Gastroenterol Clin N Am

32 (2003) 1169–1194

Emergency complications of acute and

chronic pancreatitis
Ngai-Moh Law, MD, Martin L. Freeman, MD*
University of Minnesota, Division of Gastroenterology, Hennepin County Medical Center,
701 Park Avenue, Minneapolis, MN 55415, USA

Acute pancreatitis is a common disease with a relatively high morbidity

and mortality. About 20% of patients develop severe or life-threatening
complications that require critical care [1]. Emergency complications of
severe acute pancreatitis have decreased significantly over the last few
decades because of refined imaging studies for identifying complications at
an earlier stage of disease [2]; improved critical care support [3]; and better
understanding of the need and timing of interventions, such as endoscopic
retrograde cholangiopancreatography (ERCP) and surgery [4]. Early
diagnosis of massive pancreatic necrosis [2,5] and differentiation between
infected and sterile pancreatic necrosis and associated complications have
enabled surgical debridement (necrosectomy) to be targeted at appropriately
selected patients [1]. In addition, urgent endoscopic sphincterotomy with
common bile duct stone clearance has been shown in randomized controlled
trials to reduce morbidity and mortality of severe acute gallstone
pancreatitis (Fig. 1) [6–8].
In contrast, chronic pancreatitis is a recurrent disease with multiple
potential complications that occasionally require urgent intervention. With
the advances in interventional radiology, ERCP, and endoscopic ultra-
sound, emergency complications from chronic pancreatitis can be treated
more rapidly and effectively without necessarily subjecting poor-risk patients
to extensive surgeries.
This article focuses mainly on the emergency complications of acute and
chronic pancreatitis that require urgent intervention. Recent developments
in the diagnosis and management of such complications are discussed.

* Corresponding author.
E-mail address: freem020@umn.edu (M.L. Freeman).

0889-8553/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0889-8553(03)00089-X
1170 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Fig. 1. Biliary sphincterotomy and extraction of impacted stone from papillary orifice during
ERCP in patient with severe acute gallstone pancreatitis. (A) Impacted stone in papillary orifice.
(B) Biliary sphincterotomy. (C ) Stone extraction. (See also Color Plate 18.)

Emergency complications of acute pancreatitis

Although most episodes of acute pancreatitis are mild and self limited, up
to 20% of patients may develop a severe or fatal episode. The overall
mortality of acute pancreatitis remains at 5% to 10% [9], but it may increase
to 35% or higher in complicated cases [10,11]. Severe acute pancreatitis is
a systemic disease with two distinct phases. The first phase is that of a sterile
systemic inflammatory response syndrome (SIRS) that may lead to multiple
organ failure within the first 72 hours [12–14]. SIRS is the clinical response
resulting from the extensive systemic effects of proinflammatory mediators
[15]. The second phase of uncontrolled decompensation includes progression
to local pancreatic and intra-abdominal complications. Irreversible multiple
organ failure and death may develop [16]. Recent studies have shown that
failure of more than one organ system in the early phase of acute pancreatitis is
an important complication highly predictive of mortality [16,17]. Manage-
ment of patients with acute pancreatitis focuses on identifying those patients
at risk, and aggressive management of SIRS and prevention of complications.
Emergency intervention in acute gallstone pancreatitis is the best clinical
example of an attempt to retard the progression of SIRS to prevent life-
threatening complications in acute pancreatitis.

Acute gallstone pancreatitis

Gallstone disease accounts for approximately half of the cases of acute
pancreatitis in the Western world [10,18]. Acute gallstone pancreatitis may
result in severe, necrotizing, life-threatening, or fatal pancreatitis because it
often occurs in a previously healthy gland. As many as 25% of patients with
gallstone pancreatitis may develop severe pancreatitis and mortality may be
as high as 10%. The role of ERCP in acute gallstone pancreatitis has long
been recognized and there is now substantial evidence from randomized
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1171

controlled trials that early ERCP with biliary sphincterotomy and stone
extraction can improve outcome of properly selected patients with acute
gallstone pancreatitis.
Acute gallstone pancreatitis is usually suspected in the setting of acute
abdominal pain with hyperamylasemia or hyperlipasemia, in the absence of
another etiology, such as alcohol, and in the presence of gallstones as
documented by ultrasound, computed tomography (CT), or other imaging
techniques [19,20]. There is usually elevation of liver chemistries, although
the pattern is not consistent, and may include elevated serum bilirubin,
transaminases, or alkaline phosphatase. Jaundice and a dilated bile duct are
further supporting evidence of biliary etiology in the context of gallstone
disease. The sensitivity and specificity of predictors of acute gallstone
pancreatitis are also variable but it is more likely in patients with markedly
elevated serum amylase or elevated serum transaminases.
The general consensus is that early cholecystectomy has a very limited
role even in severe cases [21]. The relevant issue for the endoscopist is
whether to perform ERCP in patients with suspected acute gallstone
pancreatitis. There are substantial data regarding efficacy of ERCP in this
setting, including four randomized controlled trials comparing early ERCP
and biliary sphincterotomy with no intervention (Table 1).
A British study was the first to prospectively evaluate the role of ERCP
in acute gallstone pancreatitis [6]. In that study, 121 patients with acute
pancreatitis and ultrasound evidence of gallstone disease were randomized
to either conventional medical management or urgent ERCP within 72
hours. Patients were stratified by severity of illness; one half of the patients
randomized to ERCP had severe pancreatitis. Common bile duct stones
were found in 63% of patients with severe pancreatitis, but only 25% of
those with mild pancreatitis. Sphincterotomy was performed in those
patients found to have bile duct stones. In the group randomized to

Table 1
Meta-analysis of ERCP plus biliary sphincterotomy versus conservative treatment for treatment
of acute gallstone pancreatitis
% Complications % Complications
Reference (ERCP plus ES) (control) RRR ARR NNT
Neoptolemos et al [6] 16.9 33.9 50.2 17 5.8
Fan et al [7] 17.5 28.6 38.8 11.1 9
Fölsch et al [8] 46 50.9 19.6 4.9 20.4
Nowak et al [22] 16.9 36.3 53.4 15.9 6.3
Pooled data 25 38.2 34.6 13.2 7.6
Abbreviations: ARR, absolute risk reduction; ES, biliary sphincterotomy; NNT, number
needed to treat; RRR, relative risk reduction.
Adapted from Sharma VK, Howden CW. Meta-analysis of randomized controlled trials of
endoscopic retrograde cholangliography and endoscopic sphincterotomy for the treatment of
acute biliary pancreatitis. Am J Gastroenterol 1999;94:3211–14.
1172 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

intervention with ERCP and sphincterotomy, there was a significant

reduction in complications in those with severe disease, 24% with 4%
mortality versus 61% with 18% mortality in the untreated group. There was
no difference, however, in outcomes of patients with mild pancreatitis.
In a subsequent study from Hong Kong [7], 195 patients with acute
pancreatitis were randomized to receive ERCP with sphincterotomy versus
conservative management within 24 hours of admission. Stones were found
in 65% of the patients. The major difference in outcome of the group
undergoing ERCP was a reduction in biliary sepsis (0% after ERCP versus
14% in the conservative group). There was a tendency toward fewer
complications in the ERCP group versus conservative management group,
especially in those with severe pancreatitis, and a slight trend toward
reduction in mortality.
Another unpublished, randomized controlled trial from Poland has been
presented only in abstract form [22]. The 280 patients with acute gallstone
pancreatitis all underwent ERCP within 24 hours of admission. All patients
with bile duct stones were treated with biliary sphincterotomy, whereas the
remaining patients without common bile duct stones were randomized to
sphincterotomy or conventional treatment. There were significant reduc-
tions in complications in sphincterotomy-treated patients versus the
conservatively treated patients (17% versus 36%) and a significant re-
duction in mortality (2% versus 13%). The benefits of intervention seemed
to apply to patients with all severities of pancreatitis, including those with
mild disease. Problems with this study include a lack of true randomization,
the fact that it has not been published in a peer-reviewed journal, and the
fact that the only patients randomized were those with empty ducts, some of
whom may not have had gallstone pancreatitis but pancreatitis caused by
other etiologies.
The most contentious study is the German multicenter study [8], in which
238 patients with suspected gallstone pancreatitis were randomized to early
ERCP within 72 hours of presentation or conservative management.
Patients with jaundice were excluded. Fifty-eight of 121 patients randomized
to the ERCP arm were found to have bile duct stones. In the control arm, 13
of 112 were crossed over to ERCP for apparent bile duct stones. In this
study, there was no improvement in outcome from early sphincterotomy.
Paradoxically, there seemed to be more severe complications including
respiratory failure in the early ERCP group, and a numerically increased
mortality. Major criticisms of this study have included the fact that patients
most likely to benefit from ERCP (ie, those with jaundice) were excluded
from the study. Furthermore, many contributing centers enrolled fewer than
two patients per year, raising questions about technical proficiency at
ERCP.
A meta-analysis of these randomized controlled trials has suggested that
early intervention with ERCP in acute gallstone pancreatitis results in a lower
complication rate and a numerically lower mortality rate (see Table 1) [23].
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1173

This meta-analysis found that complications occurred in 25% of treated

patients versus 38.2% of controls (P\0.001) with a mortality of 5.2% in
treated patients versus 9.1% in control patients (P ¼ NS). The number
needed to treat for avoidance of complications and death was 7.6 and 25.6,
respectively. It is probably safe to say that early ERCP with sphincterotomy
in patients with gallstone pancreatitis and persistent bile duct stones is
effective in reducing complications, particularly in patients with severe
pancreatitis.
Unless there is reasonably clear evidence of a bile duct stone, such as
a persistently elevated bilirubin or an imaging study clearly showing an
intraductal stone, routine use of ERCP is unnecessary and adds avoidable
risk in patients with mild to moderate biliary pancreatitis in whom
cholecystectomy is planned. For most patients with suspected biliary
pancreatitis, bile duct stones have passed by the time cholangiography is
performed. ERCP can be deferred and any remaining ductal stones can be
identified at intraoperative cholangiography during laparoscopic cholecys-
tectomy. These stones can then be removed by intraoperative or post-
operative ERCP, or in those few centers with the appropriate expertise, by
laparoscopic common bile duct exploration. If ERCP is unsuccessful, the
patient can be referred to a tertiary center where biliary access is virtually
always possible. In the postcholecystectomy patient with suspected biliary
pancreatitis, ERCP is appropriate. In many of these patients there is
a nongallstone etiology, however, such as sphincter of Oddi dysfunction,
a setting in which conventional diagnostic and therapeutic ERCP tech-
niques can be highly risky [24,25] and protective measures, such as place-
ment of a pancreatic stent, may be advisable [26,27].
Empirical biliary sphincterotomy for suspected gallstone pancreatitis
may be appropriate in certain settings without cholecystectomy, especially in
elderly patients who are not good candidates for surgery because of severe
medical comorbidity [28–31]. Under these circumstances, biliary sphinctero-
tomy is sometimes performed in absence of demonstration of a definite bile
duct stone or as a semidefinitive treatment in lieu of cholecystectomy.
Several studies have suggested effectiveness of endoscopic biliary sphinctero-
tomy in preventing future episodes of acute gallstone pancreatitis [32]. These
uncontrolled case series mostly suggest a reduction in the frequency of
pancreatitis attacks, although recurrent bile duct stones and cholecystitis
may be problematic in patients with gallbladder left in situ [33]. Caution
must be applied when performing ERCP in patients who might have other
etiologies of acute pancreatitis. Recurrent pancreatitis in patients with
mildly abnormal enzymes may in fact be caused by sphincter of Oddi dys-
function, especially in women, younger to middle-aged patients, and those
who are postcholecystectomy or do not have clearly documented gallstone
disease. Empirical biliary sphincterotomy and even diagnostic ERCP in
this setting may be quite hazardous [24,25], especially without pancreatic
stenting [27], and is less likely to be of benefit.
1174 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Multiple organ failure

Death within the first week of presentation with acute pancreatitis is
usually caused by organ failure [16,17]. Death from local complications is
more common after the first week, especially if infection has developed.
Mortality is significantly higher if pancreatic necrosis is associated with
multiple organ failure [17]. Approximately one half of the deaths in acute
pancreatitis occur because of multiple organ failure or septic complications.
The major goal in management during the first week of disease is to prevent
and optimally manage acute multiple organ failure. Organ failure as defined
in the Atlanta Symposium of 1992 [5] includes the following parameters:
shock, with systolic blood pressure less than 90 mm Hg; pulmonary
insufficiency, with PaO2 less than 60 mm Hg; renal failure, with a creatinine
greater than 2 mg/dL after fluid resuscitation; and gastrointestinal bleeding,
with more than 500 mL of blood loss within a 24-hour period. Multiple
organ failure is defined as a syndrome of progressive but potentially
reversible organ failure, involving two or more systems remote from the
original insult. The prognosis of the patient is associated with the number of
failed organs [17,34]. Acute organ system failure is the direct cause in up to
92% of mortality [16] and failure of more than one organ greatly increases
the risk of death [16,17,34]. The pulmonary, renal, cardiovascular, central
nervous, and coagulation systems are most commonly affected [34,35].
Emergency pulmonary complications are a significant factor contributing to
death, even if only moderate pancreatic damage is present [36]. Up to 60%
of deaths occurring within the first week of illness are caused by pulmonary
complications. Arterial hypoxemia with acute lung injury occurs in more
than 60% of patients during the first 48 hours of pancreatitis and adult
respiratory distress syndrome may occur in up to 20% of patients [34].
Renal failure may develop in up to 20% of patients with mortality as high as
80%. Cofactors contributing to multiple organ failure include advanced age
[35], diabetes mellitus [36], smoking [37], and obesity [38,39].
Patients with severe acute pancreatitis must be managed in the inten-
sive care unit [3]. Initial predictors of a severe course include first episode
of alcohol-induced pancreatitis, obesity, hemodynamic instability, severe
abdominal tenderness, and abdominal wall hemorrhage. Numerous stan-
dardized tools for assessment of patients with severe disease requiring in-
tensive care have been developed (Box 1) [2,40–44]. The criteria of Ranson
et al [40] remain the most commonly used, but have limitations. The five
initial criteria assess the severity of the acute inflammatory process, whereas
the six criteria measured at 48 hours determine the overall systemic effects.
The presence of three or more Ranson’s signs usually indicates severe
pancreatitis. Mortality increases with the number of Ranson’s signs
(patients with zero to two criteria, three to four criteria, or equal to or
greater than five criteria have death rates of 1%, 16%, and more than 40%,
respectively). A limitation of Ranson’s criteria and other commonly used
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1175

Box 1. Poor prognostic signs in acute pancreatitis

1. Objective data

3 Ranson’s criteria
APACHE score
8
Hematocrit
44
CT severity index
6
2. Organ failure
3. Local complications
Necrosis
Abscess
Pseudocyst

scoring systems, such as the Glasgow criteria [41], is the need to wait 48
hours to obtain a complete assessment. The Acute Physiology and Chronic
Health Evaluation II (APACHE II) system allows a more rapid deter-
mination of prognosis but is more cumbersome to use [42,43]. CT severity
index based on Ranson-Balthazar score is another useful predictor that is
readily accessible (Table 2) [2]. It has been suggested that hemoconcentra-
tion is a predictor of poor prognosis, and should be treated aggressively with
hemodilution [44].
To decrease the risk of acute multiple organ failure and early death,
intensive monitoring and critical care support are essential [43]. These include
intravenous fluid replacement, oxygen therapy and mechanical ventilation,
and inotropic and nutritional support. Immediate and aggressive fluid
resuscitation of hypovolemic shock remains the cornerstone of management.

Table 2
CT severity index
Balthazar and Ranson CT grade (based on non–contrast-enhanced appearance)
0 Normal pancreas
1 Focal or diffuse enlargement
2 Gland abnormalities with mild peripancreatic enlargement
3 Fluid collection within single location
4
2 fluid collections or gas in pancreas or surrounding inflammation
CT severity index (based on dynamic perfusion) (0–10)
CT grade + Necrosis = Total score
0 None =0
1 one third =2
2 one half =4
3 [ one half =6
4
Data from Balthazar EJ, Robinson DL, Magibow ASJ, et al. Acute pancreatitis: value of CT
in establishing prognosis. Radiology 1990;174:331–6.
1176 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Failure to provide adequate fluid resuscitation within the first 24 hours may
exacerbate or even induce pancreatic necrosis [44]. Patients with emergency
cardiorespiratory complications should be monitored by central venous or
pulmonary arterial pressure, particularly those who have developed adult
respiratory distress syndrome and renal failure requiring mechanical ventila-
tion and temporary dialysis.
Recent advances in research have led to the development of more
effective treatment strategies against multiple organ failure. The recognition
of the role of sepsis during the second phase has resulted in randomized
trials of using prophylactic antibiotics and demonstrating efficacy of
reducing complications and mortality [45,46]. Interrupting the initial phase
of SIRS, however, may be the best treatment option in preventing
progression to multiple organ failure. Novel therapies targeting proin-
flammatory cytokines including interleukins-1, -2, -6, and -8, tumor necrosis
factor-a, and platelet-activating factor and anti-inflammatory factors
including interleukin-10 and interleukin-1 receptor antagonist in the SIRS
response have potential but further clinical trails are needed [13,47,48].
Lexipafant, a platelet-activating factor antagonist, has demonstrated bene-
ficial effects in clinical and experimental studies [49–51]. A recent multi-
center trial showed that lexipafant, when administered within 48 hours of
the onset of symptoms, significantly decreased mortality to 8% compared
with 18% in the placebo-treated patients [51].

Massive or infected pancreatic necrosis

Approximately 10% to 20% of patients with acute pancreatitis develop
pancreatic necrosis, which is associated with a mortality of 15% to 20% [52].
Dynamic contrast-enhanced CT is now used routinely to determine the extent
of pancreatic necrosis, as defined by nonenhanced (nonperfused) pancreatic
parenchyma, which must be distinguished from acute fluid collections, which
also do not enhance [2,53]. In interstitial pancreatitis, there is uniform
enhancement of the pancreas, which implies a good prognosis (Fig. 2).
Limited degrees of necrosis (up to 30%) may occur in more severe cases [2].
Extensive necrosis (more than 50%) is associated with systemic complications
and frequent need for surgical intervention (Fig. 3) [10,54]. The extent of
pancreatic necrosis may increase during the first or second week of illness [2],
with secondary infected pancreatic necrosis requiring surgical intervention
occurring mainly from the second week onward [16,54].
A contrast-enhanced CT scan should be obtained for the early detection
of acute local complications and necrosis. CT scan is best performed within
24 to 48 hours of admission, after vigorous volume resuscitation. Pre-
maturely obtained scans at admission (eg, by the emergency department)
have limited prognostic value and may be associated with increased
complications, such as contrast nephrotoxicity. CT scan should be repeated
at intervals of 1 to 2 weeks or until there are signs of improvement. Extensive
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1177

Fig. 2. CT scan showing mild interstitial pancreatitis with uniform contrast-enhancement and
mild peripancreatic edema and fat-stranding.

pancreatic necrosis (usually [ 50%) and continued clinical deterioration

despite maximum support always pose a difficult management problem.
The possibility of infection in the necrotic process should be considered
when deterioration occurs after the first week. Infected necrosis occurs in
about 30% to 35% of patients typically presenting in the second or third
week of illness and sometimes later. CT-guided fine-needle aspiration with
Gram stain and cultures can be used to confirm infection [55,56]. Patients
with infected pancreatic necrosis have increased mortality and may require
immediate surgical debridement (necrosectomy) [54,55]. In contrast, the role
of necrosectomy in patients without infection remains unclear. Evidenced-
based guidelines from the International Association of Pancreatology
recommend surgical or radiologic drainage for infected pancreatic necrosis
in patients with clinical signs and symptoms of sepsis. Patients with sterile
pancreatic necrosis as defined by negative fine-needle aspiration for
bacteriology should be managed conservatively and only undergo in-
tervention in selected cases. In addition, early surgery within 14 days after
onset of the disease is not recommended unless there are specific indications
[4]. Necrosectomy carries a high risk of mortality related to the expertise of
the surgeon, patient selection, and quality of care. Necrosectomy was
associated with statistically significant deterioration in immediate post-
operative organ dysfunction and up to 43% mortality in one study of ill
patients with high APACHE II scores [57]. Radiologic drainage of organ-
ized necrotic fluid collections with one or more percutaneously placed cath-
eters may be considered in critically ill patients who are unfit for surgery
1178 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Fig. 3. CT scan showing pancreatic necrosis of head and body, with perfusion only of tail of
pancreas during dynamic phase of contrast injection.

[58,59]. ERCP may be used to document pancreatic duct disruption and

placement of pancreatic stent to bridge the disruption can be performed,
with surgical interventions, or nasopancreatic drains reserved for those
who deteriorate further [60]. A recent report has suggested, however, that
pancreatic duct disruptions are common in patients with severe acute
pancreatitis, and that an aggressive approach using early ERCP with
stenting of any duct leaks, combined with percutaneous drainage of
pancreatic fluid collections (PFCs) and organized necrosis, with surgery
reserved for refractory cases, has resulted in relatively low mortality [61].
This is an evolving but controversial approach that deserves further
investigation.
Surgery is usually reserved for massive pancreatic necrosis ([50%) with
a deteriorating clinical course. Percutaneous or endoscopic catheter drainage
is usually unsuccessful in the presence of semisolid necrosis. Intervention is
required in up to 20% of cases for local complications, specifically extensive
pancreatic necrosis (usually [50%); infected pancreatic necrosis; abscess;
and hemorrhage [3]. The role of prophylactic antibiotics in severe pancreatitis
remains unclear, but recent randomized trials have shown some benefit with
antibiotics that have good penetration into pancreatic tissue (eg, imipenem).
Three prospective randomized clinical studies of antibiotic prophylaxis
in severe acute pancreatitis have provided evidence of the role of antibiotics
in the initial treatment of severe acute pancreatitis, with improvement in
morbidity, but not clearly in mortality [62–64]. Patients with extensive
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1179

necrosis are generally given prophylactic antibiotics based on these data. A

potential concern is fungal superinfections.

Complications of PFCs
The PFCs that occur as a complication of acute pancreatitis include acute
fluid collections, pancreatic necrosis, acute pseudocysts, and pancreatic
abscesses [5]. An acute fluid collection is a collection of enzyme-rich
pancreatic secretions occurring within 48 hours in the course of acute
pancreatitis, is located in or near the pancreas, and always lacks a well-
defined wall of granulation tissue or fibrous tissue. They occur in up to 30%
to 50% of patients with acute pancreatitis and are often miscategorized as
pseudocysts. Although most acute fluid collections resolve, 10% to 15%
may evolve into pseudocysts with related complications. Acute pseudocysts
refer to acute fluid collections containing pancreatic enzymes and are lined
by a nonepithelial wall of granulation tissue devoid of solid debris. By
definition, a fluid collection must be present for at least 4 weeks or more
before it can be called a pseudocyst [59]. Most acute pseudocysts resolve
spontaneously without complications. Indications for urgent drainage of
acute pseudocysts include infection, biliary obstruction, gastric outlet
obstruction, and cardiopulmonary distress caused by massive effusion or
ascites as a result of documented pseudocyst rupture. PFCs can be drained
percutaneously, endoscopically, or surgically. A critical factor in timing and
route of drainage is the maturity of the cyst. In general, internal drainage
procedures, such as endoscopic transgastric drainage or surgery involving
a cyst-enterostomy, require a matured cyst with a wall, a process that
generally requires 4 weeks or more from the onset of the fluid collection.
Such internal drainage procedures have an inherent advantage over external
drainage by catheters. Percutaneous drainage can be done with less mature
cysts but may lead to infection or cutaneous fistulas. External surgical
drainage is another option. A recent review paper has suggested that endo-
scopic drainage of organized pancreatic necrosis, or postnecrotic pseudo-
cysts, often containing solid debris and necrotic material, is associated with
high recurrence and complication rates as compared with drainage of other
PFCs; lavage of the cyst cavity by percutaneous or transnasal route is im-
portant to prevent accumulation and infection of residual debris if non-
surgical drainage techniques are used [59]. If surgery is performed,
debridement of any necrotic debris from the cyst cavity is essential, because
simple cystoenterostomy often results in delayed infection of necrotic debris.
Large-bore percutaneous drainage and lavage can be combined with other
modalities, such as transpapillary stenting and surgical debridement. The
various modalities of pseudocyst drainage are discussed further in the
section on complications of chronic pseudocysts.
A pancreatic abscess is a well-defined collection of pus and occurs usually
very late (6 weeks or more) in the evolution of acute pancreatitis [5].
1180 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Abscesses occur in about 1% of patients and should generally be treated by

percutaneous radiologic drainage [5,65]. The mortality from pancreatic
abscess is relatively low as compared with infected pancreatic necrosis,
which has a mortality of 20% to 50% [6,12]. Surgical intervention is
indicated when radiologic percutaneous aspiration of a pancreatic abscess is
unsuitable or unsuccessful [65,66].

Massive pancreatic ascites

Massive ascites with a collection of peritoneal fluid rich in pancreatic
secretions may occur acutely in severe pancreatitis. This is usually caused by
a fistula connecting the pancreatic duct or pseudocyst with the peritoneal
cavity. If left untreated, it may lead to acute cardiopulmonary distress or
subcutaneous fat necrosis. Rapid increases in retroperitoneal and in-
traperitoneal volumes from massive pancreatic ascites may lead to the
development of abdominal compartment syndrome. This is a clinical entity
that develops from progressive, acute increase in intra-abdominal pressure
and affects multiple organ systems. The intestine is the organ most sensi-
tive to intra-abdominal pressure, and may develop ischemia before the
development of the classic renal, pulmonary, and cardiovascular signs.
Intracranial derangements with abdominal compartment syndrome are
now well described. Treatment involves expedient decompression of the
abdomen, without which the syndrome of end-organ damage and reduced
oxygen delivery may lead to the development of multiple organ failure and
ultimately death [67].
Pancreatic ascites should be suspected when ascites fails to respond to
diuretic therapy and ascitic fluid analysis reveals markedly elevated amylase
levels. CT scan and MR cholangiopancreatography may sometimes identify
the site of pancreatic ductal disruption, but ERCP is often needed to
diagnose and treat the ductal disruption. Endoscopic management with
a transpapillary stent is the main modality of treatment to close the leak and
resolve the ascites [68]; with very large volume ascites, percutaneous
decompression may be a useful adjunct. Continuous infusion of somato-
statin analogues, such as octreotide, with or without prior drainage of the
ascites, generally has poor results. Some patients, however, may eventually
require surgical drainage or pancreatic resection.

Acute hemorrhage
Acute hemorrhage caused by vessel erosion forming a pseudoaneurysm
or bleeding into the retroperitoneal or peritoneal spaces may occur rarely
[66]. Bleeding into a pseudocyst may result in a spontaneous rupture [66].
Acute and massive bleeding is more likely to occur in chronic pancreatitis
and is discussed in greater details in that section.
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1181

Fistulas
Pancreatic fistulas are caused by disruption of the pancreatic duct and
should be suspected in patients who develop pancreatic ascites or pleural
effusions. Pancreaticopleural fistula is a rare complication and commonly
presents with recurrent pleural effusions; pericarditis rarely occurs. A recent
case report showed that bilateral massive pleural effusions associated with
cardiac tamponade may present as an emergency complication [69]. Fistulas
into the bowel leading to acute bowel necrosis and perforation may also
occur spontaneously, but more often arise in association with repeated
laparotomies or incorrectly positioned drains [66].
Internal fistulas may communicate with the colon, small bowel, biliary
system, or tracking to the skin as external fistulas (Fig. 4). Fistulograms are
usually sufficient to investigate external fistulas, but ERCP remains the test
of choice for detecting internal pancreatic fistulas because these fistulas are
commonly associated with pancreatic duct disruption. ERCP with pan-
creatic stent placement beyond a ductal disruption resolves most cases of
refractory pancreatic ascites, persistent pancreaticoenteric, and pancreati-
cocutaneous fistulas (Fig. 5) [70,71]. Although the pancreatic stent may close
the leak, paracentesis may also be required to remove or decompress the
intraperitoneal fluid. Infusion of somatostatin analogues, such as octreotide,
has also been shown to be effective in the treatment of pancreatic pleural
effusion in case reports [72]. Surgical resection or other intervention may be

Fig. 4. CT scan showing pancreatic-cutaneous fistula (arrows) in patient postsurgical debride-

ment of pancreatic necrosis.
1182 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

Fig. 5. ERCP from patient in Fig. 2 showing bridging of pancreatic duct disruption with
guidewire and stent. (A) Contrast extravasating from head of pancreas. (B) Filling of fistula and
part of duct in tail. (C ) Wire across disruption to tail of pancreas. (D) Stent bridging across
disruption to tail of pancreas. (Courtesy of O.W. Cass, MD, University of Minnesota,
Minneapolis, MN.)

required to treat persistent pancreatic fistulas, especially if they arise above

a completely disconnected duct.

Emergency complications of chronic pancreatitis

Chronic pancreatitis is a disease characterized by progressive and
irreversible loss of pancreatic exocrine and endocrine function as a result
of chronic inflammation and fibrosis. This section reviews the current
management issues of the emergency complications of chronic pancreatitis.
Acute glycemic derangement in pancreatic diabetes and local complications,
such as pseudocysts, venous thromboses, ruptured pseudoaneurysms, and
biliary and gastroduodenal obstruction that require urgent intervention, are
discussed.

Hypoglycemia from pancreatic diabetes

Endocrine insufficiency and diabetes occur in 30% to 50% of patients
with chronic pancreatitis [73,74]. Hypoglycemia often complicates pancre-
atic diabetes because of irregular caloric intake from alcohol abuse and
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1183

malabsorption [75]. The impaired release of glucagon contributes to re-

current hypoglycemia in chronic pancreatitis [76]. The tendency to severe
hypoglycemic episodes makes it difficult to maintain good glycemic control
by insulin treatment (brittle diabetes). With fluctuating glucose metabolism,
it is essential to monitor blood glucose level closely and safer to use oral
hypoglycemic agents or short-acting insulin. The main aim of treatment is to
reduce the risk of life-threatening hypoglycemic attacks. These patients
should be referred to a diabetologist when early symptoms develop. Major
pancreatic resection invariably results in the development of insulin-
dependent diabetes, unless auto-islet cell transplantation is performed.
Cautious treatment with insulin is again preferred to avoid acute hypo-
glycemic episodes.

Complications of chronic pseudocysts

Acute complications of pseudocysts include acute hemorrhage; infection;
rupture; and compression of adjacent structures, such as bowel or bile duct.
Pseudocysts are localized collections of fluid rich in pancreatic enzymes
resulting from disrupted pancreatic duct or damaged parenchyma (Fig. 6).
Chronic pseudocysts have a well-defined wall composed of granulation and
fibrous tissue with no epithelial lining and usually evolve within 4 to 6 weeks
after an episode of pancreatitis. Chronic pseudocysts are less likely to resolve
spontaneously than those developing after an acute attack. Many patients
eventually require some form of drainage procedure [77]. Indications for
drainage of pseudocysts include persistence of symptoms in a nonresolving
cyst; rapid enlargement; failure of a large pseudocyst ([6 cm) to shrink after
6 weeks; and obstruction of bowel, bile duct, or other structures. Drainage is

Fig. 6. Pancreatic pseudocyst in tail of pancreas, indenting stomach.

1184 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

performed to relieve symptoms or prevent complications. Drainage options

include surgical, percutaneous, and endoscopic methods. Timing and route
of drainage are similar to those for acute pseudocysts, in that a mature cyst
wall is required for endoscopic or surgical cystenterostomies. Pseudocysts
within 1 cm of the gastric or duodenal lumen, and especially those without
solid debris, can be drained by transluminal endoscopic method, either by
direct visualization or by endoscopic ultrasound-guided puncture, dilation of
the cystenterostomy, and stenting. Smaller pseudocysts communicating with
the main pancreatic duct may be drained by the transpapillary route using
pancreatic stents with or without pancreatic sphincterotomy. A combination
of these approaches is often used.
Pseudocysts may rupture acutely into the peritoneal cavity causing severe
gross ascites or by pleuroperitoneal fistulas causing massive pleural effusion
leading to acute cardiopulmonary distress requiring emergency treatment.
Raised amylase level to more than 20,000 IU/L in the ascitic or pleural fluid
confirms the diagnosis. To decrease pancreatic secretions, total parenteral
nutrition or jejunal enteral feeding is recommended. Somatostatin analogue
infusion to hasten the closure of fistulas and repeated aspiration should be
performed. Persistent leaks require endoscopic stenting of the pancreatic
duct during ERCP as previously discussed. Radiologic percutaneous drain-
age or surgical intervention, such as open drainage or resection, may be
required in refractory cases with large volume of necrotic debris.
Endoscopic retrograde cholangiopancreatography may be used both for
delineation of the pancreatic ductal system before drainage of the
pseudocyst or to bridge disruptions or obstructing downstream strictures
or stones. ERCP allows detection and treatment of ductal stenosis, stones,
or other obstruction, which is important in the management of communi-
cating pseudocysts because percutaneous drainage of a pseudocyst with
persistent downstream ductal obstruction may result in external pancreatic
fistulas. The introduction of infection into a pseudocyst during ERCP may
occur, however, if the cyst is not drained promptly [78]. The role of
endoscopic ultrasonography in the detection and management of pseudo-
cysts is evolving. Capabilities of endoscopic ultrasonography are (1) direct
visualized puncture of pseudocysts that do not have a transmural bulge, (2)
assessment of the gut wall for vascular structures near a pseudocyst, (3)
transmural ductography if ERCP ductography fails, (4) evaluation of subtle
changes in chronic pancreatitis, and (5) differentiation of neoplastic versus
inflammatory lesions by echogenic appearance or fine-needle aspiration
[79,80].
Acute hemorrhage in association with pseudocysts may be gastrointes-
tinal, intracystic, or intraperitoneal in origin. Gastrointestinal hemorrhage
may be caused by coexisting peptic ulcers or erosions, or by direct erosion
into the lumen. Acute hemorrhage may be aggravated by portal hypertension
from splenic vein compression or thrombosis and gastric varices. Intracystic
bleeding results from direct erosion into a branch of the splenic artery in close
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1185

proximity of pseudocyst. Patients with alcohol-induced pancreatitis are most

likely to develop acute arterial hemorrhage with massive bleeding originating
from the splenic (45%), gastroduodenal (18%), and pancreaticoduodenal
arteries (18%) [81,82]. Management of pseudocyst-related acute hemorrhage
is a medical emergency. Urgent endoscopy is indicated to detect luminal
causes of hemorrhage including ulcers, erosions, gastric varices, or rarely
hemobilia. Intracystic or intraperitoneal bleeding must be suspected if
endoscopy is negative. Contrast-enhanced CT scan and angiography are then
indicated. If a pseudoaneurysm or bleeding vessel is identified, embolization
is the initial treatment of choice. Immediate surgical intervention is indicated
if angiographic embolization is unsuitable or unsuccessful. Ligation of the
splenic or gastroduodenal arteries may be required for splenic artery
aneurysm or bleeding from the pancreatic head, respectively. Direct suture
ligation of a bleeding pseudocyst wall vessel can be performed from within
the pseudocyst. Splenectomy, distal pancreatic resection, and ligation of
gastric varices may be needed to control hemorrhage secondary to splenic
vein compression or thrombosis.
Infection is an uncommon complication in pseudocysts [83]. Infected
pseudocyst carries a high mortality and antibiotics guided by cultures of
aspirates of cystic fluid should be started immediately [84,85]. Percutaneous
drainage should be performed if infection is confirmed. Surgical drainage is
indicated if pus is aspirated from the cyst. A pseudocyst may rupture into
the peritoneal cavity and lead to pancreatic ascites. Rupture may also occur
into surrounding organs including stomach and colon causing internal
fistulas. The occurrence of rupture may be silent or catastrophic, especially
in association with infection or bleeding. Pancreatic mediastinal pseudocyst
with erosion into the pericardial sac causing life-threatening cardiac
tamponade has been reported in a case study [86]. The initial management
includes antibiotics, bowel rest, and total parenteral nutrition. In a small,
uncontrolled study, octreotide has been reported to assist in spontaneous
reversal of pancreatic ascites and avoidance of surgery [87]. Definitive
surgical management may require drainage of ruptured pseudocyst or
resection of the involved portion of the pancreas.
Compression of structures adjacent to the pseudocyst may occur,
including the stomach, duodenum, jejunum, bile duct, pancreatic duct, and
the splenic portal venous system. Management of these acute complications
depends on the size and site of the pseudocyst. Immediate drainage of the
pseudocyst may be all that is required in selected patients. A pseudocyst of the
tail involving the splenic hilum with compression of the splenic vein causing
gastric varices and splenomegaly may require a pancreatic tail resection and
splenectomy. In addition to drainage, a biliary decompression procedure may
be required for pseudocysts involving the pancreatic head.
There are many options for interventional treatment of pseudocysts
depending on the expertise of the institution and clinical presentation of the
patients. The current modes of treatment are endoscopic or surgical internal
1186 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

drainage, radiologic or surgical external drainage, and surgical resection

[88]. Combinations of these may be required in a patient with multiple or
complex pseudocysts [89]. Every effort must be taken to exclude cystic
neoplasm. A variety of endoscopic techniques have been described for
drainage of pseudocysts, including transpapillary drainage after pancreatic
sphincterotomy and transmural drainage and stenting [90]. Large pseudo-
cysts adjacent to the stomach or to the duodenum can be drained by
endoscopic cystogastrostomy and cystoenterostomy, respectively, with good
results. After balloon dilating the tract, one or two double pigtail stents are
usually inserted into the cyst to ensure drainage (Fig. 7). High technical
success rates of up to 91% have been reported. Up to 90% of endoscopically
treated pseudocysts resolve within 1 to 2 months, at which time stents are
removed. A 15% recurrence rate has been reported in some series, similar to
that for surgical drainage. Complication rates are reported from 1% to 21%
with 1% mortality [91–95]. Surgical treatment may be preferable when cysts
are filled with debris or when pseudocysts are not accessible to endoscopic
drainage. Surgery may also be elected when other associated pathology
including biliary strictures or cholelithiasis requires intervention during the
same operation. External surgical drainage or resection may be required
when internal drainage is not possible or failed. Laparoscopic pseudocyst
drainage is a promising new technique but its role is unclear [96]. Ran-
domized trials comparing surgical, endoscopic, and percutaneous drainage
of pseudocysts to compare the impact of these treatments on patient out-
comes would be useful, although in clinical practice variations in patient
anatomy and comorbidity, as well as local expertise often drive the decision
as to which technique is optimal.

Fig. 7. Endoscopic drainage of pancreatic pseudocyst by cystogastrostomy. (A) Guidewire

passed into cyst through stomach wall. (B) Dual pigtail stents in air-filled cyst cavity after
balloon dilation of cystogastrostomy tract.
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1187

Biliary obstruction
Bile duct obstruction or stenosis in chronic pancreatitis is uncommon and
may occur as a result of pancreatic fibrosis or secondary to compression
by pseudocyst. Progressive obstruction of the biliary tract may lead to
cholangitis and emergency relief of the obstruction is indicated [97].
Endoscopic stenting by ERCP is used as an urgent procedure to achieve
immediate bile duct drainage but generally offers only short-term relief.
Results obtained with single 10F catheter plastic stents are satisfactory in
less than 30% of treated patients [98]. One small study with two 12F
catheter stents for 1 year has been reported to be effective in 12 patients with
a 3-year follow-up period. Self-expanding metal stents have been reported
in this context, but 2 of 20 patients developed chronic recurrent biliary
obstruction in the first 6 months [99]. The use of self-expanding metal stents
in benign diseases remains controversial and is generally not recommended.
Endoscopic stent placement may be particularly helpful in patients with
acute cholangitis or patients who have undergone pancreatic surgery with
no indication for repeat bile duct surgery. Surgical bypass is often planned
as part of operations for associated pain or gastroduodenal obstruction.
Surgical options include choledochoduodenostomy, choledochojejunos-
tomy, or Roux-en-Y bypass, or Whipple pancreaticoduodenectomy. The
latter options have the added advantage of preventing reflux of luminal
contents into the biliary tree. The Roux-en-Y can also be used in pancreatic
ductal drainage procedures at a later time if required.

Gastroduodenal obstruction
Gastroduodenal obstruction is rare and usually caused by pancreatic
fibrosis in the second part of the duodenum or compression by a large
pseudocyst. It is commonly seen at endoscopy, but intervention is not
required in the absence of symptoms. Acute gastroduodenal obstruction
may occasionally occur requiring immediate intervention. Urgent endo-
scopic or other methods of drainage of the pseudocyst are then indicated
to relieve the compression. Gastrojejunostomy or Whipple pancreaticoduo-
denectomy may be needed if pancreatic fibrosis is the cause of persistent
gastroduodenal obstruction.

Venous thromboses
The splenic vein is in close proximity to the pancreas. It joins the superior
mesenteric vein to form the portal vein behind the neck of the pancreas. The
splenic-portal venous system is commonly involved in the inflammatory
processes of chronic pancreatitis. The rate of splenic vein thrombosis is
approximately 11%, and the rate of portal venous obstruction is 2% [84].
Most thrombi are asymptomatic. Acute variceal bleeding from portal
hypertension may be an emergency complication, however, requiring
1188 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

immediate endoscopy for hemostasis. The risk of variceal bleeding is

reported as 6% and seems to be lower than varices from other causes
[100,101]. Splenic or portal vein thrombosis or compression is important in
patients undergoing surgery because the operative approach may be altered
or aborted. Splenectomy is the generally preferred approach for patients
with splenic vein thrombosis and bleeding gastric or varices.

Arterial pseudoaneurysm
Gastrointestinal bleeding in chronic pancreatitis may be caused by gastric
varices, coexisting gastroduodenal disease, or arterial pseudoaneurysms.
Endoscopy is mandatory in these patients and management has been
discussed previously. Arterial pseudoaneurysm is a rarely occurring
emergency complication of pancreatitis [102]. Bleeding is frequent and
often severe, with a hemorrhage rate of up to 75%. The proposed patho-
genesis is vascular injury by proteolytic pancreatic enzymes, particularly
trypsin and elastase [103]. This autodigestion weakens the arterial wall and
leads to the formation of a pseudoaneurysm. Acute hemorrhage from
pseudoaneurysms is the most rapidly fatal complication of chronic
pancreatitis. The mortality of untreated patients is 90% to 100% [82].
The mortality of treated patients still ranges from 12% to 50% despite
aggressive intervention [104,105]. Any artery in continuity with a collection
of pancreatic fluid may be affected. Peripancreatic arteries are most
frequently involved, with splenic artery being the most common site. Other
arteries that may be involved include left gastric, hepatic, gastroduodenal,
and pancreaticoduodenal arteries [106,107]. In addition, the largest
retrospective study of arterial complications of pancreatitis has reported
the rare but documented involvement of more distal arteries including
superior mesenteric, jejunal, and ileocecal arteries [108]. Extrapancreatic
fluid collections have also been shown to cause abdominal aortic dissection
in a case report [109]. Bleeding from pseudoaneurysms has varied clinical
presentations. The most common presentation is that of rupture into
a pseudocyst, with resultant bleeding into the gastrointestinal tract via the
pancreatic duct [110]. This process has been called hemosuccus pancreaticus.
The usual clinical presentation is that of intermittent gastrointestinal
bleeding associated with abdominal pain and raised serum amylase and
lipase. Bleeding episodes can occur infrequently over a period of months to
years or can occur in rapid succession [111]. Other less common sites of
rupture of pseudoaneurysms include the peritoneal cavity, retroperitoneum,
duodenum, common bile duct, and colon [105,112]. Vascular invasion into
the aorta, portal vein, and other venous structures has also been reported.
Early diagnosis and urgent intervention are essential because mortality of
untreated bleeding is extremely high. Endoscopy should be performed to
exclude other sources of bleeding, because visualization of bleeding from the
papilla is uncommon [110]. Angiography is the gold standard for diagnosis
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1189

with the additional benefit of offering treatment by arterial embolization.

Other advantages include the ability to define small pseudoaneurysms,
because 20% are too small to be seen by other imaging methods [113]. The
ability to identify the vessel of origin may provide important information
for surgical intervention subsequently if angiographic embolization fails.
Dynamic contrast-enhanced CT is the best noninvasive diagnostic modality
with reported sensitivities ranging from 80% to 100% [110]. Important CT
findings include the presence of an enhancing lesion within or adjacent to
a pseudocyst and in continuity with a vascular structure [113]. The intense
inflammation surrounding the pseudoaneurysm contributes to the high
complication and mortality rate of surgical intervention. Recent reports
have shown that percutaneous angiographic embolization may be the
therapy of choice with high technical success rates of 75% to 100%, low
morbidity rates of 14% to 25%, and death rates of 0% to 14% [110,113,
114]. Most of these studies are limited by small numbers of patients and
short follow-up period. Some authors advocate percutaneous angiographic
embolization as first-line therapy and surgery for other secondary
complications [97,98]. It may be useful to proceed with excision or
a drainage procedure after percutaneous angiographic embolization,
particularly when the pseudoaneurysm is large ([10 cm). Percutaneous
angiographic embolization is recommended as the initial therapy for
hemodynamically stable patients. Surgery should be reserved for unstable
patients with active bleeding; failed embolization; and for other complica-
tions, such as infection and extrinsic compression.

References
[1] de Beaux AC, Palmer KR, Carter DC. Factors influencing morbidity and mortality in
acute pancreatitis; an analysis of 279 cases. Gut 1995;37:121–6.
[2] Balthazar EJ, Robinson DL, Magibow ASJ, et al. Acute pancreatitis: value of CT in
establishing prognosis. Radiology 1990;174:331–6.
[3] Sigurdsson GH. Intensive care management of acute pancreatitis. Dig Surg 1994;11:
231–41.
[4] Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, et al. IAP Guidelines for
the Surgical Management of Acute Pancreatitis. Pancreatology 2002;2:565–73.
[5] Bradley EL. A clinically based classification system for acute pancreatitis. Arch Surg
1993;128:586–90.
[6] Neoptolemos JP, London NJ, James D, et al. Controlled trial of urgent endoscopic
retrograde cholangiopancreatography and endoscopic sphincterotomy versus conserva-
tive treatment for acute pancreatitis due to gallstones. Lancet 1988;2:979–83.
[7] Fan ST, Lai CS, Mok FPT, et al. Early treatment of acute biliary pancreatitis by
endoscopic papillotomy. N Engl J Med 1993;328:228–32.
[8] Folsch UR, Nitsche R, Ludtke R, et al. Early ERCP and papillotomy compared
with conservative treatment for acute biliary pancreatitis. N Engl J Med 1997;336:
237–42.
[9] Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997;92:377–86.
[10] Steinberg W, Tenner S. Acute pancreatitis. N Engl J Med 1994;330:1198–210.
1190 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

[11] Banerjee AK, Kaul A, Bache E, Parberry AC, Doran J, Nicholson ML. An audit of fatal
acute pancreatitis. Postgrad Med J 1995;71:472–5.
[12] Wilson PS, Manji M, Neoptolemos JP. Acute pancreatitis as a model of sepsis. J
Antimicrob Chemother 1998;41(suppl A):51–63.
[13] Makhija R, Kingsnorth AN. Cytokine storm in acute pancreatitis. J Hepatobiliary
Pancreat Surg 2002;9:401–10.
[14] Health DI, Cruickshank A, Gudgeon M, et al. Role of interleukin-6 in mediating the
acute phase protein response and potential as an early means of severity assessment in
acute pancreatitis. Gut 1993;34:41–5.
[15] Davies MG, Hagen P-O. Systemic inflammatory response syndrome. Br J Surg 1997;
84:920–35.
[16] Heath D, Alexander D, Wilson C, et al. Which complications of acute pancreatitis are
most lethal? A prospective multi-centre clinical study of 719 episodes [abstract]. Gut 1995;
36:A478.
[17] Banks PA, Tenner S, Noordhoek EC, et al. Does pancreatic necrosis predict severity in
patients with acute pancreatitis? Digestion 1996;57:218.
[18] Sakorafas GH, Tsiotou AG. Etiology and pathogenesis of acute pancreatitis: current
concepts. J Clin Gastroenterol 2000;30:343–56.
[19] Bank S, Indaram A. Causes of acute and recurrent pancreatitis. Clinical considerations
and clues to diagnosis. Gastroenterol Clin North Am 1999;28:571–89.
[20] Frakes JT. Biliary pancreatitis: a review emphasizing appropriate endoscopic inter-
vention. J Clin Gastroenterol 1999;28:97–109.
[21] Kelly TR, Wagner DS. Gallstone pancreatitis: a prospective randomized trial of the
timing of surgery. Surgery 1988;104:600–4.
[22] Nowak A, Sowakowska-Dulawa E, Marek T, Rybicka J. Final results of the prospective,
randomized, controlled study on endoscopic sphincterotomy versus conventional manage-
ment in acute biliary pancreatitis [abstract]. Gastroenterology 1995;108:A380.
[23] Sharma VK, Howden CW. Meta-analysis of randomized controlled trials of endoscopic
retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute
biliary pancreatitis. Am J Gastroenterol 1999;94:3211–4.
[24] Freeman MF, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, et al.
Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335:909–18.
[25] Freeman ML, DiSario JA, Nelson DB, Fennerty MB, Lee JG, Bjorkman DJ, et al. Risk
factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc
2001;54:425–34.
[26] Sherman S, Lehman GA. Endoscopic therapy of pancreatic disease. Gastroenterologist
1997;5:262–77.
[27] Tarnasky P, Palesch Y, Cunningham J, Maulsin P, Cotton P, Hawes RH. Pancreatic
stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of
Oddi dysfunction. Gastroenterology 1998;115:1518–24.
[28] May GR, Shaffer EH. Should elective endoscopic sphincterotomy replace cholecystec-
tomy for the treatment of high-risk patients with gallstone pancreatitis? J Clin
Gastroenterol 1991;13:125–8.
[29] Siegel JH, Veerappan A, Cohen SA, Kasmin FE. Endoscopic sphincterotomy for biliary
pancreatitis: an alternative to cholecystectomy in high-risk patients. Gastrointest Endosc
1994;40:573–5.
[30] Uomo G, Manes G, Laccetti M, Cavallera A, Rabitti PG. Endoscopic sphincterotomy
and recurrence of acute pancreatitis in gallstone patients considered unfit for surgery.
Pancreas 1997;14:2831.
[31] Welbourn CR, Beckly DE, Eyre-Brook IA. Endoscopic sphincterotomy without chole-
cystectomy for gallstone pancreatitis. Gut 1995;37:119–20.
[32] Hammarstrom LE, Stridbeck H, Ihse I. Effect of endoscopic sphincterotomy and interval
cholecystectomy on late outcome after gallstone pancreatitis. Br J Surg 1988;85:333–6.
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1191

[33] Hill J, Martin DF, Tweedle DE. Risks of leaving the gallbladder in situ after endoscopic
sphincterotomy for bile duct stones. Br J Surg 1991;78:554–7.
[34] Livingston DH, Deitch EA. Multiple organ failure: a common problem in surgical
intensive care unit patients. Ann Med 1995;27:13–20.
[35] McFadden DW. Organ failure and multiple organ system failure in pancreatitis. Pancreas
1991;6:S37–43.
[36] Shields CJ, Winter DC, Redmond HP. Lung injury in acute pancreatitis: mechanisms,
prevention, and therapy. Curr Opin Crit Care 2002;8:158–63.
[37] Talamini G, Bassi C, Falconi M, et al. Cigarette smoking: an independent risk factor in
alcoholic pancreatitis. Pancreas 1996;12:131–7.
[38] Martinez J, Sanchez-Paya J, Palazon JM, Aparicio JR, Pico A, Perez-Mateo M. Obesity:
a prognostic factor of severity in acute pancreatitis. Pancreas 1999;19:15–20.
[39] Funnell IC, Bornman PC, Weakley SP, et al. Obesity: an important prognostic factor in
acute pancreatitis. Br J Surg 1993;80:484–6.
[40] Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and
the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139:
69–81.
[41] Blarney SL, Imrie CW, O’Neill J, Gilmour WH, Carter DC. Prognostic factors in acute
pancreatitis. Gut 1984;25:1340–6.
[42] Dominguez-Monoz JE, Carballo F, Garcia MJ, de Diego JM, Campos R, Yanguela J, et al.
Evaluation of the clinical usefulness of APACHE II and SAPS systems in the initial
prognostic classification of acute pancreatitis: a multicenter study. Pancreas 1993;8:682–6.
[43] Beal AL, Cerra FB. Multiple organ failure syndrome in the 1990s. JAMA 1994;271:
226–33.
[44] Brown A, Baillargeon J-D, Hughes MD, Banks PA. Can fluid resuscitation prevent
pancreatic necrosis in severe acute pancreatitis? Pancreatology 2002;2:104–7.
[45] Luiten EJT, Hop WCJ, Lange JF, et al. Controlled clinical trial of selective decon-
tamination for the treatment of severe acute pancreatitis. Ann Surg 1995;222:57–65.
[46] Bassi C. Infections in pancreatic inflammatory disease: clinical trials for antibiotic
prophylaxis. Pancreatology 2001;1:210–2.
[47] Exley AR, Leese T, Holliday MP, et al. Endotoxaemia and serum tumour necrosis factor
as prognostic markers in severe acute pancreatitis. Gut 1992;33:1126–8.
[48] Curley P, Wernor M, Collins K, et al. Decreased interleukin-2 production in severe acute
pancreatitis: potential for immunomodulation. Gastroenterology 1996;110:583–8.
[49] Kingsnorth AN, Galloway SW, Formela LJ. Randomized, double-blind phase II trial of
lexipafant, a platelet-activating factor antagonist, in human acute pancreatitis. Br J Surg
1995;82:1414–20.
[50] Kingsnorth AN, for the British Acute Pancreatitis Study Group. Early treatment with
lexipafant, a platelet activating factor antagonist reduces mortality in acute pancreatitis:
a double blind, randomized placebo controlled study [abstract]. Gastroenterology 1997;
112:A453.
[51] Curran FJM, Sharples CE, Young CA, et al. Controlled trial of lexipafant in severe acute
pancreatitis [abstract]. Pancreas 1995;11:424.
[52] Gullo L, Migliori M, Olah A, Farkas G, Levy P, Arvanitakis C, et al. Acute pancreatitis
in five European countries: etiology and mortality. Pancreas 2002;24:223–7.
[53] Uhl W, Roggo A, Kirschstein T, Anghelacopoulos SE, Gloor B, Muller CA, et al.
Influence of contrast-enhanced computed tomography on course and outcome in patients
with acute pancreatitis. Pancreas 2002;24:191–7.
[54] Bradley EL III, editor. Surgical indications and techniques in necrotizing pancreatitis. In:
Acute pancreatitis diagnosis and therapy. New York: Raven Press; 1994. p. 105–17.
[55] Banks PA. The role of needle-aspiration bacteriology in the management of necrotizing
pancreatitis. In: Bradley EL III, editor. Acute pancreatitis diagnosis and therapy. New
York: Raven Press; 1994. p. 99–103.
1192 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

[56] Banks PA, Gerzof SG, Langevin RE, Silverman SG, Sica GT, Hughes MD. CT-guided
aspiration of suspected pancreatic infection: bacteriology and clinical outcome. Int J
Pancreatol 1995;18:265–70.
[57] Beattie GC, Mason J, Swan D, Madhavan KK, Siriwardena AK. Outcome of
necrosectomy in acute pancreatitis: the case for continued vigilance. Scand J Gastro-
enterol 2002;37:1449–53.
[58] Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M. Percutaneous CT
guided catheter drainage of infected acute necrotizing pancreatitis: techniques and results.
AJR Am J Roentgenol 1998;170:969–75.
[59] Baron T, Harewood G, Morgan D, et al. Outcome differences after endoscopic drainage
of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts.
Gastrointest Endosc 2002;56:7–17.
[60] Neoptolemos JP, London NJM, Carr-Locke DL. Assessment of main pancreatic duct
integrity by endoscopic retrograde pancreatography in patients with acute pancreatitis.
Br J Surg 1993;80:94–9.
[61] Lau ST, Simchuk EJ, Kozarek RA, Traverso LW. A pancreatic ductal leak should be
sought to direct treatment in patients with acute pancreatitis. Am J Surg 2001;18:411–5.
[62] Pederzoli P, Bassi C, Vesentini S, Campedelli A. A randomized multicentre clinical trial of
antibiotic prophylaxis of septic complications in acute pancreatitis with imipenem. Surg
Gynecol Obstet 1993;176:480–3.
[63] Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V,
et al. Early antibiotic treatment in acute necrotising pancreatitis. Lancet 1995;346:663–7.
[64] Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibiotics in treatment of severe acute
alcoholic pancreatitis. Pancreas 1996;13:198–201.
[65] van Sonnenberg E. Percutaneous therapy for pancreatic abscess. In: Bradley EL III,
editor. Acute pancreatitis diagnosis and therapy. New York: Raven Press; 1994. p. 161–4.
[66] Poston GJ, Williamson RCN. Surgical management of acute pancreatitis. Br J Surg
1990;77:5–12.
[67] Meldrum DR, Moore FA, Moore EE, et al. Prospective characterization and selective
management of the abdominal compartment syndrome. Am J Surg 1997;174:667–73.
[68] Bracher GA, Manocha AP, DeBanto JR, et al. Endoscopic pancreatic duct stenting to
treat pancreatic ascites. Gastrointest Endosc 1999;49:710–5.
[69] Lanternier F, Valcke J, Hernigou A, Wermert D, et al. Pancreatico-pleural fistula: a rare
cause of bilateral pleurisy and cardiac tamponade. Rev Mal Respir 2002;19:795–7.
[70] Kozarek RA, Traverso LW. Pancreatic fistulas and ascites. In: Brandt JL, editor.
Textbook of clinical gastroenterology. Philadelphia: Current Medicine; 1998. p. 1175–81.
[71] Telford JJ, Farrell JJ, Saltzman JR, et al. Pancreatic stent placement for duct disruption.
Gastrointest Endosc 2002;56:18–24.
[72] Akahane T, Kuriyama S, Matsumoto M, Kikuchi E, et al. Pancreatic pleural effusion
with a pancreaticopleural fistula diagnosed by magnetic resonance cholangiopancreatog-
raphy and cured by somatostatin analogue treatment. Abdom Imaging 2003;28:92–5.
[73] Lankisch PG, Lohr-Happe A, Otto J, Creutzfeldt W. Natural course in chronic
pancreatitis: pain, exocrine and endocrine pancreatic insufficiency and prognosis of the
disease. Digestion 1993;54:148–55.
[74] Wakasugi H, Funakoshi A, Iguchi H. Clinical assessment of pancreatic diabetes caused
by chronic pancreatitis. J Gastroenterol 1998;33:254–9.
[75] DiMagno EP, Layer P, Clain JE. Chronic pancreatitis. In: Go VLW, DiMagno EP,
Gardner JD, Lebenthal L, Reber HA, Scheele GA, editors. The pancreas: biology,
pathobiology and disease. New York: Plenum Press; 1993. p. 676–7.
[76] Larsen S, Hilsted J, Philipsen EK, et al. Glucose counterregulation in diabetes secondary
to chronic pancreatitis. Metabolism 1990;39:138–43.
[77] Bradley EL, Gonzalez AC, Clements JJ. Acute pancreatic pseudocysts: incidence and
implications. Ann Surg 1976;184:734–7.
 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194 1193

[78] Laxson LC, Fromkes JJ, Cooperman M. Endoscopic retrograde cholangiopancreatog-

raphy in the management of pancreatic pseudocysts. Am J Surg 1985;150:683–6.
[79] Grimm H, Binmoeller KF, Soehendra N. Endosonography-guided drainage of
a pancreatic pseudocyst. Gastrointest Endosc 1992;38:170–1.
[80] Lehman G. Role of ERCP and other endoscopic modalities in chronic pancreatitis.
Gastrointest Endosc 2002;56s:S237–40.
[81] Vitas GJ, Sarr MG. Selected management of pancreatic pseudocysts: operative versus
expectant management. Surgery 1992;111:123–30.
[82] Stabile BE, Wilson SE, Debas HT. Reduced mortality from bleeding pseudocysts and
pseudoaneurysms caused by pancreatitis. Arch Surg 1983;118:45–51.
[83] Yeo CJ, Bastidas JA, Lynch-Nyhan A, Fishman EK, Zinner MJ, Cameron JL. The
natural history of pancreatic pseudocysts documented by computed tomography. Surg
Gynecol Obstet 1990;170:411–7.
[84] Becker JM, Pemberton JH, DiMagno EP, Ilstrup DM, McIlrath DC, Dozois RR.
Prognostic factors in pancreatic abscess. Surgery 1984;96:455–61.
[85] Gerzof SG, Banks PA, Robbins AH, et al. Early diagnosis of pancreatic infection by
computed tomography-guided aspiration. Gastroenterology 1987;93:1315–20.
[86] Tan MH, Kirk G, Archibold P, Kennedy P, Regan MC. Cardiac compromise due to
a pancreatic mediastinal pseudocyst. Eur J Gastroenterol Hepatol 2002;14:1279–82.
[87] Segal I, Parekh D, Lipschitz J, Gecelter G, Myburgh JA. Treatment of pancreatic ascites
and external pancreatic fistulas with a long-acting somatostatin analogue (Sandostatin).
Digestion 1993;1:53–8.
[88] Pitchumoni CS, Agarwal N. Pancreatic pseudocysts. When and how should drainage be
performed? Gastroenterol Clin North Am 1999;28:615–39.
[89] Atabek U, Mayer D, Amin A, Camishion RC. Pancreatic cystogastrostomy by combined
upper endoscopy and percutaneous transgastric instrumentation. J Laparoendosc Surg
1993;3:501–4.
[90] Huibregtse K, Smits ME. Endoscopic management of diseases of the pancreas. Am J
Gastroenterol 1994;89:S66–77.
[91] Binmoeller KF, Seifert H, Walter A. Transpapillary and transmural drainage of
pancreatic pseudocysts. Gastrointest Endosc 1995;43:219–24.
[92] Barthet M, Sahel J, Bodiou-Bertel C, Bernard JP. Endoscopic transpapillary drainage of
pancreatic pseudocysts. Gastrointest Endosc 1995;42:208–13.
[93] Smits ME, Rauws EAJ, Tytgat GNJ, Huibregtse K. The efficacy of endoscopic treatment
of pancreatic pseudocysts. Gastrointest Endosc 1995;42:202–7.
[94] Howell DA, Elton E, Parsons WG. Endoscopic management of pseudocysts of the
pancreas. Gastrointest Endosc Clin N Am 1998;46:143–62.
[95] Libera ED, Siqueira ES, Morais M, Rohr MR, Brant CQ, Ardengh JC, et al. Pancreatic
pseudocysts transpapillary and transmural drainage. HPB Surg 2000;11:333–8.
[96] Mori T, Abe N, Sugiyama M, Atomi Y, Way LW. Laparoscopic pancreatic cysto-
gastrostomy. J Hepatobiliary Pancreat Surg 2000;7:28–34.
[97] Wilson C, Auld CD, Schlinkert R, et al. Hepatobiliary complications in chronic
pancreatitis. Gut 1989;30:520–7.
[98] Deviere J, Devaere S, Baize M, Cremer M. Endoscopic biliary drainage in chronic
pancreatitis. Gastroenterology 1990;36:96–100.
[99] Deviere J, Cremer M, Baize M, Love J, Sugai B, Vandermeeren A. Management of
common bile duct stricture caused by chronic pancreatitis with metal mesh self-
expandable stents. Gut 1994;35:122–6.
[100] Bernades P, Baetz A, Levy P, Belghiti J, Menu Y, Fekete F. Splenic and portal venous
obstruction in chronic pancreatitis: a prospective longitudinal study of a medical-surgical
series of 266 patients. Dig Dis Sci 1992;37:340–6.
[101] Poynard T, Cales P, Pasta L, et al. Beta-adrenergic-antagonist drugs in the pre-
vention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices:
1194 N.-M. Law, M.L. Freeman / Gastroenterol Clin N Am 32 (2003) 1169–1194

an analysis of data and prognostic factors in 589 patients from four randomized
clinical trials. Franco-Italian Multicenter Study Group. N Engl J Med 1991;324:
1532–8.
[102] Marshall GT, Howell DA, Hansen BL, Amberson SM, Abourjaily GS, Bredenberg CE.
Multidisciplinary approach to pseudoaneurysms complicating pancreatic pseudocysts.
Arch Surg 1996;131:278–82.
[103] Stanley JC, Frey CF, Miller TA, Lindenauer SM, Child CG. Major arterial hemorrhage:
a complication of pancreatic pseudocysts and chronic pancreatitis. Arch Surg 1976;
111:435–40.
[104] Waltman AC, Luers PR, Athanasoulis CA, Warshaw AL. Massive arterial hemorrhage in
patients with pancreatitis. Arch Surg 1986;121:439–43.
[105] Hamel AE, Parc R, Adda G, Bouteloup PY, Huguet C, Malafosse M. Bleeding
pseudocysts and pseudoaneurysms in chronic pancreatitis. Br J Surg 1991;78:1059–63.
[106] Abbott GT, McDermott VG, Smith TP. Successful endovascular treatment of a celiac
artery pseudoaneurysm complicating pancreatitis. J Vasc Interv Radiol 1996;7:103–6.
[107] Burke JW, Erickson SJ, Kellum CD, Tegtmeyer CJ, Williamson BRJ, Hansen MF.
Pseudoaneurysms complicating pancreatitis: detection by CT. Radiology 1996;161:
447–50.
[108] Boudghene F, L’Hermine C, Bigot JM. Arterial complications of pancreatitis: diagnostic
and therapeutic aspects in 104 cases. J Vasc Interv Radiol 1993;4:551–8.
[109] Goff WB, Lawrence DP, Burkhard TK. Aortic dissection in acute pancreatitis. J Am
Osteopath Assoc 1992;92:921–3.
[110] Pitkädaranta P, Haapiainen R, Kivisaari L, Schröder L. Diagnostic evaluation and
aggressive surgical approach in bleeding pseudoaneurysms associated with pancreatic
pseudocysts. Scand J Gastroenterol 1991;26:58–64.
[111] Cahow CE, Gusberg RJ, Gottlieb LJ. Gastrointestinal hemorrhage from pseudoaneur-
ysms in pancreatic pseudocysts. Am J Surg 1983;145:534–41.
[112] Yamagishi S, Yamashita H, Sasaki M, Fuchizaki U, Sakai A, Yoneshima M, et al.
Control of massive bleeding of a pancreatic pseudoaneurysm penetrating into the colon
by transcatheter arterial embolization. Am J Gastroenterol 1994;89:1268–9.
[113] Savastano S, Feltrin GP, Antonio T, Miotto D, Chiesura-Corona M, Castellan L.
Arterial complications of pancreatitis: diagnostic and therapeutic role of radiology.
Pancreas 1993;6:687–92.
[114] Hofer BO, Ryan JA, Freeny PC. Surgical significance of vascular changes in chronic
pancreatitis. Surg Gynecol Obstet 1987;164:499–505.