Introduction
Endoscopic management for pain from chronic calcifying pancreatitis (CCP) can be achieved
by draining an obstructed pancreatic duct (PD) and/or removing obstructing PD calculi
[1]. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) as first-line
treatment of PD stones. However, its limitations include lack of availability and
the need for multiple ESLW and endoscopic retrograde cholangiopancreatography (ERCP)
sessions [2]. The role of pancreatoscopy in PD stone treatment is unclear, with reported success
rates between 43 % and 100 %, based on small retrospective studies [2]
[3]
[4]
[5]
[6]
[7]. In 2015, single-operator digital video cholangiopancreaticoscopy (SOVP) (SpyGlassDS,
Boston-Scientific) was introduced. There is limited data on the role of SOVP in the
treatment of PD stones in CP. Our aim was to investigate the role of digital SOVP-guided
PD stone lithotripsy in patients with CP with regard to safety, technical and short-term
clinical success.
Material and methods
Between 2015 and 2017, all SOVP-guided lithotripsies at two tertiary referral centers
were retrospectively identified and analyzed. Inclusion criteria for SOVP were imaging-proven
PD stones with upstream dilatation and pain attributable to CCP. Patients with prior
unsuccessful ERCP or ESWL were included, as well as patients with asymptomatic pseudocysts
and patients with prior pancreatic surgery. A consensus decision to proceed with SOVP
was made by an interdisciplinary pancreatic board at each center in shared decision
with the patient. All patients meeting the inclusion criteria were consecutively and
systematically included in this retrospective study.
Exclusion criteria included age less than 18, pregnancy, abdominal pain not attributable
to CCP or unsuitability to receive sedation. All patients had endoscopic ultrasound
and abdominal computed tomography and/or magnetic resonance cholangiopancreatography
prior to SOVP ([Fig. 1]). Other treatment options (surgery, ESWL or ERCP) had already been attempted, were
deemed less suitable than SOVP or were refused by the patient.
Fig. 1 a Radiopaque stone in the main pancreatic duct (MPD), b wire-guided cannulation of MPD with SpyGlassDS catheter (Boston Scientific, Natick,
Mass, US) after pancreatic sphincterotomy, c direct visualization of the impacted stone in the pancreatic head and Electrohydraulic
lithotripsy of the large stone.
Conventional ERCP techniques such as balloon extraction, mechanical lithotripsy, and
balloon dilation of downstream strictures were already used to facilitate stone removal
and stricture dilation prior to attempting SOVP in the same session. Pancreatic sphincterotomy
preceded SOVP in all cases (either during previous or same intervention); and further
treatment of a downstream stricture (between papilla and stone) was performed at the
endoscopist’s discretion using a 4-mm dilatation balloon (Hurricane RX, Boston Scientific,
Nattick, Massachusetts, United States). SOVP was performed using 10.5 F SpyglassDS,
which was advanced over a .035-inch guidewire (Jagwire, Boston-Scientific) or freehand.
Lithotripsy was performed using a Holmium:YAG-laser (AurigaXL, StarMedTech) with a
270-μm optical fiber (8 Hz, 2400 mJ) or electrohydraulic lithotripsy (EHL) utilizing
either a Lithotron EL27 generator with a 2.4 F probe (Walz Elektronik, Rohrdorf, Germany)
or an Autolith tough biliary EHL system with 1.9 F probe (Northgate Technologies/Boston
Scientific, Nattick, Massachusetts, United States) with high power and maximum pulses
(30) at the endoscopist’s discretion. Intermittent PD irrigation with saline facilitated
target stone visualization and lithotripsy ([Fig. 1]).
After lithotripsy, fragments were extracted using balloons or baskets followed by
pancreatic plastic stent placement (5 – 10 Fr.) for prophylaxis against post-ERCP
pancreatitis (PEP) and/or PD decompression. The type/length of the PD stent was based
on the diameter, length and position of the stricture. Prophylactic rectal nonsteroidal
anti-inflammatory drugs were administered to all patients and no prophylactic antibiotics
were administered. All patients were routinely admitted post-SOVP for 48 hours.
The endpoints of the study were technical success, clinical success and adverse event
(AE) rates. Overall technical success was defined by achievement of two subitems:
SOVP success and PD clearance success. SOVP success was defined as the ability to
reach the target stone with SpyGlassDS. PD clearance success was defined as PD decompression
by complete PD stone clearance or significant duct clearance making stent placement
possible.
Clinical success was defined as a > 50 % post-interventional reduction on a numeric
rating scale (NRS) for pain. The NRS is a segmented numeric version of the visual
analog scale (VAS) in which a whole number (0 – 10) that best reflects the intensity
of their pain is chosen [8].
A systematic medical record review comprising clinical evaluation and biochemistry
was used to determine the occurrence of AEs [4]. AE rates and severity of AEs were reported according to the American Society for
Gastrointestinal Endoscopy guidelines, therefore PEP was classified by the Cotton
criteria [9].
Patients were rescheduled 3 to 6 months after SOVP for stent extraction and were also
interviewed for clinical success and quality of life using a standardized questionnaire
([Table 1]). Statistical significance was tested with two-tailed t-test or fisher’s exact test. A P < 0.05 was considered statistically significant. GraphPad prism 5, MS Excel and medcalc.org
were used as statistical tools. The study had medical ethics committee approval and
written consent was obtained from all participating patients.
Table 1
Systematic questionnaire for follow-up (in parts adjusted from UK SF-12 Score – Jenkinson et al. Journal of Puplic health medicine 1997).
|
1) How would you describe your health status in general?
|
1 excellent
2 very good
3 good
4 fair
5 poor
|
|
2) How much did pain affect you in in your daily life and work?
|
1 not at all
2 a little bit
3 moderately
4 very much
|
|
3) In a numerical range of 1 – 10 of which 10 is the worst imaginable pain: How would
you describe your pain level at the moment?
|
1 – 10
|
|
4) The interventional procedure has reduced my symptoms
|
Yes/No
|
|
5) Since the intervention my daily use of painkillers is reduced noticeable
|
Yes/No
|
Results
A total of 23 interventions in 20 patients ([Table 2]) were performed. Prior unsuccessful interventional procedures on pancreatic calculi
or strictures had been performed in 95 % of the cases ([Table 2]).
Table 2
Patient data and characteristics of stone and main pancreatic duct.
|
Study details
|
|
Patients
|
n = 20 (9 female/11 male)
|
|
Age
|
Mean ± SD = 62.4 ± 14.8
|
|
Time frame
|
November 2015 to October 2017
|
|
Follow-up
|
3 – 6 months after intervention
|
|
Prior Therapies
|
prior interventional therapies 19/20
|
|
endoscopic 17/20
|
|
ESWL 6/20 (2 – 4 sessions of ESWL in each case)
|
|
prior surgery 2/20 (resection of the pancreatic tail in both cases)
|
|
MPD Dilatation > 5 mm post concrement
|
20 /20
|
|
Number of stones
|
m = 1.9 (SD ±1.2)
|
|
Average size of stones
|
9.3 mm (SD ±2.5 mm; 5 – 15 mm, 1 – > 3 stones)
|
|
Location of stones
|
caput (n = 8), genu (n = 10), corpus/tail (n = 4)
|
|
MPD stenosis proximal of the calculi
|
8/20
|
EWSL, extracorporeal shock wave lithotripsy; MPD, main pancreatic duct;
Eight of 20 patients had a PD stenosis downstream to the stone(s) and all patients
had an upstream PD dilation > 5 mm.
SOVP success rate was achieved in 100 % of cases and PD clearance success was achieved
in 19 of 20 patients (95 %). Overall technical success rate was 95 %. The Holmium
laser was used in 21 interventions and EHL in 2. All EHL lithotripsies were successful.
Stone fragments could be completely removed with endoscopic and fluoroscopic visualization
in 13 cases (68 %), whereas in six cases (32 %) the stone could be sufficiently reduced
in size to allow for PD decompression and stent placement, which had not been possible
before. In 19 of 20 patients a plastic stent (5FR-10FR) was placed due to a persistent
stricture or for PEP prophylaxis. In two cases, remaining calculi could not be detected
3 months after POP-guided lithotripsy, when patients underwent a subsequent ERCP for
stent extraction. In another two cases calculi could be extracted in a subsequent
intervention with standard ERCP methods. Prophylactic placed stents (5FR) could be
removed at next ERCP. All eight patients with strictures still needed stenting at
6-month follow-up. Three patients needed a stent at 3-month follow-up due to persistent
dilatation, but these stents could be extracted at 6-month follow-up. All other patients
(9 of 12; 75 %) had no stents after 3-month follow-up.
Stone location, number of stones and presence of downstream PD stenosis did not significantly
influence success rates ([Table 2]). AEs occurred in seven of 23 procedures (30 %). In one case, contrast extravasation
from the PD was fluoroscopically identified and could be treated by temporary plastic
stenting in the same session. This was rated as a serious AE. The patient also developed
a moderate PEP. PEP occurred in five other procedures (total PEP rate 26 %) of which
four were classified as mild and two as moderate (Cotton criteria). PEP occurred significantly
more frequently in patients with prior PEP (n = 4, P < 0.01). Post-sphincterotomy bleeding occurred in one patient and was self-limiting.
Patients reported an improvement of pain 24 to 48 hours after treatment. At 3- to
6-months follow-up, 95 % of patients reported improvement in symptoms and reduction
in intake of analgesics. One patient was lost to follow-up. Mean NRS decreased from
5.4 [± 1.6] to 2.8 [± 1.8] (P < 0.01). Clinical success was achieved in 95 % of patients. Concerning post-interventional
quality of life, 89 % reported no or only mild disability in daily activities and
47 % described their general health status as “excellent” or “very good” afterwards.
Discussion
We report a high technical success rate and clinical success rate of 95 %, respectively
and an acceptable AE rate of 30 %, despite the fact that we included a challenging
patient population with prior unsuccessful therapies and large PD stones. Forty percent
of patients had strictures that could be successfully treated endoscopically in the
same session, suggesting that strictures are not an impediment to technical success.
ESWL as a standard of care has a reported success rate of 59 % to 80 % after an average
of three sessions and an AE rate of 5.8 % to 6.7 % [10]
[11]
[12]
[13]. Our data suggest a potentially higher success rate of 95 %, but with a higher AE
rate of 30 % and occurrence of PEP of 26 %. Due to the small cohort, no definite answer
can be provided as to whether laser lithotripsy or EHL is more effective. However,
it is in line with reported PEP rates in average high-risk ERCP patients of 20.2 %
to 40 % [14]
[15] and in SOVP patients with PEP up to 28 % [2]
[4]
[6]. Risk factors include patient-, physician- or procedure-related and are additive
[14]. Many of those factors were consistently present in our patients (e. g. prior PEP,
difficult cannulation, pancreatic sphincterotomy, pancreatic duct injection). Even
in our small patient cohort, a prior episode of PEP was identified as a risk factor
for PEP following SOVP (P = 0.01 in Fisher’s exact test, OR 25.0, 95 %-CI: 1.11 to 562.8, P = 0.043). Therefore, careful patient selection and an intensified PEP prophylaxis
scheme, with rectal NSAIDS and possibly PD stenting, is warranted in case of SOVP.
To our knowledge, this is the largest cohort of patients that have been evaluated,
focusing on PD stones only with digital SOVP (SpyGlassDS). Strengths of our study
include a high technical and clinical success rate, structured follow-up and a technically
difficult patient population that already had failed previous treatments. Limitations
of our study include its retrospective, uncontrolled design, lack of an intention-to-treat
analysis, short-term follow-up and modest number of patients. Therefore, our results
need to be interpreted cautiously given that this was a retrospective pilot study
designed primarily to assess feasibility and safety of SOVP to treat PD stones in
obstructing CCP, and to generate information for design of future trials. Looking
at the relatively high technical and clinical success rates, we cannot rule out the
possibility that the significant benefit of SOVP reflects an overestimation of the
effect size, due to the small sample size.
Initial endoscopic therapy (including ESWL) is likely to be inferior to surgery for
treatment of obstructing CCP, though a definite answer will be given by the results
of the ESCAPE trial. Therefore, use of SOVP in patients with obstructive CCP due to
PD stones is limited to a small group of patients, i. e. poor surgical candidates
and/or patients who refuse surgery. Direct cost and resource comparisons are not possible
due to the retrospective design and relatively small sample size and require assessment
through prospectively designed trials. The clinical outcome regarding quality of life
and pain suggests a significant improvement in the vast majority. It remains to be
seen if these results from our small cohort can match the long-term pain relief after
ESWL in 60 % to 90 % of the cases [10].
Conclusion
In conclusion, SOVP-guided lithotripsy was shown to be safe and effective also in
patients with prior unsuccessful interventional therapy. Complete or partial stone
removal had a significant beneficial effect on pain reduction and quality of life.
Prospective studies are required to validate our findings and to help establish the
role of SOVP in treatment of symptomatic PD stones in CCP. At this stage, this treatment
cannot be recommended as a first-line approach for fragmentation of stones in CCP,
due to its technical difficulty and the availability of less invasive alternatives,
such as ESWL.
