Seminar

Acute pancreatitis
Lotte Boxhoorn, Rogier P Voermans, Stefan A Bouwense, Marco J Bruno, Robert C Verdonk, Marja A Boermeester, Hjalmar C van Santvoort*,
Marc G Besselink*

Lancet 2020; 396: 726–34 Acute pancreatitis is an unpredictable and potentially lethal disease. The prognosis mainly depends on the
This online publication has been development of organ failure and secondary infection of pancreatic or peripancreatic necrosis. In the past 10 years,
corrected. The corrected version treatment of acute pancreatitis has moved towards a multidisciplinary, tailored, and minimally invasive approach.
first appeared at thelancet.com
Despite improvements in treatment and critical care, severe acute pancreatitis is still associated with high mortality
on November 4, 2021
rates. In this Seminar, we outline the latest evidence on diagnostic and therapeutic strategies for acute pancreatitis.
*Joint senior authors
Department of
Gastroenterology and
Introduction limit of normal, or (3) findings consistent with acute
Hepatology (L Boxhoorn MD, Acute pancreatitis is the most common gastrointestinal pancreatitis on imaging (contrast-enhanced CT [CECT],
R P Voermans MD) and disease requiring acute admission to hospital, with an MRI, or abdominal ultrasound; figure 1).7,8 If typical
Department of Surgery annual inci­dence of 34 per 100 000 person-years in high- clinical and laboratory findings are present, additional
(Prof M A Boermeester MD,
Prof M G Besselink MD),
income countries.1 The disease is characterised by a local imaging is not required to confirm the diagnosis of
Amsterdam Gastroenterology and systemic inflammatory response and has a varying acute pancreatitis. Nonetheless, imaging can be
Endocrinology Metabolism, clinical course. Most patients present with mild acute indicated in the early phase when there is diagnostic
Amsterdam UMC, University of pancreatitis, which is self-limiting and usually resolves uncertainty. Necrotising pancreatitis can commonly
Amsterdam, Amsterdam,
Netherlands; Department of
within 1 week. Approximately 20% of patients develop only be detected on imaging from 72 to 96 h after onset
Surgery, Maastricht University moderate or severe acute pancreatitis, with necrosis of the of symptoms.7
Medical Center+, Maastricht, pancreatic or peripancreatic tissue or organ failure, or
Netherlands both, and a substantial mortality rate of 20–40%.2–5 Aetiology
(S A Bouwense MD);
Department of
Treatment of acute pancreatitis has undergone Current guidelines recommend identification of the
Gastroenterology and considerable changes in the past 10 years—ie, the causes of the disease as early as possible.7 Gallstones (45%)
Hepatology, Erasmus introduction of a multidis­ ciplinary, tailored approach and alcohol abuse (20%) are the most frequent causes of
University Medical Center,
including minimally invasive endoscopic, radiological, acute pancreatitis in most high-income countries.9
Rotterdam, Netherlands
(Prof M J Bruno MD); and surgical interventions for infected pancreatic and The least common causes are medication, endoscopic
Department of peripancreatic necrosis and improvements in critical retrograde cholangiopancreatography (ERCP), hypercal­
Gastroenterology and care have reduced both morbidity and mortality.6 This caemia, hypertriglyceridaemia, infection, genetics, auto­
Hepatology (R C Verdonk MD)
Seminar provides an over­view of current evidence on immune diseases, and (surgical) trauma. Standard initial
and Department of Surgery
(Prof H C van Santvoort MD), the diagnosis, classification, and treatment of acute diagnostic testing of acute pancreatitis include evaluation
St Antonius Hospital, pancreatitis, and addresses new developments and of medical history (eg, alcohol intake and medication,
Nieuwegein, Netherlands; unanswered research questions. family history, and known gallstone disease), physical
and Department of Surgery,
examination, laboratory tests (eg, liver enzymes, serum
University Medical Center
Utrecht, Utrecht, Netherlands Diagnosis and aetiology triglycerides, and calcium), and transabdominal ultra­
(Prof H C van Santvoort) Clinical presentation sound. If no causal factor is identified by these initial
Correspondence to: Patients with acute pancreatitis commonly present with tests, an extensive evaluation is indicated to reduce the
Prof Marc G Besselink, severe upper abdominal pain. The diagnosis of acute risk of disease recurrence.
Department of Surgery,
pancreatitis is based on the fulfilment of two of three
Amsterdam Gastroenterology
Endocrinology Metabolism, criteria: (1) upper abdominal pain, (2) serum amylase Prediction of severity
Dutch Pancreatitis Study Group, or lipase (or both) of at least three times the upper Given the unpredictable course of acute pancreatitis, it is
Amsterdam UMC, University of not surprising that a plethora of studies has attempted
Amsterdam,
to predict the clinical course of the disease. Clinical
Amsterdam 1100 DD,
Search strategy and selection criteria and biochemical scoring systems include the Acute
Netherlands
m.g.besselink@ The most recent international evidence-based guidelines on Physiology and Chronic Health Evaluation II, Ranson’s
amsterdamumc.nl Criteria for Pancreatitis Mortality or Modified Glasgow
acute pancreatitis were used as the main source for this
Seminar. An additional systematic literature search done on Acute Pancreatitis Severity Score, and individual serum
July 1, 2019, in the Cochrane Library, PubMed, and Embase tests (ie, C-reactive protein and blood urea nitrogen).10,11
databases, focused on studies published after the 2013 The scoring systems are frequently used for research
International Association of Pancreatology and American pur­poses, but are without clinical relevance because of
Pancreatic Association guidelines were released. We used the their low predictive value.12
search terms “acute pancreatitis” and “necrotising Current guidelines recommend monitoring the
pancreatitis”, and selected publications from the past 5 years, presence of systemic inflammatory response syndrome
but did not exclude commonly referenced and relevant older or organ failure at admission for a minimum of 48 h
publications or guidelines. to predict the development of a severe course of the
disease.7,13

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Classification of severity
The severity of acute pancreatitis can be defined as mild,
moderately severe, or severe according to the revised
Atlanta classification (panel).8 This classification divides
disease severity into three groups on the basis of the
presence of organ failure and local (eg, pancreatic or
peripancreatic fluid collections or portal vein thrombosis)
or systemic complications (eg, exacerbation of pre-
existing comorbidities).
According to the revised Atlanta classification, acute
pancreatitis is classified as mild in the absence of local or
systemic complications and organ failure.8 Patients with
mild acute pancreatitis are generally treated conser­
vatively and are usually discharged within 1 week. Acute
pancreatitis is classified as moderately severe in the case
of local complications or systemic complications, and in
the absence of persistent organ failure.8 Patients with
moderately severe pancreatitis might require prolonged
specialist care. And lastly, acute pancreatitis is classified
as severe in the case of (persistent) single or multiple
organ failure, which is associated with mortality rates
between 20% and 40%.2–5
Alternatively, acute pancreatitis can be classified
according to the determinant-based classification. In
contrast to the revised Atlanta classification, the deter­
minant-based classification differentiates between four
categories on the basis of the presence of organ failure
(transient vs persistent) and the status of pancreatic or
peripancreatic necrosis (sterile vs infected; panel).14
Local complications
The most frequent local complications associated with
acute pancreatitis are pancreatic or peripan­creatic fluid
collections.8 A clear distinction should be made between
collections associated with interstitial oedematous
pancrea­ titis and collections arising from necrotising
pancreatitis.8 It is important to recognise the different
morphological characteristics of pancreatic or peri­
pancreatic fluid collections because they also require a
different treatment approach. Consultation of an expe­
rienced abdominal radiologist can be highly valuable.
In the case of interstitial oedematous pancreatitis,
collections are referred to as acute pancreatic or peri­
pancreatic fluid collections, which develop during the first
4 weeks of the disease and contain a homogeneous liquid
content (figure 2). Generally, these collections resolve
spontaneously over time. If these collections persist
beyond 4 weeks after onset of acute pan­creatitis, they are
referred to as pancreatic pseudocysts (figure 2). Pancreatic
pseudocysts are surrounded by a well defined wall. These
collections are thought to arise from a rup­ture of the main
pancreatic duct or one of its side branches in the absence
of pancreatic or peripancreatic necrosis.
In necrotising pancreatitis, collections during the first
4 weeks after onset of the disease are referred to as acute
necrotic collections (figure 2). Acute necrotic collections
contain variable amounts of fluid and necrotic debris.
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Seminar
Acute pancreatitis (at least two criteria)
(1) Upper abdominal pain
(2) Serum amylase or lipase (or both) >3 times the
upper limit of normal
(3) Typical findings on imaging
Aetiology
• Medical history
• Family history
• Medication and alcohol use
• Laboratory tests (liver enzymes, triglycerides, calcium)
• Transabdominal ultrasound
Initial treatment Treatment of necrotising pancreatitis
• Goal-directed fluid resuscitation with Ringer’s • Minimally invasive step-up approach in cases of
lactate solution proven or highly suspected infected necrotising
• Nutritional support after 72 h pancreatitis
• ERCP in cases of cholangitis or persistent • Intervention preferably delayed until the phase of
cholestasis walled-off necrosis
• No role for prophylactic antibiotics or probiotics • Assess for disrupted or disconnected pancreatic
• Maximal supportive care on ICU in cases of organ duct following necrotising pancreatitis
failure
Prevention of recurrence
• (Presumed) idiopathic pancreatitis:
• Repeat abdominal ultrasound
• Endoscopic ultrasound
• Mild biliary pancreatitis: cholecystectomy during admission
• Severe biliary pancreatitis: cholecystectomy after 6 weeks
Figure 1: Treatment algorithm for acute pancreatitis
ERCP=endoscopic retrograde cholangiopancreatography. ICU=intensive care unit.
Panel: Classification of disease severity
Definitions according to the revised Atlanta classification
• Mild acute pancreatitis: no local* or systemic†
complications and organ failure
• Moderately severe acute pancreatitis: local or systemic
complications, transient organ failure (<48 h), or both
• Severe acute pancreatitis: local or systemic complications,
and persistent single or multiple organ failure (>48 h)
Definitions according to the determinant-based
classification
• Mild acute pancreatitis: no pancreatic or peripancreatic
necrosis and no organ failure
• Moderate pancreatitis: sterile pancreatic or peripancreatic
necrosis, transient organ failure (<48 h), or both
• Moderately severe acute pancreatitis: infected pancreatic or
peripancreatic necrosis or persistent organ failure (>48 h)
• Severe acute pancreatitis: infected pancreatic or
peripancreatic necrosis and persistent organ failure (>48 h)
*Local complications: pancreatic or peripancreatic fluid collections, splenic and portal
vein thrombosis, intestinal ischaemia and gastric outlet dysfunction. †Systemic
complications: exacerbation of pre-existing comorbidity.
Necrosis can involve the pancreatic parenchyma alone
but is often accompanied by the presence of peripancreatic
necrosis. In approximately 50% of patients, necrosis is
 Seminar
A B
C D
Figure 2: Local complications defined according to the revised Atlanta criteria
(A) Acute peripancreatic fluid collection: interstitial oedematous pancreatitis at less than 4 weeks. (B) Acute
necrotic collection: necrotising pancreatitis at less than 4 weeks. (C) Pancreatic pseudocyst: interstitial oedematous
pancreatitis at more than 4 weeks. (D) Walled-off necrosis: necrotising pancreatitis at more than 4 weeks.
See Online for appendix solely located outside of the pancreas, without necrosis
of the pancreatic parenchyma.8,15,16 When acute necrotic
collections mature and encapsulate, usually after 4 weeks,
they are referred to as walled-off necrosis (figure 2).8,17
Other local complications of acute pancreatitis might
include abdominal compartment syndrome, intestinal
ischaemia, gastric outlet dysfunction, splenic or portal vein
thrombosis, and pseudoaneurysm. It goes beyond the
extent of this Seminar to describe the treatment of all these
complications, but in brief, abdominal compartment
syndrome and intestinal ischaemia mostly require sur­gical
intervention. Additionally, bleeding from a pseudo­
aneurysm usually requires coiling by the interventional
radiologist. Splenic or portal vein thrombosis can usually
be treated conservatively. Ultimately, endoscopic trans­
luminal drainage might be required if gastric outlet
dysfunction occurs as a result of persistent pancreatic or
peripancreatic fluid collection.13
Initial treatment
The initial treatment of acute pancreatitis is supportive and
includes close monitoring of vital signs, fluid balance, pain
relief, and nutrition. Patients are best managed by a multi­
disciplinary team, which typically includes a gastroenter­
ologist, surgeon, (interventional) radiologist, and dietitian.
Fluid resuscitation and pain management
The systemic immune response that typically accompanies
acute pancreatitis leads to extravasation of fluid in the third
space, which could result in hypovolaemia, hypo­perfusion,
organ failure, and ultimately death. Therefore, adequate
fluid resuscitation is essential to correct for fluid loss,
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maintain adequate intravascular volume, and increase
organ perfusion or microperfusion. Optimal fluid therapy
with close monitoring of the vital signs early in the disease
course improves the clinical outcome (appendix pp 1–3).18,19
However, an undirected fluid replacement can be detri­
mental and potentially lethal, as shown in two randomised
con­trolled trials.20,21 Although evidence regarding the
optimal rate of fluid infusion is scarce, current guidelines
advise intravenous fluid therapy with 5–10 mL/kg per h
until a heart rate of less than 120 per min, mean arterial
pressure between 65 mm Hg and 85 mm Hg, and urinary
output of more than 0·5–1·0 mL/kg per h are reached.7
Infusion with Ringer’s lactate solution seems to be
associated with a decreased chance of developing systemic
inflammatory response syndrome and reduced C-reactive
protein con­centrations, when compared with an infusion
with normal saline, and therefore, Ringer’s lactate solution
should be the preferred choice.7,22–25
Severe abdominal pain is the most predominant and
distressing symptom for patients and requires adequate
pain medication according to WHO’s pain treatment
ladder.26 No particular analgesic is superior in terms of
efficacy or safety.27 However, opioids could decrease
the need for supplementary analgesics.28 It has been
suggested that the perfusion of the pancreas is improved
through the administration of epidural anaesthesia.29 A
multicentre retrospective study found that the use of
epidural analgesia in patients with acute pancreatitis,
admitted to the intensive care unit, was associated with
reduced 30-day mortality compared with patients who did
not use epidural analgesia (2% vs 17% mortality).30 Further
prospective studies on the use of epidural anaesthesia for
acute pancreatitis are needed before it can be advised as
routine care.
Nutrition
Optimal nutritional support maintains the intestinal
barrier function, inhibits bacterial translocation, and
decreases systemic inflammatory response syndrome.31
The multicentre randomised PYTHON trial32 found that
early enteral tube feeding within 24 h did not reduce the
rate of infection (25% vs 26%) or mortality (11% vs 7%)
when compared with on-demand feeding. Therefore,
enteral tube feeding can be initiated once patients have
insufficient caloric intake after 72 h. Although it is often
believed that nasogastric feeding is associated with an
increased risk of aspiration compared with nasojejunal
feeding, two small randomised trials showed that
nasogastric feeding was safe and well tolerated.33,34 When
compared with enteral feeding, routine parenteral
nutrition is not advised because of its associated risk of
complications, need for surgery, and mortality.35,36
Role of ERCP in biliary pancreatitis
Acute biliary pancreatitis develops as a result of transient
obstruction of the bile and pancreatic duct by gallstones
or biliary sludge, or both. The role of ERCP in reducing

the severity of acute biliary pancreatitis has been the
focus of discussion for many years. Several studies have
shown that ERCP is not effective in patients with
predicted mild pancreatitis, mainly because the potential
benefits do not outweigh the procedural risks.37 Current
guidelines recommend that urgent ERCP is only indi­
cated in patients with biliary pancreatitis and concomitant
cholangitis, and might be considered in patients with
persistent cholestasis.7,13,38 The multicentre randomised
APEC trial39 reported that routine urgent ERCP with
biliary sphincterotomy (<24 h) did not reduce mortality
or severe complications in patients with predicted severe
biliary pancreatitis when compared with conservative
treatment (38% vs 44%). In conclusion, it seems
that ERCP, particularly in the early phase, should be
reserved for patients with acute biliary pancreatitis
who have concomitant cholangitis. A more appropriate
approach than the use of ERCP, using an early endoscopic
ultrasound and only followed by ERCP in the case
of proven choledocholithiasis or sludge, is under
investigation.
Prevention of infectious complications
In acute pancreatitis, early relevant infections, such as
pneumonia or bacteraemia, as well as a later secondary
infection of pancreatic or peripancreatic necrosis, could
result in sepsis and have a substantial effect on clinical
outcome.40
Secondary infection of pancreatic or peripancreatic
necrosis is believed to result from bacterial translocation of
microorganisms from the intestinal lumen.41 Nonetheless,
prophylactic use of antibiotics does not reduce the risk
of secondary infection.42,43 Moreover, administration of
prophylactic antibiotics is associated with the development
of multidrug-resistant bacteria and fungal superinfection.44
Therefore, antibiotics are only advised as treatment of
confirmed or clinically suspected secondary infection.7,45
The multicentre randomised PROPATRIA trial46 found
a higher mortality rate in patients who received enteral
probiotics than those who did not. Therefore, the current
guidelines do not advise the administration of probiotics
for the treatment of acute pancreatitis.7
Management of local complications: interstitial
oedematous pancreatitis
Indication and timing for intervention
Generally, acute pancreatic or peripancreatic fluid
collections in interstitial oedematous pancreatitis resolve
spontaneously in the first few weeks after onset of disease
and rarely require intervention.47 Development of a
pancreatic pseudocyst is rare after acute pancreatitis.
Generally, indication for the intervention of pancreatic
pseudocysts is determined by the presence of symptoms,
such as gastric outlet obstruction or abdominal pain.48
Current guidelines do not indicate what size the
pseudocysts need to be before intervention is necessary;
however, pseudocysts larger than 6 cm often cause
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Seminar
symptoms.47 Drainage of pancreatic pseudocysts is
preferably done after the collection is encapsulated to
reduce the risk of complications, which takes approxi­
mately 4–6 weeks from the onset of the disease.8,47
Intervention strategies
Although different drainage modalities for drainage
of pancreatic pseudocysts are available, endoscopic trans­
luminal drainage is preferred when a pseudocyst can be
reached endoscopically.47,49 If a pseudocyst communicates
with the main pancreatic duct, additional transpapillary
drainage might be needed.47 Nevertheless, the role of
combined endoscopic transluminal drainage and trans­
papillary drainage for pancreatic pseudocysts remains
debated, mainly because no additional benefit has been
shown in terms of recurrence rates.50
Management of local complications: necrotising
pancreatitis
Indication and timing for intervention
The majority of patients with sterile pancreatic or
peripancreatic necrosis can be treated conservatively,
regardless of the size and extension of the collections.7,51
Drainage of sterile pancreatic or peripancreatic necrosis
can introduce iatrogenic infection, with consequent
exposure to additional interventions and procedure-
related risks.52,53 Intervention should only be considered
in the small subgroup of patients with persistent symp­
toms, such as abdominal pain, gastric outlet obstruction,
jaundice, or failure to thrive at least 4–8 weeks after onset
of the disease. Earlier intervention might not be required
because most collections will resolve spontaneously over
time.7,54
In contrast, secondary infection of peripancreatic
necrosis nearly always requires invasive intervention.3,7
Secondary infection becomes apparent by gas configu­
rations in the necrotic collection on CECT in approxi­
mately half of the patients.17 In the other half of patients,
clinical signs of infection are often sufficient to diagnose
secondary infection of pancreatic or peripancreatic
necrosis. A positive Gram stain or culture of the necrotic
collection, obtained by transabdominal fine-needle aspi­
ration, can be required in case of diagnostic uncertainty.
However, the downside of fine-needle aspiration in this
scenario is the 25% false negative rate.7
The first step in treating patients with infected
necrotising pancreatitis is the administration of broad-
spectrum antibiotic therapy.7,45 A small proportion of
patients can be managed with supportive care and
antibiotics alone, without the need for additional invasive
interventions.3
Current guidelines advise to postpone catheter drainage
for several weeks to await the stage of walled-off necrosis.7,8,54
The process of maturation and encapsulation of the
collection facilitates safe interventions and lowers the risk
of complications.55,56 However, in the era of minimally
invasive interventions, the advantage of delay might be
 Seminar
less relevant than it was when more invasive procedures
were prevalent.17,57 Secondary infection of pancreatic or
peripancreatic necrosis can already occur in the first
3 weeks after onset of disease, and long-term administration
of antibiotics might lead to increased incidence of fungal
infections and antibiotic resis­tance.17,40,55 In a retrospective
study of 193 patients, endoscopic intervention before the
stage of walled-off necrosis did not increase complications.
However, the early approach was associated with increased
mortality when compared with the conventional approach
(13% vs 4%).58 Additionally, an interna­tional survey among
expert pancreatologists showed that 45% of experts
preferred or indicated to do catheter drainage directly
after diagnosing secondary infection of pancreatic or
peripancreatic necrosis.59 The randomised POINTER trial60
could lead to changes in the views on the optimal timing of
intervention.
Intervention strategies
In the past 10 years, traditional open surgery for infected
necrotising pancreatitis has almost completely been
replaced by minimally invasive procedures.
The step-up approach, which consists of percutaneous
catheter drainage or endoscopic transluminal drainage,
followed by minimally invasive necrosectomy only when
clinically required, is the current standard treatment.7
The multicentre randomised PANTER trial61 showed that
a step-up approach in patients with infected necrotising
pancreatitis reduced the combined primary endpoint of
major complications and mortality when compared
with open necrosectomy (40% vs 69%). This difference
persisted during follow-up (44% vs 73%), without an
increased need for additional invasive interventions in
the step-up approach group.62
The step-up approach can be done both surgically and
endoscopically. The two different approaches have been
compared with each other in two randomised trials.63,64
First, the multicentre randomised TENSION trial63 found
Figure 3: Endoscopic transluminal drainage with a lumen-apposing metal stent
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no significant difference in mortality and major morbidity
between the endoscopic step-up approach and the
surgical step-up approach (43% vs 45%). Nonetheless,
mean hospital stay was shorter (53 days vs 69 days) and
patients (5% vs 32%) treated according to the endoscopic
step-up approach developed less pancreatico-cutaneous
fistulas. Subsequently, the single-centre randomised
MISER trial64 compared minimally invasive surgery
(laparoscopic or video-assisted retroperitoneal debride­
ment) to the endoscopic step-up approach. This trial
showed no difference in mortality (9% with the endo­
scopic step-up approach vs 6% with minimally invasive
surgery) and new-onset organ failure (6% vs 9%).
However, the endoscopic step-up approach resulted in a
reduced rate of major complications (12% vs 41%), and,
in particular, less likelihood of enteral and pancreatico-
cutaneous fistulae (0% vs 28%). In conclusion, the
endoscopic step-up approach has gradually become the
preferred treatment for infected necrotising pancreatitis,
although the endoscopic step-up might not be feasible in
all patients.65 If necrotic collections extend to the flank or
pelvic region, (additional) percutaneous catheter drainage
might be needed. The preferred route for percutaneous
catheter drainage is through the retroperitoneum, so the
drain can be used as guidance for minimally invasive
retroperi­toneal necrosectomy (ie, video-assisted retroperi­
toneal debridement and sinus tract endoscopy) in a later
stage. The option of combined endoscopic transluminal
and percutaneous catheter drainage, which is also known
as dual-modality drainage, should not be overlooked in
patients with large collections extending into the paracolic
gutters or the pelvic region.66–69 Ideally, each patient with
infected necrotising pancreatitis is discussed and treated
by a multidisciplinary team with sufficient experience in
both approaches.
Lumen-apposing metal stents
Endoscopic treatment of infected necrotising pan­
creatitis has evolved rapidly over the years. Lumen-
apposing metal stents (LAMS) were developed in 2011
as an alternative to the traditionally used double-pigtail
plastic stents (figure 3). The potential benefits of
LAMS include a larger lumen (15–20 mm in diameter)
compared with double-pigtail plastic stents (7–10 Fr in
diameter). Theoretically, the larger diameter allows for
improved drainage of necrotic tissue in the gastro­
intestinal tract. Moreover, LAMS facilitate endoscopic
transluminal necrosectomy. The best avail­able evidence
on LAMS originates from one randomised trial that
compared the efficacy of endoscopic trans­ luminal
drainage with LAMS to double-pigtail plastic stents in
patients with infected and symptomatic sterile walled-
off necrosis.70 The study found no difference in the
median number of total procedures (two vs three),
readmissions, and length of hospital stay. Although
endoscopic treatment with LAMS was associated with
higher procedural costs, overall treatment costs were

equal. Nevertheless, it is noteworthy that a high rate of
LAMS-related adverse events was observed. Therefore,
the latest consensus guidelines recommend either
LAMS or double-pigtail plastic stents for endoscopic
transluminal drainage, and withdrawal of LAMS after
4 weeks to minimise the risks of complications.13,70–72 It
has been suggested that additional double-pigtail plastic
stents could be placed through LAMS to decrease the
risks of stent migration or occlusion.73–75 Nevertheless,
the high quality evidence for this approach is still scarce.
The theoretical advantage of LAMS for endoscopic
drainage of pancreatic pseudocysts is still debated. A
meta-analysis did not find improved outcomes after
endoscopic transluminal drainage of pancreatic pseudo­
cysts with metal stents.76 Therefore, double-pigtail plastic
stents should be preferred for pancreatic pseudocysts,
given their excellent safety profile and the possibility to
leave double-pigtail plastic stents in situ.
Disrupted and disconnected pancreatic duct
Necrosis of the pancreatic parenchyma frequently results
in a partially disrupted or completely disconnected
pancreatic duct. Disrupted or disconnected pancreatic
duct is believed to occur in approximately 20–40% of
patients with acute necro­ tising pancreatitis, although
reliable data are scarce.6,63,77,78 Pancreatic duct integrity can
be evaluated by a (secretin-enhanced) mag­netic resonance
cholangiopancreatography (MRCP).13,79 There are no
guidelines on the treatment of disrupted or disconnected
pancreatic duct. A widely accepted approach is endoscopic
transluminal drainage of the associated fluid collections
with double-pigtail plastic stents, which can be left in situ
indefinitely to maintain internal drainage to the stomach.13
This advice is based on the findings of one randomised
trial that found that a lower recurrence of pancreatic fluid
collections in which trans­luminal stents were left in situ
(0% vs 38%).80 Combined endoscopic transluminal
drainage and rou­tine stenting of the pancreatic duct is
not recommended for pancreatic duct disconnection, but
transpapillary bridging can be considered in patients with
pancreatic duct disruption.13
Pancreatic endocrine and exocrine insufficiency
Acute pancreatitis can be affected by the impaired
exocrine and endocrine pancreatic function. According to
a meta-analysis of 32 studies involving 1495 patients, the
pooled prevalence of pancreatic exocrine insufficiency
is 19% after mild pancreatitis and 33% after severe
pancreatitis.81 Clinical manifestations of pancreatic
exocrine insuf­ficiency include abdominal discomfort,
steatorrhoea, and impaired digestion, leading to nutrient
malabsorption and malnutrition. Therefore, patients with
pancreatic exocrine insufficiency are at risk of developing
a deficiency of fat-soluble vitamins (A, D, E, and K).
Faecal elastase-1 concentrations or, if available, ¹³C-mixed
triglyceride breath test, can identify the diagnosis
of exocrine pan­ creatic insufficiency.82,83 Treatment of
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Seminar
pan­creatic exocrine insufficiency mainly consists of oral
admin­istration of exogenous pancreatic enzymes, both to
reduce the clinical symptoms of steatorrhoea and to
prevent metabolic complications.
Additionally, special attention should be paid to the
development of endocrine pancreatic insufficiency.
A meta-analysis of 24 prospective studies, involving
1102 patients, showed that 23% of patients were diag­
nosed with diabetes following the first episode of acute
pancreatitis.84 Moreover, it is assumed that these patients
have a higher risk of mortality and admission to hospital
than patients with type 2 diabetes.85 The development of
diabetes secondary to acute pancreatitis is, according to
the most recent guidelines,86 classified as diabetes of the
exocrine pancreas, and also referred to as postpancreatitis
diabetes. Fasting glucose, glycated haemoglobin A1c, and
oral glucose tolerance testing are considered appropriate
diagnostic tools.87 Although there are no guidelines
available specifically focusing on the treat­ ment of
postpancreatitis diabetes, treatment typically used for
type 2 diabetes, including lifestyle adjustments, is
generally advised.88,89
In conclusion, both endocrine and exocrine pancreatic
dysfunction are common consequences of acute pan­
creatitis and should be monitored closely to prevent
delays in diagnosis and treatment.
Prevention of recurrence
Approximately 20% of patients with acute pancreatitis
develop recurrent attacks of pancreatitis.90,91 After mild
biliary pancreatitis, cholecystectomy during the same
hospital admission is strongly advised to prevent disease
recurrences.7 This advice is based on the multicentre
randomised PONCHO trial,92 in which same-admission
cholecystectomy was safe and substantially reduced the
rate of recurrent gallstone-related complications and
mor­ tality when compared with an elective chole­
cystectomy (5% vs 17%). Moreover, same-admission
cholecystectomy decreased overall costs.93 However,
evidence for the optimal timing of cholecystectomy in
patients with necrotising biliary pancreatitis is scarce.94,95
It is advised to delay cholecystectomy until necrotic
collections have resolved, or if they persist beyond 6 weeks
and only when the procedure can be done safely, taking
into account the location of the remaining collections.7,94
Although ERCP with sphinc­terotomy decreases but does
not eliminate the risk of recurrent biliary pancreatitis,
cholecystectomy is also advised in these patients.96
Other important risk factors for recurrence of acute
pancreatitis, as well as for progression to chronic
pancreatitis, are alcohol consumption and smoking.91,97
Alcohol abstinence after the first disease episode protects
against recurrence of disease.98–100
The cause of acute pancreatitis remains unclear
in approximately 15–25% of patients after standard
diagnostic tests.101–104 Several causes of acute pancreatitis
might be missed with such tests. The first step is to
 Seminar
repeat the transabdominal ultrasound after clinical
recovery because gallstones and biliary sludge could be
missed on initial evaluation. Additionally, the sensitivity
and diagnostic accuracy of repeated transabdominal
ultrasound are higher than the first one.7,105 A repeated
transabdominal ultrasound is also a non-invasive and
cost-effective strategy compared with other modalities.
Hereafter, endoscopic ultrasound is advised to assess for
a biliary cause, as well as the presence of pancreatic
neoplasms and chronic pancreatitis.7,103,104,106 However,
the exact role of endoscopic ultrasound in this setting
should be identified. After a recurrence of presumed
idiopathic acute pancreatitis, (secretin-enhanced) MRCP
is advised to identify anatomical anomalies, if not
already visualised by endoscopic ultrasound.7 Genetic
counselling should be considered in patients with
recurrent attacks of idiopathic acute pancreatitis.7 Gen­
etic mutations in PRSS1, the gene encoding trypsin-1,
are seen in most patients with hereditary acute
pancreatitis.107
Future research perspectives
Many questions regarding the most optimal treatment of
acute pancreatitis remain. Most importantly, research is
needed on pharmacological agents or strategies to inhibit
the early response of systemic inflammatory response
syndrome and prevent subsequent organ failure. Also,
the optimal type and rate of fluid therapy should be
elucidated. To date, the best timing of invasive inter­
vention in infected necrotising pancreatitis (ie, early vs
postponed) remains unclear. Furthermore, the safety and
cost-effectiveness of LAMS for the endoscopic step-up
approach of patients with necrotising pancreatitis should
be clarified. And lastly, future research should devise the
most optimal diagnostic and treatment algorithm to
prevent recurrent pancreatitis and related complications
such as disrupted or disconnected pancreatic duct.
Contributors
LB coordinated the project under the direct supervision of MGB and
HCvS. LB did the literature search and drafted the manuscript.
RPV, SAB, MJB, RCV, MAB, HCvS, and MGB coauthored the writing of
the manuscript. All authors approved the final manuscript.
Declaration of interests
RPV has received research support from Boston Scientific and acted as a
consultant for Boston Scientific. MJB has received research support from
Boston Scientific, Cook Medical, Pentax, and 3M, and acted as a
consultant for Boston Scientific, Cook Medical, Pentax, and Mylan.
MAB has received research support from Johnson & Johnson, Acelity–
KCI, Bard, Ipsen, New Compliance, and Mylan, and acts as a consultant,
instructor, or speaker for Johnson & Johnson, Acelity–KCI, Bard, Gore,
and Smith & Nephew. MGB has received research support from Ethicon,
Medtronic, Intuitive, and Mylan. LB, SAB, RCV, and HCvS declare no
competing interests.
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