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4 Acute Pancreatitis: Surgical Therapies
57
Fig. 4.5 (a–d) Coronal CT scan of the abdomen showing bilateral retroperitoneal walled-off
necrosis 3weeks after onset of pancreatitis, with associated uid and air within the necrosis, suggesting infected necrosis (a). This patient had features of sepsis with recurrent fever, leukocytosis,
and tachycardia. Bilateral retroperitoneal percutaneous drainage catheters were placed as part of a
step-up approach to management. Patient was subsequently taken for a staged
pneumoretroperitoneum- assisted VARD (PRA-VARD), starting with the left retroperitoneal
infected necrosis as shown in image b. A surgical drain is indwelling post left PRA-VARD procedure (b). Following recovery from the left PRA-VARD procedure, the patient was taken back to
the operating room for a right PRA-VARD procedure, and a surgical drain was placed (c). Patient
was subsequently discharged 10days later after drain removal. Follow-up 6weeks postoperatively
with CT showed complete resolution of the necrosis cavity (d)
Early Vs. Delayed Intervention forAcute
Peripancreatic Collections
As mentioned above, 80% of patients with acute pancreatitis have mild acute pancreatitis that resolves within 1week with basic supportive care [1, 15]. The remaining 20% develop moderately severe or SAP with associated organ dysfunction,
SIRS, and associated pancreatic and peripancreatic uid collections and necrosis.
These patients with SAP are usually systemically ill due to the multi-system inammatory response syndrome resulting from the severe pancreatitis [16, 17]. As a
58
O. Alser et al.
result, most of them are vulnerable to systemic decompensation from a second
pathophysiologic insult that may come in the form of superimposed infection on
pancreatic necrosis, acute bleeding from vascular erosion/pseudoaneurysm or operative intervention in the acute phase of SAP [16, 17].
As a result, a number of factors should be taken into account in managing these
acutely ill patients in a multidisciplinary team approach to minimize or prevent
patient deterioration [18]. Some of these factors include:
(a) The hemodynamic compromise and extent of organ and systemic compromise
due to severe acute pancreatitis, if any
(b) Patient’s associated comorbidities and suitability for general anesthesia
(c) Time since onset of acute pancreatitis pain
(d) Presence or absence of pancreatic necrosis
(e) Presence/absence of superimposed infection
The contribution of each of these factors to the decision-making on timing of
intervention is described in more detail in the Table4.2 below.
Table 4.2 The contribution of patient and pancreatitis factors to the decision-making on timing of
intervention for the management of pancreatic and peripancreatic uid collections and necrosis
Patient and
pancreatitis
factors Description Evaluation
Type and age of
pancreatic uid
collections
associated with
pancreatitis
(from onset of
pain)
Early (<2weeks)
PFCs are amorphous,
poorly dened, and
usually sterile. Patient
ill with systemic and
organ effects of acute
pancreatitis
Late (>4weeks) in
the course of
pancreatitis, the
patient has usually
recovered for the
SIRS response, any
PFCs will have
resolve, or walled-off
and localize
CT with IV contrast,
>1week from onset of
pain; look for associated
necrosis
CT with IV contrast.
Delineates viable and
non-viable pancreas and
its relationship to PFCs.
MRI with MRCP may be
useful
Intervention timing
recommendations
Delay intervention to
>4weeks from onset of
pain; allows patients to
recover, and PFCs to
spontaneously resolve or
wall-off
Most PFCs spontaneously
resolve and/or are
asymptomatic. Those that
need intervention will
have developed a mature
wall for safer intervention
(continued)
4 Acute Pancreatitis: Surgical Therapies
Table 4.2 (continued)
Patient and
pancreatitis
factors Description Evaluation
Pancreatic
necrosis
Infection of
pancreatic
necrosis
Not usually detected
in the rst 7days
from the onset of pain
Initially, necrosis is
patchy. Necrosis
evolves into
demarcated conuent
necrosis over time
A small proportion of
pancreatic necrosis
cases develop infected
necrosis, >75% of
infections occur
>2weeks from onset
of pain; worse
outcomes
SIRS from sepsis
difcult to distinguish
in the rst 2weeks.
Infection of necrosis
must be conrmed
before antibiotics
treatment by positive
blood culture or
presence of gas on
imaging
After the rst 14days,
clinical signs of
infection sufce for
diagnosing infected
necrosis while having
no other focus for
infection
CT with IV contrast:
Initial patchy
hypoattenuation in the
early stages, then evolves
into demarcated,
conuent necrosis after
the rst week from onset
of pain. Nonenhancement of the
pancreas on contrast CT
Pancreatic necrosis <40
Hounseld units
compared to normal
pancreas (100–150HU)
CT scan with/without
contrast: Necrosis with
pockets of air in it
Air in necrosis can be
due to gas-forming
bacteria, stulization to
the alimentary tract, or
instrumentation of the
necrosis cavity
Imaging with
intraluminal contrast may
help identify stulization
to alimentary tract
Imaging guided
aspiration of the necrosis
cavity with cultures is the
gold-standard to
diagnosis of infected
necrosis
59
Intervention timing
recommendations
Early on, developing
necrosis is patchy,
amorphous, and sterile.
Demarcates after the rst
1–2weeks from onset of
pain
Intervention if
superimposed infection or
local complications like
pseudoaneurysm with
bleeding, erosion of
nearby structures with
stulization
Understanding the timing
of development of
necrosis is critical to
decision-making on
intervention. APFC,
ANC, pseudocyst, and
WOPN are often confused
with each other, which is
inappropriate
management
Review of imaging is
necessary to differentiate
these four and accurately
diagnose each
Intervention by drainage
only for conrmed
infection of necrosis;
should follow the
STEP-UP approach
(continued)
60
Table 4.2 (continued)
Patient and
pancreatitis
factors Description Evaluation
Patient condition
and
comorbidities
Early in SAP, and due
to severe pancreatitis,
patients have
profound SIRS
sometimes with organ
dysfunction
Associated necrosis
worsens the patient
condition
Superimposed
infection causes
further deterioration
Patient’s
comorbidities can
contribute to worse
clinical outcomes
Extent of
hemodynamic,
pulmonary, and organ
compromise
determines the
prognosis
Early in the course of
SAP, clinical presentation
may be misinterpreted;
profound SIRS response
may cause high fevers,
leukocytosis, and
elevated inammatory
markers. Can be
mistaken for infected
necrosis when none is
present
Positive blood cultures
will differentiate these
two scenarios
Organ specic work-up
and invasive monitoring
will guide management
O. Alser et al.
Intervention timing
recommendations
Early intervention usually
necessary in critically ill
patients with infected
pancreatic necrosis;
STEP-UP approach
protocol best
Goal is to delay operative
necrosectomy until at
>4weeks from onset of
pain
Use of empiric antibiotics
without infected necrosis
is discouraged
Sterile Pancreatic Necrosis
About 20–30% of acute pancreatitis cases develop pancreatic necrosis. This occurs
as a result of several factors including pancreatic microcirculatory vasoconstriction,
reduced microvascular inow and outow, microvascular stasis, and TNF-alphainduced apoptosis and necrosis. All these initially lead to patchy areas of ischemia
early in the course of pancreatitis. This patchy necrosis may subsequently progress
to conuent pancreatic necrosis later on in the course of disease with clear demarcation between viable and necrotic tissue, which becomes apparent on imaging after
the rst week [19].
Pancreatic necrosis is often sterile, with no associated infection. However, a
small subset of cases develops superimposed infection. Sterile pancreatic necrosis
usually resolves spontaneously over time and rarely requires intervention. Sterile
necrosis can, therefore, be followed without intervention once the patient recovers
from acute pancreatitis and becomes asymptomatic.
Indications for intervention for sterile necrosis include persistent signs of systemic inammatory response syndrome, persistent unresolving pain, obstructive/
erosive complications involving the biliary or enteric tract by the necrosis, and general illness and unwellness after the acute pancreatitis (including inability to tolerate
oral intake, nausea, emesis, generalized fatigue, persistent fevers, etc.). These
patients’ symptoms often recover once the necrosis is debrided and cleared.
4 Acute Pancreatitis: Surgical Therapies
61
Infected Pancreatic Necrosis andSTEP-UP Approach
toManagement
Superimposed infection on pancreatic necrosis is associated with a 30–50% mortality rate and is virtually always an indication for intervention [18]. The diagnosis of
infected necrosis depends on the timing since the onset of acute pancreatitis. This is
because, in the rst 14days after onset of pain due to severe acute pancreatitis, it is
difcult to distinguish SIRS response from sepsis [20, 21]. Therefore, in patients
with suspected infection based on clinical signs of infection in the rst 14days but
without gas in the necrotic collection in contrast-enhanced CT scan, proof of infection usually by positive blood culture or presence of gas on contrast-enhanced computed tomography imaging is needed. The presence of gas in the pancreatic/
extra-pancreatic necrotic collection is an indicator of infection of the necrosis, irrespective of the source of the gas. This is because the gas in the necrotic collection is
present either from gas-forming bacterial infection or loss of integrity of the
bacteria- laden gastrointestinal tract that leads to bacterial contamination of the
necrosis [20].
Based on the PANTER trial, after the rst 14days from onset of acute pancreatitis, clinical signs alone are much more reliable at diagnosis of infection of necrosis.
Clinical criteria alone had a 91% accuracy in the diagnosis of infected necrosis. The
clinical criteria include persistent organ failure in patients admitted to the intensive
care unit or the persistence of two inammatory variables (temperature>38.5°C or
elevated C-reactive protein levels or leukocyte counts) during three consecutive
days in patients in a regular hospital room [20, 21].
Historically, intervention for infected pancreatic necrosis involved open necrosectomy via a bilateral subcostal or midline incision, with debridement of the
infected pancreatic necrosis, drainage of purulence, and placement of large bore
drains for postoperative continuous lavage of the cavity. Feeding tube access is considered as well at the completion of the procedure. This was associated with high
morbidity and mortality [20].
The optimal management strategies of infected pancreatic necrosis have evolved
in the past two decades. The PANTER trial by van Santvoort etal. compared patients
with infected pancreatic necrosis, who were randomized for open necrosectomy, or
a minimally invasive step-up approach, which consisted of percutaneous drainage
followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The
step-up approach had a reduced rate of the composite end point of major complications (new onset multi-organ failure or multiple systemic complications, perforation
of viscus or enterocutaneous stula or bleeding) of 40 vs. 69% (risk ratio with the
step-up approach, 0.57; 95% condence interval, 0.38–0.87; P=0.006). However,
the mortality rate did not differ signicantly (19 vs. 16%, P=0.70) [20]. This landmark study created a paradigm shift in the management of infected pancreatic
necrosis (Fig.4.7).
The key benets of using this step-up approach include the following:
62
O. Alser et al.
(a) Necrosectomy may be avoided: Percutaneous drainage may be all that is
needed in some patients to address the infected necrosis. From the PANTER
trial, 35% of patients were successfully managed by percutaneous catheter or
endoscopic drainage alone, without need for necrosectomy. This is hypothesized to be due to the drainage of the liquid portion (pus) of the infected contents, which is pus-under-pressure, and therefore decreasing and resolving the
pressurized translocation of the infected uid and bacteria into the systemic
circulation. Once the infected uid is drained and pressure relieved, the semisolid and solid necrosis tissue can be left in situ to resolve over time in 35% of
patients managed this way.
(b) Avoid “second-hit” on vulnerable patients: Percutaneous drainage allows for
postponement of major operative necrosectomy to a later time in the course of
disease. Therefore, a “second-hit” of pro-inammatory systemic reaction is
avoided on patients who are already critically ill and vulnerable earlier on in the
course of severe acute pancreatitis, often with signicant systemic effects from
SAP, infected necrosis and associated organ dysfunction and failure. Use of a
minimally invasive intervention decreases intervention-associated trauma and
stirring of additional systemic inammatory response. Based on the results of
the PANTER trial, this is therefore associated with lower morbidity and
mortality.
(c) Viable-pancreas-parenchymal-sparing treatment: Step-up approach allows
for a viable-pancreas-parenchymal-sparing treatment at a time when clear
demarcation of necrotic devitalized pancreatic tissue may not be complete early
in the course of SAP, and some of the presumably necrotic pancreatic parenchyma may potentially recover. Allowing for preservation of the potentially
recoverable pancreatic parenchyma likely explains the lower rates (7–17%) of
long-term new onset of pancreatic insufciency in patients managed by step-up
approach in the PANTER trial. Conversely, early maximal necrosectomy leads
to debridement and removal of potentially recoverable and viable pancreatic
tissue and therefore is associated with higher rates (33–38%) of new onset of
pancreatic insufciency.
(d) Minimize injury risk to critical structures: Early in the course of pancreatic
necrosis, the critical structures (splenic and mesenteric vessels, the alimentary
tract and retroperitoneal structures are intermixed with, and “bathing” in the
pancreatic necrosis collection, and the associated inammation, with no demarcation between these critical structures and the pathological tissue. Intervention
at this time risks injury to these structures with a higher morbidity and mortality. The postponement of operative necrosectomy to a later time (usually
>4weeks since onset of demarcated necrosis) allows for a mature thick wall to
develop around the necrosis, forming a protective interface between the necrosis cavity contents and the critical structures outside of the cavity including
major vessels, bowel and retroperitoneal structures (Fig.4.6a, b). The clear
demarcation by the mature thick wall allows for a safer debridement of the cavity with signicantly decreased risk of injury to the surrounding structures.
4 Acute Pancreatitis: Surgical Therapies
63
Fig. 4.6 Intraoperative
photos of the PRA-VARD
procedure for patient in
Fig.4.5. The Alexis
wound retractor is inserted
through the incision into
the necrosis cavity (a), and
a GelPort
system is used to achieve
wide insufation of the
necrosis cavity and
provides excellent
visualization of the
necrosis cavity (b) and
allows for a technically
easier and potentially safer
necrosectomy
®
laparoscopic
®
a
b
(e) Allow for technically easier intervention later: Delay in intervention allows
the necrotic tissues to be organized into a localized walled-off cavity (as
opposed to a widespread amorphous necrosis merging to nearby tissues), therefore allowing for a technically easier and safer necrosectomy.
Of the remaining 65% of patients who did not recover by percutaneous drainage
alone in the PANTER trial, even if they required necrosectomy after percutaneous
drainage, almost all (92%) of these patients were able to undergo a minimally invasive video-assisted retroperitoneal debridement (VARD) procedure. This indicates
that step-up approach allows a minimally invasive intervention for the majority of
patients with infected necrosis, and this represents a paradigm shift from the previous decade where open maximal necrosectomy was the standard approach [20].
The PENGUIN trial in 2012 by Bakker etal. soon followed PANTER trial to
directly compare surgical necrosectomy with endoscopic trans-gastric necrosectomy, a form of natural orice transluminal endoscopic surgery (NOTES), in 20
randomized patients. Endoscopic necrosectomy comprised of trans-gastric puncture, balloon dilatation, retroperitoneal drainage, and necrosectomy while surgical
necrosectomy comprised of video-assisted retroperitoneal debridement (VARD) or,
if not feasible, laparotomy. Post-processing pro-inammatory response as measured
by serum interleukin 6 (IL-6) levels was the primary end point while the composite
end point of major complications as dened in PANTER trial or death was the secondary end point. When compared with surgical necrosectomy, endoscopic necrosectomy reduced post procedural IL-6 level (p=0.004) and the composite clinical
64
O. Alser et al.
end point of death or major complications happened less frequently with endoscopic necrosectomy (20 vs. 80%, p=0.03) [22].
In another study, van Brunschot etal. in 2017 conducted a multicenter randomized superiority trial (TENSION) in 98 patients with infected necrotizing pancreatitis comparing the endoscopic step-up approach with surgical step-up approach. The
endoscopic approach comprised of endoscopic ultrasound-guided transluminal
drainage followed, if needed, by endoscopic necrosectomy while the surgical step up approach consisted of percutaneous catheter drainage followed, if necessary, by
video-assisted retroperitoneal debridement. The primary end point was a composite
of major complications as dened before or death during 6-month follow-up. The
study showed that the endoscopic step-up approach was not superior to the surgical
step-up approach as far as the primary end point was concerned (p=0.88), but the
rate of pancreatic stulae formation and length of hospital stay were lower in the
endoscopy group [23].
Based on information from the studies above, the current standard approach for
infected pancreatic necrosis is the step-up approach dened by catheter drainage,
followed, when necessary, by minimally invasive necrosectomy. In this approach,
catheter drainage is typically postponed till 4weeks following the onset of acute
pancreatitis with necrosis to allow for the development of WOPN. Controversies
exist whether earlier intervention for such patients could benet the current step-up
approach.
In the step-up approach, percutaneous drainage is often postponed until the
infected necrosis cavity becomes encapsulated by a “mature” wall of granulation
tissue (walled-off pancreatic necrosis, WOPN), a process that usually takes 4weeks
from onset of disease to complete. During this wait period, patients with infected
necrosis are usually managed with intravenous antibiotics, while waiting for WOPN
to develop. This may, in rare cases, lead to resolution of symptoms or reduce systemic illness, with the rationale being the postponement of invasive intervention
until the WOPN stage allows for lower morbidity and mortality. In theory, there are
a few downsides to this approach of delaying intervention until the WOPN stage,
including prolonged hospital stay, early and prolonged use of empiric antibiotics
contributes to the development of antibiotic resistance with increase in fungal infections, and increased healthcare costs. Furthermore, delaying intervention may be
associated with clinical deterioration of the patient, and mortality. The recently published POINTER trial investigated if immediate (<24h) catheter drainage in patients
with acutely infected pancreatic necrosis is superior to the current standard of stepup approach. Boxhoom etal. in 2021 published the data on a total of 104 randomly
assigned patients, indicating non-superiority of immediate drainage over postponed
drainage (comprehensive complication index: p= 0.90; death: relative risk 1.25,
95% CI—0.42–3.68) while patients assigned to the postponed-drainage strategy
needed fewer invasive interventions (catheter drainage and necrosectomy) with a
mean number interventions of 4.4 vs. 2.6 [21, 24]. In summary, the key ndings of
the POINTER trial were:
4 Acute Pancreatitis: Surgical Therapies
(a) Patients in the postponed-drainage group required fewer interventions for
infected necrosis.
(b) Antibiotic therapy was successful in 35% of patients in the postponed-drainage
group, these patients were successfully treated conservatively with antibiotics only.
(c) There was no difference in complications and mortality between the immediate
catheter drainage and postponed catheter drainage. As a result, immediate catheter drainage remains an option for patients who clinically deteriorate while on
conservative treatment with antibiotics only.
Therefore, postponed catheter drainage is still the ideal option if the patient can
tolerate delaying drainage intervention until the walled-off necrosis stage. However,
if a patient clinically deteriorates despite appropriate antibiotic treatment during the
waiting period, early catheter drainage can still be performed at any time.
The TENSION trial group published the 5–7years follow-up data from the same
trial (ex-TENSION) with similar end points. The trial revealed no difference in
achieving the primary end point (p=0.688) but fewer pancreatico-cutaneous stulae occurred in patients assigned to endoscopy group (8 vs. 34%) and fewer reinterventions took place for endoscopy group than surgery group (7 vs. 24%) [25].
Typical indications for intervention (radiological, endoscopic, or surgical) in
acute necrotizing pancreatitis include proven infected pancreatic and/or peripancreatic necrosis (IPN) [15, 26]. It may be indicated in clinically suspected IPN without
any documented IPN but with ongoing organ failure or failure to thrive for several
weeks after the onset of pancreatitis despite adequate medical management. A retrospective study on 164 such patients identied IPN in 42% of cases [26, 27].
Interventions in ANP may even be indicated in patients with organ compression
including gastric outlet obstruction, biliary or intestinal obstruction, and pain relative to the mass effect from the large WON though secondary infection remains a
major concern [26, 28, 29]. A less common scenario when intervention of ANP is
needed is abdominal compartment syndrome which may require radiological or surgical decompression without exploration of lesser sac and performance of the
necrosectomy at the same session to avoid bleeding and microbial inoculation into
sterile necrosis [26, 30, 31].
65
Detailed Management ofInfected Necrosis
Antibiotic Therapy
• For clinically suspected or documented infection as dened above, appropriate
targeted antibiotics must be initiated. According to the POINTER trial, up to
35% of these patients may recover with intravenous antibiotics alone. Patients
who clinically respond need no further intervention as long as they proceed to
recover. For non-responders or patients with infected necrosis who clinically
66
O. Alser et al.
deteriorate while on antibiotics, management should follow the step-up approach
with the next step being catheter drainage. With the latest advancement in mini-
mally invasive techniques, open necrosectomy is no longer the rst-line approach
to management of infected pancreatic necrosis. Minimally invasive techniques
include image-guided catheter drainage, endoscopic ultrasound-guided trans-
gastric/transduodenal drainage and necrosectomy, and laparoscopic/robotic
drainage and debridement [18].
Catheter Drainage
• Percutaneous or endoscopic catheter drainage is a key modality in the step-up
approach to management of patients with infected necrosis, and in up to 35%, it
is the only intervention needed and averts the need for subsequent necrosectomy.
Furthermore, catheter drainage may be useful in stabilizing infected necrosis
patients during the waiting period prior to the WOPN stage when they will then
undergo operative necrosectomy. The step-up approach is summarized in
Fig.4.7a below and Fig.4.5a–d [20].
Although the POINTER trial did not show superiority of immediate catheter
drainage over postponed catheter drainage, there was no difference in complication
rates or mortality between these two approaches. Therefore, immediate catheter
drainage is a good option for patients with infected necrosis in case of acute deterioration at any time during the wait period to WOPN.
Catheter drainage is usually performed percutaneously under image-guidance
(ultrasound or CT) by interventional radiology team, and sometimes by the surgical
team. Catheter drainage is considered successful when there is full patient recovery
after catheter drainage of the “pus under pressure” while the solid necrosis tissue is
left in situ. In these cases, the solid infected necrosis does not need to be subsequently removed in at least 35% of infected necrosis cases.
According to the PANTER trial protocol, additional drainage catheters can be
placed or existing drain(s) repositioned/re-adjusted if needed in the rst 3–6days
after initial catheter placement, to achieve optimal and complete drainage of the
“pus under pressure” (Fig. 4.7b). In patients managed by this protocol in the
PANTER trial, sepsis was able to be resolved in 62–84% of cases, therefore allowing for postponement of denitive necrosectomy until mature walled-off necrosis
stage when a safer and technically easier necrosectomy could be performed.
In the remaining 65% of cases of infected necrosis with unsuccessful catheter
drainage, percutaneous catheter drainage serves as a bridge during the wait period
to subsequent denitive operative necrosectomy at the WOPN stage.
Pre-procedure Preparation Pearls for Catheter Drainage
• A thorough review of the patient’s preoperative imaging is critical to inform the
intervention, including the anatomy around the infected necrosis cavity.
Percutaneous catheter drainage relies on availability of a safe “window” devoid