Introduction
In the last decade, transgastric ultrasound-guided (EUS) pancreatic drainage has been
promoted for complex alterations of the main pancreatic duct (MPD) that occur in cases
of chronic pancreatitis (CP) and for the altered anatomy mainly associated with the
Whipple procedure. The incidence of CP is 7.7/100,000 with a prevalence [1] of 26.4/100,000, making the condition as prevalent as inflammatory bowel disease
[2]. CP is defined as pancreatic disease in which recurrent inflammatory episodes lead
to the replacement of pancreatic parenchyma by fibrous connective tissue, which gradually
results in development of ductal and parenchymal abnormalities [3]. Pain is the main symptom, and leads to significant reduction in quality of life
[2]
[4]. Its mechanism is complex, but likely linked to ductal hyper-pressure [3] induced by obstruction from intraductal calcifications and/or fibrous stenosis.
In patient who have undergone surgery, this obstruction is secondary to pancreatic-jejunal
or pancreatic-gastric surgical anastomosis stenosis. Pain management is well documented
[5], and the drug therapy combined with endoscopy or invasive surgical typically is
required to improve duct clearance and achieve pain regression.
The endoscopic approach to MPD drainage was first described in the early 1980 s, and
since 1987, it has been widely used, with development of extracorporeal lithotripsy
to fragment stones in CP. Endoscopic retrograde cholangiopancreatography (ERCP) is
considered the first-line invasive treatment for symptomatic dilation of MPD [6]
[7]
[8]. Indeed, drainage with plastic stents allows for technical success rates of 90 %
to 97 %, with symptom regression in 60 % to 80 % of patients [9]. However, in 3 % to 10 % [10] of the cases, the drainage with ERCP is not feasible due to an impassable MPD stricture,
obstructive lithiasis, duodenal stenosis, or altered anatomy post-surgery [9]
[11]
[12]
[13]. In these situations, surgery has been the only available treatment [14], with efficacy comparable to endoscopy [15] and clinical success rates ranging from 65 % to 85 %. However, the adverse event
(AE) and mortality rates can reach 30 % and 2 %, respectively [16]
[17]
[18]. In addition, anastomotic stricture may occur after the procedure, causing painful
obstruction of the upstream duct of Wirsung [16]
[19]
[20].
Interventional ultrasound also has evolved considerably, with techniques such as transgastric
ultrasound-guided drainage of pancreatic pseudo-cysts and walled-off necrosis, and
more recently, hepatico-gastrostomy for transgastric biliary drainage [21]
[22]. Following this dynamic, the EUS-guided pancreatic duct drainage (EUS-PD) first
was described by François et al. using a cystotome. Then, various techniques for creating
the path between the pancreatic duct and the stomach were proposed with balloon dilation
[23]
[24], with an increased risk of pancreatic leakage, as indicated in the PRINCEPS study
[12].
Despite several technical improvements, the technique remains technically complex.
This has been reported in various studies, all retrospective and single-center with
small sample size [9]
[12]
[25]
[26]
[27]. More recently, multicenter studies have been published, with larger numbers of
patients [11]
[28] and longer follow-up. The technical success rate is approximately 90 %, with clinical
efficacy observed in 70 % to 90 % of patients, who have a significant reduction in
pain.
Thus, we present our series, which evaluated the results of EUS-PD in management of
symptomatic dilation of the MPD that has failed to respond to ERCP or in patients
for whom that procedure is impossible. The objectives were to evaluate the safety
and the efficacy of the procedure.
Patients and methods
Study design and patients
This was a single-center, retrospective study of consecutive cases, conducted at the
North Hospital in Marseille, to evaluate EUS-PD of the MPD. All the patients in for
whom MPD drainage was indicated because of symptomatic dilation were identified using
a retrospective database that included information on all ERCP or therapeutic EUS
procedures performed in our tertiary center between January 2010 and January 2019.
This database meets national criteria for protection of patient data and is validated
by the CNIL (Commission Nationale de l’Informatique et des Libertés).
All patients included the analysis were suffering painful pancreatic stenosis (CP
or anastomotic stricture) associated with > 4-mm MPD dilation, as confirmed by prior
imaging (computed tomography or magnetic resonance imaging), and EUS-PD had been attempted
in them because ERCP failed or could not be performed. Conversely, patients who had
a non-dilated duct associated with pancreatic atrophy, neoplastic pancreatic strictures,
or for whom anticoagulants could not be discontinued were excluded.
As shown in [Table 1], information was collected on the following patient characteristics: age, sex, active
smoking and alcohol consumption, cause of MPD dilation, etiology of CP or cause of
cephalic pancreatic duodenectomy (CDP), pain and associated analgesic consumption.
Data on morphological characteristics, such as weight and body mass index, and on
duration of hospitalization and early complications also were collected.
Table 1
Patient characteristics and etiologies of MPD dilatation.
|
Patients, n
|
27
|
|
Average age, years [min-max]
|
61.8 [36–85]
|
|
Sex, % (n)
|
|
|
29.6 % – (8)
|
|
|
70.4 % – (19)
|
|
Tobacco, % (n)
|
40.7 % (11)
|
|
Alcohol, % (n)
|
29.6 % (8)
|
|
Average BMI, [min-max]
|
22.4 [16–37]
|
|
Daily analgesic consumption[1], % (n)
|
|
|
96.2 % (26)
|
|
|
14.8 % (4)
|
|
|
18.5 % (5)
|
|
Pain, % (n)
|
|
|
40 % (11)
|
|
|
60 % (16)
|
|
Etiology of MPD dilation
|
|
|
66.6 % (18)
|
|
|
50 % (9)
|
|
|
16.6 % (3)
|
|
|
33.3 % (6)
|
|
|
33.3 % (9)
|
|
|
44.4 % (4)
|
|
|
11.1 %(1)
|
|
|
22.2 % (2)
|
|
|
11.1 % (1)
|
|
|
11.2 % (1)
|
MPD, main pancreatic duct; CDP, cephalic duodenopancreatectomy; IPMN, intraductal
papillary mucinous neoplasm; GIST, gastrointestinal stromal tumor.
1 According to OMS classification
Endoscopic procedure
The procedure was performed by interventional endoscopists who were experts in ERCP
and in therapeutic EUS. All patients received general anesthesia and were intubated
and placed in the supine position. Post-procedural acute pancreatitis prophylaxis
with nonsteroidal anti-inflammatory drugs was administered, as recommended in European
Society of Gastrointestinal Endoscopy guidelines [29]. The endoscope used was always a linear therapeutic EUS-scope with at least a 3.6-mm
operating channel (Pentax or Fujifilm, Japan), with fluoroscopic control.
Pancreatico-gastrostomy was performed following as described here ([Fig. 1] and [Fig. 2]). Step 1: Puncture of dilated MPD under EUS using a 19G fine needle aspiration needle
(EchoTip, Cook Endoscopy, United States or Boston Scientific, United States). A pancreatography
was then performed by injecting diluted contrast into the MPD. Step 2: Placement in
the main pancreatic duct of a 0.035-inch guidewire under fluoroscopic control (Jag-Wire,
Boston Scientific, United States). Step 3: Creation of a pancreatic-gastric fistula
using a 6Fr cystotome (Cysto Gastro, Endoflex, Voerde, Germany), with application
of a pure section current (120 Watts, Erbe Vio, Erlangen, Germany) to cross the gastric
wall and the pancreatic parenchyma. Step 4: Placement over the wire of a 7Fr straight
plastic stent between the MPD and the stomach. In patients without CDP, when the guidewire
crossed the stenosis and was in the duodenum, the appointment technique was performed
at a later time.
Fig. 1 Diagram of the different stages of EUS-guided Wirsungo-gastrostomy. a Expansion of the main pancreatic duct (MPD) > 4 mm. b Echo-guided puncture with a 19G needle, opacification of the MPD. c Placement of a guidewire in the MPD. d Using a 6Fr cystotome set in pure section, a pancreatic-gastric fistula is created.
e Installation of a straight transgastric pancreatic plastic prosthesis. f End of the procedure. (Source: Oscar Siame)
Fig. 2 The different stages of Wirsungo-gastrostomy under echo endoscopy. a Expansion of the main pancreatic duct (MPD > 4 mm). b Echo-guided puncture using a 19G needle. c Opacification of the MPD under fluoroscopic control. d Installation in the MPD of a wire. e Creation of a pancreatic-gastric fistula using a 6Fr cystotome and then installation
of a straight transgastric pancreatic plastic prosthesis. f Endoscopic view, resulting from pancreatic sugar at the end of the procedure.
The endoscopic data ([Table 2]) collected were on the maximum diameter of the MPD evaluated by EUS, the location
and type of stenosis, the type of equipment used (puncture needle, cystotome, guide
wire, stent), and any intraoperative complications, such as digestive bleeding, acute
pancreatitis, or pain.
Table 2
Endoscopic data.
|
Global n = 27
|
|
Type of stenosis, % (n)
|
|
|
33.3 % (9)
|
|
|
33.3 % (9)
|
|
|
33.3 % (9)
|
|
Cause of ERCP failure, % (n)
|
|
|
33.3 % (9)
|
|
|
33.3 % (9)
|
|
|
33.3 % (9)
|
|
Location of stenosis, % (n)
|
|
|
44.4 % (12)
|
|
|
22.2 % (6)
|
|
|
33.3 % (9)
|
|
Previous ERCP, % (n)
|
66.6 % (18)
|
|
Average MPD dilatation mm, [min-max]
|
6.5 [3–12]
|
MPD, main pancreatic duct; ERCP, endoscopic retrograde cholangiopancreatography.
Postoperative and long-term follow-up
The patients fasted for 24 hours after the procedure and were discharged after 3 to
5 days. They were either seen in a clinic or at the hospital at 3 and 6 months, and
every 6 months thereafter, or contacted by phone if they were living too far away
(patients referred from other centers). A standard questionnaire ([Fig. 3]) was used to assess their pain, weight variation, development of diabetes or exocrine
insufficiency, and quality of life.
Fig. 3 Follow-up survey.
More specifically, pain was systematically documented before and during follow-up,
using a visual analogic scale (VAS) from 0 to 10. The improvement was classified into
three categories: “Complete regression” if a patient had no residual pain (VAS = 0);
“partial regression” if patient had occasional and low-intensity pain episodes (VAS ≤ 3)
with a reduction of at least three points compared to the VAS collected before the
procedure; and finally, “no regression” if there were no significant changes despite
constant consumption of palliate II or III analgesics over time, according to the
World Health Organization classification.
Delayed AEs, including early recurrence, EUS-PD stent migration, and digestive perforation
were reported, as well as the need for subsequent surgery in case of complete failure.
Objectives
The main objective was to evaluate the technical success of EUS-PD in patients with
symptomatic dilation of the MPD in whom ERCP had failed or it could not be performed.
Success was defined as placement of a plastic stent between the stomach and the MPD.
The secondary objectives were to document the safety profile with the complication
rate for the procedure, the clinical success in terms of pain regression, and patient
quality of life as measured on the standard follow-up questionnaire, and to define
a standardized management algorithm.
Statistical analysis
The File Maker Pro (Apple Inc., United States) and Axigate databases of the APHM (Axigate
SAS, Paris, France) were used to collect the data. Statistical analyses were conducted
with SPSS statistics software (IBM Rochester, Minnesota, United States). The data
were expressed as means with extremes and percentages. Frequencies and percentages
were used for the qualitative variables. Medians and means were used for the quantitative
variables. A univariate subgroup analysis was performed and P < 0.05 was considered statistically significant.
Results
Patient characteristics
Twenty-seven patients (70.4 % male, average age 61 ± 12 years) were included in the
analysis between January 2010 and January 2019. Nine patients had altered anatomy
after surgery; the other 18 patients had CP without prior pancreatic resection. The
etiology of CP and the indications for MPD in patients in the group with altered anatomy
are detailed in [Table 1].
The indication for drainage was dilation of the MPD associated with presence of painful
pancreatic symptomatology in all patients. Of these, 60 % of patients had recurrent
acute pancreatitis attacks; the remaining 40 % had radiating postprandial pain (typical
pancreatic pain).
The causes of previous ERCP failure were inaccessibility to the papilla in nine patients,
obstructive lithiasis in nine patients, and fibrous stenosis impassable by the guidewire
in nine patients ([Table 2]).
Endoscopic procedure
Technical success
Technical success was achieved in 92.5 % of patients (n = 25) ([Table 3]). Access to the MPD was possible in 100 % of patients by the transgastric route.
The plastic stent was placed in an anterograde transgastric fashion in 88 % of patients
(n = 24) and in a transpapillary retrograde fashion after use of the “rendezvous”
technique in one patient (4 %). In two patients, the Wirsungo-gastric stent placement
failed. In the two cases of stent placement failure, cyanoacrylate (mixed with lipiodol)
was injected into the puncture path associated with the closure of the transgastric
access with clips (Instinct, Cook, United States), without clinical consequences.
Table 3
Technical modalities and patient follow-up after endoscopic treatment.
|
Global
n = 27
|
Altered anatomy
n = 9
|
PCC
n = 18
|
|
Technical success, % (n)
|
92.5 % (25)
|
88.8 % (8)
|
94.4 % (17)
|
|
Clinical success[1] % (n)
|
88.8 % (24)
|
88.8 % (8)
|
83 % (15)
|
|
Pain regression, % (n)
|
|
|
44.4 % (12)
|
77.8 % (7)
|
27.8 % (5)
|
|
|
44.4 % (12)
|
22.2 % (2)
|
55.5 % (10)
|
|
|
11.2 % (3)
|
0 % (0)
|
16.7 % (3)
|
|
Other clinical symptoms, % (n)
|
|
|
88.8 % (24)
|
100 % (9)
|
83 % (15)
|
|
|
74 % (20)
|
100 % (9)
|
61 % (11)
|
|
|
66.6 % (18)
|
88.8 % (8)
|
55.5 % (10)
|
|
Complications, % (n)
|
|
|
7 % (2)
|
11 % (1)
|
5.5 % (1)
|
|
|
14 % (4)
|
11 % (1)
|
16.6 % (3)
|
|
|
0
|
0
|
0
|
|
Endoscopic procedure, medium, [min-max]
|
|
|
4.2 [2–8]
|
4.1 [3–6]
|
4.3 [2–8]
|
|
|
5 [4–6]
|
6 [6–6]
|
5 [4–6]
|
|
|
3.7 [1–10]
|
4.8 [1–10]
|
3.2 [1–7]
|
|
Median follow-up, % (month)
|
34.2 [41–02]
|
44.8 [16–102]
|
28.9 [4–81]
|
Min-max, minimum-maximum.
1 Complete or partial pain regression.
Of the placed stents, 92.5 % (n = 25) were 7Fr plastic stents (7 cm or 5 cm), whereas
only one patient had a fully-covered metal stent placed.
Complications
There were no intraoperative complications. The overall rate of postoperative AEs
was 22 % (n = 6). Four patients (14 %) experienced postoperative non-specific pain,
with spontaneous improvement. The mean length of hospitalization after the EUS-PD
was 4.2 days [2]
[3]
[4]
[5]
[6]
[7]
[8]. In case of complications, the hospitalization stay was extended. Two cases of delayed benign acute edematous pancreatitis (7 %) were reported (on
Days 20 and 30 after stent placement), both requiring a 72-hour hospitalization, with
no further intervention required.
During a mean 34.2-month follow-up, five spontaneous stent migrations occurred. Four
were discovered fortuitously during the follow-up endoscopy, planned for stent exchange
(3 plastic and 1 metal). Of them, one patient still had pain and one was found based
on recurrence of abdominal pain (confirmed by imaging) in a patient in whom EUS-PD
had previously provided relief. A stent was replaced along the Wirsungo-gastric path
in these two patients, whereas the asymptomatic patients remained stent-free.
Clinical success and factors
Clinical success was achieved in 88.8 % of patients (n = 24) ([Table 3]). Half of them described a “complete regression” and half a “partial regression.”
Oppositely, 11.2 % of patients did not show any symptomatic improvement. A subgroup
analysis revealed that 100 % of patients in the altered anatomy group were improved,
compared to 83 % in the CP group.
Improved quality of life was reported in 74 % of patients and a change in appetite
in 66.6 %. Univariate analysis ([Table 4]) revealed a significant difference with regard to the consumption of class I painkillers,
weight variation, and improvement in quality of life in favor of the altered anatomy
group compared with the CP patients (P < 0.05; [Table 3]).
Table 4
Varied uni-analysis of the associated factors according to the cause of the obstruction.
|
Altered anatomy
N = 9
|
PCC
N = 18
|
P value
|
|
Consumption of Level 1 analgesics, % (n)
|
0 % (0)
|
50 % (9)
|
0.017
|
|
Weight change, % (n)
|
88.8 % (8)
|
38 % (7)
|
0.014
|
|
Improvement in quality of life, % (n)
|
100 % (9)
|
61 % (11)
|
0.030
|
PCC, portal cavernoma cholangiopathy.
Evolution during follow-up
Median follow-up was 34.2 months ( minimum 4 months – maximum 108 months) , with 92.6 %
of patients (n = 25) having more than 12 months of follow-up. The mean stent exchange
interval was 5 months (4 to 6 months) and the mean number of stent changes during
follow-up was 3.7 (1 to10). At the last reassessment, 22 patients still had a plastic
stent in place, exchanged every 6 months.
Moreover, during the whole follow-up, no patient underwent secondary surgery or celiac
plexus block under ultrasound endoscopy due to persistent pain. Two patients died
during the follow-up, one from digestive bleeding secondary to portal hypertension
and one from septic shock, in both cases unrelated to the EUS-PD procedures.
Discussion
Symptomatic MPD dilation, CP or altered anatomy-related, due to ductal hyper-pressure,
is the target of endoscopic and historically, surgical treatment. In the event that
ERCP fails or cannot be performed, even after extracorporeal shockwave lithotripsy,
resection surgery was the only option. The latter is based on the realization of a
pancreatic-jejunal or pancreatic-gastric anastomosis [14]. Two types of interventions were described: decompressive surgery or Frey intervention
in case of dilated MPD without inflammatory mass, and resection surgery or Whipple
intervention when there is an inflammatory or suspicious mass, consisting of cephalic
duodeno-pancreatectomy (CDP). Despite a good efficacy rate [15]
[30] morbidity reaches 30 % and mortality 2 % [16]
[17]
[18], still with a risk of anastomotic stricture [20]
[30].
For this reason and following the development of therapeutic EUS, EUS-PD was proposed
by François et al. in 2002 [12] as an alternative to surgery for of symptomatic MPD dilation. The literature since
then ([Table 5]) documents a technical success rate of 86 %, according to a recent review, with
a complication rate between 0 % and 20 %, and a clinical success rate between 50 %
and 100 % [31]
[32]
[33]
[34]. Our study is consistent with this literature, since the technical success rate
was 92.5 %, 92.6 % of patients had a decrease in painful attacks during long-term
follow-up, and 88.9 % had “complete” or “partial” regression of pain after a median
follow-up of almost 3 years. In addition, no severe AEs or procedural mortality were
reported.
Table 5
Summary of the various studies of EUS-PD.
|
Authors
|
No. of patients
|
Technical success
|
Clinical success
|
Complications
|
Overall follow-up in months
|
Type of stent
|
|
Francois
GIE, 2002
|
4
|
100 %
|
75 %
|
0 %
|
12
|
Plastic
|
|
Teissier
GIE, 2007
|
36
|
92 %
|
69 %
|
14 %
|
14.5
|
Plastic
|
|
Kahaleh
GIE, 2007
|
13
|
92 %
|
77 %
|
16 %
|
14
|
Plastic
|
|
Brauer
GIE, 2009
|
8
|
88 %
|
50 %
|
0 %
|
14
|
Plastic
|
|
Barkey
GIE, 2010
|
21
|
48 %
|
[1]
|
2 %
|
13
|
Plastic
|
|
Ergun
Endoscopy, 2011
|
20
|
90 %
|
72 %
|
19 %
|
37
|
Plastic
|
|
Fujii
GIE, 2013
|
45
|
74 %
|
83 %
|
6 %
|
32
|
Plastic
|
|
Will
WJG, 2015
|
94
|
88 %
|
72 %
|
15 %
|
28
|
Plastic and metal
|
|
Tyberg
GIE, 2017
|
80
|
89 %
|
81 %
|
20 %
|
24
|
Plastic
|
|
Oh
GIE, 2017
|
25
|
100 %
|
100 %
|
20 %
|
18.5
|
Metal
|
EUS-PD, EUS-guided pancreatic duct drainage; GIE; WJG
1 not evaluated
Focusing on patients with altered anatomy after cephalic duodenopancreatectomy (or
Whipple resection), a recent international multicenter study compared enteroscopic
endoscopic retrograde pancreatography (e-ERP) and EUS-PD. A total of 66 patients and
75 interventions were identified (40 EUS-PD versus 35 e-ERP). Rates of technical and
clinical success were 92.5 % and 87.5 %, respectively, in the EUS-PD group compared
with 20 % and 23 % in the e-ERP group [35]. We found similar results in our study, with 100 % of symptoms relieved.
Technically, a minimum MPD dilatation ≥ 4 mm is required to safely perform the EUS-guided
puncture. However, Umar Hayat et al [36] showed that puncture of an undilated pancreatic duct is technically feasible, although
difficult. In his study, he showed that it can be done by using a small-caliber guidewire,
4F angioplasty balloon, and reverse 3F single pigtail stents. If there was no dilation,
we did not attempt the drainage because of the uncertainty of effectiveness. Celiac
block can be proposed in such a case, as previously published.
Second, the type of stent to use is another matter, given that the majority of teams
use plastic. Indeed, migration or obstruction requiring endoscopic reintervention
occurs frequently, with a delay before obstruction of around 120 days. Few centers
recommend placement of several plastic stents after ERCP to extend the time without
dysfunction and shorten the calibration period [37]. However, when performing Wirsungo-gastrostomy, it is neither reasonable nor useful
to place multiple stents, since the purpose is not to calibrate an impassable stricture,
but to remove the ductal hyper-pressure. When multiple stents are preferable, dual
3Fr stents may provide a permanent wick to keep the fistula open, as described in
a small series [36]. Also, this would significantly increase the risk of procedural failure and complications
by leaving an active pancreatic fistula after the cystotome was passed. More recently,
Oh et al [38] reported the use of a fully-covered self-expanding metal stent when performing EUS-PD.
The technical and clinical success rates were 100 % in 25 patients with symptomatic
dilation of the main canal with prior ERCP failure. Nevertheless, 20 % of early AEs
with acute abdominal pain have been reported, probably due to poor tolerance. In addition,
the permeability time was 126.9 days during the mean follow-up (221.1 days), which
is no different than with plastic stents [39].
The final technical aspect is the approach. Although unstable, the transgastric approach
remains the most used because it allows direct access to the MPD. A recent study proposed
trans-bulbar access, arguing that the endoscope stability in the bulb is superior
[39]. The technical success rate was similar, but in cases of isthmic or corporal stenosis
or altered digestive anatomy, the trans-bulbar pathway is not feasible.
To date there is no standardized scheme for the interval between changes and the time
required to obtain calibration. In our study, the average stent replacement time was
5.4 months. We propose a management algorithm that suggests changing the stent every
6 months for 24 months, then attempting to remove it ([Fig. 4]). The fact that in the absence of a stent, EUS-PD may persist over time because
of a fibrosis phenomenon seems interesting. In five patients, we did not observe pain
recurrence after spontaneous stent migration and without new placement. Therefore,
there are two hypotheses: (1) After migration of the stents, the anastomosis remains
functional; and (2) The natural progression of the disease towards atrophy of the
pancreatic parenchyma results in a decrease in the neuropathic component of pain.
This phenomenon was described in the study by Tyberg et al [28] of two cases of pancreatic-gastric fistula that remained functional after stent
removal, which were detected with secretin MRI.
Fig. 4 Management algorithm in case of failure of ERCP or in ability to perform it. MPD,
main pancreatic duct; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic
ultrasonography; EUS-PD, EUS-guided pancreatic duct drainage
There is still a lack of prospective data on which to base a recommendation for wider
use of this technique, which should be reserved for tertiary centers experienced with
therapeutic EUS procedures. In 2018, however, the European Society of Gastrointestinal
Endoscopy (ESGE) published recommendations [29] for using EUS-PD as a bridge to surgery in patients with insoluble pain, in whom
surgery was contraindicated, or for whom surgery represented a significant risk. We
believe that rather than bridging the gap to surgery, EUS-PD should be a substitute
for ductal decompression surgery, and that in patients suspected of having resectable
malignant lesions, only surgical resection should be performed.
Conclusion
In conclusion, this study demonstrated that EUS-PD is safe, minimally invasive, and
effective in the management of symptomatic MPD dilation after ERCP has failed or cannot
be performed. This technique should be done in expert centers, but it is an alternative
to duct decompression surgery. Technical and device advancements will continue to
improve the safety and efficiency of this procedure. Prospective studies are needed
to confirm its place in the therapeutic strategy for MPD dilation.
