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Chapter 14
a
c
Figure14.5 • Retrocolic and preperitoneal extension of peripancreatic necrosis. (a) Paraduodenal abscess managed
by percutaneous drainage. (b) Preperitoneal extension pointing in the perineum via the inguinal canal. (c) Horseshoe
collection extending down right and left paracolic gutters.
Box14.5 • Escalating nutritional support algorithm
for acute pancreatitis
Diet with oral supplements
Nasogastric (NG) feeding
Nasojejunal (NJ) feeding
Total parenteral nutrition (TPN)
b
Delayed gastric emptying/gastric outlet obstruction
Gastric outlet obstruction resulting in persistent
vomiting or high-volume gastric aspirates from NG
suction may complicate up to 10% of patients with
severe acute pancreatitis. The recent trend towards
NJ intubation has rendered this complication less
troublesome and the majority of patients can be
treated by nasoenteric feeding until the local oedema/
ileus settles. Occasionally, a gastroenterostomy is
inflammatory response and organ failure in those
receiving enteral support.
32
Unfortunately there
were only 13 patients with severe disease, limiting the
validity of the conclusions. There have been several
trials comparing so-called ‘immunonutrition’ with
standard enteral feeding in critically ill patients, but
so far no evidence of benefit has been demonstrated
in acute pancreatitis.
33
Similarly, there has been
interest in the role of ‘probiotics’, but a randomised
trial from the Netherlands found an increase in
fatal complications in the probiotic group, with an
unexpectedly high incidence of intestinal necrosis.
required for long-standing gastric stasis.
Management of acute phase complications
Haemorrhage
Haemorrhage into a walled-off collection or following
necrosectomy is a relatively common problem. This is
a consequence of a combination of factors: a large
raw surface, partly controlled sepsis and exposed
major vessels leading to primary or reactionary
haemorrhage. Fresh blood in a drain, even of
modest volume, requires attention as this will often
34
represent a ‘herald bleed’ of imminent catastrophic
252
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Complicated acute pancreatitis
haemorrhage. Urgent CT angiography (CTA) to
identify a target, followed by embolisation with
endovascular metal coils, is the treatment of choice.
Fig.14.6 illustrates active bleeding from a gastro-
duodenal artery pseudoaneurysm. The increase in
intracavity pressure associated with bleeding into
an infected necrotic collection often results in a
simultaneous episode of sepsis with bacteraemia
and organ dysfunction, the hypotension being
multifactorial.
A normal CTA suggests a venous source and
bleeding in this context is usually associated with
venous congestion, often secondary to portal
venous thrombosis. Where percutaneous access
to the cavity is possible, local packing will often
arrest the bleeding, either with balloon tamponade
(Fig.14.7) or gauze strips, but surgical intervention
and suture ligation of the bleeding point may be
required. The challenges of gaining surgical access
and achieving haemostasis in a patient with active
haemorrhage, escalating organ dysfunction,
coagulopathy and venous hypertension within a
hostile abdomen should not be underestimated.
The combination of haemorrhage and subsequent
laparotomy frequently precipitates escalating
organ failure and death.
Venous thrombosis
All patients with severe acute pancreatitis
should be considered high risk for venous
thromboembolic disease and receive prophylactic
low molecular weight heparin (LMWH) and
compression stockings. Splenic vein thrombosis is
frequently identified on serial CT and is the result
of a combination of local inflammation, extrinsic
compression from collections and a low flow
state. Splenic vein thrombosis does not require
active treatment with therapeutic LMWH.
35
Superior mesenteric or portal vein thrombosis
should be managed by therapeutic LMWH for
6months in an attempt to maintain patency and
avoid cavernous transformation of the portal vein.
Despite active treatment, recanalisation rarely
occurs in practice, and collateralisation will ensue.
LMWH is preferred to warfarin, heparin, or one of
the oral Factor Xa inhibitors, as it does not require
monitoring and avoids compromising timing of
interval intervention should it be required.
Figure14.6 • Selective cannulation of the common
hepatic artery showing filling of a pseudoaneurysm
(marked with an arrow) arising from the gastroduodenal
artery in a patient with haemorrhage into central
pancreatic necrosis.
Figure14.7 • Balloon tamponade (using the
oesophageal balloon of a Sengstaken–Blakemore tube)
for venous haemorrhage following a percutaneous
necrosectomy – resolved without further intervention.
Enteric fistula
Abscess formation in conjunction with focal enteric
ischaemia can lead to fistulation between the acute
necrotic or walled off collection and the lumen of
the bowel. This is almost universally associated
with the presence of gas and sometimes a fluid level
within the cavity. Historically this was seen as an
indication for intervention, but the physiological
impact and clinical course are dependent upon the
site of fistulation into the gastrointestinal tract.
Spontaneous discharge of a post-acute collection
into the upper gastrointestinal tract is not
uncommon, effectively mimicking what happens
when an EUS-guided cystgastrostomy is performed.
This may decompress the collection and result in
clinical improvement. Fluid levels are common and
the radiological appearance does not correlate with
the clinical condition of the patient. Immediate
intervention is not usually required but care must
be taken to observe for inadequate resolution which
can lead to late recurrent sepsis.
In contrast, fistulation into the lower
gastrointestinal tract more often results in a
poorly drained collection, bacterial contamination
and persistent sepsis. These rarely settle without
intervention. Colectomy was formally proposed
as part of a debridement procedure, but adequate
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253
Chapter 14
Figure14.8 • Large pseudocyst resulting in gastric
and extrahepatic biliary obstruction with jaundice. Both
resolved following decompression by EUS-guided
cystgastrostomy.
control can often be achieved by formation of a
trephine defunctioning ileostomy minimising the
surgical hit in a compromised patient.
Biliary obstruction
Extrahepatic biliary obstruction may complicate
the management of severe acute pancreatitis due to
extrinsic compression of the common bile duct by a
large acute necrotic collection. ERCP in this situation
is extremely difficult as the duodenum is usually
oedematous and visualisation of the ampulla often
impossible. In the acute phase it is unusual to have a
true stricture and biliary decompression will often
result from endoscopic or percutaneous drainage of the
acute collection to relieve the pressure (see Fig.14.8).
Foregut fistulas often lead to clinical
improvement; hindgut fistulas usually result in
marked clinical deterioration.
Long-term complications
Pancreatic duct fistula
This complication most commonly follows prior
intervention for an acute post-inflammatory collection
or infected necrosis, and manifests as persistent
drainage of amylase-rich opalescent fluid, in the
absence of significant sepsis. Simple removal of the
drain may facilitate closure of small volume leaks, but
if persistent, the management is similar to that of a
communicating pseudocyst, initially by transpapillary
stenting where possible. Central gland necrosis may
result in stricture formation and duct occlusion at the
level of the pancreatic neck, with preferential drainage
of pancreatic juice arising from viable pancreatic tissue
in the pancreatic tail along the drain tract. A significant
advantage of the endoscopic drainage approach is that
any residual fistula from the pancreatic tail is at least
initially clinically silent as the fistula drains into the
gastric lumen.
Intraperitoneal rupture of a pseudocyst can result
in pancreatic ascites or pleural effusion (Fig.14.9).
These patients are usually profoundly catabolic.
More invasive management of a persistent fistula,
either inaccessible or failing to respond to ductal
stenting, should be delayed by percutaneous or
endoscopic control, until the patient has made a full
recovery, and again often requires surgical resection
(distal pancreatectomy and splenectomy).
Pancreatic duct stricture
Pancreatic duct stricture can occur following
resolution of an attack of acute pancreatitis as a
result of local tissue damage and fibrotic repair.
A pancreatic duct stricture may be present on its
own, or in association with a duct disruption
causing a pseudocyst or pancreatic fistula. Isolated
pancreatic duct stricture can result in recurrent
attacks of abdominal pain, hyperamylasaemia and
dilatation of the distal duct system. Management
of the stricture may be by simple dilatation and
temporary stenting at ERCP, by surgical resection
of the stricture along with the pancreatic tail, or by
surgical drainage of the pancreatic duct system into
a Roux loop.
After significant central necrosis complete occlusion
occurs, resulting in ‘disconnected duct syndrome’
should a remnant of viable tail remain. The treatment
of this is described below.
Disconnected duct syndrome
Cutaneous or gastric mucosal closure of a pancreatic
fistula may be followed by the development of a
pseudocyst lying in the former pancreatic bed. This
is preceded by necrosis, fibrosis and atrophy of the
middle of the gland. It leads eventually to ‘disconnected
duct syndrome’, with a pseudocyst forming between
the proximal pancreas and a viable distal parenchymal
remnant. Endoscopic transgastric drainage under
endoscopic ultrasound may be a useful option. The
presence of a fibrotic pancreatic ductal occlusion often
at the pancreatic neck usually precludes transpapillary
options. Surgical resection or drainage procedures are
often required if resolution is not achieved. Surgery in
this context is challenging, particularly if there are large
venous collaterals secondary to splenic vein occlusion.
A ‘salvage’ distal pancreatectomy and splenectomy is
frequently required.
Late extrahepatic biliary stricture
In contrast to biliary obstruction in the acute phase,
jaundice developing months after resolution is
usually a result of focal fibrosis and scarring within
the pancreatic head. Debris and stones may form
254
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Complicated acute pancreatitis
a
Figure14.9 • Post acute pancreatitis: (a) pancreatico-pleural fistula and (b) pancreatic ascites.
above the stricture leading to episodes of cholangitis.
Endoscopic stenting at ERCP can alleviate an acute
attack but does not address the underlying pathology.
Remodelling of the fibrotic segment using a fully
covered self-expanding metal stent (SEMS) will
often result in prolonged relief but recurrence is
common on stent removal. Failure of endoscopic
remodelling is an indication for a formal hepaticojejunostomy where fitness allows.
b
endoscopic or radiological appearance. Despite the
frequency of venous collaterals on follow-up CT, late
gastrointestinal haemorrhage due to gastric varices
is rare. Surgical intervention is more commonly
required for a disconnected duct syndrome than for
bleeding, and if there is significant concern regarding
segmental venous collateralisation prior to surgery,
preoperative embolisation of the splenic artery may
decompress the system to facilitate resection.
Right-sided, or global superior mesenteric and portal
Portal and splenic vein thrombosis and cavernous
transformation
Splenic and portal vein thrombosis is associated with
up to 15% of patients dying with acute pancreatitis.
In those patients with established thrombosis who
survive the acute attack, the venous drainage is
diverted through the short gastric, gastroepiploic and
cardinal veins resulting in large venous collaterals.
Segmental portal hypertension limited to the drainage
territory of the splenic vein may result in a concerning
venous occlusion with cavernous transformation
of the pancreatic head, duodenum and hepaticoduodenal ligament is a more significant problem as it
may preclude even intermediate surgical intervention
(e.g. hepatico-jejunostomy for extrahepatic biliary
obstruction). Recurrent low-grade sepsis in the
presence of cavernous transformation is one of the
most challenging complications of acute pancreatitis.
On rare occasions, consideration of a multivisceral
transplant may be the only option.
Key points
• Approximately 20% of patients with acute pancreatitis develop severe AP, with local and/or systemic
complications, of whom half will die.
• The Revised Atlanta Classification defines local complications according to timing and presence of
necrosis, and adds a new category (moderately severe pancreatitis).
• Necrosis per se is not an indication for intervention, but infected necrosis is the most feared
complication of AP.
• Intervention for complications of AP should be delayed for as long as possible and is guided by
patient physiology.
• Efforts should be made to minimise the negative impact of each intervention – ‘the step-up approach’.
• There is no role for ERCP in the management of AP in the absence of biliary sepsis.
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255
Chapter 14
• The nutritional support algorithm starts with oral intake and ends with TPN.
• The key to successful management of infected necrosis is control of sepsis.
• Endoscopic and other minimally invasive techniques have largely replaced open surgery in the
management of both early and late complications of AP.
• A key principle in managing the complications of AP is ‘do as little as you can, as late as you can’.
Full references available at http://
expertconsult.inkling.com
Key references
1. Working Group IAPAPAAPG. IAP/APA evidencebased guidelines for the management of acute
pancreatitis. Pancreatology 2013;13(4 Suppl. 2):e1–
15. PMID: 24054878.
These international guidelines provide 38 evidencebased recommendations relating to the clinical
management of acute pancreatitis. They offer a
comprehensive summary of the existing literature for
all those involved in the care of this patient group from
referring clinician to hospital specialist.
3. Banks PA, BollenTL, DervenisC, etal. Classification
of acute pancreatitis – 2012: revision of the Atlanta
classification and definitions by international
consensus. Gut 2013;62(1):102–11. PMID: 23100216.
International Consensus revision of the original Atlanta
classification of acute pancreatitis. It uses clinical
and radiological criteria to provide clear definitions of
severity and associated complications.
6. Uy MC, Daez ML, Sy PP, et al. Early ERCP in
acute gallstone pancreatitis without cholangitis: a
meta-analysis. JOP 2009;10(3):299–305. PMID:
19454823.
Previous data suggested that early ERCP in the context
of acute pancreatitis improved outcome. This metaanalysis only included two RCTs but demonstrated a
trend towards increasing mortality when ERCP was
used in AP in the absence of cholangitis.
11. Carter CR, McKay CJ, Imrie CW. Percutaneous
necrosectomy and sinus tract endoscopy in the
management of infected pancreatic necrosis: an
initial experience. Ann Surg 2000;232(2):175–80.
PMID: 10903593.
This paper reported the initial experience of the
minimally invasive approach to infected pancreatic
necrosis including technique and outcome. It
demonstrated that sepsis resolution can be achieved
with an apparent reduction in postoperative organ
dysfunction and critical care support.
14. SeifertH, BiermerM, SchmittW, etal. Transluminal
endoscopic necrosectomy after acute pancreatitis:
a multicentre study with long-term follow-up (the
GEPARD Study). Gut 2009;58(9):1260–6. PMID:
19282306.
This key paper demonstrated good clinical outcomes
with an endoscopic transluminal approach to infected
necrosis. Of significance, this is a large series (n
excellent long-term follow-up (mean period of 43months).
= 93) with
17. van Santvoort HC, Besselink MG, Bakker OJ,
et al. A step-up approach or open necrosectomy
for necrotizing pancreatitis. N Engl J Med
2010;362(16):1491–502. PMID: 20410514.
Landmark, multicentre randomised trial demonstrating
a reduction in the composite endpoint of major
complications or death with the ‘step-up’ approach when
compared to open necrosectomy. Of note, 35% of patients
were managed with percutaneous drainage alone.
30. KalfarentzosF, Kehagias J, MeadN, et al. Enteral
nutrition is superior to parenteral nutrition in
severe acute pancreatitis: results of a rand omized
prospective trial. Br J Surg 1997;84(12):1665–9.
Although a relatively small study (n = 38), this
randomised trial provided data to challenge the
previously held dogma that patients with acute
pancreatitis required parenteral nutrition. Feeding was
both safer and cheaper in the enteral nutrition cohort.
31. Al-OmranN, AlBalawi ZH, Tashkandi MF, et al.
Enteral versus parenteral nutrition for acute
pancreatitis. Cochrane Rev 2010;. (1):CD002837.
PMID: 20091534.
A review of eight RCTs in patients with acute pancreatitis
showing that enteral nutrition significantly reduced
mortality, multi-organ failure, systemic infections and
the need for operative interventions compared to
parenteral nutrition.
34. BesselinkMG, TimmermanHM, BuskensE, etal.
Probiotic prophylaxis in patients with predicted
severe acute pancreatitis (PROPATRIA): design
and rationale of a double-blind, placebocontrolled randomised multicenter trial
[ISRCTN38327949]. BMC Surg 2004;4:12.
PMID: 15456517.
This randomised, placebo-controlled multicentre trial
addressed the question of probiotic prophylaxis in
patients with predicted SAP. One of the key outcomes
was a reduction in bacterial translocation overall, but
an increase in bacterial translocation and enterocyte
damage in patients with organ failure.
256
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15
Chronic pancreatitis
Ajith K. Siriwardena
C. Ross Carter
Introduction
Chronic pancreatitis is defined as a benign
inflammatory disease, characterised by chronic
pancreatic inflammation and scarring, irreversibly
damaging the gland and resulting in loss of pancreatic
exocrine and endocrine function.
aetiological factor is long-term excessive consumption
of alcohol.
smoking.
mutations in trypsin activation genes and also cystic
fibrosis genes.
dominant symptom. Baseline assessment, in addition
to careful clinical examination, must include crosssectional imaging (typically CT). Treatment planning
should ideally take place on a multidisciplinary basis.
Pancreatic exocrine and endocrine function should
be assessed and insufficiency treated. Pain control
should follow the World Health Organisation’s
analgesic ladder originally developed for cancer pain.
Co-analgesics such as gabapentin may be used in
conjunction with conventional analgesics.
interventions take the form of endoscopic and surgical
treatment. Endoscopic interventions are directed
at improving pancreatic duct drainage, managing
pancreatic duct disruption, treatment of extrahepatic
biliary obstruction, and/or pain control through
coeliac plexus nerve block. Surgical interventions
depend on the morphology of the diseased pancreas.
In patients with a pancreatic head mass and
concomitant chronic pancreatitis, pancreatic cancer
must be considered in the differential diagnosis.
Endoscopic ultrasound with fine-needle aspiration
(EUS-FNA) should be considered. If concern over
cancer cannot be excluded, a resectional treatment
2
There is also an association with cigarette
2,3
Chronic pancreatitis is associated with
4,5
Abdominal pain is typically the
1
The most common
7
Specialist
6
such as pancreatico-duodenectomy is appropriate. In
patients without a pancreatic mass but with a dilated
duct, pancreatic ductal drainage procedures such as
lateral pancreatico-jejunostomy can be considered.
In patients with small duct chronic pancreatitis,
management is more difficult but can include
the V-shaped excision. In selected patients, total
pancreatectomy with islet autotransplantation can be
considered.
pancreatitis all relate to recurrent or persistent
episodes of inflammation with subsequent healing
with fibrosis. These include biliary stricture, duodenal
stenosis, pseudocyst, false aneurysms of visceral
vessels and portal or splenic vein occlusion leading
to extrahepatic portal hypertension.
long-term risks to monitor during follow-up include
development of diabetes mellitus, malnutrition and
the increased risk of cancer.
8
The long-term complications of chronic
9
Important
10
Definition
Chronic pancreatitis is defined as a benign
inflammatory disease, characterised by chronic
pancreatic inflammation and scarring, irreversibly
damaging the pancreas and resulting in loss of
exocrine and endocrine function.
1
Classification of chronic
pancreatitis
Classifications of chronic pancreatitis have been
based on the aetiology of the disease, such as
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257
Chapter 15
alcohol-related, genetic or idiopathic.1 Alternatively, the disease can be classified according
to morphology – large-duct disease, small-duct
disease and minimal-change pancreatitis.
11
Classifications incorporating the temporal changes
along the time course of chronic pancreatitis have
also been used (early-stage, late-stage disease).
12
The availability of better diagnostic tests such as
endoscopic pancreatography were the stimulus
for morphologically based categorisations,
and the Cambridge classification based on
pancreatogram appearance is still used today.
Contrast-enhanced magnetic resonance scanning
has replaced diagnostic pancreatography.
11
13
Morphologically based classifications have the
practical advantage that treatment can potentially
be tailored to the disease variant. In addition to
these systems of classification, there have since
been national classifications from (amongst
others) Japan, Switzerland and the USA.
14–16
The
most contemporary classification system is that
described in the American Pancreatic Association’s
practice guideline on chronic pancreatitis in 2014.
16
This provides criteria for the diagnosis of chronic
pancreatitis based on computed tomography (CT),
magnetic resonance imaging (MRI) and endoscopic
ultrasonography (EUS).
Incidence
Data from the North American National
Pancreas Foundation suggest an incidence of
approximately 4 new patients per 100 000 population
per year in the USA.17 As this is a chronic disease,
the prevalence is 40–50 per 100 000 people.17 There
is substantial worldwide geographic variation in the
clinical profile of the disease.
18
Aetiology
The TIGAR-O risk factor list is a modern,
comprehensive list of the aetiological causes of
chronic pancreatitis (see Table 15.1).
considers toxic-metabolic causes, idiopathic, genetic,
autoimmune, recurrent and obstructive factors. The
M-ANNHEIM aetiology list is similar but adds the
important option to consider multiple coexistent
aetiological factors.
20
Excessive alcohol consumption
is the single most common aetiologic factor.
Cigarette smoking is a common cofactor to alcohol,
and as a modifiable risk factor, smoking cessation
should be prioritised from the outset.
intake of protein and fat, and deficiency of fat-soluble
vitamins in the diet, are associated with chronic
pancreatitis but without proof of a causal link.
in understanding the genetic basis of chronic
pancreatitis.
gene PRSS1 lead to premature intra-acinar activation
of trypsin.
4
Mutations in the cationic trypsinogen
4
Similarly, mutations in the pancreatic
secretory trypsin inhibitor also termed serine protease
inhibitor Kazal Type 1 (SPINK1) compromise
intracellular inactivation of trypsin and are associated
with chronic pancreatitis.
23
Cystic fibrosis gene
mutations, especially the Δ508 mutation are associated
with chronic pancreatitis and are thought to be due to
abnormalities in mucin production and secretion.
Alcohol susceptibility genes are also associated with
alcohol-related chronic pancreatitis.
Pathogenesis of pain in chronic
pancreatitis
Pain in clinical chronic pancreatitis is complex
and multifactorial. Logically, pain in chronic
19
TIGAR-O
3
High caloric
23
21,22
19,20
24
Table15.1 • The TIGAR-O classification system of risk factors for chronic pancreatitis
Toxic–metabolic Alcohol, tobacco smoking, hypercalcaemia, hyperlipidaemia, chronic renal failure,
medications, toxins
Idiopathic Associated with early-onset CP and also with late-onset CP
Tropical CP
Genetic mutations PRSS1, CFTR, SPINK1, others
Autoimmune Isolated or as part of a syndrome
Recurrent and severe
Post-necrotic severe AP, vascular disease/ischaemic, post-irradiation
AP-associated CP
Obstructive Pancreas divisum, sphincter of Oddi disorders, duct obstruction (e.g., tumour), post-traumatic
pancreatic duct scars
AP, acute pancreatitis; CP, chronic pancreatitis.
The TIGAR-O classification is a comprehensive classification system of the risk factors for chronic pancreatitis.
remembering that in clinical practice, there may be more than one coexistent aetiological factor.
Modified from Etemad B, Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments.
Gastroenterology 2001;120:682–707.
19
It is worthwhile
258
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Chronic pancreatitis
pancreatitis can be considered as having both a
‘pancreatic’ component and an ‘extra-pancreatic’
component. Pancreatic pain relates to inflammation
of the gland and obstruction of the main pancreatic
duct. Extra-pancreatic components relate to
abnormal neural pathways and aberrant central
nervous system perception of pain.
evidence of the ‘extra-pancreatic’ component
comes from studies which show that the number
and diameter of non-myelinated type C pain fibres
are significantly increased in patients with chronic
pancreatitis.
system processing of pain may be altered with
long-standing chronic pancreatitis.
pancreatic’ factors may account for some of the
treatment failures of pancreas-directed surgery
or endoscopy. It should also be remembered that
there may be treatment related side-effects such as
opiate-induced gut dysmotility. In practical terms,
patients should be counselled before undergoing
surgical or endoscopic intervention and should
understand that no individual intervention is
associated with a guarantee of symptom relief in
chronic pancreatitis.
and can include a pancreatic parenchymal
component, an extra-pancreatic neural component
and components due to treatment-related side-effects
such as opiate-induced gut dysmotility.
27,28
In addition, central nervous
Pain in chronic pancreatitis is multifactorial
25,26
Objective
29
These ‘extra-
Chronic presentation of chronic
pancreatitis
The majority of admissions secondary to established
chronic pancreatitis are as a result of abdominal pain
with normal or marginal hyperamylasaemia. Unlike
severe acute pancreatitis, these episodes usually
require little more than a temporary escalation
of analgesia and maintenance fluids, but to avoid
recurrent admissions an effective interim strategy
is required. An important component of care is
provision of counselling to help avoid continued
alcohol overuse and there is good randomised trial
evidence that professional counselling on the harms
of alcohol consumption is associated with a reduction
in future admissions with pancreatitis.
patients may also be considered for endoscopic and/
or surgical management (see below).
32,33
These
Index presentation with
complications of chronic
pancreatitis
Occasionally the index presentation will be as a
result of a complication of chronic pancreatitis such
as a pseudocyst, bleed from false aneurysm or biliary
or duodenal obstruction from chronic fibrosis. The
management of these is discussed in the section on
complications.
Clinical presentations
Acute presentation of chronic
pancreatitis
There is a substantial overlap between acute and
chronic pancreatitis in their modes of presentation.
To address this practically, if patients present with
acute abdominal pain, hyperamylasaemia or meet
the diagnostic criteria for acute pancreatitis defined
in the Atlanta 2012 consensus
acute pancreatitis) they should be diagnosed as
acute pancreatitis and receive treatment according
to the current International Association of
Pancreatology/American Pancreatic Association
(IAP/APA) guidelines for the treatment of acute
pancreatitis.
to ensure adequate initial resuscitation and also
to detect and treat avoidable causes of recurrent
pancreatitis. Principally, gallstones should be
sought by transabdominal ultrasound and treated
by cholecystectomy. The presence of parenchymal
calcification on CT and/or a dilated main pancreatic
duct are pointers toward an underlying diagnosis of
chronic pancreatitis.
31
The practical importance of this is
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30
(see chapter on
Asymptomatic incidental finding
The widespread availability and use of CT
occasionally results in the detection of patients
with pancreatic parenchymal calcification without
associated symptoms. In this setting, it is worthwhile
assessing and excluding diabetes mellitus and
malnutrition, but there is no role for intervention in
the absence of symptoms.
Practical differential
diagnoses in chronic
pancreatitis
Three important differential diagnoses must be
considered.
Pancreatic cancer
Initial assessment of a patient presenting with a
focal pancreatic mass, on a background of known
or newly diagnosed chronic pancreatitis, should
consider the possibility of pancreatic cancer in the
259
Chapter 15
differential diagnosis. Biomarkers such as carbohydrate antigen 19-9 (CA 19-9) are insufficiently
accurate to allow for reliable distinction between
chronic pancreatitis and cancer, especially in the
setting of biliary obstruction.
is itself an independent risk factor for the development
of pancreatic ductal adenocarcinoma.
34
Chronic pancreatitis
35
Sonographic
artifact from fibrosis and calcification compromises
the accuracy of endoscopic ultrasound, and whilst
a diagnosis of cancer may be confirmed by EUS/
FNA, it cannot exclude neoplasia despite negative
cytology, and in patients in whom there is a suspicion
Autoimmune pancreatitis
Autoimmune pancreatitis (AIP) is a chronic
inflammatory condition in which patients may
present with a pancreatic mass, pain and jaundice
that can closely resemble chronic pancreatitis.
36,37
AIP is associated with extra-pancreatic stricture
of the upper and intra-hepatic bile ducts and not
typically with pancreatic calcification, and these
pointers may help differentiation from chronic
pancreatitis.
of the immunoglobulin IgG4 subtype.
38
AIP is also associated with elevation
39
The diffuse
nature of the inflammatory process leads to a classical
‘sausage-shaped’ swollen pancreas which can be
distinguished from chronic pancreatitis.
40
Ideally a
tissue diagnosis of AIP should be established, usually
by pancreatic biopsy.
Intraductal papillary mucinous
neoplasm (IPMN)
spontaneously decrease over time, coinciding with
the occurrence of exocrine insufficiency.
two large prospective cohort studies
44
However,
43,45
showed
no association between the duration of chronic
pancreatitis and pain.
Baseline assessment of a
patient with suspected chronic
pancreatitis
Clinical history is central to management and must
focus on the nature and duration of symptoms, age
of first onset of abdominal pain and associated
factors such as jaundice and/or vomiting. An
accurate history of alcohol consumption is
important and must include information on type of
alcohol, years of consumption and current intake
in units. Smoking history and counselling on the
significance of smoking on disease progression, and
an accurate family history, may identify hereditary
kindreds. Clinical examination should record body
mass index, abdominal examination findings and
urinalysis.
Baseline laboratory tests include blood count,
urea/electrolytes, biochemical liver function tests,
blood glucose (and glycosylated haemoglobin),
C-reactive protein and CA 19-9. Transabdominal
ultrasonography will provide information on the
presence or absence of gallstones and also on common
coexistent liver diseases such as steatohepatosis.
CT, and to a lesser extent MRI, are the mainstay of
detailed assessment in chronic pancreatitis.
16
Main-duct IPMN presents with dilatation of the
main pancreatic duct and can closely resemble
chronic pancreatitis.
41
Main-duct IPMN typically has
intraductal mucin which may be seen extruding from
the ampulla whereas the duct dilatation associated
with chronic pancreatitis is associated with stricture
formation and parenchymal calcification. It is
important to distinguish between the two as mainduct IPMNs are regarded as pre-malignant lesions
and require resectional surgery.
41
Clinical course
Typically the disease has a relapsing course characterised by intermittent abdominal pain.42 At the onset,
patients will have conserved exocrine and endocrine
function but both are compromised during the
clinical course. Diabetes mellitus is more frequent in
long-standing chronic pancreatitis.
proposed a ‘burnout’ hypothesis, suggesting pain may
43
Historical series
APA Practice Guidelines key points on diagnosis
of chronic pancreatitis (CP):
• Intraductal pancreatic calcifications are the most
specific and reliable sonographic and CT signs
of CP.
• Compared with ultrasound and CT, MRI is a more
sensitive imaging tool for the diagnosis of CP.
• Computed tomography is helpful for the diagnosis
of complications of CP.
• Computed tomography is helpful for diagnosis of
other conditions that can mimic CP.
• Endoscopic retrograde pancreatogram (ERP) is
rarely used for diagnostic purposes.
• The ideal threshold number of EUS criteria
necessary to diagnose CP has not been firmly
established, but the presence of 5 or more
and 2 or less strongly suggests or refutes
the diagnosis of CP. The relatively poor interobserver agreement for EUS features of chronic
pancreatitis limits the diagnostic accuracy and
overall utility of EUS for diagnosis.
260
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16
46
Chronic pancreatitis
CT features of chronic pancreatitis include dilatation
of the pancreatic duct, pancreatic calcification and
parenchymal atrophy (
Fig. 15.1). These features are
usually present late in the course of the disease and
thus may not be evident at an early stage. MRI is
reportedly more specific for the diagnosis of CP
because ductal abnormalities are very reliably
detected. The addition of intravenous secretin may
improve the accuracy of MRI, and may provide
indirect evidence of residual exocrine function.
47
EUS complements cross-sectional imaging and is
more sensitive than CT in diagnosing the early stages
of chronic pancreatitis. The Rosemont criteria,
46
derived from a consensus conference, combine the
detection of parenchymal abnormalities with ductal
irregularity or dilatation to produce a score for the
prediction of chronic pancreatitis.
Although endoscopic retrograde cholangiopancreatography (ERCP) was a mainstay of diagnosis
in the 1980s and was used in the Cambridge
classification, purely diagnostic ERCP should no
longer be undertaken as accurate information on
ductal abnormalities can be obtained by crosssectional imaging.
In addition to morphological assessment of the
gland, functional assessment of the endocrine
component of pancreatic function involves testing
for diabetes mellitus. Baseline measurement of
glycosylated haemoglobin (HbA1C) may be of value
in non-diabetics at time of index presentation.
The exocrine component of pancreatic function can
be assessed indirectly by measurement of faecal elastase,
serum trysinogen or chymotrypsin and does not require
direct hormonal stimulation of the pancreas.
48
These
tests are of practical value only in the late stages of the
disease, when clinical features such as steatorrhoea
are already present. Direct assessment of pancreatic
exocrine function by intubation of the duodenum,
provision of a secretory stimulus and collection of
pancreatic juice is not widespread and seems to be
most widely utilised in North America.
49
In many units
a clinical diagnosis of chronic pancreatitis serves as an
indication for commencement of pancreatic exocrine
replacement therapy given the high prevalence of
subclinical malnutrition and vitamin deficiency in this
48
disease.
Medical management of
chronic pancreatitis
The treatment of chronic pancreatitis and its
complications remains a major challenge. A
holistic approach is based on accurate assessment
of symptoms, nutritional status, pancreatic
endocrine and exocrine function and morphological
assessment of the integrity and patency of the duct
and the nature of the pancreatic parenchyma.
Analgesia
This is a key component of the non-operative treatment
of chronic pancreatitis. Pain control should follow the
World Health Organisation’s analgesic ladder, starting
with a non-opioid, progressing to weak opioid and
then a strong opiod.
on regular analgesic medication by the time of referral
to specialist care. Co-analgesics such as gabapentin
may be used in conjunction with these medications.
6
Typically, patients will already be
7
Figure15.1 • Pancreatic parenchymal calcification.
Venous contrast phase of a CT showing typical pancreatic
parenchymal calcification and segmental dilatation of the
main pancreatic duct. An indwelling metallic endobiliary stent
is also seen.
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Alcohol avoidance
There is good randomised trial evidence that
professional alcohol avoidance counselling results in
reduced hospital admission.
can be stopped at an early stage in the disease,
progression may also be ameliorated.
33
If alcohol consumption
32
Smoking cessation
Formal guidance on cessation of smoking is useful. Cessation of smoking may modify disease
progression.
3
If smoking cessation clinics are
available, these should be utilised.
Exocrine replacement therapy
Exocrine replacement therapy should be considered
in all patients with chronic pancreatitis. Treatment
261