Chronic pancreatitis

Chronic pancreatitis is a long-standing inflammation of the pancreas that progresses either continuously or in flare-ups, leading to fibrosis and destruction of pancreatic parenchyma, followed by exocrine and then endocrine insufficiency.

Chronic alcoholism is the overwhelmingly dominant cause. The disease usually manifests after the age of 40, with a prevalence of 50 per 100,000 inhabitants. Mortality is between 40% and 50% at 20 years of progression.

Pathophysiological Elements and Etiologies

The pathophysiology of chronic pancreatitis remains poorly understood. However, a continuum between acute pancreatitis, recurrent pancreatitis, and chronic pancreatitis is well established today. The risk of developing chronic pancreatitis after an acute episode is 10%.

Regardless of the mechanisms of the initial lesion, all chronic pancreatitis cases progress to the same histopathological picture and loss of pancreatic functions.

Although alcoholism is the overwhelmingly predominant cause, it is common for multiple etiologies—or risk factors (including genetic polymorphisms)—to coexist.

Alcoholism - 50% to over 70% of cases

The duration of alcohol consumption is generally 10 to 20 years, with the severity of consumption correlated to the clinical severity. Ten-year survival is between 70% and 80%.

It is noteworthy that smoking is considered a risk factor and severity factor for chronic pancreatitis, particularly in the case of alcoholic pancreatitis.

Idiopathic (no identified etiology) – 10% to 30% of cases

This category is decreasing as more genetic forms are identified and testing becomes more accessible.

Miscellaneous - 10% to 30% of cases

Includes hyperparathyroidism, hyperlipidemia, obstructive forms, hereditary conditions (cystic fibrosis, hereditary pancreatitis, etc.), autoimmune forms, radiation therapy, infections, etc.

Clinical Presentation

May present with chronic symptoms or acute flare-ups. The disease progresses through an initial asymptomatic phase, followed by recurrent acute inflammatory attacks over several years, eventually leading to exocrine insufficiency (malabsorption) and endocrine insufficiency (diabetes), with decreasing pain. The probability of an acute flare-up rapidly increases in the early years of progression, reaching a plateau of 40% by the 7th year.

• Abdominal pain varies: it can be acute, often epigastric and piercing, may develop over hours to days, occur postprandially, or after excessive alcohol consumption for several days to weeks, fluctuating over months, or be dull and constant. Pain reveals pancreatitis in 70% to 90% of cases but is absent in 5% to 30% of cases depending on the series and tends to diminish or even disappear over time. Five years after the onset of pain, it has disappeared in 85% of patients.

• Malabsorption (weight loss, steatorrhea, vitamin deficiencies) in advanced stages
• Late-onset insulin-dependent diabetes (30% at 5 years)

Complications

Pseudocysts and Cysts (10% to 50% of patients)

These are collections of pancreatic fluid, either within or distant from the pancreas.

Pseudocysts are bordered by fibro-inflammatory tissue and/or neighboring organs, while cysts are lined by epithelium. They can appear during chronic progression or after an acute flare-up.

The average age of onset is 45 to 50 years, often 5 years after clinical onset. Pseudocysts are categorized into necrotic pseudocysts (typically located at the pancreatic tail with complications such as hemorrhages, superinfections, ruptures; possible regression within 6 weeks if solitary) and retention pseudocysts (typically at the pancreatic head, with common complication being choledochal compression; spontaneous regression is rare) developing from a ductal cyst.

Clinical presentation includes pain (85%), vomiting (50%), palpable abdominal mass (25%), and jaundice (10%). Complications may include rupture, abscess, infections, hemorrhages, portal or splenic vein thrombosis with portal hypertension, high digestive obstruction, fistulas, etc. Twenty percent resolve spontaneously.

Diagnosis is made via ultrasound or CT scan. MRCP (magnetic resonance cholangiopancreatography) can be useful in pre-therapeutic assessment. If necessary, the treatment of choice is internal drainage (external drainage risks creating an infected fistula).

Pseudocysts requiring immediate treatment are those that are infected, hemorrhagic, painful, or compressing a neighboring organ.

Pancreatic Calcifications and Stones

These are highly specific to chronic pancreatitis. Diagnosis is primarily established by CT scan. The likelihood of stones 2 years post-chronic pancreatitis diagnosis is 33%, 50% at 4 years, and 85% at 15 years. Smoking may be a cofactor in the risk of stone formation (controversial).

Compression of the Main Bile Duct (30% to 40% of patients)

This may result from pancreatic hypertrophy (due to acute flare-up or fibrosis) and manifests as pruritus, jaundice, or cholangitis (rare). Diagnosis is established by ultrasound, endoscopic ultrasound, or ERCP. In cases of cholestasis, a decompensated cirrhosis or acute alcoholic hepatitis must be ruled out.

Digestive Hemorrhages

These occur due to rupture of a pseudocyst or rupture of gastric or esophageal varices (due to segmental portal hypertension from splenic vein compression or thrombosis or due to alcoholic cirrhosis). Splenic vein thrombosis and gastric varices are present in 10% of patients.

Serous Effusions

Ascites or pleurisy may occur during acute flare-ups. Sometimes they are the presenting symptom. The fluid is rich in protein and amylase.

Pancreatic Insufficiencies

Endocrine (diabetes) and exocrine (steatorrhea, diarrhea, abdominal discomfort, malabsorption and weight loss, osteopenia).

Others

Splenic pseudocyst and spleen rupture, duodenal or pyloric-bulbar stenosis or obstruction, pseudo-aneurysms of neighboring arteries.

The occurrence of pancreatic adenocarcinoma is rare but more frequent in hereditary pancreatitis (screening is necessary in high-risk patients) and/or with continued alcohol-tobacco use.

Additional Tests and Diagnosis

Any unexplained chronic abdominal pain in a patient with a history of acute pancreatitis should raise suspicion of chronic pancreatitis.

The diagnosis is based on three elements: fibrosis within the parenchyma + calcifications (pathognomonic) + ductal abnormalities visible on imaging. The presence of exocrine insufficiency is an additional argument but appears late.

• Ultrasound and/or CT scan (most sensitive for calcifications): irregular pancreas, dilated ducts, calcifications, pseudocyst?
• MRCP: more effective than CT for evaluating parenchyma but less so for calcifications.
• Evaluation of exocrine and endocrine functions
• Blood tests are generally not or minimally contributive (lipase and amylase may be normal, decreased, or slightly elevated. Possible increased bilirubin and ALP in cases of bile duct compression).
• Given the risks and the performance of other tests, ERCP is no longer used for diagnosis.

Radiography has no place in the assessment, but incidental discovery of pancreatic calcifications on an abdominal X-ray should prompt consideration of the diagnosis.

Differential Diagnosis

Peptic ulcers and gastritis, gallstones, pancreatic neoplasms, ampullary adenoma (which may cause obstructive chronic pancreatitis; consider in cases of nodular focal lesions, hepatic metastases, or complete Wirsung duct stenosis), acute pancreatitis flare-up (difficult differential diagnosis in non-calcifying chronic pancreatitis), etc.

Therapeutic Management - Treatments

Symptomatic Treatment of Acute Flare-Ups: see the article on acute pancreatitis.

Medical Treatment

• Mandatory cessation of alcohol and tobacco (correlated with increased survival).
• Possible other etiological treatment.
• Pain management:
  • First-line: NSAIDs
  • Second-line: Weak opioids (tramadol)
  • Third-line: SSRIs, tricyclic antidepressants, gabapentin, pregabalin, etc.
  • Fourth-line: Celiac plexus block, endoscopic or surgical treatments (see below)

• Management of exocrine insufficiency: Meal fractionation, reduction of fat intake, good hydration, pancreatic enzyme replacement ± vitamin supplements.

• Management of endocrine insufficiency: Diabetic diet, insulin therapy.
• Treatment of complications
• Correct metabolic disorders (++ calcium levels and vitamin D levels, alterations in which are a marker of poor prognosis).

Endoscopic treatment (ERCP)

• Endoscopic pancreatic sphincterotomy
  • Nasopancreatic or stent drainage post-operation
• Dilation, drilling, or stenting of ductal strictures
  • No consensus on the duration of stenting (2 months to 1 year). However, plastic stents typically occlude within 4 to 6 months… some authors leave the stent and replace it only once it’s occluded… but this carries the risk of serious complications…
  • Early complications: Acute pancreatitis (5 to 40% of cases, ++ rapidly resolving edematous pancreatitis), (pancreatic abscesses, cholangitis)
  • Late complications: Stent migration (5%), occlusion (eventual certainty), ductal lesions (20 to 80%, but half regress 4 months post-stent removal)
• Extraction of pancreatic stones (after sphincterotomy and dilation of strictures)
  • Extracorporeal lithotripsy increases success.
• Endoscopic drainage of symptomatic or complicated cysts and pseudocysts (after sphincterotomy)
  • Transpapillary
    • Placement of a nasopancreatic drain/stent
  • Via cystogastrostomy/duodenostomy
    • Placement of a double pigtail stent or nasocystic drain (if infected fluid/necrotic debris).
  • Average drainage of 2 months based on radiological monitoring of pseudocyst disappearance.

• Interventional endoscopic ultrasound
  • Primarily for cysts that do not protrude into the digestive lumen.

Surgical Treatment

Possible indication in case of complications or pain not controlled by medical or endoscopic treatment:

• Bypass procedures
  • Wirsungo-gastric or jejunal anastomosis
  • Choledocho-duodenal or jejunal anastomosis
  • Gastro-jejunal anastomosis
  • Cysto-duodenal, cysto-gastric, or cysto-jejunal anastomosis
• Pancreatic resections:
  • Cephalic duodenopancreatectomy
  • Splenopancreatectomy

Bibliography

EMC, Traité de Gastro-entérologie, Elsevier, 2018

Forsmark SE et al., Etiology and pathogenesis of chronic pancreatitis in adults, UpToDate, 2023

Freeman SD et al., Chronic pancreatitis: Clinical manifestations and diagnosis in adults, UpToDate, 2023

Freeman SD et al., Chronic pancreatitis: Management, UpToDate, 2023

Freeman SD et al., Overview of the complications of chronic pancreatitis, UpToDate, 2023

Hawkey CJ et al., Textbook of clinical Gastroenterology and Hepatology, 2d edition, Wiley-BlackWell, 2012