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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5767_Библиотеки_им_академика_М_И_Перельмана.pdf
4 Liver
e
49
f
Fig. 4.7 (continued)
50
E. I. Peniaeva and Y. R. Kamalov
g
Fig. 4.7 (continued)
Fig. 4.8 Flow chart for
the management of FNH
Contrast enhanced imaging – preferably MRI
Diagnosis
FNH - certain
Discharge
No follow-up needed
Suspected FNH
CEUS
Diagnosis
uncertain
Diagnosis
FNH - doubtful
< 3 cm
> 3 cm
Biopsy
Confirmed
FNH
4 Liver
51
The following main subtypes based on gene
mutations and the risk of malignant transformation are recognized [41]:
• HNF1α mutated hepatocellular adenoma
(HA-H, ~35%).
• β catenin mutated hepatocellular adenoma
(HA-B, ~10%).
• Inammatory hepatocellular adenoma (HA-I,
~35%).
• Sonic hedgehog (SHH) hepatocellular ade-
noma (HA-sh, ~5%).
• Hepatocellular adenoma, not otherwise speci-
ed (HA-U, ~7%).
Hepatic adenoma is also supplied with blood
from the liver artery system [6]. Histopathology
reveals large subcapsular vessels with a large number of thin-walled capillaries that spread in the
tumor, as well as wide sinusoids. With CEUS, it
causes arterial phase hyperenhancement with a
rapid ll-in from the periphery to the center. This
phenomenon can also be easily missed, which
requires repeated cine loop assessment. Visual perception of enhancement may benet from parametric mapping (Fig.4.9c, Videos 4.6 and 4.7).
Centripetal type of contrast enhancement permits differentiation of HCA from FNH.Both of
them being hyperenhancing lesions, FNH is associated with the centrifugal type of ll-in [3].
Hepatic adenoma typically demonstrates homogeneous contrast enhancement. Heterogeneity
may occur if areas of hemorrhage or necrosis are
present, especially in large-sized HCA.In the portal venous phase, the HCA becomes isoenhanced
(Fig. 4.9). The late phase may reveal slight
hypoenhancement due to the absence of blood
inow from the portal vein system. Alternatively,
or isoenhancement may preserve due to the retention of bubbles in sinusoids. In the case of a signicant washout, the differential diagnosis with
hepatic carcinoma is practically impossible.
Molecular classication of HCA contributed
to the understanding of their malignant transformation. The highest risk of malignancy is
observed in β-catenin HCA exon 3, which is typi-
cally detected in men. Accordingly, regardless of
the size of the lesion, all men with HCA are
advised hepatic resection or other treatment,
while in women with smaller than 5cm size HCA
conservative management is possible [24].
The determination of HCA subtypes led to the
search for their characteristic signs with CEUS,
analogous to MRI.A reliable difference in contrast enhancement of HNF1A-inactivated and
inammatory HCAs was reported [42]. HNF1Ainactivated HCAs exhibit hyperenhancement in
the arterial phase with a mixed type of ll-in and
no washout in the portal venous and late phases.
Inammatory HCAs are also characterized by
arterial phase hyperenhancement but accompanied by slight central hypoenhancement and
peripheral isoenhancement in the late phase.
HNF1α mutated (HA-H) and inammatory
(HA-I) hepatic adenomas, as a rule, have no
washout, whereas β-catenin inactivated (HA-B)
and non-classied adenomas (HA-U) often
exhibit late phase washout [43]. HA-H and HA-I
in most cases do not exhibit washout and no reliable differential criteria between them are identied [44]. Currently, CEUS-based differential
diagnosis of HCA subtypes is a subject of scientic research and is not recommended for clinical
practice. If HCA demonstrates obvious washout
effect and lack the reliable differential diagnostic
features from malignant FLL, these cases are
subject for histological verication.
Other rare benign liver tumors are inammatory pseudotumor and angiomyolipoma. The
publications on the patterns of contrast enhancement of these lesions are sporadic.
Hepatic inammatory pseudotumor is a rare
benign disease, which can be misdiagnosed as a
malignant primary or secondary tumor. Individual
CEUS literature data characterize it with rapid
hyperenhancement in the arterial phase and
washout in the portal venous and late phases that
do not allow their differentiation from malignant
FLLs [45–48]. In this lesion, CEUS is only capable to differentiate it from other benign FLL that
have characteristic features.
52
E. I. Peniaeva and Y. R. Kamalov
a
b
Fig. 4.9 Hepatic adenoma. (a) Rapid diffuse hyperen-
hancement in the arterial phase, CEUS image.
(b) Isoenhancement in the portal venous phase makes
adenoma invisible on the isoenhanced background liver
parenchyma. CEUS image. (c) Parametric map of
enhancement. (d) CE-CT
4 Liver
c
53
d
Fig. 4.9 (continued)
Cholangiocellular adenoma (bile duct adenoma) is a rare benign FLL of small size, usually
smaller than 1cm, which has exceptionally arterial blood supply. This tumor can also be misdiagnosed for malignancy due to arterial phase
hyperenhancement and early washout [49].
Hepatic angiomyolipoma is a rare benign mesenchymal tumor represented with histopathology
by three components in various proportions: pro-
liferating thick-walled blood vessels, smooth
muscles, and mature adipose cells [50, 51].
Although hepatic angiolipomas are considered
benign, it is believed that they may have some
malignant potential. Several patients there
reported to have histopathological signs similar
to malignant tumors and developed extrahepatic
metastases [52, 53]. Typical benign angiomyolipoma is hyperenhancing in the arterial phase and
remains moderately hyper- or isoenhanced in the
54
E. I. Peniaeva and Y. R. Kamalov
portal venous and late phases. Late phase washout in angiomyolipoma was reported in about
25% of cases, and a case of hypoenhancing angiomyolipoma in all vascular phases was published
[52, 54]. Additionally, CEUS is better than
CE-CT for the assessment of contrast agent
washout [54]. CT in the cases of angiomyolipoma determined washout in 42.6% and falsepositively declared the malignant FLL, while
CEUS—only in 18.5% of cases.
4.1.2 Malignant Liver Lesions
andMetastases
The specic feature of malignant liver tumors is
hypoenhancement in the late phase and postvascular phase (for Sonazoid) that corresponds to
the washout of the UCA. It is registered in all
cases of liver metastases regardless of contrast
enhancement in the arterial phase [3]. The exceptions to this rule are quite rare.
Liver metastases are the most common malignant FLL.They are detected in 30–50% of oncological patients and occur 20–30 times more often
than primary liver carcinoma [55]. The principal
cause for liver metastasis is colorectal, esophageal, lung, duodenal, or pancreatic cancer.
Metastases in the liver have arterial blood supply without any inow from the portal vein system [6]. With CEUS, they are characterized with
pronounced hypoenhancement in the portal
venous and late phases, looking like well-dened
dark foci in the homogeneously enhanced normal
liver parenchyma [3, 14, 15, 56–58] (Fig.4.10).
Washout usually starts within 60 s after UCA
injection. However, in rare cases with small-sized
lesions (<2cm), washout may not be observed in
the portal venous phase and begins in the late
phase after 120s [59].
In the arterial phase, various contrast enhancement of metastases are possible. Hypovascular
metastases, which have a relatively low arterial
perfusion, are hypoenhanced, sometimes with
slight enhancement on the periphery. This pattern
is often observed in the metastases of the gastrointestinal tract, lung, or breast adenocarcinoma
[30, 60–63]. Hypervascular metastases are most
often found in the cases of neuroendocrine
tumors, carcinoid, melanoma, sarcoma, urothelial carcinoma, choriocarcinoma, breast, thyroid
gland, or ovarian cancer. They have a very high
arterial perfusion and exhibit diffuse hyperenhancement often with a peripheral rim in the
arterial phase and washout in the portal venous
and late phases [30, 60–63]. The beginning of
contrast enhancement and the peak intensity in
hypervascular metastases develop earlier and
washout starts later than in hypovascular ones
[62]. In rare cases, they observed isoenhancing
metastases in the portal venous and late phases.
The authors suppose that this pattern can be
explained by an increase in arterial blood ow,
which partially compensates for the reduced portal blood ow. It may be the cause of the erroneous interpretation of such masses as a
well-differentiated hepatocellular carcinoma or
benign lesions.
However, the pattern of arterial contrast
enhancement has a limited diagnostic value. It
may help to guess the probable location of the
primary tumor and is often used for monitoring
patients during anti-angiogenic therapy [6]. The
arterial phase, which is associated with minimal
enhancement of liver parenchyma, is most appropriate for evaluation of the vascular structure of
the metastases and the detection of their feeding
vessels. The differential diagnosis of cystic
metastases from complex non-tumor cysts is feasible with the assessment of the peripheral
rim- shaped contrast enhancement and the
enhancement of the septal and mural components
(Fig.4.11, Video 4.8).
CEUS demonstrates excellent diagnostic accuracy in liver metastasis with the sensitivity of
94.4%, specicity—93.7%, and accuracy—94.11% [27]. The DEGUM multicenter
trial reported the accuracy of 91.4% [23]. However,
CEUS is limited with the assessment of the metastases located in one scanning plane. It fails to
detect remote metastases and simultaneously evaluate the lesions within the whole liver volume.
a
4 Liver
55
b
Fig. 4.10 Colorectal metastasis. CEUS images. (a) Early arterial phase. (b) Arterial phase. (c) Portal venous phase.
(d)Late phase
56
c
E. I. Peniaeva and Y. R. Kamalov
d
Fig. 4.10 (continued)
4 Liver
a
b
57
c
Fig. 4.11 Metastasis of breast carcinoma in the liver. CEUS images. (a) Early arterial phase. (b) Arterial phase.
(c)Portal venous phase
58
E. I. Peniaeva and Y. R. Kamalov
Hepatocellular carcinoma (HCC) is a primary
liver tumor accounting for 80% of all liver cancers. It takes the sixth place by prevalence and the
second among the causes of mortality from cancer [64]. HCC often develops in the cirrhotic
liver. However, liver cirrhosis is not considered a
precancerous state. Approximately 20% of the
HCCs develop in non-cirrhotic liver and is often
associated with metabolic syndrome ar chronic
hepatitis B.There are other risk factors, such as
aatoxin exposure, chronic alcoholism, nonalcoholic fatty liver disease, hereditary hemochromatosis, deciency of α1-antitrypsin, Wilson
disease, etc. [65, 66].
In the majority of cases (about 90%), HCC
develops as a multi-stage process with gradual
cellular and molecular dedifferentiation of
hepatocytes.
The developing HCC passes the following
stages [67] (Fig.4.12):
• Regenerative macronodule, which is histopath-
ologically identical to the liver parenchyma.
• Low-grade dysplastic nodule (LGDN). Its
blood supply has practically no difference
from the blood supply of the liver (about 80%
of the portal and 20% arterial inow).
• High-grade dysplastic nodule (HGDN). It
exhibits active vascular restructuring with
sinusoidal capillarization and development of
unpaired arteries but preserved portal blood
inow and venous outow.
• Early HCC, highly differentiated. Portal blood
supply switches to arterial with the increase in
the number of unpaired arteries and the disap-
pearance of paired arteries.
• Progressive HCC, moderately or poorly dif-
ferentiated. It may demonstrate invasive
growth and metastasis. At this stage, there
appears a fundamental change in the type of
blood supply with the retrograde evacuation
of blood from intra-tumor arteries to intra-
tumor portal vessels and the sinusoids of the
peritumoral space. As the tumor progreses is
completely switches to arterial blood supply
with full disappearance of the portal blood
supply
An exception is HCC in the non-cirrhotic
liver, which has no intermediate stages and histological precursors, and is dened as hepatic carcinogenesis de novo. For example, in chronic
hepatitis B, the integration of the viral genome to
the patient’s DNA directly leads to the activation
of the genes responsible for the development of
HCC [67].
Ultrasound signs of HCC are nonspecic and
largely depend on the tumor type: diffuse or nodular with the latter subdivided into a solitary nodule, solitary nodule with proliferation, multiple
nodules, and merging multiple nodules [9]. The
key point in the diagnosis of HCC is the understanding of the process of neoangiogenesis in the
tumor and, consequently, the dynamics of arrival,
accumulation, distribution, and washout of
UCAs.
In the non-cirrhotic liver, HCC exhibits arterial phase hyperenhancement, as a rule with chaotic vascular pattern and ll-in from the periphery.
If necrotic areas are present in the tumor, the
enhancement is heterogeneous [3]. Iso- and
hypoenhancing patterns in the arterial phase may
be observed less often. The portal and late phases
demonstrate slow and poor washout, which is
less prominent than in other primary liver tumors
or metastases. Washout often starts later than 60s
after the UCA introduction and in 25% of cases—
later than 180s [68].
Any FLL in the cirrhotic liver background
without condence in its benign nature is an indication for a contrast-enhanced study. The principal feature of HCC in the cirrhotic liver is
hyperenhancement in the arterial phase followed
by washout in the late phase, which is characteristic for more than 97% of HCCs [3, 68]. As a
rule, in the arterial phase, the enhancement is
homogeneous. Heterogeneous enhancement is
rare and observed in lesions larger than 5cm in
size. Peripheral rim-shaped enhancement is not
typical HCC. The UCA washout usually starts
later and is mild that differs HCC from other liver
malignancies (Figs.4.13 and 4.14, Video 4.9).
The appearance and severity of the washout
effect depend on tumor differentiation and size. It
is less characteristic of well-differentiated
HCC. If the lesion size is smaller than 2 cm,