This document summarizes a review of the pathogenesis, diagnosis, and surgical management of severe acute pancreatitis. It discusses the rising incidence of the disease and reviews two main scoring systems used to determine severity (Revised Atlanta criteria and Determinant-based system). For infected pancreatic necrosis, the current preferred procedures are minimally invasive necrosectomy or endoscopic necrosectomy over open necrosectomy due to better outcomes. The paradigm is shifting toward initially conservative management with catheter drainage and using videoscopic debridement rather than immediate open necrosectomy.

1. Severe acute pancreatitis
Hepatobiliary Pancreat Dis Int，Vol 16，No 2 • April 15，2017 • www.hbpdint.com • 155
Review Article
Author Affiliations: Department of General Surgery, University Hospital
Ayr, Ayr, KA6 6DX, UK (Portelli M and Jones CD)
Corresponding Author: Mark Portelli, MD, Department of General Sur-
gery, University Hospital Ayr, Dalmellington Road, Ayr, KA6 6DX, UK
(Email: markportellicaruana@gmail.com)
© 2017, Hepatobiliary Pancreat Dis Int. All rights reserved.
doi: 10.1016/S1499-3872(16)60163-7
Published online December 28, 2016.
BACKGROUND: Severe acute pancreatitis is a subtype of
acute pancreatitis, associated with multiple organ failure and
systemic inflammatory response syndrome. In this qualitative
review we looked at the principles of pathogenesis, classifica-
tion and surgical management of severe acute pancreatitis. We
also looked at the current shift in paradigm in the manage-
ment of severe acute pancreatitis since the guideline developed
by the British Society of Gastroenterology.
DATA SOURCES: Studies published between 1st January 1991
and 31st December 2015 were identified with PubMed, MED-
LINE, EMBASE and Google Scholar online search engines us-
ing the following Medical Subject Headings: “acute pancreati-
tis, necrosis, mortality, pathogenesis, incidence”and the terms
“open necrosectomy and minimally invasive necrosectomy”.
The National Institute of Clinical Excellence (NICE) Guide-
lines were also included in our study. Inclusion criteria for our
clinical review included established guidelines, randomized
controlled trials and non-randomized controlled trials with a
follow-up duration of more than 6 weeks.
RESULTS: The incidence of severe acute pancreatitis within
the UK is significantly rising and pathogenetic theories are
still controversial. In developed countries, the most common
cause is biliary calculi. The British Society of Gastroenterology,
acknowledges the Revised Atlanta criteria for prediction of se-
verity.A newer Determinant-based system has been developed.
The principle of surgical management of acute necrotizing
pancreatitis requires intensive care management, identifying
infection and if indicated, debridement of any infected ne-
crotic area. The current procedures opted for include standard
surgical open necrosectomy, endoscopic necrosectomy and
minimally invasive necrosectomy. The current paradigm is
shifting towards a step-up approach.
CONCLUSIONS: Severe acute pancreatitis is still a subject of
grey areas in its surgical management even though new stud-
ies have been recorded since the origin of the latest UK guide-
lines for management of severe acute pancreatitis.
(Hepatobiliary Pancreat Dis Int 2017;16:155-159)
KEY WORDS: severe acute pancreatitis;
acute pancreatitis;
necrosis;
mortality;
pathogenesis;
incidence;
open necrosectomy and minimally invasive
necrosectomy
Introduction
P
ancreatitis is defined as an inflammatory process
where autodigestion occurs due to erratic activa-
tion of trypsin with resultant zymogen activation
within the pancreas.[1-3]
Patients can go on to develop
severe acute pancreatitis. The widely understood defini-
tion is that of an acute pancreatitis in association with
multiple organ failure and systemic inflammatory re-
sponse syndrome. In most cases necrotic foci are noted
within the pancreatic tissue.[4-6]
Located within the ret-
roperitoneum, the pancreas is well protected from both
environmental and mechanical injury.[2]
Severe acute
pancreatitis can have several etiologies with gallstones
and alcohol being the most prevalent in presentations.[3]
In the majority of patients, the condition resolves with-
out complications, however it can cause substantial com-
plications and mortality in up to 25% of those affected
with hospitalization periods in an intensive care unit be-
yond 2 weeks.[7, 8]
Studies show a decreasing mortality.[9]
The incidence of mortality changes between different so-
cioeconomic population groups.[10, 11]
In this qualitative
review we looked at the principles of pathogenesis, clas-
sification and surgical management of severe acute pan-
creatitis. We also looked at the current shift in paradigm
in the management of severe acute pancreatitis since the
Severe acute pancreatitis: pathogenesis,
diagnosis and surgical management
Mark Portelli and Christopher David Jones
Ayr, UK

2. Hepatobiliary & Pancreatic Diseases International
156 • Hepatobiliary Pancreat Dis Int，Vol 16，No 2 • April 15，2017 • www.hbpdint.com
guideline developed by the British Society of Gastroen-
terology.[12]
There is a lot of discussion about whether
patients with severe acute pancreatitis should undergo
invasive surgical procedures.
Methods
Studies published between 1st January 1991 and 31st De-
cember 2015 were identified with PubMed, MEDLINE,
EMBASE and Google Scholar online search engines
using the following Medical Subject Headings: “acute
pancreatitis, necrosis, mortality, pathogenesis, incidence”
and the terms “severe acute pancreatitis, open necrosec-
tomy and minimally invasive necrosectomy”. The Na-
tional Institute of Clinical Excellence (NICE) Guidelines
were also included in our study. Inclusion criteria for our
clinical review included established guidelines, random-
ized controlled trials and non-randomized controlled tri-
als with a follow up duration of more than 6 weeks. The
literature search was performed independently by both
authors. In duplicate and independently, we extracted
data on the population, epidemiology, pathogenesis, di-
agnosis and management of severe acute pancreatitis.
Results and discussion
A total of 39 papers were recorded and analyzed. In our
study we reviewed 6 retrospective studies, 14 prospec-
tive studies, 14 systematic reviews, 2 meta-analyses and
3 guidelines. Each study was individually reviewed and
similarities and differences between studies were ob-
served and documented.
Epidemiology and pathogenesis
The British Society of Gastroenterology reports
that the incidence of acute pancreatitis in the UK ranges
between 150 and 420 cases per million population, with
the incidence significantly rising over the past decade.[12]
About 20% of affected patients develop severe acute pan-
creatitis.[4]
Many causes of severe acute pancreatitis have been
recorded in the literature but the pathogenetic theories
are still controversial. The risk of severe acute pancre-
atitis increases due to several factors including genetic,
environmental and metabolic factors.[2]
In developed
countries, the most common causes include choledocho-
lithiasis and alcohol excess, accounting for 75%-85% of
cases.[7, 13]
Alcohol lowers the threshold for trypsin activa-
tion within the pancreatitis, causing cellular necrosis.[14]
Interestingly numerous factors including age, gender,
obesity, number of attempts to cannulate papilla and
poor emptying of pancreatic duct, increase the likeli-
hood of the condition.[7]
Multiple adaptive and protective mechanisms have
been reported which prevent the onset of pancreatitis.
Disruption of such mechanisms can amplify the suscep-
tibility of the patient towards developing severe acute
pancreatitis.[2]
Studies have recorded gene variants which
result in such a loss of adaptive mechanisms includ-
ing human cationic trypsinogen [PRSS1], cymtripsin
C [CTRC], carboxypeptidase A1 [CPA1] and serine
protease inhibitor, Kazal type 1 [SPINK1] mutations.[15]
The duct cells can express sensors within the luminal
surface such as protease-activated receptors 1 and 2
[PAR1, PAR2] which detect trypsin and its activity. These
provide protective mechanisms. Other molecules such
as P2Y purinoreceptor 2 [P2Y2], P2X, ligand-gated ion
channel 4 [P2X4] and P2X ligand-gated ion channel 7
[P2X7] recognize calcium concentration. When these are
activated, secretion of fluid flushes the damaging fluid
into the duodenum. Defect in these receptors can result
in an inadequate protective mechanisms, thereby increas-
ing the risk of developing severe acute pancreatitis.[15]
A
study by Papachristou et al suggests that a single nucleo-
tide pleomorphism in the gene producing monocyte
chemotatctic protein-1, predicted a systemic inflamma-
tory response causing severe acute pancreatitis associated
with a high mortality.[16]
Cystic fibrosis transmembrane conductance regulator
[CFTR] gene mutations noted predominantly in patients
with cystic fibrosis significantly increase the susceptibil-
ity to pancreatitis. In a study by Pezzilli et al, 12.2% of
patients diagnosed with acute pancreatitis had CFTR
variants.[17]
Outlining severity
Two severity scoring systems have been identified in
the literature which include the Revised Atlanta crite-
ria and the Determinant-based Classification. They are
both based on local and systemic factors.[18]
The British
Society of Gastroenterology, acknowledges the Revised
Atlanta criteria for prediction of severity.[12]
The Revised Atlanta criteria are based on a multifac-
torial scoring system and predictive factors of severity.[17]
According to these criteria, within the first 24 hours, in-
dicators of severity include: clinical suspicion, a raised
BMI, pleural effusions and a raised Acute Physiology and
Chronic Health Evaluation II [APACHEII] Score.[12, 19]
After the first 24 hours, other indicators include: persist-
ing organ failure and/or an Imrie score of >3. A worse
severity score is also predicted if the C-reactive protein
is >150 mg/L or if biomarkers such as interleukin (IL)-8,
IL-6, procalcitonin, IL-10 and IL-1 beta-receptor antago-

3. Severe acute pancreatitis
Hepatobiliary Pancreat Dis Int，Vol 16，No 2 • April 15，2017 • www.hbpdint.com • 157
nist are raised.[12, 19]
Further scores for estimation of severity have been
developed, the most popular of which include the Ran-
son and Imrie scores. These have a sensitivity of 80%
at 48 hours.[18]
Such scores identify whether the patient
would require further management in an intensive care
setting.
A newer system for scoring severity is the Determi-
nant-based system and is a measure of actual severity.
This system was developed due to the newer imaging
modalities and a better understanding of the high risk
of organ failure in patients with pancreatitis. This scor-
ing system is based on identification of sterile or infected
pancreatic necrosis and signs of organ failure.[20]
Serum biomarkers such as urinary trypsin activation
peptide and serum amyloid A have been looked at as po-
tential early markers for prediction of severity of severe
acute pancreatitis.[19]
Surgical management of necrotizing pancreatitis
The principle of surgical management of acute nec-
rotizing pancreatitis requires intensive care management,
identifying infection and if indicated, debridement of
any infected necrotic areas.[21]
Invasive procedures for severe acute pancreatitis can
be indicated in biliary pancreatitis, infected pancreatic
necrosis, massive hemorrhage, sterile pancreatic ne-
crosis, drainage of pancreatic abscess and symptomatic
organized necrosis.[22-24]
The current consensus is that a
diagnosis of biliary pancreatitis requires a laparoscopic
cholecystectomy at the point of diagnosis or within 2
weeks of diagnosis. This may relieve the obstruction and
therefore improves the chance of successful resolution of
severe acute pancreatitis without resorting to procedures
with higher risk of complications.[12]
Initial management of severe acute pancreatitis
requires continuous monitoring because of the risk of
superadded bacterial infections in a necrosed pancreas.
Bacterial infection occurs in 3%-7% of all cases of pan-
creatitis.[25]
About 10%-50% of patients with pancreatic
necrosis develop a superadded bacterial infection.[11, 12, 26]
In these cases infection typically presents after 2-3 weeks
from the point of presentation.[25]
In view of this, some
randomized controlled studies have explored the role
of prophylactic antibiotics with results being inconclu-
sive.[12, 27, 28]
Definitive diagnosis of infective pancreatitis requires
the use of CT imaging with or without a positive fine
needle aspiration for bacteriology.[11, 12]
Patients with
persistent pain or features suspicious of underlying sep-
sis with greater than 30% necrosis confirmed radiologi-
cally should undergo fine needle aspiration.[12]
Without
treatment, mortality in such group of patients has been
reported as high as 80%.[29]
Prior to the guideline by the
British Society of Gastroenterology, the general consen-
sus was that infected necrosis is an indication for surgical
treatment or interventional drainage.[12]
If less than 30%
of pancreatic tissue is necrotic with fluid collections, this
can be managed by minimally invasive necrosectomy.[21]
Recent data showed that surgical procedures can be
avoided. A meta-analysis by Mouli et al showed that 64%
of patients who were diagnosed with infected pancre-
atic necrosis had successful resolution with conservative
management with a mortality rate of 12%. The current
paradigm is shifting towards a conservative approach.[30]
Surgery in pancreatic necrosectomy must usually
be delayed for 14 days in order to allow demarcation of
the necrosum, unless the condition can be resolved by
elimination of the cause, such as in the case of cholecys-
tectomy for gallstone induced pancreatitis.[23]
Early surgery is only opted for proven infected nec-
rotizing pancreatitis. In fact mortality rates of up to 65%
have been noted with early surgery in severe acute pan-
creatitis.[11, 31]
Patients with severe necrotizing pancreati-
tis would therefore eventually undergo surgical debride-
ment with the ideal time being set at the third or fourth
week from the onset of disease.
The choice of surgical procedure is at present very
arguable and is mainly based on the facilities and surgi-
cal ability of the surgeon performing the procedure.[11]
The current procedures opted for include the standard
surgical open necrosectomy, endoscopic necrosectomy
and minimally invasive necrosectomy.
This approach to remove the infected necrotic tis-
sue was associated with a high rate of complications
with studies noting between 34%-95% of procedures
with complications. Mortality results in several studies
are between 6% and 50%.[11, 20, 21, 32, 33]
Considering these
findings one could explain why the interest in open ne-
crosectomy is losing favor. It is noted in the literature
that preference is shifting towards the safer procedure of
minimally invasive necrosectomy.[11]
In a study by Bak-
ker et al, endoscopic necrosectomy showed better results
in terms of pro-inflammatory response and clinical end
point identified by recording IL-6 levels which were
noted to decrease after endoscopic procedures when
compared to open surgery with significant values on cor-
relation.[33]
Castellanos et al[34]
states that all patients undergo-
ing translumbar retroperitoneal endoscopy showed good
results with the procedure. They were noted to avoid
subsequent surgical operations for debridement. Similar
studies have showed high success rates.[35]
The NICE guidelines list two types of endoscopic

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necrosectomies, namely the percutaneous retroperito-
neal endoscopic necrosectomy and the endoscopic trans-
luminal necrosectomy.[36, 37]
In an interview done to Baron, despite the risk of
complications, with proper expertise 90% of patients can
have complete resolution of the necrotizing pancreatitis
with endoscopic necrosectomy. However, such a proce-
dure needs to be performed in specialised centers.[38]
Sileikis et al[21]
noted that minimally invasive necro-
sectomy is recorded as being the best option in treating
necrotising pancreatitis. Such patients have less risks of
complications including reduced incidence of bacteremia,
multiple organ failure and post-operative complications.
They also have a reduced operating table to discharge
time.[32]
Unfortunately as with the endoscopic approach,
the procedure requires multiple sittings in order to resect
the whole necrosum.[20]
The current paradigm is shifting towards a step-up
approach, where catheterization for drainage is followed
by videoscopic assisted retroperitoneal debridement.[11, 25, 39]
van Stantvoort et al[40]
noted that when compared to pri-
mary open necrosectomy, the step-up approach provided
less complications. Removal of pressure and infected
fluid from around the pancreas together with intrave-
nous antibiotics can avoid further invasive management
and any remaining necrotic tissue would be removed by
the patient’s own immune system.[39]
videoscopic assisted
retroperitoneal debridement tends to follow the initial
drainage if the symptomatology persists.
Conclusion
Severe acute pancreatitis causes significant mortality
rates. This study is a qualitative review of the literature.
Unfortunately it is difficult to encompass the whole
wealth of knowledge on the topic of severe acute pan-
creatitis in the literature. We have included the relatively
more influential studies in our review based on our in-
clusion criteria. Severe acute pancreatitis is still a subject
of grey areas in its surgical management albeit new stud-
ies have been recorded since the origin of the latest UK
guidelines for management of acute pancreatitis and se-
vere acute pancreatitis. We do encourage further studies
in this surgical topic with an aim to further reduce the
associated mortality with severe acute pancreatitis.
Contributors: PM proposed the study, performed the research
and wrote the first draft. JCD reviewed and analyzed the data.
Both authors contributed to the design and interpretation of the
study and to further drafts. PM is the guarantor.
Funding: None.
Ethical approval: Not needed.
Competing interest: No benefits in any form have been received
or will be received from a commercial party related directly or in-
directly to the subject of this article.
References
1 Munhoz-Filho CH, Batigália F, Funes HL. Clinical and thera-
peutic correlations in patients with slight acute pancreatitis.
Arq Bras Cir Dig 2015;28:24-27.
2 Whitcomb DC. Genetic risk factors for pancreatic disorders.
Gastroenterology 2013;144:1292-1302.
3 Toh SK, Phillips S, Johnson CD. A prospective audit against na-
tional standards of the presentation and management of acute
pancreatitis in the South of England. Gut 2000;46:239-243.
4 Papachristou GI. Prediction of severe acute pancreatitis: cur-
rent knowledge and novel insights. World J Gastroenterol
2008;14:6273-6275.
5 Bradley EL 3rd. A clinically based classification system for
acute pancreatitis. Summary of the International Symposium
on Acute Pancreatitis, Atlanta, Ga, September 11 through 13,
1992. Arch Surg 1993;128:586-590.
6 Pal KM, Kasi PM, Tayyeb M, Mosharraf SM, Fatmi Z. Corre-
lates of morbidity and mortality in severe necrotizing pancre-
atitis. ISRN Surg 2012;2012:215193.
7 Wang GJ, Gao CF, Wei D, Wang C, Ding SQ. Acute pancreatitis:
etiology and common pathogenesis. World J Gastroenterol
2009;15:1427-1430.
8 Swaroop VS, Chari ST, Clain JE. Severe acute pancreatitis.
JAMA 2004;291:2865-2868.
9 Agarwal S, George J, Padhan RK, Vadiraja PK, Behera S, Hasan
A, et al. Reduction in mortality in severe acute pancreatitis: A
time trend analysis over 16 years. Pancreatology 2016;16:194-
199.
10 Roberts SE, Akbari A, Thorne K, Atkinson M, Evans PA. The
incidence of acute pancreatitis: impact of social deprivation,
alcohol consumption, seasonal and demographic factors. Ali-
ment Pharmacol Ther 2013;38:539-548.
11 Werner J, Feuerbach S, Uhl W, Büchler MW. Management of
acute pancreatitis: from surgery to interventional intensive
care. Gut 2005;54:426-436.
12 Working Party of the British Society of Gastroenterology; As-
sociation of Surgeons of Great Britain and Ireland; Pancreatic
Society of Great Britain and Ireland; Association of Upper GI
Surgeons of Great Britain and Ireland. UK guidelines for the
management of acute pancreatitis. Gut 2005;54:iii1-9.
13 Diehl AK, Holleman DR Jr, Chapman JB, Schwesinger WH,
Kurtin WE. Gallstone size and risk of pancreatitis. Arch Intern
Med 1997;157:1674-1678.
14 Wang YL, Hu R, Lugea A, Gukovsky I, Smoot D, Gukovskaya
AS, et al. Ethanol feeding alters death signaling in the pancreas.
Pancreas 2006;32:351-359.
15 Genetic risk factors in chronic pancreatitis. 2015 [cited 2016
Januray 6]. Available from: http://www.pancreasgenetics.org/
16 Papachristou GI, Sass DA, Avula H, Lamb J, Lokshin A, Bar-
mada MM, et al. Is the monocyte chemotactic protein-1 -2518
G allele a risk factor for severe acute pancreatitis? Clin Gastro-
enterol Hepatol 2005;3:475-481.
17 Pezzilli R, Morselli-Labate AM, Mantovani V, Romboli E, Selva
P, Migliori M, et al. Mutations of the CFTR gene in pancreatic
disease. Pancreas 2003;27:332-336.

5. Severe acute pancreatitis
Hepatobiliary Pancreat Dis Int，Vol 16，No 2 • April 15，2017 • www.hbpdint.com • 159
18 Windsor JA, Johnson CD, Petrov MS, Layer P, Garg PK, Pa-
pachristou GI. Classifying the severity of acute pancreatitis:
towards a way forward. Pancreatology 2015;15:101-104.
19 Shelat VG, Diddapur RK. Minimally invasive retroperitoneal
pancreatic necrosectomy in necrotising pancreatitis. Singapore
Med J 2007;48:e220-223.
20 Dellinger EP, Forsmark CE, Layer P, Lévy P, Maraví-Poma E,
Petrov MS, et al. Determinant-based classification of acute
pancreatitis severity: an international multidisciplinary con-
sultation. Ann Surg 2012;256:875-880.
21 Sileikis A, Beiša V, Beiša A, Samuilis A, Serpytis M, Strupas K.
Minimally invasive retroperitoneal necrosectomy in manage-
ment of acute necrotizing pancreatitis. Wideochir Inne Tech
Maloinwazyjne 2013;8:29-35.
22 Reber HA, McFadden DW. Indications for surgery in necrotiz-
ing pancreatitis. West J Med 1993;159:704-707.
23 Doctor N, Agarwal P, Gandhi V. Management of severe acute
pancreatitis. Indian J Surg 2012;74:40-46.
24 Bucher P, Pugin F, Morel P. Minimally invasive necrosectomy
for infected necrotizing pancreatitis. Pancreas 2008;36:113-119.
25 Charbonney E, Nathens AB. Severe acute pancreatitis: a review.
Surg Infect (Larchmt) 2008;9:573-578.
26 Lapauw S, Wilmer A, Bobbaers H. Incidence of organ failure in
patients with severe acute pancreatitis. Crit Care 2003;7:211.
27 Mazaki T, Ishii Y, Takayama T. Meta-analysis of prophylac-
tic antibiotic use in acute necrotizing pancreatitis. Br J Surg
2006;93:674-684.
28 Dellinger EP, Tellado JM, Soto NE, Ashley SW, Barie PS,
Dugernier T, et al. Early antibiotic treatment for severe acute
necrotizing pancreatitis: a randomized, double-blind, placebo-
controlled study. Ann Surg 2007;245:674-683.
29 van Brunschot S, Bakker OJ, Besselink MG, Bollen TL, Fockens
P, Gooszen HG, et al. Treatment of necrotizing pancreatitis.
Clin Gastroenterol Hepatol 2012;10:1190-1201.
30 Mouli VP, Sreenivas V, Garg PK. Efficacy of conservative treat-
ment, without necrosectomy, for infected pancreatic necro-
sis: a systematic review and meta-analysis. Gastroenterology
2013;144:333-340.e2.
31 Mier J, León EL, Castillo A, Robledo F, Blanco R. Early versus
late necrosectomy in severe necrotizing pancreatitis. Am J Surg
1997;173:71-75.
32 Raraty MG, Halloran CM, Dodd S, Ghaneh P, Connor S, Evans J,
et al. Minimal access retroperitoneal pancreatic necrosectomy:
improvement in morbidity and mortality with a less invasive
approach. Ann Surg 2010;251:787-793.
33 Bakker OJ, van Santvoort HC, van Brunschot S, Geskus RB,
Besselink MG, Bollen TL, et al. Endoscopic transgastric vs
surgical necrosectomy for infected necrotizing pancreatitis: a
randomized trial. JAMA 2012;307:1053-1061.
34 Castellanos G, Piñero A, Serrano A, Llamas C, Fuster M, Fer-
nandez JA, et al. Translumbar retroperitoneal endoscopy: an
alternative in the follow-up and management of drained in-
fected pancreatic necrosis. Arch Surg 2005;140:952-955.
35 Fogel EL. Endoscopic pancreatic necrosectomy. J Gastrointest
Surg 2011;15:1098-1100.
36 Percutaneous retroperitoneal endoscopic necrosectomy. Na-
tional Institute of Clinical Excellence. 2015 [cited 2016 January
6]. Available from: https://www.nice.org.uk/guidance/ipg384/
chapter/2-the-procedure
37 Endoscopic trans-luminal necrosectomy. National Institute
of Clinical Excellence. 2015 [cited 2016 January 6]; Available
from: http://www.nice.org.uk/guance/IPG411/chapter/2-The-
procedure
38 Baron TH. Endoscopic pancreatic necrosectomy. Gastroenterol
Hepatol (N Y) 2008;4:617-620.
39 Besselink MG, van Santvoort HC, Nieuwenhuijs VB, Boer-
meester MA, Bollen TL, Buskens E, et al. Minimally invasive
‘step-up approach’ versus maximal necrosectomy in patients
with acute necrotising pancreatitis (PANTER trial): design
and rationale of a randomised controlled multicenter trial [IS-
RCTN13975868]. BMC Surg 2006;6:6.
40 van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS,
Boermeester MA, Dejong CH, et al. A step-up approach or
open necrosectomy for necrotizing pancreatitis. N Engl J Med
2010;362:1491-1502.
Received February 14, 2016
Accepted after revision July 29, 2016