DOI:10.2214/AJR.04.1588
AJR 2005; 185:1193-1200
© American Roentgen Ray Society
Comparison of IV Contrast-Enhanced Sonography and Histopathology of Pancreatic Cancer
Kenji Takeshima1,
Takashi Kumada2,
Hidenori Toyoda2,
Seiki Kiriyama2,
Makoto Tanikawa2,
Hideo Ichikawa1,
Toshiaki Kawachi1 and
Sadanobu Ogawa1
1 Department of Imaging Diagnosis, Ogaki Municipal Hospital, 4-86 Minaminhokawa,
Ogaki, Gifu 503-8502, Japan.
2 Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa,
Ogaki, Gifu 503-8502, Japan.
Received October 11, 2004;
accepted after revision November 23, 2004.
Address correspondence to T. Kumada.
Abstract
OBJECTIVE. We compared contrast-enhanced sonography findings with
pathologic findings in pancreatic cancer to evaluate the ability of
contrast-enhanced sonography to depict the pathologic changes associated with
pancreatic cancer.
SUBJECTS AND METHODS. Thirty-four patients with pancreatic cancer
who underwent surgery were investigated. Sonography was performed with
contrast material (Levovist) for all patients before surgery. Pathologic
findings were evaluated on the basis of the resected cancer specimens. We
compared contrast-enhanced sonography findings with pathologic findings.
RESULTS. All tumors that were hyperechoic on contrast-enhanced
sonography were papillary adenocarcinoma, and all tumors that were hypoechoic
on contrast-enhanced sonography were ductal adenocarcinoma. Among ductal
adenocarcinomas, five (71.4%) of seven tumors for which the size of the
hypoechoic area was unchanged on contrast-enhanced sonography had clear tumor
margins with no infiltration or inflammation in the margin. In contrast, all
tumors for which the size of the hypoechoic area was reduced on
contrast-enhanced sonography had unclear tumor margins with infiltration of
cancerous cells and inflammation. Nine (90%) of 10 tumors that showed partial
contrast enhancement or a vascular shadow in a hypoechoic area had large or
medium-sized vessels within a tumor at pathology. In contrast, only one (4.8%)
of 21 tumors that did not show the vascular shadow in a hypoechoic area had no
large or medium-sized vessels in a tumor.
CONCLUSION. Contrast-enhanced sonography well reflects the
pathologic changes of pancreatic cancer and will provide useful information in
a pretreatment evaluation. Further studies with a large number of patients
will be required to confirm this finding.
Introduction
Pancreatic cancer is one of the malignant tumors with few clinical symptoms
in its early stage, so it is frequently first observed in an advanced state.
Sonography is one of the diagnostic methods used for screening of pancreatic
tumors. Development of sonographic techniques and devices contributed to the
early detection of pancreatic tumors. Unenhanced sonography, however, cannot
provide sufficient information about the characteristics of these tumors and
is limited to the detection of the pancreatic tumor itself; the imaging
diagnosis of pancreatic cancer has usually been based on the combination of
other imaging findings such as endoscopic sonography, CT, and MRI
[1].
Contrast-enhanced sonography with the arterial infusion of CO2
microbubbles is the first technique of contrast-enhanced sonography
[2]. Initially, CO2
sonography was useful for the diagnosis of liver tumors such as hepatocellular
carcinoma and focal nodular hyperplasia
[3–6].
In addition, the use of CO2 sonography for the differential
diagnosis of pancreatic tumors has been reported
[7,
8]. However, CO2
sonography requires angiography, so patients must undergo an invasive
examination.
Recently, IV sonographic contrast agents have been developed, and
contrast-enhanced sonography with these agents has become available in
clinical practice. Contrast-enhanced sonography using the harmonic gray-scale
method with the IV injection of a contrast agent enables the visualization of
intratumoral blood flow dynamics that equals that of CO2
sonography. In addition, compared with CO2 sonography,
contrast-enhanced harmonic gray-scale sonography has that advantage that it
can be performed noninvasively at the bedside. This method has been frequently
used for the evaluation of hepatic tumor lesions
[9], but recently its
usefulness in the evaluation of pancreatic tumors has been reported
[10–14].
In our study, we compared the imaging findings of pancreatic cancer on the
arterial phase of contrast-enhanced sonography using the IV sonographic
contrast agent Levovist (SH U 508A, Schering) with macroscopic and microscopic
pathologic findings based on resected pancreatic cancer specimens from
patients who underwent surgery.
Subjects and Methods
Patients
One hundred three patients with pancreatic disease underwent
contrast-enhanced sonography in our hospital between September 1999 and
October 2002. Among them, 40 patients underwent surgery for pancreatic tumors,
and 34 patients were diagnosed with pancreatic cancer pathologically on the
basis of a resected specimen. They consisted of 21 men and 13 women with a
mean age of 66.6 ± 9.3 years (age range, 43–80 years). All
patients also underwent contrast-enhanced dynamic helical CT before treatment.
We compared contrast-enhanced sonography findings with pathologic findings of
these 34 patients.
The entire study was approved by the hospital ethics committee and was
performed in accordance with the Declaration of Helsinki
[15]. Written informed consent
was obtained from all patients before the study.
Imaging Procedures
Contrast-enhanced broadband harmonic gray-scale sonography was performed on
all patients. A Sonoline Elegra system (Siemens Medical Solutions) was used,
and images were obtained with a 3.5-MHz convex probe. The pancreas was scanned
with tissue harmonic gray-scale imaging (transmit, 2.8 MHz; and receive, 5.6
MHz) before injection of the contrast agent. After the IV bolus injection of
300 mg/mL concentration of a galactose–palmitic acid contrast agent
(Levovist), the pancreas was scanned using contrast-enhanced broadband
harmonic gray-scale sonography (transmit, 2.8 MHz; and receive, 5.6 MHz) at a
frame rate of 0.5–7 frames per second; we usually set 0.5–1 frame
per second. The transmitted acoustic power was 100%, and the mechanical index
values were between 1.7 and 1.9, which depended on the focus point. The focus
position was just below the bottom of the lesion. Seven milliliters of
contrast agent—air-filled microbubble suspension of galactose (99.9%)
stabilized with 0.1% palmitic acid—was injected at 2.0 mL/sec via a
20-gauge cannula placed in an antecubital vein. Ten milliliters of physiologic
saline was injected immediately after a bolus injection of the contrast agent.
The patients gently inspired and then held their breath for about 50 sec
(10–60 sec after contrast agent injection) while the enhancement of the
lesion was examined (observation of the arterial phase). The full examinations
were recorded on magnetooptical disks and S-VHS (super VHS) videotape.
Contrast-enhanced sonograms were evaluated by two of the authors
independently. If there was a discrepancy between them, they reached agreement
by consensus.
Histopathologic Evaluations
Resected specimens from all patients were explored both macroscopically and
microscopically. Specimens were stained with H and E, and the entire specimen
was explored. Pathologic evaluations were made independently by two authors
(one pathologist and one gastroenterologist who is a pancreatic specialist)
who were unaware of the contrast-enhanced sonography findings. If a
discrepancy in classification existed between them, they reached agreement by
consensus. Pathologic evaluation included measuring the size of the tumor
(maximal diameter) and the blood vessels within it macroscopically, histologic
classification of tumor differentiation, and microscopic evaluation of the
infiltration of cancerous cells in the border of the tumor.
Based on the results of both evaluations, contrast-enhanced sonography
images were compared with histopathologic findings from the resected
specimens.
View larger version (8K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1 —Drawing shows patterns of changes on contrast-enhanced
sonography. From top to bottom in far right column: complete hypoechoic
response with hyperechoic spot (n = 1), complete hypoechoic response
with no hyperechoic spot (n = 6), marginal isoechoic response with
hyperechoic spot (n = 9), marginal isoechoic response with no
hyperechoic spot (n = 15), and hyperechoic response (n =3)
(bottom row).
|
|
Statistical Analysis
In the analysis of patient characteristics, data are expressed as mean
± SD. Differences in proportions between groups were analyzed using the
chi-square test. Parametric data were compared using the Student's t
test, and nonparametric data were compared using the Mann-Whitney U
test. All p values were derived from two-tailed tests, and a level of
less than 0.05 was accepted as statistically significant.
Results
Tumor size was 24.9 ± 8.1 mm in diameter on unenhanced sonography.
According to the histologic classification, 31 patients had ductal
adenocarcinoma (well-differentiated type in 11, moderately differentiated type
in 18, and poorly differentiated type in two), and the other three had
papillary adenocarcinoma.
Details of the Contrast-Enhancement Pattern
Details of the contrast-enhancement pattern are shown in
Figure 1. In 31 (91.2%) of 34
patients, contrast enhancement was less marked in comparison with surrounding
parenchyma of pancreas, and these were classified as hypoechoic. In the other
three patients, contrast enhancement was distinctly strong in comparison with
surrounding parenchyma, and these were classified as hyperechoic. The patients
with a hypoechoic response were further subclassified as follows: no change
was observed in the size of hypoechoic area before and after contrast
enhancement (complete hypoechoic response), or tumor was depicted as a smaller
hypoechoic area in comparison with the tumor before contrast enhancement
(marginal isoechoic response). Seven patients had a complete hypoechoic
response, and 24 had a marginal isoechoic response. In addition, in patients
having a hypoechoic response, 10 tumors showed spotty or linear enhancement in
the hypoechoic area and were classified as hyperechoic
response–hyperechoic spot (+), whereas the other 21 tumors without the
hyperechoic spot were classified as hypoechoic response–hyperechoic spot
(–). One patient with a complete hypoechoic response and nine patients
with marginal isoechoic responses were hyperechoic spot (+) and the remaining
were hyperechoic spot (–).
View larger version (104K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2A —54-year-old man with hyperechoic response and 29 x 29
mm tumor of pancreatic head. Sonograms obtained before (A) and 18
(B), 46 (C), and 60 (D) sec after injection of contrast
agent. Tumor (arrowheads, A) is gradually stained on
contrast-enhanced sonography and becomes slightly hyperechoic compared with
surrounding tissue.
|
|
View larger version (111K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2B —54-year-old man with hyperechoic response and 29 x 29
mm tumor of pancreatic head. Sonograms obtained before (A) and 18
(B), 46 (C), and 60 (D) sec after injection of contrast
agent. Tumor (arrowheads, A) is gradually stained on
contrast-enhanced sonography and becomes slightly hyperechoic compared with
surrounding tissue.
|
|
View larger version (108K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2C —54-year-old man with hyperechoic response and 29 x 29
mm tumor of pancreatic head. Sonograms obtained before (A) and 18
(B), 46 (C), and 60 (D) sec after injection of contrast
agent. Tumor (arrowheads, A) is gradually stained on
contrast-enhanced sonography and becomes slightly hyperechoic compared with
surrounding tissue.
|
|
View larger version (116K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2D —54-year-old man with hyperechoic response and 29 x 29
mm tumor of pancreatic head. Sonograms obtained before (A) and 18
(B), 46 (C), and 60 (D) sec after injection of contrast
agent. Tumor (arrowheads, A) is gradually stained on
contrast-enhanced sonography and becomes slightly hyperechoic compared with
surrounding tissue.
|
|
Comparison of Sonography Enhancement Patterns and Pathology Findings of Resected Specimens of Ductal Adenocarcinoma
At pathologic evaluation, all three patients with a hyperechoic response
had papillary adenocarcinoma (Fig.
2A,
2B,
2C,
2D,
2E). In contrast, all 31
patients with a hypoechoic response had ductal adenocarcinoma. In microscopic
evaluation of the border of the tumor in 31 patients with ductal
adenocarcinoma, five tumors were classified as the clear margin type, in which
histopathologic findings showed no infiltration or inflammation in the margin
between cancerous and noncancerous portions, and the clear margin of the tumor
was confirmed. In contrast, the other 26 tumors were classified as the unclear
margin type, in which infiltration of cancerous cells and inflammation were
observed in the border of the tumor, and the margin of the tumor was not
clear.
Table 1 shows the tumor size
in patients with a complete hypoechoic response and in those with a marginal
isoechoic response. On unenhanced sonography, the maximal tumor size in
patients with a marginal isoechoic response was 24.7 ± 5.8 mm, which
was significantly larger than that in patients with a complete hypoechoic
response (19.2 ± 4.4 mm, p = 0.0353). In contrast, the maximal
tumor size on contrast-enhanced sonography was similar in both groups (18.7
± 4.5 mm in patients with a complete hypoechoic response and 16.4
± 4.9 mm in those with a marginal isoechoic response, p =
0.2970). In pathologic evaluation of the resected specimens, the maximal tumor
size was 18.5 ± 5.1 mm in patients with a complete hypoechoic response
and 25.3 ± 6.9 mm in those with a marginal isoechoic response. The size
of the tumor at pathology in patients with a marginal hypoechoic response was
similar to that on unenhanced sonography and was significantly larger than
that in patients with a complete hypoechoic response (p = 0.0229). In
patients with a complete hypoechoic response, well-differentiated tubular
adenocarcinoma was observed in four (57.1%) of seven patients, moderately
differentiated in two (28.6%) of seven patients, and poorly differentiated in
one (14.3%) of seven patients. In patients with a marginal isoechoic response,
well-differentiated carcinoma was observed in seven (29.2%) of 24 patients,
moderately differentiated in 16 (66.7%) of 24 patients, and poorly
differentiated in one (4.2%) of 24 patients. A trend was seen to lower
differentiation of tumors in patients with a marginal isoechoic response, but
the difference was not statistically significant (p = 0.371).
View this table:
[in this window]
[in a new window]
|
TABLE 1: Patterns of Enhancement on Contrast-Enhanced Sonography and Tumor Size
in Patients with Ductal Adenocarcinoma
|
|
Evaluation of the margin portion of the tumor revealed that clear margin
type was found in five (71.4%) of seven patients having a complete hypoechoic
response (Fig. 3A,
3B,
3C,
3D,
3E), whereas all the patients
with a marginal isoechoic response were the unclear margin type (Fig.
4A,
4B,
4C,
4D,
4E), showing a distinct and
significant difference between a complete hypoechoic response and a marginal
isoechoic response (p < 0.0001,
Table 2). In patients with an
unclear margin type, a mixture of cancerous cells and inflammatory cells was
observed in the marginal portion of the tumor that corresponded to the
peripheral area of enhancement on contrast-enhanced sonography. In patients
with a marginal isoechoic response, the size of the tumor evaluated
pathologically based on a resected specimen was similar to that measured on
unenhanced sonography (p = 0.2307) and was significantly larger than
the size measured on contrast-enhanced sonography (p < 0.0001,
Table 1).
View larger version (128K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3A —70-year-old man with complete hypoechoic response and 8
x 7 mm tumor of pancreatic head. Sonograms obtained before (A)
and 12 (B), 16 (C), and 30 (D) sec after injection of
contrast agent. Tumor is clearly depicted on contrast-enhanced sonography as
hypoechoic tumor with high contrast, but reduction of hypoechoic area is not
observed (arrowheads, A and D).
|
|
View larger version (135K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3B —70-year-old man with complete hypoechoic response and 8
x 7 mm tumor of pancreatic head. Sonograms obtained before (A)
and 12 (B), 16 (C), and 30 (D) sec after injection of
contrast agent. Tumor is clearly depicted on contrast-enhanced sonography as
hypoechoic tumor with high contrast, but reduction of hypoechoic area is not
observed (arrowheads, A and D).
|
|
View larger version (128K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3C —70-year-old man with complete hypoechoic response and 8
x 7 mm tumor of pancreatic head. Sonograms obtained before (A)
and 12 (B), 16 (C), and 30 (D) sec after injection of
contrast agent. Tumor is clearly depicted on contrast-enhanced sonography as
hypoechoic tumor with high contrast, but reduction of hypoechoic area is not
observed (arrowheads, A and D).
|
|
View larger version (130K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3D —70-year-old man with complete hypoechoic response and 8
x 7 mm tumor of pancreatic head. Sonograms obtained before (A)
and 12 (B), 16 (C), and 30 (D) sec after injection of
contrast agent. Tumor is clearly depicted on contrast-enhanced sonography as
hypoechoic tumor with high contrast, but reduction of hypoechoic area is not
observed (arrowheads, A and D).
|
|
View larger version (180K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3E —70-year-old man with complete hypoechoic response and 8
x 7 mm tumor of pancreatic head. Histopathologic image shows
well-differentiated ductal adenocarcinoma with distinct margin
(arrowheads). Infiltration of cancerous cells is not observed around
margin. (H and E, x40)
|
|
View larger version (77K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4A —56-year-old man with marginal isoechoic response and 18
x 18 mm tumor of pancreatic head. Sonograms obtained before (A)
and 15 (B), 25 (C), and 45 (D) sec after injection of
contrast agent. Peripheral region of tumor shows mild heterogeneous
enhancement on contrast-enhanced sonography, and hypoechoic area is reduced
(arrowheads, A and D).
|
|
View larger version (100K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4B —56-year-old man with marginal isoechoic response and 18
x 18 mm tumor of pancreatic head. Sonograms obtained before (A)
and 15 (B), 25 (C), and 45 (D) sec after injection of
contrast agent. Peripheral region of tumor shows mild heterogeneous
enhancement on contrast-enhanced sonography, and hypoechoic area is reduced
(arrowheads, A and D).
|
|
View larger version (108K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4C —56-year-old man with marginal isoechoic response and 18
x 18 mm tumor of pancreatic head. Sonograms obtained before (A)
and 15 (B), 25 (C), and 45 (D) sec after injection of
contrast agent. Peripheral region of tumor shows mild heterogeneous
enhancement on contrast-enhanced sonography, and hypoechoic area is reduced
(arrowheads, A and D).
|
|
View larger version (113K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4D —56-year-old man with marginal isoechoic response and 18
x 18 mm tumor of pancreatic head. Sonograms obtained before (A)
and 15 (B), 25 (C), and 45 (D) sec after injection of
contrast agent. Peripheral region of tumor shows mild heterogeneous
enhancement on contrast-enhanced sonography, and hypoechoic area is reduced
(arrowheads, A and D).
|
|
View larger version (186K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4E —56-year-old man with marginal isoechoic response and 18
x 18 mm tumor of pancreatic head. Histopathologic image shows moderately
differentiated ductal adenocarcinoma. Margin of tumor is indistinct, with
marked infiltration of cancerous cells (arrowheads). (H and E,
x200)
|
|
In the evaluation of blood vessels in the tumor in 31 ductal cell
carcinomas, vessels of 0.1–0.5 mm in diameter were macroscopically
confirmed in a tumor in 10 patients, and these tumors were classified as a
tumor positive for blood vessels. In contrast, no vessels were observed
macroscopically in a tumor in the other 21 patients, and their tumors were
classified as negative for blood vessels. Among 31 patients with a hypoechoic
response, a tumor positive for blood vessels was observed in nine (90.0%) of
10 patients who were hyperechoic spot (+) on contrast-enhanced sonography
(Fig. 5A,
5B,
5C,
5D,
5E), whereas it was observed
in only one (4.8%) of 21 patients who were hyperechoic spot (–)
(p < 0.0001, Table
3).
View larger version (95K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5A —67-year-old man with marginal isoechoic response and positive
hyperechoic spots in 29 x 24 mm tumor of pancreatic head. Sonograms
obtained before (A) and 15 (B), 18 (C), and 25 (D)
sec after injection of contrast agent. Peripheral region of tumor shows mild
heterogeneous enhancement and reduction of hypoechoic area on
contrast-enhanced sonography (arrowheads, A and D).
Blood vessels developing in tumor are also depicted (arrowhead,
C).
|
|
View larger version (95K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5B —67-year-old man with marginal isoechoic response and positive
hyperechoic spots in 29 x 24 mm tumor of pancreatic head. Sonograms
obtained before (A) and 15 (B), 18 (C), and 25 (D)
sec after injection of contrast agent. Peripheral region of tumor shows mild
heterogeneous enhancement and reduction of hypoechoic area on
contrast-enhanced sonography (arrowheads, A and D).
Blood vessels developing in tumor are also depicted (arrowhead,
C).
|
|
View larger version (95K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5C —67-year-old man with marginal isoechoic response and positive
hyperechoic spots in 29 x 24 mm tumor of pancreatic head. Sonograms
obtained before (A) and 15 (B), 18 (C), and 25 (D)
sec after injection of contrast agent. Peripheral region of tumor shows mild
heterogeneous enhancement and reduction of hypoechoic area on
contrast-enhanced sonography (arrowheads, A and D).
Blood vessels developing in tumor are also depicted (arrowhead,
C).
|
|
View larger version (93K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5D —67-year-old man with marginal isoechoic response and positive
hyperechoic spots in 29 x 24 mm tumor of pancreatic head. Sonograms
obtained before (A) and 15 (B), 18 (C), and 25 (D)
sec after injection of contrast agent. Peripheral region of tumor shows mild
heterogeneous enhancement and reduction of hypoechoic area on
contrast-enhanced sonography (arrowheads, A and D).
Blood vessels developing in tumor are also depicted (arrowhead,
C).
|
|
View larger version (168K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5E —67-year-old man with marginal isoechoic response and positive
hyperechoic spots in 29 x 24 mm tumor of pancreatic head.
Histopathologic image shows moderately differentiated ductal adenocarcinoma;
margin of tumor is indistinct, with marked infiltration of cancerous cells
(arrowheads). Dilated vessels are observed on enlarged image
(arrow). (H and E, x40)
|
|
Discussion
Several studies have evaluated the vascularity of pancreatic mass lesions
with various imaging techniques such as contrast-enhanced CT
[16–20],
Doppler sonography [21],
endoscopic Doppler sonography
[22,
23], and CO2
sonography [7,
8]. These articles mainly
focused on the differential diagnosis, based on tumor vascularity, of
pancreatic tumors, including ductal adenocarcinoma, papillary adenocarcinoma,
endocrine tumor, and benign nodule, that develop during the course of chronic
pancreatitis. Four recent studies evaluated the vascularity of pancreatic
tumors using sonography enhanced with the contrast agent Levovist
[24–27].
In three of these reports, the vascularity of pancreatic tumors on
contrast-enhanced sonography was compared with that on enhanced CT
[24–26].
The study by Takeda et al.
[27] attempted to compare
contrast-enhanced sonography findings with pathologic findings, but in most
cases pathologic findings were based on the samples of sonographically guided
fine-needle aspiration biopsy.
In our study, we focused on pancreatic cancer and compared
contrast-enhanced sonography findings with histopathologic findings based on
resected specimens in all patients, with which we could perform pathologic
analyses of the entire tumor, including tumor margins. All ductal
adenocarcinomas were hypoechoic in comparison with the surrounding pancreatic
parenchyma on contrast-enhanced sonography, indicating hypovascularity,
whereas papillary adenocarcinomas showed hypervascularity. Contrast-enhanced
dynamic CT also showed the enhancement of a tumor in all three patients with
papillary adenocarcinoma, and no enhancement in all patients with ductal
adenocarcinoma. Thus, contrast-enhanced sonography corresponded well with the
dynamic CT findings of hypervascularity and hypovascularity, and these
findings indicate that two histologic types of pancreatic cancer (i.e., ductal
and papillary adenocarcinoma) can be distinguished by contrast-enhanced
sonography findings.
In the case of ductal pancreatic cancer, two distinct patterns of
enhancement were observed on contrast-enhanced sonography in comparison with
unenhanced sonography: pancreatic tumors with a constant size of the
hypoechoic area (complete hypoechoic response) and tumors with a reduced size
of the hypoechoic area (marginal isoechoic response). This reduction in tumor
size represents the isoechoic enhancement of peritumoral regions. We
previously examined the pattern of enhancement of pancreatic cancer on
CO2 sonography but did not find as distinct a difference in
enhancement patterns as that on contrast-enhanced sonography
[28]. This difference in the
enhancement pattern between CO2 sonography and contrast-enhanced
sonography may be caused by the difference in bubble size between the two
contrast agents. The size of CO2 microbubbles is about 30 µm,
whereas that of Levovist microbubbles is about 1.3 µm. It is therefore
presumed that the latter more easily reach the site where infiltration of
cancer cells or inflammation is observed in the marginal portion and, as a
result, the peripheral portion of the tumor is contrast-enhanced and the
hypoechoic area is apparently reduced in size.
In a recent study, Ozawa et al.
[25] also reported the
isoechoic enhancement of the peripheral region of pancreatic cancer. Those
authors speculated that the presence of secondary changes of the pancreatic
parenchyma, such as inflammation and subsequent fibrosis, was associated with
pancreatic cancer causing marginal isoechoic enhancement, but they did not
state this theory as a conclusion because of the scarcity of resected samples.
Our analyses clearly showed the pathologic findings of this isoechoic
enhancement, which consisted of a mixture of cancerous and inflammatory cells.
Importantly, this area contains the cancerous cells and should be regarded as
part of the cancer, not as marginal pancreatic parenchyma. The size of a tumor
on a resected specimen was similar to that on unenhanced sonography and larger
than that on contrast-enhanced sonography. Thus, unenhanced sonography better
reflected the actual tumor size. Pancreatic cancer tends to infiltrate in the
early stage, and capsular infiltration is observed even in tumors of 20 mm or
less. Contrast-enhanced sonography findings can indicate the infiltration of
pancreatic cancer and can provide useful pretreatment information, especially
as a preoperative evaluation in patients who are candidates for surgery.
The presence of hyperechoic spots in a hypoechoic area of the pancreatic
tumor on contrast-enhanced sonography has been reported by other investigators
[25–27].
Pathologically, hyperechoic spots correspond to large or medium-sized muscular
arteries (0.1–0.5 mm in diameter) involved in the tumor. Park et al.
[29] suggested that
hypervascularity in pancreatic cancer that was evaluated on arterial phase
helical CT was characterized by a large feeding artery. They reported that
large and medium-sized arteries were found in the pancreatic cancer on
microscopic examination, which is consistent with our results. In our previous
study of CO2 sonography, hyperechoic spots were depicted in two
(6.9%) of 29 patients with ductal adenocarcinoma
[28]; this rate is lower than
that in patients with ductal adenocarcinoma with positive hyperechoic spots
(10/31 patients, 32.3%). This difference is also caused by the difference in
the size of microbubbles between CO2 and Levovist. As well as the
evaluation of tumor margins, contrast-enhanced sonography using Levovist has
an advantage over CO2 sonography in evaluating these tumor blood
vessels because of its smaller bubble size.
In conclusion, pancreatic cancer that was more hyperechoic than the
surrounding pancreatic parenchyma on contrast-enhanced sonography was
considered to be papillary adenocarcinoma. In ductal adenocarcinoma, the tumor
was more hypoechoic than the surrounding pancreatic parenchyma on
contrast-enhanced sonography. Tumors that showed reduced tumor size on
contrast-enhanced sonography had indistinct tumor margins with infiltrative
invasion of cancerous cells and inflammation. Most ductal adenocarcinomas in
which a hyperechoic spot was depicted on contrast-enhanced sonography had
feeding arteries of 0.1–0.5 mm in diameter in the tumor. Thus, our study
showed the ability of contrast-enhanced sonography to depict the details of
pathologic changes associated with pancreatic cancer. Contrast-enhanced
sonography can provide useful information on pancreatic cancer in a
pretreatment evaluation. However, further studies with a larger number of
patients will be required to confirm our findings.
References
- Tamm E, Charnsangavej C. Pancreatic cancer: current concepts in
imaging for diagnosis and staging. Cancer J2001; 7:298
–311[Medline]
- Matsuda Y, Yabuuchi I. Hepatic tumors: US contrast enhancement with
CO2 microbubbles. Radiology1986; 161:701
–705[Abstract/Free Full Text]
- Kudo M, Tomita S, Tochio H, Kashida H, Hirasa M, Todo A. Hepatic
focal nodular hyperplasia: specific findings at dynamic contrast-enhanced US
with carbon dioxide microbubbles. Radiology1991; 179:377
–382[Abstract/Free Full Text]
- Kudo M, Tomita S, Tochio H, et al. Small hepatocellular carcinoma:
diagnosis with US angiography with intraarterial CO2 microbubbles.
Radiology 1992;182
: 155–160[Abstract/Free Full Text]
- Kudo M, Tomita S, Tochio H, et al. Sonography with intraarterial
infusion of carbon dioxide microbubbles (sonographic angiography): value in
differential diagnosis of hepatic tumors. AJR1992; 158:65
–74[Abstract/Free Full Text]
- Nomura Y, Matsuda Y, Yabuuchi I, Nishioka M, Tarui S.
Hepatocellular carcinoma in adenomatous hyperplasia: detection with
contrast-enhanced US with carbon dioxide microbubbles.
Radiology 1993;187
: 353–356[Abstract/Free Full Text]
- Kato T, Tsukamoto Y, Naitoh Y, Hirooka Y, Furukawa T, Hayakawa T.
Ultrasonographic and endoscopic ultrasonographic angiography in pancreatic
mass lesions. Acta Radiol 1995;36
: 381–387[Medline]
- Koito K, Namieno T, Nagakawa T, Morita K. Inflammatory pancreatic
masses: differentiation from ductal carcinomas with contrast-enhanced
sonography using carbon dioxide microbubbles. AJR1997; 169:1263
–1267[Abstract/Free Full Text]
- Harvey CJ, Blomley MJ, Eckersley RJ, Heckemann RA, Butler-Barnes J,
Cosgrove DO. Pulse-inversion mode imaging of liver specific microbubbles:
improved detection of subcentimetre metastases. Lancet2000; 355:807
–808[CrossRef][Medline]
- Heckemann RA, Cosgrove DO, Blomley MJ, Eckersley RJ, Harvey CJ,
Mine Y. Liver lesions: intermittent second-harmonic gray-scale US can increase
conspicuity with microbubble contrast material—early experience.
Radiology 2000;216
: 592–596[Abstract/Free Full Text]
- Harvey CJ, Blomley MJ, Eckersley RJ, et al. Hepatic malignancies:
improved detection with pulse-inversion US in late phase of enhancement with
SH U 508A—early experience. Radiology2000; 216:903
–908[Abstract/Free Full Text]
- Numata K, Tanaka K, Kiba T, et al. Contrast-enhanced, wide-band
harmonic gray scale imaging of hepatocellular carcinoma: correlation with
helical computed tomographic findings. J Ultrasound
Med 2001; 20:89
–98[Abstract]
- Blomley MJ, Sidhu PS, Cosgrove DO, et al. Do different types of
liver lesions differ in their uptake of the microbubble contrast agent SH U
508A in the late liver phase? Early experience.
Radiology 2001;220
: 661–667[Abstract/Free Full Text]
- von Herbay A, Vogt C, Haussinger D. Late-phase pulse-inversion
sonography using the contrast agent Levovist: differentiation between benign
and malignant focal lesions of the liver. AJR2002; 179:1273
–1279[Abstract/Free Full Text]
- World Medical Association. Declaration of Helsinki:
ethical principles for medical research involving human subjects,
revised. Edinburgh, Scotland: World Medical Association,2000
- Hollett MD, Jorgensen MJ, Jeffrey RB Jr. Quantitative evaluation of
pancreatic enhancement during dual-phase helical CT.
Radiology 1995;195
: 359–361[Abstract/Free Full Text]
- Diehl SJ, Lehmann KJ, Sadick M, Lachmann R, Georgi M. Pancreatic
cancer: value of dual-phase helical CT in assessing resectability.
Radiology 1998;206
: 373–378[Abstract/Free Full Text]
- Graf O, Boland GW, Warshaw AL, Fernandez-del-Castillo C, Hahn PF,
Mueller PR. Arterial versus portal venous helical CT for revealing pancreatic
adenocarcinoma: conspicuity of tumor and critical vascular anatomy.
AJR 1997; 169:119
–123[Abstract/Free Full Text]
- Lu DSK, Vedantham S, Krasny RM, Kadell B, Berger WL, Reber HA.
Two-phase helical CT for pancreatic tumors: pancreatic versus hepatic phase
enhancement of tumor, pancreas, and vascular structure.
Radiology 1996;199
: 697–701[Abstract/Free Full Text]
- Boland GW, O'Malley ME, Saez M, Fernandez-del-Castillo C, Warshaw
AL, Mueller PR. Pancreatic-phase versus portal vein-phase helical CT of the
pancreas: optimal temporal window for evaluation of pancreatic adenocarcinoma.
AJR 1999; 172:605
–608[Abstract/Free Full Text]
- Rickes S, Unkrodt K, Neye H, Ocran KW, Wermke W. Differentiation of
pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced
power Doppler sonography. Scand J Gastroenterol2002; 37:1313
–1320[CrossRef][Medline]
- Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and
power-Doppler EUS for the discrimination between focal pancreatitis and
pancreatic carcinoma. Gastrointest Endosc2001; 53:784
–789[CrossRef][Medline]
- Hirooka Y, Goto H, Ito A, et al. Contrast-enhanced endoscopic
Doppler ultrasonography in pancreatic diseases: a preliminary study.
Am J Gastroenterol 1998;93
: 632–635[CrossRef][Medline]
- Oshikawa O, Tanaka S, Ioka T, Nakaizumi A, Hamada Y, Mitani T.
Dynamic sonography of pancreatic tumors: comparison with dynamic CT.
AJR 2002; 178:1133
–1137[Abstract/Free Full Text]
- Ozawa Y, Numata K, Tanaka K, et al. Contrast-enhanced sonography of
small pancreatic mass lesions. J Ultrasound Med2002; 21:983
–991[Abstract/Free Full Text]
- Kitano M, Kudo M, Maekawa K, et al. Dynamic imaging of pancreatic
diseases by contrast enhanced coded phase inversion harmonic ultrasonography.
Gut 2004; 53:854
–859[Abstract/Free Full Text]
- Takeda K, Goto H, Hirooka Y, et al. Contrast-enhanced
transabdominal ultrasonography in the diagnosis of pancreatic mass lesions.
Acta Radiol 2003;44
: 103–106[CrossRef][Medline]
- Takeshima K, Ogawa S, Kawachi T, et al. Comparison between contrast
enhanced ultrasonography with Levovist and CO2 US-angiography of
pancreatic cancer [in Japanese]. (abstr) J Med
Ultrasonics 2002; 29:S361
- Park CM, Cha IH, Choi SY, Kim HK. Hyperdense enhancement of
pancreatic adenocarcinoma on spiral CT: two case reports. Clin
Imaging 1999; 23:187
–189[CrossRef][Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. D'Onofrio, A. J. Megibow, N. Faccioli, R. Malago, P. Capelli, M. Falconi, and R. P. Mucelli
Comparison of Contrast-Enhanced Sonography and MRI in Displaying Anatomic Features of Cystic Pancreatic Masses
Am. J. Roentgenol.,
December 1, 2007;
189(6):
1435 - 1442.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
