Introduction
Peroral cholangiopancreatoscopy (POCP) is used to evaluate indeterminate biliary strictures,
intraductal papillary mucinous neoplasia, and treat difficult biliary or pancreatic
stones [1]. POCP provides direct visualization of abnormalities not readily identified by radiography;
targets stones for intraductal lithotripsy and lesions to biopsy, assessing the extent
of tumor for surgical resection; and has emerging applications such as extracting
inwardly migrated pancreatic or biliary stents and guiding tumor ablative therapies
[2]
[3]
[4].
While use of endoscope-based “mother-daughter” cholangioscopy systems was first reported
more than four decades ago, the fiber-optic, single-operator, semi-disposable cholangioscope
system (FSOC; Legacy SpyGlass, Boston Scientific Corporation, Marlborough, Massachusetts,
United States) has resulted in wider utilization of POCP over the last decade. The
FSOC was the first commercialized system to integrate optical bundles into a catheter-based
system rather than an endoscope-based system [3]
[4]. Several series describe use of FSOC for evaluation of indeterminate biliary strictures
and lesions [5]
[6]
[7]
[8]
[9]. In a prospective, multi-enter, international clinical registry of 297 patients
requiring evaluation of bile duct disease or biliary stone therapy, adequate tissue
for histological examination was collected in 88 % of patients who underwent biopsy.
Procedure success was achieved in 92 % of patients with stones and the overall incidence
of procedure-related adverse events was 7.5 % for diagnostic cases and 6.1 % for stone
therapy cases. Importantly, in 64 % of patients, addition of FSOC to endoscopic retrograde
cholangiopancreatography led to changes in clinical management [10]. In difficult biliary stone cases, FSOC-guided intraductal lithotripsy has shown
complete stone clearance rates of 73 % to 100 % [11]
[12]
[13]
[14].
Nearly a decade of clinical experience suggested a need to improve the optical resolution,
tip characteristics, accessory introduction, and tip articulation of the FSOC [15]
[16]
[17]
[18]
[19]
[20]. A digital and fully disposable single-operator cholangioscopy system (DSOC; SpyGlass
DS, Boston Scientific Corporation, Marlborough, Massachusetts, United States) was
developed. The goal of this bench study was to compare FSOC with DSOC in terms of
image quality, ease of use, and ability to visualize and target fixed and variable
markers utilizing miniature biopsy forceps (MBF, Spybite, Boston Scientific Corporation,
Marlborough, Massachusetts, United States).
Materials and methods
Digital single operator cholangioscopy system
The DSOC has a 10.8 French access and delivery catheter with a shorter working length
for
potential use with short wire technology, two dedicated 0.6-mm irrigation channels,
and four-way
tip deflection. Removal of the fiber-optic cable provided a potential opportunity
for additional
enhancements. This included a slightly larger working channel diameter through part
of its
course (maximal diameter 1.3 mm but tapers to 1.2 mm) that may improve the ability
to pass
accessories, increased maneuverability of the catheter tip, increased field-of-view
(120
degrees), and a simplified set-up ([Fig. 1]). Comparative
specifications of FSOC with DSOC are detailed in [Table 1].
Fig. 1 SpyGlass Direct Visualization System with SpyScope DS.
Table 1
FSOC and DSOC specification changes.
|
Component
|
FSOC
|
DSOC
|
|
SpyGlass optical probe
|
|
Field-of-view
|
70°
|
120°
|
|
Disposability
|
Semi-disposable, up to 10 times reuse
|
Fully-disposable, single-use
|
|
Camera
|
Fiber-optic
|
Digital with 4 × greater resolution
|
|
Imager
|
Fiber-optic probe independent of SpyScope
|
Digital sensor embedded at the distal tip of the SpyScope
|
|
SpyScope access and delivery catheter
|
|
Working length
|
220 cm
|
214 cm
|
|
Outer diameter
|
10 French
|
10.8 French
|
|
Working channel diameter
|
1.2 mm
|
1.3 mm
|
Development of the cholangioscopy biliary tract model
The watertight urethane rubber biliary tract bench model was designed by Pulse Research
and
Development (Southampton, Pennsylvania, United States) with input from the authors.
The model
features a fixed section representing a bifurcation 10.5 cm from the ampulla with
a transition
to a trifurcation intended to represent acutely angulated left intrahepatic ducts
(LIHD). The
three LIHD lumina were each 5 mm in diameter and 35 mm in length with a visual target
at the distal segment designed to represent a 0°, 15°, and 30° angle from the takeoff
of the trifurcation. The model also featured two variable inserts representing the
common bile duct (CBD) and right intrahepatic (RIHD) tracts. The first insert was
approximately 9 cm long and varied in diameter from 6.5 mm (RIHD) to 20 mm (CBD). The
pseudopapilla served as the entry of this insert and was 3.8 mm in diameter. This
segment contained two raised lesions (e. g. target areas) of a contrasting color in
variable locations. The second insert was approximately 3 cm long and also contained
two colored lesions in variable locations. A total of seven lesions were placed inside
the LIHD, RIHD, and CBD of the bench model. There were 60 different configurations
in total. The model also featured a cystic duct and pancreatic duct which served as
visual references only and did not need to be cannulated. [Fig. 2] contains an image of the cholangioscopy biliary tract model.
Fig. 2 Biliary model. a External view of the biliary model and duodenoscope entrance. b Open view of the model demonstrating the papilla and spaces for insertion of randomized
inserts. c Placement of randomized inserts into the papilla model.
Description of timed trials
Five investigators from the United States, Asia, and Europe participated in the study.
All investigators were experts in the field of cholangioscopy and had utilized FSOC
clinically but had only ex-vivo or porcine model experience with the DSOC system prior
to initiation of this trial. Immediately prior to the timed trials, each investigator
completed a single practice run with both the FSOC and DSOC systems, followed by sequential
timed runs randomized to the two systems. Randomization to choose FSOC or DSOC was
based on a blinded pull from an allotment of numbers assigned to one of two groups
equally represented in the pool (overall 1:1). The goal of each run was to visualize
the four variable colored targets and simulate biopsy by touching the target with
the MBF which was passed through the system’s working channel. In the fixed portion
of the model (e. g. LIHD) the goal was to enter and visualize each of the three lumina
with terminal targets. A technologist was present during testing to time the run using
a stopwatch and document the results. The technologist also changed out the model
configurations between runs to provide variations in location of lesions in the model.
The following outcomes were collected to document performance of the devices during
testing: Visual success was defined as the ability to visualize the targets. Targeting
success was defined as the ability to touch the targets with the MBF. Complete run
was defined as identification and targeting of all seven targets within 25 minutes.
Total time of run was the duration between entering and exiting the pseudopapilla.
A maximum time of 25 minutes was allotted for each run. Each outcome was analyzed
by type of target (fixed or variable). Additionally, after completion of all runs,
investigators completed a single assessment of image quality and ease of use for FSOC
and DSOC using a visual analog scale (VAS) of zero to 10, where zero was unacceptably
poor and 10 was excellent.
Data were entered into a database for analysis. All analyses were generated using
SAS software version 9.4. (SAS Institute Inc., Cary, North Carolina, United States).
Visual success was analyzed using a Fisher’s Exact test. Targeting success was analyzed
using a negative binomial model between the groups. Time of run and VAS were analyzed
using a t-test. Time to completion was analyzed using a t-test and a negative binomial model was used to test visual and targeting success
between the groups.
Results
A total of 39 runs were completed by five investigators prior to clinical availability
of the Spy
DS system in February 2015. Data from two of the runs were excluded due to inadequate
randomization, resulting in 37 evaluable runs used for analysis (17 FSOC, 20 DSOC;
259 total
targets). [Table 2] contains the summary of all results.
Table 2
Time trial outcomes.
|
FSOC
17 total trials
119 total targets
|
DSOC
20 total trials
140 total targets
|
P value
|
|
Visual success (%)
|
67 % (80 of 119)
|
99 % (139 of 140)
|
< 0.001
|
|
|
90 % (61 of 68)
|
100 % (80 of 80)
|
< 0.001
|
|
|
37 % (19 of 51)
|
98 % (59 of 60)
|
< 0.001
|
|
Targeting success per run
Mean (SD) (Min, Max)
|
4.5 (0.7)
(3.0, 5.0)
|
6.6 (0.7)
(5.0, 7.0)
|
0.009
|
|
Variable targets
|
3.5 (0.7)
(2.0, 4.0)
|
3.9 (0.2)
(3.0, 4.0)
|
0.449
|
|
Fixed targets
|
1.1 (0.2)
(1.0, 2.0)
|
2.6 (0.7)
(1.0, 3.0)
|
< 0.001
|
|
Complete runs (%)
|
0 % (0 of 17)
|
65 % (13 of 20)
|
< 0.001
|
|
Time of run
Mean (SD) (min, max)
|
15.4 (4.0)
(7.6, 21.6)
|
10.1 (3.7)
(4.1, 17.0)
|
< 0.001
|
|
Image quality (VAS)
Mean (SD) (Min, Max)
|
4.3 (1.0)
(3.0, 5.0)
|
8.3 (0.5)
(8.0, 9.0)
|
< 0.001
|
|
Ease of use (VAS)
Mean (SD) (Min, Max)
|
4.8 (1.0)
(4.0, 6.0)
|
8.5 (0.6)
(8.0, 9.0)
|
< 0.001
|
SD, standard deviation; VAS, vsual analog scale
Visual success was superior with DSOC compared with FSOC (99 % versus 67 %, P < 0.001).
As noted in [Fig. 3], the difference in visual success was more striking with the fixed, acutely angled
“LIHD” targets which were correctly identified in 37 % of FSOC runs compared with
98 % of the DSOC runs (P < 0.001). The ability to successfully visualize and target (targeting success per
run) was superior in the DSOC compared with FSOC groups (6.6 of 7 versus 4.5 of 7,
P = 0.009). With regard to targeting success, the DSOC group had statistically higher
success with fixed targets (2.6 versus 1.1, P < 0.001) but not variable targets (P = 0.449). The proportion of complete runs was statistically higher in the DSOC group
(13/20, 65 %) compared to the FSOC group (P < 0.001).
Fig. 3 Visual success.
The time of run was faster with DSOC (average 10.1 minutes) compared to the FSOC system
(average
of 15.4 minutes) (P < 0.001). In general, the time it took to complete a run improved
over time reflecting a learning curve on the part of the investigator ([Fig. 4]). Of note, despite investigators’ prior extensive experience with FSOC, both the
initial and final time of run was faster with DSOC. Further, the slope of the learning
curve was steeper with DSOC.
Fig. 4 Time of run learning curve.
Each investigator preferred the image quality, as well as the ease of use, with DSOC
compared to
FSOC ([Fig. 5]). On the VAS, average image quality was rated 4.3 with FSOC compared to 8.3 with
DSOC (P < 0.001). Similarly, ease of use was rated 4.8 with FSOC versus 8.5 with DSOC (P < 0.001).
Fig. 5 Physician evaluation of devices following all runs.
Discussion
Redesign of the fiberoptic device included a tapered insertion tip, digital and higher
resolution image, an increased field-of-view from 70° to 120°, and an increase in
working channel diameter through most of its length, which improved upon several of
the shortcomings seen with the first-generation SOC system.
Frequently, perceived advances in medical device technology that are often more expensive
than their predecessors are incorporated into practice without preclinical bench data
to demonstrate superiority. Endoscopic devices are no exception and though limited
retrospective clinical data using DSOC do exist, objective comparative studies are
lacking [21]
[22]. Results from our bench model study which was performed prior to the clinical availability
of the DSOC system suggest that these theoretical improvements, though unblinded,
have been objectively realized with significantly higher rates of visual and targeting
success and reduced total times with DSOC. Of note, no investigator was able to achieve
a complete run (7 of 7 targets identified and simulated biopsies completed) with the
FSOC in the allotted time primarily due to the limited tip articulation of the fiber-optic
system. A difference in targeting of the CBD lesions was not seen between the two
arms likely due to minimal need for tip angulation. When utilizing the DSOC, the physicians
achieved complete runs in 65 % of cases. Clinical implications for this finding may
be an enhanced ability to enter tortuous intrahepatic ducts, cystic duct insertion
points, and traversing and visualizing the often-angulated genu during pancreatoscopy.
Though efficiency is an ever-increasing requirement for endoscopists, visualizing
pathology and targets with confidence by an improved optical image is essential. To
further enhance our ability and interest in utilizing new technology, an improvement
in device set-up is apparent. The device has automatic illumination, white balance
and focus with a “plug-and-play” configuration given the absence of a separate optical
bundle as in the FSOC system. Clinically, this may result in shorter procedure times
with potential reductions in anesthesia time and fluoroscopy use. Further, the DSOC
device is fully disposable which eliminates the need for reprocessing of the optical
bundle that was required with FSOC [4].
Although each endoscopist had extensive experience with FSOC and limited to no experience
with DSOC, each individual adapted to use of DSOC with quicker times to completion
and more complete trials, demonstrating the impact of the improved image quality and
maneuverability.
The ex-vivo biliary model utilized in this study had visual targets and angulations
that may be seen during examination of the extrahepatic ducts and tortuous intrahepatic
ducts, respectively. Unique aspects of this ex-vivo biliary model study were the blinding
of endoscopists to the location of targets in the extrahepatic exchangeable segment
and ability to standardize and quantify visual targets for biopsy, which permitted
a direct comparison of the two devices.
Several limitations of this study warrant discussion. First, the investigators who
participated in the study were experienced users of the FSOC system and the ability
to adapt to potentially improved image quality and maneuverability with DSOC was seamless.
This may not translate to a simple transition for less experienced users. The endoscopists
were not blinded to type of catheter used as the reusable and movable optical probe
in the FSOC is a visible distinguishing feature. Further, their knowledge and, in
some cases, input for development of the new device could have introduced bias in
their utilization of it. The investigators did not have a set minimum or maximum time
limit to identify each individual target, which may have influenced the time of run
but each investigator was aware of the total time restriction. It is nevertheless
encouraging that the results of the objective measures of time and successful visualization
correlate with the physicians’ purely subjective perceptions of their experience according
to the VAS. Use of the bench model, while convenient and anatomically simulating acute
intrahepatic angulations, made it difficult to collect actual biopsy samples. Therefore,
the surrogate measure of touching the targets with forceps was as close to simulating
a biopsy as possible but would not be able to assess tissue adequacy. Extrahepatic
portions of the model were interchangeable so investigators were not aware of the
location of lesions in this area with each pass through. The bench model was not able
to simulate some real-world clinical situations such as use of irrigation and suction
to clear debris and mucus from the visual field or passage of accessories such as
biopsy forceps through the two devices’ working channels or wire exchanges for advancement
of the SOC system.
Conclusion
In conclusion, in this ex-vivo biliary bench model, the digital single-operator cholangioscopy
system demonstrated superior performance when compared with the fiber-optic single-operator
system. The DSOC has improved digital image capability and maneuverability. Further,
and perhaps most importantly as continued expanded use of intraductal endoscopy is
realized, this novel bench biliary model could be utilized in training endoscopists
that are less experienced with cholangiopancreatoscopy.
Further, whether the simpler setup and ease of use will permit wider adoption by high-volume
ERCP users new to cholangioscopy remains to be seen.
