Keywords endoscopic ultrasound - pancreatitis - lumen apposing metal stents - walled-off necrosis
Introduction
Disconnected pancreatic duct (DPD) complicates the clinical course of patients with
acute necrotizing pancreatitis (ANP) resulting in multiple interventions including
surgery and prolonged hospital stay.[1 ]
[2 ]
[3 ]
[4 ]
[5 ] The complicated clinical course occurs due to the fact that the disconnected viable
segment of pancreas continues to pour pancreatic secretions that do not drain into
the lumen of gastrointestinal tract resulting in recurrent pancreatic fluid collections
(PFCs), refractory external pancreatic fistula, and chronic abdominal pain/recurrent
pancreatitis.[3 ]
[6 ] One of the strategies employed to decrease the risk of these clinical problems is
to maintain the iatrogenic internal fistula created at the time of endoscopic transluminal
drainage of PFCs by leaving transmural plastic stents in situ permanently.[7 ]
[8 ] This strategy of leaving plastic stents permanently has been shown to be safe as
well as effective in preventing the recurrence of PFCs.[1 ]
[4 ]
[7 ]
[8 ]
[9 ]
The availability of lumen apposing metal stents (LAMSs) has improved the results of
endoscopic drainage of pancreatic necrotic collections.[10 ]
[11 ] Few studies have also shown that risk of recurrence of PFC following successful
endoscopic drainage of PFC with LAMS in patients with DPD is very low, and therefore,
there is no need of permanent indwelling plastic stents in patients treated with LAMS.[2 ]
[12 ] Basha et al in a retrospective study did not replace LAMS with permanent indwelling
plastic stents and reported recurrence of PFC in 17.4% patients and only 6.6% patients
required intervention for PFC.[2 ] Dhir et al also did not replace LAMS with permanent indwelling plastic stents and
also reported similar results with a recurrence rate of 13.2% with reintervention
in only one patient.[12 ]
However, few studies have reported discordant results. Bang et al reported that PFC
recurred in 1.4% patients with DPD in whom metal stent was replaced with plastic stent
and in 25% patients without a plastic stent (25.0%) (p = 0.001).[1 ] Rana and Gupta also found similar results in a preliminary retrospective comparative
analysis. The PFC recurred in 27% patients without plastic stent versus none in patients
with a permanent indwelling plastic stent.[13 ] These discordant results suggest that factors other than the use of LAMS determine
the risk of recurrence of PFC or symptoms in patients with DPD as patients with PFC
and DPDs treated with large caliber metal stents still have uncorrected physiological
abnormality of undrained upstream viable pancreatic parenchyma.
The clinical consequences of DPD, along with the uncorrected physiological abnormality
of undrained pancreatic segment, also depend on various other factors including etiology
of ANP, site of disruption (proximal/distal), and volume of pancreatic juice secreted
from the disconnected segment, as well as the ability of body to contain this secretion.[5 ] Rana et al reported that patients with distal disconnection, post-ANP diabetes,
as well as steatorrhea and pancreatic atrophy had low risk of recurrence of PFC in
patients with DPD and without permanent indwelling plastic stents.[9 ] It appears that the amount of pancreatic parenchyma left viable after an episode
of ANP is an important factor that determines the long-term clinical outcome of patients
with DPD. Therefore, we hypothesized that direct endoscopic necrosectomy (DEN) could
impact the long-term outcome of patients of walled-off necrosis (WON) with DPD treated
with LAMS and thus, could be responsible for discordant results among studies on impact
of LAMS on the long-term outcome of patients with ANP and DPD. In this retrospective
study, we compared the frequency of recurrence of symptoms as well as PFC in patients
with WON and DPD undergoing DEN with that of not requiring DEN and not having permanent
indwelling plastic stents.
Patients and Methods
Retrospective analysis of prospectively maintained database of patients with WON (as
defined by the revised Atlanta classification[14 ]) successfully treated with endoscopic transmural drainage using LAMS over the past
5 years was done to identify patients with DPD and not having permanent indwelling
transmural plastic stents. We, at our center, follow a policy of leaving plastic stents
in the transmural tract for an indefinite period in patients with DPD. In patients
initially treated with LAMS, the metal stent is replaced with a permanent indwelling
plastic stent following resolution of the PFC. However, it is not possible to replace
LAMS with plastic stents in all the patients as the PFC cavity collapses completely
in approximately one-third of patients following resolution of PFC. These patients
in whom the LAMS could not be replaced with plastic stent following resolution of
PFC were identified and retrospectively analyzed.
These patients were divided into two groups: Group A: patients who had undergone DEN
after placement of LAMS and Group B: patients who did not require DEN and were successfully
treated with LAMS drainage alone. The patient demographics, etiology of acute pancreatitis
(AP), size of WON, type of stent used, outcome details, as well as long-term follow-up
data including recurrence of symptoms or PFC or new-onset diabetes mellitus were retrieved
from the database. All the endoscopic procedures were performed after obtaining informed
consent from the patients.
Endoscopic Drainage
Endoscopic ultrasound (EUS)-guided drainage was performed using a linear scanning
echoendoscope (EG-3870 UTK linear echoendoscope, Pentax Inc., Tokyo, Japan or UCT180
linear echoendoscope, Olympus Optical Co Ltd, Tokyo, Japan). The technical details
of the EUS-guided drainage procedure have been published previously by us.[15 ] The patients included in this study underwent initial transmural drainage using
LAMS (NAGI stent [14 or 16 mm], Taewoong Medical Co., Ltd., Seoul, South Korea or
Plumber Stent [16 mm diameter], MI Tech Gyeonggi-Do, Korea or Hot Axios stent [15/20 mm
diameter], Boston Scientific, Natick, Massachusetts, United States). Following drainage,
patients underwent computed tomography (CT) of the abdomen 72 hours after the drainage
procedure. Patients with new-onset fever or worsening of existing symptoms with persistent
WON on CT (<50% reduction in size) underwent repeat endoscopic transmural drainage.
If the LAMS was clogged with necrotic material, the stent was declogged and 7-Fr nasocystic
catheter (NCC) was inserted through the LAMS into necrotic cavity. The NCC was flushed
and aspirated with 200 mL normal saline or hydrogen peroxide (3%) every 4 to 6 hours.
Following symptomatic improvement, the NCC catheter was removed. In nonresponders,
DEN was performed through the LAMS using a combination of accessories such as grasping
forceps, snare, Dormia basket, and Roth basket ([Figs. 1 ]
[2 ]
[3 ]
[4 ]).
Fig. 1 Computed tomography: large walled-off necrosis with extensive pancreatic necrosis.
Fig. 2 Endoscopic ultrasound-guided drainage of walled-off necrosis with lumen apposing
metal stent.
Fig. 3 Computed tomography: postdrainage with lumen apposing metal stent (LAMS) shows a
large residual necrotic collections with LAMS in situ.
Fig. 4 Direct endoscopic necrosectomy being done through the lumen apposing metal stent.
Following clinical improvement, cross-sectional imaging to document resolution of
WON was done at the discretion of the treating clinician. In patients with symptomatic
improvement and resolved WON on CT, endoscopic retrograde cholangiopancreatography
(ERCP) or magnetic resonance cholangiography (MRCP) was done at the discretion of
the treating clinician to document DPD. Thereafter, an attempt was made to replace
LAMS with a 7- or 10-Fr double pigtail plastic stent and leave the plastic stents
for an indefinite period. As mentioned earlier, patients included in this study had
collapsed WON cavity at the time of removal of LAMS, and therefore, a permanent indwelling
plastic stent could not be placed.
Follow-up and Outcome Measures
All these patients without a permanent indwelling transmural plastic stent were followed
up in outpatient clinic once every 3 months for first year and thereafter every 6
monthly. The patients not reporting to the clinic were contacted telephonically. The
patients underwent measurements of fasting blood sugar as well as glycosylated hemoglobin
(HbA1c) levels once in 6 months or when the patients reported symptoms of hyperglycemia.
Patients having new symptoms such as abdominal pain, fever, or jaundice underwent
CT for detecting recurrence of PFCs. The patients with recurrence of PFCs underwent
further investigations such as MRCP, EUS, and ERCP at the discretion of treating clinician.
Statistical Analysis
The data were presented as percentages for categorical variables, and mean ± standard
deviation for quantitative variables. The continuous variables were compared using
Student's t -test, whereas the categorical variables were compared using the chi-square or Fisher's
exact test. A p -value of <0.05 was considered as significant.
Results
Thirty-eight patients (mean age: 37.7 ± 6.8 years; male: n = 31) with WON and DPD successfully treated with LAMS and without permanent indwelling
transmural plastic stents were retrospectively identified and analyzed. Seventeen
of these patients required DEN (Group A; mean age 37.8 ± 7.9 years), whereas 21 patients
were successfully treated without the need of DEN (Group B; mean age: 37.7 ± 5.8 years).
There was no significant difference in the demographics as well as the etiology of
AP between the two groups ([Table 1 ]). Contrast-enhanced CT of the abdomen done between 3 and 7 day of onset of ANP revealed
>50% parenchymal necrosis in significantly more patients in Group A as compared with
patients in Group B (76.4 vs. 23.8%; p < 0.05) ([Fig. 1 ]). The size of WON was comparable between the two groups, but the amount of solid
necrotic debris was significantly more in patients requiring DEN compared with patients
who had successful outcome without DEN (48 vs. 22%, respectively; p < 0.05) ([Table 1 ]). Also, patients needing DEN required longer time for resolution as compared with
patients not requiring DEN (mean of 33.5 vs. 26.3 days; p < 0.05).
Table 1
Demographics, etiology of acute pancreatitis, baseline imaging characteristics, and
outcomes between the two groups
Parameter
Group A (requiring DEN)
(n = 17)
Group B (DEN not done) (n = 21)
p -Value
Age (mean ± SD)
37.8 ± 7.9 y
37.7 ± 5.8 y
>0.05
Males (%)
15 (88)
16 (76)
>0.05
Etiology
Alcohol
13 (76.4%)
13 (61.9%)
>0.05
Gall stones
2 (11.8%)
5 (23.8%)
Idiopathic
2 (11.8%)
2 (9.5%)
Others
0
1 (4.8%)
>50% necrosis on CT done at days 3–7 of onset of illness
13 (76.4%)
5 (28%)
<0.05
Drainage for infected PFC
6 (28.5%)
13 (61.9%)
>0.05
Size of WON (mean ± SD)
12.6 ± 1.9 cm
11.7 ± 2.0 cm
>0.05
% Solid debris as documented on EUS
48.2 ± 9.2%
21.9 ± 9.3%
<0.05
Time taken for resolution of WON (d)
33.5 ± 5.8
26.3 ± 9.3
<0.05
Abbreviations: CT, computed tomography; DEN, direct endoscopic necrosectomy; EUS,
endoscopic ultrasound; PFC, pancreatic fluid collection; SD, standard deviation; WON,
walled-off necrosis.
Recurrence of Symptoms/PFC after Resolution
In Group A, none of the patients developed either recurrence of any symptoms or PFC
over a mean follow-up period of 7 months. In Group B, 5 of 21 (23.8%) patients developed
abdominal pain over a mean follow-up period of 22 months (median time of recurrence
from stent removal was 6 months; range: 3–13 months). On cross-sectional imaging,
three of these patients had developed recurrent PFC and two patients needed repeat
endoscopic transmural drainage using plastic stent. Following resolution of PFC, the
plastic stent has been left in situ for an indefinite period and patients continue
to be asymptomatic on last follow-up. The remaining one patient with PFC had a small
collection (4 cm in size) and responded to pain killers. Thereafter, the patient continues
to be asymptomatic and there has been no increase in the size of PFC on last follow-up.
Two patients presented with upper abdominal pain not associated with either increase
in serum pancreatic enzyme levels nor any imaging features of pancreatitis. The pain
responded to nonsteroidal anti-inflammatory drugs and one of these patients developed
one more episode of pain 4 months after the first episode of recurrent abdominal pain.
Both these patients currently are on antioxidants and pancreatic enzymes supplement
and continue to be asymptomatic on last follow-up. On comparing both groups at 7 months
of follow-up, 3 of 21 (14.2%) patients in Group B had recurrence of symptoms, whereas
none of the patients in Group A had recurrent symptoms. New-onset diabetes mellitus
developed in five (29%) patients in Group A and two (9%) patients in Group B (p > 0.05). None of the patients in either group developed steatorrhea.
Discussion
Pancreatic duct disconnection is a frequent occurrence in ANP and this can complicate
the clinical course of the illness.[5 ] Bang et al studied 361 patients with PFCs and found that DPD had a significant effect
on endoscopic management of PFCs as patients with DPD required more hybrid treatment,
reinterventions, and rescue surgery for achieving optimal clinical outcomes.[16 ] Another important issue is the risk of recurrence of PFC after successful endoscopic
treatment of PFCs in patient with DPD. Recurrence rates varying from 13 to 40% have
been reported previously in patients with DPD.[1 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[13 ]
[17 ]
[18 ] It has also been reported that maintaining the patency of iatrogenic transmural
fistula by leaving plastic stents in situ for an indefinite period significantly decreases
the risk of recurrence of PFCs.[1 ]
[3 ]
[4 ]
[7 ]
[8 ]
[9 ]
[18 ]
However, the issue of leaving transmural plastic stents for an indefinite period in
patients with DPD is debated in patients who have undergone initial drainage with
LAMS. Few studies have reported very low frequency of recurrence of symptomatic PFCs
in patients with DPD who had their initial PFC treated with LAMS and therefore, do
not support the practice of leaving transmural stents for an indefinite period.[2 ]
[12 ] Discordant results have been reported by other studies of PFC being drained initially
by LAMS where significantly high frequency of recurrence of PFC has been reported
in patients with DPD without transmural stents compared with patients with permanent
indwelling plastic stents.[1 ]
[5 ]
[13 ]
[17 ] These discordant results suggest that factors other than the use of LAMS determine
the risk of recurrence of PFC in patients with DPD.
Rana et al reported that 37% patients of DPD without a permanent indwelling transmural
plastic stent developed recurrent PFC.[9 ] All these patients with DPD had undergone successful transmural drainage of WON
with multiple plastic stents. The authors reported that patients who had distal disconnection,
post-ANP diabetes, as well as steatorrhea and pancreatic atrophy on imaging had low
risk of recurrence of PFC in patients with DPD and without permanent indwelling plastic
stents.[9 ] This observation suggests that patients with more extensive pancreatic necrosis
are less likely to develop symptomatic DPD because of significant loss of viable pancreatic
parenchyma upstream to the disconnection. Maatman et al also reported that patients
with more extensive necrosis (>50% necrosis) are less likely to develop symptomatic
DPD compared with patients with 30 to 50% parenchymal necrosis.[19 ] In the current study also, patients in the DEN group had significantly higher frequency
of extensive pancreatic necrosis compared with patients in no DEN group. This observation
suggests that patients with more extensive parenchymal necrosis are more likely to
need DEN, and this observation is in accordance with our previous results as well
as results from other studies.[20 ]
[21 ]
[22 ] The results of our current study also suggest that need for DEN is a surrogate marker
for extensive pancreatic necrosis, and these patients despite having presence of duct
disconnection are less likely to have symptomatic DPD because of lack of significant
amount of viable pancreatic parenchyma. This observation also explains that the recurrence
of PFC following successful endoscopic transmural drainage using LAMS in patients
with DPD without permanent indwelling transmural stent is low.
There are, however, many limitations to the study. First and foremost, it is a retrospective
study from a tertiary hospital and thus suffers from the inherent drawbacks of a retrospective
study, including the selection bias. Also, there is unequal distribution of subjects
in the comparing groups, and the sample size is also relatively small. This is however
expected, considering the rarity of patients of PFC undergoing endoscopic transluminal
drainage and not having long-term indwelling transmural stents. The study was conducted
in the unit with extensive experience in pancreatic endotherapy, and therefore, the
results may not be generalizable. Moreover, the follow-up was relatively shorter in
patients in the DEN group compared with patients not requiring DEN. This is expected
as DEN is a recent addition to the armamentarium and is being performed more frequently
in recent times only.
In conclusion, patients with WON and DPD treated with LAMS and requiring DEN seem
to be having low risk of developing recurrence of pain or PFC and therefore do not
require permanent indwelling transmural plastic stents. However, further, large sample
prospective studies are needed to confirm these results.
