Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) has been used as a primary diagnostic
modality in the diagnosis of biliary pathology, but its role has been superseded by
other noninvasive imaging procedures. However, ERCP remains an indispensable tool
for obtaining tissue/cytological samples from the biliary system in the evaluation
of strictures. The diagnostic performance of fluoroscopically guided transpapillary
biopsies and brush cytology is suboptimal. Direct intraductal visualization of lesions
and strictures of the biliary system has been achieved using a number of different
instruments and techniques, each of which have benefits and limitations [1]
[2]
[3].
The SpyGlass Direct Visualization System (SpyGlass DVS; Boston Scientific, Marlborough,
Massachusetts, USA) was developed as a single-operator catheter-based cholangiopancreatoscope
and was first described in a preclinical study in 2007 [4]. Also in 2007, a study describing its use in 35 patients was reported by the same
author [5], with its utility in obtaining samples for histological evaluation, as well as providing
targeted therapy for biliary stone disease, being demonstrated. The largest prospective,
multicenter, consecutive series on peroral cholangioscopy (POCS) using the SpyGlass
system included 297 cases in the USA and Europe, and was published in 2011 [6]. Biliary strictures and biliary stone disease were the indications for POCS in that
cohort. Since then a prospective, multicenter study was completed in the Asia, Middle
East, and Africa (AMEA) regions and included 522 patients who underwent POCS for various
indications, including biliary stone disease, as well as indeterminate biliary strictures.
The outcomes of a subcohort of this study with difficult biliary stone disease were
recently published [7].
The aim of the current study was to evaluate the performance of POCS using the SpyGlass
DVS throughout the AMEA regions for patients with indeterminate biliary strictures
(289 patients) in a real-life clinical setting.
Methods
Study design, study conduct, and patient population
The SpyGlass AMEA Registry was a prospective, observational, open-label, multicenter
post-market study conducted at 20 sites in the AMEA region (NCT02281019 at http://www.clinicaltrials.gov; and CTRI/2014 /11 /005173 at http://ctri.nic.in/Clinicaltrials/login.php) after clearance or approval of the SpyGlass system in all participating countries.
The centers that participated in the registry were tertiary care centers with relevant
experience in the use of POCS. As per the study protocol, participating centers were
required to have completed at least 10 SpyGlass procedures prior to enrolling patients
undergoing SpyGlass into the SpyGlass AMEA Registry. There was no central committee
monitoring data collection and image quality in this study.
Boston Scientific Corporation sponsored and funded the study. A statistician (M.J.R.)
who is a full-time employee of Boston Scientific Corporation performed the data management
and statistical analysis. Review and input to the analysis of the study data was provided
by two Boston Scientific employees (J.P. and M.J.R.) and by all participating physicians
at 11 Investigator Meetings between 2014 and 2017.
Consecutive patients with a definite or possible indication for POCS during an ERCP
procedure were enrolled. Patients were stratified by their indication for POCS: biliary
stone disease or indeterminate biliary strictures. The POCS evaluation of indeterminate
biliary strictures is presented in this report. The inclusion criteria were patients
who were: 18 years of age or older, willing and able to provide written informed consent
to participate in the study, and willing and able to comply with the study procedures.
Patients requiring anticoagulation therapy that could not be safely stopped at least
7 days prior to the procedure were excluded. In four patients, stones were found during
their procedure for indeterminate biliary stricture. Data for these four patients
were included in both the current study and a previous SpyGlass AMEA registry study
of cholangioscopy-guided lithotripsy for difficult bile duct stone clearance [7].
Data were collected through a web-based system that was password protected with an
electronic trail of any data entry or change. Baseline data collected included: patient
demographics (age, sex); history of chronic pancreatitis, liver cirrhosis, cholecystectomy,
living-donor liver transplantation, previous ERCP; as well as the indication for cholangioscopy
(indeterminate strictures or undefined filling defects). Any episode of cholangitis
or acute pancreatitis occurring within the 4 weeks preceding cholangioscopy was also
recorded. Data related to the cholangioscopy included: the procedure setting (outpatient
vs. inpatient); administration of prophylactic antibiotics; and the need for a sphincterotomy
or extension of an existing sphincterotomy to be performed to facilitate either the
insertion of the SpyGlass catheter or any other intervention. Recorded findings on
cholangioscopy included: the location of the dominant lesion/stricture; the quality
of the SpyGlass image; whether the target lesion/stricture could be adequately visualized;
a description of the lesion/stricture; whether a visual impression of malignancy could
be made; and the number and adequacy of the biopsies if obtained. The severity of
adverse events and their outcomes were also recorded.
All centers obtained approval from their respective local ethics committees and all
patients provided signed informed consent before the procedure. The study sponsor
had read-only rights to the data and could not make any data entries or data changes.
Safety oversight consisted of all serious adverse events being regularly tallied and
their incidence being compared with values in the literature.
The procedure was deemed unsuccessful when the stricture/lesion was not visualized,
a visual impression was not provided, or the SpyBite biopsy was not adequate for assessment.
Cholangioscopy procedure and sample processing
Two systems were used in the study cohort: the SpyGlass Legacy system and the more
recent SpyGlass DS digital system (Boston Scientific Corporation). POCS-guided biopsies
were taken using a dedicated biopsy forceps, the SpyBite forceps (Boston Scientific
Corporation), which is designed to pass through the channel of the POCS catheter.
The administration of prophylactic antibiotics was determined by local standards of
practice within each institution and/or at the discretion of the endoscopist. In patients
where a previous sphincterotomy had not been performed or had been performed but was
inadequate to facilitate biliary cannulation with the SpyGlass system, a sphincterotomy
was either performed or extended, respectively. The processing and reporting of biopsies
obtained during the POCS were according to each center’s standards.
Outcome measures
The primary end point for this study was procedural success, which for the indeterminate
strictures or undefined filling defects was defined as: (i) the ability to visualize
the stricture or defect (with image quality rated “excellent,” “good,” “fair,” “poor,”
or “unable to visualize”); (ii) the ability to provide a visual impression of malignancy;
and (iii) when applicable, the ability to obtain SpyBite biopsies that were adequate
for histology.
Secondary end points included: (i) evaluation of serious adverse events related to
the POCS procedure up to 72 hours post-procedure; (ii) impact of the SpyGlass procedure
on the suspected diagnosis compared to a prior ERCP; (iii) evaluation of the impact
of antibiotic use on the incidence of serious adverse events related to the device
and/or procedure; (iv) for patients undergoing SpyBite biopsies, correlation between
the number of biopsies and a conclusive histopathology diagnosis being obtained.
The direct visualization image features that were reported during the POCS included:
the absence of any features; the presence of a growth, stricture, hyperplasia, ulceration,
a mass, dilated tortuous vessels, papillary or villous projections, intraductal nodules;
or the presence of mucus.
Statistical analysis
Summary statistics were used to analyze the results of this study. Specifically, categorical
measures were analyzed using rates, and comparisons (e. g. image quality in two Spyglass
systems) were performed using a Fisher’s exact test. Confidence intervals (CI) were
calculated using Clopper – Pearson exact methods. Continuous measures were analyzed
using either mean and standard deviation (SD) or median and range, and comparisons
were tested using a t test or Wilcoxon’s rank sum test. Count variables (e. g. number of SpyBite biopsies)
were analyzed using mean (SD) and were tested using a negative binomial model.
Univariate and multivariate analyses were performed to identify predictive factors
for the primary end point of procedural success in the evaluation of indeterminate
biliary strictures using POCS. The baseline variables included in the analysis were:
age, sex, previous ERCP, previous cholangitis, acute pancreatitis in the last 4 weeks,
prior cholecystectomy, chronic pancreatitis, liver cirrhosis, location, and whether
the target lesion was located in the common bile duct. These were performed using
logistic regression with a Firth penalized likelihood method. Multivariate model building
was performed using stepwise model building procedures, with entry and exit significance
level set a P < 0.1.
Ad hoc analyses were performed to evaluate the associations between the accuracy of
the visual impression of the endoscopist, as well as the histological diagnosis reached,
when compared to the final 6-month diagnosis reached. These were performed using the
same univariate and multivariate methods as described above, along with the same baseline
variables.
All P values were two-sided, and all results were considered significant if the P value was < 0.05. All analyses were performed in SAS version 9.4. The Sankey diagram
was generated using R Studio [8] using the R statistical language [9] for data visualization [10].
Results
Patient and procedure characteristics
Between September 2014 and April 2016, 289 patients with indeterminate biliary strictures
were evaluated with 290 procedures. The procedures were performed by the Legacy system
in 173 patients (58.9 %), and by the newer DS digital system in 116 patients (40.1 %).
Baseline characteristics of the patients included in the analysis are provided in
[Table 1].
Table 1
Baseline characteristics of the 289 enrolled patients.
|
Characteristic
|
|
|
Age, mean (SD), years
|
61.5 (13.8)
|
|
Male, n (%)
|
177 (61.2 %)
|
|
Medical and surgical history, n (%)
|
|
|
68 (23.5 %)
|
|
|
4 (1.4 %)
|
|
|
3 (1.0 %)
|
|
|
9 (3.1 %)
|
|
|
30 (10.4 %)
|
|
|
1 (0.3 %)
|
|
|
174 (60.2 %)
|
* This case was a living-donor liver transplantation.
Cholangitis was reported in the 4 weeks preceding the POCS procedure in 23.5 % of
patients and 1.4 % had an episode of acute pancreatitis. Liver cirrhosis was present
in 3.1 % of the study cohort, and 1 % had a history of chronic pancreatitis. There
was one patient who had undergone living-donor liver transplantation, and 10.4 % of
the cohort had undergone a prior cholecystectomy. A sphincterotomy was performed in
almost all patients, either at the time of the prior ERCP (which in some cases required
extension) or at the time of the POCS. The majority of the lesions found were in the
common bile duct (47.6 %), common hepatic duct (16.2 %), or hilar region (16.9 %),
which represented 80.7 % of all the lesions evaluated ([Table 2]).
Table 2
Lesion location, image quality, and biopsy procedural information.
|
Legacy
(n = 173 procedures)
|
DS
(n = 117 procedures)
|
Overall
(n = 290 procedures)
|
P value
|
|
Location of lesion, n (%)
|
0.72
|
|
|
84 (48.6 %)
|
54 (46.2 %)
|
138 (47.6 %)
|
|
|
31 (17.9 %)
|
18 (15.4 %)
|
49 (16.9 %)
|
|
|
27 (15.6 %)
|
20 (17.1 %)
|
47 (16.2 %)
|
|
|
11 (6.4 %)
|
8 (6.8 %)
|
19 (6.6 %)
|
|
|
5 (2.9 %)
|
8 (6.8 %)
|
13 (4.5 %)
|
|
|
7 (4.0 %)
|
2 (1.7 %)
|
9 (3.1 %)
|
|
|
4 (2.3 %)
|
4 (3.4 %)
|
8 (2.8 %)
|
|
|
1 (0.6 %)
|
0 (0.0 %)
|
1 (0.3 %)
|
|
|
1 (0.6 %)
|
0 (0.0 %)
|
1 (0.3 %)
|
|
|
2 (1.2 %)
|
3 (2.6 %)
|
5 (1.7 %)
|
|
Quality of SpyGlass image, n (%)
|
< 0.001
|
|
|
56 (32.4 %)
|
85 (72.6 %)
|
141 (48.6 %)
|
|
|
76 (43.9 %)
|
27 (23.1 %)
|
103 (35.5 %)
|
|
|
37 (21.4 %)
|
4 (3.4 %)
|
41 (14.1 %)
|
|
|
3 (1.7 %)
|
0 (0.0 %)
|
3 (1.0 %)
|
|
|
1 (0.6 %)
|
1 (0.9 %)
|
2 (0.7 %)
|
|
Biopsy performed, n (%)
|
121 (69.9 %)
|
89 (76.1 %)
|
210 (72.4 %)
|
0.29
|
|
|
102 (59.0 %)
|
80 (68.4 %)
|
182 (62.8 %)
|
0.11
|
|
|
1.1 (0.5)
|
1.0 (0.2)
|
1.1 (0.4)
|
0.55
|
|
|
2.6 (1.4)
|
3.7 (2.0)
|
3.1 (1.8)
|
< 0.001
|
|
|
95 (93.1 %)
|
74 (92.5 %)
|
169 (92.9 %)
|
0.99
|
SD, standard deviation.
Quality of SpyGlass image and diagnostic accuracy of POCS visualization
The image quality was described as excellent in 141/290 of the procedures (48.6 %),
good in 103 /290 (35.5 %), fair in 41 /290 (14.1 %), and poor in 3/290 (1 %) ([Table 2]). There were two procedures where the endoscopist was unable to visualize the bile
duct adequately. The image quality of the DS system was described as excellent more
frequently than that for the Legacy system (72.6 % vs. 32.4 %, respectively; P < 0.001).
The visual impression as to whether the stricture was malignant or benign ([Fig. 1]) had a sensitivity of 86.7 %, specificity of 71.2 %, a positive predictive value
(PPV) of 65.8 %, and a negative predictive value (NPV) of 89.4 % with an overall accuracy
of 77.2 % ([Table 3]). A total of 39 % of the patients were diagnosed to have malignancy by 6 months
of follow-up.
Fig. 1 Indeterminate biliary strictures identified using peroral cholangioscopy (POCS) as:
a benign; b malignant.
Table 3
Diagnostic accuracy based on peroral cholangioscopy (POCS) visualization or histopathology
of malignancy compared to diagnosis at 6 months of follow-up.
|
Diagnosis based on POCS visualization (95 %CI)
(n = 290 procedures)
|
Diagnosis based on SpyBite histopathology (95 %CI)
(n = 163 procedures)
|
|
Sensitivity
|
86.7 % (79.1 % – 92.4 %)
|
75.3 % (65.0 % – 83.8 %)
|
|
Specificity
|
71.2 % (63.9 % – 77.7 %)
|
100 % (95.1 % – 100 %)
|
|
Positive predictive value
|
65.8 % (57.6 % – 73.3 %)
|
100 % (94.6 % – 100 %)
|
|
Negative predictive value
|
89.4 % (83.1 % – 93.9 %)
|
77.1 % (67.4 % – 85.0 %)
|
|
Overall accuracy
|
77.2 % (72.0 % – 81.9 %)
|
86.5 % (80.3 % – 91.3 %)
|
CI, confidence interval.
There was no difference in the diagnostic accuracy between the Legacy and DS systems
when comparing the final diagnosis to the visual impression obtained during the procedure.
Image quality and diagnostic accuracy of the visual impression did not vary significantly
by location.
Histological sampling
Biopsies were obtained in 210 /290 of the procedures (72.4 %) with 182/290 (62.8 %)
performed using the dedicated biopsy forceps (SpyBite) ([Table 2]). On average, a single biopsy forceps was used per procedure (mean [SD], 1.1 [0.4]).
There was a higher mean number of biopsies obtained in the DS cohort than with the
Legacy group (3.7 biopsies vs. 2.6 biopsies; P < 0.001) but there was no difference in the adequacy in the samples obtained (92.5 %
vs. 93.1 %; P = 0.99).
When compared to the final diagnosis after the 6-month follow-up period, the POCS-guided
biopsy histology had a sensitivity of 75.3 %, specificity of 100 %, PPV of 100 %,
NPV of 77.1 %, and an overall accuracy of 86.5 % ([Table 3]).
There was no difference in the diagnostic accuracy of biopsies obtained by the Legacy
system compared with the DS system. Additionally, there was no optimum number of biopsies
where a histological diagnosis of malignancy was more probable in patients with indeterminate
biliary strictures ([Fig. 2]) as demonstrated by an area under the receiver operating characteristic (ROC) curve
of 0.578 ([Fig. 3]). The diagnostic accuracy of biopsy histopathology did not vary significantly by
location.
Fig. 2 Predicted probability of making a diagnosis of malignancy as a function of the number
of biopsies based on linear regression that showed no association (P = 0.16).
Fig. 3 Receiver operating characteristic (ROC) curve to estimate the optimal number of biopsies
needed to make a diagnosis of malignancy in patients with indeterminate biliary strictures.
AUC, area under the curve.
Procedural success
The procedure was considered successful in visualizing the stricture/defect in 286/290
procedures (98.6 %) and in providing a visual impression as to whether the lesion
appeared malignant or benign in 253/290 procedures (87.2 %). For the procedures where
a biopsy was obtained, 169/182 (92.9 %) were deemed adequate for analysis. Therefore,
the overall procedural success was 241/290 (83.1 %; 95 %CI 78.3 % – 87.2 %).
Impact of the SpyGlass procedure on patient management
In this cohort, POCS influenced the management in 249/289 patients (86.2 %; 95 %CI
81.6 % – 89.9 %) by determining the cause of the biliary stricture (50.9 %) or the
cause of an unexplained filling defect or biliary dilatation (37.4 %), or by detecting
stones missed by other evaluation methods (1.7 %). The sequence of visual impression
and histological diagnosis and the final diagnosis for the patients evaluated in the
study is shown in [Fig. 4].
Fig. 4 A Sankey diagram depicting the patient flow throughout the duration of the study
using diagnostic evaluation with peroral cholangioscopy (POCS).
A biliary stent was inserted in 29.4 % of patients during the same ERCP procedure
as the cholangioscopy. Surgery was avoided in 22.2 % of patients, while 19.0 % were
referred to surgery and 5.19 % were referred for combined chemoradiotherapy.
Adverse events
Five serious adverse events related to the POCS procedure occurred in this cohort
(1.7 %; 95 %CI 0.5 % – 4.0 %)). Three patients in the cohort developed cholangitis
(1.0 %), all of whom had received prophylactic antibiotics. There was a single patient
with acute pancreatitis and a single patient with bleeding. There was no mortality
related to the POCS procedures in this cohort of patients.
Multivariate analyses
On univariate analysis, the only factor associated with a higher odds of success was
older age, with an odds ratio (OR) of 1.3 (95 %CI 1.1 – 1.6) for each 10-year increment
in age, which persisted on multivariate analysis (OR 1.4 [95 %CI 1.1 – 1.7]).
None of the baseline variables included in the ad hoc analysis were associated, either
on univariate or multivariate analysis, with the accuracy of the visual impression
made during POCS; these included age, sex, previous ERCP, use of the newer DS system,
previous cholangitis, acute pancreatitis in the last 4 weeks, prior cholecystectomy,
chronic pancreatitis, liver cirrhosis, location, whether the target lesion was located
in the common bile duct, and the number of biopsies obtained.
Discussion
Indeterminate biliary strictures pose a significant challenge to endoscopists and
their patients. The primary aim is to differentiate benign from malignant pathology
so as to guide appropriate therapy and avoid the morbidity, mortality, and healthcare
costs associated with unnecessary treatment, in particular surgical intervention.
Although the majority of indeterminate biliary strictures are neoplastic, approximately
30 % are benign. A quarter of surgical resections for suspected neoplastic lesions
ultimately confirm benign pathology [11]. Interestingly, in our cohort, the rate of malignant diagnosis was higher, which
might represent a more aggressive evaluation strategy with a lower threshold for performing
POCS at these referral centers.
Although ERCP is still considered the main diagnostic modality for tissue/cytology
acquisition from biliary lesions, without the use of cholangioscopy, the diagnosis
of biliary malignancy using brush cytology and intraductal biopsy suffers from limited
sensitivity being 45 % (95 %CI 40 % – 50 %) and 48.1 % (95 %CI 42.8 % – 53.4 %), respectively
[12]. Therefore, other diagnostic modalities are needed. The current study demonstrates
that POCS can be performed with a high success rate for visualizing indeterminate
strictures, in addition to facilitating a visual impression of benign versus malignant
etiology. Also, POCS was associated with an acceptable adverse event rate that was
no higher than standard ERCP.
To ensure clinical relevance, the diagnostic performance of POCS must provide an improvement
relative to the currently performed techniques. A Spanish study including 52 patients
with indeterminate biliary strictures demonstrated that POCS had a sensitivity, specificity,
and diagnostic accuracy of 88.5 %, 80 %, and 83 %, respectively [13], while a SpyGlass DS subanalysis (n = 19, including 13 indeterminate bile duct strictures)
found that the visual appearance had a sensitivity of 89 %, specificity of 100 %,
a PPV of 100 %, an NPV of 75 %, and an overall diagnostic accuracy of 91 %. In a meta-analysis
by Navaneethan et al. [14], the visual appearance on POCS had a pooled sensitivity of 83.3 % (95 %CI 77.7 % – 88 %)
and a specificity of 81.8 % (95 %CI 75.9 % – 86.7 %), while for the detection of cholangiocarcinoma
the pooled sensitivity was 68.4 % (95 %CI 61.7 % – 74.6 %), specificity 97.2 % (95 %CI
93.9 % – 99.0 %), and the pooled diagnostic OR was 63.8 (95 %CI 27.1 – 150.5). Our
cohort demonstrated numbers similar to this meta-analysis, with a sensitivity of 86.7 %
and a specificity of 71.2 %.
The definition of indeterminate biliary strictures in earlier studies included strictures
with no evidence of a mass lesion on cross-sectional imaging and negative brushings
and/or biopsies on evaluation [15]. Other studies have used ERCP findings of a bile duct stricture with nondiagnostic
intraductal biliary brushings and/or biopsies, and/or nondiagnostic endoscopic ultrasound
fine-needle aspiration cytology [16]. Some groups used imaging as a possible criterion in the presence of a strong suspicion
of malignancy [12]. These might be stricter definitions compared with that used in this cohort as negative
brushings were not a prerequisite and a number of patients had not had a prior ERCP.
Nonetheless, there is no unified definition and the patients included in our cohort
represent cases that would typically be encountered in clinical practice.
In a large, multicenter study from Japan, the visualization of the target lesion was
lower in those with intrahepatic (80 %) and distal lesions (86.7 %) compared with
hilar, proximal (both 100 %), and mid-bile duct lesions (94.1 %) [17]. In our cohort, the procedure was considered successful in visualizing the stricture/defect
in 286 /290 procedures (98.6 %). In the study by Pons Beltran et al. [13], adequate samples were obtained in only 73 % of cases. This is much lower than our
results (92.9 % of samples being adequate for histological analysis).
The most common complication reported with POCS is cholangitis, which occurs in 0 % – 14 %
of procedures [18] and is often mild and treated with oral antibiotics. Reports of severe or fatal
cholangitis are rare [19]. In our cohort, the cholangitis rate was only 1 %; importantly, prophylactic antibiotics
were administered to all three of these patients. Other centers have reported cholangitis
rates as high as 10.6 % despite the use of prophylactic antibiotics [20].
A major issue that limits the dissemination of a diagnostic test is the variability
in its performance and reproducibility. This is true for POCS, as a 2014 study found
the interobserver agreement between the initial findings and final diagnosis to be
slight (Fleiss’ kappa statistic 0.01 – 0.20) [21]. Also, the assessment of the diagnostic accuracy of visual assessment of the strictures
could not be isolated from the pretest probability that the endoscopist had based
on the clinical presentation and context of the test. Endoscopists reviewing POCS
recordings when blinded from the patients’ details would ideally mitigate this bias.
Although the generalizability of the results of this series could be challenged as
a consequence of being performed in high volume centers, the American Society of Gastrointestinal
Endoscopy (ASGE) considers POCS a level III procedure [22]; as such, it is reasonable that such a study be performed in tertiary care centers.
A limitation of this study was that the processing and reporting of the biopsies obtained
was not centralized, potentially resulting in interinstitutional variability. The
potential impact of this was reduced by using the 6-month clinical end point or definitive
histology provided by surgical resection. Another potential unmeasured confounder
was the method of sedation, which was determined by the treating endoscopist and institution.
In a study by Kalaitzakis et al. [23], patients receiving conscious sedation had successful procedures less frequently
when compared with those undergoing general anesthesia (75 % vs. 87 %, respectively;
P = 0.04).
We acknowledge strengths and limitations that affect the interpretation of results
from this study. This is one of the largest, if not the largest, cohorts reported
of patients evaluated by POCS. Its multinational, multi-unit, multi-endoscopist methodology
confers great generalizability relative to other studies. The prospective nature of
the registry also captures the impressions of the endoscopists and time stamps them
through an electronic system prior to the results of the biopsy and the final diagnosis
at 6 months. This helps avoid a number of biases that are associated with retrospective
studies. In addition, we applied the gold standard criterion of a 6-month follow-up
end point. This is the most common timeframe used in the literature, with some studies
specifying 6 months [16]
[17]
[24], while others have ranged from 12 to 18 months [23]
[25]
[26], or in between [15].
With regard to limitations, the baseline patient characteristics were collected by
patient self-report and may have been subject to recall bias. Data were not available
for some items that might have been of interest to clinicians, for example the number
of procedures performed with ultraslim scopes, the proportion of patients who had
previous stents or ERCP with standard transpapillary biopsies, or past imaging or
laboratory data that might have influenced their management. Also, the findings in
our cohort might not be generalizable to other patient populations, such as those
with primary sclerosing cholangitis, as demonstrated in a recent publication from
the Netherlands [27]
[28]. Additionally, five of the authors have received monetary or research support from
the study sponsor.
In conclusion, this large, real-life, prospective registry demonstrates that POCS
is an effective and safe intervention in guiding the management of patients with indeterminate
biliary strictures.
