Introduction
In patients with biliary stricture and obstructive jaundice and/or cholangitis, endoscopic
retrograde cholangiopancreatography (ERCP) is the first-line modality because this
approach can be used to perform simultaneous tissue sampling and endoscopic biliary
drainage for biliary strictures. However, the diagnostic yield of ERCP-based tissue
sampling is unsatisfactory, and several new diagnostic modalities have been introduced
recently to improve the diagnostic accuracy of biliary strictures [1 ]
[2 ].
Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and peroral
cholangioscopy (POC)-guided target biopsy are representative methods for tissue sampling
from biliary strictures. In previous studies, EUS-FNAB was sensitive and highly specific
for diagnosing malignancy in biliary strictures [3 ]
[4 ]
[5 ]
[6 ]. However, EUS-FNAB is unlikely to be used as a routine clinical procedure for proximal
biliary strictures because its sensitivity was reported to be significantly lower
than that for distal strictures, owing to the technical difficulty and risk of needle-tract
seeding [7 ]
[8 ]
[9 ].
Newly developed POC systems, such as the SpyGlass direct visualization system (DVS;
Boston Scientific Corp., Marlborough, Massachusetts, USA) and direct POC using an
ultraslim endoscope, have led to great improvements in technical performance and diagnostic
yields for biliary strictures [10 ]
[11 ]. However, the performance of POC-guided target biopsy for distal bile duct strictures
is technically difficult, and this approach has a limited ability to diagnose biliary
strictures caused by nonintraductal, extrinsic compressed malignancies, such as a
pancreatic cancer [12 ]
[13 ]
[14 ].
Therefore, an approach that considers the characteristics of each diagnostic method
is required in order to optimize the diagnosis of biliary stricture. In this study,
we evaluated the usefulness of diagnostic approaches using peroral cholangioscopy-guided
forceps biopsy (POC-FB) or EUS-FNAB according to the stricture location in patients
with suspected malignant biliary stricture (MBS).
Methods
This was a prospective observational study comparing the diagnostic yields of POC-FB
and EUS-FNAB by stricture location in patients with suspected MBS. Our institutional
review board approved the study, and written informed consent was obtained from all
patients. The study has been registered with the UMIN Clinical Trial Registry (UMIN
000020193).
Patients
Consecutive patients with suspected MBS that required tissue sampling were prospectively
enrolled in the study. The inclusion criteria were: 1) stricture of the extrahepatic
bile duct that was revealed by cross-sectional radiological imaging (computed tomography
and/or magnetic resonance imaging); 2) clinical findings of obstructive jaundice and/or
cholangitis; 3) age > 18 years; and 4) ability to provide informed consent.
The exclusion criteria were: 1) known bile duct stricture without clinical and radiological
image findings suggestive of malignancy (e. g. primary biliary cirrhosis or postoperative
biliary stricture); 2) the presence of contraindications for ERCP; 3) altered gastrointestinal
anatomy or duodenal obstruction; and 4) coagulopathy (international normalized ratio
> 1.5 or platelet count < 80 000/mm3 ).
Diagnostic approach for suspected MBS
All procedures were achieved using standardized protocols by three experienced investigators.
Initially, ERCP was performed on enrolled patients for biliary drainage for obstructive
jaundice and/or cholangitis, and transpapillary forceps biopsy (TPB) was used for
biliary stricture tissue sampling. ERCP was performed using a standard duodenoscope
(JF or TJF-260V; Olympus Medical Systems, Co., Ltd., Tokyo, Japan) on patients under
conscious sedation. To identify the location and length of the biliary stricture,
cholangiography was achieved by injecting contrast medium (Omnipaque; GE Healthcare,
Seoul, Korea), and intraductal ultrasonography (IDUS) was performed immediately. The
IDUS probe (UM-G20-29R; Olympus Optical, Co., Ltd., Tokyo, Japan) was 2.0 mm in diameter
and had a radial scanning catheter with a scanning frequency of 20 MHz.
Strictures were classified as proximal or distal, according to their location. Based
on prior radiological imaging and IDUS, biliary strictures located in suprapancreatic
portions were defined as proximal and those in intrapancreatic portions were defined
as distal. A fluoroscopy-guided TPB of each biliary stricture was performed during
ERCP after endoscopic sphincterotomy. A 5 Fr conventional forceps with a cup diameter
of 1.8 mm (FB-39Q; Olympus Medical Systems) was used for TPB, and four to six specimens
were obtained from each stricture.
When malignancy was not detected on the initial TPB for suspected MBS, the stricture
was defined as an indeterminate biliary stricture. The diagnostic modality for follow-up
biopsy was decided according to the location of the indeterminate biliary stricture.
In patients with proximal strictures, POC-FB was performed; EUS-FNAB was applied for
patients with distal strictures.
POC-guided biopsy for proximal biliary strictures
Prophylactic antibiotics were administered to all patients, and carbon dioxide (Colosense
CO-3000; Mirae Medics, Co., Seoul, Korea) was used for insufflation during ERCP and
POC. POC-guided biopsy was performed using one of two types of single-operator cholangioscope
according to the diameter of the distal common bile duct (CBD). When the diameter
of the distal CBD was < 10 mm, the indeterminate biliary stricture was evaluated using
a first-generation or digital system (DS) of the SpyGlass (Boston Scientific Corp.).
Tissue sampling was achieved using SpyBite biopsy forceps (Boston Scientific Corp.)
with a cup diameter of 1.0 mm. The SpyGlass was advanced through the accessory channel
of a duodenoscope. Cannulation into the biliary tree was performed with an over-the-guidewire
or a free-hand technique ([Fig. 1 ], [Video 1 ]).
Fig. 1 Peroral cholangioscopy (POC)-guided biopsy was used with the SpyGlass digital system
(DS; Boston Scientific Corp., Marlborough, Massachusetts, USA) to diagnose indeterminate
proximal biliary stricture. a Cholangiogram showing a stricture of the proximal common bile duct, which was not
malignant on initial transpapillary forceps biopsy. b A cholangioscopic image taken with the SpyGlass DS, shows a stricture with irregular
tortuous vessels at the site of the proximal biliary stricture. POC-guided target
biopsy using SpyBite forceps was achieved. c Adenocarcinoma was diagnosed by histology (hematoxylin and eosin stain, × 100).
Video 1 Peroral cholangioscopy-guided biopsy using the SpyGlass digital system (Boston Scientific
Corp., Marlborough, Massachusetts, USA) on indeterminate proximal biliary stricture.
In patients with distal CBD > 10 mm in diameter, direct POC using an ultraslim endoscope
(GIF-XP260NS and GIF-XP290N; Olympus Medical Systems) was performed, and 5 Fr conventional
biopsy forceps (FB-39Q; Olympus Medical Systems) with a cup diameter of 1.8 mm was
used for tissue sampling of indeterminate biliary strictures. Direct POC using an
ultraslim endoscope was performed by three experienced investigators using a standardized
protocol ([Fig. 2 ], [Video 2 ]) [15 ].
Fig. 2 Direct peroral cholangioscopy (POC)-guided biopsy for diagnosis of indeterminate
proximal biliary stricture. a, b Cholangiograms. a An indeterminate stricture located at the proximal common bile duct. b An ultraslim endoscope advancing toward the stricture for direct POC. c, d Cholangioscopic images. c An infiltrative stricture with irregularly dilated and tortuous vessels. d Target biopsy of the stricture using forceps under direct visualization. e Adenocarcinoma (hematoxylin and eosin stain, × 100) was diagnosed by direct POC-guided
target biopsy.
Video 2 Direct peroral cholangioscopy-guided biopsy using an ultraslim endoscope on indeterminate
proximal biliary stricture.
EUS-FNAB for distal biliary strictures
In patients with distal biliary strictures, when malignancy was not detected on the
initial TPB, EUS-FNAB was performed as follow-up biopsy. EUS-FNAB was performed according
to a standardized protocol by three experienced investigators using a linear-array
echoendoscope (GF-UCT240; Olympus Medical Systems) in patients under conscious sedation.
FNAB was performed from the stomach using a standard 22-gauge, or from the duodenum
with a 25-gauge, FNAB device (Echotip ProCore; Wilson-Cook Medical, Winston-Salem,
North Carolina, USA). After puncturing the stricture, the stylet was removed, and
suction was applied using a 5 – 10-mL syringe. A triple approach comprising simultaneous
cytopathological and histological evaluations with on-site examination was used for
specimen preparation and analysis ([Fig. 3 ]) [16 ].
Fig. 3 Endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (EUS-FNAB) for a
diagnosis of indeterminate distal biliary stricture. a Cholangiogram showing narrowing of the distal common bile duct with dilation of the
proximal bile duct. b As malignancy was not confirmed by transpapillary forceps biopsy, EUS-FNAB was conducted
for the diagnosis of distal biliary strictures, and malignancy was confirmed by cytology
and histology. c Cytology (Papanicolaou stain, × 200). d Histology (hematoxylin and eosin stain, × 200
Histological diagnosis
One expert unblinded pathologist examined the pathological results of TPB, POC-FB,
and EUS-FNAB. The acquired tissue samples were classified using the following categories:
1) malignant, 2) atypical, 3) benign, or 4) nondiagnostic (insufficient tissue sampling
for pathological diagnosis). Samples classified as malignant were categorized as malignant,
whereas samples classified as atypical, benign, and nondiagnostic were categorized
as nonmalignant. The diagnosis of malignancy on EUS-FNAB was established when at least
one specimen preparation method (on-site cytology, definite cytology, or histology)
yielded positive findings for malignancy.
Standard references for final diagnosis
Final diagnosis was confirmed using one of the following criteria: 1) definite result
of malignancy in a surgical specimen or biopsy of a metastatic lesion; 2) malignant
diagnosis by TPB or EUS-FNAB or POC-FB, and clinical/imaging follow-up compatible
with malignant disease; and 3) malignancy not found on TPB and EUS-FNAB or POC-FB,
and clinical/imaging follow-up compatible with benign disease for at least 12 months.
Outcome measurements
The primary outcome was the diagnostic accuracy of the approach using POC-FB and EUS-FNAB
according to the location of the indeterminate biliary stricture.
The secondary outcomes were as follows: the diagnostic accuracy of initial TPB and
diagnostic yield of initial TPB combined with POC-FB or EUS-FNAB for suspected MBS;
technical success of POC-FB and EUS-FNAB; and number of adverse events associated
with POC-FB and EUS-FNAB.
The diagnostic accuracy was defined as the ratio of the sum of true-positive and true-negative
values divided by the number of lesions, where “true-positive” referred to the presence
of malignant cells. The technical success of POC was defined as successful advancement
of the ultraslim endoscope or SpyScope into the obstructed segment of the biliary
tree. Technical success of POC-guided tissue sampling was established when tissue
sampling using biopsy forceps was achieved under direct visualization of the target
stricture and macroscopically visible tissue was confirmed. Technical success of EUS-FNAB
was defined as proper puncture of the target stricture with the acquisition of some
visible samples or fragments of tissue. Adverse events were defined as any postprocedure
events that could be attributed to POC-FB or EUS-FNAB.
All patients underwent follow-up investigations with laboratory and radiological tests
for at least 1 day after POC-FB or EUS-FNAB. Excessive bleeding at the site of biopsy,
perforation, cholangitis, and pancreatitis were recorded as per normal practice.
Statistical analysis
Categorical parameters including sex, location of stricture, final diagnosis, technical
success, needle gauge, and adverse events were expressed as frequencies and percentages.
Continuous variables including age, length of stricture, follow-up duration, number
of samplings during POC, and number of needle passes during EUS-FNAB were summarized
and expressed as medians with interquartile ranges (IQRs). Sensitivity, specificity,
and accuracy analyses were performed, and the data were reported with exact 95 % confidence
intervals (CIs) and compared using the chi-squared test used to compute P values.
All statistical analyses were performed using the SPSS for Windows software package
(version 19.0; IBM Corp., Armonk, New York, USA). P values of < 0.05 were taken to indicate statistical significance.
Results
In total, 188 patients were screened between January 2014 and November 2016. Among
them, seven were excluded for the following reasons: contraindication for ERCP (n = 3),
inability to perform ERCP because of duodenal obstruction (n = 3), and coagulopathy
(n = 1). The remaining 181 patients underwent ERCP with TPB for suspected MBS.
Finally, a total of 181 patients (103 males, 78 females; median age 73.0 years [IQR
61.5 – 79.0 years]) with biliary obstruction by suspected MBS were analyzed. Findings
of initial TPB performed during ERCP were positive for malignancy in 122 patients
with suspected MBS, and the sensitivity of the initial TPB was 70.5 % (95 %CI 63.3 % – 76.8 %).
The overall diagnostic accuracy of initial TPB was 71.8 % (95 %CI 65.3 % – 78.4 %),
and was significantly greater in patients with proximal biliary strictures than in
those with distal biliary strictures (78.0 % vs. 60.3 %; P = 0.01) ([Fig. 4 ]).
Fig. 4 Patient flow through the study. MBS, malignant biliary stricture; CI, confidence
intervals; POC-FB, peroral cholangioscopy-guided forceps biopsy; EUS-FNAB, endoscopic
ultrasound-guided fine-needle aspiration biopsy.
Among the 59 patients with indeterminate biliary strictures, tissue sampling was respectively
obtained by POC-FB in 32 patients with proximal biliary strictures and by EUS-FNAB
in 27 patients with distal biliary strictures. Of the 59 patients with indeterminate
biliary strictures, previously obtained cross-sectional radiological imaging showed
that the strictures were not caused by visible masses in five patients with proximal
biliary stricture and in seven patients with distal biliary stricture. The final diagnoses
of suspected MBS in patients with proximal biliary strictures were cholangiocarcinoma
(n = 23), hepatocellular carcinoma (n = 2), gallbladder cancer (n = 1), and benign
stricture (n = 6). The final diagnoses in patients with distal biliary strictures
were pancreatic cancer (n = 21), cholangiocarcinoma (n = 2), gallbladder cancer (n = 2),
and benign stricture (n = 2) ([Table 1 ]).
Table 1
Baseline characteristics and final diagnoses for patients with indeterminate biliary
strictures.
Location of biliary stricture
P
Proximal (n = 32)
Distal (n = 27)
Age, median (IQR), years
71.5 (56.5−76.5)
66.0 (59.0−77.0)
0.40
Sex (male/female), n
20/12
16/11
0.51
Length of stricture, median (IQR), mm
21.5 (15.5−38.8)
25.0 (19.0−32.0)
0.50
Final diagnosis, n (%)
0.19
26 (81.3)
25 (92.6)
23
2
0
21
1
2
2
0
6 (18.8)
2 (7.4)
IQR, interquartile range.
The median follow-up duration of 181 patients was 108 days (IQR 65 – 192 days). Malignancy
was observed in 173 of 181 patients (95.6 %) with final diagnoses. The diagnosis of
malignancy was based on surgical pathology in 47 patients and other tissue diagnosis
in 38 patients. In 88 patients, malignancy was confirmed by TPB or POC-FB or EUS-FNAB
results and clinical/imaging follow-up. Among the eight patients (4.4 %) diagnosed
with benign disease, the diagnosis was based on surgical pathology in one patient,
and negative TPB and POC-FB or EUS-FNAB results and clinical/imaging follow-up in
seven patients. The median follow-up duration of eight patients with benign disease
was 481 days (IQR 407 – 568.5 days).
Technical characteristics of POC-FB and EUS-FNAB
POC was performed successfully in all 32 patients with proximal biliary strictures.
POC was performed using a direct POC with an ultraslim endoscope in 12 patients (37.5 %)
and with SpyGlass DVS in 20 patients (62.5 %). Direct POC-FB was successful in all
12 patients. In one patient, insertion of the SpyBite forceps up to the stricture
segment failed. POC-FB was a technical success in 31 patients (96.9 %), and tissue
specimens that were adequate for histological examination were obtained from all 31
patients. Cholangitis was observed in two patients (6.3 %) after POC.
No technical failure of EUS-FNAB occurred, and tissue specimens that were adequate
for histological examination were obtained from 27 patients with distal biliary strictures.
One episode of minor bleeding occurred during EUS-FNAB and was managed conservatively
([Table 2 ]).
Table 2
Technical characteristics and outcomes of peroral cholangioscopy-guided forceps biopsy
and endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with indeterminate
biliary strictures.
POC-FB in proximal biliary strictures (n = 32)
Technical success of POC, n (%)
32 (100)
Direct POC using an ultraslim endoscope, n (%)
12 (37.5)
20 (62.5)
14
6
Technical success of POC-guided biopsy, n (%)
31 (96.9)
Number of tissue samples, median (IQR)
4.0 (3.0−4.0)
Tissue specimen adequate for histological examination, n (%)
31 (100)
Adverse events, n (%)
2 (6.3)
EUS-FNAB in distal biliary strictures (n = 27)
Technical success of EUS-FNAB, n (%)
27 (100)
Number of needle passes, median (IQR)
3.0 (2.0−3.0)
Tissue specimen adequate for histological examination, n (%)
27 (100)
Needle gauge, n (%)
22 (81.5)
5 (18.5)
Adverse events, n (%)
1 (3.7)
POC-FB, peroral cholangioscopy-guided forceps biopsy; EUS-FNAB, endoscopic ultrasound-guided
fine-needle aspiration biopsy; DVS, direct visualization system; IQR, interquartile
range.
Diagnostic yields of POC-FB and EUS-FNAB
In 32 patients with proximal biliary strictures that were negative for malignancy
on initial TPB, POC-FB was performed as follow-up biopsy for suspected MBS in 31 patients. Of
these, 24 patients (77.4 %) were found to be positive for malignancy by POC-FB. EUS-FNAB
was performed as follow-up biopsy for 27 patients with distal biliary strictures that
were negative for malignancy on initial TPB. Among them, malignancy was observed in
24 patients (88.9 %) by EUS-FNAB. The sensitivity for malignancy of POC-FB in patients
with proximal biliary strictures and EUS-FNAB in patients with distal biliary strictures
was 92.3 % (95 %CI 74.9 %−99.1 %) and 96.0 % (95 %CI 79.7 %−99.9 %), respectively.
The diagnostic accuracy was 93.6 % (95 %CI 84.9 %−100 %) in patients with proximal
biliary strictures and 96.3 % (95 %CI 89.2 %−100 %) in patients with distal biliary
strictures ([Table 3 ]).
Table 3
Pathological results and diagnostic yield of peroral cholangioscopy-guided forceps
biopsy and endoscopic ultrasound-guided fine-needle aspiration biopsy according to
location of the indeterminate biliary stricture.
Biopsy method by stricture location
POC-FB in proximal strictures (n = 31)
EUS-FNAB in distal strictures (n = 27)
Pathological result, n
24
24
6
1
1
2
0
0
Diagnostic yield, % (95 %CI)
92.3 (74.9−99.1)
96.0 (79.7−99.9)
100 (47.8−100)
100 (15.8−100)
93.6 (84.9−100)
96.3 (89.2−100)
POC-FB, peroral cholangioscopy-guided forceps biopsy; EUS-FNAB, endoscopic ultrasound-guided
fine needle aspiration biopsy; CI, confidence interval.
Overall diagnostic yield of initial TPB combined with follow-up biopsy
Among patients with proximal biliary strictures, the combination of initial TPB and
follow-up POC-FB for patients with initial TPB findings that were negative for malignancy
showed a sensitivity of 98.2 % (95 %CI 93.7 %−99.8 %) for the diagnosis of malignancy.
Among patients with distal biliary strictures, the combination of initial TPB and
follow-up EUS-FNAB showed a sensitivity of 98.4 % (95 %CI 91.2 %−99.9 %). The overall
diagnostic accuracies of initial TPB combined with follow-up biopsy using POC-FB in
patients with proximal biliary strictures and EUS-FNAB in patients with distal biliary
strictures were 98.3 % (95 %CI 95.9 %−100 %) and 98.4 % (95 %CI 95.3 %−100 %), respectively
([Table 4 ]). In two patients with false-negative results for malignancy in initial TPB and
POC-FB, malignancy was confirmed by percutaneous liver biopsy and follow-up TPB, respectively.
One patient with false-negative results for malignancy in initial TPB and EUS-FNAB
was diagnosed as having malignancy by surgical resection.
Table 4
Overall diagnostic yield of first transpapillary forceps biopsy combined with follow-up
biopsy methods according to location of the suspected malignant biliary stricture.
Total
Proximal stricture
Distal stricture
Diagnostic yield, % (95 %CI)
98.3 (95.0−99.6)
98.2 (93.7−99.8)
98.4 (91.2−99.9)
100 (59.0−100)
100 (47.8−100)
100 (15.8−100)
98.3 (96.5−100)
98.3 (95.9−100)
98.4 (95.3−100)
TPB, transpapillary forceps biopsy; CI, confidence interval; POC-FB, peroral cholangioscopy-guided
forceps biopsy; EUS-FNAB, endoscopic ultrasound-guided fine-needle aspiration biopsy.
Discussion
The diagnostic capabilities of ERCP-based tissue sampling techniques, such as brush
cytology and/or TPB, are not very good. However, ERCP is still a first-line diagnostic
modality for MBS, especially in patients with jaundice and/or cholangitis. This prioritization
is because tissue sampling of the biliary stricture and decompression of the bile
duct can be performed simultaneously during ERCP, and the exact location and extent
of the stricture can be determined. Several diagnostic modalities for suspected MBS
have been developed and studied to complement TPB. IDUS has been used to differentiate
malignant from benign strictures, and to confirm local tumor T- and-N staging, with
high sensitivity and specificity [17 ]
[18 ]. IDUS provides additional clinically important information, such as the extent of
potentially cancerous infiltration and the origin of the stricture (intrinsic or extrinsic)
[19 ]
[20 ]. However, pathological analysis of tissues acquired from strictures or metastatic
lesions is still required for management decisions. Among new diagnostic modalities,
POC and EUS-FNAB are representative methods that can be used for tissue sampling and
imaging in patients with suspected MBS.
Direct visualization of the bile duct by POC in a mother – baby system was possible
several decades ago, but the clinical application of the mother – baby system is restricted
because of its inconvenience and limitations in the performance of the endoscope [21 ]. The recent development of new types of POC, such as the SpyGlass DVS and direct
POC using an ultraslim endoscope, has led to expansion of the use of POC in multiple
diagnostic and therapeutic areas for pancreaticobiliary diseases. The SpyGlass DVS
is a dedicated single-operator cholangioscopic system. It is advanced over a guidewire
into the bile duct through the working channel of a therapeutic duodenoscope. In a
meta-analysis, a first-generation SpyGlass DVS showed a pooled sensitivity of 74.7 %
(95 %CI 63.3 %−84.0 %) for the diagnosis of suspected MBS with negativity for malignancy
in samples obtained through brushing and/or TPB [22 ]. The first-generation SpyGlass DVS had several limitations, including inferior image
quality compared with that of conventional endoscopes, poor image stability, and difficulty
in catheter manipulation [10 ]
[21 ]
[23 ]. A new digital version of the SpyGlass DVS with enhanced functionality was introduced.
Although few studies have been performed, forceps biopsy guided by this new SpyGlass
DVS showed a high sensitivity of 80 %−85 % for the diagnosis of suspected MBS [10 ]
[24 ].
Direct POC using an ultraslim upper endoscope is another single-operator cholangioscopic
system that incorporates optical enhancement techniques and takes high resolution
images. In particular, an ultraslim endoscope with a large working channel diameter
of 2.0 mm enables the performance of interventional procedures, such as tissue sampling.
Furthermore, a previous study showed that it had a high technical success rate when
used with direct POC-guided biopsy sampling [21 ].
Although newly developed POC-guided biopsy techniques have shown high diagnostic yields
for suspected MBS, the acquisition of adequate tissue samples from biliary strictures
in the distal CBD remains difficult. The maintenance of a stable POC position is difficult
in patients with distal CBD strictures because POCs can be withdrawn easily from the
distal CBD. In addition, many distal CBD strictures develop through extrinsic malignancies,
such as pancreatic cancer, and even POC-guided biopsy has a significantly lower sensitivity
for the diagnosis of extrinsic malignant lesions (8 %) compared with intrinsic malignant
lesions (66 %) of biliary strictures [12 ].
Compared with POC-guided biopsy, EUS-FNAB is technically easier to perform in patients
with distal CBD strictures than in those with proximal CBD strictures. This difference
exists because the distal CBD is located close to the duodenal wall and is visualized
on EUS without difficulty, whereas the proximal perihilar bile ducts are closer to
the liver and farther away from the duodenal wall [6 ]. The sensitivity of EUS-FNAB was reported to be significantly higher for distal
biliary strictures than for proximal biliary strictures in previous studies [6 ]
[7 ]; however, the impact of biliary stricture location on the diagnostic accuracy of
EUS-FNAB has not been established because few relevant studies have been performed
[3 ].
In the present study, our approach to the diagnosis of suspected MBS was based on
stricture location, and the advantages and disadvantages of POC-FB and EUS-FNAB. Our
results showed that POC-FB for proximal biliary strictures and EUS-FNAB for distal
biliary strictures had high sensitivities of 92.3 % (95 %CI 74.9 %−99.1 %) and 96.0 %
(95 %CI 79.7 %−99.9 %), respectively. The improved technical success rates in this
study suggest that POC-FB will be used more readily for the diagnosis of inconclusive
biliary stricture in clinical practice. Finally, the initial TPB combined with follow-up
biopsy using POC-FB in patients with proximal biliary strictures and EUS-FNAB in patients
with distal biliary strictures showed high overall diagnostic accuracies of 98.3 %
(95 %CI 95.9 %−100 %) and 98.4 % (95 %CI 95.3 %−100 %), respectively. Based on our
results, we propose the tailored diagnostic approach based on the use of POC-FB or
EUS-FNAB according to the location of the stricture when malignancy is not diagnosed
on ERCP-based tissue sampling in patients with suspected MBS and obstructive jaundice
([Fig. 5 ]).
Fig. 5 Proposed tailored approach using optimized endoscopic modalities for the diagnosis
of suspected malignant biliary stricture in patients with obstructive jaundice. MBS,
malignant biliary stricture; ERCP, endoscopic retrograde cholangiopancreatography;
IDUS, intraductal ultrasonography; POC, peroral cholangioscopy; EUS-FNAB, endoscopic
ultrasound-guided fine-needle aspiration biopsy.
However, there are several limitations to evaluating suspected malignant biliary stricture
using POC systems, including high costs and the possibility of adverse event (cholangitis,
pancreatitis). Also, the standardization of endoscopic techniques and prevention of
air or carbon dioxide embolization are still required for direct POC using an ultraslim
endoscope [11 ]
[21 ]
[25 ]
[26 ]. In addition, clear criteria guiding the choice of POC systems for individual patients
are lacking. In the current study, direct POC using an ultraslim endoscope was used
for the patients with distal CBD > 10 mm in diameter considering the cost, image quality,
and diameter of the working channel. In addition, POC-FB during direct POC was performed
using a conventional biopsy forceps with larger cup diameter than that of SpyBite
biopsy forceps. Although no randomized, prospective, comparative study on the diagnostic
yields of biopsies performed using the SpyBite forceps and a conventional biopsy forceps
has appeared, the diagnostic yields of POC-FB could be affected by the type of POC
system employed. A biopsy forceps with a large cup may obtain more biliary stricture
tissue, improving the diagnostic yield of POC-FB [27 ].
This study has several limitations. First, it lacked a control group. POC-FB and EUS-FNAB
were not compared because this study was descriptive and our goal was to determine
the diagnostic yields of approaches involving these modalities according to stricture
location in patients with suspected MBS. Second, no crossover analysis of EUS-FNAB
and TPB in patients with negative findings for malignancy was performed. Third, two
types of POC system were used in the study; direct POC was preferred because it involved
the use of larger forceps, which increased the accuracy of histopathological diagnosis.
Therefore, the diagnostic yields of our study may be different from results obtained
when using only one type of POC system. Fourth, although biliary decompression in
distal CBD stricture was needed for the management of cholangitis and/or jaundice,
a small cholangiocarcinoma or small pancreatic head mass may not be easily visible
on EUS when the biliary system is decompressed after initial ERCP. Finally, three
highly experienced endoscopists at a single center conducted all procedures; thus,
the results may not reflect practices or technologies used at other institutions.
Despite the development of new technologies, accurate pathological diagnosis of biliary
stricture remains problematic because biliary strictures develop into various morphological
types and have various causes. Therefore, a tailored approach using optimized endoscopic
modalities that are specific to the characteristics of a given biliary stricture is
needed to achieve a high diagnostic yield for suspected MBS. In conclusion, an approach
using POC-FB or EUS-FNAB according to the stricture location may be useful for the
diagnosis of suspected MBS.
