bacteriologic results of FNA and those of surgical specimens is greater than 95%.34 The peak occurrence

of infected necrosis is between 2 and 4 weeks after presentation but it may occur at any time during the

clinical course.

COMPLICATIONS

Table 53-4 Local Complications of Acute Pancreatitis

10 Invasive intervention is usually indicated in the presence of infected necrosis. In contrast, sterile

necrotic collections almost never require intervention in the acute phase of necrotizing pancreatitis. As

infected necrosis often consists of thick and tenacious materials, traditionally mechanical débridement

via an open surgical approach was the primary treatment. Recently, less invasive approaches have been

popularized. Minimally invasive approaches for the treatment of infected pancreatic necrosis are

associated with fewer complications, however the mortality rate and the length of hospital stay appear

to be predominantly determined by the disease process itself rather than the interventional approach. In

centers with the appropriate expertise, most cases of infected pancreatic necrosis can now be managed

using minimally invasive techniques.

11 Procedures for the treatment of infected necrosis are best performed when collections become

walled-off and demarcated from viable pancreatic tissue with at least partial liquefaction, which

typically requires a delay of 4 to 6 weeks after disease onset. This is especially true for débridement, as

when it is performed too early, bleeding, incomplete removal of infected necrosis, resection of vital

tissue, and loss of endocrine and exocrine function are more likely to ensue. Convincing evidence now

supports delaying intervention whenever possible. Antibiotics can often be used to temporize the

situation allowing necrotic collections to mature. A subset of patients may even be successfully treated

with antibiotics alone. Patients with clinical deterioration and signs of sepsis despite the use of

antibiotics who have clearly infected acute necrotic collections may require intervention within the first

few weeks of acute pancreatitis.9,10,35

12 Drainage alone is the initial recommended intervention for infected pancreatic necrosis. This is

most often accomplished through a percutaneous image-guided approach, which is technically feasible

in the vast majority of cases. When percutaneous drains are placed, preference should be given to a

retroperitoneal approach so that the drain tract can be used to perform video-assisted retroperitoneal

débridement (VARD, see below). Drainage can also be accomplished through an endoscopic transluminal

approach, particularly in the rare cases where a percutaneous approach is not feasible. Drainage alone

can successfully treat infected necrosis in approximately 1/3 to 1/2 of cases.9,10,35–38

13 When required, débridement can often be performed through minimally invasive techniques.

These techniques are reserved for patients without intra-abdominal catastrophes or other complications

of acute pancreatitis mandating surgical exploration. VARD and direct endoscopic necrosectomy (DEN)

are the two most widely utilized techniques for minimally invasive débridement.

VARD is usually accomplished through a retroperitoneal approach via flank incisions. The previously

placed drain tracts are dilated to insert an operative nephroscope over a wire or to place laparoscopic

ports that follow the drain tract into the retroperitoneum. Fluid that is encountered is suctioned and

submitted for culture. Hydrodissection is used liberally. Gentle débridement of solid debris can be

accomplished under direct vision through the entry site or under visualization with the videoscope. The

goal of VARD is to facilitate drainage and not necessarily to perform a complete necrosectomy.

Irrigation is usually continued postoperatively through surgically placed drains. In a multicenter

randomized controlled trial, patients with infected pancreatic necrosis were randomized to undergo

primary open necrosectomy or a step-up approach consisting of percutaneous or endoscopic drainage

followed, in most cases (65%), by VARD. Open necrosectomy was rarely used when VARD could not be

1376

accomplished. Although mortality between the two groups did not differ, primary open necrosectomy

was associated with a higher incidence of major complications and increased cost.39

DEN is performed via transmural puncture into a necrotic collection after insertion of an endoscopic.

It is required that the collection abuts or is in close proximity to the stomach or duodenum. The

collection can be visualized as a bulge in the wall of the viscera or using EUS. The tract into the

collection is then dilated and large bore stents are placed. Mechanical débridement can be performed

with endoscopic instruments and/or irrigation. Nasocystic or percutaneous drains can be used to provide

irrigation after the procedure. Typically, multiple sessions are necessary to completely débride the

cavity. A small randomized controlled trial showed a decreased inflammatory response as well as

decreased complications for patients undergoing endoscopic transgastric necrosectomy as opposed to

VARD after failure of drainage for infected pancreatic necrosis.

Open necrosectomy may still be performed in the subset of patients not amenable to a minimally

invasive approach or in centers without expertise in these techniques. For open necrosectomy, the

abdomen is usually entered through a vertical midline or bilateral subcostal incision. The anterior

surface of the pancreas can be exposed by dividing the gastrocolic ligament (greater omentum) and

entering the lesser sac. If inflammatory changes have obliterated the lesser sac, an alternative route to

the pancreas is achieved by dividing avascular portions of the transverse mesocolon. Clearly nonviable

tissue should be débrided bluntly without attempting to perform anatomic resections. The débridement

field is irrigated with several liters of sterile saline. There are several options for assuring that all

necrotic tissue is removed after surgery. Traditionally, when the abdomen is closed, large-bore drains

are placed, and postoperatively the drains are left in place at least 7 days and until the effluent becomes

clear. This procedure is known as necrosectomy with closed drainage. Several authors prefer variants of

this procedure in which either both gauze packing and drains are placed at the time of surgery and

gradually withdrawn postoperatively (necrosectomy with closed packing) or where high-volume lavage of

the lesser sac is performed through the drains placed at the time of surgery until the effluent becomes

clear and the patient’s clinical course improves (necrosectomy with continuous lavage). Other procedures

including necrosectomy with open packing, where the retroperitoneum is marsupialized and the abdomen

left open, and necrosectomy with planned, staged relaparotomy, in which the initial operation is followed

by repeat laparotomies to change gauze packing or to perform additional débridement have fallen out

of favor but may be necessary if necrosectomy is performed early in the course of disease before clear

demarcation between necrotic and viable tissues has occurred. Modern mortality rates associated with

necrosectomy performed for infected necrosis range from 10% to 20%.40,41 On long-term follow-up,

approximately 25% of survivors develop exocrine insufficiency, and 30% develop endocrine

insufficiency. It should be noted that open necrosectomy is associated with better results in more recent

series due to improvements in ICU care and implementation of delayed timing for surgery. The results

of open necrosectomy in relation to VARD or DEN have not been directly compared after initial

drainage. Although surgical débridement is clearly indicated for infected necrosis, its role in sterile

necrosis has undergone evolution. In the past, early necrosectomy was recommended for patients with

necrotizing pancreatitis, even in the absence of documented infection. The rationale for this approach

was to prevent infection from developing and to remove the source of toxins and inflammatory

mediators. Today, it is recommended that surgery should be avoided in patients without documentation

of infected necrosis, based on favorable outcomes reported using this conservative approach.40,41

However, there remains a subset of patients with sterile necrosis who, despite prolonged supportive

care, have persistent problems, including disabling pain, malaise, and gastric outlet obstruction who

may benefit from interventions for sterile necrosis late in the course of disease.

Because of the high morbidity and mortality rates associated with infected necrosis, there has been

much investigation into the use of antibiotics as prophylaxis against infection. Initial clinical trials failed

to demonstrate a benefit of prophylactic antibiotics; however, these studies were flawed by the

inclusion of patients with mild disease who were at low risk for developing infected necrosis and the

use of antibiotics with poor penetration into the pancreas. Trials were published in the 1990s showing a

significant reduction in the incidence of pancreatic infection among patients receiving antibiotic

prophylaxis, and based on this evidence, the use of antibiotic prophylaxis in patients documented to

have necrotizing pancreatitis has become a widespread practice. Several recent trials that failed to show

a benefit for prophylactic antibiotics have now been published.42,43 Similarly, recent meta-analyses of

the available trials have failed to demonstrate a benefit for patients receiving prophylactic

antibiotics.44,45 Disadvantages of using prophylactic antibiotics include the risks of fungal superinfection

and the selection of resistant organisms. Another strategy for prophylaxis against infection in patients

1377

with acute pancreatitis has been the administration of probiotic bacteria to reduce the load of

pathogenic bacteria in the bowel; however, prospective evaluation has yielded disappointing results.46

An algorithm for the general management of acute pancreatitis and pancreatic necrosis is shown in

Algorithm 53-1.

Algorithm 53-1. Algorithm for the management of acute pancreatitis.

Pseudocysts and Sterile Walled-Off Necrosis

Acute fluid collections develop in up to 30% to 50% of patients with acute pancreatitis. As most resolve

spontaneously, no specific treatment directed at acute fluid collections is necessary in the absence of

evidence that the fluid is infected. However, in up to 10% of patients with acute pancreatitis, these fluid

collections progress to develop a wall of fibrous granulation tissue. Until recently, predominantly liquid

collections with a well-formed wall appearing after an episode of acute pancreatitis were classified as

pseudocysts. It is now appreciated that many of the chronic collections seen after bouts of acute

pancreatitis contain variable amounts of solid materials from the necrosis of pancreatic and

peripancreatic tissues. In the new taxonomy, these collections are called walled-off necrosis. This

distinction may better indicate how these collections should be treated, however, there is no distinction

in the indication for intervention between pseudocysts and sterile walled-off necrosis.35 The walls of

these collections generally require at least 4 weeks from the onset of pancreatitis to mature. In contrast

to true cysts, pseudocysts (and walled-off necrosis) do not have epithelium-lined walls.

Most pseudocysts and sterile walled-off necrosis are asymptomatic; however, they can cause upper

abdominal pain, gastric outlet obstruction, and obstructive jaundice. Pseudocysts and walled-off necrosis

can be diagnosed on ultrasonography or CT scanning (Figs. 53-5 and 53-6). It is important to distinguish

1378

 

Accurate prediction of severity early in the course of disease offers potential benefits in that

complications can be anticipated and detected early through the use of intensive monitoring and

frequent clinical assessment, and early and aggressive therapies can be instituted to attempt to prevent

these complications. Several methods for assessing disease severity based on clinical parameters, serum

markers, imaging, and scoring systems have been widely studied.

Revised Atlanta and Determinant-Based Classifications

An optimal system for the classification of severity of acute pancreatitis has not been universally

accepted. Nevertheless, it is widely recognized that organ failure and local complications, particularly

necrosis, are the two most important predictors of disease severity. While these two variables are often

associated, they differ as to when in the course of disease they typically arise and the manner in which

they contribute to disease severity. The early phase of acute pancreatitis (generally the first week after

onset of symptoms) is characterized by the host response to the local pancreatic injury. Disease severity

in the early phase is thus determined by organ failure resulting from the systemic inflammatory

response. Organ failure can be immediately apparent on clinical presentation, and in fact, organ failure

occurring in the early phase of disease is usually present on admission. In contrast, pancreatic necrosis,

which occurs in 5% to 10% of cases of acute pancreatitis, may not be apparent on initial presentation

and the extent of local complications can continue to evolve into the late phase of disease. Organ failure

and death in the late phase are often determined by local complications, particularly infected necrosis.3

While local complications can contribute to the mortality of patients with organ failure, there is also a

subset of patients with pancreatic necrosis without organ failure who experience significant morbidity

but have very low mortality.13

Two classification schemes based on organ failure and local complications have been proposed (Table

53-3).3,13,15 While these classification schemes are quite useful and validated in predicting mortality,11,14

their utility in predicting the course of disease on admission or within the first few days of

hospitalization is limited by the fact that local complications and the resultant organ failure occurring in

the late phase of the disease have not become apparent. Furthermore, a distinction is made between

transient organ failure and persistent organ failure. This distinction cannot be made at the time of

presentation. Similarly, the distinction between sterile necrosis and infected necrosis in the

Determinant-Based Classification cannot be made with certainty until a patient with necrotizing

pancreatitis shows signs of resolution.

Scoring Systems

The Ranson criteria, which is based on age, white blood cell count (WBC), glucose, serum lactate

dehydrogenase (LDH), and serum aspartate aminotransferase (AST) all determined on admission as well

as hematocrit drop, blood urea nitrogen (BUN), serum calcium, arterial partial pressure of oxygen

(PaO2

), base deficit, and fluid requirement all determined after 48 hours, are easily tabulated, and the

resulting scores are well correlated with morbidity and mortality rates.16 The presence of three or more

of these criteria is indicative of severe acute pancreatitis. Important limitations of the Ranson criteria

are that the predictive score cannot be determined prior to 48 hours following admission and that it can

only be used once. Furthermore, because these criteria were developed using a cohort of patients for

whom alcohol was the predominant etiology of pancreatitis, their generalizability may be limited. A

similar predictive scoring system developed in Glasgow using a cohort of patients for whom gallstones

were the predominant etiology of pancreatitis is available.17

Acute Physiology and Chronic Health Evaluation (APACHE) II scores, which are based on patient age,

indices of chronic health, and physiologic parameters, can be determined at any time after admission,

can be updated continuously during the course of disease and may have greater predictive power than

Ranson scores.18 However, the complexity of calculating APACHE II (or related APACHE III) scores

limits its application in routine clinical practice.

STAGING

Table 53-3 Criteria for Assessing Severity of Pancreatitis

1372

Recently another scoring system, the Bedside Index for Severity in Acute Pancreatitis (BISAP), based

on five relatively straightforward parameters that are obtained within the first 24 hours of hospital

admission, has been proposed. One point is assigned for the presence of each of the following: BUN

>25 mg/dL, impaired mental status, SIRS, age >60 years, and the presence of a pleural effusion.19 The

BISAP has been validated and is comparable to the Ranson criteria20,21 and the APACHE II Score19,21,22

in its prediction of mortality.

Computed Tomography Scanning

The diagnostic application of CT scanning was discussed previously. Although not required for making a

diagnosis on admission, a CT is often useful in patients who deteriorate or fail to improve. This

technique is associated with greater than 90% sensitivity in the detection of pancreatic necrosis, a

finding that is predictive of disease severity. Furthermore, CT scanning can also diagnose and

characterize collections and can indicate infection (e.g., if air bubbles are present) in some cases.

Because necrosis takes time to develop (in some patients up to 5 days), a contrast-enhanced CT scan

obtained too early in the disease course (e.g., at the time of admission) does not have predictive value

beyond clinical assessment (i.e., APACHE II or BISAP scoring).23 In addition, concerns that early

administration of iodinated intravenous contrast agents used in CT scanning may exacerbate pancreatic

injury have been raised, although these agents have not been shown to cause or exacerbate pancreatitis

in humans.24

Serum and Urinary Markers

C-reactive protein (CRP) is an easily assayed marker for which serum concentrations are well correlated

with disease severity. However, CRP levels do not become significantly elevated until 48 hours after

onset of disease; therefore, this marker is not useful for early prediction of disease severity.

Lipopolysaccharide-binding protein (LBP), a class 1 acute-phase protein that binds and transfers

bacterial lipopolysaccharide (LPS), has also been shown to correlate with disease severity but its

elevation is similarly delayed. Serum concentrations of IL-6, IL-8, neutrophil elastase, angiopoietin-2,

procalcitonin, and urinary concentrations of TAP (a product of trypsinogen activation) are also

correlated with disease severity. Because these markers become elevated within 24 hours of disease

1373

onset, they may be relevant to early prediction strategies in the future. Currently, however, assays for

these markers are not widely available.

MANAGEMENT

The goals of management for patients with acute pancreatitis are summarized below.

Correcting Pathophysiologic Derangements and Ameliorating Symptoms

6 The most important component of initial management is fluid resuscitation. In severe pancreatitis,

third-space fluid losses can be large, with up to one-third of plasma volume being sequestered. The

failure to appropriately resuscitate these patients is associated with increased morbidity and mortality.

An indwelling urinary catheter should be placed, intravascular volume should be frequently assessed,

and aggressive fluid and electrolyte replacement should be ensured. It should be noted, however, that

adverse consequence of massive resuscitation can also complicate the course of patients with severe

pancreatitis, and some recent studies have suggested an association between overresuscitation and

increased complications and death. While the optimal fluid resuscitation strategy is not known, critically

ill patients with pancreatitis should likely be aggressively and promptly resuscitated with lactated

Ringer solution with the amount of fluid administered tailored individually based on signs of end- organ

perfusion such as stabilization of blood pressure and heart rate and production of adequate urine

output.9,10,25

Patients with potentially severe pancreatitis, as well as those for whom initial resuscitation fails, are

best managed in a dedicated intensive care unit (ICU). Central venous monitoring may facilitate fluid

management. Patients should be closely monitored for development of distant organ failure,

particularly respiratory, cardiovascular, and renal failure, so that supportive management of these

conditions (positive-pressure ventilation, administration of vasopressor agents, and hemodialysis,

respectively) can be instituted without delay.

Abdominal pain is usually ameliorated with intravenous narcotics. In the past, morphine was avoided

because of concerns that morphine-induced increases in sphincter of Oddi pressure might exacerbate an

episode of pancreatitis. However, there is no clinical evidence that morphine can induce or exacerbate

acute pancreatitis. Other analgesic agents commonly used in patients with acute pancreatitis include

meperidine and fentanyl. Evacuation of gastric contents using a nasogastric tube should be instituted if

vomiting is a prominent symptom; otherwise, it is unnecessary.

A fraction of patients with severe pancreatitis develop abdominal compartment syndrome (ACS). ACS

is defined as a life-threatening sustained elevation of intra-abdominal pressure associated with newonset organ failure or acute worsening of existing organ failure. ACS usually manifests with a tensely

dilated abdomen, oliguria, and increased peak airway pressures. The diagnosis and treatment of ACS is

discussed in more detail elsewhere in this book. In acute pancreatitis, ACS is associated with very severe

disease, and approximately half of patients with ACS do not survive. ACS is treated by attempting to

decrease intra-abdominal pressure. In some patients this can be accomplished by draining intraabdominal collections and/or decompressing the bowel with nasogastric and rectal tubes. More than

half of the patients with ACS in the setting of acute pancreatitis require a decompressive laparotomy.9,26

Minimizing Progression of Pancreatic Inflammation and Injury

Identification of strategies for interrupting the inflammatory cascades that induce pancreatic injury and

distant organ failure is an area of active investigation. Currently, the only method used in routine

clinical practice is bowel rest (nothing by mouth). The rationale underlying this approach is that

avoidance of bolus oral nutrient intake may limit stimulation of pancreatic exocrine secretion induced

by the presence of nutrients in the intestine, particularly the duodenum.

Patients with mild acute pancreatitis generally need no nutritional support, as their disease typically

resolves within 1 week. In contrast, patients with severe pancreatitis usually have a more prolonged

disease course and should begin to receive nutritional support as early as feasible. Although these

patients traditionally have been administered total parenteral nutrition (TPN), accumulating evidence

suggests that enteral nutrition is safe, is less costly, and may be associated with a lower complication

rate than TPN.27 Administration of enteral nutrition is also associated with the theoretical advantage of

helping to maintain the integrity of the intestinal mucosal barrier, thus potentially limiting or

preventing bacterial translocation. Enteral nutrients have typically been delivered to the jejunum

1374

through nasojejunal tubes to avoid stimulating pancreatic exocrine secretion, however, randomized

controlled trials indicate that continuous feedings delivered through nasogastric tubes are equally safe

and effective.28,29 TPN is still required in many patients who do not tolerate enteral nutrition due to

ileus.

Clinical trials of agents that inhibit activated pancreatic enzymes, inhibit pancreatic secretion, or

interrupt the inflammatory cascade have yielded disappointing results. Meta-analyses of clinical trials of

gabexate mesylate (a proteinase inhibitor), somatostatin, and octreotide suggest these agents have

limited, if any, efficacy in improving outcomes in acute pancreatitis. A platelet-activating factor

antagonist, lexipafant, showed promise in an initial study but not in a subsequent larger trial and is not

currently recommended. Other adjuncts for which clinical trials have failed to demonstrate efficacy in

limiting pancreatic injury in patients with acute pancreatitis include glucagon, anticholinergics, fresh

frozen plasma, and peritoneal lavage.

Treating the Underlying Cause

7 This discussion is particularly relevant to patients with gallstone pancreatitis. There are both

theoretical and experimental rationales to believe that removal of gallstones impacted at the ampulla of

Vater early in the course of an episode of acute gallstone pancreatitis might limit disease severity. On

the other hand, most gallstones that cause acute pancreatitis readily pass into the small intestine. The

benefit of early ERCP in acute pancreatitis has been subjected to extensive study.30 It has been shown

that early ERCP with stone extraction and sphincterotomy clearly benefits the subset of patients with

gallstone pancreatitis who have cholangitis.There also may be a benefit in patients with biliary

obstruction who do not have cholangitis, although this is less clear. In patients, with cholangitis, ERCP

should be performed urgently (within 24 hours). The timing of ERCP in patients with biliary obstruction

is not clear (24 to 72 hours). It is reasonable to wait up to 48 hours for biliary obstruction to resolve.

MRCP and endoscopic ultrasound (EUS) may be reasonable to screen for persistent choledocholithiasis

in equivocal cases to prevent unnecessary intervention. In the absence of obstructive jaundice and/or

cholangitis, early ERCP is associated with high complication rates but no apparent benefits and is

therefore not recommended.

There is an approximately 18% incidence of recurrent pancreatitis or other gallstone-related

complications during the 6-week period following an episode of gallstone pancreatitis in patients who

do not undergo cholecystectomy.31 Indeed, there is a substantial incidence of recurrent pancreatitis and

gallstone-related complications in patients with biliary pancreatitis whose cholecystectomy is delayed

even 2 weeks after hospital discharge.32 Therefore, cholecystectomy should be performed during the

same hospitalization for most patients with mild gallstone pancreatitis. This strategy does not increase

operative complications, conversion to open procedures, or mortality.31 In severe biliary pancreatitis,

the risk of deferring surgery needs to be balanced against the risk of performing early surgery in

patients who are debilitated and nutritionally compromised. Endoscopic sphincterotomy is another

option, however, the high risk of recurrent gallstone-related complications and the higher mortality

compared to cholecystectomy suggest that this strategy should be reserved for patients with severe

comorbidities precluding safe surgery.31,33

Examples of other measures directed at correcting the underlying cause of pancreatitis include

cessation of drugs known to cause pancreatitis and treatment of hypercalcemia or hyperlipidemia.

Preventing and Treating Complications

Complications of acute pancreatitis include pancreatic abscesses and infected necrosis, pseudocysts and

walled-off necrosis, pancreatic ascites and fistulas, splenic vein thrombosis, and arterial

pseudoaneurysms (Table 53-4). Infected necrosis as well as pseudocysts and sterile walled-off necrosis

are discussed in detail below.

Infected Necrosis

8, 9 Infection of pancreatic and peripancreatic necrosis complicates 30% to 70% of cases of acute

necrotizing pancreatitis and most commonly becomes established during the second to third weeks after

onset of disease. Historical data suggest that mortality rates associated with untreated infected necrosis

approach 100%. Infected necrosis is suggested by clinical signs such as persistent fever, increasing

leukocytosis, and imaging findings such as gas in peripancreatic collections. When necessary, infected

necrosis can be confirmed by cultures of aspirates of fluid or necrotic tissue obtained during CT-guided

fine needle aspiration (FNA) or specimens collected during surgery. The concordance rate between

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recognition (i.e., damage/danger-associated pattern molecules and toll-like receptors (TLRs) as well as

the activation of transcription factors such as NF-κB play a role.8

The result of these events is pancreatic autodigestion, with injury to the vascular endothelium,

interstitium, and acinar cells. Increases in vascular permeability lead to interstitial edema.

Vasoconstriction, thrombosis, and capillary stasis can lead to ischemic (and perhaps ischemia–

reperfusion) injury and the development of pancreatic necrosis. With severe pancreatic injury, the

systemic inflammatory response syndrome (SIRS) and distant organ failure can occur. The systemic

complications are believed to be mediated by digestive enzymes and inflammatory mediators released

from the injured pancreas. For example, activated phospholipase A–induced digestion of lecithin (an

important component of pulmonary surfactant) may play a role in pathogenesis of acute respiratory

distress syndrome (ARDS) that occurs in the setting of acute pancreatitis. In addition, the circulatory

and inflammatory effects induced by acute pancreatitis are postulated to impair intestinal epithelial

barrier function, allowing for the translocation of bacteria from the intestinal lumen into the systemic

circulation. This phenomenon has been demonstrated to occur in animal models and may account for the

pathogenesis of pancreatic and peripancreatic infection that can complicate necrotizing pancreatitis.

ETIOLOGY

1 Although many etiologies of acute pancreatitis have been described, in the United States, more than

75% of cases are attributable to either gallstones or alcohol.

Gallstones

Gallstones cause approximately 35% of episodes of acute pancreatitis in the United States. In a

mechanistic model proposed over a century ago, a gallstone lodged at the papilla of Vater occludes the

ampullary orifice, leading to retrograde reflux of bile into the pancreatic duct through a common

channel shared by the common bile duct and the pancreatic duct (Fig. 53-2). Although elements of this

model have been challenged, the prevailing view is that transient or persistent obstruction of the

ampullary orifice by a gallstone or edema induced by stone passage is the inciting factor in the

pathogenesis of gallstone-induced pancreatitis. Microlithiasis refers to aggregates (<5 mm in diameter)

of cholesterol monohydrate crystals or calcium bilirubinate granules detected as “sludge” within the

gallbladder on ultrasonography or on examination of bile obtained during endoscopic retrograde

cholangiopancreatography (ERCP). An etiologic role for microlithiasis in acute pancreatitis remains

unproved; however, data derived from case-control studies suggest that cholecystectomy or endoscopic

sphincterotomy can reduce the risk of recurrent acute pancreatitis in patients with microlithiasis.

Figure 53-2. Illustration of the common channel concept. A gallstone lodged at the ampulla of Vater can cause reflux of bile into

the pancreatic duct.

Alcohol

1368

Ethanol causes approximately 40% of cases of acute pancreatitis in the United States. Most patients with

alcohol-induced acute pancreatitis also have underlying chronic pancreatitis. Potential mechanisms by

which alcohol-induced pancreatitis include sphincter of Oddi spasm, obstruction of small pancreatic

ductules by proteinaceous plugs, alcohol-induced metabolic abnormalities (e.g., hyperlipidemia), and

direct toxic effects induced by alcohol and its metabolites (e.g., acetaldehyde, acetate, and nonesterified

fatty acids).

Other Etiologies

A wide range of other etiologies of acute pancreatitis have been identified (Table 53-2). Ongoing

investigations are beginning to reveal specific gene abnormalities (e.g., mutations in cationic

trypsinogen PRSS1, pancreatic secretory trypsin inhibitor SPINK1, and the cystic fibrosis transmembrane

conductance regulator CFTR) that can be associated with pancreatitis. Patients for whom no etiology

can be identified despite thorough evaluation are classified as having idiopathic pancreatitis.

ETIOLOGY

Table 53-2 Etiology of Acute Pancreatitis

CLINICAL PRESENTATION

Abdominal pain, nausea, and vomiting are the most prevalent symptoms associated with acute

pancreatitis. The pain is visceral in quality, is localized to the epigastrium, often radiates to the back,

and may be alleviated with the patient leaning forward. Abdominal tenderness is the most prevalent

sign of acute pancreatitis. Tachycardia and hypotension may result from intravascular hypovolemia.

Low-grade fevers are common, but high-grade fevers are unusual in the absence of intra- or

extrapancreatic infection. Jaundice may be evident in the presence of cholangitis (e.g., with gallstoneinduced pancreatitis and persistent choledocholithiasis) or liver disease (alcohol-induced pancreatitis in

a patient with cirrhosis). Evidence of retroperitoneal hemorrhage may be become apparent if blood

dissects into the subcutaneous tissues of the flanks (Grey Turner sign), umbilicus (Cullen sign), or

1369

inguinal region (Fox sign); however, these findings are unusual. In approximately 20% of cases, acute

pancreatitis is associated with SIRS, hemodynamic lability, and/or organ failure (particularly

compromise of the cardiovascular, pulmonary, and renal systems) on presentation.

DIAGNOSIS

2 The differential diagnosis of acute pancreatitis includes other conditions causing acute upper

abdominal pain, such as biliary colic and cholecystitis, acute mesenteric ischemia, small bowel

obstruction, visceral perforation, and ruptured aortic aneurysm. Acute exacerbations of chronic

pancreatitis can also be associated with clinical features resembling those of acute pancreatitis. In

general, a diagnosis of acute pancreatitis can be made with the presence of two of the following three

features: (1) characteristic abdominal pain (acute onset of severe, persistent epigastric pain often

radiating to the back); (2) serum lipase (or amylase) levels at least three times greater than the upper

limit of normal; and (3) findings of acute pancreatitis on contrast-enhanced computed tomography (CT)

or magnetic resonance imaging (MRI).9,10 Imaging tests should be used selectively, to rule out other

diagnoses and for the indications discussed later. In cases of typical abdominal pain and confirmatory

laboratory tests, imaging is usually not needed at the time of admission.

Laboratory Tests

With pancreatic injury, a variety of digestive enzymes escape from acinar cells and enter the systemic

circulation. Of these enzymes, amylase is the most widely assayed to confirm the diagnosis of acute

pancreatitis. Amylase levels rise within several hours after onset of symptoms and typically remain

elevated for 3 to 5 days during uncomplicated episodes of mild acute pancreatitis. Because of the short

serum half-life of amylase (10 hours), levels can normalize as soon as 24 hours after disease onset. The

sensitivity of this test depends on what threshold value is used to define a positive result (90%

sensitivity with a threshold value just above the normal range vs. 60% sensitivity with a threshold value

at three times the upper limit of normal). Specificity (which also varies with the threshold values

selected) is limited because a wide range of disorders can cause elevations in serum amylase

concentration. Assays that detect increases in the serum concentration of amylase of pancreatic origin

(P-isoamylase) alone are associated with greater specificity. Increased urinary amylase concentrations

and amylase-to-creatinine clearance ratios occur with acute pancreatitis; however, these parameters

offer no advantage over serum amylase concentrations, except in the evaluation of macroamylasemia

(in which urinary amylase excretion is not increased despite elevations in serum amylase

concentration).

Serum lipase concentrations increase with kinetics similar to those of amylase. It has a longer serum

half-life than amylase, however, and may be useful for diagnosing acute pancreatitis late in the course

of an episode (at which time serum amylase concentrations may have already normalized). Although

lipase is more specific than amylase in the diagnosis of acute pancreatitis, note that lipase is produced at

a range of nonpancreatic sites, including the intestine, liver, biliary tract, and stomach, and tongue.

The magnitude of the increases in amylase or lipase concentrations has no correlation with severity of

pancreatitis. In general, the magnitude of increases in amylase concentrations tends to be greater in

patients with gallstone pancreatitis than in those with alcohol-induced pancreatitis; however, this

finding is unreliable in distinguishing between these two etiologies.

Imaging Tests

Findings on plain radiographs associated with acute pancreatitis are nonspecific and include ileus that

may be generalized or localized to a segment of small intestine (“sentinel loop”) or transverse colon

(“colon cut-off sign”), psoas muscle margins that are obscured by retroperitoneal edema, an elevated

hemidiaphragm, pleural effusions, and basilar atelectasis.

Ultrasonography may reveal a diffusely enlarged, hypoechoic pancreas. However, overlying bowel

gas (particularly prominent with ileus) limits visualization of the pancreas in a large percentage of

cases. Although ultrasonography has poor sensitivity in the diagnosis of acute pancreatitis, it plays an

important role in the identification of the etiology of pancreatitis (e.g., the detection of gallstones).

CT scanning is the most important imaging test in the evaluation of acute pancreatitis. CT findings of

mild acute pancreatitis include pancreatic enlargement and edema, effacement of the normal lobulated

contour of the pancreas, and stranding of peripancreatic fat (Fig. 53-3). In addition, dynamic CT

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scanning performed after the bolus administration of intravenous contrast can demonstrate regions of

pancreas that have poor or no perfusion, as seen with pancreatic necrosis (Fig. 53-4). Detection of

necrosis plays an important role in assessment of disease severity, as discussed further later. CT can also

characterize collections and other complications associated with acute pancreatitis.

Figure 53-3. Computed tomography scan of acute interstitial pancreatitis.

Figure 53-4. Computed tomography scan of acute necrotizing pancreatitis.

MRI and magnetic resonance cholangiopancreatography (MRCP) are being used with increasing

frequency in patients with acute pancreatitis. These examinations have the potential to offer better

definition of pancreatic and biliary ductal abnormalities than CT scanning, and they are applicable in

patients for whom ionizing radiation or iodinated intravenous contrast agents used in CT scanning are

contraindicated. MRI can suggest the presence of pancreatic necrosis even without the use of

intravenous gadolinium. MRI also has the advantage of better characterizing collections associated with

acute pancreatitis, in particular with respect to differentiating solid from liquid components.

Disadvantages of MRI include high cost, limited availability, and the long duration of examinations.

ASSESSMENT OF DISEASE SEVERITY

3 Approximately 80% of cases of acute pancreatitis are mild, associated with minimal systemic

derangements, and generally resolve within 5 to 7 days, even with minimal therapy. The mortality rate

associated with mild acute pancreatitis is less than 1%.

4, 5 Approximately 20% of cases are associated with either organ failure or the development of local

complications. The mortality rate for these patients ranges from approximately 10% to 20% in

contemporary series.11–14 One-half of deaths occur within the first 2 weeks after the onset of symptoms;

these deaths are primarily the result of SIRS-induced multisystem organ failure. Most of the remaining

deaths occur beyond 2 weeks after presentation and result from complications of pancreatic necrosis,

especially infection.

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32. Bell GI, Kayano T, Buse JB, et al. Molecular biology of mammalian glucose transporters. Diabetes

Care 1990;13(3):198–208.

33. Orci L, Unger RH, Ravazzola M, et al. Reduced beta-cell glucose transporter in new onset diabetic

BB rats. J Clin Invest 1990;86(5):1615–1622.

34. Ebert R, Creutzfeldt W. Gastrointestinal peptides and insulin secretion. Diabetes Metab Rev

1987;3(1):1–26.

35. Leahy JL, Bonner-Weir S, Weir GC. Abnormal glucose regulation of insulin secretion in models of

reduced B-cell mass. Diabetes 1984;33(7):667–673.

36. Mulvihill S, Pappas TN, Passaro E Jr, et al. The use of somatostatin and its analogs in the treatment

of surgical disorders. Surgery 1986;100(3):467–476.

37. Alghamdi AA, Jawas AM, Hart RS. Use of octreotide for the prevention of pancreatic fistula after

elective pancreatic surgery: a systematic review and meta-analysis. Can J Surg 2007;50(6):459–466.

38. Allen PJ, Gonen M, Brennan MF, et al. Pasireotide for postoperative pancreatic fistula. N Engl J

Med 2014;370(21):2014–2022.

39. Malleo G, Pulvirenti A, Marchegiani G, et al. Diagnosis and management of postoperative

pancreatic fistula. Langenbeck’s Arch Surg. 2014;399(7):801–810.

40. Cubilla AL, Fortner J, Fitzgerald PJ. Lymph node involvement in carcinoma of the head of the

pancreas area. Cancer 1978;41(3):880–887.

41. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal

gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma,

part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg

2002;236(3):355–366; discussion 366–358.

42. Japanese Pancreas Society. Classification of Pancreatic Carcinoma, First English Edition. Tokyo:

Kanehara and Complany, Ltd.; 1996.

43. Ahren B, Taborsky GJ Jr, Porte D Jr. Neuropeptidergic versus cholinergic and adrenergic regulation

of islet hormone secretion. Diabetologia 1986; 29(12):827–836.

44. Havel PJ, Taborsky GJ Jr. The contribution of the autonomic nervous system to changes of

glucagon and insulin secretion during hypoglycemic stress. Endocr Rev 1989;10(3):332–350.

45. Yeo TP, Hruban RH, Leach SD, et al. Pancreatic cancer. Curr Probl Cancer 2002;26(4):176–275.

46. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results,

outcomes, and prognostic indicators. J Gastrointest Surg 2000;4(6):567–579.

47. Lillemoe KD, Cameron JL, Hardacre JM, et al. Is prophylactic gastrojejunostomy indicated for

unresectable periampullary cancer? a prospective randomized trial. Ann Surg 1999;230(3):322–328;

discussion 328–330.

48. Nagaraja V, Eslick GD, Cox MR. Endoscopic stenting versus operative gastrojejunostomy for

malignant gastric outlet obstruction-a systematic review and meta-analysis of randomized and nonrandomized trials. J Gastrointest Oncol 2014;5(2):92–98.

49. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic

Adenocarcinoma. Version I.2016. Available from:

https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed June 24, 2016.

50. Seicean A. Celiac plexus neurolysis in pancreatic cancer: the endoscopic ultrasound approach. World

J Gastroenterol 2014;20(1):110–117.

51. Michaels AJ, Draganov PV. Endoscopic ultrasonography guided celiac plexus neurolysis and celiac

plexus block in the management of pain due to pancreatic cancer and chronic pancreatitis. World J

Gastroenterol 2007; 13(26):3575–3580.

52. Lillemoe KD, Cameron JL, Kaufman HS, et al. Chemical splanchnicectomy in patients with

unresectable pancreatic cancer. A prospective randomized trial. Ann Surg 1993;217(5):447–455;

discussion 456–447.

53. Gao L, Yang YJ, Xu HY, et al. A randomized clinical trial of nerve block to manage end-stage

pancreatic cancerous pain. Tumour Biol 2014;35(3):2297–2301.

54. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the

management of IPMN and MCN of the pancreas. Pancreatology 2012;12(3):183–197.

55. Chong AK, Hawes RH, Hoffman BJ, et al. Diagnostic performance of EUS for chronic pancreatitis: a

comparison with histopathology. Gastrointest Endosc 2007;65(6):808–814.

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Chapter 53

Acute Pancreatitis

Jason S. Gold and Edward E. Whang

Key Points

1 In the United States, more than 75% of cases of acute pancreatitis are attributable to either

gallstones or alcohol.

2 In general, a diagnosis of acute pancreatitis can be made with the presence of two of the following

three features: (1) characteristic abdominal pain (acute onset of severe, persistent epigastric pain

often radiating to the back); (2) serum lipase (or amylase) levels at least three times greater than

the upper limit of normal; and (3) findings of acute pancreatitis on contrast-enhanced CT or MRI.

3 Approximately 80% of cases of acute pancreatitis are mild, associated with minimal systemic

derangements, and generally resolve within 5 to 7 days, even with minimaltherapy.

4 Severe acute pancreatitis accounts for about 20% of cases and is defined as acute pancreatitis

associated with one or more of the following: pancreatic necrosis, distant organ failure, and the

development of local complications such as hemorrhage, abscess, or pseudocyst.

5 The mortality rate associated with severe acute pancreatitis ranges from 10% to 20%, with half of

the deaths in the first 2 weeks as the result of SIRS-induced multisystem organ failure and the

remaining occurring later as the result of pancreatic necrosis/infection.

6 The most important component of initial management of acute pancreatitis is fluid resuscitation.

7 Early ERCP in acute pancreatitis has been subjected to extensive study. Early ERCP with stone

extraction and sphincterotomy clearly benefits the subset of patients with gallstone pancreatitis who

have cholangitis.

8 Infection of pancreatic and peripancreatic necrosis complicates 30% to 70% of cases of acute

necrotizing pancreatitis and most commonly becomes established during the second to third weeks

after onset of disease.

9 Infected necrosis is suggested by clinical signs such as persistent fever, increasing leukocytosis, and

imaging findings such as gas in peripancreatic collections. When the necessary, infected necrosis can

be confirmed by CT-guided fine needle aspiration.

10 Invasive intervention is usually indicated in the presence of infected necrosis. In contrast, sterile

necrotic collections almost never require intervention in the acute phase of necrotizing pancreatitis.

11 Procedures for the treatment of infected necrosis are best performed when collections become

walled off and demarcated from viable pancreatic tissue with at least partial liquefaction, which

typically requires a delay of 4 to 6 weeks after disease onset.

12 Drainage alone is now the initial recommended intervention for infected pancreatic necrosis. This is

most often accomplished through a percutaneous image-guided approach. When percutaneous drains

are placed, preference should be given to a retroperitoneal approach. Drainage can also be

accomplished through an endoscopic transluminal approach.

13 When required, débridement can often be performed through minimally invasive techniques.

14 Current well-accepted indications for intervention on pseudocysts and walled-off necrosis in the

absence of infection include the presence of symptoms attributable to the collection such as

intractable pain or obstruction of the stomach, duodenum or bile duct.

15 There are multiple treatment options available for the treatment of pancreatic pseudocysts and

sterile walled-off necrosis, including percutaneous aspiration, percutaneous drainage, and internal

drainage (performed transabdominally or endoscopically).

Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other

regional tissues or remote organ systems.1 In the United States, more than 250,000 patients are

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hospitalized annually with acute pancreatitis as the primary diagnosis. It is the principal cause of

approximately 3,000 deaths per year and a contributing factor in an additional 2,500 deaths. The direct

cost attributable to acute pancreatitis exceeds $2.5 billion per year in the United States.2

CLASSIFICATION AND DEFINITIONS

A useful system for defining and classifying acute pancreatitis and its complications was recently

developed through an iterative process involving several national and international pancreas

organizations.3 This new system is a modification of widely accepted but outdated classification system

originally derived from a multidisciplinary symposium held in 1992.1 The clinically based definitions

reached by consensus are shown in Table 53-1.

PATHOLOGY AND PATHOPHYSIOLOGY

The typical pathologic correlate of mild acute pancreatitis is interstitial edematous pancreatitis, in which

the pancreatic parenchyma is edematous and infiltrated with inflammatory cells. Gross architectural

features are preserved. In contrast, in necrotizing pancreatitis variable amounts of pancreatic parenchyma

and peripancreatic fat have undergone tissue necrosis, with vascular inflammation and thrombosis being

prominent features.

Studies using experimental models suggest that prototypical molecular and cellular derangements lead

to pancreatic injury, regardless of the specific etiology or inciting event that triggers an episode of acute

pancreatitis. Among the earliest of these derangements appears to be abnormal activation of proteolytic

enzymes within pancreatic acinar cells.4 Under normal conditions, trypsinogen and other digestive

zymogens are stored in granules that are segregated from lysosomal enzymes (e.g., cathepsin B) and

acid. Early in the course of acute pancreatitis, cytoplasmic vacuoles containing activated proteolytic

enzymes appear. How the digestive enzymes are activated, and what role these vacuoles play has been

the subject of much investigation. In the prevailing model, trypsinogen is believed to be activated to

yield trypsin either by colocalization with the lysosomal hydrolase cathepsin B5 or through

autoactivation due to a moderately acidic pH6. It has been noted that the cytoplasmic vacuoles

appearing in the acinar cell in experimental acute pancreatitis share expression of proteins with

autophagosomes. Autophagosomes are vacuoles that degrade cellular components such as organelles in

the process of autophagy. Highlighting the possible importance of autophagy in the development of

pancreatitis, mice lacking expression of the autophagy-related gene Atg5 in the pancreas fail to exhibit

prototypical features of acute pancreatitis.7

CLASSIFICATION

Table 53-1 Terms Used in the Classification of Acute Pancreatitis

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Figure 53-1. Schematic diagram depicting activation of proteolytic enzymes, possibly through colocalization of zymogen granules

and lysosomes, and subsequent rupture of zymogen granules releasing the activated enzymes into the cytoplasm of the pancreatic

acinar cell. The activated enzymes then undergo disordered basolateral discharge from the acinar cell into the pancreatic

parenchyma.

Acinar cell injury induced by active trypsin allows it to be released into the pancreatic parenchyma

(Fig. 53-1) where it activates more trypsin and other digestive enzymes (e.g., chymotrypsin,

phospholipase, and elastase). Trypsin can also activate the complement, kallikrein-kinin, coagulation,

and fibrinolysis cascades within the pancreatic parenchyma. Activation of these enzymes is believed to

initiate a vicious cycle in which activated enzymes cause cellular injury, an event that leads to the

release of even more destructive enzymes. This cycle can overwhelm defense mechanisms that normally

serve to limit the injurious consequences of premature trypsin activation within the pancreas (e.g.,

pancreatic secretory trypsin inhibitor–mediated inhibition of trypsin activity).

An inflammatory response is then generated in response to the initial acinar cell injury. This

inflammatory response is marked by the infiltration of the pancreatic parenchyma with immune cells

such as neutrophils, macrophages, monocytes, and lymphocytes and the release of a broad range of

proinflammatory mediators such as tumor necrosis factor (TNF) α; interleukins (IL) 1β, 6, and 8;

platelet-activating factor; chemokines (i.e., CXCL2 and CCL2); prostaglandins; and leukotrienes. The

inflammatory response, to a large extent, determines the severity of pancreatitis, and the blockade of

several components of the inflammatory response ameliorates the disease and reduces mortality in

experimental models. The understanding of how the initial acinar cell injury provokes an inflammatory

response is incomplete, but it appears that reactive oxygen species (ROS) and innate molecular pattern

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The intrapancreatic location of the distal common bile duct is critical to many pancreatic disease

processes. Gallstone pancreatitis, the second most common cause of pancreatitis in the United States, is

caused by gallstones passed into the common bile duct. These gallstones can obstruct the duct distally

and lead to transient obstruction of the pancreatic duct with resulting reflux of pancreatic juice and bile

into the pancreatic duct, causing pancreatitis.

In benign pancreatic diseases such as chronic pancreatitis, disease in the pancreatic head may cause

benign biliary strictures and jaundice, whereas disease in the body and tail more often presents with

abdominal pain. Pancreatic ductal anatomy and the presence or absence of ductal dilation dictate the

choices for operative management. In the setting of a dilated pancreatic duct, drainage procedures may

impact pancreatic pain and recurrent acute episodes. Conversely, in the setting of small duct disease,

ablative therapy with resection (duodenum-preserving pancreatic head resection,

pancreaticoduodenectomy, and distal pancreatectomy) is the treatment of choice when medical

management fails.

Figure 52-11. Large pancreatic pseudocyst in the lesser sac. The pseudocyst is compressing the stomach anteriorly.

In the setting of acute or chronic pancreatitis, ductal disruption can lead to the formation of a

pancreatic pseudocyst. In many cases, these pseudocysts occur anterior to the pancreas in the lesser sac

(Fig. 52-11). This often leads to early satiety and abdominal pain. When large pseudocysts abut the

stomach, drainage can be achieved with endoscopic or operative cystgastrostomy.

Trauma and Pancreatic Injury

The pancreatic body lies anterior to the second lumbar vertebra deep in the retroperitoneum. In cases of

blunt abdominal trauma, specifically deceleration injury, the pancreatic body is crushed against the

second vertebral body and can be transected at this point. In trauma patients with elevated amylase and

lipase levels, the trauma surgeon should be aware of this possibility and obtain cross-sectional

pancreatic imaging to rule out ductal disruption. In the case of complete ductal disruption distal

pancreatectomy or drainage of the pancreas into the intestine may be necessary.

Penetrating injury to the duodenum or pancreas often involves major vascular injury and in many

cases is not survivable. In the case of injury to the IVC, the pancreas and duodenum must be mobilized

out of the retroperitoneum (Kocher maneuver) in order to expose the vessels.

DIAGNOSTIC APPROACH TO PATIENTS WITH PANCREATIC DISEASE

Pancreatic Imaging (Studies of Pancreatic Structure)

If pancreatic disease is suspected, the pancreas can be imaged by several radiographic modalities

including plain abdominal x-rays, upper gastrointestinal series, abdominal ultrasonography, CT MRCP,

endoscopic retrograde cholangiopancreatography (ERCP), and EUS.

Abdominal Plain Films

Plain films of the abdomen may be useful in patients with acute and chronic pancreatitis. In patients

with acute pancreatitis, the most common finding on plain film include a generalized ileus with air fluid

levels, a localized ileus or “sentinel loop” of jejunum or duodenum in the area of the inflamed pancreas,

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or a cutoff of the colon due to distention of the transverse colon. In the setting of acute pancreatic fluid

collections or pseudocysts, one may see an actual mass on plain film with displacement of the stomach

or duodenum.24 These findings are not sensitive or specific for acute pancreatitis, but in the setting of

elevated amylase and lipase and associated abdominal symptoms can provide support for the diagnosis

and an indication for more sensitive pancreatic imaging studies.

In the setting of chronic pancreatitis the most common finding on plain film is the presence of

calcifications within the pancreas. These are most commonly seen at the level of the second lumbar

vertebrae, where the pancreas lies in the retroperitoneum.

Upper Gastrointestinal Series

In the setting of a mass or mass effect on plain film, an upper gastrointestinal series can demonstrate

displacement of the stomach or duodenum by a retroperitoneal mass. Displacement or narrowing of the

duodenal C-loop suggests the presence of a pancreatic mass. However, the character of the mass

(inflammatory, neoplastic, cystic, etc.) cannot be further defined on upper gastrointestinal series.24 For

this reason, upper gastrointestinal series has been largely replaced by ultrasound and other crosssectional imaging modalities such as CT or MRCP.

Ultrasonography

Abdominal ultrasound can be useful in the setting of acute pancreatitis, chronic pancreatitis, pancreatic

cystic lesions, pancreatic pseudocysts, and pancreatic cancer. In acute pancreatitis, the abdominal

ultrasound may demonstrate gallstones, suggesting a potential etiology. In addition, the ultrasound can

identify an enlarged pancreas, pancreatic edema and peripancreatic fluid collections consistent with the

diagnosis of acute pancreatitis. Ultrasound can also identify pancreatic pseudocysts, cystic lesions, and

other pancreatic masses.24 Pancreatic pseudocysts usually appear as a smooth, round fluid collection

without acoustic shadowing. A pancreatic cancer is more likely to distort the underlying pancreatic

anatomy and appear as a localized, solid lesion on ultrasound, also without acoustic shadowing. Cystic

neoplasms of the pancreas can have both solid and cystic components. They can be uniloculated or

multiloculated and contain cysts of varying size. A large uniloculated neoplastic cyst is difficult to

differentiate from a pancreatic pseudocyst.

Ultrasound examination can be limited by obesity, overlying bowel gas, recently performed barium

contrast studies. Small masses or fluid collections can be easily missed. The presence of a mass on

ultrasound is an indication for more extensive workup via CT or MRCP imaging.

Computed Tomography

Contrast enhanced, multidetector helical 3D CT is the most commonly performed study for the detection

and characterization of pancreatic solid and cystic tumors. It is also useful in defining the pancreatic

anatomy in the presence of chronic pancreatitis and identifying and following the complications of acute

pancreatitis. CT is very sensitive for identifying pancreatic masses as small as 1 cm and can accurately

distinguish solid from cystic lesions. The density of the lesion on CT can provide clues as to the

diagnosis. Pancreatic adenocarcinomas are usually solid and hypodense, whereas pancreatic

neuroendocrine tumors are vascular and appear hyperdense. Both pseudocysts and cystic lesions have

components with fluid density.

CT is sensitive for the diagnosis of a malignant pancreatic adenocarcinoma. However, it is less

sensitive and accurate in the diagnosis of cystic lesions. As CT scans are more commonly performed for

a variety of indications, many cystic lesions are found incidentally. CT can be useful in identifying the

characteristics associated with malignancy including tumor size greater than 3 cm, a dilated main

pancreatic duct, and solid components within the cystic lesion.54 However, significant controversy

remains regarding observation versus resection of pancreatic cystic lesions.

Endoscopic Ultrasound

Compared to transabdominal ultrasound, EUS provides higher-resolution images of the pancreatic

parenchyma and pancreatic duct. This procedure uses a transducer fixed to an endoscope that can be

directed to the surface of the pancreas through the stomach or duodenum. EUS provides a useful adjunct

to CT in the diagnosis of mucinous cystic lesions and malignancies. Pancreatic masses and cystic lesions

can be well visualized on EUS, providing information about tumor size and invasion of major vascular

structures. While more invasive than CT, EUS can provide useful additional information. EUS allows for

fine-needle aspiration and/or biopsy, providing a tissue diagnosis, which is critical in the setting of

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planned neoadjuvant therapy for pancreatic adenocarcinoma. EUS can also provide information about

pancreatic ductal anatomy without the risk of invasive ERCP, which can cause severe pancreatitis.

A list of 11 EUS criteria has been defined for the diagnosis of chronic pancreatitis. The ductal criteria

include pancreatic duct stones, echogenic ductal walls, irregular ductal walls, pancreatic duct strictures,

visible side branches, and ductal dilatation. The parenchyma criteria include echogenic strands,

echogenic foci, calcifications, lobular contour, and pancreatic cysts. Recent studies have determined that

three or more EUS criteria provides the best balance of sensitivity and specificity for histologic

pancreatic fibrosis.55

Finally, in the setting of intractable pain in unresectable pancreatic cancer, chemical neurolysis of the

celiac ganglion can be performed under EUS guidance. As with any endoscopic procedure, the risks

include perforation of the stomach and/or duodenum.

Magnetic Resonance Cholangiopancreatography

MRCP is now being used more commonly as a noninvasive way to image both the biliary and pancreatic

ducts. MRCP can provide excellent images and detect abnormalities of the common bile duct and main

pancreatic duct, but it is more limited in its ability to detect abnormalities in the secondary ducts. This

noninvasive imaging technique is very useful in high-risk patients and pregnant patients. It is also useful

in diagnosis of persistent choledocholithiasis in the setting of gallstone pancreatitis. MRCP is most

useful in settings where intervention such as biopsy or biliary drainage are unnecessary, thereby

avoiding the risk of ERCP. MRCP can be a good modality for defining pancreatic ductal anatomy in

patients with chronic pancreatitis and pancreatic pseudocysts to help plan operative management.

Endoscopic Retrograde Cholangiopancreatography

ERCP is the gold standard for providing information about pancreatic ductal anatomy. However, it is

associated with significant complications and can often be avoided by using the previously described

noninvasive tests. Five percent to 20% of patients develop clinical pancreatitis after ERCP and 25% to

75% have elevated amylase and lipase levels.24 There is no way to prevent post-ERCP pancreatitis;

however, high-pressure injection of the pancreatic duct is thought to contribute. Perforation of the

gastrointestinal tract is a potential complication of ERCP.

ERCP is performed less commonly since much of the information can now be obtained with CT,

MRCP, and/or EUS. However, it remains the procedure of choice when there is a high likelihood for the

need of therapeutic intervention. For example, in patients with persistently elevated liver function tests

in the setting of common duct stones ERCP is both diagnostic and therapeutic.

Pancreatic cancer is characterized by obstruction or stenosis of the pancreatic duct and or common

bile duct (double-duct sign). ERCP remains the primary modality for palliation of obstructive jaundice

with endostent placement. In chronic pancreatitis, the pancreatic duct may have irregularities including

stenosis, dilation, sacculation, and ectasia. Pancreatic duct stones may be present within the pancreatic

duct. Similar ductal changes can be observed immediately following acute attacks of pancreatitis.

However, these abnormalities can be detected on MRCP or CT.

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Figure 52-8. 3D CT reconstructions of (A) Normal arterial supply to the pancreas, (B) Replaced right hepatic artery arising from

the superior mesenteric artery, (C) Replaced common hepatic artery arising from the superior mesenteric artery and (D) Replaced

left hepatic artery arising from the splenic artery.

Variations or anomalies in the pancreatic and biliary blood supply are found in 20% to 30% of people.

In most cases, all or part of the hepatic arterial blood supply does not arise from the celiac axis. As

much of the pancreatic blood supply is derived from the hepatic arterial blood supply, these variations

lead to variations in the pancreatic blood supply. In approximately 20% of patients, the replaced right

hepatic artery arises from the superior mesenteric artery (Fig. 52-8B) in the retropancreatic position and

traverses the upper edge of the uncinate process, then runs posterolateral to the portal vein. In this case,

a pulse remains in the hepatoduodenal ligament and the gastroduodenal artery can arise from the

replaced right or the left hepatic artery. The right hepatic artery can also originate from the right

gastric in 2% of cases or from the gastroduodenal artery in 6% of cases.

The entire hepatic arterial supply can be replaced, with the common hepatic artery originating from

the SMA instead of the celiac axis (Fig. 52-8C). In this case, there is no hepatic arterial pulse medially in

the hepatoduodenal ligament. The replaced common hepatic artery runs anterior to the portal vein, but

posterior to the bile duct and gives rise to a gastroduodenal branch, which is also posterior to the bile

duct. In approximately 10% of cases, the left hepatic artery can be aberrant, most commonly arising

from the left gastric artery instead of the proper hepatic artery.

Venous Drainage

The venous drainage of the pancreas follows the arterial blood supply and is eventually returned to the

portal circulation and delivered back to the liver. There are four main routes of venous drainage in the

pancreas. In the pancreatic head the superior venous arcades drain either directly into the portal vein

superiorly or laterally. The anterior and inferior pancreaticoduodenal arcades drain directly into the

infrapancreatic SMV. There are rarely any anterior branches from the pancreatic head and neck into the

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superior mesenteric and portal veins. When they do occur, it is most commonly at the superior border

of the pancreatic neck.

The body and tail of the pancreas has many venous tributaries that drain into the splenic vein, which

joins the SMV posterior to the pancreatic neck forming the portal vein (PV). The three named

tributaries of the splenic are the inferior pancreatic vein, the caudal pancreatic vein, and the great

pancreatic vein. The inferior mesenteric vein (IMV) does not drain the pancreas, but joins the splenic

vein posterior to the pancreatic body. The PV then drains the intestinal blood supply to the liver.

Lymphatic Drainage

Throughout the pancreas there is a rich periacinar network of lymphatic vessels which drain to five

major nodal groups: superior, inferior, anterior, posterior, and splenic.40 The superior nodal group runs

along the superior border of the pancreas and celiac trunk. They drain the superior portion of the

pancreatic head. The inferior nodal group along the inferior border of the head and body of the

pancreas drain the inferior pancreatic head and uncinate process, eventually draining to the superior

mesenteric and paraaortic lymph nodes. The anterior lymphatics drain to the prepyloric and infrapyloric

nodes. The posterior lymph nodes include the distal common bile duct and ampullary lymphatics and

drain directly into the paraaortic lymph nodes. Finally, the splenic lymph nodes drain the lymphatics of

the pancreatic body and tail into the interceliomesenteric lymph nodes.

The Japanese Pancreas Society has classified the pancreatic lymphatic drainage into 18 lymph node

stations (Table 52-5).42 The greater and lesser curves of the stomach drain into lymph node stations 1

through 4. The anterior lymphatics described above drain into lymph node stations 5 and 6. The

superior nodal group includes lymph node stations 7 through 9 along the left gastric artery, common

hepatic artery, and celiac axis. The posterior lymph nodes include lymph node stations 12 (and all

subdivisions) and 13, while the inferior nodal group comprises stations 14 through 17. The splenic

lymph node group corresponds to Japanese lymph node stations 10 and 11.

Innervation

The innervation to the pancreas is derived from the vagus and thoracic splanchnic nerves as well as

peptidergic neurons that secrete amines and peptides.43 Parasympathetic and sympathetic fibers for

ganglia along the celiac axis and superior mesenteric artery, which give rise to the pancreatic branches

reach the pancreas by passing along the arteries from the celiac axis and superior mesenteric arteries.

The parasympathetic nerves stimulate both exocrine and endocrine secretion, while the sympathetic

fibers have a predominantly inhibitory effect (Fig. 52-9).44 The peptidergic neurons secrete hormones

including somatostatin, VIP, calcitonin gene–related peptide (CGRP), and galanin. While the peptidergic

neurons influence exocrine and endocrine secretion, their precise physiologic role is unclear. The

pancreas also has a rich network of afferent sensory fibers.

Table 52-5 Japanese Lymph Node Stations

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SURGICAL SIGNIFICANCE OF PANCREATIC ANATOMY

10 Knowledge of the anatomy and anatomical variants can give clues to the diagnosis of pancreatic

disease based on signs and symptoms. In addition, an understanding of the pancreatic anatomy in

relation to adjacent structures is essential when performing operative procedures on the pancreas or

surrounding structures including the duodenum, bile duct, and spleen.

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Figure 52-9. Schematic diagram of the neurohormonal control of the exocrine cells. Visceral receptors line the ductule system and

carry the sensation of pain to the spinal cord. Sympathetic fibers first synapse in the celiac plexus after traveling through the

thoracic ganglia and splanchnic nerves. Postganglionic fibers then synapse on intrapancreatic arterioles. Parasympathetic

preganglionic fibers travel through the celiac plexus after leaving the vagus nerves and course with vessels and ducts to synapse on

postganglionic fibers near acinar cells, islet cells, and smooth muscle cells of major ducts. Stimulation of these parasympathetic

fibers results in an immediate release of pancreatic enzymes. Secretin and CCK first enter the pancreas through the capillary

network of the islet cells, and then enter the separate capillary network of the acinar tissue through the insuloacinar portal vessels.

Glucagon, somatostatin, pancreatic polypeptide, and insulin from the islets cells reach the acinar tissue immediately after release.

In this way, the islet cells can influence the acinar tissue responses to CCK and secretin.

Pancreatic Anatomy and Pancreatic Cancer

Approximately, 75% of pancreatic adenocarcinomas occur in the pancreatic head at the genu of the

pancreatic duct.45 As a result, people who develop cancer in the head of the pancreas most commonly

present with obstructive jaundice secondary to occlusion of the intrapancreatic bile duct by tumor,

leading to earlier diagnosis. People with body and tail tumors present with abdominal pain and other

vague abdominal symptoms, often leading to a delay in diagnosis. Nearly 85% of resected pancreatic

tumors are in the head, neck, or uncinate process of the pancreas.46

Similarly, patients with cancer in the pancreatic head often have invasion of the adjacent duodenum.

They may present with or develop signs and symptoms of duodenal or gastric outlet obstruction. In

patients with unresectable disease, late gastric outlet obstruction in patients requiring

gastrojejunostomy or duodenal stenting occurs in 10% to 20% of patients. A prospective, randomized

trial demonstrated that the addition of prophylactic gastrojejunostomy in addition to

hepaticojejunostomy significantly reduced gastric outlet obstruction in patients with unresectable

disease undergoing open biliary bypass.47 However, in the modern era, biliary stenting is so effective

that operative hepaticojejunostomy for unresectable disease is rarely indicated. In the setting of isolated

gastric outlet obstruction in unresectable disease, duodenal stenting is an option. When successful this

can avoid surgery and its negative impact on the remaining quality of life. In a meta-analysis of trials

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comparing endoscopic stenting to gastrojejunostomy, stenting was associated with shorter time to oral

intake and shorter length of stay, with similar complication rates, and decreased mortality.48

11 The ability to resect a pancreatic cancer depends on the presence or absence of metastatic disease

and the extent of local vascular involvement. Pancreatic cancers are classified as resectable, borderline

resectable, or unresectable (including locally advanced unresectable disease and metastatic disease).

Table 52-6 shows the 2014 National Comprehensive Cancer Network definitions for resectable,

borderline resectable, and unresectable disease.49 Tumors are considered resectable if they have: (1) no

distant metastases, (2) no radiographic evidence of SMV or PV distortion, and (3) clear fat planes

around the celiac axis, hepatic artery, and SMA (Fig. 52-10A).

Table 52-6 Criteria for Resectability in Pancreatic Cancer

Tumors are considered borderline resectable if they have: (1) no distant metastases, (2) venous

involvement of the SMV or PV with distortion or narrowing of the vein or occlusion of the vein with

suitable vessel proximal and distal, allowing for safe resection and replacement, (3) gastroduodenal

artery encasement up to the hepatic artery with either short segment encasement or direct abutment of

the hepatic artery, without extension to the celiac axis, and (4) tumor abutment of the SMA not to

exceed greater than 180 degrees of the circumference of the vessel wall (Fig. 52-10B).

Tumors are considered to be locally unresectable if there is: (1) no distant metastatic disease, (2)

greater than 180 degrees SMA encasement, (3) any celiac axis abutment, (4) unreconstructable

SMV/portal occlusion, (5) invasion or encasement of the aorta or inferior vena cava (IVC), and (6)

nodal involvement outside the field of resection. Patients with any distant metastatic disease, most

commonly to the liver or lymph nodes outside the field of resection, or the presence of peritoneal

carcinomatosis are considered unresectable.

Pancreatic head cancers may also involve adjacent organs including the hepatic flexure of the colon,

the gallbladder, or the stomach. If there are no distant metastases, resection of these organs en bloc is

indicated. For cancers in the body and tail without distant metastasis, involvement of the splenic artery

and/or vein does not preclude resection as these vessels are normally taken during the operation.

However, involvement of the celiac axis or superior mesenteric artery precludes resection. Involvement

of adjacent organs including the left kidney, left adrenal, spleen, and left colon can be resected if

involved with tumor and there is no distant disease.

Knowledge of the normal pancreatic blood supply is critical in order to perform an adequate cancer

operation. As the duodenum and head of pancreas share a blood supply, it is necessary to remove these

organs en bloc when performing an operation for carcinoma. While the duodenum can be preserved in

resections performed for benign disease (duodenum-preserving pancreatic head resection), this is not

the case in patients with cancer. Likewise, for cancers in the body and tail of the pancreas it is necessary

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to resect the spleen and its blood supply since it shares a blood supply with the tail of the pancreas. For

benign diseases of the pancreatic tail, the spleen can be preserved.

There has been significant debate regarding the extent of lymph node dissection necessary in patients

undergoing curative resection for pancreatic cancer. Table 52-5 shows the difference in extent of

lymphadenectomy between the standard and radical procedure. The standard procedure includes the

bile duct (station 12b2) and cystic duct lymph nodes (station 12c), the posterior (station 13) and

anterior (station 17) pancreaticoduodenal lymph nodes, the SMV nodes (station 14v), and the nodes on

the right side of the superior mesenteric artery (station 14b). Radical resection adds a distal

gastrectomy (stations 3, 4, 5, and 6) and a retroperitoneal dissection extending from the right renal

hilum to the left lateral border of the aorta horizontally with samples of celiac nodes, and from the

portal vein to below the third portion of the duodenum vertically (lymph node stations 16a1, 16b2, and

9). In the United States, standard resection is most commonly performed.

Figure 52-10. A: Resectable pancreatic head cancer. There is a clear plane between the tumor and both the superior mesenteric

artery and superior mesenteric vein. B: Borderline resectable pancreatic cancer. Involvement of the superior mesenteric vein with

distortion and narrowing; tumor abutment of the superior mesenteric artery less than 80 degrees of the circumference.

Awareness of the common anatomic variants in biliary and pancreatic arterial supply is necessary to

prevent major vascular injury and damage to the hepatic blood supply during pancreatic resection. The

gastroduodenal artery is the largest named artery taken during pancreaticoduodenectomy. In the case of

a replaced right hepatic artery arising from the superior mesenteric artery, the gastroduodenal artery

can arise from this replaced vessel and enter the pancreas posterior to the bile duct. In addition, this

replaced right hepatic artery courses to the liver lateral to the bile duct and can easily be injured during

dissection of the pancreatic uncinate process off of the superior mesenteric vessels. A replaced right

hepatic artery often supplies the entire right lobe of the liver causing significant hepatic ischemia if

injured. In the case of a replaced right hepatic artery, there will still be a pulse medially in the

hepatoduodenal ligament from the left hepatic artery, but this will supply only the left lobe of the liver.

In the case of a replaced common hepatic artery, the entire hepatic blood supply will be from the

SMA. There will be no pulse medially in the hepatoduodenal ligament. The replaced vessel will again be

posterior and lateral to the bile duct and at risk of injury if not correctly identified. Given the closer

proximity of the replaced vessels to the pancreatic head and uncinate process, these replaced vessels

may also be more prone to direct involvement by tumor. If injured or involved with tumor and

resected, these often require reconstruction to restore adequate hepatic blood supply.

Due to the rich afferent sensory fiber network within the pancreas, abdominal pain and back pain are

common presenting symptoms in patients with pancreatic cancer. As pancreatic cancer progresses, the

nervous plexuses along the celiac axis in the retroperitoneum can be invaded by a tumor causing the

characteristic intractable back pain. In this setting, celiac ganglion blockade (sympathectomy) or

neurolysis using alcohol can provide significant pain relief by interrupting these somatic fibers. A celiac

block can be performed endoscopically,50 percutaneously, or intraoperatively. Endoscopic ultrasound

(EUS)- or CT-guided celiac plexus neurolysis should be considered first-line therapy in patients with pain

secondary to unresectable, locally advanced pancreatic cancer.51 Celiac blockade has been shown to

reduce pain in patients with unresectable pancreatic cancer undergoing operative bypass procedures for

obstructive jaundice and duodenal obstruction.52,53

Pancreatic Anatomy and Pancreatitis

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data from randomized trials failed to show any advantage of somatostatin analogs for accelerating

fistula closure after pancreatic surgery.39

Pancreatic Polypeptide Synthesis, Secretion, and Action

Pancreatic polypeptide is a 36-amino-acid polypeptide secreted by the F cells of the pancreatic islet. The

physiologic role of pancreatic polypeptide remains unclear. It has been shown to inhibit pancreatic

exocrine secretion and gallbladder emptying. Cholinergic innervation predominantly regulates

pancreatic polypeptide secretion. In diabetes and normal aging pancreatic polypeptide secretion is

increased resulting in increased circulating pancreatic polypeptide levels.

Other Peptide Products

Other peptides are secreted within the pancreatic islet. These include neuropeptides such as VIP,

galanin, amylin, pancreastatin, chromogranin A, and serotonin, which are believed to play a role in the

regulation of islet cell secretion. Amylin, a 36-amino-acid polypeptide, is secreted by the B cells, but not

in equimolar amounts to proinsulin. Amylin inhibits secretion of insulin and its uptake in the periphery.

Amylin has been found to be deposited in the pancreas of patients with type II diabetes and has been

implicated in the pathogenesis of the disease. Pancreastatin is another peptide found in large amounts in

the pancreas. It is a derivative of chromogranin A, but its physiologic significance is unknown.

Chromogranin A is produced by most neuroendocrine tumors and is a good marker for diagnosis and

recurrence of pancreatic neuroendocrine tumors.

Tests of Pancreatic Endocrine Function

The most widely used tests of pancreatic endocrine function measure the body’s ability to utilize

glucose. The oral glucose tolerance test provides an indirect assessment of the insulin response to an

oral glucose load; it measures the glucose profile and not the actual insulin response. After an overnight

fast, two basal blood samples are drawn and glucose levels are analyzed. Patients are then given an oral

glucose load of 40 g/m2 over 10 minutes. Blood samples are then drawn every 30 minutes for 2 hours.

The fasting glucose level should be less than 110 mg/dL. Fasting levels between 110 and 126 mg/dL are

considered borderline, and fasting levels above 126 mg/dL are diagnostic of diabetes. The 2-hour

glucose level should be below 140 mg/dL. Two-hour levels between 140 and 200 mg/dL are borderline,

and 2-hour levels over 200 mg/dL are again diagnostic of diabetes mellitus. The test takes into account

the gastrointestinal influences of glucose metabolism and can be affected by antecedent diet, drug use,

exercise, and patient age.

The intravenous glucose tolerance test can be used to eliminate gastrointestinal influences on glucose

metabolism. After basal glucose levels are obtained, this test is performed in similar fashion to the oral

glucose tolerance test, except the glucose load is delivered as an intravenous bolus of 0.5 g/kg over 2 to

5 minutes. Blood is then drawn every 10 minutes for an hour. The disappearance of glucose per minute

(K value) is calculated. A K value of 1.5 or higher is normal. The results are age adjusted, as the

response to the intravenous glucose load decreases with age.

An insulinoma is a pancreatic neuroendocrine tumor that secretes insulin. The gold standard for

diagnosis of insulinoma is the 72-hour monitored fast. This test documents Whipple triad of

hypoglycemia, neuroglycopenic symptoms concurrent with hypoglycemia, and resolution of symptoms

with administration of glucose. It also allows the clinic to rule out surreptitious administration of

exogenous insulin. Within the B cell, proinsulin is cleaved into insulin and C-peptide prior to secretion.

Therefore, both insulin and C-peptide levels can be measured in the blood stream and should be present

in a 1:1 ratio. Surreptitious administration of exogenous insulin can be differentiated from insulinoma

by the absence of C-peptide in the case of the exogenously administered insulin. Patients are fasted in a

monitored setting. All nonessential medications are stopped and patients can only drink water, black,

decaffeinated coffee, and diet sodas. Glucose and insulin levels as well as neuroglycopenic symptoms

are closely monitored. The criteria for discontinuing the fast include serum glucose levels less than 45

mg/dL and the patient must be symptomatic. The 72-hour fast is highly sensitive for insulinoma and a

patient rarely finishes this test without an unequivocal diagnosis. Urine should also be screened for the

presence of sulfonylureas and other oral hypoglycemic medications.

The intravenous arginine test and tolbutamide response test are used to help in diagnosis of more rare

hormone-secreting pancreatic neuroendocrine tumors. After an overnight fast, a patient is given a 30-

minute intravenous infusion of 0.5 g/kg of arginine, which stimulates secretion of islet cell hormones.

Blood samples are taken every 10 minutes and radioimmunoassays are performed for the hormone in

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question. This test is most useful for glucagon-secreting tumors and is not commonly used. Elevations of

plasma glucagon levels to over 400 pg/mL are diagnostic for glucagonoma.

Tolbutamide is a sulfonylurea that stimulates insulin secretion and secretion of other pancreatic

endocrine hormones. After fasting overnight, blood samples are drawn and a patient is given 1 g of

tolbutamide intravenously. Blood glucose is monitored for 1 hour and blood samples are drawn to

determine levels of the hormone of interest. Sustained hypoglycemia with hypersecretion of insulin is

diagnostic of insulinoma. Somatostatin levels more than twice as high as the normal values of the

particular assay used are considered diagnostic of somatostatinoma.

PANCREATIC ANATOMY

The pancreas lies in the retroperitoneum at the level of the second lumbar vertebrae. It lies obliquely

and transversely from its most caudal point at the duodenal C-loop on the right to its most cranial point

in the splenic hilum on the left. The pancreas is composed of four anatomic parts: the head (including

the uncinate process), the neck, the body, and the tail (Fig. 52-7).

Figure 52-7. Normal pancreatic anatomy. The pancreatic head lies within the C-loop of the duodenum. The main pancreatic duct

and common bile duct run through the head of the pancreas and drain into the duodenum at the ampulla of Vater. The superior

mesenteric artery and vein lie posterior to the pancreatic neck.

Relationship to Adjacent Structures

The pancreatic head is further subdivided into the head and uncinate process. The head and uncinate

process lie within the C-loop of the duodenum and include all the pancreatic parenchyma to the right of

the superior mesenteric vessels. The pancreatic head is attached to the medial aspect of the descending

and third portion of the duodenum and the two organs share a blood supply. The uncinate process

projects from the inferior portion of the pancreatic head medially to the left, then posterior to the

superior mesenteric vessels. The inferior vena cava, right renal artery and vein, and left renal vein lie

posterior to the uncinate process and pancreatic head. The bile duct runs through the posterior and

superior aspect of the pancreatic head, joining the pancreatic duct and draining into the duodenum

medially at the ampulla of Vater (Fig. 52-7).

The pancreatic neck is the portion of pancreatic tissue that overlies the superior mesenteric artery and

vein anteriorly. The anterior surface of the pancreatic neck lies directly posterior to the pylorus of the

stomach. The body of the pancreas continues left from the pancreatic neck. The anterior surface of the

pancreatic neck, body, and tail are covered with peritoneum and forms the floor of the omental bursa

within the lesser sac. The stomach overlies the pancreatic body/lesser sac anteriorly. The posterior

surface of the pancreatic body is not peritonealized and directly contacts the aorta, left adrenal gland,

left kidney, and left renal artery and vein. The body of the pancreas is the portion overlying the second

lumbar vertebrae. The tail of the pancreas begins anterior to the left kidney and extends superolaterally

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to the hilum of the spleen. The splenic artery and vein run along the posterior surface of the pancreas.

The tail of the pancreas is in close proximity to the spleen and splenic flexure of the colon.

Pancreatic Ductal Anatomy

The main pancreatic duct, or duct of Wirsung, begins in the pancreatic tail. It most commonly runs

within the posterior aspect of the pancreatic parenchyma, midway between the superior and inferior

border of the gland. In the head of the pancreas, the pancreatic duct turns inferiorly at the genu of the

pancreatic duct and joins the common bile duct, draining into the second portion of the duodenum at

the ampulla of Vater. A common channel may exist between the common bile duct and main pancreatic

duct and it varies in length across the population. At the level of the ampulla of Vater, the pancreatic

duct is anterior and inferior to the common bile duct. At the ampulla of Vater, the sphincter of Oddi

prevents reflux of duodenal contents into the bile duct and pancreatic duct. This sphincter of Oddi is

controlled by a variety of neural and hormonal factors that regulate relaxation and constriction.

A normal main pancreatic duct is 2 to 4 mm in diameter and has a ductal pressure of approximately

15 to 30 mm Hg. This is higher than the pressure in the common bile duct (7 to 17 mm Hg) and serves

to prevent reflux of bile into the pancreatic ductal system. There are over 20 side branches of the main

pancreatic duct throughout the pancreas providing drainage of acinar units. The accessory pancreatic

duct, or duct of Santorini, is more variable than the main pancreatic duct. It typically drains the

uncinate process and inferior portion of the pancreatic head into the duodenum at the minor papilla,

proximal to the ampulla of Vater.

Arterial Blood Supply

The pancreatic blood supply arises from the celiac axis and superior mesenteric artery. The celiac axis

arises from the abdominal aorta and most commonly gives rise to the splenic artery, the left gastric

artery, and the common hepatic artery (Fig. 52-8A). The splenic artery courses along the posterior

surface of the pancreatic body and tail and gives rise to more than 10 branches which supply the

pancreatic body and tail. The first branch of the splenic artery is the dorsal pancreatic artery; it arises

close to the origin of the splenic artery and supplies blood to the proximal body. Further distally, the

great pancreatic artery supplies the midportion of the body and the caudal pancreatic artery supplies the

pancreatic tail.

The head of the pancreas is supplied by both the celiac and superior mesenteric artery (SMA). The

gastroduodenal artery is the first branch off the common hepatic artery. Distal to the first portion of the

duodenum, the gastroduodenal artery becomes the superior pancreaticoduodenal artery and divides into

anterior and posterior branches. The SMA gives rise to the inferior pancreaticoduodenal artery, which

also divides into anterior and posterior branches. The inferior and superior pancreaticoduodenal arcades

form an extensive collateral network with the superior pancreaticoduodenal arcades, supplying both the

duodenum and head of the pancreas. Anteriorly these arcades lie in the groove between the pancreas

and duodenum. Posteriorly, they cross the common bile duct. The arterial blood supply of ampulla of

Vater is from three pedicles off the superior and inferior pancreaticoduodenal arteries. The posterior

pedicle, located at 11 o’clock, arises from the superior pancreaticoduodenal artery. The ventral

commissural pedicle, located at 1 o’clock, arises from both arcades. Finally, the inferior pedicle at 6

o’clock arises from the anterior branch of the inferior pancreaticoduodenal artery. Near the head of the

pancreas, branches arising from the splenic artery form collaterals with the inferior pancreaticoduodenal

arcades.

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