if it fails , laparoscopic drainage may succeed .
- if the cause is biliary obstruction then we need to consider decompression .

Surgery may be required if :

1- Failure of resolution with percutaneous drainage .

2- Intraperitoneal rupture .

* Both situations ( non-surgical and surgical treatment ) are associated with high
mortality (>30%) .

Amoebic liver abscess :

Due to infection with a protozoan parasite called Entamoeba histolytica , found in
the stool of carriers in the cysts of the trophozoite form . this organism is
transmitted by the fecal-oral route .

The liver is the most common extra-intestinal site of infection as 10% of

affected patients develop liver abscess . theses abscess can be multiple or solitary
and 80% of them develop in the right lobe of the liver .

Clinical features :
Patients present with malaise , pyrexia , weight loss , mild right hypochondrial pain and
fatigue . less than 20% of patients present with diarrhea or had past history of
diarrhea . Jaundice is uncommon .
Complications can arise as a result of abscess rupture or extension of infection . these
complications include : amoebic empyema , hepato-bronchial fistula , lung abscess and
pericarditis .

Investigations :
* Serology shows raised WBC and ESR .
* Latex agglutination assay is positive in more than 90% .
* Sigmoidoscopy , stool microscopy and rectal biopsy may identify the organism (we
see the cysts of the trophozoite) .
* Chest X-ray may show a raised right hemidiaphragm , atelectasis or abscess .
* Aspiration produces a typical 'anchovy sauce' appearing odorless pus (appears like
chocolatein color) which is a diagnostic feature for amoebic liver abscess . it's sterile
on routine culture .

On the other hand the pus in the pyogenic abscess (like any other pus) is white to
yellow and has an odor .

Note : always patients with amoebic abscess will have pyrexia (their temperature
increase to 39.5 c) at 6:00 AM .


Management :
* Metronidazole is the antibiotic of choice after evacuation of the pus collection
inside the cyst . if ineffective ; chlorquine and dihydrometine may be considered .
* Ultrasound guided aspiration may be useful .
* Surgery is rarely required .

Prognosis :
prognosis in uncomplicated cases is good , but if pulmonary complications occur ,
mortality can be as high as 20% .

Done by: Saed Jarrar

Modified by : Hamzeh Al-Domaidat

Good Luck