Pancreaticopleural Fistula

Pancreaticopleural fistula is an abnormal connection between the pancreatic duct (or a pseudocyst) and the pleural space, causing a massive, recurrent pleural effusion rich in pancreatic enzymes. It complicates 0.4 to 4.5% of chronic pancreatitis, mainly alcohol related, and is rarer after acute pancreatitis, trauma or surgery.

It is mostly found in middle aged men with a history of alcohol use and chronic pancreatitis, and the effusion is on the left in about two thirds, right in a fifth and bilateral in the rest. Many have no abdominal symptoms, so the diagnosis is delayed, and the effusion is often treated as a primary pleural disease.

Pathophysiology. Disruption or leak of a pancreatic duct (from pancreatitis, stones or strictures) tracks through the retroperitoneum and the aortic or oesophageal hiatus into the mediastinum and pleural space, either directly or through a pseudocyst. Pancreatic juice in the pleural space provokes inflammation and a persistent, high volume effusion.

Progressive dyspnoea, cough and chest pain with a large pleural effusion, and weight loss. Abdominal pain and signs of pancreatitis (epigastric pain, vomiting, diarrhoea) may be minimal or absent. Fever suggests infection. Ascites accompanies it in a third.

Fever, hypotension, respiratory failure or sepsis in a patient with a pancreatic effusion needs urgent assessment since infection of the effusion or a collection is life threatening.

• Thoracentesis: an exudate (protein above 30 g/L, often above 50 g/L) with a very high pleural fluid amylase (commonly above 1000 IU/L, several times the serum value), lymphocytic or neutrophilic cells, and a bloody or straw colour. Pleural fluid lipase is also high. Low pH is unusual unless infected.
• Serum amylase and lipase may be normal or mildly raised.
• Imaging: chest radiograph shows a unilateral effusion. CT of the chest and abdomen shows pancreatic changes (atrophy, calcification, duct dilation, pseudocyst) and the track of the fistula in about half.
• Magnetic resonance cholangiopancreatography (MRCP) with secretin stimulation is the best non-invasive test, showing the fistula tract in about 80%.
• Endoscopic retrograde cholangiopancreatography (ERCP) shows the duct leak in about 80% to 90%, and allows treatment. Endoscopic ultrasound shows duct stones, strictures and pseudocysts.
• Exclude malignancy: pleural cytology, CT, and CA 19-9 if mass is present, since pancreatic cancer can cause it.
• Evaluate for alcohol use and nutritional state.

Differential diagnosis.

• Oesophageal rupture (high pleural amylase from saliva, low pH)
• Malignant pleural effusion with amylase elevation (lung cancer)
• Pleural effusion from acute pancreatitis (small, transient)
• Tuberculous or parapneumonic effusion
• Hepatic hydrothorax
• Pancreatic cancer with duct obstruction

• Initial conservative management for 2 to 3 weeks: therapeutic thoracentesis or a small bore chest drain (12 to 14 French) to relieve dyspnoea and to monitor output, bowel rest with nasojejunal or parenteral nutrition, and abstinence from alcohol.
• Octreotide 100 micrograms subcutaneously three times daily (or 25 to 50 micrograms per hour as an infusion) to reduce pancreatic secretion, for a course of 2 to 3 weeks. Success is reported in about 30 to 60% of patients, higher when combined with drainage and nutrition.
• Endoscopic therapy if there is no response in 2 to 3 weeks (or early where the duct is dilated): ERCP with pancreatic sphincterotomy and a transpapillary pancreatic duct stent (5 to 10 French) bridging the leak, with clearance of stones and treatment of strictures. Success is about 60 to 80%. Stents are changed or removed after 2 to 3 months.
• Surgery when endoscopic or medical therapy fails, or for complex disease (disconnected duct, distal stricture, large pseudocyst): distal pancreatectomy, pancreaticojejunostomy (Roux-en-Y), or cystojejunostomy. Success about 80 to 90%.
• Antibiotics for infection of the effusion (piperacillin-tazobactam 4.5 g intravenously every 8 hours), with drainage.
• Pancreatic enzyme replacement (for example pancrelipase 25,000 to 50,000 units with meals) and diabetes care in chronic pancreatitis. Alcohol cessation and analgesia.
• Avoid repeated thoracentesis alone, since it does not close the leak.

Complications and prognosis. Recurrent effusion, malnutrition, empyema, pseudocyst infection and bleeding. Relapse follows incomplete closure, and mortality is low in treated disease.

Monitoring. Weekly pleural fluid volume and chest radiograph during treatment, nutritional parameters, and follow up imaging at 3 months after stent removal, then periodic review of the pancreas.

Referral and escalation. Refer to a gastroenterologist for ERCP and a pancreatic surgeon in failed cases, and to a respiratory physician for pleural drainage.