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TABLE 6.5. Essentials: Liver Abscess
Bacterial abscess
Causes Escherichia coli
Klebsiella
Pseudomonas
Proteus
Enterococcus
Streptococcus pyogenes
Symptoms Fever and chills
Jaundice
RUQ pain
Treatment Broad-spectrum antibiotics (6 weeks)
Percutaneous drainage (unilocular abscess)
Surgical drainage
Amebic abscess
Cause Entamoeba histolytica
Symptoms High fever
Jaundice
Antecedent bloody diarrhea (10%)
Diagnosis Serologic (hemagglutination, complement
fixation, ELISA)
US or CT-guided aspiration (“anchovy paste”)
Treatment Medical (metronidazole)
Surgical drainage (rarely)
Abbreviations: CT, computerized tomography; ELISA, enzyme-linked
immunosorbent assay; RUQ, right upper guadrant; US, ultrasonography.
Laboratory Studies
A high level of leukocytosis is usually present. Anemia is
frequent in bacterial abscesses. Serum bilirubin is usually
normal, but alkaline phosphatase is frequently elevated.
Blood cultures are positive in 50% of patients and are
more likely to be positive if obtained while the patient is
experiencing chills.
In amebic abscess, the laboratory findings are indistinguishable from those of bacterial abscess. Specific diagnosis may be obtained from serologic tests, including
hemagglutination, complement fixation, indirect fluorescent antibody assays, enzyme-linked immunosorbent
assay (ELISA), countercurrent immunoelectrophoresis,
and agar gel diffusion. Aspiration of amebic abscesses is
performed as a last resort. If done, the result is typical
“anchovy paste” aspirate.
Radiologic Studies
Ultrasonography is the initial imaging test of choice. CT
is more accurate but also more expensive. Ultrasonographic or CT-guided aspiration of abscess may be done
for Gram stain, culture, and sensitivity studies.
Treatment
Medical therapy is usually adequate and differs for bacterial and amebic abscesses. Surgery may be required in
special circumstances.
FIGURE 6.12. Liver abscess. This CT scan shows one large (arrow) and several small abscesses, the
margins of which are irregular in contour; one contains an air bubble due to bacterial infection (tiny
black opaque dot). The irregular contour and shape of these lesions are typical of infection or tumor
and help distinguish them from hepatic cysts. (Courtesy of Henry I. Goldberg, MD.)
M anagement: L iver A bscess ................................................................................................................. 179
180 ................................................................................................................................................. Liver
Bacterial Abscess
Patients should be placed on broad-spectrum antibiotics
(usually a combination of an aminoglycoside, metronidazole, and ampicillin) given intravenously. This regimen
will cover the most common offending bacteria and may
be changed later when the results of culture and sensitivity are obtained.
Multiple liver abscesses are treated with intravenous
antibiotics for 2 weeks followed by oral antibiotics for
6 weeks. Streptococcal abscess may require as long as
6 months of treatment. Large single abscesses are best
treated with antibiotics and percutaneous catheter
drainage. Surgical drainage is reserved for cases in which
catheter drainage either fails or is technically impossible.
Surgery is also indicated when an underlying disease
(e.g., cholangitis, cholecystitis) must be treated with an
operation.
Amebic Abscess
Metronidazole, the treatment of choice, is given in doses
of 750 mg tid either orally or intravenously. A second oral
amebicide (e.g., diloxanide) is usually added. Surgical
drainage may be necessary if bacterial superinfection is
present.
MANAGEMENT: LIVER CYSTS
CONGENITAL CYSTS
Solitary Cysts
Unilocular cysts are rare but can sometimes attain large
size (Figure 6.13). They have a serous lining and must be
differentiated from cystadenomas, which have cuboidal
epithelial lining and are premalignant. Solitary cysts are
usually discovered incidentally, but they might produce
clinical symptoms if they (1) attain large size, causing
dull ache and mass, and (2) become infected, a very rare
occurrence.
Large and symptomatic cysts are best treated laparoscopically. The cyst is unroofed and the cavity filled
with omentum. Rarely, the cyst may communicate with
the biliary tree. This may be detected preoperatively
but is readily determined by aspirating the cyst fluid. If
should be drained into the intestine by Roux-en-Y
cyst-jejunostomy.
Multiple Cysts
Multiple cysts occur in polycystic disease, which affects the
liver, kidney, and spleen. The disease is congenital with
autosomal dominant inheritance but occurs in adults. A
nonlethal polycystic disease occurs in children as a result
of autosomal recessive inheritance. Polycystic liver disease
rarely requires surgical treatment.
ECHINOCOCCUS (HYDATID) CYST
Two types of hydatid cyst exist, the unilocular cyst caused
by Echinococcus granulosus and the alveolar type caused by
Echinococcus multilocularis. Approximately 70% are single
cysts, and the right lobe is affected in 85% of cases. The
cysts have a double membrane, contain colorless alkaline
fluid on the inner side of the membrane, and are usually
found to have numerous daughter cysts. The fluid may be
highly allergenic and can precipitate anaphylaxis if spilled
intraperitoneally (Table 6.6).
Over two-thirds of patients present with a palpable
mass, abdominal pain, and tenderness. If intrabiliary
rupture occurs, biliary colic, jaundice, and urticaria
result. Patients may also have emesis or pass feces
containing hydatid membrane. When cysts are secondarily infected, the typical picture of liver abscess
emerges with fever, chills, and hepatic tenderness.
Spontaneous intraperitoneal rupture may lead to anaphylactic shock.
Complications
The complications of hydatic cysts are:
1. Intrabiliary rupture, which occurs in 5% to 10% of
cases.
2. Intraperitoneal rupture, which is uncommon but may
lead to the formation of new cysts in the peritoneal
cavity.
3. Secondary bacterial infection, leading to abscess formation and death of the scolices.
4. Transdiaphragmatic extension into the pleural
cavity.
Investigations
Useful tests in echinococcal liver cysts include laboratory
studies, skin testing, and radiologic studies.
FIGURE 6.13. Hepatic cyst. This CT scan shows one large and three small cysts in the liver, all characterized by thin walls, smooth margins, and homogeneous low density. (Courtesy of Henry I. Goldberg,
MD.)
Laboratory Studies
A blood test will reveal eosinophilia in less than 30%
of patients. The indirect agglutination test is positive in
85% of patients. The complement fixation test is less
sensitive.
TABLE 6.6. Essentials: Echinococcus (Hydatid) Cyst
Most common in
䊏
Australia
䊏
South America
䊏
Greece
Causes
䊏
Echinococcus granulosus or E. multilocularis
䊏
Intermediary hosts: sheep, pigs, cattle
Clinical presentation
䊏
Palpable mass
䊏
Pain
䊏
Fever and chills if secondary infection
Diagnosis
䊏
Eosinophilia in 30%
䊏
Positive indirect agglutination test in 85%
䊏
Positive Casoni skin test in 90%
䊏
Imaging shows cyst with daughter cysts, calcification
Treatment
䊏
Surgical excision of cyst
䊏
Prevent peritoneal spillage (anaphylaxis)
䊏
Occasionally liver resection
Skin Test
The Casoni skin test is positive in approximately 90% of
cases of hydatid cysts. A positive Casoni test persists in
patients for years after an initial infection.
Radiologic Testing
Ultrasound or CT scan will show the cyst. The CT scan
may show multiple septa, even daughter cysts, and sometimes a calcified shadow (Figure 6.14).
Treatment
Large symptomatic cysts are treated laparoscopically or
with open surgery. The steps in operative management
include:
1. Isolation of the cyst from the peritoneal cavity to min-
imize spillage of cyst fluid.
2. Aspiration of the cyst as completely as possible,
exercising caution as cyst fluid is often under
pressure.
3. Instillation into the cyst cavity of a scolecocidal agent
such as hypertonic saline or alcohol.
4. Excision of the hydatid cyst by separating the cyst from
the liver along a cleavage plane between the germinal
layer and adventitia.
5. Alternatively, the cyst may be removed by liver resec-
tion or, when extensive, it may be marsupialized and
filled with omentum.
M anagement: L iver C ysts .................................................................................................................... 181
FIGURE 6.14. Echinococcus cysts of the liver. This CT scan shows a single large cyst containing two
smaller daughter cysts (arrows), typical of cysts caused by Echinococcus granulosa. (Courtesy of Henry I.
Goldberg, MD.)
MANAGEMENT: BENIGN NEOPLASMS OF THE LIVER
Benign liver tumors are less common than malignant
tumors, from which they must be distinguished. These
lesions are often found incidentally at laparotomy or
during ultrasonographic or radiologic investigation of
other hepatobiliary disease. Most commonly, they are
asymptomatic, but occasionally they may produce complications of hemorrhage and necrosis.
HEMANGIOMA
The most common benign lesion, hemangiomas, are of
two types: small capillary hemangiomas or cavernous
hemangiomas. The former tend to be small, multiple, and
asymptomatic (Figure 6.15). Cavernous hemangiomas, on
the other hand, can attain a large size and are usually solitary. They are more common in women and may enlarge
during pregnancy, suggesting dependency on female sex
hormones. They are not known to undergo malignant
degeneration.
Most hemangiomas are asymptomatic. When symptoms occur, they are usually nonspecific, consisting of
vague abdominal pain and fullness. Rarely, they may cause
acute pain or rupture, causing intra-abdominal hemorrhage. Occasionally, they may cause obstruction of the
biliary tract, resulting in jaundice. They are rarely palpable and may cause a bruit.
Investigations
Ultrasonography will show hyperechoic lesions. CT is the
most useful examination for showing well-delineated hypodense lesions (Figure 6.16). When intravenous contrast
is injected during CT, the periphery of the lesion is enhanced and pooling of the dye will occur. The CT findings
are often sufficient to distinguish the lesion from hepatocellular carcinoma. MRI gives similar accuracy to CT.
Angiography is rarely indicated but produces a characteristic cotton wool appearance with the filling of large
vascular spaces. Needle biopsy should not be performed.
If biopsy is considered necessary, the lesion should be
examined laparoscopically and biopsy obtained only if the
lesion does not appear to be a hemangioma. It is usually
better to remove the lesion in its entirety if the diagnosis
is difficult.
Treatment
When lesions are found incidentally and are asymptomatic,
no therapy is needed. Instead, the patient is simply
182 ................................................................................................................................................. Liver
A
B
FIGURE 6.15. Hemangioma of the liver. Gross appearance of a fixed specimen shows a multifocal
hemangioma (A). Microscopic examination demonstrates wide vascular channels lined with flat
endothelial cells (B). (Courtesy of Linda D. Ferrell, MD.)
M anagement: B enign N eoplasms of the L iver...................................................................................... 183
FIGURE 6.16. This CT scan using an intravenous contrast agent shows a large hypodense lesion at the
periphery of the liver, with several puddles of dense contrast material seen in the periphery of the
lesion. This is a characteristic appearance for cavernous hemangioma. Incidentally noted is a small cyst at
the margin of the liver (small arrow) and a large hyperdense lesion in the center of the liver, which was
proven by biopsy to be focal nodular hyperplasia (large arrow). (Courtesy of Henry I. Goldberg, MD.)
reassured and informed that large cavernous hemangiomas
have been followed for many years without evidence of
complication. Surgical resection can usually be performed
safely but is indicated only if the patient is symptomatic or
the diagnosis uncertain. Wedge resection may suffice, but
formal hepatic lobectomy may be required. Hepatic artery
ligation and embolization therapy are less effective than
surgical resection and are rarely recommended.
HEPATIC ADENOMA
The risk of presenting with this benign hepatocellular neoplasm occurs mostly in women 30 to 50 years of age. A
history of oral contraceptive use is present in 90% of
women who develop the tumor; risk increases with the
duration and strength of the oral contraceptive used. The
reported incidence of 3 to 4 per 100,000 of oral contraceptive users who have taken the contraceptive beyond 2
years has been significantly reduced with the administration of low estrogen contraceptives. Typically, the tumor is
solitary and smooth-surfaced. Malignant degeneration can
occur, but its incidence is not known (Table 6.7).
Investigations
Ultrasonography usually shows a solid tumor, but computerized tomography provides better definition. An
isotope scan shows the tumor as a filling defect. Angiography will show a hypervascular lesion. Needle biopsy is
apt to precipitate hemorrhage because of the hypervascularity of the lesion. When hepatocellular carcinoma cannot
be excluded, laparoscopic evaluation is useful, and biopsy
can then be obtained under direct vision.
Treatment
Asymptomatic patients with lesions less than 6 cm in
diameter can be treated conservatively if, after discontinuing contraceptive therapy, the tumor regresses. All symptomatic patients and those with asymptomatic tumors
larger than 6 cm are best treated by hepatic resection.
Patients with intra-abdominal hemorrhage may be preoperatively palliated with angiographic embolization, but
early surgical resection is the definitive approach.
TABLE 6.7. Essentials: Hepatic Adenoma
Demographics
䊏
Benign neoplasm common in women 30–50 years old
䊏
History of contraceptive use in 90%
Clinical presentation
䊏
Abdominal pain in 40%
䊏
Incidentally found in 30%
䊏
Palpable mass in 30%
䊏
Spontaneous hemorrhage in 20%
Diagnosis
䊏
Computerized tomography: Solid tumor
䊏
Isotope scan: Shows as filling defect
䊏
Angiogram: Hypervascular lesion
䊏
Biopsy: Only under vision (laparoscopy)
Treatment
䊏
Lesion <6 cm: Discontinue contraceptive drugs
䊏
Lesion >6 cm: Hepatic resection
184 ................................................................................................................................................. Liver
A
B
FIGURE 6.17. Gross appearance of benign focal nodular hyperplasia. (A) A 3-cm-diameter lesion
typical of focal nodular hyperplasia shows central fibrosis. (B) Histologically, nodules of liver and bile
ductular proliferation are seen within a fibrous stroma. (Courtesy of Linda D. Ferrell, MD.)
FOCAL NODULAR HYPERPLASIA
Unlike hepatic adenoma, FNH neither bleeds nor
undergoes malignant transformation. Most patients
Because most focal nodular hyperplasia (FNH) occurs
in women of the same age group as adenomas,
diagnostic differentiation may be difficult (Figure 6.17).
M anagement: B enign N eoplasms of the L iver...................................................................................... 185
have no symptoms, but mild and episodic pain
may be present. Spontaneous bleeding may rarely
occur.
186 ................................................................................................................................................. Liver
Investigations
Ultrasound and computerized tomography fail to show
the lesion in detail because it is isodense. Angiogram will
show a typical sunburst hypervascular lesion. Deep biopsy
is necessary to reach the central scar, which is diagnostic.
Otherwise, the liver parenchyma is normal.
Treatment
Treatment is not usually necessary. Occasionally, the lesion
is resected if it causes significant pain or ruptures.
MISCELLANEOUS BENIGN LESIONS
Other benign tumors include bile duct adenoma and
hamartoma. Occasional mesenchymal hamartomas may
grow into large masses in children and may require
resection.
The most common malignant primary tumors are hepatocellular carcinoma (HCC) or hepatoma and cholangiocarcinoma. HCC arises from the hepatocytes and
cholangiocarcinoma from the epithelium of the intrahepatic biliary tract. Although the causes of these two types of
primary liver cancer are not known, several etiological
associations are evident (Table 6.8). A mixed form, hepatocholangioma, has also been described but is very rare. In
children, hepatoma has malignant cells that resemble fetal
hepatocytes. The tumor, referred to as hepatoblastoma,
occurs almost exclusively in the first 3 years of life. Primary
malignant tumors can also arise from the stroma of the
liver (i.e., sarcoma), but these are rare.
HEPATOCELLULAR CARCINOMA
Uncommon in North America but endemic in subSaharan Africa, China, and Southeast Asia, hepatocellular
carcinoma (HCC) is five times more common in men
(Table 6.9) than in women. The peak incidence in endemic
regions is the third and fourth decades, but the peak incidence in North America is in the fifth and sixth decades.
MANAGEMENT: MALIGNANT PRIMARY LIVER NEOPLASMS
TABLE 6.8. Primary Liver Cancer: Etiological Associations
Hepatocellular carcinoma
䊏
Viral infections
Hepatitis B (HB5Ag seropositivity)
Hepatocellular carcinoma (7% of cases)
䊏
Mycotoxins (e.g., aflatoxin)
䊏
Iron overload (primary hemochromatosis)
䊏
Steroids (androgenic, anabolic, contraceptives)
䊏
Tyrosinemia type 1
䊏
Cirrhosis (alcoholic and others)
Cholangiocarcinoma
䊏
Primary sclerosing cholangitis
䊏
Ulcerative colitis
䊏
Clonorchis sinensis
䊏
a1-tripsin deficiency
TABLE 6.9. Essentials: Hepatocellular Carcinoma
Principal causes
Hepatitis B (HBsAg seropositivity)
Hepatitis C
Diagnosis (often late)
Clinical
䊏
Pain, weight loss, jaundice
䊏
Mass, bruit
䊏
Rapid deterioration of liver function
Laboratory
䊏
Abnormal LFT (30%–40%)
䊏
HBsAg seropositivity (50%)
䊏
Elevated AFP (30% U.S., 80% Africa)
Imaging
䊏
MRI to assess hepatic vein invasion
Biopsy
䊏
Risk of bleeding
䊏
Laparoscopic biopsy under vision safest
Treatment
Resection or transplantation only chance of cure
Criteria for respectability
䊏
Tumor removable by local excision or lobectomy
䊏
Adequate functional reserve in residual liver
䊏
No hepatic or portal vein invasion
䊏
No metastases or extrahepatic extension
Criteria for transplantation
䊏
Three or fewer lesions
䊏
Less than 5 cm in diameter
䊏
Presence of cirrhosis
Prognosis
䊏
Resectability rate 20%
䊏
Five-year survival after curative resection: 33%–64%
䊏
Five-year survival after transplantation: 19%–70%
䊏
Average survival in unresectable disease: 4 months
Abbreviations: AFP, alpha-fetoprotein; LFT, liver function test; MRI,
magnetic resonance imaging.
Early recognition is difficult because symptoms and
signs develop late. Abdominal pain, weight loss, and jaundice are the most common symptoms. In patients with
known cirrhosis, development of HCC may be manifested
by rapid deterioration of liver function. Physical examina-
tion may reveal hepatomegaly and ascites. A bruit is
heard in the liver in about 10% of patients. Occasionally,
patients present acutely, either with fever and pain
or with massive intraperitoneal hemorrhage. Rarely,
patients may present with paraneoplastic syndromes,
most commonly hypoglycemia, hypercalcemia, and
polycythemia.
Pathogenesis and Pathology
The principal causative factor of HCC is chronic hepatitis
B virus (HBV) infection. Seropositivity for HBsAg is
associated with the highest incidence of HCC. In some
countries, HCC is commonly associated with hepatitis
virus infection. Other conditions associated with the
development of HCC include alcoholic cirrhosis,
hemochromatosis, and a
1
-anti-trypsin deficiency. At one
time, thorotrast was used as a contrast material for
radiological studies, and some 20 years later, a high incidence of HCC was seen in these patients studied
with thorotrast. Vinyl chloride is hepatotoxic and a
chemical carcinogen that can cause HCC. Aflatoxin, produced by the aspergillus group of fungi, contaminates
grain in Africa and China and is thought to act as a
carcinogen.
HCC can produce a tumor, which can be either a single
mass, multinodular (Figure 6.18), or a diffuse infiltrative
type. By the time of diagnosis, metastasis has occurred in
over two-thirds of patients. The most common sites of
metastasis are the nodes at the liver hilum and the celiac
axis. The tumor may invade the capsule and spread
transcoelomically in the peritoneal cavity. Metastasis can
also occur in the lungs.
Investigations
In addition to laboratory and radiological testing, laparoscopy and liver biopsy may be required to arrive at a
definitive diagnosis.
Laboratory Studies
Abnormal liver function tests (hyperbilirubinemia and/or
elevated serum alkaline phosphatase) will be present in
30% to 40% of patients. About half of these will be HBsAgpositive. Alpha-fetoprotein (AFP) will be elevated in some
75% of patients with HCC in Africa but only in 30% of
patients in the U.S. and Europe.
Radiological Studies
A variety of imaging techniques will show the tumor,
including CT, MRI, and scintiscan (Figure 6.19). MRI
has the advantage of detecting extension into hepatic
veins. On angiography, hepatomas appear as hyper-
vascular lesions supplied primarily by the hepatic
artery. Chest x-ray may show elevated right diaphragm,
pleural effusion, and sometimes, pulmonary metastasis.
The chief value of ultrasonographic examination is
that it will distinguish a solid from a cystic tumor,
but it is not as sensitive as CT or MRI. Ultrasound
Doppler studies, however, are useful in assessing the
patency of the portal vein, hepatic vein, and inferior vena
cava.
Laparoscopy and Liver Biopsy
CT-guided percutaneous core biopsy can establish the
diagnosis. Since HCC is hypervascular, the risk of bleeding is high. Hence, laparoscopy and biopsy under vision is
preferable.
Treatment: Definitive Surgical Options
Unfortunately, only about 20% of patients meet the
criteria for surgical treatment. The outlook is, therefore,
dismal, except in those with early lesions amenable to surgical treatment. The only definitive treatment options are
complete tumor resection or total hepatectomy and liver
transplantation. Patients with unresectable tumor live, on
average, 4 months.
Hepatic Resection
Great regenerative capacity allows resection of up to 85%
of the liver, as long as the remaining organ is normal. Two
limiting factors are extent of tumor within the liver and
extent of cirrhosis in residual liver. The criteria for
resection, therefore, are:
1. The entire tumor with a 1-cm margin of normal
liver can be removed by local excision, lobectomy, or
trisegmentectomy.
2. Residual parenchyma must provide adequate liver
function. Thus, if the residual liver is cirrhotic, liver
reserve may be inadequate.
3. Hepatic and portal vein invasion must be absent.
4. Extrahepatic extension and distant metastases must
also be absent.
Intraoperative ultrasound and anatomic-based resec-
tion have improved the adequacy of this procedure and
lowered operative mortality to approximately 5%. After
curative resection, which is possible in less than 20% of
patients, the 5-year survival rate varies from 33% to 64%.
15
The best prognosis is associated with lesions <3 cm in
diameter and an absence of cirrhosis.
T
YPES OF RESECTION Several types of liver resection
techniques are possible, including wedge resection, seg-
M anagement: M alignant P rimary Liver N eoplasms ............................................................................. 187
A
B
FIGURE 6.18. Hepatoma. (A) A large, partially encapsulated, multinodular hepatoma with areas of
hemorrhage involving much of the right lobe (B). Microscopically, tumor cells are arranged in a trabecullar pattern with broad plates, sometimes giving the impression of floating islands. (Courtesy of
Linda D. Ferrell, MD.)
䉴
FIGURE 6.19. CT and MRI are the most commonly used techniques for imaging hepatoma. (A) CT scan
of the liver of a patient with a known hepatoma in the right posterior portion of the liver (arrows)
was obtained 70 sec after injection of intravenous contrast material. (B) The same area pictured 25
seconds after contrast injection not only shows the dominant lesion but three smaller lesions (arrows)
in the left lobe that ruled out the option of performing resection in this patient. (C) The dual-phase
CT scan is designed specifically to uncover vascular tumors. MRI is equally sensitive in detecting the
large hepatoma (arrow). (Courtesy of Henry I. Goldberg, MD.)
188 ................................................................................................................................................. Liver
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