Introduction
Complete resection is a significant factor influencing long-term survival in patients
with cholangiocarcinoma (CCA). A negative margin is required for complete resection;
therefore, an accurate preoperative diagnosis of tumor extension is important. In
patients with perihilar CCA (PCCA), preoperative assessment of the superficial ductal
spread (SDS) is important for deciding resectability; however, this is sometimes difficult
due to the anatomical complexity of the bile ducts. Magnetic resonance cholangiopancreatography
(MRCP) can provide a clear three-dimensional (3 D) image of the anatomy of the bile
duct without being invasive [1]. The bile duct outline can be evaluated using MRCP imaging; however, the SDS of
PCCA is sometimes difficult to evaluate with MRCP as well [2]. As a solution to this, virtual endoscopic imaging has been developed; using two-dimensional
(2 D) images obtained with MRCP, 3 D images can be created. For this, the 3 D image
software (SYNAPSE VINCENT system [Fujifilm Medical, Tokyo, Japan]) is primarily used.
We named this technique magnetic resonance cholangioscopy (MRCS). MRCS makes arbitrary
visualization of the bile duct in all directions possible through the use of 3 D images.
Patients and methods
Study design
This retrospective, observational study aimed to evaluate the accuracy of MRCS for
the preoperative SDS of PCCA. This study also evaluated whether MRCS, which is a non-invasive
test, has diagnostic capabilities different from those of the existing diagnostic
methods for ERC and POCS. We enrolled the patients who met the enrollment criteria
from clinical databases. The study protocol was approved by the institutional review
board of Gifu Municipal Hospital, Gifu University Hospital, and Gifu Prefectural General
Medical Center, and registered with the University Hospital Medical Information Network
Clinical Trial Registry (UMIN000040708).
Patients
Patients diagnosed with resectable PCCA based on pathological and typical radiologic
findings were included and evaluated using MRCP before the endoscopic retrograde cholangiography
(ERC) procedure and surgical treatment between May 2005 and January 2020. The exclusion
criteria were as follows: those aged < 20 years, those who underwent magnetic resonance
imaging (MRI) after biliary drainage, and those unable to provide informed consent.
Fifteen consecutive PCCA patients were enrolled. Peroral cholangioscopy (POCS) was
performed in seven of 15 patients before surgical treatment. The final diagnosis of
the SDS of PCCA was confirmed based on the pathological findings of the surgical specimens.
Written informed consent was obtained from all patients. The study was conducted in
accordance with the guidelines provided in the Declaration of Helsinki.
Magnetic resonance cholangioscopy
Patients underwent 1.5 T MRI scans (Intera 1.5 T or Achieva 1.5T; Philips, Netherlands).
MRI data were transferred to a SYNAPSE VINCENT workstation. MRCS was created using
the software in the 3 D view mode by an endoscopist. The opacity of MRCP data was
set to less than 1000 to enable tracing the bile duct outline ([Fig. 1A]). The created 3 D image was evaluated using the virtual endoscopic view mode available
in the software ([Fig. 1B]). The MRCS image was evaluated by two expert therapeutic endoscopists who had a
combined experience of performing over 50 POCS and 2000 ERC procedures. They did not
determine the accurate location of the SDS based on pathological findings.
Fig. 1 A The opacity of the MRCP data was set to less than 1000 for tracing the outline of
the bile duct. B The created MRCS image was evaluated using virtual endoscopic view mode of SYNAPSE
VINCENT system (Fujifilm Medical, Tokyo, Japan). MRCP, magnetic resonance cholangiopancreatography;
MRCS, magnetic resonance cholangioscopy.
ERC procedure
ERC was performed using a standard duodenoscope (TJF-200, TJF-240, or TJF-260V; Olympus
Medical System, Tokyo, Japan). Seven patients were evaluated using a video cholangioscope
(CHF-B260; Olympus Medical System, Tokyo, Japan, or SpyGlass DS; Boston Scientific,
Massachusetts, United States) after endoscopic sphincterotomy. To observe the biliary
mucosa clearly during POCS, the bile duct was irrigated with sterile saline through
the working channel. White light imaging with/without narrow-band imaging, which was
used when the CHF-B260 was selected, was utilized for evaluating the bile duct. The
SDS of malignancy was defined as the presence of irregular surface, easy oozing from
the bile duct mucosa, irregularly dilated vessels, and luminal narrowing.
Study outcomes
The outcome of this study was determining the accuracy of MRCS in the preoperative
SDS diagnosis of PCCA. The SDS was evaluated on both the distal bile duct side (papillary
side) and the hepatic duct using antegrade and retrograde virtual endoscopic views
([Fig. 2]). The other visual findings of SDS accuracy, including ERC and POCS, were also evaluated.
Diagnostic accuracy was determined by comparing the results of visual findings to
the pathological findings of surgical specimens.
Fig. 2 MRCS can evaluate the superficial ductal spread of the distal and hepatic bile duct.
A-R The distal biliary stricture (arrow) can be detected under the retrograde view from distal bile duct. A-A The main papilla (arrowhead) can be detected from the distal end of tumor, with the
smooth common bile duct wall under the antegrade view. B-R The sharp corner of the hepatic bile duct branching without tumor invasion (blue
arrowhead) can be evaluated under the retrograde view from the hepatic bile duct. B-A The papillary tumor that is invasive to the opposite side of the hilar bile duct branch
(blue arrowhead) can be evaluated under the antegrade view. MRCS: magnetic resonance cholangioscopy.
Results
Patient characteristics
Fifteen patients (14 men; median age, 71 years [range, 46–85 years] were enrolled.
The patients’ basic characteristics are summarized in [Table 1]. The Bismuth classifications of MRCP and the initial ERC findings were type I in
five patients, type II in six, type IIIa in two, and type IV in two patients. Seven
patients (47 %) underwent POCS for preoperative assessment. The operative procedures
performed were hepatectomy + bile duct resection in 10 patients, pancreatoduodenectomy
in three, and hepatopancreatoduodenectomy in two.
Table 1
Overall characteristics of 15 patients who were evaluated using MRCP for perihilar
cholangiocarcinoma.
|
Age (years), mean (IQR)
|
71 (46 – 85)
|
|
Female sex, n (%)
|
1 (7 %)
|
|
Bismuth classification
|
|
|
5/6/2/2
|
|
|
7 (47 %)
|
|
|
4/ 7 (57 %)
|
|
Type of operation, n (%)
|
|
|
10 (67 %)
|
|
|
3 (20 %)
|
|
|
2 (13 %)
|
IQR, interquartile range; MRCP, magnetic resonance cholangiopancreatography; POCS,
peroral cholangioscopy.
Evaluation of the superficial ductal spread with MRCS, ERC, and POCS
MRCS was successfully created and evaluated in all patients. The main tumor, the branches
of the hepatic bile duct (hepatic side), and the intrapancreatic common bile duct
(papillary side) were evaluated. The obstructed branched bile duct and the common
bile duct, or the irregular surface of the bile duct, were detected as tumor invasion
using retrograde and antegrade view ([Fig. 2]). The intact bile duct (benign) could be identified as a smooth bile duct wall and
a sharp corner of the branched bile duct in the hepatic duct ([Fig. 2B-R]). The intact intrapancreatic common bile duct could also be identified with the
smooth bile duct wall ([Fig. 2A-A]). The presence of a distal biliary stricture ([Fig. 2A-R]) and the irregular surface of the bile duct wall ([Fig. 2B-A]) were evaluated as malignant SDS. Debris was present in the obstructed bile duct
in one case; as the debris appeared as suspended matter, this case was considered
overdiagnosed. The accuracy rate of the SDS diagnosis in MRCS was 93 % (14/15) in
the hepatic side and 100 % (15/15) in the papillary side ([Table 2]).
Table 2
Diagnostic accuracy values of MRCS, ERC, and POCS for the superficial ductal spread
of perihilar cholangiocarcinoma.
|
MRCS
|
|
ERC
|
|
POCS
|
|
|
Hepatic side (n = 15)
|
Papillary side (n = 15)
|
Hepatic side (n = 15)
|
Papillary side (n = 15)
|
Hepatic side (n = 4)*
|
Papillary side (n = 7)
|
|
Accuracy
|
93 % (14/15)
|
100 % (15/15)
|
87 % (13/15)
|
100 % (15/15)
|
100 % (4/4)
|
100 % (7/7)
|
|
Overdiagnosis
|
7 % (1/15)
|
0 %
|
13 % (2/15)
|
0 %
|
0 %
|
0 %
|
|
Underdiagnosis
|
0 %
|
0 %
|
0 %
|
0 %
|
0 %
|
0 %
|
MRCS, magnetic resonance cholangioscopy; ERC: endoscopic retrograde cholangiography;
POCS: peroral cholangioscopy.
* Excluding the three patients in whom POCS did not pass through the tumor obstruction
The accuracy rate of the SDS diagnosis in ERC was 87 % (13/15) in the hepatic side
and 100 % (15/15) in the papillary side ([Table 2]). Because the contrast medium could not pool accurately in the obstructed bile duct
due to the bile duct bending in the hepatic side, two patients were considered as
cases of SDS overdiagnosis. However, these two cases could be accurately diagnosed
using MRCS. The accuracy rate of the SDS diagnosis in ERC with MRCS was 100 % (15/15)
in the hepatic side ([Table 3]).
Table 3
Hepatic side bile duct diagnostic accuracy values of ERC or POCS with/without MRCS
for the superficial ductal spread of perihilar cholangiocarcinoma.
|
Accurate diagnosis
|
Over diagnosis
|
Under diagnosis
|
|
ERC alone
|
87 % (13/15)
|
13 % (2/15)
|
0 %
|
|
ERC with MRCS
|
100 % (15/15)
|
0 %
|
0 %
|
|
Accurate diagnosis
|
Non-evaluation due to tumor obstruction
|
|
POCS alone
|
57 % (4/7)
|
43 % (3/7)
|
|
POCS with MRCS
|
100 % (7/7)
|
0 %
|
ERC, endoscopic retrograde cholangiography; MRCS, magnetic resonance cholangioscopy;
POCS: peroral cholangioscopy.
POCS was performed in seven cases. POCS findings of the SDS in the bile duct mucosa
included an irregular fine granular pattern and a fish-egg-like pattern with small
red nodules in the center. The scope did not pass through the tumor obstruction in
three patients during POCS; the SDS at the hepatic side could, therefore, not be diagnosed
in them. When these three cases were excluded, the accuracy rate of the hepatic side
SDS diagnosis in POCS was 100 % (3/3). The intrapancreatic bile duct could be evaluated
in all seven POCS cases. The accuracy rate of the SDS diagnosis was 100 % (7/7) in
the papillary side ([Table 2]). MRCS could evaluate the SDS of the hepatic side correctly in these three cases.
MRCS enabled definite evaluation of the sharp corner of the hepatic bile duct branch
without tumor invasion in the retrograde view, and the obstructed bile duct wall was
observed from the opposite side of the hilar bile duct branching using the antegrade
view ([Fig. 3]). The accuracy rate of the SDS diagnosis in POCS with MRCS was 100 % (7/7) in the
hepatic side ([Table 3]). With the addition of MRCS to ERC or POCS, SDS was diagnosed in all cases.
Fig. 3 A POCS (distal bile duct retrograde view) cannot pass the tumor obstruction. MRCS shows
the obstructed common bile duct by the tumor in the retrograde view. B-R MRCS evaluating the hepatic side of the tumor, which was evaluated as the sharp corner
of the distal branched bile duct in the retrograde view (arrow). B-A The obstructed bile duct wall can be observed from the opposite side of the hilar
bile duct branch under the antegrade view (arrowhead). MRCS, magnetic resonance cholangioscopy;
POCS, peroral cholangioscopy.
Discussion
Preoperative SDS of PCCA is important information for determining the surgical resectability
of the condition. MRCP is used routinely for evaluating biliary strictures. The accuracy
rate of MRCP in diagnosing biliary strictures was reported to be 82 % to 98 % [3]
[4]
[5]
[6]
[7]. MRCP provides results similar to those provided by ERC and is also useful for situations
where ERC is difficult, such as those involving a complex hilar stricture [5]
[8]. MRCP evaluates the outline of the bile duct; therefore, smaller tumors may often
be obscured by overlapping bile ducts and thus missed.
MRCS was created from the 2 D images obtained using MRCP, which only shows the bile
duct lumen. The bile duct lumen displays as white in MRCP. The whiteness is stronger
in the center of the bile duct than around its surface; hence, just setting the opacity
to less than 1000 in the software when assessing MRCP data can enable clear tracking
of only the outline of the bile duct ([Fig. 1a]).
ERC is the most common imaging test for diagnosing the SDS of PCCD. However, it is
difficult to evaluate the presence of mass lesions around the PCCA because the contrast
medium is sometimes difficult to pool accurately around the tumor [8]. In our study, the accuracy rate of ERC for bile duct diagnosis was 87 % (13/15)
in the hepatic side, which includes the two overdiagnosis cases that were caused by
difficulty in pooling the contrast medium around the tumor. These overdiagnosis cases
could be diagnosed accurately in MRCS. Because the obstructed side bile duct, including
the area around the tumor, is filled by bile, MRCS could detect and evaluate the surface
of the bile duct around the tumor. This advantage can improve the accuracy of diagnosis.
POCS is a useful procedure for diagnosing SDS because the video endoscope can provide
high-resolution images [9]
[10]. [Fig. 4] shows the comparison of MRCS and POCS images from our study. MRCS can evaluate the
surface structure, which is similar to the POCS image. However, MRCS cannot evaluate
the vascular structure; this is a disadvantage of MRCS.
Fig. 4 Comparison of POCS and MRCS images. a The benign bile duct wall. The smooth bile duct wall and the sharp corner of the
branched bile duct were detected in MRCS. b The malignant bile duct wall. The bulged and irregular surface of the bile duct wall
was detected in MRCS. MRCS can evaluate the surface structure similar to the POCS
image. However, MRCS cannot evaluate the vascular structure. MRCS, magnetic resonance
cholangioscopy; POCS, peroral cholangioscopy.
The major advantage of MRCS is that it enables non-invasive arbitrary evaluation of
the bile duct in all directions. In previous reports on POCS, the scope could not
be passed through the tumor obstruction in some cases, which reduced the diagnostic
accuracy of POCS [9]. Bends in the bile duct also make it difficult to insert the scope during POCS. In
our study, there were 3 cases wherein the hepatic side could not be evaluated due
to tumor obstruction. MRCS enabled accurate evaluation in all these three cases. Therefore,
MRCS may be an alternative method and good indication for evaluation when POCS cannot
be performed in case of tumor obstruction and bile duct bending. Moreover, substituting
POCS with MRCS has the potential to reduce the cost of POCS-related adverse events
and devices.
Our study has some limitations. This study was retrospective and had a small number
of cholangiocarcinoma cases that included only four intrahepatic bile duct invasion
cases (Bismuth type III or IV). There were also only seven POCS cases, and POCS could
not be performed in the remaining eight cases due to a narrow distal bile duct and/or
long (> 30 mm) malignant biliary stricture. There was no difference in the bile duct
lumen evaluation for the SDS diagnosis between MRCS and POCS in this study; however,
further verification of the effectiveness of MRCS images confirmed using prospective
studies with a greater number of patients, focusing on image comparison between POCS
and MRCS, is necessary. Second, the cases of obstructed bile duct filled by debris
could not be evaluated by MRCS; this has a significant potential to be misidentified
as the tumor. Therefore, when ERC indicates obstructed bile duct with debris, it can
be difficult to evaluate the SDS of PCCA using MRCS.
Conclusions
In conclusion, MRCS is considered as a new method for the accurate diagnosis of the
SDS of PCCA. This novel method can be easily created from MRI data and can noninvasively
evaluate arbitrary bile ducts.
