Acute pancreatitis is defined as an acute inflammation of the pancreatic parenchyma and peripancreatic tissues.
Acute pancreatitis varies from a mild uneventful disease to a severe life-threatening illness with multisystemic organ failure (MOF) with shock, renal failure, respiratory failure, and death.
The frequency of acute pancreatitis varies among different countries (1).
In the US, 270 cases of acute pancreatitis occur per 100,000, which accounts for more than 200.000 hospital admissions each year.
In Finland, the rate is 70 cases per 100,000 and in the Netherlands 18 per 100,000.
Gallstones and alcohol abuse are the most common causes of acute pancreatitis, accounting for 80% of cases.
Post-ERCP pancreatitis is the third most common cause of pancreatitis, but usually has a mild course.
In the Netherlands there are approximately 3500 admissions for acute pancreatitis a year.
In the last 10 years the incidence of acute pancreatitis has increased by 75%, due to increased alcohol consumption and increasing obesity.
In about 80-85% of cases of acute pancreatitis run a mild course without the development of (multiple) organ failure.
This group has a mortality of less than 1% In 15-20% of cases of acute pancreatitis run a severe clinical course with necrosis of pancreatic and peripancreatic tissues and the development of multiple organ failure.
Of these, pancreatic necrosis remains sterile in 60% of patients, whereas in 40% of these patients the necrosis becomes infected.
The latter category has the highest mortality rate of 25-70%.
It is generally assumed that severe acute pancreatitis runs a biphasic course (2).
During the first 1-2 weeks there is a pro-inflammatory response, which results in a systemic inflammatory response syndrome (SIRS).
It is essentially a sterile response in which sepsis or infection rarely occurs.
Severe SIRS may lead to early multi-organ failure.
After the first 1-2 weeks there is a transition from a pro-inflammatory to an anti-inflammatory response.
It is during this anti-inflammatory response that the patient is at risk for translocation of intestinal flora and development of infection of necrotic pancreatic and peripancreatic tissues.
The subsequent sepsis will result in late (multiple) organ failure.
Early mortality in acute pancreatitis is the result of severe systemic inflammatory response with multi-organ failure.
Late mortality is the result of infection of pancreatic necrosis and peripancreatic tissues which results in sepsis.
Imaging of Acute Pancreatitis
CT is the imaging modality of choice for diagnosis and staging of acute pancreatitis and its complications.
Ultrasound is important in determining whether gallstones are the cause of the acute pancreatitis (i.e. biliary pancreatitis).
ERCP with sphincterotomy and stone extraction is indicated in patients with biliary pancreatitis and signs of biliary obstruction.
MRI is as sensitive as CT, but not as practical or readily accessible in most centers.
In specific cases, however, it can be of additional value.
There is no additional value of an early CT (within 72 hours after symptom onset) in patients with acute pancreatitis.
The diagnosis is usually made on clinical and laboratory findings.
An early CT may be misleading regarding the morphologic severity of the pancreatitis, because it may underestimate the presence and amount of necrosis.
Early CT is only recommended when the diagnosis is uncertain, or in case of suspected early complications such as bowel perforation or ischemia.
The case on the left shows a normally enhancing pancreas with enhancement comparable to that of the spleen on day 1.
As the patient's condition worsened, a second CT was performed on day 3.
Notice how the greater part of the pancreatic body and tail no longer enhance - in fact only a small part of the pancreatic head enhances.
The patient died on day 5 due to severe SIRS and multiple organ failure.
Staging of Acute Pancreatitis
Early severity stratification of acute pancreatitis is important for several reasons. Identification of patients with the highest morbidity and mortality is critical because these patients may benefit most from timely transfer to the intensive care unit or tertiary referral centres for supportive treatment or for targeted therapy (i.e. endoscopic intervention or enteral feeding).
In addition, stratification is essential for reliable interinstitutional comparison of new methods of therapy and for inclusion of patients in randomized trials.
Scoring systems related to CT are the most studied imaging test in acute pancreatitis.
Since the introduction of CT for diagnosis and severity assessment of acute pancreatitis in the eighties, many imaging-based systems have been developed.
Determinants of most radiologic scoring systems include pancreatic changes, peripancreatic features and extrapancreatic features.
Of all radiologic staging systems available, the CT severity index (CTSI) is the most studied. The CTSI combines the Balthazar grade (0-4 points) with the extent of pancreatic necrosis (0-6 points) on a 10-point severity scale.
The calculated CTSI can then be subdivided in three categories (CTSI 0-3, 4-6, and 7-10; corresponding to predicted mild, moderate, and severe disease, respectively) that have subsequent increases in morbidity and mortality.
Predicting severity of disease is most helpful for the clinician on the day of admission; which patient must be transferred to medium or intensive care and which patient can be treated on the ward.
Recent studies show that scoring systems based on imaging do not outperform scoring systems based on clinical and biochemical parameters on the day of admission with regard to predicting clinical outcome and death. Therefore, performing CT on day of admission solely for prediction purposes is not recommended.
2012 Revised Atlanta Classification
The 1992 Atlanta Symposium on Acute Pancreatitis has classified the disease into mild acute pancreatitis and severe acute pancreatitis.
Recently, the 1992 Atlanta Classification has been revised after a web-based consultation of pancreatologists worldwide. The 2012 Revised Atlanta Classification discriminates two morphologic types of acute pancreatitis and classifies the clinical severity of acute pancreatitis into three categories based on clinical and morphologic findings; mild, moderately severe, and severe acute pancreatitis, depending on the presence of organ failure, local and/or systemic complications.
Mild acute pancreatitis is defined as absence of organ failure and local or systemic complications.
Moderately severe acute pancreatitis is defined as presence of transient organ failure (lasting less than 48h) and/or presence of local or systemic complications.
Severe acute pancreatitis is defined as presence of persistent organ failure (lasting longer than 48h).
Acute pancreatitis basically has two different morphologic forms: interstitial or edematous pancreatitis and necrotizing pancreatitis. In interstitial pancreatitis the pancreas enhances normally on contrast-enhanced CT (CECT) with or without surrounding peripancreatic inflammatory changes or fluid. The hallmark of necrotizing pancreatitis is the presence of tissue necrosis, either of the pancreatic parenchyma (depicted as areas of nonenhancement of the pancreas), the peripancreatic tissues (manifested as heterogeneous areas surrounding the pancreas), or both (see below).
In practice, the morphologic severity and clinical severity frequently overlap (i.e. patients with interstitial pancreatitis have clinically mild disease, and conversely, most patients with necrotizing pancreatitis will sustain clinically severe acute pancreatitis). However, this premise does not always hold true. Therefore, it is important to realize that clinical severity prevails over morphologic severity.
Patients with pancreatitis but no collections or necrosis (i.e. Balthazar grade A-C) have a mild pancreatitis.
This is also called 'edematous or interstitial pancreatitis' (no pancreatic necrosis).
It is a self-limiting disease with an uneventfull recovery occurring in 80% of patients with acute pancreatitis.
There is an intermediate form of pancreatitis without pancreatic necrosis with an intermediate clinical course.
This is called extrapancreatic necrosis (EXPN) (5,6).
Sometimes the term exudative pancreatitis is used.
These patients have Balthazar grade D or E.
These patients have a relatively mild course because there is no pancreatic necrosis, but there is higher morbidity than in interstitial pancreatitis, because they have peripancreatic collections, that can become infected (7).
Severe pancreatitis or necrotizing pancreatitis
Severe pancreatitis, also called 'necrotizing pancreatitis' occurs in 20% of patients.
It is characterized by a protacted clinical course, a high incidence of local complications and a high mortality rate.
Patients with normal enhancing pancreas (i.e. Balthazar grade A-C) without necrosis of extrapancreatic tissue.
Usually, this is a self-limiting disease with an uneventful recovery occurring in about 80% of patients with acute pancreatitis.
The images show normal enhancement of the entire pancreatic gland with only mild surrounding fatty infiltration.
There are no fluid collections or necrosis
(Balthazar grade C, CTSI: 2).
EXPN - Exudative Pancreatitis
In EXPN, there is normal enhancement of the entire pancreas associated with extensive peripancreatic collections.
These are often heterogeneous in appearance (i.e. have liquid and non-liquid densities on CT) and may be progressive.
EXPN consists of necrosis of peripancreatic fat, extravasated pancreatic fluid and inflammatory and hemorrhagic components.
When peripancreatic collections persist or increase, it is usually due to the presence of fat necrosis.
Because fat does not enhance on CT, the diagnosis of fat necrosis can be difficult.
In the case on the left on day 18 there is expansion of the peripancreatic collections.
There are at least two collections, but no pancreatic parenchymal necrosis (Balthazar grade E, CTSI: 4).
Necrosis of pancreatic parenchyma and/or peripancreatic tissues occurs in 20% of patients.
It is characterized by a protracted clinical course, a high incidence of local complications, and a high mortality rate.
There are 3 subtypes of necrotizing pancreatitis:
- Necrosis of pancreatic parenchyma without surrounding necrosis of peripancreatic tissue (very rare)
- Necrosis of extrapancreatic tissue without necrosis of pancreatic parenchyma or extrapancreatic necrosis (EXPN)
- Necrosis of both pancreatic parenchyma and peripancreatic tissues
The CT shows an acute necrotizing pancreatitis.
There are 2 or more fluid collections and more than 50% of the pancreatic gland does not enhance
(Balthazar grade E, CTSI :10).
This patient died two days later due to severe systemic inflammatory response syndrome (SIRS) and multi organ failure.
The detection of pancreatic necrosis in clinical practice is important because most life-threatening complications occur in patients with pancreatic necrosis (1,2).
Necrotizing Pancreatitis (2)
In the case on the left the body and tail of the pancreas do not enhance after i.v. contrast (blue arrows).
There is however normal enhancement of the pancreatic head (yellow arrow).
More than 50% of the pancreas is necrotic and there are at least two collections (CTSI : 10).
Two weeks later the collection in the omental bursa and pancreatic body has increased significantly.
The pancreatic tail still enhances and so does the pancreatic head (arrows).
This patient developed septicaemia and underwent surgery.
The 2012 revised Atlanta Classification discerns 4 types of peripancreatic collections in acute pancreatitis depending on their content and degree of encapsulation (see Table 1)
- Acute Peripancreatic Fluid Collection (APFC): contains fluid only, no or partially encapsulated
- Acute Necrotic Collection (ANC): contains mixture of fluid and necrotic material, no or partially encapsulated
- Pseudocyst: contains fluid only, fully encapsulated
- Walled-off Necrosis (WON): contains mixture of fluid and necrotic material, fully encapsulated
APFC and pseudocyst occur only in interstitial pancreatitis whereas ANC and WON occur only in necrotizing pancreatitis. Thus, in the new classification the term "pseudocyst" does not occur in necrotizing pancreatitis (with one exception, see below). The primary determinants that differentiate each peripancreatic collection are its content (fluid only in APFC and pseudocyst; mixture of fluid and necrotic material in ANC and WON) and degree of encapsulation (none or partial wall in APFC and ANC; complete encapsulation in pseudocyst and WON). On CT, the discrimination between an APFC and ANC may be difficult, especially in the first weeks; then the term "indeterminate peripancreatic collections" can be used.
All these collections may remain sterile or become infected.
Intraabdominal fluid collections and collections of necrotic tissue are common in acute pancreatitis.
These collections develop early in the course of acute pancreatitis.
In the early stage, such a collection does not have a wall or capsule.
Preferred locations are the lesser sac and the retroperitoneal space (anterior and posterior pararenal space) and subperitoneal spaces (transverse mesocolon and small bowel mesentery).
These collections are the result of the release of activated pancreatic enzymes (i.e. lipase, trypsin, and amylase) which also causes necrosis of the surrounding tissues.
This explains why many of these collections harbor solid necrotic debris (ANC).
About 50% of these collections show spontaneous regression (image on the left).
The remaining 50% either remain stable or increase and undergo organization and demarcation with liquefaction.
They may remain sterile or develop infection (infected necrosis = infected ANC / WON).
Based on CT alone it is sometimes impossible to determine whether these collections contain fluid only or a mixture of fluid and necrotic tissue and whether they are infected or not. Consequently, instead of naming them as 'pseudocysts', or 'APFC', it is better to describe these as 'indeterminate peripancreatic collections'.
On the left CT scans of a patient with acute pancreatitis. There is a collection in the area of the pancreatic head in the right anterior pararenal space (impossible to distinguish between an APFC and ANC). On a follow-up scan the collection in the right anterior pararenal space increased in size. It has a fluid density and a thin enhancing wall (could be a pseudocyst or WON). One day later the patient developed septicaemia and percutaneous drainage was performed. After drainage the collection has barely diminished in size and consequently there was suspicion of necrotic tissue. The patient underwent surgery and the collection was found to consist of necrotic debris, which was not appreciated on CT (hence this was WON and not a pseudocyst!). The necrotic debris was too viscous for successful percutaneous drainage.
- Infected necrosis is:
- Infection of necrotic pancreatic parenchyma
- And/or necrotic extrapancreatic fatty tissue
- Usually occurs in the 2nd-3rd week.
- Most severe local complication of acute pancreatitis
- Most common cause of death in patients with acute pancreatitis
- Air bubbles are seen in 20% of cases with infected necrosis.
The case on the left is a typical example of infected pancreatic necrosis.
On day 3 there is no enhancement of the pancreas, consistent with necrosis (compare to enhancing spleen).
On follow up the peripancreatic collections increase in size and finally there are air bubbles in the heterogeneous collection, consistent with infected pancreatic necrosis.
Pseudocyst versus Walled-off Necrosis (WON)
- Collection of pancreatic juice or fluid enclosed by a complete wall of fibrous tissue
- Occurs in interstitial pancreatitis
- Absence of necrotic tissue is imperative for its diagnosis
- Often communication with the pancreatic duct
- Requires 4 or more weeks to develop
- Differential diagnosis includes walled-off necrosis and sometimes pseudoaneurysm or even a cystic tumor
- Most often, they occur in the lesser sac
- Pseudocyst in acute pancreatitis is a rare occurrence because in the acute phase of acute pancreatitis most collections contain some amount of necrotic material (ANC / WON)
This patient presented with a gastric outlet obstruction 2 months after an episode of acute pancreatitis. There is a large, homogeneous, well-demarcated peripancreatic collection in the lesser sac, which abuts the stomach and the pancreas. The patient did not have fever.
The collection was successfully drained and showed clear fluid with a high amylase.
This proved to be a true pancreatic pseudocyst.
On the left a CT of an ICU patient on day 40 with central gland necrosis with a spiking fever. The CT shows a similar collection (fluid density) to that of the previous patient, except for its pancreatic location. The collection is homogeneous and well-demarcated with a thin wall abutting the stomach.
During endoscopic debridement this collection contained fluid and necrotic tissue (i.e. WON), which was removed from the area of the pancreas (image on the right).
Although the imaging characteristics in this case are similar to the previous case, this proved to be infected WON.
The patient on the left also has a homogeneous pancreatic and peripancreatic collection, well-demarcated with an enhancing wall, on day 25 of an episode of acute necrotizing pancreatitis. This patient had fever and multiple organ failure. Therefore, this collection was suspected to be infected WON and not a pseudocyst. At surgery, the collection contained much necrotic debris, which was not depicted on CT.
MRI is superior to CT in differentiating between fluid and solid necrotic debris. On the left a patient with several homogeneous peripancreatic collections on CT. These collections show homogeneous high signal intensity on a fat-suppressed T2 MRI sequence and, hence, contain clear fluid (i.e pseudocysts).
On the left another patient 2 months after an episode of acute necrotizing pancreatitis (subtype EXPN) with a homogeneous peripancreatic collection in the transverse mesocolon (arrow). A T2-weighted MRI sequence, however, shows that the collection has low signal intensity (arrow). Most likely this is necrotic fat tissue (WON). This patient had no fever or signs of sepsis (sterile necrosis or sterile WON). Endoscopic or percutaneous drainage would have little or no effect on its size. However, there would be an increased risk of infection when the collection is colonized following drain placement.
These cases illustrate that at times CT cannot reliably differentiate between collections that consist of fluid only and those that contain fluid and solid necrotic debris with or without infection.
Infected necrosis (2)
In the patient on the left there is a normal enhancement of the pancreas with surrounding septated heterogeneous peripancreatic collections with fluid- and fat densities (images on the left).
Two weeks later (images on the right) there are air bubbles in the peripancreatic collection, consistent with infected necrosis.
This patient underwent surgery.
The surgeon had to remove a lot of necrotic tissue and estimated he had removed over 90% of the pancreas.
Remarkably, a CT performed 6 months after surgery showed a normal pancreas.
This indicates that during surgery the differentiation between pancreatic necrosis and necrosis of the peripancreatic tissue is sometimes impossible.
The current management of acute pancreatitis is to be conservative for as long as possible.
During the first two weeks patients with severe acute pancreatitis and multi organ failure should be stabilized in the ICU (8).
Interventions should be delayed for as long as possible.
Allow for demarcation of collections.
Remember that many collections will resorb spontaneously.
FNA and Drainage
Once the clinical condition of the patient deteriorates and the patient is febrile, fine needle aspiration (FNA) can be used to differentiate between sterile and infected collections.
Important remarks concerning FNA:
- No role for FNA in early collections
- Not transgastric for diagnosis only
- Be sure no pseudoaneurysm
- Think ahead - What is the plan:
- Pus > tube
- Indeterminate or clear > Gram stain, culture
- No flow > solid > saline > culture
Important remarks concerning Drainage:
- Indications for access to evolving fluid collections or necrosis decided on full evaluation of clinical, lab, and imaging
- No role for drainage in early collections
- Can be used as a guide for surgical approach
Collections can be approached through the transhepatic, transgastric or transabdominal route, but the preferred approach is to stay in the retroperitoneal compartment.
This approach has some advantages over the others:
- Same abdominal compartment as the pancreas
- No contamination with intestinal flora
- Drain runs parallel to pancreatic bed
- This route can be used to guide surgery
Surgical intervention in infected necrotizing pancreatitis generally consists of necrosectomy
via laparotomy (2,9).
The morbidity and mortality after this procedure might be reduced by minimally invasive strategies.
In the Netherlands there is a nationwide study into the optimal treatment of patients with infected necrotizing pancreatitis: the PANTER trial. (10).
The 20 hospitals of the Dutch Acute Pancreatitis Study Group are currently enrolling patients in a randomised trial to compare:
- Laparotomy with necrosectomy and continuous postoperative lavage with
- CT-guided or endoscopic transgastric drainage, if necessary, followed by videoscopic assisted retroperitoneal debridement (VARD).
Take home messages
- Severity of acute pancreatitis and pancreatic necrosis can only be reliably assessed by imaging after 72 hours.
- Absence of pancreatic parenchymal necrosis does not preclude a serious course of the illness.
- CT can not reliably differentiate between collections that consist of fluid and those that contain solid debris.
In these cases MRI can be of additional value.
- Avoid words such as 'pseudocyst' or 'pseudocyst formation' and 'pancreatic abscess' in the early stages of the disease.
These are rare complications!
- Central gland necrosis is a subtype of necrotizing pancreatitis with important implications.
- Avoid early drainage of collections and avoid introducing infection!