LIVER TUMOURS
ROSE CHERIAN
History
• First recorded successful elective resection of a liver
tumor in the United States was performed by Tiffany in
1890
• Surgeons were reminded of the risk of massive
hemorrhage from the liver by Elliot in 1897 reported
“liver is so friable, so full of gaping vessels and so
evidently incapable of being sutured that it seemed
impossible to successfully manage large wounds of its
substance.”
Classification
Liver tumors
Primary
Benign
Metastatic
Malignant
Primary liver tumors
Malignant neoplasms
 Hepatocellular carcinoma
 Cholangiocarcinoma
 Hepatoblastoma
 Epithelioid hemangiendothelioma
 Hepatic sarcomas
Benign
 Hepatic adenomas
 Focal nodular hyperplasia
 Hemangiomas
Patient evaluation
Clinical
 Complete history and
physical examination.
 Since detection of advanced co morbid disease
or more extensive tumor spread, usually
extrahepatic metastases, will often eliminate
the patient from further consideration of surgery
as the principal therapy.
LAB STUDIES
 Complete blood count
 Serum electrolytes
 Liver function test (LFT).
 Tumour markers
LFT
 Parenchymal (hepatocytes)-AST, ALT
 Canalicular (biliary)-ALP, 5´NT, GGT, bilirubin
 Synthetic function and metabolism-INR,
albumin
 History of hepatitis- anti-hepatitis B
antibody, hepatitis B surface antigen, and
anti-hepatitis C antibody
Tumour markers
 Screening for tumors or monitoring tumor status
following treatment
 Elevated a-fetoprotein levels (normal 1 to 10 ng/ml)
has a sensitivity of 68% for early Hepatocellular
carcinoma(HCC)
 Combined with trans-abdominal ultrasound in
patients with chronic hepatitis and cirrhosis for
early diagnosis of HCC
 Sharp steady rise in serum AFP - highly diagnostic
 α-fetoprotein-L3, an isotype more closely associated
with HCC
 abnormal prothrombin or PIVKA-II another tumor
marker in HCC.
IMAGING STUDIES
 The single most important factor for the current
success of liver-directed therapy is better patient
selection due to the accuracy of modern imaging
studies.
 Imaging studies have the following goals:
(i) Determination of the number and distribution of the
liver lesion(s)
(ii) Anatomic and functional characterization of liver
lesion(s)
(iii)Delineation of the lesion(s) relationship to significant
vascular and biliary structures
(iv)Detection of extrahepatic and extra-abdominal tumor.
ULTRASOUND
 Readily available, least expensive, and least
invasive of the imaging modalities for the liver.
 Greater detail about intratumoral anatomy
and tissue characteristics is provided by
ultrasound when compared with CT.
 Valuable therapeutic role when used in the
ablation of liver lesions, particularly in alcohol
ablation.
Intraoperative ultrasonography
(IOUS)
 Gold standard to detect the number, extent, and
association of tumors with intrahepatic blood
vessels.
 IOUS can be performed laparoscopically or during
laparotomy
 Prior to proceeding with liver resection for
malignancy, all patients should undergo IOUS as
a way of excluding the presence of smaller
lesions not detected by preoperative studies.
 IOUS is necessary for intraoperative imageguided procedures such as biopsy and
radiofrequency ablation (RFA).
The use of intraoperative ultrasonography in a laparoscopic left lateral sector liver
resection. The ultrasound probe (inset photograph) is used to delineate the
thickness of the liver and the location of the portal structures and left hepatic vein
in the left lateral sector. Asterisk = inferior vena cava; white arrow = thickness of
the liver at the ligamentum venosum groove.
Computed tomography
 Modern helical CT scans are and are highly
sensitive at spatial discrimination
 The smallest detectable lesion size is
approximately 1 cm.
 Post-liver resection, residual liver volumes
can be calculated with CT volumetricsImportant in planning extensive liver
resections and living donor transplantation
A CT scan of the upper abdomen showing a widespread
(disseminated) carcinoma of the liver (hepato cellular
carcinoma). The liver is the large organ on the left side
of the picture. Note the moth-eaten appearance.
Triphasic CT
 Liver receives vascular inflow from both hepatic
artery (30%) and portal vein (70%), while tumors
receive their blood flow almost exclusively from
the hepatic artery.
 After the noncontrast images are obtained
contrast injected, scanning repeated at 25 sec
(arterial phase) and 70 sec (portovenous phase)
 HCCs therefore enhance early on during the
infusion of contrast, in the arterial phase
 The liver parenchyma enhances during the
portal venous phase
Lipiodol computed
tomography(LCT)
 Lipiodol, which is an ethiodized oil
emulsion, is unique in that it is retained
(indefinitely) within tumors but not normal
or cirrhotic liver.
 Lipiodol is mixed with chemotherapeutic
drugs so that these drugs will have both a
higher concentration and duration of action
when retained within the tumor.
Magnetic resonance imaging
 MRI has not achieved the same widespread popularity as CT for
routine imaging of the liver
 MRI does offer excellent delineation of lesion morphology and
characteristics as a result of using multiple pulse sequences.
 MRI scans are more sensitive for detecting early HCC
and in distinguishing HCC from macroregenerative
nodules.
 Ability to characterize reliably benign liver lesions,
such as cysts or hemangiomas, from malignant
lesions is a major advantage of MRI.
Nuclear scans
 Normal liver tissue contains Kupffer cells- take up 99Tcmsulfur colloid. Tumours lack Kupffer cells, and are
visualized as photopenic defects on liver–spleen scans.
 99Tc- albumin scan is useful in distinguishing complex
FNH from an adenoma. This agent is taken up by Kupffer
cells in FNH while most adenomas are "cold" because they
lack Kupffer cells.
Positron emission tomography
(PET)
 The alteration of biochemical processes within tumors
usually precedes their detection by gross anatomic
changes.
 Enhanced glycolysis and glucose retention in tumor cells is
the basis for 18F-fluorodeoxyglucose PET imaging
 Only modest success in hepatocellular carcinoma.
Fusion of positron emission tomography and computed tomography to demonstrate
a large malignant tumor involving the right liver lobe(CT-PET)
Percutaneous Biopsy
• As the specificity of
imaging studies had
improved percutaneous
biopsy is rarely
indicated
• In patients in whom the
diagnosis is not evident
a percutaneous biopsy
can be done with
ultrasound or CT
guidance.
• The target lesion should
be accessed through a
quantity of normal liver
tissue sufficient to avoid
free rupture of tumor
into the peritoneum
Diagnostic laparoscopy
 Because of the
limitations of CT and
MRI for detection of
extrahepatic tumor
recurrences, diagnostic
laparoscopy has been
considered as an initial
step in surgical
exploration.
 One-third of patients with HCC will be
deemed unresectable by laparoscopy due
to the detection of unrecognized
intrahepatic tumor spread or peritoneal
seeding
MALIGNANT NEOPLASMS
Hepatocellular carcinoma
 Most common primary malignant tumor of liver in
adults.
 Hepatocellular carcinoma causes an estimated
one million deaths annually
 High mortality - both patient presentation at a late
stage of the disease and poor hepatic function
resulting from cirrhosis
HCC- Etiology
Environmental and viral.
 The most prominent factor worldwide is chronic hepatitis
from HBV and HCV infection.
 The annual cumulative risk in chronic viral hepatitis
without cirrhosis is approximately 1 %, while with cirrhosis
the risk ranges from 3 to 10 %.
 Most potent natural carcinogen is a product of Aspergillus
fungus called aflatoxin B1.
 In low-incidence areas, alcohol-induced hepatic cirrhosis
has a major etiologic association -its role as a
cocarcinogen rather than a direct carcinogenic agent.
Other risk factors:
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Wilson’s disease,
Tyrosinemia,
glycogen storage disease,
oral contraceptives(by causing hepatic
adenoma),
Androgens and anabolic steroids,
Organochlorine pesticides,
Tamoxifen (animal studies)
Hemochromatosis
Alpha 1-antitrypsin deficiency.
HCC-Clinical presentation
Presenting symptoms and signs are related to the
tumor stage
 The most common, and often the first complaint is right upper
quadrant abdominal pain, which may be accompanied by abdominal
distention.
 Anorexia or early satiety with weight loss is present in one-third of
patients.
 In a patient with cirrhosis, the development of unexplained upper
abdominal pain, weight loss, fever, enlargement of the liver, or
ascites should alert the possibility of HCC.
The physical findings associated with HCC
depend on the stage of the disease.
 Hepatomegaly is present in more than 90% of
patients; the liver is irregular and nodular on
palpation.
 A hepatic arterial bruit or a friction rub may be
present.
 Ascites is found in up to
50% of patients. Splenomegaly
indicates long-standing cirrhosis.
 If present, jaundice is usually slight or moderate; it
tends to become deeper with progression of the
disease.
 The Budd-Chiari syndrome - malignant invasion of
the hepatic veins.
 Paraneoplastic manifestations hypoglycemia caused by ectopic production of
insulin like growth factor(IGF)(most common)
 erythrocytosis
 hypercholesterolemia
PATHOLOGIC DIAGNOSIS
Four major gross patterns and two special forms of
HCC have been described.
 (1) expanding type, the tumor is encapsulated and
grows by compressing the surrounding parenchyma.
 (2) spreading type, the tumor is poorly defined and
occurs in hepatic cirrhosis.
 (3) multifocal pattern in which several small tumors
of similar size are found in multiple sites in the liver.
 (4) A indeterminate pattern is seen in up to 25% of
cases.
Two special forms of HCC.
(1) The fibrolamellar form - 2% to 4% of cases
 In young women and is characterized by neoplastic hepatocytes
with fibrosis arranged in lamellar fashion.
 Not associated with elevated serum AFP, chronic viral hepatitis, or
cirrhosis.
 Survival following surgical resection is significantly better, even with
extrahepatic metastases.
(2) The other special form, cholangiocellular carcinoma,
appears to be a combination of cholangiolar elements as well as
hepatocellular elements.
 These tumors behave more like cholangiocarcinoma and tend to
occur in noncirrhotic livers, with a male predominance.
 The outcome for patients with this form of HCC is uniformly fatal.
Patient evaluation and selection
 Prognosis of patients with HCC is determined not only by
the tumor's stage, but also by the functional status of the
patient's liver.
 Child's classification give an excellent initial idea of
treatment limitations imposed by hepatic dysfunction.
 quantitative assessment of liver function is usually
required. Indocyanine green clearance - accurate
indicator of hepatic reserve.
Adverse tumor factors include
 multicentricity, bilobar distribution,
 size greater than 5 cm,
 capsular invasion, extrahepatic
metastases, and
 vascular invasion or thrombosis.
Surgical resection
Patients selected meet the following criteria:
 a solitary HCC less than 10 cm in diameter or
 up to three smaller HCC in a surgically accessible location(s);
 no vascular invasion of main portal trunk, or hepatic vein;
 no extrahepatic tumor (with the exception of fibrolamellar
hepatocellular carcinoma);
 Child's class A or well compensated B;
 adequate liver function by quantitative studies;
 intact performance status; excellent control of significant
comorbid medical illnesses, particularly diabetes mellitus and
renal insufficiency.
The operative goal is as limited a resection as possible to achieve a
1-cm margin of normal tissue
A right subcostal incision (A) with a midline extension to the xiphoid (D) is the most
common choice; an extension to the left subcostal area (C) is sometimes added to
provide further operative exposure
HEPATIC RESECTIONS
Non-anatomic resection
 A non-anatomic resection or partial
lobectomy is frequently used,
particularly in patients with cirrhosis.
 Regardless of technique, the principal
goal during parenchymal transection is
to maintain more than a 1-cm margin
Ablative techniques
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Percutaneous ethanol injection
Cryoablation
Radiofrequency ablation
Embolization and chemoembolization
Systemic chemotherapy
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Cryosurgical techniques also have shown applicability to treating
hepatocellular carcinoma. A probe containing circulating liquid nitrogen is
introduced directly into the primary liver tumor and the lesion is frozen
using ultrasound guidance. Cryosurgery can be applied to tumors up to
six centimeters in size but, unlike ethanol injection, requires an open
surgical procedure.
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Radiofrequency ablation is a newer technique that is particularly well-suited for
destruction of hepatocellular cancers. A 14 gauge needle is directed into the
tumor by ultrasound or CT guidance and an alternating current is applied, similar
to microwave. The heat generated exceeds 100 degrees Celsius and destroys
the tumor. RFA appears to be safer than cryosurgery, although it's effectiveness
compared to cryosurgery is less clear. RFA can be done using minimally
invasive techniques such as percutaneously (through the skin) or
laparoscopically using a video camera system. For larger, more difficult tumors,
a more traditional surgical approach may be needed.
 A schematic diagram demonstrating a patient undergoing
radiofrequency (RF) ablation of a malignant liver tumor (top half of
illustration). The multiple array RF electrode is inserted into the liver
tumor with the intent of producing complete coagulative necrosis of the
tumor and a surrounding zone of nonmalignant hepatic parenchyma.
The RF needle electrode and grounding pads from the patient are
attached to a radiofrequency generator. The lower portion of the
diagram shows the ionic agitation that occurs around the multiple array
RF needle electrode when alternating current from the RF generator is
applied. Ionic agitation produces frictional heating in the tissue,
resulting in coagulative necrosis of tissue around the electrode.
CHEMOEMBOLIZATION
PREVENTION
PRIMARY PREVENTION
 Prevention of HBV and HCV infection are the most
effective ways of preventing HCC.
 Vaccination in early childhood, particularly in endemic
areas, has been the most effective strategy in preventing
chronic HBV infection

 Prevention of HCV infection is more difficult because
there is no vaccine or effective postexposure prophylaxis
available.
 Because transmission is primarily parenteral, universal
precautions against exposure to blood-borne infectious
agents will be effective against HCV.
SECONDARY PREVENTION
 Effective secondary prevention is dependent
on early detection and resection of small
tumors.
 Patients with chronic viral hepatitis or
cirrhosis of any etiology are candidates for
semiannual or annual screening with αfetoprotein, with ultrasonographic follow-up of
those with α-fetoprotein > 20 ng/mL for early
detection of liver tumors.
Cholangiocarcinoma
 Cholangiocarcinomas account for 10 per cent of
all primary hepatic malignancies and are second
to hepatocellular carcinoma in incidence.
 Two types – Hilar and peripheral
cholangiocarcinoma
 The much commoner hilar form usually situated
at the confluence of the right and left hepatic
duct.
 Peripheral cholangiocarcinoma develops in the
small intrahepatic bile ducts and is associated
with etiologic factors including
 Hepatobiliary parasites, particularly flukes, and
intrahepatic lithiasis.
CLINICAL FEATURES
 Hilar
cholangiocarcinoma –
jaundice,pruritus,
abdominal pain, fever ,
wt loss .
 Peripheral
cholangiocarcinoma vague abdominal pain
,unexplained wt loss ,
progressive weakness.
Technique of transhepatic percutaneous cholangiography; B,
corresponding percutaneous cholangiograph (after catheter is
introduced).
Computed tomography (CT) image showing cholangiocarcinoma in the
hilum of the liver.
TREATMENT
 Hilar Cholangiocarcinoma – resection of
bifurcation of common hepatic duct.
 Peripheral cholangiocarcinoma – hepatic
lobectomy or segmentectomy
 Results with liver transplantation(assoc.with
tumour recurrence) and chemotherapy
disappointing
Hepatoblastoma
 Hepatoblastoma is the most common primary
hepatic malignancy in children
 The serum a-fetoprotein level
is elevated in 75 to 95
per cent of patients
 Surgical resection is the mainstay of
therapy.
 Preoperative chemotherapy with cisplatin, 5fluorouracil, and vincristine has been shown
to be effective for improving resectability
and decreasing recurrence rates.
Hepatoblastoma. (a) CT scan at diagnosis before 4 courses of PLADO
(Cisplatin/doxorubicin) chemotherapy ; (b) CT scan after chemotherapy.
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Patient with hepatoblastoma: (a) at 18 months, at diagnosis. She had a huge
"PRETEXT 3" primary tumor and multiple lung metastases; (b) after four
courses of PLADO via the Hickman catheter, but before surgical resection of
primary; and (c) at 12 years, 10 years off treatment, with hearing aids as a
result of cisplatin ototoxicity.
Benign neoplasm
Hepatic adenoma
 Occur in reproductive-aged
women, and are more
common in women who use
oral
contraceptive
pills
(OCPs).
 Histologically these lesions
are composed of sheets of
hepatocytes
with
no
nonparenchymal
cells
(Kupffer cells) or bile ducts
present.
 Up to 75% of adenomas may be symptomatic at the
time of presentation, with abdominal pain being the
most common presenting symptom.
 Hepatocellular adenomas are significant in that they
can rupture and as many as 25% of these lesions are
identified after an acute episode of hemorrhage.
 Malignant change can occur.
Adenoma with hemorrhage
Treatment
 Cessation of OCPs in patients with lesions less
than 4 cm in diameter can result in regression.
 Surgical resection standard treatment
Surgical intervention is recommended in
 Patients with lesions larger than 4 cm in
diameter.
 Patients whose lesions do not shrink after
cessation of OCP use .
 Patients who plan to become pregnant.
Focal Nodular Hyperplasia
 In contrast to hepatic adenomas, focal nodular
hyperplasia typically is not associated with
symptoms and does not pose any risks of rupture
or malignant degeneration.
 The lesions are often peripherally located and
histologically composed of regenerative nodules
with hyperplastic bile ducts and connective tissue
septae.
 In patients with symptoms related to FNH,
resection is indicated.
 Resection of the lesion with a thin margin of
normal liver parenchyma is curative,
 Radiographically, it is difficult to distinguish hepatic
adenomas from focal nodular hyperplasia (FNH).
 Adenomas may demonstrate increased fat signal on
MRI and do not have a central scar, which is
frequently seen in FNH.
 If the diagnosis is unclear obtaining a 99Tcmacroaggregated albumin (99Tc-MAA) liver scan
should be considered.
 Typically, adenomas will be "cold" and FNH "hot"
owing to the presence of nonparenchymal cells in
the latter.
 Figure 2. On CT scan, focal nodular hyperplasia
appears as lobulated intrahepatic lesions with central
lucency (scar).
Cavernous hemangioma
 Generally discovered incidentally on axial imaging
studies.
 Most hemangiomas are small and seldom need
treatment, except when an ill-advised biopsy provokes
hemorrhage.
 Contrast enhanced CT and MRI investigations of
choice.
 MRI : Hypointense in T1 and hyperintense in T2
 Resection can be recommended if symptoms
can be clearly ascribed to a large hemangioma
or if it ruptures
 Hemangiomas can be resected by enucleation
or more standard formal liver resection.
 There is no cause for concern if the resection
margin contains evidence of hemangioma,
since they do not recur.
Post-contrast MR imaging of the
liver demonstrating nodular
peripheral enhancement of the
right hepatic lobe lesion. First
image demonstrates completely
hypointense rounded lesion, which
shows peripheral enhancement in
the subsequent phases. This
enhancement pattern is typical for
liver venous malformations
("cavernous hemangiomas").
coronal T2 weighted MR
image demonstrating a
slightly larger rounded
bright lesion. Liver
venous malformations
("hemangiomas")
demonstrate bright signal
on T2 MRI images.
Metastatic tumors
 Most common malignant
liver tumor
 40% of patients dying with
a solid tumor develop liver
metastasis.
 10-20% of patients with
liver metastasis from
colorectal cancer have
potentially resectable
disease.
 Bronchogenic carcinoma most common primary lesion.
Metastasis: When breast cancers spread, their most common
destination is the liver, bones, or lungs
Colorectal cancer and liver metastasis
 Elevated CEA (>9ng/ml) with
positive results of liver
imaging predicts metastasis
with 98% accuracy.
 Resection of liver metastasis
improves survival.
 Predictors of survival after
resection of liver metastasis
are size,number of liver
metastasis and presence of
residual local disease.
Other treatment modalities
Hepatic artery infusion of chemotherapeutic agents and
systemic chemotherapy.
Pre-treatment colorectal liver
metastases
Liver metastases following
hepatic arterial pump
chemotherapy
Resection of non colorectal metastases
 Neuroendocrine malignancies including
metastatic carcinoid second most
common indication for resection of
secondary liver tumors.
 Resection is mainly palliative and
produce symptomatic improvement.
 Resection of liver metastasis from
other primary tumors not
indicated.
Color-enhanced
angiogram of a carcinoid
tumor metastasis to the
liver.
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