Mark E. Baker, MD

Acute pancreatitis accounted for more than 300,000 admissions and $2.6 billion in associated healthcare costs in the United States in 2012.¹ First-line management is early aggressive fluid resuscitation and analgesics for pain control. Guidelines recommend estimating the clinical severity of each attack using a validated scoring system such as the Bedside Index of Severity in Acute Pancreatitis.² Clinically severe pancreatitis is associated with necrosis.

Acute pancreatitis results from inappropriate activation of zymogens and subsequent auto­digestion of the pancreas by its own enzymes. Though necrotizing pancreatitis is thought to be an ischemic complication, its pathogenesis is not completely understood. Necrosis increases the morbidity and mortality risk of acute pancreatitis because of its association with organ failure and infectious complications. As such, patients with necrotizing pancreatitis may need admission to the intensive care unit, nutritional support, antibiotics, and radiologic, endoscopic, or surgical interventions.

Here, we review current evidence regarding the diagnosis and management of necrotizing pancreatitis.

PROPER TERMINOLOGY HELPS COLLABORATION

Managing necrotizing pancreatitis requires the combined efforts of internists, gastroenterologists, radiologists, and surgeons. This collaboration is aided by proper terminology.

A classification system was devised in Atlanta, GA, in 1992 to facilitate communication and interdisciplinary collaboration.³ Severe pancreatitis was differentiated from mild by the presence of organ failure or the complications of pseudocyst, necrosis, or abscess.

The original Atlanta classification had several limitations. First, the terminology for fluid collections was ambiguous and frequently misused. Second, the assessment of clinical severity required either the Ranson score or the Acute Physiology and Chronic Health Evaluation II score, both of which are complex and have other limitations. Finally, advances in imaging and treatment have rendered the original Atlanta nomenclature obsolete.

In 2012, the Acute Pancreatitis Classification Working Group issued a revised Atlanta classification that modernized the terminology pertaining to natural history, severity, imaging features, and complications. It divides the natural course of acute pancreatitis into early and late phases.⁴

Early vs late phase

The early phase is within 1 week of symptom onset. In this phase, the diagnosis and treatment are based on laboratory values and clinical assessment. Clinical severity is classified as mild, moderate, or severe (Table 1) based on organ dysfunction assessed using the Marshall score.⁵

In the early phase, findings on computed tomography (CT) neither correlate with clinical severity nor alter clinical management.⁶ Thus, early imaging is not indicated unless there is diagnostic uncertainty, lack of response to appropriate treatment, or sudden deterioration.

Moderate pancreatitis describes patients with pancreatic necrosis with or without transient organ failure (organ dysfunction for ≤ 48 hours).

Severe pancreatitis is defined by pancreatic necrosis and persistent organ dysfunction.⁴ It may be accompanied by pancreatic and peripancreatic fluid collections; bacteremia and sepsis can occur in association with infection of necrotic collections.

Interstitial edematous pancreatitis vs necrotizing pancreatitis

The revised Atlanta classification maintains the original classification of acute pancreatitis into 2 main categories: interstitial edematous pancreatitis and necrotizing pancreatitis.

Interstitial edematous pancreatitis (Figure 1) is rarely clinically severe (approximately 1% to 3% of cases), and mortality risk correlates with the patient’s comorbid medical conditions.⁷

Necrotizing pancreatitis is further divided into 3 subtypes based on extent and location of necrosis:

• Parenchymal necrosis alone (5% of cases)
• Necrosis of peripancreatic fat alone (20%)
• Necrosis of both parenchyma and peripancreatic fat (75%).

Peripancreatic involvement is commonly found in the mesentery, peripancreatic and distant retroperitoneum, and lesser sac.

Of the three subtypes, peripancreatic necrosis has the best prognosis. However, all of the subtypes of necrotizing pancreatitis are associated with poorer outcomes than interstitial edematous pancreatitis.

Fluid collections

Fluid collections in acute pancreatitis are classified on the basis of the time course, location, and fluid or solid components (Figure 2). In the first 4 weeks, interstitial edematous pancreatitis is associated with acute pancreatic fluid collections, and necrotizing pancreatitis is associated with acute necrotic collections.

Acute pancreatic fluid collections contain exclusively nonsolid components without an inflammatory wall and are typically found in the peripancreatic fat. These collections often resolve without intervention as the patient recovers. If they persist beyond 4 weeks and develop a nonepithelialized, fibrous wall, they become pseudocysts. Intervention is generally not recommended for pseudocysts unless they are symptomatic.

Acute necrotic collections contain both solid and liquid components and can progress to walled-off pancreatic necrosis (Figure 3). Both early and late collections may be sterile or infected.

 

 

ROLE OF IMAGING

Radiographic imaging is not usually necessary to diagnose acute pancreatitis. However, it can be a valuable tool to clarify an ambiguous presentation, determine severity, and identify complications.

The timing and appropriate type of imaging are integral to obtaining useful data. Any imaging obtained in acute pancreatitis to evaluate necrosis should be performed at least 3 to 5 days from the initial symptom onset; if imaging is obtained before 72 hours, necrosis cannot be confidently excluded.⁸

COMPUTED TOMOGRAPHY

CT is the imaging test of choice when evaluating acute pancreatitis. In addition, almost all percutaneous interventions are performed with CT guidance. The Balthazar score is the most well-known CT severity index. It is calculated based on the degree of inflammation, acute fluid collections, and parenchymal necrosis.⁹ However, a modified severity index incorporates extrapancreatic complications such as ascites and vascular compromise and was found to more strongly correlate with outcomes than the standard Balthazar score.¹⁰

Contrast-enhanced CT is performed in 2 phases:

The pancreatic parenchymal phase

The pancreatic parenchymal or late arterial phase is obtained approximately 40 to 45 seconds after the start of the contrast bolus. It is used to detect necrosis in the early phase of acute pancreatitis and to assess the peripancreatic arteries for pseudoaneurysms in the late phase of acute pancreatitis.¹¹

Pancreatic necrosis appears as an area of decreased parenchymal enhancement, either well-defined or heterogeneous. The normal pancreatic parenchyma has a postcontrast enhancement pattern similar to that of the spleen. Parenchyma that does not enhance to the same degree is considered necrotic. The severity of necrosis is graded based on the percentage of the pancreas involved (< 30%, 30%–50%, or > 50%), and a higher percentage correlates with a worse outcome.^12,13

Peripancreatic necrosis is harder to detect, as there is no method to assess fat enhancement as there is with pancreatic parenchymal enhancement. In general, radiologists assume that heterogeneous peripancreatic changes, including areas of fat, fluid, and soft tissue attenuation, are consistent with peripancreatic necrosis. After 7 to 10 days, if these changes become more homogeneous and confluent with a more mass-like process, peripancreatic necrosis can be more confidently identified.^12,13

The portal venous phase

The later, portal venous phase of the scan is obtained approximately 70 seconds after the start of the contrast bolus. It is used to detect and characterize fluid collections and venous complications of the disease.

Drawbacks of CT

A drawback of CT is the need for iodinated intravenous contrast media, which in severely ill patients may precipitate or worsen pre-existing acute kidney injury.

Further, several studies have shown that findings on CT rarely alter the management of patients in the early phase of acute pancreatitis and in fact may be an overuse of medical resources.¹⁴ Unless there are confounding clinical signs or symptoms, CT should be delayed for at least 72 hours.^9,10,14,15

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) is not a first-line imaging test in this disease because it is not as available as CT and takes longer to perform—20 to 30 minutes. The patient must be evaluated for candidacy, as it is difficult for acutely ill patients to tolerate an examination that takes this long and requires them to hold their breath multiple times.

MRI is an appropriate alternative in patients who are pregnant or who have severe iodinated-contrast allergy. While contrast is necessary to detect pancreatic necrosis with CT, MRI can detect necrosis without the need for contrast in patients with acute kidney injury or severe chronic kidney disease. Also, MRI may be better in complicated cases requiring repeated imaging because it does not expose the patient to radiation.

On MRI, pancreatic necrosis appears as a heterogeneous area, owing to its liquid and solid components. Liquid components appear hyperintense, and solid components hypointense, on T2 fluid-weighted imaging. This ability to differentiate the components of a walled-off pancreatic necrosis can be useful in determining whether a collection requires drainage or debridement. MRI is also more sensitive for hemorrhagic complications, best seen on T1 fat-weighted images.^12,16

Magnetic resonance cholangiopancreatography is an excellent method for ductal evaluation through heavily T2-weighted imaging. It is more sensitive than CT for detecting common bile duct stones and can also detect pancreatic duct strictures or extravasation into fluid collections.¹⁶

SUPPORTIVE MANAGEMENT OF EARLY NECROTIZING PANCREATITIS

In the early phase of necrotizing pancreatitis, management is supportive with the primary aim of preventing intravascular volume depletion. Aggressive fluid resuscitation in the first 48 to 72 hours, pain control, and bowel rest are the mainstays of supportive therapy. Intensive care may be necessary if organ failure and hemodynamic instability accompany necrotizing pancreatitis.

Prophylactic antibiotic and antifungal therapy to prevent infected necrosis has been controversial. Recent studies of its utility have not yielded supportive results, and the American College of Gastroenterology and the Infectious Diseases Society of America no longer recommend it.^9,17 These medications should not be given unless concomitant cholangitis or extrapancreatic infection is clinically suspected.

Early enteral nutrition is recommended in patients in whom pancreatitis is predicted to be severe and in those not expected to resume oral intake within 5 to 7 days. Enteral nutrition most commonly involves bedside or endoscopic placement of a nasojejunal feeding tube and collaboration with a nutritionist to determine protein-caloric requirements.

Compared with enteral nutrition, total parenteral nutrition is associated with higher rates of infection, multiorgan dysfunction and failure, and death.¹⁸

 

 

MANAGING COMPLICATIONS OF PANCREATIC NECROSIS

Necrotizing pancreatitis is a defining complication of acute pancreatitis, and its presence alone indicates greater severity. However, superimposed complications may further worsen outcomes.

Infected pancreatic necrosis

Infection occurs in approximately 20% of patients with necrotizing pancreatitis and confers a mortality rate of 20% to 50%.¹⁹ Infected pancreatic necrosis occurs when gut organisms translocate into the nearby necrotic pancreatic and peripancreatic tissue. The most commonly identified organisms include Escherichia coli and Enterococcus species.²⁰

This complication usually manifests 2 to 4 weeks after symptom onset; earlier onset is uncommon to rare. It should be considered when the systemic inflammatory response syndrome persists or recurs after 10 days to 2 weeks. Systemic inflammatory response syndrome is also common in sterile necrotizing pancreatitis and sometimes in interstitial pancreatitis, particularly during the first week. However, its sudden appearance or resurgence, high spiking fevers, or worsening organ failure in the later phase (2–4 weeks) of pancreatitis should heighten suspicion of infected pancreatic necrosis.

Imaging may also help diagnose infection, and the presence of gas within a collection or region of necrosis is highly specific. However, the presence of gas is not completely sensitive for infection, as it is seen in only 12% to 22% of infected cases.

Before minimally invasive techniques became available, the diagnosis of infected pancreatic necrosis was confirmed by percutaneous CT-guided aspiration of the necrotic mass or collection for Gram stain and culture.

Antibiotic therapy is indicated in confirmed or suspected cases of infected pancreatic necrosis. Antibiotics with gram-negative coverage and appropriate penetration such as carbapenems, metronidazole, fluoroquinolones, and selected cephalosporins are most commonly used. Meropenem is the antibiotic of choice at our institution.

CT-guided fine-needle aspiration is often done if suspected infected pancreatic necrosis fails to respond to empiric antibiotic therapy.

Debridement or drainage. Generally, the diagnosis or suspicion of infected pancreatic necrosis (suggestive signs are high fever, elevated white blood cell count, and sepsis) warrants an intervention to debride or drain infected pancreatic tissue and control sepsis.²¹

While source control is integral to the successful treatment of infected pancreatic necrosis, antibiotic therapy may provide a bridge to intervention for critically ill patients by suppressing bacteremia and subsequent sepsis. A 2013 meta-analysis found that 324 of 409 patients with suspected infected pancreatic necrosis were successfully stabilized with antibiotic treatment.^21,22 The trend toward conservative management and promising outcomes with antibiotic therapy alone or with minimally invasive techniques has lessened the need for diagnostic CT-guided fine-needle aspiration.

Hemorrhage

Spontaneous hemorrhage into pancreatic necrosis is a rare but life-threatening complication. Because CT is almost always performed with contrast enhancement, this complication is rarely identified with imaging. The diagnosis is made by noting a drop in hemoglobin and hematocrit.

Hemorrhage into the retroperitoneum or the peritoneal cavity, or both, can occur when an inflammatory process erodes into a nearby artery. Luminal gastrointestinal bleeding can occur from gastric varices arising from splenic vein thrombosis and resulting left-sided portal hypertension, or from pseudoaneurysms. These can also bleed into the pancreatic duct (hemosuccus pancreaticus). Pseudoaneurysm is a later complication that occurs when an arterial wall (most commonly the splenic or gastroduodenal artery) is weakened by pancreatic enzymes.²³

Prompt recognition of hemorrhagic events and consultation with an interventional radiologist or surgeon are required to prevent death.

Inflammation and abdominal compartment syndrome

Inflammation from necrotizing pancreatitis can cause further complications by blocking nearby structures. Reported complications include jaundice from biliary compression, hydronephrosis from ureteral compression, bowel obstruction, and gastric outlet obstruction.

Abdominal compartment syndrome is an increasingly recognized complication of acute pancreatitis. Abdominal pressure can rise due to a number of factors, including fluid collections, ascites, ileus, and overly aggressive fluid resuscitation.²⁴ Elevated abdominal pressure is associated with complications such as decreased respiratory compliance, increased peak airway pressure, decreased cardiac preload, hypotension, mesenteric and intestinal ischemia, feeding intolerance, and lower-extremity ischemia and thrombosis.

Patients with necrotizing pancreatitis who have abdominal compartment syndrome have a mortality rate 5 times higher than patients without abdominal compartment syndrome.²⁵

Abdominal pressures should be monitored using a bladder pressure sensor in critically ill or ventilated patients with acute pancreatitis. If the abdominal pressure rises above 20 mm Hg, medical and surgical interventions should be offered in a stepwise fashion to decrease it. Interventions include decompression by nasogastric and rectal tube, sedation or paralysis to relax abdominal wall tension, minimization of intravenous fluids, percutaneous drainage of ascites, and (rarely) surgical midline or subcostal laparotomy.

 

 

ROLE OF INTERVENTION

The treatment of necrotizing pancreatitis has changed rapidly, thanks to a growing experience with minimally invasive techniques.

Indications for intervention

Infected pancreatic necrosis is the primary indication for surgical, percutaneous, or endoscopic intervention.

In sterile necrosis, the threshold for intervention is less clear, and intervention is often reserved for patients who fail to clinically improve or who have intractable abdominal pain, gastric outlet obstruction, or fistulating disease.²⁶

In asymptomatic cases, intervention is almost never indicated regardless of the location or size of the necrotic area.

In walled-off pancreatic necrosis, less-invasive and less-morbid interventions such as endoscopic or percutaneous drainage or video-assisted retroperitoneal debridement can be done.

Timing of intervention

In the past, delaying intervention was thought to increase the risk of death. However, multiple studies have found that outcomes are often worse if intervention is done early, likely due to the lack of a fully formed fibrous wall or demarcation of the necrotic area.²⁷

If the patient remains clinically stable, it is best to delay intervention until at least 4 weeks after the index event to achieve optimal outcomes. Delay can often be achieved by antibiotic treatment to suppress bacteremia and endoscopic or percutaneous drainage of infected collections to control sepsis.

Open surgery

The gold-standard intervention for infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis is open necrosectomy. This involves exploratory laparotomy with blunt debridement of all visible necrotic pancreatic tissue.

Methods to facilitate later evacuation of residual infected fluid and debris vary widely. Multiple large-caliber drains can be placed to facilitate irrigation and drainage before closure of the abdominal fascia. As infected pancreatic necrosis carries the risk of contaminating the peritoneal cavity, the skin is often left open to heal by secondary intention. An interventional radiologist is frequently enlisted to place, exchange, or downsize drainage catheters.

Infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis often requires more than one operation to achieve satisfactory debridement.

The goals of open necrosectomy are to remove nonviable tissue and infection, preserve viable pancreatic tissue, eliminate fistulous connections, and minimize damage to local organs and vasculature.

Minimally invasive techniques

Percutaneous drainage guided by CT or ultrasonography is currently the most common intervention for infected pancreatic necrosis. After needle access and aspiration of necrotic material for culture, one or more large drains are placed into the necrotic collections for drainage and irrigation. When possible, left flank catheters should be placed 2 to 4 cm apart to provide access for laparoscopically guided debridement (Figure 4). Often, drains are upsized in subsequent sessions to optimally resolve the collections or to provide access (Figure 5).

Percutaneous drainage is not always definitive, as surgery is eventually required in half of cases. However, it usually controls sepsis and permits delay in surgical debridement pending further maturation of the collection.

Video-assisted retroperitoneal debridement has been described as a hybrid between endoscopic and open retroperitoneal debridement.²⁸ This technique requires first placing a percutaneous catheter into the necrotic area through the left flank to create a retroperitoneal tract. A 5-cm incision is made and the necrotic space is entered using the drain for guidance. Necrotic tissue is carefully debrided under direct vision using a combination of forceps, irrigation, and suction. A laparoscopic port can also be introduced into the incision when the procedure can no longer be continued under direct vision.^29,30

Although not all patients are candidates for minimal-access surgery, it remains an evolving surgical option.

Endoscopic transmural debridement is another option for infected pancreatic necrosis and symptomatic walled-off pancreatic necrosis. Depending on the location of the necrotic area, an echoendoscope is passed to either the stomach or duodenum. Guided by endoscopic ultrasonography, a needle is passed into the collection, allowing subsequent fistula creation and stenting for internal drainage or debridement. In the past, this process required several steps, multiple devices, fluoroscopic guidance, and considerable time. But newer endoscopic lumen-apposing metal stents have been developed that can be placed in a single step without fluoroscopy. A slimmer endoscope can then be introduced into the necrotic cavity via the stent, and the necrotic debris can be debrided with endoscopic baskets, snares, forceps, and irrigation.^9,31

Similar to surgical necrosectomy, satisfactory debridement is not often obtained with a single procedure; 2 to 5 endoscopic procedures may be needed to achieve resolution. However, the luminal approach in endoscopic necrosectomy avoids the significant morbidity of major abdominal surgery and the potential for pancreaticocutaneous fistulae that may occur with drains.

In a randomized trial comparing endoscopic necrosectomy vs surgical necrosectomy (video-assisted retroperitoneal debridement and exploratory laparotomy),³² endoscopic necrosectomy showed less inflammatory response than surgical necrosectomy and had a lower risk of new-onset organ failure, bleeding, fistula formation, and death.³²

Selecting the best intervention for the individual patient

Given the multiple available techniques, selecting the best intervention for individual patients can be challenging. A team approach with input from a gastroenterologist, surgeon, and interventional radiologist is best when determining which technique would best suit each patient.

Surgical necrosectomy is still the treatment of choice for unstable patients with infected pancreatic necrosis or multiple, inaccessible collections, but current evidence suggests a different approach in stable infected pancreatic necrosis and symptomatic sterile walled-off pancreatic necrosis.

The Dutch Pancreatitis Group²⁸ randomized 88 patients with infected pancreatic necrosis or symptomatic walled-off pancreatic necrosis to open necrosectomy or a minimally invasive “step-up” approach consisting of up to 2 percutaneous drainage or endoscopic debridement procedures before escalation to video-assisted retroperitoneal debridement. The step-up approach resulted in lower rates of morbidity and death than surgical necrosectomy as first-line treatment. Furthermore, some patients in the step-up group avoided the need for surgery entirely.³⁰

 

 

SUMMING UP

Necrosis significantly increases rates of morbidity and mortality in acute pancreatitis. Hospitalists, general internists, and general surgeons are all on the front lines in identifying severe cases and consulting the appropriate specialists for optimal multidisciplinary care. Selective and appropriate timing of radiologic imaging is key, and a vital tool in the management of necrotizing pancreatitis.

While the primary indication for intervention is infected pancreatic necrosis, additional indications are symptomatic walled-off pancreatic necrosis secondary to intractable abdominal pain, bowel obstruction, and failure to thrive. As a result of improving technology and inpatient care, these patients may present with intractable symptoms in the outpatient setting rather than the inpatient setting. The onus is on the primary care physician to maintain a high level of suspicion and refer these patients to subspecialists as appropriate.

Open surgical necrosectomy remains an important approach for care of infected pancreatic necrosis or patients with intractable symptoms. A step-up approach starting with a minimally invasive procedure and escalating if the initial intervention is unsuccessful is gradually becoming the standard of care.

Acute pancreatitis accounted for more than 300,000 admissions and $2.6 billion in associated healthcare costs in the United States in 2012.¹ First-line management is early aggressive fluid resuscitation and analgesics for pain control. Guidelines recommend estimating the clinical severity of each attack using a validated scoring system such as the Bedside Index of Severity in Acute Pancreatitis.² Clinically severe pancreatitis is associated with necrosis.

Acute pancreatitis results from inappropriate activation of zymogens and subsequent auto­digestion of the pancreas by its own enzymes. Though necrotizing pancreatitis is thought to be an ischemic complication, its pathogenesis is not completely understood. Necrosis increases the morbidity and mortality risk of acute pancreatitis because of its association with organ failure and infectious complications. As such, patients with necrotizing pancreatitis may need admission to the intensive care unit, nutritional support, antibiotics, and radiologic, endoscopic, or surgical interventions.

Here, we review current evidence regarding the diagnosis and management of necrotizing pancreatitis.

PROPER TERMINOLOGY HELPS COLLABORATION

Managing necrotizing pancreatitis requires the combined efforts of internists, gastroenterologists, radiologists, and surgeons. This collaboration is aided by proper terminology.

A classification system was devised in Atlanta, GA, in 1992 to facilitate communication and interdisciplinary collaboration.³ Severe pancreatitis was differentiated from mild by the presence of organ failure or the complications of pseudocyst, necrosis, or abscess.

The original Atlanta classification had several limitations. First, the terminology for fluid collections was ambiguous and frequently misused. Second, the assessment of clinical severity required either the Ranson score or the Acute Physiology and Chronic Health Evaluation II score, both of which are complex and have other limitations. Finally, advances in imaging and treatment have rendered the original Atlanta nomenclature obsolete.

In 2012, the Acute Pancreatitis Classification Working Group issued a revised Atlanta classification that modernized the terminology pertaining to natural history, severity, imaging features, and complications. It divides the natural course of acute pancreatitis into early and late phases.⁴

Early vs late phase

The early phase is within 1 week of symptom onset. In this phase, the diagnosis and treatment are based on laboratory values and clinical assessment. Clinical severity is classified as mild, moderate, or severe (Table 1) based on organ dysfunction assessed using the Marshall score.⁵

In the early phase, findings on computed tomography (CT) neither correlate with clinical severity nor alter clinical management.⁶ Thus, early imaging is not indicated unless there is diagnostic uncertainty, lack of response to appropriate treatment, or sudden deterioration.

Moderate pancreatitis describes patients with pancreatic necrosis with or without transient organ failure (organ dysfunction for ≤ 48 hours).

Severe pancreatitis is defined by pancreatic necrosis and persistent organ dysfunction.⁴ It may be accompanied by pancreatic and peripancreatic fluid collections; bacteremia and sepsis can occur in association with infection of necrotic collections.

Interstitial edematous pancreatitis vs necrotizing pancreatitis

The revised Atlanta classification maintains the original classification of acute pancreatitis into 2 main categories: interstitial edematous pancreatitis and necrotizing pancreatitis.

Interstitial edematous pancreatitis (Figure 1) is rarely clinically severe (approximately 1% to 3% of cases), and mortality risk correlates with the patient’s comorbid medical conditions.⁷

Necrotizing pancreatitis is further divided into 3 subtypes based on extent and location of necrosis:

• Parenchymal necrosis alone (5% of cases)
• Necrosis of peripancreatic fat alone (20%)
• Necrosis of both parenchyma and peripancreatic fat (75%).

Peripancreatic involvement is commonly found in the mesentery, peripancreatic and distant retroperitoneum, and lesser sac.

Of the three subtypes, peripancreatic necrosis has the best prognosis. However, all of the subtypes of necrotizing pancreatitis are associated with poorer outcomes than interstitial edematous pancreatitis.

Fluid collections

Fluid collections in acute pancreatitis are classified on the basis of the time course, location, and fluid or solid components (Figure 2). In the first 4 weeks, interstitial edematous pancreatitis is associated with acute pancreatic fluid collections, and necrotizing pancreatitis is associated with acute necrotic collections.

Acute pancreatic fluid collections contain exclusively nonsolid components without an inflammatory wall and are typically found in the peripancreatic fat. These collections often resolve without intervention as the patient recovers. If they persist beyond 4 weeks and develop a nonepithelialized, fibrous wall, they become pseudocysts. Intervention is generally not recommended for pseudocysts unless they are symptomatic.

Acute necrotic collections contain both solid and liquid components and can progress to walled-off pancreatic necrosis (Figure 3). Both early and late collections may be sterile or infected.

 

 

ROLE OF IMAGING

Radiographic imaging is not usually necessary to diagnose acute pancreatitis. However, it can be a valuable tool to clarify an ambiguous presentation, determine severity, and identify complications.

The timing and appropriate type of imaging are integral to obtaining useful data. Any imaging obtained in acute pancreatitis to evaluate necrosis should be performed at least 3 to 5 days from the initial symptom onset; if imaging is obtained before 72 hours, necrosis cannot be confidently excluded.⁸

COMPUTED TOMOGRAPHY

CT is the imaging test of choice when evaluating acute pancreatitis. In addition, almost all percutaneous interventions are performed with CT guidance. The Balthazar score is the most well-known CT severity index. It is calculated based on the degree of inflammation, acute fluid collections, and parenchymal necrosis.⁹ However, a modified severity index incorporates extrapancreatic complications such as ascites and vascular compromise and was found to more strongly correlate with outcomes than the standard Balthazar score.¹⁰

Contrast-enhanced CT is performed in 2 phases:

The pancreatic parenchymal phase

The pancreatic parenchymal or late arterial phase is obtained approximately 40 to 45 seconds after the start of the contrast bolus. It is used to detect necrosis in the early phase of acute pancreatitis and to assess the peripancreatic arteries for pseudoaneurysms in the late phase of acute pancreatitis.¹¹

Pancreatic necrosis appears as an area of decreased parenchymal enhancement, either well-defined or heterogeneous. The normal pancreatic parenchyma has a postcontrast enhancement pattern similar to that of the spleen. Parenchyma that does not enhance to the same degree is considered necrotic. The severity of necrosis is graded based on the percentage of the pancreas involved (< 30%, 30%–50%, or > 50%), and a higher percentage correlates with a worse outcome.^12,13

Peripancreatic necrosis is harder to detect, as there is no method to assess fat enhancement as there is with pancreatic parenchymal enhancement. In general, radiologists assume that heterogeneous peripancreatic changes, including areas of fat, fluid, and soft tissue attenuation, are consistent with peripancreatic necrosis. After 7 to 10 days, if these changes become more homogeneous and confluent with a more mass-like process, peripancreatic necrosis can be more confidently identified.^12,13

The portal venous phase

The later, portal venous phase of the scan is obtained approximately 70 seconds after the start of the contrast bolus. It is used to detect and characterize fluid collections and venous complications of the disease.

Drawbacks of CT

A drawback of CT is the need for iodinated intravenous contrast media, which in severely ill patients may precipitate or worsen pre-existing acute kidney injury.

Further, several studies have shown that findings on CT rarely alter the management of patients in the early phase of acute pancreatitis and in fact may be an overuse of medical resources.¹⁴ Unless there are confounding clinical signs or symptoms, CT should be delayed for at least 72 hours.^9,10,14,15

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) is not a first-line imaging test in this disease because it is not as available as CT and takes longer to perform—20 to 30 minutes. The patient must be evaluated for candidacy, as it is difficult for acutely ill patients to tolerate an examination that takes this long and requires them to hold their breath multiple times.

MRI is an appropriate alternative in patients who are pregnant or who have severe iodinated-contrast allergy. While contrast is necessary to detect pancreatic necrosis with CT, MRI can detect necrosis without the need for contrast in patients with acute kidney injury or severe chronic kidney disease. Also, MRI may be better in complicated cases requiring repeated imaging because it does not expose the patient to radiation.

On MRI, pancreatic necrosis appears as a heterogeneous area, owing to its liquid and solid components. Liquid components appear hyperintense, and solid components hypointense, on T2 fluid-weighted imaging. This ability to differentiate the components of a walled-off pancreatic necrosis can be useful in determining whether a collection requires drainage or debridement. MRI is also more sensitive for hemorrhagic complications, best seen on T1 fat-weighted images.^12,16

Magnetic resonance cholangiopancreatography is an excellent method for ductal evaluation through heavily T2-weighted imaging. It is more sensitive than CT for detecting common bile duct stones and can also detect pancreatic duct strictures or extravasation into fluid collections.¹⁶

SUPPORTIVE MANAGEMENT OF EARLY NECROTIZING PANCREATITIS

In the early phase of necrotizing pancreatitis, management is supportive with the primary aim of preventing intravascular volume depletion. Aggressive fluid resuscitation in the first 48 to 72 hours, pain control, and bowel rest are the mainstays of supportive therapy. Intensive care may be necessary if organ failure and hemodynamic instability accompany necrotizing pancreatitis.

Prophylactic antibiotic and antifungal therapy to prevent infected necrosis has been controversial. Recent studies of its utility have not yielded supportive results, and the American College of Gastroenterology and the Infectious Diseases Society of America no longer recommend it.^9,17 These medications should not be given unless concomitant cholangitis or extrapancreatic infection is clinically suspected.

Early enteral nutrition is recommended in patients in whom pancreatitis is predicted to be severe and in those not expected to resume oral intake within 5 to 7 days. Enteral nutrition most commonly involves bedside or endoscopic placement of a nasojejunal feeding tube and collaboration with a nutritionist to determine protein-caloric requirements.

Compared with enteral nutrition, total parenteral nutrition is associated with higher rates of infection, multiorgan dysfunction and failure, and death.¹⁸

 

 

MANAGING COMPLICATIONS OF PANCREATIC NECROSIS

Necrotizing pancreatitis is a defining complication of acute pancreatitis, and its presence alone indicates greater severity. However, superimposed complications may further worsen outcomes.

Infected pancreatic necrosis

Infection occurs in approximately 20% of patients with necrotizing pancreatitis and confers a mortality rate of 20% to 50%.¹⁹ Infected pancreatic necrosis occurs when gut organisms translocate into the nearby necrotic pancreatic and peripancreatic tissue. The most commonly identified organisms include Escherichia coli and Enterococcus species.²⁰

This complication usually manifests 2 to 4 weeks after symptom onset; earlier onset is uncommon to rare. It should be considered when the systemic inflammatory response syndrome persists or recurs after 10 days to 2 weeks. Systemic inflammatory response syndrome is also common in sterile necrotizing pancreatitis and sometimes in interstitial pancreatitis, particularly during the first week. However, its sudden appearance or resurgence, high spiking fevers, or worsening organ failure in the later phase (2–4 weeks) of pancreatitis should heighten suspicion of infected pancreatic necrosis.

Imaging may also help diagnose infection, and the presence of gas within a collection or region of necrosis is highly specific. However, the presence of gas is not completely sensitive for infection, as it is seen in only 12% to 22% of infected cases.

Before minimally invasive techniques became available, the diagnosis of infected pancreatic necrosis was confirmed by percutaneous CT-guided aspiration of the necrotic mass or collection for Gram stain and culture.

Antibiotic therapy is indicated in confirmed or suspected cases of infected pancreatic necrosis. Antibiotics with gram-negative coverage and appropriate penetration such as carbapenems, metronidazole, fluoroquinolones, and selected cephalosporins are most commonly used. Meropenem is the antibiotic of choice at our institution.

CT-guided fine-needle aspiration is often done if suspected infected pancreatic necrosis fails to respond to empiric antibiotic therapy.

Debridement or drainage. Generally, the diagnosis or suspicion of infected pancreatic necrosis (suggestive signs are high fever, elevated white blood cell count, and sepsis) warrants an intervention to debride or drain infected pancreatic tissue and control sepsis.²¹

While source control is integral to the successful treatment of infected pancreatic necrosis, antibiotic therapy may provide a bridge to intervention for critically ill patients by suppressing bacteremia and subsequent sepsis. A 2013 meta-analysis found that 324 of 409 patients with suspected infected pancreatic necrosis were successfully stabilized with antibiotic treatment.^21,22 The trend toward conservative management and promising outcomes with antibiotic therapy alone or with minimally invasive techniques has lessened the need for diagnostic CT-guided fine-needle aspiration.

Hemorrhage

Spontaneous hemorrhage into pancreatic necrosis is a rare but life-threatening complication. Because CT is almost always performed with contrast enhancement, this complication is rarely identified with imaging. The diagnosis is made by noting a drop in hemoglobin and hematocrit.

Hemorrhage into the retroperitoneum or the peritoneal cavity, or both, can occur when an inflammatory process erodes into a nearby artery. Luminal gastrointestinal bleeding can occur from gastric varices arising from splenic vein thrombosis and resulting left-sided portal hypertension, or from pseudoaneurysms. These can also bleed into the pancreatic duct (hemosuccus pancreaticus). Pseudoaneurysm is a later complication that occurs when an arterial wall (most commonly the splenic or gastroduodenal artery) is weakened by pancreatic enzymes.²³

Prompt recognition of hemorrhagic events and consultation with an interventional radiologist or surgeon are required to prevent death.

Inflammation and abdominal compartment syndrome

Inflammation from necrotizing pancreatitis can cause further complications by blocking nearby structures. Reported complications include jaundice from biliary compression, hydronephrosis from ureteral compression, bowel obstruction, and gastric outlet obstruction.

Abdominal compartment syndrome is an increasingly recognized complication of acute pancreatitis. Abdominal pressure can rise due to a number of factors, including fluid collections, ascites, ileus, and overly aggressive fluid resuscitation.²⁴ Elevated abdominal pressure is associated with complications such as decreased respiratory compliance, increased peak airway pressure, decreased cardiac preload, hypotension, mesenteric and intestinal ischemia, feeding intolerance, and lower-extremity ischemia and thrombosis.

Patients with necrotizing pancreatitis who have abdominal compartment syndrome have a mortality rate 5 times higher than patients without abdominal compartment syndrome.²⁵

Abdominal pressures should be monitored using a bladder pressure sensor in critically ill or ventilated patients with acute pancreatitis. If the abdominal pressure rises above 20 mm Hg, medical and surgical interventions should be offered in a stepwise fashion to decrease it. Interventions include decompression by nasogastric and rectal tube, sedation or paralysis to relax abdominal wall tension, minimization of intravenous fluids, percutaneous drainage of ascites, and (rarely) surgical midline or subcostal laparotomy.

 

 

ROLE OF INTERVENTION

The treatment of necrotizing pancreatitis has changed rapidly, thanks to a growing experience with minimally invasive techniques.

Indications for intervention

Infected pancreatic necrosis is the primary indication for surgical, percutaneous, or endoscopic intervention.

In sterile necrosis, the threshold for intervention is less clear, and intervention is often reserved for patients who fail to clinically improve or who have intractable abdominal pain, gastric outlet obstruction, or fistulating disease.²⁶

In asymptomatic cases, intervention is almost never indicated regardless of the location or size of the necrotic area.

In walled-off pancreatic necrosis, less-invasive and less-morbid interventions such as endoscopic or percutaneous drainage or video-assisted retroperitoneal debridement can be done.

Timing of intervention

In the past, delaying intervention was thought to increase the risk of death. However, multiple studies have found that outcomes are often worse if intervention is done early, likely due to the lack of a fully formed fibrous wall or demarcation of the necrotic area.²⁷

If the patient remains clinically stable, it is best to delay intervention until at least 4 weeks after the index event to achieve optimal outcomes. Delay can often be achieved by antibiotic treatment to suppress bacteremia and endoscopic or percutaneous drainage of infected collections to control sepsis.

Open surgery

The gold-standard intervention for infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis is open necrosectomy. This involves exploratory laparotomy with blunt debridement of all visible necrotic pancreatic tissue.

Methods to facilitate later evacuation of residual infected fluid and debris vary widely. Multiple large-caliber drains can be placed to facilitate irrigation and drainage before closure of the abdominal fascia. As infected pancreatic necrosis carries the risk of contaminating the peritoneal cavity, the skin is often left open to heal by secondary intention. An interventional radiologist is frequently enlisted to place, exchange, or downsize drainage catheters.

Infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis often requires more than one operation to achieve satisfactory debridement.

The goals of open necrosectomy are to remove nonviable tissue and infection, preserve viable pancreatic tissue, eliminate fistulous connections, and minimize damage to local organs and vasculature.

Minimally invasive techniques

Percutaneous drainage guided by CT or ultrasonography is currently the most common intervention for infected pancreatic necrosis. After needle access and aspiration of necrotic material for culture, one or more large drains are placed into the necrotic collections for drainage and irrigation. When possible, left flank catheters should be placed 2 to 4 cm apart to provide access for laparoscopically guided debridement (Figure 4). Often, drains are upsized in subsequent sessions to optimally resolve the collections or to provide access (Figure 5).

Percutaneous drainage is not always definitive, as surgery is eventually required in half of cases. However, it usually controls sepsis and permits delay in surgical debridement pending further maturation of the collection.

Video-assisted retroperitoneal debridement has been described as a hybrid between endoscopic and open retroperitoneal debridement.²⁸ This technique requires first placing a percutaneous catheter into the necrotic area through the left flank to create a retroperitoneal tract. A 5-cm incision is made and the necrotic space is entered using the drain for guidance. Necrotic tissue is carefully debrided under direct vision using a combination of forceps, irrigation, and suction. A laparoscopic port can also be introduced into the incision when the procedure can no longer be continued under direct vision.^29,30

Although not all patients are candidates for minimal-access surgery, it remains an evolving surgical option.

Endoscopic transmural debridement is another option for infected pancreatic necrosis and symptomatic walled-off pancreatic necrosis. Depending on the location of the necrotic area, an echoendoscope is passed to either the stomach or duodenum. Guided by endoscopic ultrasonography, a needle is passed into the collection, allowing subsequent fistula creation and stenting for internal drainage or debridement. In the past, this process required several steps, multiple devices, fluoroscopic guidance, and considerable time. But newer endoscopic lumen-apposing metal stents have been developed that can be placed in a single step without fluoroscopy. A slimmer endoscope can then be introduced into the necrotic cavity via the stent, and the necrotic debris can be debrided with endoscopic baskets, snares, forceps, and irrigation.^9,31

Similar to surgical necrosectomy, satisfactory debridement is not often obtained with a single procedure; 2 to 5 endoscopic procedures may be needed to achieve resolution. However, the luminal approach in endoscopic necrosectomy avoids the significant morbidity of major abdominal surgery and the potential for pancreaticocutaneous fistulae that may occur with drains.

In a randomized trial comparing endoscopic necrosectomy vs surgical necrosectomy (video-assisted retroperitoneal debridement and exploratory laparotomy),³² endoscopic necrosectomy showed less inflammatory response than surgical necrosectomy and had a lower risk of new-onset organ failure, bleeding, fistula formation, and death.³²

Selecting the best intervention for the individual patient

Given the multiple available techniques, selecting the best intervention for individual patients can be challenging. A team approach with input from a gastroenterologist, surgeon, and interventional radiologist is best when determining which technique would best suit each patient.

Surgical necrosectomy is still the treatment of choice for unstable patients with infected pancreatic necrosis or multiple, inaccessible collections, but current evidence suggests a different approach in stable infected pancreatic necrosis and symptomatic sterile walled-off pancreatic necrosis.

The Dutch Pancreatitis Group²⁸ randomized 88 patients with infected pancreatic necrosis or symptomatic walled-off pancreatic necrosis to open necrosectomy or a minimally invasive “step-up” approach consisting of up to 2 percutaneous drainage or endoscopic debridement procedures before escalation to video-assisted retroperitoneal debridement. The step-up approach resulted in lower rates of morbidity and death than surgical necrosectomy as first-line treatment. Furthermore, some patients in the step-up group avoided the need for surgery entirely.³⁰

 

 

SUMMING UP

Necrosis significantly increases rates of morbidity and mortality in acute pancreatitis. Hospitalists, general internists, and general surgeons are all on the front lines in identifying severe cases and consulting the appropriate specialists for optimal multidisciplinary care. Selective and appropriate timing of radiologic imaging is key, and a vital tool in the management of necrotizing pancreatitis.

While the primary indication for intervention is infected pancreatic necrosis, additional indications are symptomatic walled-off pancreatic necrosis secondary to intractable abdominal pain, bowel obstruction, and failure to thrive. As a result of improving technology and inpatient care, these patients may present with intractable symptoms in the outpatient setting rather than the inpatient setting. The onus is on the primary care physician to maintain a high level of suspicion and refer these patients to subspecialists as appropriate.

Open surgical necrosectomy remains an important approach for care of infected pancreatic necrosis or patients with intractable symptoms. A step-up approach starting with a minimally invasive procedure and escalating if the initial intervention is unsuccessful is gradually becoming the standard of care.

Acute pancreatitis accounted for more than 300,000 admissions and $2.6 billion in associated healthcare costs in the United States in 2012.¹ First-line management is early aggressive fluid resuscitation and analgesics for pain control. Guidelines recommend estimating the clinical severity of each attack using a validated scoring system such as the Bedside Index of Severity in Acute Pancreatitis.² Clinically severe pancreatitis is associated with necrosis.

Acute pancreatitis results from inappropriate activation of zymogens and subsequent auto­digestion of the pancreas by its own enzymes. Though necrotizing pancreatitis is thought to be an ischemic complication, its pathogenesis is not completely understood. Necrosis increases the morbidity and mortality risk of acute pancreatitis because of its association with organ failure and infectious complications. As such, patients with necrotizing pancreatitis may need admission to the intensive care unit, nutritional support, antibiotics, and radiologic, endoscopic, or surgical interventions.

Here, we review current evidence regarding the diagnosis and management of necrotizing pancreatitis.

PROPER TERMINOLOGY HELPS COLLABORATION

Managing necrotizing pancreatitis requires the combined efforts of internists, gastroenterologists, radiologists, and surgeons. This collaboration is aided by proper terminology.

A classification system was devised in Atlanta, GA, in 1992 to facilitate communication and interdisciplinary collaboration.³ Severe pancreatitis was differentiated from mild by the presence of organ failure or the complications of pseudocyst, necrosis, or abscess.

The original Atlanta classification had several limitations. First, the terminology for fluid collections was ambiguous and frequently misused. Second, the assessment of clinical severity required either the Ranson score or the Acute Physiology and Chronic Health Evaluation II score, both of which are complex and have other limitations. Finally, advances in imaging and treatment have rendered the original Atlanta nomenclature obsolete.

In 2012, the Acute Pancreatitis Classification Working Group issued a revised Atlanta classification that modernized the terminology pertaining to natural history, severity, imaging features, and complications. It divides the natural course of acute pancreatitis into early and late phases.⁴

Early vs late phase

The early phase is within 1 week of symptom onset. In this phase, the diagnosis and treatment are based on laboratory values and clinical assessment. Clinical severity is classified as mild, moderate, or severe (Table 1) based on organ dysfunction assessed using the Marshall score.⁵

In the early phase, findings on computed tomography (CT) neither correlate with clinical severity nor alter clinical management.⁶ Thus, early imaging is not indicated unless there is diagnostic uncertainty, lack of response to appropriate treatment, or sudden deterioration.

Moderate pancreatitis describes patients with pancreatic necrosis with or without transient organ failure (organ dysfunction for ≤ 48 hours).

Severe pancreatitis is defined by pancreatic necrosis and persistent organ dysfunction.⁴ It may be accompanied by pancreatic and peripancreatic fluid collections; bacteremia and sepsis can occur in association with infection of necrotic collections.

Interstitial edematous pancreatitis vs necrotizing pancreatitis

The revised Atlanta classification maintains the original classification of acute pancreatitis into 2 main categories: interstitial edematous pancreatitis and necrotizing pancreatitis.

Interstitial edematous pancreatitis (Figure 1) is rarely clinically severe (approximately 1% to 3% of cases), and mortality risk correlates with the patient’s comorbid medical conditions.⁷

Necrotizing pancreatitis is further divided into 3 subtypes based on extent and location of necrosis:

• Parenchymal necrosis alone (5% of cases)
• Necrosis of peripancreatic fat alone (20%)
• Necrosis of both parenchyma and peripancreatic fat (75%).

Peripancreatic involvement is commonly found in the mesentery, peripancreatic and distant retroperitoneum, and lesser sac.

Of the three subtypes, peripancreatic necrosis has the best prognosis. However, all of the subtypes of necrotizing pancreatitis are associated with poorer outcomes than interstitial edematous pancreatitis.

Fluid collections

Fluid collections in acute pancreatitis are classified on the basis of the time course, location, and fluid or solid components (Figure 2). In the first 4 weeks, interstitial edematous pancreatitis is associated with acute pancreatic fluid collections, and necrotizing pancreatitis is associated with acute necrotic collections.

Acute pancreatic fluid collections contain exclusively nonsolid components without an inflammatory wall and are typically found in the peripancreatic fat. These collections often resolve without intervention as the patient recovers. If they persist beyond 4 weeks and develop a nonepithelialized, fibrous wall, they become pseudocysts. Intervention is generally not recommended for pseudocysts unless they are symptomatic.

Acute necrotic collections contain both solid and liquid components and can progress to walled-off pancreatic necrosis (Figure 3). Both early and late collections may be sterile or infected.

 

 

ROLE OF IMAGING

Radiographic imaging is not usually necessary to diagnose acute pancreatitis. However, it can be a valuable tool to clarify an ambiguous presentation, determine severity, and identify complications.

The timing and appropriate type of imaging are integral to obtaining useful data. Any imaging obtained in acute pancreatitis to evaluate necrosis should be performed at least 3 to 5 days from the initial symptom onset; if imaging is obtained before 72 hours, necrosis cannot be confidently excluded.⁸

COMPUTED TOMOGRAPHY

CT is the imaging test of choice when evaluating acute pancreatitis. In addition, almost all percutaneous interventions are performed with CT guidance. The Balthazar score is the most well-known CT severity index. It is calculated based on the degree of inflammation, acute fluid collections, and parenchymal necrosis.⁹ However, a modified severity index incorporates extrapancreatic complications such as ascites and vascular compromise and was found to more strongly correlate with outcomes than the standard Balthazar score.¹⁰

Contrast-enhanced CT is performed in 2 phases:

The pancreatic parenchymal phase

The pancreatic parenchymal or late arterial phase is obtained approximately 40 to 45 seconds after the start of the contrast bolus. It is used to detect necrosis in the early phase of acute pancreatitis and to assess the peripancreatic arteries for pseudoaneurysms in the late phase of acute pancreatitis.¹¹

Pancreatic necrosis appears as an area of decreased parenchymal enhancement, either well-defined or heterogeneous. The normal pancreatic parenchyma has a postcontrast enhancement pattern similar to that of the spleen. Parenchyma that does not enhance to the same degree is considered necrotic. The severity of necrosis is graded based on the percentage of the pancreas involved (< 30%, 30%–50%, or > 50%), and a higher percentage correlates with a worse outcome.^12,13

Peripancreatic necrosis is harder to detect, as there is no method to assess fat enhancement as there is with pancreatic parenchymal enhancement. In general, radiologists assume that heterogeneous peripancreatic changes, including areas of fat, fluid, and soft tissue attenuation, are consistent with peripancreatic necrosis. After 7 to 10 days, if these changes become more homogeneous and confluent with a more mass-like process, peripancreatic necrosis can be more confidently identified.^12,13

The portal venous phase

The later, portal venous phase of the scan is obtained approximately 70 seconds after the start of the contrast bolus. It is used to detect and characterize fluid collections and venous complications of the disease.

Drawbacks of CT

A drawback of CT is the need for iodinated intravenous contrast media, which in severely ill patients may precipitate or worsen pre-existing acute kidney injury.

Further, several studies have shown that findings on CT rarely alter the management of patients in the early phase of acute pancreatitis and in fact may be an overuse of medical resources.¹⁴ Unless there are confounding clinical signs or symptoms, CT should be delayed for at least 72 hours.^9,10,14,15

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) is not a first-line imaging test in this disease because it is not as available as CT and takes longer to perform—20 to 30 minutes. The patient must be evaluated for candidacy, as it is difficult for acutely ill patients to tolerate an examination that takes this long and requires them to hold their breath multiple times.

MRI is an appropriate alternative in patients who are pregnant or who have severe iodinated-contrast allergy. While contrast is necessary to detect pancreatic necrosis with CT, MRI can detect necrosis without the need for contrast in patients with acute kidney injury or severe chronic kidney disease. Also, MRI may be better in complicated cases requiring repeated imaging because it does not expose the patient to radiation.

On MRI, pancreatic necrosis appears as a heterogeneous area, owing to its liquid and solid components. Liquid components appear hyperintense, and solid components hypointense, on T2 fluid-weighted imaging. This ability to differentiate the components of a walled-off pancreatic necrosis can be useful in determining whether a collection requires drainage or debridement. MRI is also more sensitive for hemorrhagic complications, best seen on T1 fat-weighted images.^12,16

Magnetic resonance cholangiopancreatography is an excellent method for ductal evaluation through heavily T2-weighted imaging. It is more sensitive than CT for detecting common bile duct stones and can also detect pancreatic duct strictures or extravasation into fluid collections.¹⁶

SUPPORTIVE MANAGEMENT OF EARLY NECROTIZING PANCREATITIS

In the early phase of necrotizing pancreatitis, management is supportive with the primary aim of preventing intravascular volume depletion. Aggressive fluid resuscitation in the first 48 to 72 hours, pain control, and bowel rest are the mainstays of supportive therapy. Intensive care may be necessary if organ failure and hemodynamic instability accompany necrotizing pancreatitis.

Prophylactic antibiotic and antifungal therapy to prevent infected necrosis has been controversial. Recent studies of its utility have not yielded supportive results, and the American College of Gastroenterology and the Infectious Diseases Society of America no longer recommend it.^9,17 These medications should not be given unless concomitant cholangitis or extrapancreatic infection is clinically suspected.

Early enteral nutrition is recommended in patients in whom pancreatitis is predicted to be severe and in those not expected to resume oral intake within 5 to 7 days. Enteral nutrition most commonly involves bedside or endoscopic placement of a nasojejunal feeding tube and collaboration with a nutritionist to determine protein-caloric requirements.

Compared with enteral nutrition, total parenteral nutrition is associated with higher rates of infection, multiorgan dysfunction and failure, and death.¹⁸

 

 

MANAGING COMPLICATIONS OF PANCREATIC NECROSIS

Necrotizing pancreatitis is a defining complication of acute pancreatitis, and its presence alone indicates greater severity. However, superimposed complications may further worsen outcomes.

Infected pancreatic necrosis

Infection occurs in approximately 20% of patients with necrotizing pancreatitis and confers a mortality rate of 20% to 50%.¹⁹ Infected pancreatic necrosis occurs when gut organisms translocate into the nearby necrotic pancreatic and peripancreatic tissue. The most commonly identified organisms include Escherichia coli and Enterococcus species.²⁰

This complication usually manifests 2 to 4 weeks after symptom onset; earlier onset is uncommon to rare. It should be considered when the systemic inflammatory response syndrome persists or recurs after 10 days to 2 weeks. Systemic inflammatory response syndrome is also common in sterile necrotizing pancreatitis and sometimes in interstitial pancreatitis, particularly during the first week. However, its sudden appearance or resurgence, high spiking fevers, or worsening organ failure in the later phase (2–4 weeks) of pancreatitis should heighten suspicion of infected pancreatic necrosis.

Imaging may also help diagnose infection, and the presence of gas within a collection or region of necrosis is highly specific. However, the presence of gas is not completely sensitive for infection, as it is seen in only 12% to 22% of infected cases.

Before minimally invasive techniques became available, the diagnosis of infected pancreatic necrosis was confirmed by percutaneous CT-guided aspiration of the necrotic mass or collection for Gram stain and culture.

Antibiotic therapy is indicated in confirmed or suspected cases of infected pancreatic necrosis. Antibiotics with gram-negative coverage and appropriate penetration such as carbapenems, metronidazole, fluoroquinolones, and selected cephalosporins are most commonly used. Meropenem is the antibiotic of choice at our institution.

CT-guided fine-needle aspiration is often done if suspected infected pancreatic necrosis fails to respond to empiric antibiotic therapy.

Debridement or drainage. Generally, the diagnosis or suspicion of infected pancreatic necrosis (suggestive signs are high fever, elevated white blood cell count, and sepsis) warrants an intervention to debride or drain infected pancreatic tissue and control sepsis.²¹

While source control is integral to the successful treatment of infected pancreatic necrosis, antibiotic therapy may provide a bridge to intervention for critically ill patients by suppressing bacteremia and subsequent sepsis. A 2013 meta-analysis found that 324 of 409 patients with suspected infected pancreatic necrosis were successfully stabilized with antibiotic treatment.^21,22 The trend toward conservative management and promising outcomes with antibiotic therapy alone or with minimally invasive techniques has lessened the need for diagnostic CT-guided fine-needle aspiration.

Hemorrhage

Spontaneous hemorrhage into pancreatic necrosis is a rare but life-threatening complication. Because CT is almost always performed with contrast enhancement, this complication is rarely identified with imaging. The diagnosis is made by noting a drop in hemoglobin and hematocrit.

Hemorrhage into the retroperitoneum or the peritoneal cavity, or both, can occur when an inflammatory process erodes into a nearby artery. Luminal gastrointestinal bleeding can occur from gastric varices arising from splenic vein thrombosis and resulting left-sided portal hypertension, or from pseudoaneurysms. These can also bleed into the pancreatic duct (hemosuccus pancreaticus). Pseudoaneurysm is a later complication that occurs when an arterial wall (most commonly the splenic or gastroduodenal artery) is weakened by pancreatic enzymes.²³

Prompt recognition of hemorrhagic events and consultation with an interventional radiologist or surgeon are required to prevent death.

Inflammation and abdominal compartment syndrome

Inflammation from necrotizing pancreatitis can cause further complications by blocking nearby structures. Reported complications include jaundice from biliary compression, hydronephrosis from ureteral compression, bowel obstruction, and gastric outlet obstruction.

Abdominal compartment syndrome is an increasingly recognized complication of acute pancreatitis. Abdominal pressure can rise due to a number of factors, including fluid collections, ascites, ileus, and overly aggressive fluid resuscitation.²⁴ Elevated abdominal pressure is associated with complications such as decreased respiratory compliance, increased peak airway pressure, decreased cardiac preload, hypotension, mesenteric and intestinal ischemia, feeding intolerance, and lower-extremity ischemia and thrombosis.

Patients with necrotizing pancreatitis who have abdominal compartment syndrome have a mortality rate 5 times higher than patients without abdominal compartment syndrome.²⁵

Abdominal pressures should be monitored using a bladder pressure sensor in critically ill or ventilated patients with acute pancreatitis. If the abdominal pressure rises above 20 mm Hg, medical and surgical interventions should be offered in a stepwise fashion to decrease it. Interventions include decompression by nasogastric and rectal tube, sedation or paralysis to relax abdominal wall tension, minimization of intravenous fluids, percutaneous drainage of ascites, and (rarely) surgical midline or subcostal laparotomy.

 

 

ROLE OF INTERVENTION

The treatment of necrotizing pancreatitis has changed rapidly, thanks to a growing experience with minimally invasive techniques.

Indications for intervention

Infected pancreatic necrosis is the primary indication for surgical, percutaneous, or endoscopic intervention.

In sterile necrosis, the threshold for intervention is less clear, and intervention is often reserved for patients who fail to clinically improve or who have intractable abdominal pain, gastric outlet obstruction, or fistulating disease.²⁶

In asymptomatic cases, intervention is almost never indicated regardless of the location or size of the necrotic area.

In walled-off pancreatic necrosis, less-invasive and less-morbid interventions such as endoscopic or percutaneous drainage or video-assisted retroperitoneal debridement can be done.

Timing of intervention

In the past, delaying intervention was thought to increase the risk of death. However, multiple studies have found that outcomes are often worse if intervention is done early, likely due to the lack of a fully formed fibrous wall or demarcation of the necrotic area.²⁷

If the patient remains clinically stable, it is best to delay intervention until at least 4 weeks after the index event to achieve optimal outcomes. Delay can often be achieved by antibiotic treatment to suppress bacteremia and endoscopic or percutaneous drainage of infected collections to control sepsis.

Open surgery

The gold-standard intervention for infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis is open necrosectomy. This involves exploratory laparotomy with blunt debridement of all visible necrotic pancreatic tissue.

Methods to facilitate later evacuation of residual infected fluid and debris vary widely. Multiple large-caliber drains can be placed to facilitate irrigation and drainage before closure of the abdominal fascia. As infected pancreatic necrosis carries the risk of contaminating the peritoneal cavity, the skin is often left open to heal by secondary intention. An interventional radiologist is frequently enlisted to place, exchange, or downsize drainage catheters.

Infected pancreatic necrosis or symptomatic sterile walled-off pancreatic necrosis often requires more than one operation to achieve satisfactory debridement.

The goals of open necrosectomy are to remove nonviable tissue and infection, preserve viable pancreatic tissue, eliminate fistulous connections, and minimize damage to local organs and vasculature.

Minimally invasive techniques

Percutaneous drainage guided by CT or ultrasonography is currently the most common intervention for infected pancreatic necrosis. After needle access and aspiration of necrotic material for culture, one or more large drains are placed into the necrotic collections for drainage and irrigation. When possible, left flank catheters should be placed 2 to 4 cm apart to provide access for laparoscopically guided debridement (Figure 4). Often, drains are upsized in subsequent sessions to optimally resolve the collections or to provide access (Figure 5).

Percutaneous drainage is not always definitive, as surgery is eventually required in half of cases. However, it usually controls sepsis and permits delay in surgical debridement pending further maturation of the collection.

Video-assisted retroperitoneal debridement has been described as a hybrid between endoscopic and open retroperitoneal debridement.²⁸ This technique requires first placing a percutaneous catheter into the necrotic area through the left flank to create a retroperitoneal tract. A 5-cm incision is made and the necrotic space is entered using the drain for guidance. Necrotic tissue is carefully debrided under direct vision using a combination of forceps, irrigation, and suction. A laparoscopic port can also be introduced into the incision when the procedure can no longer be continued under direct vision.^29,30

Although not all patients are candidates for minimal-access surgery, it remains an evolving surgical option.

Endoscopic transmural debridement is another option for infected pancreatic necrosis and symptomatic walled-off pancreatic necrosis. Depending on the location of the necrotic area, an echoendoscope is passed to either the stomach or duodenum. Guided by endoscopic ultrasonography, a needle is passed into the collection, allowing subsequent fistula creation and stenting for internal drainage or debridement. In the past, this process required several steps, multiple devices, fluoroscopic guidance, and considerable time. But newer endoscopic lumen-apposing metal stents have been developed that can be placed in a single step without fluoroscopy. A slimmer endoscope can then be introduced into the necrotic cavity via the stent, and the necrotic debris can be debrided with endoscopic baskets, snares, forceps, and irrigation.^9,31

Similar to surgical necrosectomy, satisfactory debridement is not often obtained with a single procedure; 2 to 5 endoscopic procedures may be needed to achieve resolution. However, the luminal approach in endoscopic necrosectomy avoids the significant morbidity of major abdominal surgery and the potential for pancreaticocutaneous fistulae that may occur with drains.

In a randomized trial comparing endoscopic necrosectomy vs surgical necrosectomy (video-assisted retroperitoneal debridement and exploratory laparotomy),³² endoscopic necrosectomy showed less inflammatory response than surgical necrosectomy and had a lower risk of new-onset organ failure, bleeding, fistula formation, and death.³²

Selecting the best intervention for the individual patient

Given the multiple available techniques, selecting the best intervention for individual patients can be challenging. A team approach with input from a gastroenterologist, surgeon, and interventional radiologist is best when determining which technique would best suit each patient.

Surgical necrosectomy is still the treatment of choice for unstable patients with infected pancreatic necrosis or multiple, inaccessible collections, but current evidence suggests a different approach in stable infected pancreatic necrosis and symptomatic sterile walled-off pancreatic necrosis.

The Dutch Pancreatitis Group²⁸ randomized 88 patients with infected pancreatic necrosis or symptomatic walled-off pancreatic necrosis to open necrosectomy or a minimally invasive “step-up” approach consisting of up to 2 percutaneous drainage or endoscopic debridement procedures before escalation to video-assisted retroperitoneal debridement. The step-up approach resulted in lower rates of morbidity and death than surgical necrosectomy as first-line treatment. Furthermore, some patients in the step-up group avoided the need for surgery entirely.³⁰

 

 

SUMMING UP

Necrosis significantly increases rates of morbidity and mortality in acute pancreatitis. Hospitalists, general internists, and general surgeons are all on the front lines in identifying severe cases and consulting the appropriate specialists for optimal multidisciplinary care. Selective and appropriate timing of radiologic imaging is key, and a vital tool in the management of necrotizing pancreatitis.

While the primary indication for intervention is infected pancreatic necrosis, additional indications are symptomatic walled-off pancreatic necrosis secondary to intractable abdominal pain, bowel obstruction, and failure to thrive. As a result of improving technology and inpatient care, these patients may present with intractable symptoms in the outpatient setting rather than the inpatient setting. The onus is on the primary care physician to maintain a high level of suspicion and refer these patients to subspecialists as appropriate.

Open surgical necrosectomy remains an important approach for care of infected pancreatic necrosis or patients with intractable symptoms. A step-up approach starting with a minimally invasive procedure and escalating if the initial intervention is unsuccessful is gradually becoming the standard of care.

A 55-year-old woman presents with an intermittent sensation of food getting stuck in her mid to lower chest. The symptoms have occurred several times per year over the last 2 or 3 years and appear to be slowly worsening. She says she has no trouble swallowing liquids. She has a history of gastroesophageal reflux disease, for which she takes a proton pump inhibitor once a day. She says she has had no odynophagia, cough, regurgitation, or weight loss.

How should her symptoms best be evaluated?

DYSPHAGIA CAN BE OROPHARYNGEAL OR ESOPHAGEAL

Dysphagia is the subjective sensation of difficulty swallowing solids, liquids, or both. Symptoms can range from the inability to initiate a swallow to the sensation of esophageal obstruction. Other symptoms of esophageal disease may also be present, such as chest pain, heartburn, and regurgitation. There may also be nonesophageal symptoms related to the disease process causing the dysphagia.

Dysphagia can be separated into oropharyngeal and esophageal types.

Oropharyngeal dysphagia arises from problems in the oropharynx and cervical esophagus and is commonly caused by neurologic disorders of the central or peripheral nervous system (eg, stroke, myasthenia gravis), inflammatory myopathy, or a structural abnormality of the oropharynx, hypopharynx, or cervical esophagus such as a cricopharyngeal bar or tumor (Table 1). Patients typically complain of not being able to initiate a swallow or of food getting stuck in the cervical region immediately upon swallowing, accompanied by nasal regurgitation.¹

Interestingly, many patients with symptoms of oropharyngeal dysphagia in fact have referred symptoms from primary esophageal dysphagia²; many patients with a distal mucosal ring describe a sense of something sticking in the cervical esophagus.

Esophageal dysphagia arises in the mid to distal esophagus or gastric cardia, and as a result, the symptoms are typically retrosternal.¹ It can be caused by structural problems such as strictures, rings, webs, extrinsic compression, or a primary esophageal or gastroesophageal neoplasm, or by a primary motility abnormality such as achalasia (Table 1). Eosinophilic esophagitis is now a frequent cause of esophageal dysphagia, especially in white men.³

ESOPHAGOGRAPHY VS ENDOSCOPY IN EVALUATING DYSPHAGIA

Many gastroenterologists recommend endoscopy rather than barium esophagography as the initial examination in patients with dysphagia.^4–8 Each test has certain advantages.

Advantages of endoscopy. Endoscopy is superior to esophagography in detecting milder grades of esophagitis. Further, interventions can be performed endoscopically (eg, dilation, biopsy, attachment of a wireless pH testing probe) that cannot be done during a radiographic procedure, and endoscopy does not expose the patient to radiation.

Advantages of esophagography. Endoscopy cannot detect evidence of gastroesophageal reflux disease unless mucosal injury is present. In dysphagia, the radiologic findings correlate well with endoscopic findings, including the detection of esophageal malignancy and moderate to severe esophagitis. Further, motility disorders can be detected with barium esophagography but not with endoscopy.^9,10

Subtle abnormalities, especially rings and strictures, may be missed by narrow-diameter (9.8–10 mm) modern upper-endoscopic equipment. Further, esophagography is noninvasive, costs less, and may be more convenient (it does not require sedation and a chaperone for the patient after sedation). This examination also provides dynamic evaluation of the complex process of swallowing. Causes of dysphagia external to the esophagus can also be determined.

In view of the respective advantages and disadvantages of the two methods, we believe that in most instances barium esophagography should be the initial examination,^1,9,11–15 and at our institution most patients presenting with dysphagia undergo barium esophagography before they undergo other examinations.¹⁴

OBTAIN A HISTORY BEFORE ORDERING ESOPHAGOGRAPHY

Before a barium examination of the esophagus is done, a focused medical history should be obtained, as it can guide the further workup as well as the esophageal study itself.

An attempt should be made to determine whether the dysphagia is oropharyngeal or if it is esophageal, as the former is generally best initially evaluated by a speech and language pathologist. Generally, the physician who orders the test judges whether the patient has oropharyngeal or esophageal dysphagia. Often, both an oropharyngeal examination, performed by a speech and language pathologist, and an esophageal examination, performed by a radiologist, are ordered.

Rapidly progressive symptoms, especially if accompanied by weight loss, should make one suspect cancer. Chronic symptoms usually point to gastroesophageal reflux disease or a motility disorder such as achalasia. Liquid dysphagia almost always means the patient has a motility disorder such as achalasia.

In view of the possibility of eosinophilic esophagitis, one should ask about food or seasonal allergies, especially in young patients with intermittent difficulty swallowing solids.³

 

BARIUM ESOPHAGOGRAPHY HAS EIGHT SEPARATE PHASES

Barium esophagography is tailored to the patient with dysphagia on the basis of his or her history. The standard examination is divided into eight separate phases (see below).¹⁴ Each phase addresses a specific question or questions concerning the structure and function of the esophagus.

At our institution, the first phase of the examination is determined by the presenting symptoms. If the patient has liquid dysphagia, we start with a timed barium swallow to assess esophageal emptying. If the patient does not have liquid dysphagia, we start with an air-contrast mucosal examination.

The patient must be cooperative and mobile to complete all phases of the examination.

Timed barium swallow to measure esophageal emptying

The timed barium swallow is an objective measure of esophageal emptying.^16–18 This technique is essential in the initial evaluation of a patient with liquid dysphagia, a symptom common in patients with severe dysmotility, usually achalasia.

In the upright position, the patient is asked to ingest up to 250 mL of low-density barium, as tolerated. The height and width of the barium column at 1 minute and 5 minutes are measured and recorded (Figure 1).

We use this examination in our patients with suspected or confirmed achalasia and to follow up patients who have been treated with pneumatic dilatation, botulinum toxin injection, and Heller myotomy.^17,18 In addition, this timed test is an objective measure of emptying in patients who have undergone intervention but whose symptoms have not subjectively improved, and can suggest that further intervention may be required.

Air-contrast or mucosal phase

The air-contrast phase of the examination is designed to evaluate the esophageal mucosa and to determine if there is a fixed (nonreducible) hernia. In the upright position, the patient ingests CO₂ gas-producing crystals with a small amount of water and then ingests high-density barium in order to coat the mucosa. Spot films are taken of the gas-distended, barium-coated esophagus (Figure 2A).

Although this phase is not as sensitive as endoscopy, it can detect masses, mucosal erosions, ulcers, and—most importantly in our experience—fixed hernias. Patients with a fixed hernia have a foreshortened esophagus, which is important to know about before repairing the hernia. Many esophageal surgeons believe that a foreshortened esophagus precludes a standard Nissen fundoplication and necessitates an esophageal lengthening procedure (ie, Collis gastroplasty with a Nissen fundoplication).¹⁴

Motility phase

The third phase examines esophageal motility. With the patient in a semiprone position, low-density barium is given in single swallows, separated by 25 to 30 seconds. The images are recorded on digital media to allow one to review them frame by frame.

The findings on this phase correlate well with those of manometry.¹⁹ This portion of the examination also uses impedance monitoring to assess bolus transfer, an aspect not evaluated by manometry.^20,21 Impedance monitoring detects changes in resistance to current flow and correlates well with esophagraphic findings regarding bolus transfer.

While many patients with dysphagia also undergo esophageal manometry, the findings from this phase of the esophagographic examination may be the first indication of an esophageal motility disorder. In fact, this portion of the examination shows the distinct advantage of esophagography over endoscopy as the initial test in patients with dysphagia, as endoscopy may not identify patients with achalasia, especially early on.⁴

Single-contrast (full-column) phase to detect strictures, rings

The fourth phase of the esophagographic evaluation is the distended, single-contrast examination (Figure 2B). This is performed in the semiprone position with the patient rapidly drinking thin barium. It is done to detect esophageal strictures, rings, and contour abnormalities caused by extrinsic processes. Subtle abnormalities shown by this technique, including benign strictures and rings, are often not visualized with endoscopy.

Mucosal relief phase

The fifth phase is performed with a collapsed esophagus immediately after the distended, single-contrast phase, where spot films are taken of the barium-coated, collapsed esophagus (Figure 2C). This phase is used to evaluate thickened mucosal folds, a common finding in moderate to severe reflux esophagitis.

Reflux evaluation

Provocative maneuvers are used in the sixth phase to elicit gastroesophageal reflux (Figure 2D). With the patient supine, he or she is asked to roll side to side, do a Valsalva maneuver, and do a straight-leg raise. The patient then sips water in the supine position to assess for reflux (the water siphon test). If reflux is seen, the cause, the height of the reflux, and the duration of reflux retention are recorded.

Solid-bolus phase to assess strictures

In the seventh phase, the patient swallows a 13-mm barium tablet (Figure 2E). This allows one to assess the significance of a ring or stricture and to assess if dysphagia symptoms recur as a result of tablet obstruction. Subtle strictures that were not detected during the prior phases can also be detected using a tablet. If obstruction or impaired passage occurs, the site of obstruction and the presence or absence of symptoms are recorded.

 

 

Modified esophagography to assess the oropharynx

The final or eighth phase of barium esophagography is called “modified barium esophagography” or the modified barium swallow. However, it may be the first phase of the examination performed or the only portion of the examination performed, or it may not be performed at all.

Modified barium esophagography is used to define the anatomy of the oropharynx and to assess its function in swallowing.¹² It may also guide rehabilitation strategies aimed at eliminating a patient’s swallowing symptoms.

Most patients referred for this test have sustained damage to the central nervous system or structures of the oropharynx, such as stroke or radiation therapy for laryngeal cancer. Many have difficulty in starting to swallow, aspirate when they try to swallow, or both.

In this test, thin liquids are given to the patient in escalating amounts. The patient is then given thicker foods, including thick liquids, purees, and food requiring chewing. If the patient has difficulty swallowing, intervention and therapeutic strategies are initiated. If the test is done by itself and the speech pathologist cannot find a cause of the patient’s symptoms, then barium esophagography should be performed by a radiologist.

The final esophagographic report should document the findings of each phase of the examination (Table 2).

WHAT HAPPENED TO OUR PATIENT?

Our patient underwent barium esophagography (Figure 2). A distal mucosal ring that transiently obstructed a 13-mm tablet was found. The patient underwent endoscopy and the ring was dilated. No biopsies were necessary.

A 55-year-old woman presents with an intermittent sensation of food getting stuck in her mid to lower chest. The symptoms have occurred several times per year over the last 2 or 3 years and appear to be slowly worsening. She says she has no trouble swallowing liquids. She has a history of gastroesophageal reflux disease, for which she takes a proton pump inhibitor once a day. She says she has had no odynophagia, cough, regurgitation, or weight loss.

How should her symptoms best be evaluated?

DYSPHAGIA CAN BE OROPHARYNGEAL OR ESOPHAGEAL

Dysphagia is the subjective sensation of difficulty swallowing solids, liquids, or both. Symptoms can range from the inability to initiate a swallow to the sensation of esophageal obstruction. Other symptoms of esophageal disease may also be present, such as chest pain, heartburn, and regurgitation. There may also be nonesophageal symptoms related to the disease process causing the dysphagia.

Dysphagia can be separated into oropharyngeal and esophageal types.

Oropharyngeal dysphagia arises from problems in the oropharynx and cervical esophagus and is commonly caused by neurologic disorders of the central or peripheral nervous system (eg, stroke, myasthenia gravis), inflammatory myopathy, or a structural abnormality of the oropharynx, hypopharynx, or cervical esophagus such as a cricopharyngeal bar or tumor (Table 1). Patients typically complain of not being able to initiate a swallow or of food getting stuck in the cervical region immediately upon swallowing, accompanied by nasal regurgitation.¹

Interestingly, many patients with symptoms of oropharyngeal dysphagia in fact have referred symptoms from primary esophageal dysphagia²; many patients with a distal mucosal ring describe a sense of something sticking in the cervical esophagus.

Esophageal dysphagia arises in the mid to distal esophagus or gastric cardia, and as a result, the symptoms are typically retrosternal.¹ It can be caused by structural problems such as strictures, rings, webs, extrinsic compression, or a primary esophageal or gastroesophageal neoplasm, or by a primary motility abnormality such as achalasia (Table 1). Eosinophilic esophagitis is now a frequent cause of esophageal dysphagia, especially in white men.³

ESOPHAGOGRAPHY VS ENDOSCOPY IN EVALUATING DYSPHAGIA

Many gastroenterologists recommend endoscopy rather than barium esophagography as the initial examination in patients with dysphagia.^4–8 Each test has certain advantages.

Advantages of endoscopy. Endoscopy is superior to esophagography in detecting milder grades of esophagitis. Further, interventions can be performed endoscopically (eg, dilation, biopsy, attachment of a wireless pH testing probe) that cannot be done during a radiographic procedure, and endoscopy does not expose the patient to radiation.

Advantages of esophagography. Endoscopy cannot detect evidence of gastroesophageal reflux disease unless mucosal injury is present. In dysphagia, the radiologic findings correlate well with endoscopic findings, including the detection of esophageal malignancy and moderate to severe esophagitis. Further, motility disorders can be detected with barium esophagography but not with endoscopy.^9,10

Subtle abnormalities, especially rings and strictures, may be missed by narrow-diameter (9.8–10 mm) modern upper-endoscopic equipment. Further, esophagography is noninvasive, costs less, and may be more convenient (it does not require sedation and a chaperone for the patient after sedation). This examination also provides dynamic evaluation of the complex process of swallowing. Causes of dysphagia external to the esophagus can also be determined.

In view of the respective advantages and disadvantages of the two methods, we believe that in most instances barium esophagography should be the initial examination,^1,9,11–15 and at our institution most patients presenting with dysphagia undergo barium esophagography before they undergo other examinations.¹⁴

OBTAIN A HISTORY BEFORE ORDERING ESOPHAGOGRAPHY

Before a barium examination of the esophagus is done, a focused medical history should be obtained, as it can guide the further workup as well as the esophageal study itself.

An attempt should be made to determine whether the dysphagia is oropharyngeal or if it is esophageal, as the former is generally best initially evaluated by a speech and language pathologist. Generally, the physician who orders the test judges whether the patient has oropharyngeal or esophageal dysphagia. Often, both an oropharyngeal examination, performed by a speech and language pathologist, and an esophageal examination, performed by a radiologist, are ordered.

Rapidly progressive symptoms, especially if accompanied by weight loss, should make one suspect cancer. Chronic symptoms usually point to gastroesophageal reflux disease or a motility disorder such as achalasia. Liquid dysphagia almost always means the patient has a motility disorder such as achalasia.

In view of the possibility of eosinophilic esophagitis, one should ask about food or seasonal allergies, especially in young patients with intermittent difficulty swallowing solids.³

 

BARIUM ESOPHAGOGRAPHY HAS EIGHT SEPARATE PHASES

Barium esophagography is tailored to the patient with dysphagia on the basis of his or her history. The standard examination is divided into eight separate phases (see below).¹⁴ Each phase addresses a specific question or questions concerning the structure and function of the esophagus.

At our institution, the first phase of the examination is determined by the presenting symptoms. If the patient has liquid dysphagia, we start with a timed barium swallow to assess esophageal emptying. If the patient does not have liquid dysphagia, we start with an air-contrast mucosal examination.

The patient must be cooperative and mobile to complete all phases of the examination.

Timed barium swallow to measure esophageal emptying

The timed barium swallow is an objective measure of esophageal emptying.^16–18 This technique is essential in the initial evaluation of a patient with liquid dysphagia, a symptom common in patients with severe dysmotility, usually achalasia.

In the upright position, the patient is asked to ingest up to 250 mL of low-density barium, as tolerated. The height and width of the barium column at 1 minute and 5 minutes are measured and recorded (Figure 1).

We use this examination in our patients with suspected or confirmed achalasia and to follow up patients who have been treated with pneumatic dilatation, botulinum toxin injection, and Heller myotomy.^17,18 In addition, this timed test is an objective measure of emptying in patients who have undergone intervention but whose symptoms have not subjectively improved, and can suggest that further intervention may be required.

Air-contrast or mucosal phase

The air-contrast phase of the examination is designed to evaluate the esophageal mucosa and to determine if there is a fixed (nonreducible) hernia. In the upright position, the patient ingests CO₂ gas-producing crystals with a small amount of water and then ingests high-density barium in order to coat the mucosa. Spot films are taken of the gas-distended, barium-coated esophagus (Figure 2A).

Although this phase is not as sensitive as endoscopy, it can detect masses, mucosal erosions, ulcers, and—most importantly in our experience—fixed hernias. Patients with a fixed hernia have a foreshortened esophagus, which is important to know about before repairing the hernia. Many esophageal surgeons believe that a foreshortened esophagus precludes a standard Nissen fundoplication and necessitates an esophageal lengthening procedure (ie, Collis gastroplasty with a Nissen fundoplication).¹⁴

Motility phase

The third phase examines esophageal motility. With the patient in a semiprone position, low-density barium is given in single swallows, separated by 25 to 30 seconds. The images are recorded on digital media to allow one to review them frame by frame.

The findings on this phase correlate well with those of manometry.¹⁹ This portion of the examination also uses impedance monitoring to assess bolus transfer, an aspect not evaluated by manometry.^20,21 Impedance monitoring detects changes in resistance to current flow and correlates well with esophagraphic findings regarding bolus transfer.

While many patients with dysphagia also undergo esophageal manometry, the findings from this phase of the esophagographic examination may be the first indication of an esophageal motility disorder. In fact, this portion of the examination shows the distinct advantage of esophagography over endoscopy as the initial test in patients with dysphagia, as endoscopy may not identify patients with achalasia, especially early on.⁴

Single-contrast (full-column) phase to detect strictures, rings

The fourth phase of the esophagographic evaluation is the distended, single-contrast examination (Figure 2B). This is performed in the semiprone position with the patient rapidly drinking thin barium. It is done to detect esophageal strictures, rings, and contour abnormalities caused by extrinsic processes. Subtle abnormalities shown by this technique, including benign strictures and rings, are often not visualized with endoscopy.

Mucosal relief phase

The fifth phase is performed with a collapsed esophagus immediately after the distended, single-contrast phase, where spot films are taken of the barium-coated, collapsed esophagus (Figure 2C). This phase is used to evaluate thickened mucosal folds, a common finding in moderate to severe reflux esophagitis.

Reflux evaluation

Provocative maneuvers are used in the sixth phase to elicit gastroesophageal reflux (Figure 2D). With the patient supine, he or she is asked to roll side to side, do a Valsalva maneuver, and do a straight-leg raise. The patient then sips water in the supine position to assess for reflux (the water siphon test). If reflux is seen, the cause, the height of the reflux, and the duration of reflux retention are recorded.

Solid-bolus phase to assess strictures

In the seventh phase, the patient swallows a 13-mm barium tablet (Figure 2E). This allows one to assess the significance of a ring or stricture and to assess if dysphagia symptoms recur as a result of tablet obstruction. Subtle strictures that were not detected during the prior phases can also be detected using a tablet. If obstruction or impaired passage occurs, the site of obstruction and the presence or absence of symptoms are recorded.

 

 

Modified esophagography to assess the oropharynx

The final or eighth phase of barium esophagography is called “modified barium esophagography” or the modified barium swallow. However, it may be the first phase of the examination performed or the only portion of the examination performed, or it may not be performed at all.

Modified barium esophagography is used to define the anatomy of the oropharynx and to assess its function in swallowing.¹² It may also guide rehabilitation strategies aimed at eliminating a patient’s swallowing symptoms.

Most patients referred for this test have sustained damage to the central nervous system or structures of the oropharynx, such as stroke or radiation therapy for laryngeal cancer. Many have difficulty in starting to swallow, aspirate when they try to swallow, or both.

In this test, thin liquids are given to the patient in escalating amounts. The patient is then given thicker foods, including thick liquids, purees, and food requiring chewing. If the patient has difficulty swallowing, intervention and therapeutic strategies are initiated. If the test is done by itself and the speech pathologist cannot find a cause of the patient’s symptoms, then barium esophagography should be performed by a radiologist.

The final esophagographic report should document the findings of each phase of the examination (Table 2).

WHAT HAPPENED TO OUR PATIENT?

Our patient underwent barium esophagography (Figure 2). A distal mucosal ring that transiently obstructed a 13-mm tablet was found. The patient underwent endoscopy and the ring was dilated. No biopsies were necessary.

A 55-year-old woman presents with an intermittent sensation of food getting stuck in her mid to lower chest. The symptoms have occurred several times per year over the last 2 or 3 years and appear to be slowly worsening. She says she has no trouble swallowing liquids. She has a history of gastroesophageal reflux disease, for which she takes a proton pump inhibitor once a day. She says she has had no odynophagia, cough, regurgitation, or weight loss.

How should her symptoms best be evaluated?

DYSPHAGIA CAN BE OROPHARYNGEAL OR ESOPHAGEAL

Dysphagia is the subjective sensation of difficulty swallowing solids, liquids, or both. Symptoms can range from the inability to initiate a swallow to the sensation of esophageal obstruction. Other symptoms of esophageal disease may also be present, such as chest pain, heartburn, and regurgitation. There may also be nonesophageal symptoms related to the disease process causing the dysphagia.

Dysphagia can be separated into oropharyngeal and esophageal types.

Oropharyngeal dysphagia arises from problems in the oropharynx and cervical esophagus and is commonly caused by neurologic disorders of the central or peripheral nervous system (eg, stroke, myasthenia gravis), inflammatory myopathy, or a structural abnormality of the oropharynx, hypopharynx, or cervical esophagus such as a cricopharyngeal bar or tumor (Table 1). Patients typically complain of not being able to initiate a swallow or of food getting stuck in the cervical region immediately upon swallowing, accompanied by nasal regurgitation.¹

Interestingly, many patients with symptoms of oropharyngeal dysphagia in fact have referred symptoms from primary esophageal dysphagia²; many patients with a distal mucosal ring describe a sense of something sticking in the cervical esophagus.

Esophageal dysphagia arises in the mid to distal esophagus or gastric cardia, and as a result, the symptoms are typically retrosternal.¹ It can be caused by structural problems such as strictures, rings, webs, extrinsic compression, or a primary esophageal or gastroesophageal neoplasm, or by a primary motility abnormality such as achalasia (Table 1). Eosinophilic esophagitis is now a frequent cause of esophageal dysphagia, especially in white men.³

ESOPHAGOGRAPHY VS ENDOSCOPY IN EVALUATING DYSPHAGIA

Many gastroenterologists recommend endoscopy rather than barium esophagography as the initial examination in patients with dysphagia.^4–8 Each test has certain advantages.

Advantages of endoscopy. Endoscopy is superior to esophagography in detecting milder grades of esophagitis. Further, interventions can be performed endoscopically (eg, dilation, biopsy, attachment of a wireless pH testing probe) that cannot be done during a radiographic procedure, and endoscopy does not expose the patient to radiation.

Advantages of esophagography. Endoscopy cannot detect evidence of gastroesophageal reflux disease unless mucosal injury is present. In dysphagia, the radiologic findings correlate well with endoscopic findings, including the detection of esophageal malignancy and moderate to severe esophagitis. Further, motility disorders can be detected with barium esophagography but not with endoscopy.^9,10

Subtle abnormalities, especially rings and strictures, may be missed by narrow-diameter (9.8–10 mm) modern upper-endoscopic equipment. Further, esophagography is noninvasive, costs less, and may be more convenient (it does not require sedation and a chaperone for the patient after sedation). This examination also provides dynamic evaluation of the complex process of swallowing. Causes of dysphagia external to the esophagus can also be determined.

In view of the respective advantages and disadvantages of the two methods, we believe that in most instances barium esophagography should be the initial examination,^1,9,11–15 and at our institution most patients presenting with dysphagia undergo barium esophagography before they undergo other examinations.¹⁴

OBTAIN A HISTORY BEFORE ORDERING ESOPHAGOGRAPHY

Before a barium examination of the esophagus is done, a focused medical history should be obtained, as it can guide the further workup as well as the esophageal study itself.

An attempt should be made to determine whether the dysphagia is oropharyngeal or if it is esophageal, as the former is generally best initially evaluated by a speech and language pathologist. Generally, the physician who orders the test judges whether the patient has oropharyngeal or esophageal dysphagia. Often, both an oropharyngeal examination, performed by a speech and language pathologist, and an esophageal examination, performed by a radiologist, are ordered.

Rapidly progressive symptoms, especially if accompanied by weight loss, should make one suspect cancer. Chronic symptoms usually point to gastroesophageal reflux disease or a motility disorder such as achalasia. Liquid dysphagia almost always means the patient has a motility disorder such as achalasia.

In view of the possibility of eosinophilic esophagitis, one should ask about food or seasonal allergies, especially in young patients with intermittent difficulty swallowing solids.³

 

BARIUM ESOPHAGOGRAPHY HAS EIGHT SEPARATE PHASES

Barium esophagography is tailored to the patient with dysphagia on the basis of his or her history. The standard examination is divided into eight separate phases (see below).¹⁴ Each phase addresses a specific question or questions concerning the structure and function of the esophagus.

At our institution, the first phase of the examination is determined by the presenting symptoms. If the patient has liquid dysphagia, we start with a timed barium swallow to assess esophageal emptying. If the patient does not have liquid dysphagia, we start with an air-contrast mucosal examination.

The patient must be cooperative and mobile to complete all phases of the examination.

Timed barium swallow to measure esophageal emptying

The timed barium swallow is an objective measure of esophageal emptying.^16–18 This technique is essential in the initial evaluation of a patient with liquid dysphagia, a symptom common in patients with severe dysmotility, usually achalasia.

In the upright position, the patient is asked to ingest up to 250 mL of low-density barium, as tolerated. The height and width of the barium column at 1 minute and 5 minutes are measured and recorded (Figure 1).

We use this examination in our patients with suspected or confirmed achalasia and to follow up patients who have been treated with pneumatic dilatation, botulinum toxin injection, and Heller myotomy.^17,18 In addition, this timed test is an objective measure of emptying in patients who have undergone intervention but whose symptoms have not subjectively improved, and can suggest that further intervention may be required.

Air-contrast or mucosal phase

The air-contrast phase of the examination is designed to evaluate the esophageal mucosa and to determine if there is a fixed (nonreducible) hernia. In the upright position, the patient ingests CO₂ gas-producing crystals with a small amount of water and then ingests high-density barium in order to coat the mucosa. Spot films are taken of the gas-distended, barium-coated esophagus (Figure 2A).

Although this phase is not as sensitive as endoscopy, it can detect masses, mucosal erosions, ulcers, and—most importantly in our experience—fixed hernias. Patients with a fixed hernia have a foreshortened esophagus, which is important to know about before repairing the hernia. Many esophageal surgeons believe that a foreshortened esophagus precludes a standard Nissen fundoplication and necessitates an esophageal lengthening procedure (ie, Collis gastroplasty with a Nissen fundoplication).¹⁴

Motility phase

The third phase examines esophageal motility. With the patient in a semiprone position, low-density barium is given in single swallows, separated by 25 to 30 seconds. The images are recorded on digital media to allow one to review them frame by frame.

The findings on this phase correlate well with those of manometry.¹⁹ This portion of the examination also uses impedance monitoring to assess bolus transfer, an aspect not evaluated by manometry.^20,21 Impedance monitoring detects changes in resistance to current flow and correlates well with esophagraphic findings regarding bolus transfer.

While many patients with dysphagia also undergo esophageal manometry, the findings from this phase of the esophagographic examination may be the first indication of an esophageal motility disorder. In fact, this portion of the examination shows the distinct advantage of esophagography over endoscopy as the initial test in patients with dysphagia, as endoscopy may not identify patients with achalasia, especially early on.⁴

Single-contrast (full-column) phase to detect strictures, rings

The fourth phase of the esophagographic evaluation is the distended, single-contrast examination (Figure 2B). This is performed in the semiprone position with the patient rapidly drinking thin barium. It is done to detect esophageal strictures, rings, and contour abnormalities caused by extrinsic processes. Subtle abnormalities shown by this technique, including benign strictures and rings, are often not visualized with endoscopy.

Mucosal relief phase

The fifth phase is performed with a collapsed esophagus immediately after the distended, single-contrast phase, where spot films are taken of the barium-coated, collapsed esophagus (Figure 2C). This phase is used to evaluate thickened mucosal folds, a common finding in moderate to severe reflux esophagitis.

Reflux evaluation

Provocative maneuvers are used in the sixth phase to elicit gastroesophageal reflux (Figure 2D). With the patient supine, he or she is asked to roll side to side, do a Valsalva maneuver, and do a straight-leg raise. The patient then sips water in the supine position to assess for reflux (the water siphon test). If reflux is seen, the cause, the height of the reflux, and the duration of reflux retention are recorded.

Solid-bolus phase to assess strictures

In the seventh phase, the patient swallows a 13-mm barium tablet (Figure 2E). This allows one to assess the significance of a ring or stricture and to assess if dysphagia symptoms recur as a result of tablet obstruction. Subtle strictures that were not detected during the prior phases can also be detected using a tablet. If obstruction or impaired passage occurs, the site of obstruction and the presence or absence of symptoms are recorded.

 

 

Modified esophagography to assess the oropharynx

The final or eighth phase of barium esophagography is called “modified barium esophagography” or the modified barium swallow. However, it may be the first phase of the examination performed or the only portion of the examination performed, or it may not be performed at all.

Modified barium esophagography is used to define the anatomy of the oropharynx and to assess its function in swallowing.¹² It may also guide rehabilitation strategies aimed at eliminating a patient’s swallowing symptoms.

Most patients referred for this test have sustained damage to the central nervous system or structures of the oropharynx, such as stroke or radiation therapy for laryngeal cancer. Many have difficulty in starting to swallow, aspirate when they try to swallow, or both.

In this test, thin liquids are given to the patient in escalating amounts. The patient is then given thicker foods, including thick liquids, purees, and food requiring chewing. If the patient has difficulty swallowing, intervention and therapeutic strategies are initiated. If the test is done by itself and the speech pathologist cannot find a cause of the patient’s symptoms, then barium esophagography should be performed by a radiologist.

The final esophagographic report should document the findings of each phase of the examination (Table 2).

WHAT HAPPENED TO OUR PATIENT?

Our patient underwent barium esophagography (Figure 2). A distal mucosal ring that transiently obstructed a 13-mm tablet was found. The patient underwent endoscopy and the ring was dilated. No biopsies were necessary.