Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually leads to impairment of both exocrine and endocrine functions of the pancreas.
Specific risk factors for CP include alcohol and smoking, genetics, and obstructive diseases. In 10-30% of patients, no identifiable causitive factor for CP is found.
The most common cause of chronic pancreatitis in Western societies is alcohol abuse and accounts for 50% of cases of CP in the United States.
However, a recent study found that moderate alcohol intake (less than 2 drinks per day) was protective against recurrent acute and CP.
An association between genetic variants of CLDN2 in alcoholic patients has been proposed as second risk factor in alcoholics. CLDN2 is an X-linked gene that encodes the protein Claudin-2, which is highly expressed by pancreatic acinar cells during stressful conditions, and may contribute to pathologic inflammation of CP.31
The most common symptom of CP is abdominal pain, usually epigastric, dull and constant in nature. It is almost always localized in the upper half of the abdomen and radiates directly through to the back, or laterally around to the left or right flank. Initially the duration of pain ranges from several hours to several days, but as the disease progresses the attacks become more frequent and pain-free intervals shrink. However, pain can be absent in CP and patients present with steatorrhea, weight loss and diabetes caused by exocrine or endocrine insufficiency.
Less common initial presentations include biliary obstruction with recurrent episodes of mild jaundice, cholangitis, or vague attacks of indigestion. Obstruction of the splenic vein by an inflamed tail of the pancreas can lead to left-sided portal hypertension, gastric varices and GI bleeding. Chronic pancreatitis and pancreatic cancer may present in a similar manner, making it difficult to distinguish between them.
A diagnosis of chronic pancreatitis is difficult to establish, especially in the early stages of disease. Typical symptoms such as weight loss, pain, steatorrhea, and malnutrition are vague and nonspecific. The diagnosis of CP is based on a combination of clinical history, risk factors, imaging, endoscopy, and pancreatic function testing.
Various imaging modalities are used to diagnose CP including endoscopic ultrasound (EUS), computerized tomography (CT) scan, and magnetic resonance imaging (MRI). Pancreatic calcifications are pathognomonic for severe CP and are located exclusively in the ductal system. The diagnosis of advanced CP is usually straightforward; however, the diagnosis of early, mild, non-calcific, or minimal change CP is challenging. The accurate diagnosis of CP in its early stages remains difficult for many reasons, including an inability to differentiate pancreatic versus nonpancreatic chronic upper abdominal, the lack of consensus on the degree of histological changes needed to diagnose chronic pancreatitis, and the fact that advanced imaging (EUS and secretin-stimulated magnetic resonance cholangiopancreatography) and endoscopic pancreatic function tests can be abnormal in asymptomatic patients who are older, obese, smoke, and/or use alcohol.
(See the images of chronic pancreatitis below.)
Chronic pancreatitis. Nonenhanced axial CT scan through the pancreas shows granular calcification in the pancreas, associated with a 4-cm pseudocyst to the right of the head of the pancreas.
Chronic pancreatitis. Transverse sonogram shows an echogenic, enlarged pancreas with multiple small hyperechoic nonshadowing foci in the pancreas.
Distinct classification systems have been developed for CP, but only the Toxic/metabolic, Idiopathic, Genetic, Autoimmune, Recurrent acute pancreatitis, and Obstructive (TIGAR-O) and the M-ANNHEIM classification systems take the etiology of CP into account.
In the TIGAR-O system, the major risk factors for the development of chronic pancreatitis are categorized as follows:
T: toxic-metabolic (e.g. alcohol)
I: idiopathic (cystic fibrosis must be ruled out in these patients before diagnosis is made)
G: genetic (more commonly seen in the pediatric population)
O: obstructive (e.g. choledocholithiasis, pancreatic head tumour)
In the M-ANNHEIM system, the stage, severity and clinical findings of CP are integrated. The M-ANNHEIM system is the only one offering a severity index and is used accordingly. After a complex procedure, a score of between 0–25, representing the severity of CP, is calculated.
Chronic pancreatitis can also be classified into 3 categories:
Chronic calcifying pancreatitis
Chronic obstructive pancreatitis
Chronic inflammatory pancreatitis
Chronic calcifying pancreatitis
Chronic calcifying pancreatitis is invariably related to alcoholism. The earliest finding is precipitation of proteinaceous material in the pancreatic ducts that forms protein plugs that subsequently calcify. The ducts and lobules are initially involved in a random manner, and they are surrounded by normal parenchymal tissue. However, as the disease progresses, these normal areas become more diffuse. The pancreatic ductal epithelium undergoes atrophy, hyperplasia, and metaplasia at the site of the protein plugs. Many of the small pancreatic ductules dilate, while others are obliterated by fibrosis.
The main pancreatic duct shows a chain-of-lakes appearance due to alternating stenoses and dilatation. In approximately 50% of patients with chronic calcific pancreatitis, the pancreatic parenchyma contains cysts of varying sizes (several millimeters to 5 cm). These cysts are lined by cuboidal epithelium and contain pancreatic enzymes. Peripancreatic fibrosis is usually a late finding that involves the portal and/or splenic veins. Peripancreatic fibrosis causes stenosis or occlusion of retroperitoneal lymph channels. Ascites may complicate chronic calcific pancreatitis as a result of portal hypertension or lymphatic obstruction in 1-2% patients.
Chronic obstructive pancreatitis
In chronic obstructive pancreatitis, the prominent histologic changes are periductal fibrosis and subsequent ductal dilatation. These changes are much more focal than those in the other forms, and in most patients, the changes involve only the portion of the pancreas in which ductal drainage is impaired. Diffuse changes may occur, in which the main pancreatic duct or ampulla is obstructed. Although protein inspissation may occur, histologic changes in the ductal mucosa are less common, and calcification is unusual. Moreover, the pancreatic duct is dilated, and the pancreas is normal in size, atrophic, or focally and/or globally enlarged. A variety of factors are implicated in chronic obstructive pancreatitis; these include ductal obstruction due to ampullary stenosis, inflammatory or neoplastic causes, surgical ductal ligation, and fibrosis due to a pseudocyst as a complication of an episode of acute pancreatitis.
Chronic inflammatory pancreatitis
Chronic inflammatory pancreatitis is rare and can affect elderly persons without a previous history of alcohol excess.
Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis characterized clinically by frequent presentation with obstructive jaundice with or without a pancreatic mass, histologically by a lymphoplasmacytic infiltrate and fibrosis, and therapeutically by a dramatic response to steroids. The International Consensus Diagnostic Criteria (ICDC) for AIP has proposed two distinctive type of AIP, type 1 and type 2.
Type 1 AIP is believed to be the pancreatic manifestation of an IgG4 related systematic disease and is often accompanied with some extrapancreatic lesions, such as sclerosing cholangitis, sclerosing sialadenitis, and retroperitoneal fibrosis. This type of AIP usually presents with obstructive jaundice in elderly male subjects and responds well to steroid therapy.
Type 1 and 2 share some features in histopathology, such as periductal lymphoplasmacytic infiltration and storiform fibrosis. Type 2 has no or few IgG4-positive cells and seems to be a pancreatic-specific disorder and is not associated with other organ involvement. Patients with type 2 are often a decade younger and do no show gender preference.
The diagnosis of AIP depends on serum IgG4 concentration, pancreatic histology, pancreatic parenchymal and duct imaging, other organ involvement, and steroid reaction.
Endoscopic retrograde cholangiopancreatography (ERCP) provides the most accurate visualization of the pancreatic ductal system and is considered the gold standard for diagnosing chronic pancreatitis. It combines the use of endoscopy and fluoroscopy to visualize and treat problems of the biliary and pancreatic ducts.
ERCP is considered a sensitive test for the diagnosis of chronic pancreatitis, having the ability to show dilation or stricture of the pancreatic duct and its branches, as well as early features of chronic pancreatitis. ERCP provides therapeutic options, such as dilation, stone extraction, and stenting of the duct. An additional benefit is the possibility of procuring pancreatic juice during ERCP.
However, ERCP is invasive, expensive, and time consuming and can only evaluate for ductal changes. The use of ERCP is generally reserved for patients in whom the diagnosis remains inconclusive despite pancreatic function testing CT/MRI or EUS.
Angiography is reserved for patients with suspected complications resulting from chronic pancreatitis.
Ultrasonography is the first modality to be used in patients presenting with upper abdominal pain, although the direct diagnosis of chronic pancreatitis is not always possible. Sonography can help in determining the cause of chronic pancreatitis (eg, alcoholic liver disease, calculus disease) and in assessing the complications of the disease (eg, pseudocysts, ascites, splenic/portal venous obstruction).
Endoscopic ultrasound (EUS) is an important imaging modality to detect early morphologic changes in CP. It can detect mild parenchymal and ductal changes not seen on CT scan, and can be used when CT and MR imaging are non-diagnostic. The most predictive endosonographic feature of chronic pancreatitis is the presence of stones.
The Rosemont classification system is designed to standardize the endosonographic assessment of CP and categorize patients undergoing endosonography by the likelihood of having CP on the basis of particular EUS criteria. Major criteria include hyperechoic foci with shadowing and main pancreatic duct calculi, and lobularity with honeycombing. Minor criteria include cysts, dilated ducts ≥3.5 mm, irregular pancreatic duct contour, dilated side branches ≥1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules. However, these criteria for predicting prognosis and outcome of therapy in patients with chronic pancreatitis is unknown.
EUS, in which the probe can approach the pancreas, is capable of yielding high-resolution visualization of abnormal pancreatic parenchyma and the pancreatic duct that may not be possible with other modalities. Although EUS can detect subtle changes that cannot be detected by other diagnostic imaging modalities, interpretation of the results can be challenging, particularly in early CP, in which interpretation is dependent on examiners and may result in false positives.
One of the greatest limitations in using EUS is the low interobserver agreement. Studies show good agreement in two features, duct dilatation (κ = 0.6) and lobularity (κ = 0.51), but low agreement for the other seven features (κ< 0.4) .
Magnetic resonance cholangiopancreatography (MRCP) and MRI have also been used to diagnose CP and have the advantage of no radiation exposure. Moreover, MRI has the advantage of detecting both parenchymal and ductal changes.
The use of secretin-stimulated magnetic resonance cholangiopancreatography (s-MRCP) can demonstrate pancreatic exocrine reserve, as well as a “santorinocele” (ie, a dilated Santorini duct seen in pancreas divisum).
For the diagnosis of early CP, s-MRCP has a sensitivity of 77% and specificity of 83%.
CT is a widely-used imaging modality and while diagnosis of early chronic pancreatitis is not reliable, CT should nevertheless be performed in all patients to exclude a mass or gastro-intestinal malignancy. It is excellent for imaging of the retroperitoneum, and it is useful in differentiating chronic pancreatitis from pancreatic carcinoma.
In addition, CT may be used in the assessment of chronic pancreatitis-related complications, such as pseudocysts, pseudoaneurysm and duodenal stenosis. Overall, CT remains the best screening tool for detection of chronic pancreatitis and exclusion of other intra-abdominal pathology that may be indistinguishable from chronic pancreatitis based on clinical symptoms.
EUS, ERCP, MRI and CT all have comparable high diagnostic accuracy in the initial diagnosis of chronic pancreatitis. EUS and ERCP are outperformers and US has the lowest accuracy. The choice of imaging can be made based on clinical considerations.
Limitations of techniques
On anteroposterior radiographs, the spine may mask small punctate calcifications; therefore, the acquisition of additional oblique or lateral imaging may be indicated.
On sonograms, the pancreas may appear normal even in the presence of advanced disease. In patients who are obese, excessive intraperitoneal gas may obscure the pancreas. Gas overlying the pancreas also can make visualization of the pancreas difficult.
Chronic pancreatitis and pancreatic carcinoma share many features on CT, which makes differentiation difficult. Further, it can be challenging and sometimes impossible to differentiate between the two conditions on US. Gerstenmaier and Malone proposed a diagnostic algorithm based on Bayesian analysis and recommended EUS and fine needle aspiration as next steps when a mass is detected on US or CT.
An understanding of pancreatic anatomy is important in delineating the cross-sectional anatomy of the pancreas and the causation of pain in pancreatic disease. The pancreas varies in shape and lies in the anterior pararenal space. The head of the pancreas lies within the curve of the duodenal loop, and the inferior vena cava and right renal vessels lie posteriorly. The common bile duct receives the main pancreatic duct as it passes through the pancreatic head and then drains into the duodenum at the ampulla.
The gastroduodenal artery may be seen anteriorly at the pancreatic head and neck. The head of the pancreas is the most bulbous part of the gland, which then narrows to the neck. The union of the superior mesenteric and splenic veins, which forms the portal vein posteriorly, marks the anatomic position of the pancreatic neck. The pylorus lies anteriorly. The lesser sac lies anterior to the pancreas, whereas the splenic vein runs along its posterosuperior surface. The tail of the pancreas is related to the spleen, left adrenal gland, and upper pole of the left kidney.
Sonograms of the pancreas typically demonstrate a homogeneous echo pattern, and the pancreas is more echogenic than the liver. The pancreatic head measures 2.5-3.5 cm; the body, 1.75-2.5 cm; and the tail, 1.5-3.5 cm. The size of the pancreas varies considerably; therefore, reliance on size alone can lead to diagnostic errors. Generally, the size of the gland decreases with patient age, while echogenicity increases. The pancreas is more echogenic than the liver in 52% of young adults and equally echogenic in 48%. With the use of modern ultrasonographic machines, the main pancreatic duct can be identified in 85% of patients. On sonograms, the normal duct diameter is 1.3 mm ± 0.3. In patients with gallstones, the average diameter is 1.4 mm.
The typical criteria for pancreatic size on CT scans are the following: the head is 23 mm; neck, 19 mm; body, 20 mm; and tail, 15 mm. By using optimal CT techniques, the pancreatic duct can be identified in just more than 50% of the patients. Normally, the pancreatic diameters demonstrated on CT scans vary from 2-4 mm, but the effect of pixel averaging on normal pancreatic duct measurements is significant and can make such measurements unreliable. Errors of 1 or 2 mm may occur.
In most patients, a normal pancreatic duct is seen on images obtained with T2-weighted short-tau inversion recovery MRI sequences and magnetic resonance cholangiopancreatography (MRCP).
Chronic pancreatitis imaging guidelines
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 and include the following
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.
The 2017 United European Gastroenterology guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU) include the following key imaging recommendations
There is no preferred classification system for defining the etiology of CP since the available classification systems have not been evaluated in randomized prospective trials with endpoints of morbidity and mortality.
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.
The use of IV secretin increases the diagnostic potential of MRCP in the evaluation of patients with known/suspected CP.
Duodenal filling (DF) during secretin-stimulated MRCP does not help to evaluate the grade of severity of CP.
Abdominal ultrasonography can only be used to diagnose CP at an advanced stage.
Ultrasonography can be used in patients with suspected CP complications
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 has a potential role in the follow-up of patients with CP in the detection of complications, mainly due to its ability in detecting pancreatic malignancy.
EUS-guided fine needle biopsy can be considered as the most reliable procedure for detecting malignancy.
For patient education information, see the Liver, Gallbladder, and Pancreas Center, as well as Pancreatitis.