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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_775_Библиотеки_им_академика_М_И_Перельмана.pdf
126
de
K. Murakami
a
b
c
Fig. 15.3 A case of mixed type HCC with extrahepatic metastases. (a)
Arterial phase of dynamic CT; (b) Portal phase of dynamic CT.A tumor
showed early enhancement which is a feature of HCC, though it also
had lobular border and delayed enhancement that are the features of
resolution and specicity of PET is superior to that offered
by plain or contrast-enhanced CT (Fig. 15.5). In addition,
recent technological advances in PET cameras have signicantly improved spatial resolution, and the detection rate of
small lesions is improving year by year.
CT alone is sometimes inadequate for differentiating
small liver tumors, such as cysts from hemangiomas or
hepatic metastases even if dynamic contrast imaging is performed, because small tumors do not always show characteristic hemodynamics. MRI (especially contrast MRI and
diffusion weighted MRI) may be currently the best imaging
method for detecting small liver metastases, but it is also difcult to make differential diagnosis of small liver tumor by
means of MR signal. In such cases, FDG-PET is highly use-
CCC (cholangiocellular carcinoma). Pathological diagnosis was mixed
type HCC; (c) This type of HCC showed strong FDG accumulation; (d,
e) This case also had lymph node and bone matastases (arrow)
ful for deciding diagnosis due to its high specicity, though
it should be noted that it is effective for tumors with strong
FDG accumulation such as colon cancer and pancreatic cancer, but weak accumulation such as renal cell cancer.
PET has another advantage of being able to screen the
whole body. Ruers etal. [10] focusing on the usefulness of
PET for the detection of metastatic lesions in addition to primary hepatic tumors. There is a literature also emphasis of
the merit of FDG-PET to nd restaging disease and it has
additional clinical value in management of solitary liver
metastases [11].
PET is expected to play an important role in the future for
assessment of the therapeutic response of molecular-targeted
drugs. Molecular-targeted drugs have been reported to show
15 FDG-PET forManagement onHepato-Pancreato-Biliary Disease
a b
Fig. 15.4 A case of cholangiocellular carcinoma (CCC). (a) Non-contrast CT obtained by PET/CT (low-dose CT); (b) FDG-PET.CCC is usually
depicted as FDG-avid tumor unlike HCC
127
less effective for decreasing tumor size compared to conventional cytotoxic anticancer drugs because of its cytostatic
feature. Consequently, the ndings of PET have attracted
attention as surrogate markers for evaluating the effects of
the molecular-targeted drugs. At present, molecular-targeted
drugs are widely used in the treatment of lung cancer, breast
cancer and gastrointestinal stromal tumors, which are frequently happens liver metastases. Since PET allows detection of not only liver metastases but also metastases elsewhere
in the body, it is expected to play a more important role in the
future as surrogate markers [12].
15.3 FDG-PET Examination forBiliary
Cancer
According to the report of Petrowsky etal. [8], the diagnostic
accuracy of FDG-PET was 53% for extrahepatic bile duct
cancer that is indicative of a poor diagnostic performance.
The at “inltrating” type, which is the most common histological type of extrahepatic bile duct cancer, is characterized
with abundant brosis and endoluminal extension not to
form “mass”. Such histological and morphological features
are major reasons for the poor diagnostic value in FDG-PET
of this tumors.
On the other hand, the papillary type (one of minor subtype of bile duct cancer) that are characterized by a massive
form and protruding growth into the lumen sometimes shows
increased uptake of FDG. PET has been shown to have a
high sensitivity for the detection of this histological type of
bile duct cancer [9, 13].
PET examination for bile duct cancer is desirable to be
performed prior to the insertion of PTCD tube, because stimulation to the tip of the inserted tube causes cholangitis. It
may cause pseudo-positive result.
Although FDG also accumulate to the lymph node metastases of extrahepatic bile duct cancer, it is incapable of
revealing microscopic metastases. In other words, FDG-PET
is not useful for the detection of lymph node metastases from
extrahepatic bile duct cancer because of its low sensitivity
[13]. Thus, FDG-PET appears to be limited usefulness for
the diagnosis of bile duct cancer for staging before therapy.
Most valuable occasion to perform PET in biliary cancer is
to nd distant metastases or early detection of recurrence.
Though morphological or anatomical change caused by surgical procedure sometimes makes difcult to nd tumor recurrence, PET can play a great role to nd missed tumors [14].
15.4 FDG-PET Examination forGallbladder
Cancer
FDG-PET has a sensitivity of 75–100% and specicity of
80–89% for the detection of primary gallbladder cancer in
the literature (Fig. 15.6). However, ultrasound, MRI, and
contrast-enhanced CT would be better for the detection of
this cancer because of its high spatial resolutions. FDG-PET
is reported to be useful for differentiating benign from malignant gallbladder tumors [15] though acute cholecystitis and
mass-forming xanthogranulomatous cholecystitis may also
show marked FDG uptake (Fig.15.7). Thus, the ability of
this modality to allow differentiation among these tumors
128
a
b
K. Murakami
c
d
e
Fig. 15.5 A case of cecum cancer with small liver metastases; (a) MIP
(Maximum Intensity Projection) image (b) fusion image of PET/
CT.Both of PET images clearly shows liver metastases (arrow) besides
f
primary cecum cancer (arrow head). (c) contrast CT; (d) T2WI; (e) contrast MRI using EOB-DTPA; (f) Diffusion weighted MRI.The small
liver lesion is hard to pointed out both by CT and MRI except DWI
ab
15 FDG-PET forManagement onHepato-Pancreato-Biliary Disease
129
Fig. 15.6 Gall bladder cancer with hilar lymph node metastases. (a)
CE-MRI (coronal section) showed poorly enhanced tumor near pancreatic head (arrow). The tumor was thought to be primary lesion at rst;
a
(b) PET/CT (with CE) demonstrated two FDG-avid lesions (arrow).
Gall bladder cancer and its metastases usually shows strong FDG
deposit
b
Fig. 15.7 A case of acute cholecystitis. (a) CE-MRI (coronal section)
showed irregular wall thickening of gall bladder (arrow) with hilar bile
duct stenosis; (b) PET/CT performed after PTC.Gall bladder showed
strong FDG accumulations (arrow) though pathological diagnosis was
acute cholecystitis. Discrimination between active inammation and
tumor is difcult by accumulation of FDG
130
bc
K. Murakami
remains controversial. For gallbladder cancer, the primary
aim of performing FDG-PET would be to nd distant metastases and recurrence same as that of biliary cancer mentioned
before.
15.5 FDG-PET Examination forPancreatic
Cancer
The 2019 edition of the Clinical Practice Guidelines for
Pancreatic Cancer in Japan [16] recommends contrastenhanced (dynamic) CT as the rst-line diagnostic imaging
method in pancreatic cancer practice, followed by MRI and
US for detection and qualitative diagnosis. According to this
guideline, FDG-PET is “weakly recommended not to be performed” the reason of which is that FDG accumulates in
inammation, so the specicity is insufcient. Other reason
includes PET to be economically expensive and having radiation exposure. In other words, if contrast-enhanced dynamic
CT is performed and additional examinations such as US,
MRI, ERCP, and EUS are performed, it can be said that the
information that can be added by FDG-PET is limited.
On the other hand, when the pancreas is not the target
organ, plain CT or CT with only one phase contrastenhancement is often performed. In such cases, small pancreatic cancers are sometimes missed especially in the case
of uncinate pancreatic cancer without dilation of the main
pancreatic duct. In the past, small pancreatic cancer which is
overlooked by CT was also difcult to detect by PET because
of its low spatial resolution, but recent advances in PET/CT
detectors and image reconstruction algorithm have dramatically improved spatial resolution. Therefore, the number of
cases of small pancreatic cancer that is missed by CT but is
detected by FDG-PET is increasing (Fig.15.8).
Regarding to qualitative diagnosis, it is sure that chronic
pancreatitis can be differentiated from cancer because of its
lower FDG uptake compared to those of cancer. However,
the inammatory cells also show increased FDG uptake
because of the accelerated glucose metabolism, differentiation between acute pancreatitis and cancer is difcult.
Accordingly, positive ndings obtained in patients who have
clinical symptoms of pancreatitis or biochemical evidence of
inammation should be interpreted with caution. Imdahl
etal. [17] reported that delayed PET imaging is useful for the
differentiation of cancer from acute pancreatitis as cancer
shows increasing deposit in delayed phase. However, a controversial study has reported that FDG uptake is enhanced in
the delayed phase even in cases of inammation. Thus,
FDG-PET cannot be regarded as a reliable imaging tool for
differentiation between acute pancreatitis and cancer even
though obtaining delayed images.
FDG-PET has been reported to play signicant roles in
the differentiation of IgG4-related pancreatitis among cases
of pancreatitis. This disease has been dened to be a systemic disease complicated by inammation in various organs
other than pancreas. FDG-PET is reported as effective tools
for evaluating the lesions [18] because various organs, such
as the salivary glands, hilar lymph nodes, lungs (interstitial
pneumonia), kidney (nephritis) and retroperitoneum are
sometimes suffered simultaneously. In other words, abnormal FDG uptake other than the pancreas may raise a suspicion of IgG4-related pancreatitis rather than pancreatic
cancer (Fig.15.9).
In cases of pancreatic cancer, PET is the most powerful
tool for nding distant metastasis (Fig.15.10) and recurrence
(Fig.15.11). Local recurrence is sometimes difcult to evaluate by conventional morphological imaging alone because it
is associated with treatment-related morphological changes,
a
Fig. 15.8 A case of pancreatic uncinate cancer incidentally found by
FDG-PET performed for staging of ascending colon cancer. (a) MIP
(b) fusion of PET/CT.Both of FDG-PET image revealed abnormal
accumulation at the pancreatic head (arrow) besides ascending colon
(arrow head). (c) contrast CT performed for staging of colon cancer. It
was difcult to detect pancreatic tumor by this image
bc
15 FDG-PET forManagement onHepato-Pancreato-Biliary Disease
a b
131
Fig. 15.9 IgG4 related pancreatitis. (a) PET/CT showed strong FDG
accumulation to whole pancreas with swelling (arrow). (b) MIP image
of PET.Besides diffuse uptake to pancreas, symmetrical FDG deposit
was noted at bilateral salivary glands and hilar, mediastinal lymph
nodes (arrow). Distribution of suffered organ is characteristic of this
disease
a
Fig. 15.10 A case of pancreatic tail cancer with multiple metastases. (a) MIP image clearly shows all lesions at pancreatic tail (arrow), liver and
spine (arrow heads). (b, c) fusion image of PET/CT.PET only could be able to point out the bone metastases at the spine
such as brosis, hemorrhage, etc. Moreover, as pancreatic
cancer has character of poor vascularity, it is difcult to evaluate the tumor based on the dynamic contrast study. Under
this circumstance, PET may be of great value for visualizing
the lesion because of its high contrast resolution.
Another reason of difculty to detect distant metastasis
based on conventional imaging is difculty to predict the site
of metastasis. The merit of whole body imaging on PET is of
great value particularly when recurrence is suspected by
clinical symptoms such as the development of pain or
increased serum levels of tumor markers, etc. Ruf etal. [19]
performed PET, CT and MRI in 23 patients with clinically
suspected recurrence of pancreatic cancer based on the
development of postoperative pain, decreased body weight
and increased serum levels of tumor markers, and conrmed
recurrence by PET in 22 of the patients (96%) on PET, but in
only nine patients (39%) by CT/MRI.
Besides FDG-PET, Somatostatin Receptor Scintigraphy
(SRS) are very benecial for clinical practice in pancreatic
neuroendocrine tumor (PNET). Some advanced countries
have already applied SRS as clinical PET imaging using
68
Ga-DOTA-TOC or 68Ga-DOTA-TATE.
As FDG accumulation represents the proliferative capacity of tumor cells, low-grade G1 accumulation is low, high-
132
K. Murakami
a
Fig. 15.11 A case of elevating tumor marker after resection of pancreatic cancer. (a) Small nodule (arrow) was missed by initial survey by CECT.
(b) PET could detect the recurrent nodule much more clearly
grade G3 and NEC (Neuroendocrine Cancer) have strong
accumulation [20]. Therefore, FDG-PET is effective for
searching metastasis of high-grade PNET, and is recommended as Grade A in “Pancreatic and gastrointestinal
neuroendocrine tumor (NEN) clinical guidelines 2nd edition” in Japan [21].
On the other hand, SRS has strong accumulation in G1
with high somatostatin receptor expression and low accumulation in poorly differentiated G3/NEC, which is inversely
related to FDG accumulation. Therefore, it is important to
use FDG-PET and SRS properly according to the degree of
differentiation and malignancy of the tumor, and they play
complementary roles.
Since this chapter focuses on FDG, details are omitted,
though SRS using PET is very promising modality in the
b
imaging tools, such as MRI, EUS and IDUS, are also available for detailed evaluation of these organs. All of these
methods are used as “high-resolution” diagnostic imaging
for visualizing “locoregional areas,” and PET is unlikely to
play an important role in the local diagnosis of the lesion.
On the contrary, PET (PET/CT) involves whole-body imaging and is quite useful for visualizing distant metastases and
unexpected recurrences. Therefore, PET/CT appears to be
of signicance in the evaluation of the whole body in cases
with somewhat advanced or atypical tumors. On the other
hands, recent advancement in PET/CT dramatically
improved spatial resolution and enable us to nd unexpected
pancreatic lesions. SRS using PET/CT also is very promising modality in the future because it is directly linked to
PRRT for PNET.
future because it is directly linked to internal radiation therapy if the labeled radioisotope is replaced from positron
emitter to α-ray or β-ray emitting nuclides, the therapy of
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15.6 Conclusion
In this review, the usefulness and limitations of PET/CT for
the evaluation of lesions in the liver, gallbladder, and pancreas were outlined. Ultrasound and dynamic CT are the
simplest and most economical imaging modalities for the
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YasunobuYamashita andMasayukiKitano
Abstract
Endoscopic ultrasound (EUS) equipped with an ultrasound transducer at the tip of gastrointestinal endoscopy
plays crucial roles for diagnosis of hepato-pancreatobiliary diseases because of high spatial resolution. In particular, EUS has advantages over the other imaging
methods in detection of small lesions. In addition, recent
advances in ultrasound technology such as contrast
enhancement and tissue elastography allowed characterization of the undetermined lesions. EUS-guided neneedle aspiration has a high sensitivity and specicity in
pathological diagnosis of pancreatic tumors with <1% of
complications. This technique has been extensively
applied to treatment of hepato-pancreato-biliary diseases
with puncture of a needle, through which we can perform
injection with liquid materials and ablation of the tumors
as well as drainage of pancreato-biliary ducts and abdominal abscess.
Owing to its high spatial resolution, endoscopic ultrasound
(EUS) equipped with an ultrasound transducer at the tip of a
gastrointestinal endoscope plays a crucial role in the diagnosis of hepato-pancreato-biliary diseases. In particular, EUS
has advantages over other imaging methods with respect to
the detection of small lesions. Furthermore, recent advances
in ultrasound technology such as contrast enhancement and
tissue elastography has enabled the characterization of undetermined lesions.
EUS-guided ne-needle aspiration (EUS-FNA) for the
pathological diagnosis of lesions with a complication rate of
Y. Yamashita · M. Kitano (*)
Second Department of Internal Medicine, Wakayama Medical
University, Wakayama, Japan
e-mail: kitano@wakayama-med.ac.jp
<1% has a high sensitivity and specicity (Fig.16.3). EUSFNA with needle puncture, through which liquid material
injection, tumor ablation, and pancreatobiliary duct and
abdominal abscess drainage can all be performed, has been
extensively applied to the treatment of hepato-pancreatobiliary diseases.
EUS images of pancreatic cancer show heterogeneous
hypoechoic lesions with irregular margins. The sensitivity of
EUS has been reported to be superior to that of computed
tomography (CT) (98% vs. 74%) in 19 studies and abdominal ultrasound (94% vs. 67%) in four studies [1]. EUS is a
particularly valuable tool for diagnosing early pancreatic
cancers. Kanno et al. reported stage 0 pancreatic tumor
detection rates of 8.8%, 10%, 10.9%, and 24.4% as well as
stage I pancreatic tumor detection rates of 67.3%, 65.8%,
57.5%, and 92.4% for abdominal ultrasound, CT, magnetic
resonance imaging (MRI), and EUS, respectively [2]. A
meta-analysis focusing on the diagnostic performance of
EUS in detecting pancreatic cancers missed on CT reported
a pooled sensitivity of 85%, pooled specicity of 58%, and
area under the curve (AUC) of 0.8 [3].
Considering the usefulness of EUS in diagnosing pancreatic cancers that are not detectable on CT, EUS is strongly
recommended to be performed in patients with indirect ndings (e.g., dilated main pancreatic duct with no visible lesion
on other imaging modalities) in order to diagnose pancreatic
cancer (Fig.16.1). Nonetheless, characterization of pancreatic lesions is difcult with conventional EUS because most
solid pancreatic lesions are detected as hypoechoic lesions
on EUS. In this regard, contrast-enhanced harmonic EUS
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022
M. Makuuchi et al. (eds.), The IASGO Textbook of Multi-Disciplinary Management of Hepato-Pancreato-Biliary Diseases,
https://doi.org/10.1007/978-981-19-0063-1_16
135
136
ab
cinoma which contrast-enhanced multidetector-row computed tomography (MDCT) detected only main pancreatic duct dilation (indirect
ndings) without depiction of the lesion. (a) MDCT: Although the main
Y. Yamashita and M. Kitano
pancreatic duct dilation (arrow) was detected by contrast-enhanced
MDCT, it failed to depict the pancreatic lesion. (b) Endoscopic ultrasonography (EUS): EUS shows a hypoechoic lesion of 8 mm in size
(arrowhead) with main pancreatic duct dilation (arrow)
(CH-EUS) and EUS elastography can improve the ability to
characterize pancreatic lesions.
Signals from microbubbles produced by intravenously
administered contrast agents are detected and selectively ltered in CH-EUS.Pancreatic cancer, inammatory masses,
and neuroendocrine tumors generally exhibit hypoenhancement, iso-enhancement, and hyper-enhancement
patterns, respectively (Fig. 16.2), on CH-EUS. A metaanalysis involving 887 patients from nine articles investigating the differential diagnosis of pancreatic lesions reported a
pooled sensitivity of 93%, pooled specicity of 80%, and
area under the summary receiver operating characteristic
(SROC) curve of 0.97 [4]. Moreover, CH-EUS is superior to
contrast-enhanced CT and MRI in patients with contraindications, such as renal failure and contrast allergy, given that
adverse reactions to contrast agents for CH-EUS are rare in
humans [5]. Hence, CH-EUS is both useful and effective in
the differential diagnosis of pancreatic carcinomas.
As malignant tumors are generally harder than benign
tumors, EUS elastography can enhance the ability to characterize elastic pancreatic lesions. With respect to the underlying principle, the strain created by the compression of target
tissues with the EUS probe or cardiovascular pulsation
through the aorta is expressed on ultrasound images [6], with
a higher strain indicating softer tissues and a lower strain
EUS-FNA is employed for the acquisition of tissue samples
from pancreatic lesions using 19–25G needles and is currently regarded as the most effective method for obtaining
pancreatic samples with a complication rate of <1% [9]. A
meta-analysis involving 31 studies reported a pooled sensitivity of 89%, specicity of 96%, and AUC of 0.97 for the
ability of EUS-FNA to diagnose pancreatic cancers [10].
Therefore, EUS-FNA is useful for the pathological diagnosis
of pancreatic lesions (Fig.16.3).
A previous study investigating needle tract seeding after
preoperative EUS-FNA in patients who underwent surgery
for pancreatic body and tail cancers reported a ve-year
cumulative needle tract seeding rate of 3.8% (95% condence interval [CI], 1.6–7.8%), which was estimated using
the Fine and Gray method, and showed no signicant difference in the median recurrence-free survival or overall survival between the EUS-FNA and non-EUS-FNA groups
[11]. Preoperative EUS-FNA for pancreatic body and tail
cancers has no negative effect on recurrence-free survival or
overall survival; nevertheless, needle tract seeding after
EUS-FNA was observed to have a non-negligible rate.
Hence, we should always consider the possibility of needle
tract seeding when performing EUS-FNA for pancreatic
cancers.
reecting harder tissues [7]. A meta-analysis of 19 studies
enrolling 1687 patients reported a pooled sensitivity of 98%,
pooled specicity of 63%, and area under the SROC curve of
0.91 for the differential diagnosis of pancreatic lesions using
EUS elastography [8]. Thus, EUS elastography is also effective for the differential diagnosis of pancreatic cancers.
Pooled summary estimates from a meta-analysis indicated a
sensitivity of 85%, specicity of 91%, and AUC of 0.94 for
the assessment of vascular invasion with EUS and a sensitivity of 69%, specicity of 81%, and AUC of 0.83 for nodal