Research Article
Extracorporeal Shock Wave Lithotripsy in Combination with Endoscopic Retrograde Cholangiopancreatography for Treatment of Initial Endotherapy-Failed Pancreatic Ductal Stones: A Retrospective Clinical Study
Zhang J-T1, Lu X-S1, Gui Y-P2 and Fan Y-Z11
1Department of General Surgery, Tongji University School of Medicine, China
2Department of Urology, Tongji University School of Medicine, China
*Corresponding author: Yue-Zu Fan, Department of General Surgery, Tongji University School of Medicine, Tongji University, Shanghai, 200065, China
Published: 15 Sep, 2016
Cite this article as: Zhang J-T, Lu X-S, Gui Y-P, Fan Y-Z.
Extracorporeal Shock Wave Lithotripsy
in Combination with Endoscopic
Retrograde Cholangiopancreatography
for Treatment of Initial Endotherapy-
Failed Pancreatic Ductal Stones: A
Retrospective Clinical Study. Clin Surg.
2016; 1: 1120.
Abstract
Objectives: To evaluate the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) in
combination with Endoscopic Retrograde Cholangiopancreatography (ERCP) for treatment of
initial Endotherapy failed Pancreatic Ductal Stones (PDSs).
Methods: The clinical data of patients with initial Endotherapy failed PDSs treated by ESWL in combination with ERCP in our hospital were analyzed retrospectively. Radiographic assessments
are performed for these patients before treatment. These patients underwent ESWL for stone
fragmentation and post-ESWL therapeutic ERCP for endoscopic clearance of stone fragments.
Patients’ outcomes including successful stones clearance, pain relief, complications, mortality and
stone recurrence were followed-up and observed, respectively.
Results: A total of 12 patients with initial Endotherapy failed PDSs received our treatment. Abdominal pain, episodes of pancreatitis, associated diabetes mellitus, concomitant alcohol abuse,
malnutrition and idiopathic were observed in 100%, 83.3%, 83.3%, 66.7%, 16.7% and 8.3% of
patients, respectively. The causes of the initial Endotherapy failure included: multiple, radiopaque
stones with a mean size of >6.33±2.06 mm; concomitant pancreatic duct stricture with upstream
main pancreatic duct dilation; and endoscopic pancreatic sphinterotomy inadequacy; in particular,
no combination with ESWL. By following-up of a median period of 21 (range 4~60) months, a high
rate of effective clearance of PDSs (75.0% complete clearance, 16.7% partial clearance) and a high
rate of pain relief (75.0% complete pain relief and 16.7% partial pain relief) were achieved in 91.6%
of patients, respectively. No procedure-related major complication and mortality occurred.
Conclusion: ESWL in combination with ERCP is an effective and safe treatment procedure for initial Endotherapy failed PDSs.
Keywords: Robot-assisted laparoscopy; Gynecologic; Oncology
Introduction
Pancreatic ductal stone (PDS) i.e. pancreatolithiasis is a main complication of chronic
pancreatitis (CP). PDSs develop during the natural course of longstanding CP and are observed
in 50% ~ 90% of patients during long-term follow-up [1-3]. These PDSs contribute to ductal
hypertension by impeding pancreatic juice outflow and obstructing pancreatic duct, ischemia
from increased parenchymal pressure and destruction of the pancreatic parenchyma and ductal
structures, and thus leading to continual abdominal pain [1-5]. Therefore, the main aim of calcific
CP treatment is to decompress the main pancreatic duct (MPD) by pancreatic stone removal and
pancreatic duct dilation in order to alleviate pain and improve outcome of the patients with PDSs
[1,4-7].
Surgical removal, endoscopic therapy (Endotherapy) and extracorporeal shock wave lithotripsy
(ESWL) are options for treatment of PDSs in the multidisciplinary plans [1-7]. A variety of
treatment modalities have been described in clinical research of PDSs, although lingering
controversies have hindered a consensus recommendation. The most common surgical treatment for painful obstructing main PDSs is a lateral pancreaticojejunostomy
(Puestow procedure) and its modified procedure [8,9]. This operation
is best suited for patients with stones in a dilated MPD (preferred
≥8 mm), which permits mucosa to mucosa anastomosis. Over the
last 30 years, endoscopic procedures are developed to manage main
PDSs and pancreatic duct strictures in CP patients. Endotherapy
for PDSs is at present considered because of its minimally invasive
and its aim to decompress the MPD by performing complete stone
clearance and ductal drainage, thus relieving the obstruction and
pain [6]. ESWL has lately been used in treatment of PDSs [1,4,6,10- 14]. A significant advancement in PDS removal has been achieved by
using ESWL for fragmentation with the aid of endoscopic retrograde
cholangiopancreatography (ERCP) techniques [12-14]. But, ESWL in
combination with ERCP for treatment of initial Endotherapy failed
PDSs has rarely been reported.
In this study, we retrospectively analyzed the clinical data of
12 patients with initial Endotherapy failed PDSs received ESWL in
combination with ERCP in our hospital to evaluate the efficacy, safety
and outcome of ESWL in combination with ERCP for treatment of
Endotherapy failed PDSs.
Materials and Methods
Patients
This was a retrospectively clinical study for patients with PDSs
from January 2008 to December 2012 in our hospital. All patients
were transferred from other hospital, in which initial Endotherapy
for PDSs was unsuccessful and in them pancreatic duct stent was
still placed; in order to treat symptomatic Endotherapy failed PDSs
in our treatment center. These patients provided informed consent
for treatment and review of their records; the study was carried out
according to the official recommendations of Chinese Community
Guidelines and was approved by the Ethics Committee and the
Institutional Review Board at the Tongji Hospital.
These initial Endotherapy-failed patients underwent radiographic
assessments before ESWL in combination with ERCP for treatment
of their PDSs. Radiographic assessments included plain radiography,
abdominal enhanced computed tomography (CT) scan, magnetic
resonance imaging (MRI) and/or diagnostic ERCP to confirm the
diagnosis of chronic calculi pancreatitis, to determine the location,
number, size of stones, the morphology of the pancreatic duct and its
anomalies such as strictures or dilatation, and to find out the causes
of the failure of initial Endotherapy for PDSs.
Treatments
ESWL: In this study, all of symptomatic patients with PDSs are
firstly considered for ESWL, especially those who have stones that
are >5 mm in size. The objective of ESWL is to fragment the stones
successfully until they are < 3 mm in size, or to completely pulverize
the stones until they are almost a granular powder form, so that they
can be removed by subsequent ERCP via a successful stone clearance.
ESWL were performed with an electromagnetic lithotripter
(Shenhang Co, Shanghai, China) with fluoroscopic focusing system,
power setting at 9~10EKV, and 1000~1500 shock waves were
delivered in one ESWL session. The shockwave energy settings
were adapted to the individual patient’s tolerance and comfort. If
the patients can’t tolerate the treatment, the power and the number
of shock waves would be adjusted or treatment paused. Successful
fragmentation was determined based on the change of density and
volume of stones. Repeat ESWL sessions are carried out on successive
days until the stone fragments are < 3 mm in diameter, or almost a
granular powder form.
ERCP: After successful fragmentation by ESWL, therapeutic
ERCP for endoscopic clearance of stone fragments is performed in
all patients by endoscopic pancreatic sphinterotomy(EPS), balloon
dilation, stone extraction and pancreatic duct stent, depending on the
conditions of the patients and the causes of the initial Endotherapy
failure such as more, larger or compacted stones, EPS inadequacy and
dominant pancreatic stricture.
This therapeutic ERCP is performed with duodenoscope (JF-
240 or TJF-240, Olympus Optical Co, Tokyo, Japan), which begins
with cannulation of the pancreatic orifice and contrast instillation
to delineate the ductal anatomy and assess the pancreatic ductal
morphology (stricture or dilation) and the number, size and location
of the stone fragments. Subsequently, a standard EPS was performed
with a pull-type sphincterotome (Clevercut, Olympus Optical Co)
passed over a guide wire or with a needle-knife incision over a
guiding pancreatic stent via irrigation of the pancreatic duct with
saline solution. In patients with pancreas divisum, ductal access via
the minor papilla is followed by minor papilla sphinterotomy (MPS).
Extraction balloon or basket trawling is performed for removing of
residual fragmented stones of the pancreatic duct. When pancreatic
duct strictures are present, stricture dilation may be required to
facilitate stone removal by using radial expansion balloon (10~12 mm),
dilator catheters or stent placement. A plastic stent (5~7Fr) is inserted
in patients with pancreatic duct strictures after stone extraction, or
when residual stones cannot be removed completely to guarantee
an unobstructed flow of pancreatic juice. Pancreatic duct stricture
is often densely fibrotic and is a main factor of stone recurrence,
balloon dilation alone generally do not result in satisfactory longterm
resolution, thus pancreatic duct stents are placed through the
strictures even in patients with complete stone clearance for about
three months to prevent the recurrence of stricture and stone.
Follow-up and outcome measures
Follow-up data were recorded from the patient's medical records
and completed by a telephone survey, routine visit record and
address. Clinical outcome was followed from the date of treatment or
until the end of December 30, 2012.
The primary outcome measures were performed and defined as
follows [11]: 1. Complete clearance: fragmentation of PDS to < 3 mm
in size with clearance of 90%~100% of stone fragments; 2. partial
clearance: clearance of 50%~90% of stone fragments; 4. unsuccessful
or fail clearance: presence of PDS >3 mm in size or clearance of < 50%
of stone. The secondary outcome measures included pain relief at the
end of follow-up, complications and mortality, and stone recurrence.
Pain relief at the end of follow-up was classified as complete (Izbicki
pain score, ≤ 10) or partial (Izbicki pain score, >10 after a decrease
of >50%) [15]. Complications of ESWL in combination with ERCP
included ESWL complications and ERCP complications. The
complications from ESWL such as skin or duodenal contusions,
pancreatitis, asymptomatic hyperamylasemia, right renal subcapsular
hematoma, and collateral spleen damage [6 and 16] and the complications
from ERCP such as acute pancreatitis, bleeding, perforations, and
soon on [17] were observed. Treatment was considered to have
failed in patients whose treatment was converted from ESWL in
combination with ERCP to surgery. Stone recurrence of patients is
observed by radiographic assessments such as CT scan and/or MRI.
Table 1
Table 1
Demographics and clinical manifestation and causes of initial Endotherapy failure of 12 patients with PDS.
Table 2
Results
Patient cohort
A total of 12 patients with initial Endotherapy-failed PDSs were
treated in our hospital. These patients consisted of 9 men (75%) and
3 women (25%) with a mean age of 48.17 ± 17.78 years (mean ± SD,
range 12~67 years). The mean duration of PDS was 5.6 ± 3.2 years
(mean ± SD, range 1.4 years~32 years) with 83.3% (10/12) of patients
reporting prior episodes of pancreatitis. Of these, all patients had
upper abdominal pain radiating to the back; 83.3% (10/12) of patients
had associated diabetes mellitus; two-thirds (66.7%) of patients (only
male) had concomitant alcohol abuse; malnutrition and idiopathic
were noted in 16.7% and 8.3% of patients, respectively (Table 1).
Imaging findings
Imaging findings according to plain radiography, CT scan, MRI
and/or diagnostic ERCP in this study were presented in Table 1.
Overall, frequent findings included PDSs, concomitant pancreatic
duct stricture with upstream main pancreatic duct dilation, and
EPS inadequacy, which were present 66.7%, 100%, and 75.0% of
patients, respectively. Of these PDSs, multiple stones were present
in 83.3% of patients, of whom 100% had stones in the pancreatic
head, while in patients with stones in the head, 50% had associated
stones in the body and/or tail, 8.3% of stones scattered throughout
both main and accessory pancreatic duct. And for all patients, 100%
of stones were radio-opaque with hardness and irregular natures
underlying duct stricture, and a mean size of >6.33 ± 2.06 mm (mean
± SD, range>5~10 mm). Characteristics of these imaging findings, in
particular, no combination with effective lithotripsy modalities such
as ESWL could be the main causes of the failure of initial Endotherapy
for patients with PDSs.
Treatments and outcomes
Overall, all the patients received ESWL in combination with
ERCP for PDSs. A total of 19 ESWL sessions with a mean session
of 1.58 ± 0.79 (mean ± SD, range 1~3 sessions) were performed for
adequate fragmentation: 58.3% of patients required a single session,
25.0% required two sessions and 16.7% required three sessions.
Post-ESWL therapeutic ERCP procedures included EPS, extraction
balloon, basket trawling, and plastic stent which were present 66.7%,
75.0%, 100%, and 100% of patients, respectively; of them, 8.3% of
patients received EPS and MPS simultaneously.
All the patients were followed up, with median follow-up period
of 21 (range, 4~60) months. The primary and secondary outcomes are
summarized in Table 2. Complete clearance of PDSs was achieved in
75.0% of patients; partial clearance was achieved in 16.7% patients,
thus a high rate of effective clearance of PDSs or MPD decompression
was achieved in 91.6% patients. It was showed as Figure 1~2, the
pulverized stones with less dense and spread along the duct were
observed in ESWL procedure on fluoroscopy (Figure 1); the patient
underwent post-ESWL therapeutic ERCP including balloon dilation
and stone extraction in whose loosened or fragmented stones
were observed in MPD and were extracted easily (Figure 2). But,
unsuccessful or fail clearance was observed in 8.3% patients due
to extensive stones in the head, body and tail of the pancreas with
multiple stricture of the pancreatic duct.
A high rate of effective pain relief was achieved in 91.6% of
patients (75.0% complete reliefs of pain and 16.7% partial reliefs
of pain, respectively); only 8.36% (1/12) of patients with pain
relief was failed owing to extensive stones and multiple strictures,
subsequently received surgery. Per-procedural ESWL and ERCP
related complications occurred in 8.36% (1/12) and 16.7 (2/12) of
patients, respectively. These complications included mile pancreatitis
and asymptomatic hyperamylasemia, which could be cured by
observation or conservative medical treatment. Other complications
such as skin or duodenal contusions, right renal subcapsular
hematoma, and collateral spleen damage from ESWL, and severer
pancreatitis, bleeding, perforations from ERCP were not observed.
There were no severe or life-threatening complications in procedures.
Stone recurrence is observed in one patient, who has concomitant
alcohol abuse, 18 months after treatment.
Figure 1
Figure 1
Endoscopic clearance of pancreatic duct stones after extracorporeal shock wave lithotripsy. (A) Abdominal computed tomography scan shows multiple calcified stones (red arrow) in pancreatic head. (B) After two sessions of ESWL, endoscopic retrograde cholangiopancreatography displays multiple small filling defects (red arrow) and stricture in the main pancreatic duct at the pancreatic genu, with upstream dilation of the main duct. (C) Endoscopic pancreatic sphincterotomy. A papillotome (black arrow) is inserted into the orifice of the pancreatic duct. Stone was visualized intraluminally. (D) Many fragmented stones (black arrow) were removed with a basket.
Figure 2
Figure 2
Endoscopic clearance of pancreatic duct stones after
extracorporeal shock wave lithotripsy. (A) Plain radiography shows multiple
radioopaque stones with a stone of 8 mm in size (black arrow) in the main
pancreatic duct. (B) After one session of ESWL, endoscopic retrograde
cholangiopancreatography displays multiple small filling defects (black arrow)
and stricture in the main pancreatic duct opening, with upstream dilation of
the main duct. (C) Many fragmented stones (black arrow) were removed with
an extraction balloon after sphincterotomy followed by endoscopic balloon
dilation of the pancreatic orifice. (D) No filling defect (black arrow) but smaller
duct diameter was synchronously observed in the main pancreatic duct after
complete stone removal.
Discussion
As a main complication of CP, PDSs have been brought to
the patient suffering and trouble, and their pathogenesis remains
unknown. Most studies have revealed that there was a tight
relation between formation of PDSs and CP. PDSs are generally
considered to be consequence of CP and almost occur in 50% to
90% of patients with long-stand disease [1-3]. These stones tend to
cause further obstruction of outflow from pancreas, pancreatic duct
hypertension, worsen pathologic changes of pancreatic parenchyma,
pancreatic inflammation and continual abdominal pain, and even
result in inflammatory masses or carcinoma [1-5]. Another factor
associated with PDSs is alcohol abuse. Inui et al. [18] reported that
alcohol drinkers make up 76.6% of PDS patients. Some studies have
demonstrated a direct correlation between stone formation and
long-term alcohol abuse. Other factors including biliary disease,
hyperparathyroidism, and malnutrition, hereditary or idiopathic
factors are also related to PDS formation. Abdominal pain is the
predominant symptom in patients with PDSs and has affected the
patient's life. In this study, all of patients with initial Endotherapyfailed
PDSs had upper abdominal pain radiating to the back; 83.3%
of patients had clinical presentation of CP and associated diabetes
mellitus; two-thirds (66.7%) of patients (only male) had concomitant
alcohol abuse; malnutrition was noted in 16.7% of patients (Table 1).
The results showed that a correlation between the formation of PDSs
and CP, alcohol abuse as well as malnutrition.
Abdominal pain is the predominant clinical symptom requiring
therapy in most patients with calculi CP, due to obstruction and
hypertension of the pancreatic duct either by stones or stricture with
increasing intraductal pressure and parenchymal ischemia [6,7].
Therefore, the main aim of treatment for PDSs is to decompress the
MPD by performing complete stone clearance and ductal drainage
[4,6,7]. Multiple series have demonstrated that removing obstructing
stones from the MPD improves symptoms in the majority of CP
patients. Prior to the introduction of ESWL by Sauerbruch in 1987
[19], surgery and endoscopic therapy were the main options for
clearance of PDSs.
With advancement in noninvasive technology and improvement
in accessory, therapeutic ERCP as a less invasive treatment had
popularly been used for treatment of patients with PDSs. The current
American Society for Gastrointestinal Endoscopy (ASGE) suggests
endoscopic therapy as the first-line treatment of CP and PDSs because
of its lower degree of invasiveness [20]. Endoscopic techniques for
stone removal include EPS, stone retrieval using balloons, baskets,
or rat tooth forceps, stent placement, mechanical lithotripsy,
and endoscopic balloon dilation of the pancreatic orifice after
sphincterotomy [1]. But successful clearance of PDSs via therapeutic
ERCP greatly depends on the location, size, number of stones as
well as the morphological change of pancreatic duct. Selection of the
proper candidates is crucial because endoscopic treatment cannot
be used for all patients. It was reported that the indications for
endoscopic treatment of PDSs or factors favoring successful stone
clearance by Endotherapy were ≤ 3 stones, location of stones at the
pancreatic head and/or body, absence of stricture downstream to the
stone, stone diameter ≤ 10 mm, and absence of impacted stone(s)
[5 and 21]. The best candidates for endoscopic removal are MPD stones of
the head or body with upstream MPD dilation [6]. If a PDS is situated
at the MPD and is small, removal is more likely to be successful. In
contrast, patients with many stones with hardness, impacting natures
underlying duct stricture, or PDSs scattered throughout the pancreatic
duct or stones at the side branch duct without MPD dilatation are
poor candidates for endoscopic removal of PDSs [1,21,22]. In a large
series of 1,000 CP patients who were treated endoscopically with
long-term follow-up, 65% of patients with strictures and/or stones
showed pain improvement after Endotherapy [23]. But, large stones,
presence of strictures, stones impacted behind strictures, stuck to the
ductal epithelium or sited predominantly in the pancreatic tail do not
usually respond well to endoscopic therapy. Complete clearance of
PDSs with standard endoscopic techniques alone was approximately
40~50% [6,17, 21,24,25]. Even in a retrospective series of 125 patients,
less than 10% of them had successful endoscopic ductal clearance
without prior ESWL [26]. In this study, all of patients with PDSs had
received Endotherapy at the other hospital, but initial Endotherapy for
PDSs was unsuccessful, these patients still had continual abdominal
pain. Main causes of the failure of initial Endotherapy for the patients
with PDSs according to imaging findings by CT scan, MRI and/or
diagnostic ERCP could be included as follows: 1) multiple stones
(83.3%); 2) the presence of concomitant pancreatic duct stricture
with upstream MPD dilation (75.0%); 3) radio-opaque stones (100%),
with hardness and irregular natures underlying duct stricture; 4) a
large stone burden, with a mean size of >6.33 ± 2.06 mm (mean ± SD,
range >5~10 mm); 5) EPS inadequacy (66.7%) in initial Endotherapy.
These factors eventually lead to the failure of initial Endotherapy for
PDSs. Therefore, it is necessary to combine therapeutic ERCP with
other effective modalities for treatment of these initial Endotherapyfailed
PDSs.
It is necessarily emphasized that surgery is an older treatment
method than Endotherapy. Surgery, as a more invasive treatment and
almost 25% of patients experience
pain recurrence, and considerable
procedure-related morbidity and mortality, is often considered
second-line therapy for patients in whom endoscopic therapy fails,
[6]. Surgery should be option in patients in whom Endotherapy for
PDSs has failed or in those with stone recurrence or presence of other
complications such as a pancreatic mass with suspicion of malignancy,
and/or duodenal stenosis [7,17,26,27]. In two prospective randomized
controlled trials (RCTs) that compared Endotherapy with surgery for
patients with PDSs, surgery was more effective and better clinical
outcomes than endoscopic therapy [7,17,27,28-30]. But, it is worth
noting that in Díte et al. trial [28], patients in the Endotherapy group
did not receive ESWL, and the protocol also excluded cumulative
stenting or repeat sessions for recurrent symptoms; that Cahen
DL’ trial [29] was limited by a lower than usual overall technical
success (53%) in the Endotherapy group, perhaps due to a very high
proportion of pancreatic duct strictures (84%), and these patients
were probably treated with inadequate short-term stenting (median,
27 weeks); thus reducing the maximum potential of Endotherapy to
provide good clinical outcome [4]. So, it should be considered that
some forms of lithotripsy rather than surgery are used for treatment
of the larger and impacted PDSs before stone removal by therapeutic
ERCP.
ESWL seems to be the best technique for pulverizing PDSs. As PDSs
consist of radiopaque calcium salts with carbonate and phosphate,
these stones in about 90% of patients can be effectively fragmented
by ESWL, which works by concentrating focused shock waves on
stones under fluoroscopy. By pulverizing the stones and reducing the
stone burden, ESWL overcomes the problem of stone size, an obstacle
of endoscopic therapy, thus facilitating the endoscopic clearance of
stones of the duct [5,12-14]. ESWL is safe, effective, and noninvasive
because broken pieces can be removed out of the pancreatic duct once
they are reduced in size. Endoscopic therapy, combined with ESWL,
can remove stones in the MPD, even as well as those in the accessory
pancreatic duct [1,31,32]. In a randomized study that compared
ESWL alone to ESWL with endoscopic therapy, ESWL alone was
safer and more effective [33]. Therefore, ESWL can be used as a
primary treatment, in addition to its compensatory role in endoscopic
therapy [33 and 34]. The European Society of Gastrointestinal Endoscopy
(ESGE) regarding therapeutic intervention in CP patients [33 and 35]
recommends ESWL and ERCP as the first-line treatment method;
ESWL as a first step in treating patients with radiopaque PDSs ≥5 mm
obstructing the MPD, immediately followed by endoscopic extraction
of stone fragments. In CP patients with a MPD stricture, the ESGE
recommends placement of a single 10-Fr plastic stent [33,35]. For
fewer stones that are < 5 mm and located between the pancreatic
head and body, the ESGE recommends endoscopy [35]. Both ASGE
guideline and ESGE guideline recommend endoscopic treatment as
the first-line treatment for such stones, rather than surgery, but the
ESGE guideline emphasizes the role of ESWL more than the ASGE
guideline [20 and 35]. In Japan, ESWL is predominant with endoscopic
treatment used adjunctively [36-37]. Surgery is indicated for patients
who do not meet these indications or for whom nonsurgical treatment
has failed [1], while ESWL was decided upon if stone volume was
deemed too high for successful endoscopic therapy or if therapeutic
endoscopy was unsuccessful [11]. According to literatures, successful
stone fragmentation was achieved by ESWL in a very high percentage
[1,36,37], and ESWL is necessary to fragment the stones prior to
endoscopic extraction in 36%~68% of patients with CP and PDSs
[26-31], while attempts at endoscopic removal without fragmentation
have unsatisfactory results [39]. Approximately 50% of PDSs can
be removed by alone Endotherapy, the addition of ESWL increased
the success rate to 60% to 90% as ESWL can fragment large stones
to lessen the burden [1]. Long-term follow-up studies have shown
that ESWL combined with endoscopic therapy relieves pain and may
avoid the need for surgery in approximately two-thirds of patients
[34]. ESWL can assist in long-term pain relief, when it is combined
with endoscopic therapy to treat PDSs under the proper indications
[1]. Therefore in this study, ESWL in combination with ERCP rather
than surgery is considered for treatment of initial Endotherapy- failed
PDSs.
With regard to the standard of successful PDS fragmentation,
most authors believed that the production of stone fragments ≤ 3
mm was associated with the successful removal of stones. Previously
reported predictors of successful PDS fragmentation and duct
clearance included single PD stone, absence of PD stricture and
PD stone location in the head of the pancreas [26-35]. As multiple,
large stones may prevent complete endoscopic removal; particularly,
Stones >5 mm in diameter are often impacted in the MPD and
require fragmentation
to facilitate their expulsion [40-41]. Solitary
PDSs and location in the head of the pancreas and stone attenuation
have been associated with successful ESWL and complete duct
clearance [26,35,42]. ESWL is indicated in all patients of chronic
calcific pancreatitis with large PDS (>5 mm) that are not amenable to
routine Endotherapy - where pain is the predominant symptom. The
aim is to break the calculi to fragments of ≤ 3 mm, so that they can be
removed by subsequent ERCP. And, over 95% of patients with PDSs
require three sessions or fewer of ESWL for adequate fragmentation
[16]. Repeat sessions are carried out on successive days until the
stone fragments are < 3 mm in diameter. Recently, Lapp RT et al. [43]
reported that PDS diameter of < 9 mm, number of PDSs of < 2, MPD
diameter of < 7 mm, and need for only 1 ESWL session were predictive
of successful fragmentation; that pre-ESWL pancreatic Endotherapy
appears to have no affect on the success of PDS fragmentation by
ESWL; that patients with PDSs of < 12 mm and MPD diameter of
< 8 mm may benefit from early referral to ESWL without pancreatic
duct stent placement as initial intervention regardless if a pancreatic
duct stricture is present. However, ESWL is not indicated in patients
with extensive calculi in the head, body and tail of the pancreas, or
in patients with isolated calculi in the tail area because of increased
chance of collateral damage to the spleen are high [16]. In addition,
patients with pancreatic duct >12 mm in diameter and PDSs >12 mm
are associated with ESWL and endoscopic failure and may benefit
from early referral to surgery [43].
In this study, 100% of patients’ PDSs were located in the
pancreatic head, accompanied by 50% in the body and/or tail and
8.3% throughout both main and accessory pancreatic duct, a mean
size of stone >6.3 ± 2.1 mm (mean ± SD, range >5~10 mm) and 100%
of radiopaque stones; and 75.0% of concomitant pancreatic duct
stricture with upstream MPD dilation and 66.7% of EPS inadequacy.
All patients received ESWL and subsequent therapeutic ERCP. A
total of 19 ESWL sessions with a mean session of 1.58 ± 0.79 (mean ±
SD, range 1~3 sessions) were performed for adequate fragmentation.
Post-ESWL therapeutic ERCP procedures including EPS, extraction
balloon, basket trawling, and plastic stent were used for clearance of
PDSs. By following-up 21 (range, 4~60) months, complete clearance
of PDSs was achieved in 75.0% patients; partial clearance was
achieved in 16.7% (2/12) patients, one of them whose PDSs located
predominantly in the pancreatic tail, and another one whose stones
partially located in the accessory pancreatic duct where stones could
not reached by extraction basket; thus total effective clearance of
PDSs was achieved in 91.6% patients. Complete and partial reliefs of
pain were observed in 75.0% and 16.7% of patients, respectively. And,
there were no severe or life-threatening complications in procedures.
But clearance of PDSs and pain relief were failed in 8.3% (1/12) of
patients in whom both main and accessory pancreatic duct were filled
with stones. In this patient, successful fragmentation was achieved
but the stone extraction basket could not open in pancreatic duct,
leading to failed extraction, subsequently to surgery. Stone recurrence
is observed in one patient (8.3%). The stone recurrence rate was
lower than 22% reported by Inui K et al. [36]. Serial studies have
showed that pre-Endotherapy ESWL could confer a higher rate of
successful Endotherapy to achieve effective clearance of PDSs; ESWL
fragmentation of PDSs in conjunction with endoscopic clearance
of the MPD is associated with significant improvement in clinical
outcomes in most patients with CP; ESWL followed by Endotherapy
is the accepted initial step for most patients with stones larger than
5 mm in the MPD [1,23,34,44,45]. Thus, this study showed that
the proper ESWL for adequate fragmentation and the subsequent
effective therapeutic ERCP for stone clearance help to treat initial
Endotherapy-failed PDSs.
There are several limitations in this study. Firstly, this study is a
retrospective analysis at a single treatment center. Such retrospective
studies can overestimate clinical success and underestimate
complications. Secondly, the sample size of the study is less, which
is not conducive to the evaluation of the curative effect. Thirdly, our
patients are transferred from other different hospital in which initial
Endotherapy for PDSs is failed, thus an accurate comparison with
ESWL followed by ERCP studies remains difficult. Finally, the cohort
presented here likely suffers from referral bias as patients who have
more symptomatic or complex disease are more likely to be referred
to a treatment center.
Conclusion
The clearance of multiple main PDSs in patients with initial Endotherapy-failure is effectively, safely performed via the nonsurgical methods of ESWL in combination with ERCP. If in patients with the appropriate indications or who are at high risk for surgery, ESWL in combination with ERCP can be considered a firstline treatment for patients with initial Endotherapy failure. Of course, large sample, prospective, multicenter studies for treatment of patients with initial Endotherapy failed PDSs will be needed. We expect that the development of advanced endoscopic and ESWL techniques and equipments will expand the role of nonsurgical treatments i.e. ESWL in combination with ERCP in complete clearance of initial Endotherapy failed PDSs.
References
- Kim YH, Jang SIII, Rhee K, Lee DK. Endoscopic Treatment of Pancreatic Calculi. Clin Endosc. 2014; 47: 227-235.
- Maydeo A, Soehendra N, Reddy N, Bhandari S. Endotherapy for chronic pancreatitis with intracanalar stones. Endoscopy. 2007; 39: 653-658.
- Hirota M, Shimosegawa T, Masamune A, Kikuta K, Kume K, Hamada S, et al. The sixth nationwide epidemiological survey of chronic pancreatitis in Japan. Pancreatology. 2012; 12: 79-84.
- Kwek AB, Ang TL, Maydeo A. Current status of endotherapy for chronic pancreatitis. Singapore Med J. 2014; 55: 613-620.
- CLiu BN, Zhang TP, Zhao YP, Liao Q, Dai MH, Zhan HX. Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes. Hepatobiliary Pancreat Dis Int. 2010; 9: 423-427.
- Choi EK, Lehman GA. Update on endoscopic management of main pancreatic duct stones in chronic calcific pancreatitis. Korean J Intern Med. 2012; 27: 20-29.
- Jabłońska B. Is endoscopic therapy the treatment of choice in all patients with chronic pancreatitis? World J Gastroenterol. 2013; 19: 12-16.
- Haggard WD, Kirtley JA. Pancreatic calculi: a review of sixty-five operative and one hundred thirty-nine non-operative cases. Ann Surg. 1939; 109: 809-826.
- Fragulidis GP, Vezakis Α, Dellaportas D, Sotirova I, Koutoulidis V, Kontis E, et al. Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report. Int J Surg Case Rep. 2015; 15: 85-88.
- Ohara H, Hoshino M, Hayakawa T, Kamiya Y, Miyaji M, Takeuchi T, et al. Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones. Am J Gastroenterol. 1996; 91: 1388-1394.
- Ong WC, Tandan M, Reddy V, Rao GV, Reddy N. Multiple main pancreatic duct stones in tropical pancreatitis: Safe clearance with extracorporeal shockwave lithotripsy. J Gastroenterol Hepatol. 2006; 21: 1514–1518.
- Delhaye M, Arvanitakis M, Bali M, Matos C, Deviere J. Endoscopic therapy for chronic pancreatitis. Scand J Surg. 2005; 94: 143-153.
- Parsi MA, Stevens T, Lopez R, Vargo JJ. Extracorporeal shock wave lithotripsy for prevention of recurrent pancreatitis caused by obstructive pancreatic stones. Pancreas. 2010; 39: 153-155.
- Guda NM, Partington S, Freeman ML. Extracorporeal shock wave lithotripsy in the management of chronic calcific pancreatitis: a metaanalysis. JOP. 2005; 6: 6-12.
- Cahen DL, Gouma DJ, Nio Y, Rauws EAJ, Boermeester MA, Busch OR, et al. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med. 2007; 356: 676-684.
- Tandan M, Reddy DN. Extracorporeal shock wave lithotripsy for pancreatic and large common bile duct stones. World J Gastroenterol. 2011; 17: 4365-4371.
- Clarke B, Slivka A, Tomizawa Y, Sanders M, Papachristou G, Whitcomb DC, et al. Endoscopic therapy is effective for patients with chronic pancreatitis. Clin Gastroenterol Hepatol. 2012; 10: 795-802.
- Inui K, Tazuma S, Yamaguchi T, Ohara H, Tsuji T, Miyagawa H, et al. Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: result of a multicenter survey. Pancreas. 2005; 30: 26-30.
- Sauerbruch T, Holl J, Sackmann M, Werner R, Wotzka R, Paumgartner G. Disintegration of a pancreatic duct stone with extracorporeal shock waves in a patient with chronic pancreatitis. Endoscopy. 1987; 19: 207–208.
- Adler DG, Lichtenstein D, Baron TH, Davila R, Egan JV, Gan SL, et al. The role of endoscopy in patients with chronic pancreatitis. Gastrointest Endosc. 2006; 63: 933-937.
- Sherman S, Lehman GA, Hawes RH, Ponich T, Miller LS, Cohen LB, et al. Pancreatic ductal stones frequency of successful endoscopic removal and improvement in symptoms. Gastrointest Endosc. 1991; 37: 511-517.
- Tringali A, Boskoski I, Costamagna G. The role of endoscopy in the therapy of chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22: 145-165.
- Rösch T, Daniel S, Scholz M, Huibregtse K, Smits M, Schneider T, et al. Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up. Endoscopy. 2002; 34: 765-771.
- Heyries L, Sahel J. Endoscopic treatment of chronic pancreatitis. World J Gastroenterol. 2007; 13: 6127-6133.
- Smits ME, Rauws EA, Tytgat GN, Huibregtse K. Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis. Gastrointest Endosc. 1996; 43: 556-560.
- Farnbacher MJ, Schoen C, Rabenstein T, Benninger J, Hahn EG, Schneider HT. Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success. Gastrointest Endosc. 2002; 56: 501-506.
- Fragulidis GP, Vezakis A, Dellaportas D, Sotirova I, Koutoulidis V, Kontis E, et al. Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis: A two cases report. Int J Surg Case Rep. 2015; 15: 85-88.
- Díte P, Ruzicka M, Zboril V, Novotný I. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy. 2003; 35: 553-558.
- Cahen DL, Gouma DJ, Nio Y, Rauws EA, Boermeester MA, Busch OR, et al. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med. 2007; 356: 676-684.
- Cahen DL, Gouma DJ, Laramée P, Nio Y, Rauws EA, Boermeester MA, et al. Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis. Gastroenterology. 2011; 141: 1690-1695.
- CBrand B, Kahl M, Sidhu S, Nam VC, Sriram PV, Jaeckle S, et al. Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis. Am J Gastroenterol. 2000; 95: 3428- 3438.
- Ohara H, Hoshino M, Hayakawa T, Kamiya Y, Miyaji M, Takeuchi T, et al. Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones. Am J Gastroenterol. 1996; 91: 1388-1394.
- Dumonceau JM, Costamagna G, Tringali A, Vahedi K, Delhaye M, Hittelet A, et al. Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomized controlled trial. Gut. 2007; 56: 545-552.
- Kozarek RA, Brandabur JJ, Ball TJ, Gluck M, Patterson DJ, France R, et al. Clinical outcomes in patients who undergo extracorporeal shock wave lithotripsy for chronic calcific pancreatitis. Gastrointest Endosc. 2002; 56: 496-500.
- Dumonceau JM, Delhaye M, Tringali A, Dominguez-Munoz JE, Poley JW, Arvanitaki M, et al. Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2012; 44: 784-800.
- Inui K, Tazuma S, Yamaguchi T, Ohara H, Tsuji T, Miyagawa H, et al. Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey. Pancreas. 2005; 30: 26–30.
- Inui K, Yoshino J, Miyoshi H, Yamamoto S, Kobayashi T. New developments in diagnosis and non-surgical treatment of chronic pancreatitis. J Gastroenterol Hepatol. 2013; 28: 108–112.
- Dumonceau JM, Devière J, Le Moine O, Delhaye M, Vandermeeren A, Baize M, et al. Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results. Gastrointest Endosc. 1996; 43: 547–555.
- Luetmer PH, Stephens DH, Ward EM. Chronic pancreatitis: reassessment with current CT. Radiology. 1989; 171: 353-357.
- Maydeo A, Soehendra N, Reddy N, Bhandari S. Endotherapy for chronic pancreatitis with intracanalar stones. Endoscopy. 2007; 39: 653–658.
- Maydeo A, Soehendra N, Reddy N, Lehman GA. Role of ERCP and other endoscopic modalities in chronic pancreatitis. Gastrointest Endosc. 2002; 56: S237-S240.
- Ohyama H, Mikata R, Ishihara T, Tsuyuguchi T, Sakai Y, Sugiyama H, et al. Efficacy of stone density on noncontrast computed tomography in predicting the outcome of extracorporeal shock wave lithotripsy for patients with pancreatic stones. Pancreas. 2015; 44: 422–428.
- Lapp RT, Wolf JS Jr, Faerber GJ, Roberts WW, McCarthy ST, Anderson MA, et al. Duct diameter and size of stones predict successful extracorporeal shock wave lithotripsy and endoscopic clearance in patients with chronic pancreatitis and pancreaticolithiasis. Pancreas. 2016; 45: 1208-1211.
- Tandan M, Reddy DN, Santosh D, Vinod K, Ramchandani M, Rajesh G, et al. Extracorporeal shock wave lithotripsy and endotherapy for pancreatic calculi: a large single center experience. Indian J Gastroenterol. 2010; 29: 143-148.
- OTandan M, Reddy DN, Talukdar R, Vinod K, Santosh D, Lakhtakia S, et al. Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic pancreatitis. Gastrointest Endosc. 2013; 78: 726-733.