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Walled-Off Pancreatic Necrosis
41
Percutaneous Drainage
Percutaneous drainage (PD) can be used as initial or complementary
treatment. PD is not usually effective as definitive treatment [12, 23] although
it is occasionally useful if the patient presents clinical, analytical and
radiological improvement [31]. It can also be used as a bridging technique to
decompress retroperitoneal fluid collections or if the intention is to continue
with other more invasive treatments or to allow the stabilization of patients
with sepsis before surgical debridement [12, 20, 21, 23, 32, 33, 35]. The main
indications for PD are as a first step combined with endoscopic procedures and
puncture in order to rule out infection [1, 15, 21].
Incomplete percutaneous drainage of the WOPN and the infection may
lead to complications [12]. PD is likely to be more successful in patients
without pancreatic duct pathology, since in patients with this condition it may
predispose to a pancreaticocutaneous fistula [36].
The solid component of WOPN limits the management of patients with
PD, and so the resolution rate is low [18, 21]. Percutaneous therapy alone has
a worse success rate and prolonged length of stay, more complications, greater
need for surgery and higher mortality compared with combined therapy [1,
23]. PD is only effective if multiple large drains are used with frequent
upsizing, removal of solid debris, and aggressive irrigation.
Endoscopic Drainage
Endoscopic drainage (ED) of WOPN is one of the most frequently used
therapeutic approaches. Among its multiple advantages, it uses the puncture
route with the shortest distance between the gastrointestinal tract and the wall
of the WOPN [8].
At experienced centers, virtually all pancreatic fluid collections in contact
with the stomach or duodenum are treated through an endoscopic approach;
surgical drainage procedures are reserved for unsuccessful ED attempts,
recurrence of collections after ED, or when the criteria for ED or PD are not
met [12].
ED is usually performed (with or without endoscopic necrosectomy) when
the collection is technically accessible and when there is no evidence of
hemorrhage [12]. The choice of a transpapillary or transmural approach
depends on the size of the collection, its relationship with the pancreatic duct,
its location, and underlying disease [11]. ED should be performed in patients
under deep sedation or general anesthesia. The use of broad-spectrum
antibiotics is recommended in those who were not previously receiving
antibiotics for suspected infection. All procedures are performed with
V. Arteaga Peralta, A. A. Medina Velasco, R. de la Plaza Llamas et al.
42
insufflation of carbon dioxide (CO
2
) since fatal gas embolism has been
reported after ED [29].
ED is contraindicated in encapsulated collections located more than 1 cm
from the gastrointestinal tract [11], and the presence of neovascularization due
to portal hypertension is considered a relative contraindication [11, 37].
Factors that make ED more difficult to perform are:
Abundant pancreatic necrosis in the collection to be drained [12]; this
means that therapy with ED alone is insufficient to treat WOPN [38].
Peripancreatic necrosis extending into the paracolic gutter due to the
lack of continuity with the central necrosis. Size alone is not
considered a risk factor for failure [20, 39].
Currently it is debated whether the presence of a pseudoaneurysm in
the WOPN is a contraindication for drainage. Some authors consider
that if it is previously embolized, ED can be performed [11, 12].
In 1992, Grimm et al. first described endoscopic ultrasound-guided
drainage (ED-US). Since then, conventional endoscopy has been shown to be
inferior to ED-US in numerous studies and has been rendered obsolete for
drainage of pancreatic collections [11, 37]. ED of pancreatic pseudocysts is
simpler and more effective than draining of WOPN [11, 35]. The use of ED-
US allows a better study of collections and may lead to a modification of
management in 5%-9% of cases, either by providing an alternative diagnosis
or by achieving resolution of the collection [11].
In ED-US, as we have stated, the puncture route is the shortest distance
between the gastrointestinal tract and the cyst wall. The route can be chosen
under US guidance, that is, under direct vision to facilitate the process [8, 40].
But it is essential that the puncture is in contact with the WOPN. The
transgastric route is the most frequent access (73%-85%), but the duodenal
route [1, 15, 18, 19] is also used. ED-US is safer than a simple endoscopic
drainage because the cysts can be punctured after checking the absence of
blood vessels with Doppler flow in the puncture area [8, 29]. This is especially
useful in cases in which the WOPN presents associated portal hypertension
with obstruction of the portal vein or splenic vein with secondary collateral
circulation around the stomach. ED-US also allows direct endoscopic access
inside the collection in order to perform debridement. Between three and six
sessions may be needed to achieve complete debridement, which is
inconvenient for patients [1, 12, 15, 16, 18, 23]. The response rate of infected
WOPN to ED-US alone is currently reported to be roughly 40-50% [8].
Walled-Off Pancreatic Necrosis
43
ED-US presents complication rates between 1% and 18% [35], severe
morbidity in 10-26% of cases (the most common being bleeding and
perforation), mortality of 2.7% and the need for laparotomy in 0-23% [1, 15,
16, 19, 20, 21, 35].
Several devices have been used to improve the drainage of the necrotic
content. WOPN drainage with plastic prostheses such as the ones used in
treating pseudocysts may be insufficient, due to their small internal diameter
[8]. Therefore, fully covered self-expanding metal stents combined with an
axial stent with an internal pigtail are being used more and more frequently,
achieving a success rate of 87.8% and an adverse event rate of 9.5% (Figure 2)
[38]. The self-expanding metal stent with an inner diameter of 1 cm has a
lower rate of occlusion and needs only a single insertion of the stent due to its
large diameter, thus offering clear advantages over conventional stents. Some
authors insert a double pigtail stent through the metal stent to prevent
migration [27]. One of the criticisms of metal stents is their displacement
when the cyst size decreases, which may cause the stent to touch the cyst wall
and lead to bleeding [8]. Other technical options used to improve WOPN
emptying are the placement of a single pigtail stent along with a nasocystic
tube to allow irrigation of the cavity, an approach that has obtained good
clinical outcomes [12, 23, 38], and percutaneous drainage of the WOPN
without emptying, followed by ED using the standard technique for treating
pseudocysts (double pigtail stents) or coated stents.
In this way, the percutaneous route with large drains is used to irrigate the
WOPN, while the stents allow necrotic debris to pass into the gastric cavity
[12, 23].
In cases of multiloculated cysts, even without contact between the
cavities, Mukai et al. described an efficient method called transluminal single
gateway transcystic multiple drainages (SGTMD) for cases with sub-cavities
located away from the gastrointestinal tract [8], although currently drainage
with multiple internal passages is preferred [5, 19]. Another modification in
these patients is the use of multiple transluminal stents in order to increase
drainage in multiseptated necrotic collections.
This can be done either by creating several transluminal pathways if the
collections do not seem to communicate with each other, or by placing
multiple double pigtail stents and a nasocystic catheter in different subcavities
via the same route.
V. Arteaga Peralta, A. A. Medina Velasco, R. de la Plaza Llamas et al.
44
This method has proved superior to the conventional technique with a
single stent and can be combined with direct necrosectomy. In some cases, it
may avoid the need for endoscopic debridement or open surgery [8, 27,
29, 37].
A potential complication whenever any type of stent is used is the
possibility of migration, which has an incidence of between 1% and 2% [19].
External migration merely requires repetition of the procedure, but internal
migration of the stent represents a serious complication and a major
therapeutic challenge. It is advisable to remove the stent as early as possible to
avoid closure of the previously created fistula [11].
Figure 2. CT: WOPN treated by endoscopic ultrasound guided drainage (prosthesis and
pigtail).
Endoscopic Transluminal Necrosectomy
Currently, it is very difficult to predict the cases of WOPN that can be
managed efficiently and safely without necrosectomy. In cases of large
anfractuous collections with considerable amounts of necrosis, necrosectomy
is generally required in order to induce the healing process. Necrosectomy is
usually performed when the initial endoscopic drainage has not been effective
[11]. Classically, necrosectomy was performed by surgery, but in 2000 Seifert
described a new concept termed endoscopic transluminal necrosectomy
(ETN), developed as a minimally invasive alternative to surgical treatment
[41]. ETN requires the creation of a large caliber transmural orifice between
the gastric or duodenal area and the lumen of the cyst to allow passage of a
standard endoscope into the cystic cavity and thus remove the pancreatic
necrosis through the communication made. ETN has proved more effective for
Walled-Off Pancreatic Necrosis
45
WOPN than simple ED [1, 15, 18], and is successful in around 90% of cases,
compared with 50% when standard ED is used [1, 15, 18, 19, 20].
Conventional endoscopic snares and dormia baskets can be used to
carefully extract necrotic debris from the stomach or duodenum. An average of
four repeated endoscopic sessions are needed to completely mobilize the
necrotic tissue. Complications such as perforation (4%) and bleeding (18%)
may occur during ETN [27, 29, 42]. In the GEPARD study, a multicenter
study of ETN after acute pancreatitis with long-term follow-up, a procedure-
related adverse event rate of 26% was observed, with a mortality rate of 2.1%
[5, 28]. It is recommended that ETN be performed two or three days after first
draining in order to evaluate the adhesion of the cyst wall to the stomach wall,
since performance of necrosectomy after drainage increases the risk of the
stent migrating into the peritoneal cavity and causing a perforation. If clinical
findings improve with drainage alone there is no need for necrosectomy, and
the most common complication of ETN (bleeding caused by balloon dilatation
of the fistula) is avoided. The delay in dilatation reduces the risk of bleeding
[8, 29]. A retrospective multicenter study published in 2011 of 104
symptomatic patients with WOPN treated with ETN recorded successful
resolution in 95 of 104 patients (91%), with a mean resolution time of 4.1
months. BMI> 32 was a risk factor for failure of the procedure. The team
concluded that ETN is effective for treating WOPN and has an acceptable
safety profile [15, 18]. A systematic review published in 2014 also showed
ETN to be a safe and effective minimally invasive treatment; over 80% of
patients were successfully treated with endoscopic management and rates of
mortality and complications were 6% and 36% respectively. However, most of
the studies included were retrospective and the methodological quality was
moderate to low [42]. Another meta-analysis and systematic review conducted
in 2014 also aimed to assess the value of ETN for treating WOPN. In the
pooled analysis, ETN emerged as an efficient procedure with a successful
resolution rate of 81.8% and a mean of four procedures per patient. Significant
complications such as bleeding, perforation of organs and sepsis were reported
in 21.3% of cases. Mean hospital stay after ETN was 32.85 days. Despite the
success rate mentioned above, surgery could not be avoided in 13%. It appears
that the sickest patients were the ones who most frequently needed surgery.
One limitation of this review, as the authors acknowledged, was that most
studies included were retrospective case series with small sample sizes. There
were also significant technical differences between the studies [39].
V. Arteaga Peralta, A. A. Medina Velasco, R. de la Plaza Llamas et al.
46
ETN is considered successful when the fever and inflammatory response
recede. Endoscopic examination shows complete removal of necrotic tissue
and good exposure of granulation tissue. By contrast, in cases where it is
difficult to control the infection even with necrosectomy, ETN is unlikely to
be sufficient [8]. It has been suggested that infection after ETN is due to the
occlusion of the stent caused by solid debris and subsequent bacterial
colonization.
Surgery
Necrosectomy via laparotomy has been the standard treatment of infected
necrosis for decades. The classical approach is to reach the pancreas located in
the retroperitoneum via a laparotomy, and to remove the necrotic tissue by
blunt dissection. The aim is to preserve as much viable pancreatic tissue as
possible, thereby minimizing the risk of postoperative bleeding or pancreatic
fistula. Several surgical techniques have been applied to perform necroscopy:
open surgery, closed surgery, planned reoperation or continuous postoperative
lavage [1, 16, 20, 21, 31]. However, the complication rate (25-55%) and
mortality (5-14%) are high [8, 23].
Initially, these were the necrosectomy techniques applied in WOPN, but
today techniques similar to the ones performed via endoscopic approaches are
gaining ground. For example, open surgical drainage can be accomplished via
cyst gastrostomy, cystenterostomy (direct drainage or via a Roux limb) or in
selected cases by resection [12]. Open surgery is reserved for those patients
who do not meet the criteria for percutaneous or endoscopic treatment [35],
with complications of endoscopic and/or laparoscopic treatment, or in cases in
which these treatments have failed [1, 20, 21].
In a bid to reduce the morbidity and mortality rates recorded with
laparotomy, several minimally invasive approaches have been developed. For
example, laparoscopic necrosectomy is progressively replacing classical
necrosectomy for both AP and WOPN. Laparoscopic approaches for
necrosectomy can be classified according to the access route (transperitoneal,
retroperitoneal or transgastric) [1, 12, 35] and the equipment used (endoscopy,
laparoscopy or nephroscopy). Minimally invasive surgical necrosectomy is
technically feasible and the results are acceptable [1, 16, 43]. The main
stumbling block of the laparoscopic approach is the possibility of incomplete
or unsuccessful drainage [1, 21].
Walled-Off Pancreatic Necrosis
47
The most commonly used technique is a hybrid approach known as video-
assisted retroperitoneal debridement (VARD). First, the collection is drained
percutaneously. Then, via a 5 cm subcostal incision in the left side near the
exit point of the PD, the drainage is followed closely towards the collection.
After opening the collection and removing the liquid and solid debris, a 0-
degree laparoscopic camera is introduced into the necrotic cavity. The camera
is inserted through a single laparoscopic port, which is placed directly through
the incision. Carbon dioxide is infused through the percutaneous drain to
inflate the cavity. After surgery, continuous lavage is started using two large-
diameter drains. This technique allows vigorous debridement of the necrotic
cavity and usually requires only a single procedure [8, 31].
The PANTER (Patients with acute necrotizing pancreatitis) study of 88
patients compared primary necrosectomy by laparotomy vs the step-up
approach (percutaneous drainage and VARD if required). The study found a
significantly lower rate of the composite endpoint of major morbidity or death
in the step-up group (40% vs 69%; p = 0.006). New-onset multiple organ
failure was also significantly less frequent in the step-up group (12% vs 40%;
p = 0.002) [30, 31]. The PENGUIN (Pancreatitis endoscopic transgastric vs
Primary necrosectomy in patients with Infected Pancreatic Necrosis) trial in
2012 compared endoscopic necrosectomy vs surgical necrosectomy (VARD
and laparotomy) in 20 patients (ten in each arm). The points evaluated were
the pro-inflammatory response after the procedure, as measured by IL-6 levels,
the clinical endpoints such as major complications (new onset of multiple
organ failure, intra-abdominal bleeding, enterocutaneous fistula, or pancreatic
fistula) or death. The study found that ETN reduces IL-6 levels compared with
surgical necrosectomy (p = 0.004). The clinical endpoint occurred less
frequently after endoscopic necrosectomy (20% vs 80% in the surgical
necrosectomy). Endoscopic necrosectomy did not cause new onset multiple
organ failure (0% vs 50%), and reduced the rate of pancreatic fistula (10% vs
70%) [44].
A multicenter randomized controlled trial (the TENSION trial) is
currently underway comparing the endoscopic approach (ETN) and minimally
invasive surgical approach after performing PD in both cases. The variables
studied are deaths, major complications, hospital stay and associated costs in
patients with infected necrotizing pancreatitis [45]. At the time of writing,
neither method has demonstrated superiority. Although these studies are
specific to AP rather than to WOPN, we feel that they are likely to establish
the bases for future therapeutic approaches.
V. Arteaga Peralta, A. A. Medina Velasco, R. de la Plaza Llamas et al.
48
FOLLOW-UP
The presence of a multidisciplinary medical team is essential in the
treatment of WOPN. Only a multidisciplinary team including a surgeon,
gastroenterologist, radiologist and intensivist can provide proper care at all
stages of the disease.
Hospitals lacking a team of this kind should promptly transfer the patient
to another facility [31]. Patients with WOPN can be best treated applying a
multimodal approach and follow-up, including a combination of ETN, PD and
VARD when necessary.
Several authors recommend radiological monitoring with CT or MRI
repeated every three to six months, or sooner if the patient develops symptoms
such as abdominal pain, chills, jaundice, early satiety, or fever [12].
THE FUTURE
Some authors suggest that the amount of necrosis is a major predictor of
successful outcome for the drainage of a pancreatic collection, and classify
these collections according to the percentage of necrotic waste in their
composition or as indicated by radiological images [35]. They propose a
classification system according to the necrotic intracystic component: less than
20%, between 20% and 50%, and more than 50%. For collections with <20%,
transmural drainage with one or two double pigtail plastic stents or lumen-
apposing metal stents or trans-papillary drainage through ERCP is indicated if
the pancreatic duct is involved. For collections with internal necrosis between
20% and 50% a similar treatment is recommended, increasing the number of
stents or providing transmural drainage with a nasocystic drain. In collections
with internal necrosis of more than 50%, endoscopic necrosectomy should be
performed with the placement of multiple plastic stents or a lumen-apposing
metal stent, with or without transcutaneous ultrasound drainage depending on
size, location and content [35]. This new algorithm is an interesting proposal
and should now undergo validation studies. Robotic surgery is an attractive
though as yet undeveloped option for the treatment of WOPN [8].
In general, further research into WOPN is required to be able to make
recommendations regarding nutritional management, indications for
necrosectomy, and the approach to the pancreatic duct. These are questions
that remain unanswered at present.
Walled-Off Pancreatic Necrosis
49
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