Chronic Pancreatitis 

Updated: Jul 15, 2019
Author: Jason L Huffman, MD; Chief Editor: BS Anand, MD 

Overview

Practice Essentials

Chronic pancreatitis is commonly defined as a continuing, chronic, inflammatory process of the pancreas, characterized by irreversible morphologic changes.

Signs and symptoms

For most patients with chronic pancreatitis, abdominal pain is the presenting symptom. The patient experiences intermittent attacks of severe pain, often in the mid-abdomen or left upper abdomen and occasionally radiating in a bandlike fashion or localized to the midback. The pain may occur either after meals or independently of meals, but it is not fleeting or transient and tends to last at least several hours.

Other symptoms associated with chronic pancreatitis include diarrhea and weight loss.

See Presentation for more detail.

Diagnosis

Diagnosis is based on tests of pancreatic structure and function.

Imaging tests

Imaging studies such as abdominal radiography and CT scanning can show inflammation or calcium deposits in the pancreas or changes in the pancreatic ducts. Pancreatic calcifications, often considered pathognomonic of chronic pancreatitis, are observed in approximately 30% of cases.

Endoscopic retrograde cholangiopancreatography

The endoscopic retrograde cholangiopancreatography (ERCP) test provides the most accurate visualization of the pancreatic ductal system and has been regarded as the criterion standard for diagnosing chronic pancreatitis. It combines the use of endoscopy and fluoroscopy to visualize and treat problems of the biliary and pancreatic ducts. See the image below.

This endoscopic retrograde cholangiopancreatograph This endoscopic retrograde cholangiopancreatography (ERCP) shows advanced chronic pancreatitis. The pancreatogram has blunting of the lateral branches, dilation of the main pancreatic duct, and filling defects consistent with pancreatolithiasis. The cholangiogram also shows a stenosis of the distal bile duct and a dilated biliary tree.

Magnetic resonance cholangiopancreatography

MRCP provides information on the pancreatic parenchyma and adjacent abdominal viscera, and it uses heavily T2-weighted images to visualize the biliary and pancreatic ductal systems. This procedure is relatively safe, reasonably accurate, noninvasive, fast, and very useful in planning surgical or endoscopic intervention.

Endoscopic ultrasonography

The most predictive endosonographic feature of chronic pancreatitis is the presence of stones. Other suggestive features include the following:

  • Visible side branches

  • Cysts

  • Lobularity

  • An irregular main pancreatic duct

  • Hyperechoic foci and strands

  • Dilation of the main pancreatic duct

  • Hyperechoic margins of the main pancreatic duct

See Workup for more detail.

Management

Treatment is typically directed at the underlying cause of the pancreatitis and to relieve pain and malabsorption.

Pain relief

Pancreatic enzyme supplementation may be helpful in reducing pain. The hypothesis is that stimulation of the pancreas by food causes pain. Cholecystokinin (CCK) is one of the possible mediators of this response. When exogenous pancreatic enzymes are taken with a meal, CCK-releasing factors are degraded and CCK release in response to a meal is reduced. This decreases pancreatic stimulation and pain.

If conventional medical therapy is unsuccessful and the patient has severe, intractable pain, celiac ganglion blockade can be considered.[1] This approach tries to alleviate pain by modifying the afferent sensory nerves in the celiac plexus, using agents that anesthetize, reduce inflammation, or destroy the nerve fibers.

Endoscopic therapy aimed at decompressing an obstructed pancreatic duct can be associated with pain relief in some patients. The rationale for this approach is based on the hypothesis that ductal hypertension due to strictures of the main pancreatic duct leads to pain.[2, 3]

Surgery

The choice of operation depends on the clinical problem and the preoperative assessment of the abnormality. In general, the approach aims either to improve pancreatic duct drainage or to resect the diseased organ. Data suggest that surgical drainage of the pancreatic duct is more effective than endoscopic drainage in patients with obstruction of the pancreatic duct due to chronic pancreatitis.

In patients with a dilated pancreatic duct, a Roux-en-Y side-to-side pancreaticojejunostomy is indicated. If the disease is limited to the head of the pancreas, a Whipple operation (pancreaticoduodenectomy) can produce good results.

See Treatment and Medication for more detail.

Background

Chronic pancreatitis is commonly defined as a continuing, chronic, inflammatory process of the pancreas, characterized by irreversible morphologic changes.[4] This chronic inflammation can lead to chronic abdominal pain and/or impairment of the endocrine and exocrine functions of the pancreas. (See Pathophysiology and Etiology.)

Chronic pancreatitis usually is envisioned as an atrophic fibrotic gland with dilated ducts and calcifications. However, the findings on conventional diagnostic studies may be normal in the early stages of chronic pancreatitis, as the inflammatory changes can be seen only by histologic examination (see the images below). (See Workup.)

This endoscopic retrograde cholangiopancreatograph This endoscopic retrograde cholangiopancreatography (ERCP) shows advanced chronic pancreatitis. The pancreatogram has blunting of the lateral branches, dilation of the main pancreatic duct, and filling defects consistent with pancreatolithiasis. The cholangiogram also shows a stenosis of the distal bile duct and a dilated biliary tree.
This patient has recurrent abdominal pain. She use This patient has recurrent abdominal pain. She used alcohol heavily in the past and was involved in a motor vehicle accident. The pancreatogram shows subtle blunting of the side branches consistent with chronic pancreatitis. A stricture also is present in the body of the pancreas where it drapes over the spine, probably resulting from the trauma she sustained in the motor vehicle accident. Air in the stomach makes it difficult to observe that contrast is filling a pseudocyst on the other side of the stricture. These findings are not amenable to endoscopic intervention, and the patient was sent for a distal pancreatectomy.

By definition, chronic pancreatitis is a completely different process from acute pancreatitis.[5] In acute pancreatitis, the patient presents with acute and severe abdominal pain, nausea, and vomiting. The pancreas is acutely inflamed (neutrophils and edema), and the serum levels of the pancreatic enzymes (amylase and lipase) are elevated. Full recovery is observed in most patients with acute pancreatitis, whereas in chronic pancreatitis, the primary process is a chronic, irreversible inflammation (monocyte and lymphocyte) that leads to fibrosis with calcification. (See Pathophysiology, Etiology, Presentation, and Workup.)

The patient with chronic pancreatitis clinically presents with chronic abdominal pain and normal or mildly elevated pancreatic enzyme levels. When the pancreas loses its endocrine and exocrine function, the patient presents with diabetes mellitus and steatorrhea. (See Presentation and Workup.)

Patient education

For patient education information, see the Digestive Disorders Center and the Cancer Center, as well as Pancreatitis and Pancreatic Cancer.

Pathophysiology

Whatever the etiology of chronic pancreatitis,[6] pancreatic fibrogenesis appears to be a typical response to injury. This involves a complex interplay of growth factors, cytokines, and chemokines, leading to the deposition of extracellular matrix and fibroblast proliferation. In pancreatic injury, the local expression and release of transforming growth factor beta (TGF-beta) stimulates the growth of cells of mesenchymal origin and enhances the synthesis of extracellular matrix proteins, such as collagens, fibronectin, and proteoglycans.

Evidence indicates the involvement of distinct chemokines in the initiation and perpetuation of chronic pancreatitis.

Etiology

The cause of chronic pancreatitis usually is metabolic in nature. The proposed pathologic mechanisms of chronic pancreatitis are as follows:

  • Intraductal plugging and obstruction - Eg, ethanol (ETOH) abuse, stones, tumors

  • Direct toxins and toxic metabolites - These act on the pancreatic acinar cells to stimulate the release of cytokines, which stimulate the stellate cells to produce collagen and to lay down fibrous tissue; cytokines also act to stimulate inflammation by neutrophils, macrophages, and lymphocytes (eg, ETOH, tropical sprue)

  • Oxidative stress - Eg, idiopathic pancreatitis

  • Necrosis-fibrosis - Recurrent acute pancreatitis that heals with fibrosis

  • Ischemia - From obstruction and fibrosis; important in exacerbating or perpetuating disease rather than in initiating disease

  • Autoimmune disorders - Chronic pancreatitis has been found in association with other autoimmune diseases, such as Sjögren syndrome, primary biliary cirrhosis, and renal tubular acidosis.

  • Secondary forms of autoimmune chronic pancreatitis are associated with primary biliary cirrhosis, primary sclerosing cholangitis, and Sjögren syndrome.

  • Although alcohol greatly influences the understanding of its pathophysiology because it is the most common etiology (60-70%), approximately 20-30% of cases are idiopathic and 10% of cases are due to rare diseases.

Autoimmune pancreatitis

Autoimmune pancreatitis is a more recently described entity. Clinical characteristics include symptomatic or asymptomatic, diffuse enlargement of the pancreas, diffuse and irregular narrowing of the main pancreatic duct, increased circulating levels of gamma globulin, the presence of autoantibodies, and a possible association with other autoimmune diseases. Fibrosis with lymphocytic infiltration is seen on pathology. The disorder is associated with elevated immunoglobulin G4 (IgG4) concentrations.

In a study of 51 patients with autoimmune pancreatitis, Kawa et al suggested that a strong link exists between pancreatic stone formation and the recurrence of autoimmune pancreatitis and that following several recurrences, this disease may develop into chronic pancreatitis. In the study, the authors found that during a long-term follow-up period, 21 patients suffered a recurrence of the condition and 9 of the 51 patients developed pancreatic stones.[7]

The investigators also found that the stones developed more frequently in the recurrence group (7 [33%] of 21 patients) than in the other patients (2 [7%] of 30 patients). In addition, within a group of 175 patients with chronic hepatitis, 13 patients were found to have high serum concentrations of IgG4.

Alcoholic chronic pancreatitis

Excessive alcohol consumption is the most common cause of chronic pancreatitis, accounting for about 60% of all cases.

In the affected gland, alcohol appears to increase protein secretion from the acinar cells while decreasing fluid and bicarbonate production from the ductal epithelial cells. The resulting viscous fluid results in proteinaceous debris becoming inspissated within the lumen, causing ductular obstruction, upstream acinar atrophy, and fibrosis. GP2, which is secreted from the acinar cell and is homologous to a protein involved in renal tubular casts, is an integral component of these ductal plugs.

Lithostathine (formerly called pancreatic stone protein), which also is produced by the acinar cells, accounts for about 5% of secretory protein and inhibits the growth of calcium carbonate crystals. Abnormal lithostathine S1, whether inherited or acquired through trypsin digestion, appears to play a role in stone formation; it is insoluble at the neutral pH of pancreatic juice and is the major constituent of pancreatic stones.

A competing theory suggests that the persistent demands of metabolizing alcohol (and probably other xenobiotics, such as drugs, tobacco smoke, environmental toxins, and pollution) cause oxidative stress within the pancreas and may lead to cellular injury and organ damage, especially in the setting of malnutrition. Oxidative and nonoxidative pathways metabolize ethanol. Alcohol dehydrogenase oxidatively metabolizes ethanol first to acetaldehyde and then to acetate. When the alcohol concentration increases, cytochrome P-450 2E1 is induced to meet the metabolic demands.

Although these reactions occur principally in the liver, further increases in ethanol concentration induce pancreatic cytochrome P-450 2E1, and the level of acetate within the pancreas begins to approach that observed in the liver. Reactive oxygen species produced by this reaction may overwhelm cellular defenses and damage important cellular processes.

Although nonoxidative metabolism of ethanol is a minor pathway, the fatty acid ethyl esters produced by this reaction may cause cellular injury and are synthesized in the pancreas to a greater extent than in other organ systems.

Because fewer than 5-10% of people with alcoholism develop chronic pancreatitis, other factor(s) must place these individuals at risk. Researchers have studied genetic polymorphisms of ethanol-oxidizing enzymes, but to date, none have correlated with a susceptibility to alcohol-induced pancreatitis.

A mutation in the gene encoding the serine protease inhibitor, Kazal type 1, has been identified in patients with chronic pancreatitis. The N34S mutation was detected in 5.8% of 274 patients with alcoholic chronic pancreatitis, compared with 1.0% of people with alcoholism without pancreatitis. Although all patients were heterozygous for the mutation, it provides evidence for abnormalities in the pancreatic protease/protease inhibitor system playing a role in the pathogenesis of alcoholic chronic pancreatitis.

Hereditary pancreatitis

Several inherited disorders also are considered metabolic in origin.[8] Hereditary pancreatitis is an autosomal dominant disorder with an 80% penetrance, accounting for about 1% of cases. Research of families with hereditary pancreatitis has led to the identification of several mutations in the cationic trypsinogen gene on chromosome 7. These mutations apparently render the activated enzyme resistant to the second-line proteolytic control mechanisms. Mutations were found in the pancreatic secretory serine protease inhibitor Kazal type 1 (SPINK1) gene in 18 of 96 patients with idiopathic or hereditary chronic pancreatitis.

Cystic fibrosis in pancreatitis

Cystic fibrosis, one of the most common genetic abnormalities, is an autosomal recessive disorder accounting for a small percent of patients with chronic pancreatitis. The cystic fibrosis transmembrane regulator (CFTR) gene transcribes a protein important in regulating chloride transport across cellular membranes.

Several hundred mutations of the CFTR gene have been identified, and the clinical manifestation of any given mutation depends on how severely it affects the protein's ability to regulate chloride transport. Different mutations in CFTR are associated with different functional statuses of the exocrine pancreas.

Specific CFTR genotypes are significantly associated with pancreatitis. Patients with genotypes associated with mild phenotypic effects have a greater risk of developing pancreatitis than do patients with genotypes associated with moderate-severe phenotypes.[9]

Idiopathic chronic pancreatitis

This form of chronic pancreatitis accounts for approximately 30% of cases. It has been arbitrarily divided into early onset and late-onset forms. While the cause of idiopathic chronic pancreatitis is not yet known, some evidence points to atypical genetic mutations in CFTR, cationic trypsinogen, and other proteins.

Congenital abnormalities in chronic pancreatitis

Congenital abnormalities, such as pancreas divisum and annular pancreas, are uncommon (even rare) causes of chronic pancreatitis and usually require an additional factor to induce chronic pancreatitis. For example, while pancreas divisum usually does not cause chronic pancreatitis, patients with divisum and minor papilla stenosis are at risk. In these patients, clear evidence of disease exists in the dorsal pancreas, whereas the ventral pancreas is normal histologically.

Acquired obstructive chronic pancreatitis

Acquired obstructive forms typically result from blunt abdominal trauma or accidents involving motor vehicles, bicycles, horses, or, on occasion, severe falls. In these cases, the pancreas is whiplashed against the spine, causing trauma to the ductal system, resulting in a stricture close to the surgical genu. In rare instances, chronic inflammatory conditions affecting the duodenum, or primarily the duodenal papilla, can induce fibrosis and papillary stenosis in a subset of patients, leading to chronic pancreatitis.

Additional causes

Other causes of chronic pancreatitis include the following:

  • Hyperlipidemia (usually type I and type V) - However, hyperlipidemia usually presents with repeated attacks of acute pancreatitis

  • Hypercalcemia due to hyperparathyroidism - Now is a rare cause of chronic pancreatitis, probably because automation of serum chemistries reveals hypercalcemia before it results in pancreatitis

  • Nutritional, or tropical, chronic pancreatitis - Rare in the United States, but an important cause of disease in other parts of the world

  • Medications - An infrequent, or possibly underrecognized, cause of chronic pancreatitis

  • Obstruction of the flow of pancreatic juice can cause chronic pancreatitis. Obstructive forms account for less than 10% of cases and may be congenital or acquired.

Epidemiology

Based on the estimates from hospital discharge data in the United States, approximately 87,000 cases of pancreatitis occur annually.

Comparing the hospital admissions data from several cities around the globe, the overall frequency is similar. Expressed as number of cases per 1000 hospital admissions, the value for Marseille is 3.1; for Cape Town, 4.4; for Sao Paulo, 4.9; and for Mexico City, 4.4. When the data from several centers were compared over time, the incidence of chronic pancreatitis from 1945-1985 appeared to be increasing.

Race-, sex-, and age-related demographics

Hospitalization rates for blacks are 3 times higher than for whites in the United States. In population studies, males are affected more commonly than females (6.7 vs 3.2 per 100,000 population).

Differences in the hospitalization rates of patients with chronic pancreatitis exist with respect to sex. Rates in males peak between ages 45 and 54 years and then decline; female rates reach a plateau, which remains stable after age 35 years.

Sex differences with respect to etiology also exist. Alcohol-induced illness is more prevalent in males, idiopathic and hyperlipidemic-induced pancreatitis is more prevalent in females, and equal sex ratios are observed in chronic pancreatitis associated with hereditary pancreatitis.

In aggregate, the mean age at diagnosis is 46 years, plus or minus 13 years. In idiopathic chronic pancreatitis, a bimodal age distribution has been reported, designated as the early onset form (median age 19.2 y) and the late-onset form (median age 56.2 y).

Prognosis

The prognostic factors associated with chronic pancreatitis are age at diagnosis, smoking, continued use of alcohol, and the presence of liver cirrhosis.

The overall survival rate is 70% at 10 years and 45% at 20 years. In an international study, 559 deaths occurred among patients with chronic pancreatitis, compared with an expected number of 157, which creates a standard mortality ratio of 3.6. Taking the opposite view, the 10-year mortality rate is 30%, and the 20-year mortality rate is 55%. The risk of developing pancreatic cancer is approximately 4% at 20 years.

The most common complications of chronic pancreatitis are pseudocyst formation and mechanical obstruction of the duodenum and common bile duct. Less frequent complications include pancreatic ascites or pleural effusion, splenic vein thrombosis with portal hypertension, and pseudoaneurysm formation of the splenic artery.

Pseudocyst

A pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue. It arises as a consequence of acute pancreatitis, pancreatic trauma, or chronic pancreatitis. The clinical challenge is to diagnose a cystic pancreatic structure correctly as a pseudocyst. As many as 5% of cysts are retention cysts, another 5% of these cysts are either congenital in origin or acquired (as in von Hippel-Lindau syndrome), and 10% are neoplastic in origin (mucinous vs serous cyst).

Pseudocysts develop in approximately 10% of patients with chronic pancreatitis. They develop as a result of ductal disruptions rather than from peripancreatic fluid accumulations that lead to pseudocyst formation in the setting of acute pancreatitis. Pseudocysts may be single or multiple and can be small or large, and they can be located either within or outside of the pancreas. Most pseudocysts communicate with the pancreatic ductal system and contain high concentrations of digestive enzymes.

The walls of pseudocysts are formed by adjacent structures, such as the stomach, transverse mesocolon, gastrocolic omentum, and pancreas. The lining of the pancreatic pseudocysts consists of fibrous and granulation tissue; the lack of an epithelial lining distinguishes pseudocysts from true cystic lesions of the pancreas. Most pseudocysts are asymptomatic. They can, however, produce a wide range of clinical problems, depending upon the location and extent of the fluid collection.

Expansion of the pseudocyst can produce abdominal pain, duodenal or biliary obstruction, vascular occlusion, or fistula formation into adjacent viscera, the pleural space, or pericardium. Spontaneous infection with abscess formation can occur. (See the images below.)

Chronic pancreatitis. Abdominal CT scan showing  a Chronic pancreatitis. Abdominal CT scan showing a pancreatic pseudocyst causing distortion of the ductal system.
Chronic pancreatitis. Pancreatogram in a patient w Chronic pancreatitis. Pancreatogram in a patient with a pancreatic pseudocyst. Note how the pancreatic ducts are extrinsically distorted by a mass lesion.

Digestion of an adjacent vessel can result in a pseudoaneurysm, which can produce a sudden expansion of the cyst or gastrointestinal bleeding due to bleeding into the pancreatic duct (hemosuccus pancreaticus).

Pancreatic ascites and pleural effusion can result from disruption of the pancreatic duct, leading to fistula formation to the abdomen or chest, or rupture of a pseudocyst with tracking of pancreatic juice into the peritoneal cavity or pleural space.

The indications for drainage of pseudocysts include rapid enlargement, compression of surrounding structures, pain, or signs of infection. Endoscopic retrograde pancreatograms may be helpful prior to drainage to rule out a stricture of the pancreatic duct, which can lead to persistent drainage from the pseudocyst.

Bile obstruction and duodenal obstruction

Symptomatic obstruction of the bile duct and/or duodenum develops in 5-10% of patients with chronic pancreatitis. Postprandial pain and early satiety are characteristic of duodenal obstruction, while pain and abnormal liver function test results (including hyperbilirubinemia) are suggestive of a bile duct stricture. These complications are most commonly seen in patients with dilated pancreatic ducts; they are either due to inflammation and fibrosis in the head of the pancreas or are the result of a pseudocyst.

Drainage of an obstructing pseudocyst can be accomplished surgically by cystogastrostomy, cystenterostomy, or choledochoenterostomy. Endoscopic stenting may be helpful for benign bile duct strictures.

Additional complications of chronic pancreatitis

Diabetes mellitus is a late manifestation in about one third of patients. The tendency to develop ketoacidosis is low.

The presence of the splenic vein at the posterior surface of the pancreas predisposes it to thrombosis from adjacent pancreatic inflammation. Patients who are affected can develop gastric varices as a result of associated portal hypertension. Splenectomy is usually curative for patients who develop bleeding from gastric varices.

Pseudoaneurysm is rare, but it can be a deadly complication. Affected vessels, including the splenic, hepatic, gastroduodenal, and pancreaticoduodenal arteries, are in close proximity to the pancreas. Surgery for bleeding pseudoaneurysms is challenging and is associated with high morbidity and mortality.

 

Presentation

History

For most patients with chronic pancreatitis, abdominal pain is the presenting symptom. Either the patient's age or the etiology of the disease has some influence on the frequency of this presentation. Ninety-six percent of those with early onset idiopathic pancreatitis present with abdominal pain, compared with 77% with alcohol-induced disease and 54% with late-onset idiopathic chronic pancreatitis.

Clinically, the patient experiences intermittent attacks of severe pain, often in the midabdomen or left upper abdomen and occasionally radiating in a bandlike fashion or localized to the midback. The pain may occur either after meals or independently of meals, but it is not fleeting or transient and tends to last at least several hours. Unfortunately, patients often are symptomatic for years before the diagnosis is established; the average time from the onset of symptoms until a diagnosis of chronic pancreatitis is 62 months. The delay in diagnosis is even longer in people without alcoholism, in whom the average time is 81 months from the onset of symptoms to diagnosis.

The natural history of pain in chronic pancreatitis is highly variable. Most patients experience intermittent attacks of pain at unpredictable intervals, while a minority of patients experience chronic pain. In most patients, pain severity either decreases or resolves over 5-25 years. Nevertheless, ignoring pain relief with the expectation that the disease eventually will resolve itself is inappropriate. In alcohol-induced disease, eventual cessation of alcohol intake may reduce the severity of pain. Variability in the pain pattern contributes to the delay in the diagnosis and makes determining the effect of any therapeutic intervention difficult.

Other symptoms associated with chronic pancreatitis include diarrhea and weight loss. This may be due either to fear of eating (eg, postprandial exacerbation of pain) or due to pancreatic exocrine insufficiency and steatorrhea.

Physical Examination

In most instances, the standard physical examination does not help to establish a diagnosis of chronic pancreatitis; however, a few points are noteworthy.

During an attack, patients may assume a characteristic position in an attempt to relieve their abdominal pain (eg, lying on the left side, flexing the spine and drawing the knees up toward the chest).

Occasionally, a tender fullness or mass may be palpated in the epigastrium, suggesting the presence of a pseudocyst or an inflammatory mass in the abdomen. Patients with advanced disease (ie, patients with steatorrhea) exhibit decreased subcutaneous fat, temporal wasting, sunken supraclavicular fossa, and other physical signs of malnutrition.

 

DDx

Diagnostic Considerations

Some patients with cystic neoplasms have undergone cyst-enteric anastomoses, only to develop malignancy later. Consider a cystic neoplasm in any patient without a clinical history of pancreatitis, even if no septa, solid component, or rim calcification is present on the imaging study.

Although aspiration of the cyst fluid and measurement of its viscosity, carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, and other factors are helpful in differentiating the various types of cysts, surgical resection of the cyst is the standard of care in a good surgical candidate.

Groove pancreatitis is a unique form of segmental pancreatitis in which the inflammatory process is confined to the groove between the duodenum and the common bile duct, without necessarily involving the entire head of the pancreas.[10]

Differential Diagnoses

 

Workup

Approach Considerations

See Pancreatic Function Tests, Radiography and CT Scanning, Endoscopic Retrograde Cholangiopancreatography, Magnetic Resonance Cholangiopancreatography, and Endoscopic Ultrasonography for information on elements of the workup.

In regard to childhood pancreatitis, the European Pancreatic Club and Hungarian Pancreatic Study Group note that chronic pancreatitis is an irreversible inflammatory process that culminates in changes in the pancreatic parenchyma and function.[11] Therefore, to make the diagnosis, documentation of characteristic histologic and morphologic alterations or decreased exocrine or endocrine pancreas function is required.[11]

Blood tests

Serum amylase and lipase levels may be slightly elevated in chronic pancreatitis; high levels are found only during acute attacks of pancreatitis. In the later stages of chronic pancreatitis, atrophy of the pancreatic parenchyma can result in normal serum enzyme levels because of significant fibrosis of the pancreas, resulting in decreased concentrations of these enzymes within the pancreas.

Although low concentrations of serum trypsin are relatively specific for advanced chronic pancreatitis, they are not sensitive enough to be helpful in most patients with mild to moderate disease.

Laboratory studies to identify the causative factors of chronic pancreatitis include serum calcium and triglyceride levels. When common etiologies are not found, research protocols are available to test for genetic mutations in cationic trypsinogen and CFTR.

Fecal tests

Because maldigestion and malabsorption do not occur until more than 90% of the pancreas has been destroyed, steatorrhea is a manifestation of advanced chronic pancreatitis. Neither qualitative nor quantitative fecal fat analysis can detect early disease.

Assays of fecal chymotrypsin and human pancreatic elastase 1 have the same limitations but are useful in confirming advanced chronic pancreatitis with exocrine insufficiency.

2018 Working Group for the International Consensus Guidelines for Chronic Pancreatitis recommendations

The clinical practice guidelines for the diagnostic cross-sectional imaging and severity scoring of chronic pancreatitis were released in October 2018 by the Working Group for the International Consensus Guidelines for Chronic Pancreatitis.[12]

Computed tomography (CT) is often the most appropriate initial imaging modality to evaluate suspected chronic  pancreatitis (CP); it depicts most of the changes in pancreatic morphology.

CT is also indicated to exclude other potential intra-abdominal pathologies that present with symptoms similar to those of chronic pancreatitis, but CT cannot exclude a diagnosis of CP and cannot exclusively diagnose early or mild CP.

Magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP) are superior and are indicated especially in patients in whom no specific pathologic changes are seen on CT.

Secretin-stimulated MRCP is more accurate than standard MRCP to identify subtle ductal changes. Secretin-stimulated MRCP should be performed after a negative MRCP if there is still clinical suspicion of CP. 

Secretin-stimulated MRCP can provide assessment of exocrine function and ductal compliance.

Endoscopic ultrasound (EUS) can also be used to diagnose parenchymal and ductal changes mainly during the early stage of CP.

There are no known validated radiologic severity scoring systems for CP, but a modified Cambridge Classification has been used for MRCP.

A new and validated radiologic CP severity scoring system is needed that is based on imaging criteria (CT and/or MRI), including glandular volume loss, ductal changes, parenchymal calcifications, and parenchymal fibrosis.​

Pancreatic Function Tests

Direct tests

These tests are the most sensitive and can be used to detect chronic pancreatitis at its earliest stage; however, they are somewhat invasive, labor intensive, and expensive.

Determination in duodenal aspirates

Intubation of the duodenum usually is performed with a Dreiling tube, which allows for separate aspiration of the gastric and duodenal contents. The methodology varies depending on the specific laboratory; however, exogenous secretin with cholecystokinin (CCK) is used to achieve maximal stimulation of the pancreas. The output of pancreatic bicarbonate, protease, amylase, and lipase then is measured in the duodenal aspirates.

This test currently is available only in specialized centers. While the greatest sensitivity can be obtained in prolonged infusions of a secretagogue to uncover a decreased pancreatic secretory reserve, it is impractical for general clinical use.

Determination in pancreatic juice

This test generally is performed in conjunction with ERCP. The pancreatic duct is freely cannulated, an exogenous secretagogue is administered as above, and the pancreatic juice then is aspirated out of the duct as it is produced. The output of pancreatic bicarbonate, protease, amylase, and lipase are measured.

Indirect tests

Noninvasive tests of pancreatic function have been developed for detecting chronic pancreatitis. In principle, these tests work via oral administration of a complex substance that is hydrolyzed by a specific pancreatic enzyme to release a marker substance. The intestine absorbs the marker, which then is measured in the serum or urine. These tests are capable of detecting moderate to severe chronic pancreatitis. The presence of renal, intestinal, and liver disease may interfere with the accuracy of these tests. Neither currently is freely available in the United States.

Radiography and CT Scanning

Hallmarks of chronic pancreatitis that can be detected on advanced imaging studies include calcifications, pancreatic duct dilatation, chronic pseudocysts, focal pancreatic enlargement, and biliary ductal dilatation.[13]

Abdominal radiography

Pancreatic calcifications, often considered pathognomonic of chronic pancreatitis, are observed in approximately 30% of cases. Paired anteroposterior (AP) and oblique views are preferred because the vertebral column otherwise could obscure small flecks of calcium. The calcifications form within the ductal system—initially in the head, and later in the body and tail, of the gland. Calcium deposition is most common with alcoholic pancreatitis, hereditary pancreatitis, and tropical pancreatitis; however, it is rare in idiopathic pancreatitis.

CT scanning

The advantage of CT scanning is that interpretation of pancreatic CT images is relatively intuitive. However, although CT scanning excels at depicting the morphologic changes of advanced chronic pancreatitis described above, the subtle abnormalities of early to moderate chronic pancreatitis are beyond its resolution, and a normal finding on this study does not rule out chronic pancreatitis.

CT scan studies are indicated to look for complications of the disease and are useful in planning surgical or endoscopic intervention. The sensitivity and specificity of CT scanning are 80% and 85%, respectively. (See the images below.)

Chronic pancreatitis. CT scans of the abdomen foll Chronic pancreatitis. CT scans of the abdomen following an endoscopic transgastric pseudocystogastrostomy. Note that 2 stents are placed through the stomach and into the pseudocyst. Before undertaking this type of endoscopic intervention, the endoscopist must be confident that a cystadenoma has not been mistaken for a pseudocyst.
Chronic pancreatitis. This patient developed abdom Chronic pancreatitis. This patient developed abdominal pain several weeks after being accidentally hit with a baseball bat. A CT scan showed a large splenic hematoma, and the patient underwent a splenectomy. His postoperative course was notable for recurrent pain, abdominal distension, and elevation of serum amylase levels over the course of 2-3 months. This repeat CT scan shows postsurgical changes in the left upper quadrant and a large fluid collection.

Endoscopic Retrograde Cholangiopancreatography

ERCP, demonstrated in the image below, provides the most accurate visualization of the pancreatic ductal system and has been regarded as the criterion standard for diagnosing chronic pancreatitis. One limitation of ERCP, however, is that it cannot be used to evaluate the pancreatic parenchyma, and histologically proven chronic pancreatitis has been documented in the setting of normal findings on pancreatogram.

This endoscopic retrograde cholangiopancreatograph This endoscopic retrograde cholangiopancreatography (ERCP) shows advanced chronic pancreatitis. The pancreatogram has blunting of the lateral branches, dilation of the main pancreatic duct, and filling defects consistent with pancreatolithiasis. The cholangiogram also shows a stenosis of the distal bile duct and a dilated biliary tree.

Pancreatograms can be interpreted and classified according to several schemes, such as the Cambridge criteria. A comparison of ERCP scoring with direct pancreatic function tests demonstrated good correlation. However, pancreatography tended to show significantly more severe changes.

The problems with ERCP are that it is invasive and expensive, requires complete opacification of the pancreatic duct to visualize side branches, and carries a risk (operator-dependent) of pancreatitis.

Magnetic Resonance Cholangiopancreatography

MRCP, demonstrated in the image below, provides information on the pancreatic parenchyma and adjacent abdominal viscera, and MRCP uses heavily T2-weighted images to visualize the biliary and pancreatic ductal system. The use of secretin during the study enhances the quality of the pancreatogram. Accuracy is improving, and MRCP is relatively safe, reasonably accurate, noninvasive, fast, and very useful in planning surgical or endoscopic intervention.

Chronic pancreatitis. This magnetic resonance chol Chronic pancreatitis. This magnetic resonance cholangiopancreatography (MRCP) shows a healthy biliary system. The pancreatic ductal system is not well visualized. A subsequent endoscopic retrograde cholangiopancreatography (ERCP [not pictured]) showed pancreas divisum, with no evidence of a communication with the pseudocyst. The endoscopic features were ideal for an endoscopic transgastric pseudocystogastrostomy.

Endoscopic Ultrasonography

Although studies suggest that endoscopic ultrasonography (EUS) may be the best test for imaging the pancreas, it requires a highly skilled gastroenterologist.[14]

Eleven sonographic criteria have been developed that identify characteristic findings of chronic pancreatitis. The most predictive endosonographic feature is the presence of stones. Other suggestive features include the following:

  • Visible side branches

  • Cysts

  • Lobularity

  • An irregular main pancreatic duct

  • Hyperechoic foci and strands

  • Dilation of the main pancreatic duct

  • Hyperechoic margins of the main pancreatic duct

Before 2001, three or more of these criteria on EUS were used to diagnose chronic pancreatitis. However, subsequent data has suggested the use of five or more criteria to have higher specificity, rather than sensitivity, to diagnose chronic pancreatitis. In general, the presence of five or more of these features is considered highly suggestive of chronic pancreatitis.

EUS may be as sensitive and specific as tube tests for mild and advanced disease, especially when combined with fine needle aspiration or Tru-Cut biopsy.

Histologic Findings

In the early stages of chronic pancreatitis, the parenchyma exhibits an increase in connective tissue around the ducts and between the lobules. The degree of inflammation is minimal to moderate, consisting mostly of T lymphocytes, and a patchy, focal process unevenly affects the pancreas. With increasing severity, the connective tissue progresses between the acini, which gradually become distorted and tend to disappear. In advanced disease, fibrous tissue replaces the acinar tissue, and the pancreas becomes contracted, small, and hard. The islets of Langerhans are relatively spared until very late in the disease process.

Patients can have severe histopathologic changes of chronic pancreatitis despite normal findings on imaging studies. In patients undergoing resection of the pancreas for chronic pancreatitis, focal necrosis is found in 11.9% of cases and segmental fibrosis is observed in approximately 40% of cases.

In chronic calcific pancreatitis, plugs of precipitated protein develop within the ductal system. While they may be observed in all types of chronic pancreatitis, in alcoholic and tropical forms these plugs tend to evolve into calculi by deposition of calcium within them. The calcified pancreatic calculi are distributed irregularly, affecting ducts of various sizes, and may be associated with ulcerations of the ductal epithelium. Periductal connective tissue may encroach into the lumen and cause ductal stenoses, creating the "chain of lakes" pancreatogram appearance observed in advanced chronic calcific pancreatitis.

 

Treatment

Approach Considerations

The goals of medical treatment are as follows:

  • Modify behaviors that may exacerbate the natural history of the disease

  • Enable the pancreas to heal itself

  • Determine the cause of abdominal pain and alleviate it

  • Detect pancreatic exocrine insufficiency and restore digestion and absorption to normal

  • Diagnose and treat endocrine insufficiency

The benefit of antioxidants in the early stages of chronic pancreatitis is still controversial. Most patients can be managed medically. Even in patients with asymptomatic pseudocysts, relatively few develop serious complications (eg, bleeding, infection) requiring urgent surgery, and half will never require surgical intervention.

See the Guidelines section for recommendations on the diagnosis and management of chronic pancreatitis, guidelines for the understanding and management of pain in chronic pancreatitis, as well as for  the diagnosis and management of asymptomatic neoplastic pancreatic cysts.

Inpatient care

The need for hospitalization and further inpatient management of patients with an attack of chronic pancreatitis depends on the severity of the disease.

Patients with mild pancreatitis are kept on nothing by mouth and administered intravenous (IV) fluid hydration. Narcotic analgesics generally are required for pain control. Nutritional supplementation is recommended in patients with malnutrition and in patients who are not able to take oral medication after a long hospitalization.

A small percentage of patients with severe pancreatitis may become critically ill, especially early in the natural history of recurrent acute or chronic pancreatitis. Intensive care management is required, and the clinician must look for developing complications, such as shock, pulmonary failure, renal failure, gastrointestinal bleeding, and multiorgan system failure.

Surgical care

Intervention is indicated when an anatomical complication that is correctable by a mechanical intervention exists. Generally, this is an acquired abnormality, such as one of the following:

  • Pancreatic pseudocyst

  • Abscess

  • Fistula

  • Ascites

  • Fixed obstruction of the intrapancreatic portion of the distal common bile duct

  • Stenosis of the duodenum with gastric outlet obstruction

  • Variceal hemorrhage due to splenic vein thrombosis

Depending on the individual case, the appropriate intervention may involve endoscopic, radiologic, or surgical techniques.

Radiologic evaluation and drainage

Prior to percutaneous drainage, performing pancreatography is important in order to understand the anatomy of the pancreatic ductal system and plan appropriate treatment. If a communication exists between the pancreatic ductal system and the pseudocyst, percutaneous drainage may create a persistent pancreaticocutaneous fistula, especially if the duct has a stricture downstream from the site of the disruption.

If the anatomy of the pseudocyst does not lend itself to transpapillary, transgastric, or transduodenal endoscopic drainage, then percutaneous drainage under ultrasonographic or CT scan guidance is an option. Transgastric pseudocyst drainage has been used to treat pancreatic pseudocysts successfully, but a high failure rate has been reported.

Consultations

Successful treatment of alcoholism and tobacco addiction requires a team approach, including the involvement and expertise of a chemical dependency counselor and a psychologist trained in cognitive therapy.

In patients with uncontrolled abdominal pain, early referral to a pain management specialist may allow better pain control.

Behavior Modification

Cessation of alcohol consumption and tobacco smoking are important. In early stage alcohol-induced chronic pancreatitis, lasting pain relief can occur after abstinence from alcohol, but in advanced stages, abstinence does not always lead to symptomatic improvement. Patients continuing to abuse alcohol develop either marked physical impairment or have a death rate 3 times higher than do patients who abstain.

Recommending abstinence from alcohol usually is not sufficient; the physician must use available resources for evaluation and treatment of alcohol and chemical dependency. Successful treatment requires a team approach, including the involvement and expertise of a chemical dependency counselor and a psychologist trained in cognitive therapy.

Tobacco smoking is a strong and independent risk factor for chronic alcoholic pancreatitis. Because much of the reported excess morbidity and mortality in these patients is related to smoking tobacco, patients also need to overcome their tobacco addiction.

Pharmacologic Alleviation of Abdominal Pain

See the Guidelines section for guidelines for the understanding and management of pain by the Working Group for the International Consensus Guidelines for Chronic Pancreatitis.[15]

A number of factors may contribute to the pain in chronic pancreatitis, and the principal mechanisms of pain may change with the course of the disease. Sources of pain can include the following:

  • Acute disease with inflammation and pseudocyst formation may be superimposed on chronic disease

  • Obstruction of the pancreatic duct by strictures or stones may cause increased duct pressure and pain

  • Pancreatic ischemia, with decreased pancreatic oxygenation and a decreased tissue pH, caused by a compartment syndrome may cause pain that is relieved by duct decompression

  • Pancreatic nerves become enlarged, lose some of their cellular sheath, and are inflamed

  • Obstruction of the duodenum or biliary tract may worsen with acute episodes and improve with time

Diagnostic tests may be necessary to identify an anatomic explanation for the pain and to plan appropriate treatment. If no anatomic explanation for abdominal pain can be found, medical therapy can be attempted. This therapy includes pain control with analgesic agents and a trial of noncoated pancreatic enzymes.

Exogenous pancreatic enzymes and CCK

The impetus for using exogenous pancreatic enzymes to reduce pain begins with the hypothesis that stimulation of the pancreas by food causes pain. Cholecystokinin (CCK) is one of the possible mediators of this response.

CCK releasing factor (CRF) typically is secreted into the duodenum. During the interdigestive period, proteolytic enzymes within the pancreatic juice rapidly degrade CRF. After a meal, the proteolytic enzymes are occupied with digesting dietary proteins, and enough CRF escapes to bind to duodenocytes, which stimulates CCK release, in turn stimulating pancreatic secretion.

In severe chronic pancreatitis with exocrine insufficiency, CCK levels may be high because proteolytic enzymes are low. When pancreatic enzyme supplements are administered in high doses, degradation of CRF is restored and the stimulus for CCK release is reduced.

This hypothesis is supported by one report that a CCK-receptor antagonist reduces pain in patients with chronic pancreatitis. The digestive products of a meal and the CCK-releasing factor stimulate CCK release from the duodenal mucosa. CCK acts directly on the pancreatic cells and indirectly through neural pathways to stimulate the pancreas. Through unknown mechanisms, such stimulation has been hypothesized to cause pain.

When exogenous pancreatic enzymes are taken with a meal, CCK-releasing factors are degraded and CCK release in response to a meal is reduced, as indicated by the smaller CCK response. This decreases pancreatic stimulation and pain. Any benefit from this treatment is likely limited to nonalcoholic patients with early chronic pancreatitis and requires the use of uncoated preparations.

Clinical trials investigating the benefits of this approach have provided mixed results. While four trials using enteric-coated enzyme preparations demonstrated no effect, these studies may have been flawed if the coating failed to release the enzymes into the feedback-sensitive portion of the duodenum. Two studies using non–enteric-coated tablets have demonstrated a reduction in pain compared with placebo. Female patients and those with idiopathic chronic pancreatitis appear to respond best.

Celiac ganglion blockade

If conventional medical therapy is unsuccessful and the patient has severe, intractable pain, celiac ganglion blockade can be considered.[1] This approach tries to alleviate pain by modifying afferent sensory nerves in the celiac plexus, using agents that anesthetize, reduce inflammation, or destroy nerve fibers.

In a study in which alcohol injections were administered, 12 of 23 patients obtained complete pain relief, and 6 of 23 patients obtained partial pain relief. However, the mean pain-free interval was only 2 months; the longest pain-free interval was only 4 months. Repeated blocks generally were not effective.

Because of the risks of paralysis resulting from a transverse myelopathy and catastrophic hemorrhage resulting from injury to major abdominal vasculature, the use of alcohol blocks should be restricted to patients with intractable, severe pain due to terminal pancreatic cancer.

Percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis and should be considered an unproven therapy.

Pharmacologic Restoration of Digestion and Absorption

Although reduced fat intake is often recommended in patients with chronic pancreatitis, the clinical benefit is unknown. Indeed, the efficiency of fat absorption in dogs increases with increased fat intake. Whether humans have a similar response is unknown.

Medium chain triglycerides are directly absorbed by the small intestine without a requirement for digestion by lipase or micellar solubilization. To supply lipids and calories, medium-chain triglycerides can be used in patients with severe fat malabsorption. There is occasionally sufficient loss of fat-soluble vitamins to cause disease.

Enteric-coated preparations protect lipase from inactivation by gastric acid. Uncoated preparations are often less costly and adequate to relieve steatorrhea. Reducing gastric acid secretion may enhance the effectiveness of uncoated preparations. Enzyme preparations with high lipase content are available and recombinant lipase preparations will probably soon be marketed. Some of the recombinant enzymes are resistant to acidic denaturation. To provide adequate mixing with food, enzymes should be ingested during and just after a meal.

The most serious adverse effects (ie, colonic strictures) were observed with coated preparations that contained high concentrations of enzymes. In recent years, this adverse effect has not been seen, probably due to a reformulation of enzyme preparations.

Cobalamin or vitamin B-12 is absorbed complexed to intrinsic factor in the terminal ileum. Some vitamin B-12 absorption that is independent of intrinsic factor occurs throughout the small bowel. When vitamin B-12 enters the stomach, it binds to a protein known as haptocorrin or R-protein. The haptocorrin is proteolytically degraded in the small intestine by pancreatic enzymes, and the released vitamin B-12 then binds to intrinsic factor. In patients with pancreatic insufficiency, vitamin B-12 can remain bound to haptocorrin and is not available for absorption by the terminal ileum. Although vitamin B-12 malabsorption can be demonstrated in patients with chronic pancreatitis, it rarely causes clinical vitamin B-12 deficiency.

Endoscopic Treatment

Endoscopic therapy aimed at decompressing an obstructed pancreatic duct can be associated with pain relief in some patients (see the images below). The rationale for this approach is based on the hypothesis that ductal hypertension due to strictures of the main pancreatic duct leads to pain.[2, 3]

Chronic pancreatitis. A nasopancreatic tube course Chronic pancreatitis. A nasopancreatic tube courses through the esophagus, stomach, and duodenum and into the pancreatic duct. Externally, the end of the tube is attached to a suction bulb to decompress the ductal system and monitor its function on a daily basis. In contrast to patients treated with transpapillary stents, none of these patients ever has failed to return for a follow-up appointment. In addition, while stent obstruction and subsequent infection can occur with transpapillary stents, the author has not observed this complication while using nasopancreatic tubes.
Chronic pancreatitis. Nine days after placement of Chronic pancreatitis. Nine days after placement of a nasopancreatic tube, a pancreatogram obtained via the tube showed that the disruption had healed (see the above image). The tube then was removed.
Chronic pancreatitis. This follow-up CT scan (see Chronic pancreatitis. This follow-up CT scan (see the above 2 images) shows a percutaneous tube in the left upper quadrant that was used to drain a fluid collection. It was removed after 4 weeks. The patient returned to work, regained his weight, and had no recurrence of abdominal pain or signs of a recurrent pancreatic leak.

At best, endoscopic treatment can offer pain relief in up to 60% of well-selected patients after 5 years of follow-up care. The one report with long-term follow-up included 1018 patients treated at 8 different centers who were followed for an average of 5 years. Obstruction of the pancreatic duct was due to strictures (47%), stones (18%), or strictures plus stones (32%). Patients were treated using various endoscopic techniques.

At the end of follow-up, 60% had completed the endoscopic therapy, while 16% were still undergoing some form of endoscopic therapy and 24% had undergone surgery. Pain relief (based upon a structured questionnaire) was achieved in 65% of patients on intention-to-treat analysis. Pancreatic function did not improve. The techniques involved can be technically challenging, and complications have been described. Currently, it should be performed only in centers with expertise in this area on carefully selected patients.

Endoscopic therapy may be beneficial in chronic pancreatitis in any of the following situations:

  • Papillary stenosis

  • Pancreatic duct strictures

  • Pancreatic duct stones

  • Pancreatic pseudocysts

Papillary stenosis

In a subset of patients with chronic pancreatitis, the papillary sphincter pressure and pancreatic ductal pressure are increased. In appropriately selected patients, a pancreatic duct sphincterotomy will facilitate drainage and reduce ductal pressures and may help to alleviate pain.

Pancreatic duct strictures

Suitable candidates for endoscopic therapy are patients with a dominant distal pancreatic stricture and upstream ductal dilatation. The procedure involves placing a guidewire through the stricture into the proximal duct, performing a pancreatic sphincterotomy, dilating the stricture, and placing a stent. While technical success is achieved in more than 90% of patients, nearly 20% will have a complication and less than two thirds of patients will benefit clinically. Pain relief correlates with a reduction in the diameter of the duct by more than 2mm. Patients with recurrent pancreatitis are more likely to benefit than are those with chronic daily pain.

The stricture rarely disappears, and the stent invariably clogs; therefore, repeated procedures are required to exchange the stent. Prolonged or inappropriate stenting can injure the pancreatic duct.

Pancreatic duct stones

While pancreatic duct stones are a sequelae of chronic pancreatitis, they also may be responsible for recurrent acute pancreatitis or exacerbations of chronic pain related to ductal obstruction and increased ductal pressure. Stones usually form proximal to the ductal strictures and usually require a pancreatic duct sphincterotomy and stricture dilation to enable their extraction. In addition to various endoscopic techniques, extracorporeal shockwave lithotripsy often is necessary to break up impacted or large stones into smaller pieces suitable for removal.

Technical success is achieved in approximately 60% of patients and complications occur in 20%. Approximately 70% of patients report improvement in their symptoms.

Pancreatic pseudocysts

Advances in interventional endoscopy now enable endoscopic treatment of many pseudocysts. In the appropriate clinical setting, obtain a pancreatogram to determine whether the pancreatic duct communicates with the pseudocyst. Ideally, communicating pseudocysts found in the head or body can be treated with transpapillary stents (see the images below), with a success rate of 83% and a complication rate of 12%.

This pancreatogram shows a pseudocyst communicatin This pancreatogram shows a pseudocyst communicating with the main pancreatic duct in a patient with chronic pancreatitis and recurrent abdominal pain. He was treated endoscopically with a transpapillary stent placed into the pancreatic duct.
Four weeks after placement of a transpapillary ste Four weeks after placement of a transpapillary stent, a patient with a pseudocyst communicating with the main pancreatic duct (chronic pancreatitis with recurrent abdominal pain) had not had a recurrence of pain. The CT scan showed resolution of the cyst, and the follow-up pancreatogram showed marked improvement. Transpapillary stenting of the pancreatic duct should be reserved for patients with established chronic pancreatitis.

Noncommunicating pseudocysts that bulge into the foregut and have a mature wall less than 1 cm thick are treatable by endoscopic transduodenal or transgastric pseudocystostomy. The success rate is 85%, with a 17% complication rate. The transduodenal approach has fewer complications and recurrences than the transgastric approach. The long-term success rate of the initial procedure is reported at 62%.

Surgical Therapy

The choice of operation depends on the clinical problem and the preoperative assessment of the abnormality. In general, the approach aims either to improve pancreatic duct drainage or to resect the diseased organ. Data suggest that surgical drainage of the pancreatic duct is more effective than endoscopic drainage in patients with obstruction of the pancreatic duct due to chronic pancreatitis.

Pancreatic duct drainage

In patients with a dilated pancreatic duct, a Roux-en-Y side-to-side pancreaticojejunostomy is indicated. The operative mortality rate is about 3%, and pain relief is obtained in approximately 75% of patients (patients' cases were followed for a mean of 8 y). Pancreatic dysfunction progresses similarly in surgical and nonsurgical groups, suggesting that drainage procedures do not affect the natural evolution of the disease significantly. The long-term result for pain relief is reported in 42% of patients.

Pancreatic resection

If the disease is limited to the head of the pancreas, a Whipple operation (pancreaticoduodenectomy) can produce good results. In patients with intractable pain and diffuse disease with nondilated ducts, a subtotal or total pancreatectomy can be offered; however, the pancreatic function and quality of life are impaired after these procedures, and the operative mortality rate of total pancreatectomy is about 10%. Pain is treated successfully in approximately 70% of cases. (See the images below.)

Chronic pancreatitis. This patient had a persisten Chronic pancreatitis. This patient had a persistent postoperative leak from the site of a distal pancreatectomy. In the mid-1990s, the author sought to facilitate enteric drainage using transpapillary stents placed into the pancreatic duct. While this changed the fluid dynamics in favor of healing the disrupted duct, some patients developed complications from this technique.
Chronic pancreatitis. The persistent postoperative Chronic pancreatitis. The persistent postoperative leak from the site of a distal pancreatectomy has healed at 1-month follow-up (see the image above). However, after 4 weeks of transpapillary stenting, the pancreatogram now shows a stent-induced stenosis near the surgical genu (arrow). Based on this experience, the author stopped using pancreatic stents in this setting.

Total pancreatectomy and islet autotransplantation

In 46 patients undergoing near-total pancreatectomy, pain relief occurred in 82% (resolved in 39% and improved in 43%). Although 51% were insulin independent initially, this decreased to 34% (one third) from 2-10 years after transplantation.

In selected patients, the long-term morbidity caused by diabetes following total pancreatectomy can be avoided. Doing so involves harvesting the islets from the resected pancreas and injecting them into the portal system, which then lodges them in the liver. Increasing severity of pancreatic fibrosis correlates positively with poor recovery of islets (< 300,000) and insulin dependence.

Diet

A diet low in fat and high in protein and carbohydrates is recommended, especially in patients with steatorrhea. The degree of fat restriction depends on the severity of fat malabsorption; generally, an intake of 20 g/day or less is sufficient. Patients who continue to suffer from steatorrhea following fat restriction require medical therapy.

Clinically significant protein and fat deficiencies do not occur until over 90% of pancreatic function is lost. Steatorrhea usually occurs prior to protein deficiencies, since lipolytic activity decreases faster than proteolysis.

Specific recommendations include a daily diet of 2000-3000 calories, consisting of 1.5-2 g/kg of protein, 5-6 g/kg of carbohydrates, and 20-25% of total calories consumed as fat (about 50-75g) per day.

Malabsorption of the fat soluble vitamins (A, D, E, and K) and vitamin B-12 may also occur. Oral supplementation of these enzymes is recommended.

 

Guidelines

Guidelines

2017 United European Gastroenterology guidelines

In March 2017, the United European Gastroenterology (UEG) released their updated recommendations for the diagnosis and therapy of chronic pancreatitis (CP).

A diagnosis of cystic fibrosis needs to be ruled out in all patients with CP onset before the age of 20 yr, as well as in patients with so-called idiopathic CP, regardless of the age of onset.

All patients with a family history or early onset disease (< 20 yr) should be offered genetic testing for associated variants. In patients with alcoholic CP, routine genetic testing cannot be recommended. Variants in SPINK1 and CTRC and, to a lesser extent, common single-nucleotide polymorphisms (SNPs) in the PRSS1 and CLDN2-MORC4 loci, are associated with alcoholic CP.

In pediatric patients, cystic fibrosis needs to be ruled out by chloride iontophoresis, while genetic causes seem to be much more important in children than in adults. Laboratory evaluation needs to include Ca2+ and triglyceride levels. Recommended imaging modalities are abdominal ultrasound or magnetic resonance cholangiopancreatography (MRCP). Testing should include PRSS1 (sequencing of exon 2 and 3 to cover mainly p.A16V, p.N29I and p.R122H), SPINK1 (all 4 exons, mainly p.N34S and IVS3 + 2T > C in exon 3 and intron 3), CPA1 (several variants, mainly in exons 7, 8, and 10), CTRC (especially exon 7), and CEL (hybrid allele only), and may include screening for variants in CFTR. In every pediatric patient, cystic fibrosis has to be ruled out, since 10-15% of cystic fibrosis patients with pancreatic sufficiency (comprising 1-2% of all patients with cystic fibrosis) present clinically with recurrent attacks of acute pancreatitis.

EUS, MRI, and CT are the best imaging methods for establishing a diagnosis of CP. CT examination is the most appropriate method for identifying pancreatic calcifications, while for very small calcifications, non-enhanced CT is preferred. The presence of typical imaging findings for CP with MRI/MRCP is sufficient for diagnosis; however, a normal MRI/MRCP result cannot exclude the presence of mild forms of the disease.

Abdominal US can only be used to diagnose CP at an advanced stage. EUS is the most sensitive imaging technique for the diagnosis of CP, mainly during the early stages of the disease, and its specificity increases with increasing diagnostic criteria. EUS is an essential tool in the differential diagnosis of CP with other pancreatic masses or cystic lesions. EUS-guided fine-needle biopsy can be considered as the most reliable procedure for detecting malignancy.

Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes (acinar function) and/or sodium bicarbonate (ductal function).

Mild PEI is defined as the reduced secretion of one or more enzymes with normal bicarbonate concentration in duodenal juice and normal fecal fat excretion; moderate PEI is defined as having a reduced enzyme output and bicarbonate concentration but normal fecal fat excretion; while severe PEI has a reduced enzyme output and bicarbonate concentration plus steatorrhoea.

The main causes of PEI are loss of the pancreatic parenchyma, obstruction of the main pancreatic duct, decreased stimulation of the exocrine pancreas, and inactivation of pancreatic enzymes.

For exocrine pancreatic insufficiency, in a clinical setting, a noninvasive pancreatic function test (PFT) should be performed. The fecal elastase (FE-1) test is feasible and widely available and is therefore most frequently used in this setting, while the 13C mixed triglyceride breath test (13C-MTG-BT) offers an alternative. The s-MRCP test may also be used as an indicator of PEI but provides only semiquantitative data.

A pancreatic function test is required for the diagnosis of CP. Every patient with a new diagnosis of CP should be screened for PEI.

Surgery is superior to endoscopy in terms of mid-term and long-term pain relief in patients with painful CP.

To achieve optimal long-term pain relief in patients suffering from CP, early surgery is favored over surgery at a more advanced stage of the disease.

A total pancreatectomy should be considered in CP patients without duct system dilatation, who are resistant to conventional medical, endoscopic, and previous surgical treatment and who have severe pain.

Pancreatic enzyme replacement therapy (PERT) is indicated for patients with CP and PEI in the presence of clinical symptoms or laboratory signs of malabsorption. An appropriate nutritional evaluation is recommended to detect signs of malabsorption.

The optimal dose of pancreatic enzymes for PEI in CP is a minimum lipase dose of 40,000–50,000 PhU with main meals, and half that dose with snacks. The addition of a PPI to oral pancreatic enzymes is of help in patients with an unsatisfactory response to PERT.

In patients with uncomplicated painful CP and a dilated main pancreatic duct (MPD), endoscopic therapy (ET) is recommended as the first-line treatment after failed medical therapy following discussions by a multidisciplinary team (MDT). The clinical response should be evaluated at 6-8 wk; if it appears unsatisfactory, the patient’s case should be discussed again by a multidisciplinary team of endoscopists, surgeons, and radiologists, and surgical options should be considered, in particular for patients with a predicted poor outcome following ET.

ET is performed first in most cases, with surgery reserved for the minority of patients whose painful symptoms do not respond well to ET.

Pain is the first presentation of CP in the majority of patients. Paracetamol is the preferred level I analgesic because of its limited side effects, while nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided because of their gastrointestinal toxicity. If necessary, PPIs should be used in patients with CP who are at high risk of developing peptic ulcers.

Tramadol is the preferred level II analgesic and was shown to be superior to morphine in patients with CP, with fewer gastrointestinal side effects for the same level of analgesia.

Level III analgesia constitutes the group of strong opioids, such as morphine, which are widely used for pain relief in CP. In general the lowest possible dose should be used and the drug should always be taken orally to avoid dose escalation and addiction. Note: in many patients (up to 50% of chronic pain patients in general), opioids do not alleviate pain, and treatment should be stopped.

ET is effective in patients with an obstructive type of pancreatic pain and in patients with a pancreatic duct dilatation.

Extracorporeal shock wave lithotripsy (ESWL) therapy is effective for disintegrating stones in the main pancreatic duct.

Resection, decompression, or mixed surgical techniques achieve pain relief in CP that is maintained over time in approximately 80% of patients.

Parenteral nutrition is indicated in patients with gastric outlet obstruction secondary to duodenal stenosis, in patients with complex fistulating disease, and in patients with apparent severe malnutrition prior to pancreatic surgery if enteral feeding is not possible.

Enteral nutrition is indicated in patients with malnutrition who are not responding to oral nutritional support.

2017 Working Group for the International (IAP-APA-JPS-EPC) Consensus Guidelines for Chronic Pancreatitis

In September 2017, the Working Group for the International Consensus Guidelines for Chronic Pancreatitis published their guidelines for understanding and management of pain in chronic pancreatitis.[15]

Although abdominal pain is the most frequent symptom of CP, the severity, temporal nature, and natural history of pain varies greatly.

In addition to administering adequate treatment, strongly advise patients with CP to abstain from alcohol and smoking.

Routinely refer all patients with presumed or established CP to expert pancreatic centers for workup and management of their disease.

Pain in CP remains poorly understood and inadequately correlated with neurobiologic mechanisms. Although CP is defined by inflammation, few therapeutic attempts have been made to target this aspect of its pathophysiology. In addition, the presence of striking changes in peripheral and central nervous system structure and function suggests a maladaptive state that includes both neuropathic and dysfunctional pain. In the absence of effective anti-inflammatory approaches, it is clearly important to focus on the alteration of function that accompanies these changes in the nociceptive system as a potential therapeutic target.

Assessment of pain in CP follows the guidelines for other types of chronic pain, taking into account the multidimensional nature of symptom presentation. Although few validated instruments exist for subjective CP pain assessment, there are appropriate measures available, albeit not rigorously validated in this population.

An initial attempt with pancreatic enzyme therapy with high protease content is reasonable for pain relief in patients with CP. Include a combination of antioxidants in sufficient dosages as options for pain treatment.

The current standard guideline for analgesic therapy in CP follows the principles of the “pain relief ladder” provided by the World Health Organization (WHO) adjusted to the pain characteristics of this condition.

The best candidates for successful treatment of painful CP with first-line endoscopic therapy are those with distal obstruction of the main pancreatic duct (single stone and/or single stricture in the head of the pancreas) and in the early stage of the disease. Endoscopic therapy can be combined with extracorporeal shock wave lithotripsy (ESWL) in the presence of large (>4 mm) obstructive stone(s) located in the pancreatic head, and with ductal stenting in the presence of a dominant main pancreatic duct stricture that induces a markedly dilated duct.

In cases of uncomplicated painful calcified CP, ESWL alone is a safe and effective treatment. Best candidates for benefiting from initial first-line ESWL are patients with obstructive calcifications, more than 4 mm confined to the head of pancreas. It is not cost effective nor is it likely to improve pain outcomes to combine systematic endoscopical therapy with ESWL.

ESWL for pancreatic stones is indicated for patients with all of the following:

  • Recurrent attacks of pancreatic pain
  • Moderate to marked changes in the pancreatic ductal system
  • Obstructing ductal stones (minimal diameter: 2-5 mm, calcified or radiolucent)

Neurolytic interventions can be used in selected patients with painful CP refractory to endoscopic and surgical treatment. Thoracoscopic splanchnic denervation is more effective regarding long-term pain relief in patients who are not on chronic opioid treatment. Include behavioral interventions as part of the multidisciplinary approach in CP pain, particularly in patients who experience psychological impact of pain and reduced quality of life. Early intervention in children may be particularly important.

Depending on the morphologic changes of the pancreas and pain processing status a (partial) resection, decompression of the pancreatic duct or combined interventions can be performed to reduce pain. Although long-term effects vary, success rates up to 80% have been reported. Total pancreatectomy is emerging as a promising initial surgical treatment but needs further investigation.

Current evidence on the timing of surgery for painful CP suggests a beneficial role for early surgery, ie, 1) within the first 2-3 years after diagnosis or symptom onset, 2) for patients who had equal to or fewer than five endoscopic procedures, and 3) for patients who have not yet required opioid analgesics for medical pain treatment.

Current evidence suggests that the first step for the management of pain relapse should be exclusion of obstructing stones or strictured anastomosis via imaging, followed by a limited number endoscopic interventions, and early consideration of resurgery to achieve pain control.

2015 American Gastroenterological Association guidelines

The American Gastroenterological Association (AGA) recommends the following in the diagnosis and management of asymptomatic neoplastic pancreatic cysts[16] :

  • For asymptomatic mucinous cysts, a 2-year interval is recommended for a cyst of any size undergoing surveillance, with surveillance being stopped after 5 years if there is no change.

  • Perform surgery only if there is more than one concerning feature on MRI confirmed on endoscopic ultrasonography (EUS) and only in centers with high volumes of pancreatic surgery, and there should be no surveillance after surgery if there is no invasive cancer or dysplasia.

  • The risk of malignant transformation of pancreatic cysts is approximately 0.24% per year, and the risk of cancer in cysts without a significant change over a 5-year period is likely to be lower.

  • The small risk of malignant progression in stable cysts is likely to be outweighed by the cost of surveillance and the risks of surgery.

  • Positive cytology on EUS-guided fine-needle aspiration (FNA) has the highest specificity for diagnosing malignancy; if there is a combination of high-risk features on imaging, then this is likely to increase the risk of malignancy even further. Similarly, if a cyst has both a solid component and a dilated pancreatic duct (confirmed on both EUS and MRI), the specificity for malignancy is likely to be high even in the absence of a positive cytology.

  • There is lower immediate postoperative mortality, as well as long-term mortality, for patients who undergo surgery in high-volume pancreatic centers.

  • It seems sensible to offer screening even after the cyst has been resected, provided the patients have not undergone total pancreatectomy. Surveillance should continue as long as the patient remains a good candidate for surgery. MRI every 2 years may be a reasonable approach for these patients. The clinician may elect to offer more frequent surveillance in the case of invasive cancer resection, particularly if there is concern that the lesion has not been fully resected.

 

Medication

Medication Summary

No curative treatment for chronic pancreatitis exists. Medical therapy is determined primarily by symptoms. If no anatomic explanation for abdominal pain can be found, medical therapy can be attempted. This therapy includes pain control with analgesic agents and a trial of noncoated pancreatic enzymes.

The use of exogenous pancreatic enzymes to reduce pain is linked to the hypothesis that pancreatic stimulation by food causes pain. Cholecystokinin (CCK) is one of the possible mediators of this response.

Analgesics, Other

Class Summary

Initial therapy consists of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). For severe, refractory pain, narcotic analgesics often are required, starting with the least potent agents and progressing to more potent formulations as necessary.

Acetaminophen (Acephen, Cefotan, Mapap, Tylenol, FeverAll, Aspirin Free Anacin)

Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs, those with upper GI disease, and those who are taking oral anticoagulants.

Opioid Analgesics

Class Summary

These medications provide control of moderate to severe pain.

Hydrocodone and acetaminophen (Vicodin, Lorcet, Lortab, Norco, Zolvit)

This drug combination is indicated for moderate to severe pain.

Acetaminophen with codeine (Tylenol-3)

This drug combination is indicated for treatment of mild to moderate pain.

Tramadol (Ultram, Ryzolt)

Tramadol inhibits the ascending pain pathways, altering the perception of and response to pain. It also inhibits the reuptake of norepinephrine and serotonin.

Nonsteroidal Anti-Inflammatory Drugs

Class Summary

NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Naproxen (Naprosyn, Aleve, Naprelan, Anaprox)

Naproxen is indicated for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease in prostaglandin synthesis.

Diclofenac (Voltaren, Cataflam, Cambia, Zipsor)

These NSAIDs inhibit prostaglandin synthesis by decreasing cyclooxygenase activity and by decreasing the formation of prostaglandin precursors.

Ketorolac

Ketorolac is an intravenously administered NSAID and a very powerful analgesic. It inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors. In turn, this results in reduced inflammation.

Ibuprofen (Advil, Motrin, Caldolor)

Ibuprofen is usually the drug of choice for the treatment of mild to moderate pain, if no contraindications exist. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase, resulting in inhibition of prostaglandin synthesis.

Celecoxib (Celebrex)

Celecoxib inhibits primarily cyclooxygenase-2 (COX-2). COX-2 is considered an inducible isoenzyme; it is induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, celecoxib does not inhibit the COX-1 isoenzyme; thus, GI toxicity may be decreased. The increased cost of celecoxib must be weighed against the benefit of avoidance of GI bleeds. Seek the lowest dose of celecoxib for each patient.

Hormones

Class Summary

Hormones can be used for the reduction of pancreatic exocrine secretion.

Octreotide (Sandostatin)

Octreotide has an 8 ̶ amino acid sequence containing the active portion of somatostatin. In a study, subcutaneous injection of octreotide 3 times daily at 200mcg provided pain relief in 66% of patients. Note that 35% of the control group also experienced pain relief.

Antidepressants, TCAs

Class Summary

In addition to alleviating coexistent depression, tricyclic antidepressants may ameliorate pain and potentiate the effects of opiates.

Amitriptyline hydrochloride

This agent is an analgesic for certain chronic and neuropathic pain.

Clomipramine (Anafranil)

Clomipramine is a dibenzazepine compound belonging to the family of TCAs. The drug inhibits the membrane pump mechanism responsible for the uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.

Clomipramine affects serotonin uptake while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine. It is believed that these actions are responsible for its antidepressant activity.

Doxepin (Silenor)

Doxepin increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. It inhibits histamine and acetylcholine activity and has proven useful in the treatment of various forms of depression associated with chronic pain.

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

Desipramine (Norpramin)

This is the original TCA used for depression. These agents have been suggested to act by inhibiting the reuptake of noradrenaline at synapses in the central descending pain-modulating pathways located in the brainstem and spinal cord.

Pancreatic Enzyme Supplements

Class Summary

These are used as dietary supplementation to aid digestion in patients with pancreatic enzyme deficiency. Several preparations are available. The aim is to provide at least 30,000 units of lipase. Because the cost of different preparations is variable, consider the unit price of the enzyme supplement based on the lipase content.

Uncoated pancrelipase is used to treat painful chronic pancreatitis based on the following rationale. Serum CCK levels are higher in patients with severe chronic pancreatitis, ductal or parenchymal hypertension is believed to cause pain, increased CCK levels stimulate pancreatic secretion (which increases ductal hypertension and exacerbates pain), and exogenous pancreatic enzyme supplements trigger a negative feedback inhibition.

Pancrelipase (Creon, Pancreaze, Ultresa, Viokace, Zenpep)

Pancrelipase assists in the digestion of protein, starch, and fat. Nonenteric-coated products are used for pain caused by pancreatitis (ie, Viokace) in combination with a proton pump inhibitor. The enteric-coated products may be used for the restoration of digestion and absorption.

 

Questions & Answers

Overview

What is chronic pancreatitis?

What are the signs and symptoms of chronic pancreatitis?

How is chronic pancreatitis diagnosed?

What is the role of imaging in the diagnosis of chronic pancreatitis?

What is the role of ERCP and MRCP in the diagnosis of chronic pancreatitis?

What are endosonographic findings suggestive of chronic pancreatitis?

How is treatment for chronic pancreatitis directed?

What is the role of pancreatic enzyme supplementation in the treatment of chronic pancreatitis?

What is the role of celiac ganglion blockade the treatment of chronic pancreatitis?

What is the role of endoscopic therapy in the treatment of chronic pancreatitis?

What are the surgical options for treatment of chronic pancreatitis?

What is chronic pancreatitis?

What is the appearance of chronic pancreatitis on imaging?

How does chronic pancreatitis differ from acute pancreatitis?

What is the clinical presentation of chronic pancreatitis?

Where can patient education information be found for chronic pancreatitis?

What is the pathophysiology of chronic pancreatitis?

What are the possible mechanisms in the pathogenesis of chronic pancreatitis?

What are the clinical characteristics of autoimmune pancreatitis?

What is the relationship between pancreatic stone formation and chronic pancreatitis?

What is the most common cause of chronic pancreatitis?

What is the role of alcohol in the pathogenesis of chronic pancreatitis?

What is the role of lithostathine in the etiology of chronic pancreatitis?

What is the role of ethanol in the etiology of chronic pancreatitis?

What is the role of genetics in the etiology of chronic pancreatitis?

Which hereditary disorders cause chronic pancreatitis?

What is the role of cystic fibrosis (CF) in the etiology of chronic pancreatitis?

What are possible causes of idiopathic chronic pancreatitis?

What is the role of congenital abnormalities in the etiology of chronic pancreatitis?

What is the cause of acquired obstructive chronic pancreatitis?

What are less common causes of chronic pancreatitis?

What is the incidence of chronic pancreatitis in the US?

What is the global incidence of chronic pancreatitis?

What are the racial predilections for chronic pancreatitis?

How does the incidence of chronic pancreatitis vary by sex?

How does the incidence of chronic pancreatitis vary by age?

What are prognostic factors associated with chronic pancreatitis?

What are the survival and mortality rates for chronic pancreatitis?

What are common complications of chronic pancreatitis?

What is a pseudocyst in chronic pancreatitis?

What causes pseudocysts in chronic pancreatitis?

What causes pseudoaneurysm in chronic pancreatitis?

What causes ascites and pleural effusion in chronic pancreatitis?

What are the indications for drainage of pseudocysts in chronic pancreatitis?

What causes bile and duodenal obstruction in chronic pancreatitis?

What are less common complications of chronic pancreatitis?

Presentation

What is the typical presenting symptom of chronic pancreatitis?

What are the clinical signs of chronic pancreatitis?

What is the natural history of pain in chronic pancreatitis?

Other than pain, what are the symptoms of chronic pancreatitis?

Which physical findings suggest chronic pancreatitis?

What is included in the physical exam for chronic pancreatitis?

DDX

How are cystic neoplasms differentiated from chronic pancreatitis?

What are the differential diagnoses for Chronic Pancreatitis?

Workup

What is included in the workup of chronic pancreatitis?

What is the role of blood tests in the evaluation of chronic pancreatitis?

What is the role of fecal tests in the diagnosis of chronic pancreatitis?

What is the role of pancreatic function tests in the diagnosis of chronic pancreatitis?

What is the role of duodenal aspirates in the diagnosis of chronic pancreatitis?

How is pancreatic juice tested in the evaluation of chronic pancreatitis?

Which noninvasive pancreatic function tests are used in the diagnosis of chronic pancreatitis?

What are the hallmarks of chronic pancreatitis on imaging studies?

What is the role of abdominal radiography in the diagnosis of chronic pancreatitis?

What is the role of CT scanning in the diagnosis of chronic pancreatitis?

What is the role of ERCP in the diagnosis of chronic pancreatitis?

What is the role of pancreatograms in the diagnosis of chronic pancreatitis?

What are the limitations of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of chronic pancreatitis?

What is the role of magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of chronic pancreatitis?

What is the limitation of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis?

What are the endoscopic ultrasonography (EUS) criteria for diagnosis of chronic pancreatitis?

Which histologic findings are characteristic of the early stages of chronic pancreatitis?

Which histologic changes suggest chronic pancreatitis?

Treatment

What are the goals of medical treatment for chronic pancreatitis?

What are the treatment options in the early stages of chronic pancreatitis?

What determines the need for hospitalization to treat chronic pancreatitis?

What is included in inpatient treatment of mild chronic pancreatitis?

When is ICU treatment indicated for chronic pancreatitis?

What are anatomical complications of chronic pancreatitis?

What are intervention options for the treatment of chronic pancreatitis?

How is percutaneous drainage performed in the treatment of chronic pancreatitis?

Which specialist consultations are needed for the treatment of chronic pancreatitis?

Which lifestyle changes are indicated for the treatments of chronic pancreatitis?

What are sources of pain in chronic pancreatitis?

How is pain managed in chronic pancreatitis?

What is the role of exogenous pancreatic enzymes in the treatment of chronic pancreatitis?

What is the role of cholecystokinin (CCK) releasing factor (CRF) in the treatment of chronic pancreatitis?

How do exogenous pancreatic enzymes relive pain in chronic pancreatitis?

What are the benefits of the exogenous pancreatic enzymes for treatment of chronic pancreatitis?

What is the role of celiac ganglion blockade in the treatment of chronic pancreatitis?

What is the benefit of a reduced fat intake in the treatment of chronic pancreatitis?

What is the role of triglycerides in the treatment of chronic pancreatitis?

What is the role of enteric-coated agents for the treatment of chronic pancreatitis?

What are the most serious adverse effects of enteric-coated agents for the treatment of chronic pancreatitis?

What is the role of vitamin B-12 in the treatment of chronic pancreatitis?

What is the goal of endoscopic therapy for chronic pancreatitis?

What are the benefits of endoscopic treatment of chronic pancreatitis?

What is the efficacy of endoscopic therapy for chronic pancreatitis?

When is endoscopic therapy beneficial in the treatment of chronic pancreatitis?

How is papillary stenosis in chronic pancreatitis?

How are pancreatic duct strictures treated in patients with chronic pancreatitis?

How are pancreatic duct stones treated in patients with chronic pancreatitis?

How are pancreatic pseudocysts treated in patients with chronic pancreatitis?

How are noncommunicating pseudocysts treated in patients with chronic pancreatitis?

What is the basis for selection of surgery in chronic pancreatitis?

How is pancreatic duct drainage performed in the treatment of chronic pancreatitis?

What is the role of pancreatic resection in patients with chronic pancreatitis?

What is the efficacy of total pancreatectomy for the treatment of chronic pancreatitis?

What is the recommended diet for patients with chronic pancreatitis?

Guidelines

What are the guidelines on the diagnosis and management of chronic pancreatitis?

Medications

What is the curative treatment for chronic pancreatitis?

How do exogenous pancreatic enzymes reduce pain in chronic pancreatitis?

Which medications in the drug class Pancreatic Enzyme Supplements are used in the treatment of Chronic Pancreatitis?

Which medications in the drug class Antidepressants, TCAs are used in the treatment of Chronic Pancreatitis?

Which medications in the drug class Hormones are used in the treatment of Chronic Pancreatitis?

Which medications in the drug class Nonsteroidal Anti-Inflammatory Drugs are used in the treatment of Chronic Pancreatitis?

Which medications in the drug class Opioid Analgesics are used in the treatment of Chronic Pancreatitis?

Which medications in the drug class Analgesics, Other are used in the treatment of Chronic Pancreatitis?