Keywords
alcohol-induced pancreatitis - alcoholic pancreatitis - binge pancreatitis - fatty
acid ethyl esters - high-intensity drinking - pancreatic stellate cells
Introduction
Acute pancreatitis (AP) is a necroinflammatory disorder of the exocrine pancreas,
potentially leading to fibrosis and chronic pancreatitis. Alcohol abuse is the leading
cause of both acute and chronic pancreatitis in the United States.[1] Alcohol accounts for nearly one-third of AP cases in the United States.[2] Chronic alcohol consumption is the second most common cause of AP after gallstones,
accounting for 17 to 25% of cases.[3] In the United States, the annual incidence of AP is estimated to be approximately
40/100,000 persons, making it a significant cause of hospital admissions.[4] The incidence is proportionally highest in males between 35 and 54 years old. Although
a single episode of alcohol consumption can induce alcohol-related AP, chronic consumption
is a major risk factor for the development of pancreatitis. The single most common
etiology of chronic pancreatitis (CP) is alcohol-induced CP (ACP), responsible for
up to 49.0% of cases.[5]
Research by Yang et al indicates a rise in AP diagnoses despite stable alcohol consumption
rates, suggesting drinking patterns as contributors.[6] Binge drinking episodes have increased since 1995, with alcohol consumption in the
week before symptom onset affecting AP severity. Alcoholic AP is strongly associated
with organ failure and pancreatic necrosis (PNEC), with higher mortality rates than
nonalcoholic AP. Patients with alcoholic pancreatitis have a 36% higher mortality
rate than the general population, with about half dying within 20 years postonset.[7] According to the Centers for Disease Control and Prevention, alcohol-related deaths
have increased over the past 20 years. It has been reported that alcohol-related death
numbers increased by 25.5% between 2019 and 2020, the first year of the pandemic.[8]
AP manifests in various ways, including acute attacks, PNEC, recurrent episodes, and
eventual progression to CP. Smoking alongside heavy alcohol use increases the risk
of malignancy.[9] Pathophysiological mechanisms involve premature enzyme activation, protein plug
formation, acinar cell damage from alcohol byproducts, and stellate cell-induced fibrosis.[10]
[11] Smoking can be an additional trigger for pancreatic injury.[12]
Pathophysiology of Alcohol-Related Acute and Chronic Pancreatitis
Pathophysiology of Alcohol-Related Acute and Chronic Pancreatitis
According to the American College of Gastroenterology guidelines, alcohol can be considered
to be the cause of AP, only if a patient has a history of over 5 years of heavy alcohol
consumption (> 50 g/per day).[13] The risk of developing pancreatic injury/pancreatitis appears to be directly proportional
to the amount and duration of alcohol intake.[14] Since only 5% alcoholics develop pancreatitis, a search for additional insult (trigger)
or individual susceptibility is being explored like genetic and metabolic factors.[15] Complete pathophysiology is not fully understood. More recent evidence suggests
that combination of remote events like increased gut permeability to bacterial products
such as lipopolysaccharide and more proximal effects like altered pancreatic cholinergic
inputs and direct toxic effects of alcohol or the products of its metabolism play
a major role in alcoholic pancreatitis.[14]
[16] The major sites of alcohol-induced injury are acinar cells, pancreatic stellate
cells, and small ducts.
Pancreatic Acinar Cell and Function
Pancreatic Acinar Cell and Function
The pancreatic acinar cell is a major functional unit of the exocrine pancreas.[17] It is a highly specialized structure developed for synthesis, storage, and secretion
of digestive enzymes.[18] To protect it from digesting itself, the enzymes are synthesized as inactive precursors
(zymogens). These are secreted into small ducts, leading into the main pancreatic
duct (MPD). Under normal physiological conditions, digestive enzymes are activated
only once they have reached the duodenum.[17]
Alcohol Metabolism and Its Effect on the Pancreas
Alcohol Metabolism and Its Effect on the Pancreas
Pancreatic Acinar Cells
Alcohol metabolism in the pancreas induces acinar cell toxicity and triggers inflammation.
Chronic alcohol intake leads to enzyme activation within cells, increasing the risk
of autodigestive damage.[15] Metabolism generates acetaldehyde, acetate, and reactive oxygen species, while nonoxidative
pathways produce fatty acid ethyl esters (FAEEs). These metabolites disrupt intracellular
processes, causing mitochondrial dysfunction, impaired autophagy, and cell death.[19] Elevated FAEE levels contribute to sustained calcium elevations and acinar cell
injury. Necrotic cell death exacerbates inflammation, worsening pancreatic injury.
Alcohol also affects pancreatic ducts by reducing secretions, increasing viscosity,
and forming protein plugs, potentially leading to ductal blockage and calcification.[7]
Pancreatic Stellate Cells
Pancreatic stellate cells (PSCs) are key in pancreatic fibrogenesis and remodeling.[20] They are activated by alcohol, its metabolites, and cytokines released during alcohol-induced
pancreatic necroinflammation. Activated PSCs transform into myofibroblast-like cells,
triggering inflammatory responses and releasing excessive extracellular matrix proteins,
which create a proinflammatory microenvironment that promotes pancreatic fibrosis.[11] PSCs also play a role in regeneration after necrotizing pancreatitis. [Table 1] and [Flowchart 1] show the changes happening.
Table 1
Various events seen at the microscopic level in the pancreatic gland
|
Key sites of injury and events
|
|
Acinar cell
|
Duct level
|
Stellate cell activation
|
|
Mitochondrial dysfunction
|
Increased viscosity of secretions
|
Conversion to myofibroblast-like cells
|
|
Decreased cellular NAD +/NADH balance
|
Precipitation and formation of protein plugs
|
Release of extracellular matrix proteins
|
|
Increased Ca2+ Levels
|
Calcification
|
Initiate pancreatic fibrosis
|
|
Premature activation of zymogens
|
|
|
|
Reduced ATP
ER stress
Altered autophagy
|
|
|
Abbreviations: ATP, adenosine triphosphate; ER, endoplasmic reticulum; NAD + , nicotinamide
adenine dinucleotide; NADH, nicotinamide adenine dinucleotide hydrogen.
Flowchart 1 Pathophysiology of alcoholic pancreatitis at cellular and ductal levels.
Natural History of Pancreatitis
Pancreatitis is clinically diagnosed by severe abdominal pain and elevated blood amylase
levels. The disease can progress from an initial AP event (sentinel acute pancreatitis
event hypothesis) to recurrent or chronic inflammation, leading to fibrosis.[21] A significant delay typically occurs between the start of heavy drinking and the
first manifestation of alcoholic pancreatitis, often requiring more than 80 g of alcohol
per day for 6 to 12 years.[22] Abstinence after the first episode can prevent recurrent attacks.[23]
Progression of Alcoholic Pancreatitis
After the first episode of alcoholic pancreatitis, 25 to 50% of patients develop acute
recurrent pancreatitis (ARP), with 42 to 80% of those progressing to ACP.[24] Mild initial attacks result in fewer long-term changes, but even a single episode
can cause chronic changes. A meta-analysis found a 10% prevalence of CP after an initial
acute episode, rising to 36% for those who experience recurrent AP (RAP).[25] The risk is higher among smokers, alcoholics, and men.[26]
[Flowchart 2] depicts the natural history of alcoholic pancreatitis and its progression to CP.
Flowchart 2 Natural history of alcoholic pancreatitis.
Drinking Pattern
A standard drink has been defined by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) as one that contains 14 g of pure alcohol (about 0.6 fluid oz or 1.2 tablespoons),
as is found in one 12-oz beer, one 5-oz glass of wine, or one 1.5-oz shot of distilled
spirits.[27]
[28]
Typically, alcohol use disorder (AUD) is a long-term pattern of alcohol use that becomes
difficult to control. However, the number of drinks a person consumes and the rate
at which they consume can influence the outcome. Episodic drinking can escalate the
blood alcohol content to dangerous, even life-threatening levels.
Though there is no seasonal association, it has been shown to increase significantly
during the holidays, including Christmas and New Year's.[29] Adolescents, although they may drink less often, tend to consume higher quantities
of alcohol on these occasions compared with adults.[30]
[31]
[32]
Binge Drinking
NIAAA defines binge drinking as a pattern of drinking that brings blood alcohol concentration
to 0.08 g per deciliter (0.08%) or higher. This typically occurs after a woman consumes
4 drinks or a man consumes 5 drinks in a 2-hour time frame.[33]
It is uncertain if and how much alcohol is necessary during a binge to induce an attack
of “AP” in persons with established or without chronic alcoholic pancreatitis, but
there is evidence that bingeing or acute withdrawal after bingeing precipitates an
attack.[34] Typically, and particularly in binge drinkers, an attack begins 12 to 48 hours after
cessation of drinking (“the afternoon after the night before”) ([Fig. 1]).
Fig. 1 Dual-energy computed tomography (CT) in a 27/M with acute alcohol-related necrotizing
pancreatitis due to binge drinking. (A) Noncontrast-enhanced CT (NECT) in axial plane done 72 hours after acute pain following
alcohol binge with a history of alcohol abuse, shows bulky pancreas (white arrowhead)
with heterogeneity. The white star represents peripancreatic edema. (B) Dual-energy iodine image (late arterial phase) showing multiple focal areas of lack
of iodine/enhancement (long white arrow). The short white arrow represents iodine/enhancement
in the intervening areas. (C) Contrast-enhanced CT (CECT) (portovenous phase) at the same level as B shows bulky
pancreas with multiple necrotic areas (white star) alternating with enhancing areas
(black star) corresponding to image B.
Multiple studies indicate that patients who develop alcohol-induced pancreatitis (ALP)
frequently report short-term heavy drinking or bingeing. In a Swedish study by Sadr
Azodi et al, it was found that there was a 52% increased risk of AP for every increment
of five standard drinks of spirits consumed on a single occasion.[35]
The risk of AP was associated with the amount of spirits consumed on a single occasion
but not with wine or beer consumption. In a multicenter prospective study done in
Munich during Oktoberfest, despite a sale of 6.6 million liters of beer in 16 days,
the incidence of acute attacks of alcoholic pancreatitis did not increase.[36]
Extreme Binge Drinking or High-Intensity Drinking
Research indicates that a substantial portion of binge drinkers often drink at levels
two or three times the binge threshold, resulting in high peak blood alcohol concentrations.
There is no common consensus, and is defined as at least twice the typical binge drinking
threshold (i.e., 10+ drinks) or twice the gender-specific binge threshold (i.e., 8+
for women/10+ for men).[37] High-intensity drinking is of particular concern because of the adverse consequences
associated with it ([Fig. 2]).
Fig. 2 Computed tomography (CT) in a 20/M with acute alcohol-related necrotizing pancreatitis
due to high-intensity drinking. (A) Contrast-enhanced CT (CECT) in axial plane shows bulky pancreas (P) and hypoenhancement of the parenchyma. No
definite necrotic areas could be identified. F represents peripancreatic acute fluid
collection. (B) CECT done at 1 week follow-up, shows necrosis of the entire body and tail with nonenhancement
(N). F represents peripancreatic acute fluid collections.
The causal relationship between single instances of high-intensity drinking in the
absence of chronic alcohol consumption and the onset of AP remains unclear. Cubillan
and Raphael documented a case of acute necrotizing pancreatitis following transcoronary
alcohol infusion during cardiac ablation for recurrent atrial fibrillation.[38] The patient reported lifelong abstinence from alcohol and tobacco use, with no other
identifiable cause of pancreatitis. Approximately 9 mL of pure alcohol was administered
during the procedure, equivalent to the blood alcohol level typically resulting from
8 to 9 drinks in an average man. Further investigation is required to corroborate
or refute this association.
Role of Imaging
There are no specific imaging features in the pancreatic gland to distinguish alcoholic
pancreatitis from other etiology. Diagnosis relies on a clinical history of chronic
alcohol use. Due to the lack of distinct imaging features, it is important to use
a comprehensive diagnostic approach, integrating clinical, laboratory, and imaging
data to accurately identify and manage alcoholic pancreatitis. Multiple imaging modalities
are available including ultrasound, computed tomography (CT) scan, magnetic resonance
imaging (MRI), and endoscopic ultrasound (EUS).
Ultrasound
Sonography in patients with AP plays a role in the initial evaluation of suspected
or confirmed AP.[39] However, it can be challenging due to difficulties in visualizing the pancreas caused
by ileus and bowel gas interference. Sick patients may not cooperate, further limiting
its role. Its primary role in imaging AP is limited to detecting cholelithiasis and
choledocholithiasis.
CT Scan
Contrast-enhanced CT (CECT) is the most used imaging modality for the diagnosis and
staging of AP.[40] CT can visualize characteristic findings like pancreatic enlargement, peripancreatic
inflammation, and fluid collection. CT is the most accurate to detect calcifications.
The protocol has been outlined in [Table 2].
Table 2
CT scan protocols to be used for evaluation of pancreatitis
|
CT scan protocol (64-slice scanner)
|
|
Sequence
|
Timing from tigger[a]
|
Purpose
|
|
NECT
|
|
Look for calcification
|
|
Portovenous phase
|
65 seconds
|
Look for contrast enhancement in the gland and vessels
|
|
Optional sequences
|
|
|
|
Early arterial phase
|
6 seconds
|
Suspected bleed
|
|
Late arterial phase
|
15 seconds
|
When you suspect necrosis or vascular complications
|
|
Dual energy (iodine image)
|
Can be used during late arterial or venous phase
|
When you suspect necrosis
|
Abbreviations: CT, computed tomography; NECT, noncontrast-enhanced computed tomography.
a Trigger is based on 100 HU achieved in the aorta after contrast injection for a 64-slice
CT scanner independent of the vendor.
MRI
MRI offers diagnostic capabilities similar to those of CT, with additional intrinsic
advantages including lack of ionizing radiation and exquisite soft tissue characterization.[41] MRI emerges as an alternative imaging modality in patients with severe renal dysfunction
during the acute phase. It has the added advantage of evaluating pancreatic and biliary
ductal systems. Magnetic resonance cholangiopancreatography (MRCP) and secretin MRCP
(S-MRCP) are especially useful in CP. It is superior to a CT scan in detecting a mild
form of pancreatitis than CECT.[42] The typical sequences used in MRI/MRCP have been outlined in [Table 3].
Table 3
MRI protocols to be used for evaluation of pancreatitis
|
MRI and MRCP sequences
|
|
T2W
|
Single-shot fast spin-echo/HASTE
|
|
MRCP
|
Thick-slab high TE T2-weighted half-Fourier RARE
Thin high-resolution high TE T2W 3D FS
|
|
T1W
|
DIXON
T1W FS
|
|
Diffusion
|
B 50-800 and ADC
|
|
Post-gadolinium
|
Dynamic T1W FS 3D gradient echo
Delayed 2D T1W FS axial
|
Abbreviations: 2D, two-dimensional; 3D, three-dimensional; ADC, apparent diffusion
coefficient; FS, fat-suppressed; MRCP, magnetic resonance cholangiopancreatography;
MRI, magnetic resonance imaging; T1W, T1-weighted; T2W, T2-weighted.
Mild Acute Pancreatitis
In 85% of patients, the inflammation is mild and self-limiting and typically resolves
within a week. The initial episode of alcoholic pancreatitis typically presents as
acute interstitial edematous pancreatitis, seen as an enlarged pancreas and peripancreatic
fat stranding and fluid on imaging.
On ultrasound, AP typically presents as an enlarged hypoechoic gland, with the ability
to visualize peripancreatic acute fluid collections. However, ultrasound imaging lacks
sensitivity in detecting necrosis.
On CT, the pancreas may appear enlarged and hypodense on the noncontrast images, usually
with diffuse involvement, although focal manifestations are occasionally observed
([Fig. 3]).
Fig. 3 Computed tomography (CT) in acute alcohol-related interstitial pancreatitis with
history of alcohol abuse. (A) Noncontrast-enhanced CT (NECT) in axial plane shows a bulky pancreas [P] with normal
density. White arrow is a gallstone in a partially distended, normal-looking gallbladder.
(B) Contrast-enhanced CT (CECT) at the same levels shows bulky and edematous pancreatitis
(P) with parenchymal enhancement. White star (*) represents peripancreatic fat stranding
and edema.
On MRI, T2-weighted images typically show an enlarged pancreas with hyperintensity.
T1-weighted images with fat suppression may exhibit normal signal intensity or more
hypointense. Peripancreatic fat stranding, a hallmark feature of AP, is optimally
visualized using T1 gradient-echo and T2 fat-suppressed sequences. Diffusion-weighted
imaging (DWI) shows greater diffusion restriction in AP patients compared to healthy
individuals.[43]
Upon administration of contrast agents, both CT and MRI typically demonstrate homogeneous
enhancement of the viable edematous parenchyma, albeit less intense than normal. However,
the presence of edema may induce slight heterogeneity in enhancement patterns.
Peripancreatic inflammation commonly manifests as peripancreatic fat stranding and
fluid accumulation. Acute peripancreatic fluid collections are typically unencapsulated
and conform to the contours of the peripancreatic fascial planes that envelop them.
These collections often exhibit spontaneous resolution, with approximately 5 to 15%
persisting beyond the initial 4 weeks and potentially progressing into pseudocysts.
These collections vary in size and shape, frequently clustering adjacent to the pancreas
and often occupying the lesser sac or anterior pararenal space. In some cases, collections
may extend to remote areas such as the pelvis or mediastinum.
Cross-sectional imaging, such as CT scans and MRI, reveal these collections as uniformly
fluid-filled with a lack of capsules. They typically appear hypodense on CT scans
and demonstrate T1 hypointensity and T2 hyperintensity on MRI.
Severe Acute Pancreatitis
Severe Acute Pancreatitis
Approximately 20% of patients develop severe AP, in which the mortality rate is much
higher due to complications from the systemic inflammatory reaction.[44]
The amount of alcohol consumed may be an important determinant of the severity of
the first alcoholic AP episode. Jaakkola et al found that in patients having their
first alcoholic AP episode, the reported 2-month alcohol consumption correlated significantly
with the number of positive Ranson criteria, the length of the hospital stay, and
more complications.[45]
In a study by Papachristou et al, alcohol consumption was identified as a significant
risk factor for the development of PNEC.[46] Necrotizing pancreatitis represents the severest form of AP with a high mortality
rate ranging from 15 to 30%,[47] due to complications from the systemic inflammatory reactions. Necrosis can present
in three configurations: combined PNEC and peri-PNEC (75%), peri-PNEC alone (20%),
and PNEC alone (< 5%). Patients with peri-PNEC alone have lower morbidity and mortality
rates. The various imaging findings are summarized in [Table 4].
Table 4
Multimodality imaging changes seen in acute pancreatitis
|
Imaging changes in acute pancreatitis
|
|
Acute interstitial pancreatitis
|
Acute necrotizing pancreatitis
|
Peripancreatic fat necrosis
|
|
Pancreas:
CT: Enlarged and hypodense on noncontrast
T2W: Enlarged and hyperintense
DWI: Restricted diffusion
Peripancreatic region:
- Peripancreatic fat stranding
- Acute peripancreatic fluid collections
|
NECT: The pancreas may appear heterogeneous and slightly hyperdense due to hemorrhage
MRI: T1W – hypointense Hyperintense if hemorrhage
MRI T2W: Heterogeneous
CECT/MR contrast: Nonenhancing regions and necrotic fluid collection later
Dual-energy CT:
Lack of iodine enhancement in necrotic areas
|
Mixed intensity depending on the degree of necrotic material
Hemorrhage can be differentiated
|
Abbreviations: CECT, contrast-enhanced computed tomography; CT, computed tomography;
DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; NECT, noncontrast-enhanced
computed tomography; T1W, T1-weighted; T2W, T2-weighted.
Necrotizing pancreatitis shares similarities with interstitial edematous pancreatitis,
but it presents additional findings indicative of necrosis. On noncontrast-enhanced
CT, the pancreas may exhibit hyperdensity or heterogeneity with hyperdense areas,
often attributed to hemorrhage. The process of PNEC evolves gradually and may not
become apparent until 72 hours to a week following the initial event. While imaging
is typically recommended after 72 hours, CT scans are frequently performed early in
cases of acute abdomen in the emergency room. In such scenarios, dual-energy CT scans
can aid in detecting ischemic regions at risk of necrosis using iodine imaging. The
iodine image shows reduced iodine uptake/enhancement in the area around the necrosis.[48]
Following the first week of presentation, areas of impaired perfusion and necrosis
mature, appearing as confluent nonenhancing regions on imaging. Peripancreatic fat
necrosis initially presents with a heterogeneous appearance on CECT, with later stages
revealing disintegrating fat more prominently ([Fig. 4]).
Fig. 4 Computed tomography (CT) in a 32 /M with acute alcohol-related necrotizing pancreatitis
with extrapancreatic fat necrosis with history of alcohol abuse. (A) Noncontrast-enhanced CT (NECT) in axial plane shows a bulky pancreas [white arrowhead]
and raised density in the distal body (black star). (B) Contrast-enhanced CT (CECT) at the same levels after a week shows necrosis in the
distal body (black star), corresponding to A. Peripancreatic fluid in relation to
the distal body has increased and now shows fat necrosis (white arrow). White arrowhead
shows normal enhancement in the proximal body of pancreas.
Out-of-phase T1-weighted imaging can demonstrate peripancreatic fat necrosis by eliciting
a signal drop. On MRI, necrotic parenchyma or peripancreatic tissue is hypointense
on T1-weighted images and nonenhancing on gadolinium-enhanced T1-weighted imaging.
On T2-weighted images, necrotic tissue is typically hypointense, though it can be
hyperintense if liquefied. Abnormal hyperintensity on T1-weighted fat-suppressed images
corresponds to hemorrhage, necrosis, and is usually associated with an extremely poor
prognosis ([Fig. 5]).
Fig. 5 Magnetic resonance imaging (MRI) in a 50/M with acute alcohol-related necrotizing
pancreatitis and hemorrhage. (A) T2-weighted (T2W) fat-suppressed (FS) in axial plane shows a bulky pancreas with
hypointense areas in the body (white arrow). The black star represents peripancreatic
fluid. (B) T1W FS in axial plane shows hyperintense areas (white arrow), corresponding to the
hypointense areas in image A. (C) Diffusion-weighted imaging (DWI) in axial plane shows these areas to be heterogeneous
(white arrow). (D) Apparent diffusion coefficient (ADC) in axial plane shows these areas are hypointense
(white arrow).
Noncontrast MRI is superior to noncontrast CT for the detection of PNEC.[47] MRI can distinguish between necrotic pancreatic and peripancreatic tissues and adjacent
fluid collections or hemorrhage, whereas differentiating between necrosis and adjacent
fluid may be difficult with CT.
Persistent collections of fluid and necrotic material can develop in necrotizing pancreatitis
and should not be called fluid collections, but rather acute necrotic collections
or walled-off necrosis, because they contain solid necrotic material.[49] The necrotic collections can communicate with the pancreatic duct or may sometimes
rupture or have fistulous communication with the bowel.
Pancreatic Regeneration following Necrosis
Pancreatic Regeneration following Necrosis
The process of pancreatic regeneration is well-known after AP. After PNEC, the morphological
and functional regeneration is associated with the normalization of glycemia and the
exocrine function.[50]
In normal tissue, only a few stellate cells and myofibroblasts are present around
ducts and ductules. In contrast, numerous stellate cells and myofibroblasts are detected
after AP exhibiting increased proliferative activity and appear to participate in
regeneration.[20]
[Fig. 6] is a case involving the phenomenon of pancreatic regeneration following necrosis.
This intriguing aspect of the pancreas' capability to regenerate after experiencing
necrotic damage warrants further investigation and understanding in the medical community.
Fig. 6 Computed tomography (CT) showing pancreatic regeneration in alcohol-related necrotizing
pancreatitis. (A) Contrast-enhanced CT (CECT) in axial plane shows a lack of enhancement in a segment
of the pancreatic head (white star), consistent with pancreatic necrosis. (B) Follow up CECT done after a few weeks in the same patient shows an increase in areas
of parenchymal enhancement and reduction of necrotic area (white star). This is due
to parenchymal regeneration.
Acute Recurrent Pancreatitis
Acute Recurrent Pancreatitis
Clinically, ACP is a multifaceted disease characterized in most instances chronologically
by two phases, (1) an early stage of ARP, characterized by episodes of AP that occurs
on more than one occasion, due to continued drinking ([Fig. 7]), and (2) a late stage of CP, dominated by steatorrhea and diabetes pancreatic calcification.[51] In the clinical course, a phase comes, when patients develop early changes of CP
with pancreatic insufficiency. If the patient continues the alcohol abuse, the deterioration
can be marked with rapid progression to advanced changes.[52]
Fig. 7 Computed tomography (CT) in a 55/M with alcohol-related recurrent acute pancreatitis
(RAP), due to a continuous history of alcohol abuse. (A) Noncontrast-enhanced CT (NECT) in axial plane shows the pancreas of normal bulk
and enhancement but has peripancreatic fat stranding (white arrow) suggesting mild
acute pancreatitis. (B) Same patient reported to the emergency room (ER) after 6 years due to acute pancreatitis.
Contrast-enhanced CT (CECT) in axial plane shows necrotic regions with acute fluid
collections (white star).
Alcohol-Related Chronic Pancreatitis
Alcohol-Related Chronic Pancreatitis
ACP arises from multiple factors, with disease progression risk closely tied to the
continuation of alcohol and tobacco use.[24] Spicak et al, in their study, identified sociobehavioral factors influencing the
development of ACP, including early initiation of drinking and smoking, high alcohol
consumption at a young age, and lower educational attainment.[53]
Observations by Lankisch et al revealed that CP predominantly occurred in individuals
with a history of alcoholism, irrespective of the severity of the initial pancreatitis
episode or cessation of alcohol and nicotine intake.[54] Furthermore, they noted that 38% of patients developed CP within 2 years following
survival of a second pancreatitis attack, with smoking significantly heightening the
risk of progression from acute to chronic alcoholic pancreatitis.
Histologically, chronic alcoholic pancreatitis is characterized by fibrosis, chronic
inflammation, and acinar cell depletion. Early changes in CP are reversible but can
progress to irreversible and advanced stages. Notable features of established and
advanced CP include pancreatic atrophy, fibrosis, ductal distortion and strictures,
calcifications, and dysplasia.[55] Clinically, patients typically present with pain syndromes, pancreatic exocrine
dysfunction, and pancreatic endocrine dysfunction. Alcohol consumption accelerates
the progression of pancreatic duct stones (PDS) formation in patients with CP. Shorter
periods between diagnosis of CP and PDS formation were found in ACP patients than
in non-ACP patients[56] ([Fig. 8]).
Fig. 8 Computed tomography (CT) in 62/M showing alcohol-related rapid progression to chronic
pancreatitis in 2 years, due to a continuous history of alcohol abuse. (A) Noncontrast-enhanced CT (NECT) in axial plane shows the pancreas of normal bulk
but has peripancreatic fat stranding (white arrow) suggesting mild acute pancreatitis.
(B) NECT of the same patient done after 1 year following a binge, shows increased bulk
of the pancreas (black star) with significant peripancreatic fat stranding (white
arrow). New calcification is seen (white arrowhead). (C) NECT of the same patient done after 18 months shows reduced bulk of the pancreas
and significantly increased calcifications (white arrowhead).
There are multiple classifications to evaluate CP like Cambridge and M-ANNHEIM.[57] The Cambridge classification was developed for endoscopic retrograde cholangiopancreatography
(ERCP) and has been used in MRCP. However, it only considers ductal changes and parenchymal
observations are lacking. Currently, no standardized reporting system for CT, MRI,
or MRCP is universally used. Consortium for the Study of Chronic Pancreatitis, Diabetes,
and Pancreatic Cancer (CPDPC) has proposed a new reporting standard to promote standardized
reporting for CT and MRI.[58]
MRI combined with MRCP is an excellent modality for assessing clinically suspected
CP.[59] The changes have been summarized in [Table 5]. MRI demonstrates parenchymal abnormalities like atrophy and reduced signal intensity
([Fig. 9]). Normal pancreas has high signal intensity on fat-suppressed T1-weighted images
due to excess protein. Chronic inflammation and fibrosis diminish the proteinaceous
fluid content of the pancreas, resulting in the loss of the usual high signal intensity
on T1-weighted fat-suppressed images. The signal change can be segmental or diffuse.
Volume depletion reduces the pancreas anterior-posterior diameter.[60]
Table 5
MRI imaging changes seen in chronic pancreatitis
|
Changes in chronic pancreatitis on MRI
|
|
Early changes
|
Late changes
|
|
Parenchymal:
- Low-signal intensity pancreas on T1-weighted fat-suppressed images
- Decreased and delayed enhancement after IV contrast administration
|
Parenchymal:
- Parenchymal atrophy
- Pseudocysts
|
|
Ductal:
- Dilated side branches irregular contouring and stricture
|
Ductal:
Main ductal changes:
- Diffuse duct dilatation and loss of normal tapering
- Irregularities in the duct wall
- Segmental stenosis and dilatation
- Communication with pseudocyst
Intraductal calcifications
|
Abbreviations: IV, intravenous; MRI, magnetic resonance imaging.
Fig. 9 Normal and abnormal appearance of the pancreas on T1-weighted (T1W) fat-suppressed
(FS) magnetic resonance imaging (MRI). (A) Normal pancreas in axial plane shows a normal bright signal of the pancreas (black
star), as compared to the spleen. (B) Alcohol-related chronic pancreatitis in TRA shows reduced volume of the pancreas
and the gland is of low signal intensity (white arrow) as compared to the spleen.
DWI gives MRI a distinct benefit over other imaging modalities for evaluating functional
information. The presence of parenchymal fibrosis in CP causes diffusion restriction
and results in lower apparent diffusion coefficient (ADC) values on baseline DWI.
The ADC values reveal either delayed peak after secretin stimulation or lower peak
values in patients with early CP, which may help depict CP in its earliest stage.[61]
[62]
[63] ADC values further reduce with acute attacks in the background of CP ([Fig. 10]).
Fig. 10 Magnetic resonance imaging (MRI) in 62/M with recurrent acute alcohol pancreatitis
showing early chronic changes on MRI. (A) T2 HASTE (half-Fourier acquired single-shot turbo spin echo) in axial plane shows
bulky pancreas (white arrow) with a dilated pancreatic duct (white arrowhead) in the
body. The black star represents pseudocysts. (B) Three-dimensional (3D) maximum intensity projection (MIP) magnetic resonance cholangiopancreatography
(MRCP) shows dilated and tortuous pancreatic duct with few early dilatations of side
branches (white arrowhead). C is common bile duct (CBD), G is gallbladder. (C) T1-weighted (T1W) fat-suppressed (FS) in axial plane shows the pancreas as low signal
intensity (white arrowhead). The white arrow is the pancreatic duct. The white star
is a pseudocyst.
Contrast dynamic MRI has been found useful in evaluating CP. The pancreas has a rich
arterial capillary blood supply. Serial contrast-enhanced MRI reveals arterial peak
enhancement and diminished early venous enhancement in the normal population. Arteriolar
damage during AP attacks and pancreatic fibrosis is responsible for the reduced blood
vessel density. In cases with CP, pancreatic parenchymal enhancement is delayed. Progressive
enhancement, peaking on the portal venous phase, indicates fibrosis.[64]
[65]
MRCP provides a noninvasive means of visualizing the pancreatic and biliary ductal
system. MRCP leverages the extended T2 relaxation time of pancreatic secretions or
bile to delineate ductal structures, offering a safer and more accessible alternative
to ERCP. MRCP is accurate in depicting strictures of the pancreatic duct or biliary
tract.
Chronic alcoholic pancreatitis leads to initial abnormalities affecting the side branches
before involving the MPD. Periductal fibrosis can cause a dilated MPD ([Fig. 10]).
As the disease progresses, various changes are seen. The presence of a solitary stricture
in the MPD prompts consideration of neoplasm or pseudocyst in the differential diagnosis.
Stenosis associated with pancreatitis tends to be shorter, smoother, and more symmetric
compared to those seen with neoplastic conditions.[66] There can be associated stricture of common bile duct due to chronic changes in
the head ([Fig. 11]). Differentiation from malignancy in such a situation can be difficult.
Fig. 11 Magnetic resonance (MR) in a 47/M, showing acute on chronic alcohol-related pancreatitis
with common bile duct (CBD) stricture. (A) Three-dimensional (3D) maximum intensity projection (MIP) magnetic resonance cholangiopancreatography
(MRCP) shows dilated and tortuous pancreatic duct with abrupt cutoff in the body (small
white arrow). The long white arrow is CBD stricture. C is CBD and F is fluid. (B) Two-dimensional (2D) thin MIP high-resolution T2-weighted (T2W) image shows a bulky
pancreas (P). The pancreatic duct in the body and tail is dilated with an abrupt cutoff
(small white arrow). The long white arrow is CBD. (C) Apparent diffusion coefficient (ADC) image in axial plane shows diffuse restriction
of the parenchyma (P). S is spleen and L is liver.
Pancreatic calcifications can be seen on X-rays in advanced stages, which is indicative
of chronic inflammation and fibrosis. CT scan is very accurate in demonstrating the
stones ([Fig. 8]). MRI can demonstrate intraductal calculi if there is fluid around them. High-resolution
thin T2-weighted images are helpful for this evaluation ([Fig. 12]).
Fig. 12 Magnetic resonance (MR) in alcohol-related chronic calcific pancreatitis. (A) Three-dimensional (3D) maximum intensity projection (MIP) magnetic resonance cholangiopancreatography
(MRCP) shows dilated and tortuous pancreatic duct with dilated side branches (white
arrow). There are multiple filling defects in the duct. The short white arrow is common
bile duct (CBD), the white arrowhead is cystic duct, and G is the gallbladder. (B) T2-weighted (T2W) SPACE thin high resolution shows an atrophic pancreatic gland
with a dilated and tortuous pancreatic duct (long white arrow). Filling defects in
the pancreatic duct are calculi (short white arrow).
Additional Imaging Techniques Used for Problem-Solving
Additional Imaging Techniques Used for Problem-Solving
S-MRCP: S-MRCP can estimate pancreatic exocrine function, and at the same time an
increased number of side branch ectasia and/or decreased pancreatic duct compliance
after secretin stimulation can be demonstrated as early imaging findings of CP.
EUS: The proximity of the EUS probe to the pancreas results in superior spatial resolution
compared to CT scan and MRI. The normal pancreas has a homogeneous fine granular echo-pattern
(salt and pepper appearance), with a thin and regular MPD. “EUS criteria” have been
developed for CP. The criteria can be divided into pancreatic duct findings and parenchymal
findings. Parenchymal findings include hyperechoic foci, hyperechoic strands, lobularity,
heterogeneity, shadowing calcifications, and cysts. Pancreatic duct findings include
dilation (> 4 mm in the head, > 3 mm in the body, > 2 mm in the tail), irregularity,
hyperechoic duct margins, and visible side branches.[67]
ERCP: Over the last 15 years, ERCP has evolved from a diagnostic tool to one that
is primarily used to provide therapy. When the diagnosis of CP is sought, ERCP should
be reserved for patients in whom the diagnosis is still unclear after noninvasive
methods.[68] ERCP may not detect changes in less advanced CP. Benefits of ERCP over MRCP include evaluating communicating pseudocysts and pancreatic
duct leaks.
Concomitant Liver Involvement
Concomitant Liver Involvement
AUD is a disease affecting over 14 million adults in the United States.[69] Individual sensitivity to alcohol results not only in variable addiction but also
in variable organ damage.
Since the liver and pancreas share development and functional attributes, they are
both vulnerable to the damaging effects of alcohol.[70]
[71] Studies have shown varying frequencies of cooccurrence between pancreatic and liver
diseases. Lowenfels et al noted no significant difference in alcohol consumption between
groups with alcoholic cirrhosis and alcoholic pancreatitis, although smoking was more
prevalent among men with ALP.[72]
A review of 1,022 autopsies where the cause of death was alcoholic liver disease showed
that 28% had histological signs of pancreatitis, ranging from mild inflammation to
moderate fibrosis.[73] A high prevalence of exocrine pancreatic insufficiency and CP was observed among
patients with alcoholic liver disease. CP can exacerbate alcohol-related liver disease,
leading to pancreatic insufficiency and issues with nutrient absorption that worsen
liver fibrosis.
Conclusion
The imaging characteristics of ALP do not markedly differ from other pancreatitis
causes like gallstones and recognizing its unique natural progression and underlying
mechanisms is crucial for precise diagnosis and management. Radiologists play a pivotal
role by utilizing various imaging modalities and being well-versed in ALP's distinct
features, thereby significantly contributing to its clinical management.
Highlights
-
Alcohol-related pancreatitis (ALP) is a spectrum of manifestations ranging from acute
interstitial pancreatitis (AIP), acute pancreatic necrosis (PNEC), and recurrent acute
pancreatitis (RAP), which can progress to alcohol-related chronic pancreatitis (ACP)
with continued use of alcohol.
-
The yearly incidence is increasing, especially in the young, and early intervention
can prevent disease progression.
-
The natural history of this disease is different from other causes of pancreatitis
and suggesting the diagnosis on imaging can help in early detection and guide the
management. CECT is usually the imaging investigation of choice in the acute setting.
In a chronic setting, MRI is more sensitive to subtle changes and provides both morphological
and functional information. It can also be used for monitoring the disease activity.
