Pancreatic fistula

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

A pancreatic fistula is an abnormal communication between the pancreas and other organs due to leakage of pancreatic secretions from damaged pancreatic duct. An external pancreatic fistula is one that communicates with the skin, and is also known as a pancreaticocutaneous fistula, whereas an internal pancreatic fistula communicates with other internal organs or spaces. Pancreatic fistulas can be caused by pancreatic disease, trauma, or surgery. Pancreatic fistula can be classified anatomically as internal fistula and external fistula. Pancreatic fistula can also be classified based on the anatomy of the pancreatic duct and the location of injury as Type 1 pancreatic fistula, Type 2 pancreatic fistula and Type 3 pancreatic fistula. The disruption of the pancreatic duct either from an iatrogenic insult, underlying inflammatory process or trauma results in the leakage of the pancreatic fluid inducing inflammation and erosions, thereby forming abnormal connections with the surrounding structures. The etiology of pancreatic fistula include iatrogenic and non-iatrogenic insults. Differential diagnosis of pancreatic fistula may include chronic liver disease, renal failure, heart failure, malignancy, pleural effusion, pancreatitis, retroperitoneal bleeding and bowel ischemia. The incidence of pancreatic fistula following pancreatic resection surgery varies from 5% to 26%. The overall mortality risk due to pancreatic fistula is 1%, however patients with grade C pancreatic fistula carries a mortality risk of 25%. According to Fistula Risk Scoring (FRS) system, the risk factors for the development of pancreatic fistula depends upon the texture of the gland, underlying pathology, diameter of the pancreatic duct, underlying carcinoma involving the pancreatic duct, intraoperative blood loss and other risk factors such as male gender, obesity, malnutrition, increase gland remnant volume, fasting blood glucose level <108 mg/dl and excessive fluid administration during surgery. Clinical presentation may range from being asymptomatic to showing a variety of signs and symptoms resulting from fluid accumulation such as nausea, vomiting, hypotension, infection, tachycardia, pain, weight loss, ileus and severe symptoms such as unrelenting pain and sepsis. External pancreatic fistula presents with pancreatic fluid accumulation noticeable on the skin surface. Internal pancreatic fistula may present with ascites or pleural effusion as fluid accumulates within the abdominal or thoracic cavity. Complications following a pancreatic fistula may include Wound infection and sepsis, Hemorrhage, Internal and/or external fistula, Pancreatic pseudocyst, Delayed gastric emptying, Walled off pancreatic necrosis, Prolongation of the hospital stay, Pancreatic ascites, High amylase pleural effusion, Disconnected duct syndrome, Multisystem involvement eventually leading to multiorgan failure and/or death. Pancreatic fistula that are less severe are reported to heal in a duration of 4-6 weeks with conservative management only. 80% of the external fistula and 50-65% of the internal fistula are reported to close eventually with conservative measures which involve stabilization of the patient with supportive therapies. However, pancreatic fistula can lead to significant morbidity if not addressed on time. Surgical intervention provides resolution of the fistula with a 90-92% success rate. A pancreatic fistula with leakage of fluid can be diagnosed in some cases with typical history and clinical presentation, such as patient presenting with pancreatitis followed by recurrence, persistent symptoms or post pancreatic resection fluid drainage with increase amylase level. Patients diagnosed with pancreatic fistula are sometimes asymptomatic while some patients may present with symptoms such as marked recent weight loss, unresponsiveness of the ascites to diuretics, non-specific symptoms such as nausea, vomiting, hypotension, infection, and tachycardia and some patients with a high grade fistula may present with sepsis. Patients with pancreatic fistula usually appear normal and in some they appear malnourished. Physical examination of patients with pancreatic fistula is usually remarkable for infection, dyspnea, pleuritic chest pain and ascites. Pleural or ascitic fluid should be sent for analysis. An elevated amylase level, usually > 1,000 IU/L, with protein levels over 3.0 g/dL is diagnostic. Complete blood count is necessary to check for any ongoing infection or hemorrhage. Complete metabolic panel including inflammatory markers, serum electrolytes, liver function tests, calcium, albumin, amylase and lipase should be sent to laboratory for evaluation. Furthermore, pancreatic fistula leak presenting as ascites or pleural effusion should be analyzed for fluid protein, albumin, lactate dehydrogenase, glucose, gram cultures and total cell count. Thoracopancreatic fistula may lead to pleural effusion which can be detected incidentally on a plain chest radiograph. Pancreatic fistula can be diagnosed using abdominal CT scan as it is primarily used to rule out other causes of the abdominal discomfort. The CT scan may demonstrate fluid collections in the thoracic or abdominal cavity or changes associated with acute or chronic pancreatitis leading to pancreatic fistula. Magnetic resonance imaging can be used to predict the formation of pancreatic fistula by calculating the pancreatic remnant volume (PRV) and measuring the width of the pancreatic duct at the line of resection. Endoscopic retrograde cholangiopancreatography (ERCP) is used to diagnose as well as treat the fistula with placement of pancreatic stent during the procedure. ERCP demonstrate filling of the pancreatic duct with contrast and extravasation of the contrast suggesting disruption of the pancreatic duct. Pancreatic fistula is a known complication following a pancreatic surgery. Post operation management is focused towards prevention of complications arising as a consequence of pancreatic secretion from an anastomotic stump or the surface of skin which can subsequently complicate into intraabdominal abscess formation or life threatening hemorrhage. To reduce the risk of development of a post-operative pancreatic fistula, prophylactic measures such as nutrition support, prophylactic somatostatin analogues, drain management and a post-operation follow up is taken to reduce the risk of pancreatic fistula formation. Treatment of pancreatic fistula includes early recognition of the problem which is the key to careful management in order to prevent the consequent complications. Medical therapy is tailored towards the suppression of pancreatic enzymes by restricting the patient’s oral intake of food in conjunction with the use of long-acting somatostatin analogues such as octreotide. Correction of the fluid and electrolyte abnormalities. The patient’s nutrition is maintained with total parenteral nutrition. This treatment is continued for 2-3 weeks, and the patient is observed for improvement. Patients with expanding peripancreatic fluid on abdominal imaging or with persistent symptoms undergo endoscopic therapy via endoscopic retrograde cholangiopancreatography (ERCP) as it is a preferred approach towards the management of a symptomatic pancreatic fistula due to its diagnostic as well as therapeutic value. A transpapillary pancreatic stent is placed during ERCP and/or a pancreatic sphincterectomy is done. If no improvement is seen or endoscopic therapy is not feasible, the patient may receive surgical treatment. Surgical treatment depends upon the location of the fistula where the duct is disrupted, the size of the peripancreatic fluid collection, presence of vascular thrombosis, tissue necrosis and history of previous interventions. Surgical treatment may involve the drainage of pancreatic pseudocyst if indicated, which is often associated with chronic pancreatic fistula. Other options may include fistulojejunostomy, pancreatic resection and decompression of the pancreatic duct with pancreatojejunostomy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

There is no historical perspective related to pancreatic fistula.

• There is no historical perspective related to pancreatic fistula.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Pancreatic fistula can be classified anatomically as internal fistula and external fistula. Pancreatic fistula can also be classified based on the anatomy of the pancreatic duct and the location of injury as Type 1 pancreatic fistula, Type 2 pancreatic fistula and Type 3 pancreatic fistula.

Pancreatic fistula can be classified anatomically as;

• Internal fistula: The pancreatic duct communicates with internal organs or body cavity such as pleural or peritoneal cavity.

• External fistula: The pancreatic duct communicates with the skin, otherwise known as pancreaticocutaneous fistula.^[1]

Pancreatic fistula can also be classified based on the anatomy of the pancreatic duct and the location of injury as;

• Type 1 pancreatic fistula: Involves injury to the pancreatic parenchyma with leakage from the distal part of the pancreatic duct or the side branches.
• Type 2 pancreatic fistula: Involves injury to and leak from the main pancreatic duct.
• Type 3 pancreatic fistula: Occurs as a result of proximal or distal pancreatectomy.^[2]

Pancreatic fistula is classified into two categories on the basis of clinical manifestations, complications and severity by the ISGPF as;

• Biochemical pancreatic fistula: This category includes fistula with no significant clinical symptoms.
• Clinically relevant pancreatic fistula: This category includes fistulas under grade B and C, which shows significant clinical symptoms and require surgical interventions, re-surgeries and can complicate into organ failure and death.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The disruption of the pancreatic duct either from an iatrogenic insult, underlying inflammatory process or trauma results in the leakage of the pancreatic fluid inducing inflammation and erosions, thereby forming abnormal connections with the surrounding structures.

• The pathophysiology of pancreatic fistula involves the disruption of the pancreatic duct either from an iatrogenic insult, underlying inflammatory process or trauma.
• The disruption of the pancreatic duct causes gradual loss of the integrity of the tissue resulting in the leakage of the pancreatic fluid which induces inflammation and erosions, thereby leading to the formation of abnormal connections between the duct and the surrounding structures.^[1][2]
• Pseudocyst is a complication of pancreatic fistula when fibroinflammatory rind is formed due to fluid collections and the leak which is caused by pancreatic fistula.
• Pancreatic secretions are rich in bicarbonate and protein, in some cases where the fistulas are big in size it might lead to the following conditions:
  • Dehydration
  • Metabolic acidosis (due to loss of bicarbonate)
  • Malnutrition (due to malabsorption of fats)
• Based on the anatomical location of the pancreatic fistulas it will result in the following complications:^{[3][4][5][6][7]}
  • Anterior pancreatic fistula results in pancreatic ascites
  • Posterior pancreatic fistula results in pleural effusions or mediastinitis
  • Thoracopancreatic fistulas when pancreatic secretions leaks from through openings in the diaphragm
  • Pancreaticobronchial fistulas
  • Pancreaticomediastinal fistulas
  • Pancreaticopericardial fistulas

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

The etiology of pancreatic fistula include iatrogenic and non-iatrogenic insults.

Pancreatic fistula can result from different types of insults such as;^[1][2]

• Iatrogenic: External pancreatic fistula is most commonly iatrogenic in etiology.
• Trauma to the duct during surgery such as pancreaticoduodenectomy, distal pancreatectomy, during endoscopic intervention, extraction of a biopsy sample, pancreatic resection or as a complication of drainage of pancreatic pseudocyst.
• Non-iatrogenic: Includes pathology of the gland such as acute or chronic pancreatitis or trauma to the abdominal structures or organs leading to fistula formation.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zarlakhta Zamani, M.B.B.S[zamanizarlashta@yahoo.com]

Differential diagnosis of pancreatic fistula may include chronic liver disease, renal failure, heart failure, malignancy, pleural effusion, pancreatitis, retroperitoneal bleeding and bowel ischemia.

Differential diagnosis of a pancreatic fistula may include evaluation for:^{[1][2][3][4][5][6][7][8][9][10]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

The incidence of pancreatic fistula following pancreatic resection surgery varies from 5% to 26%. The overall mortality risk due to pancreatic fistula is 1%, however patients with grade C pancreatic fistula carries a mortality risk of 25%.

• Pancreatic fistula is a known complication following surgical resection of the pancreas.
• The incidence rate varies from as low as 5% in high volume centers to as high as 26%.^[1]
• The incidence of pancreatic fistula varies depending on the type of pancreatic resection as it can be as low as 3% following a pancreatic head resection to as high as 30% after distal pancreatectomy.^[2][3]
• Acute fluid collection is recorded in up to 40% patients with acute pancreatitis, out of which some cases develops true pancreatic fistula depending upon the severity of the insult.^[4]

• Pancreatic fistula can lead to certain severe complications if not addressed on time, as it carries a mortality risk of 25% in patients with grade C pancreatic fistula.
• Post-operative pancreatic fistulae can affect 13% to 41% of patients after pancreatic resection, making it a known source of morbidity and mortality.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

According to Fistula Risk Scoring (FRS) system, the risk factors for the development of pancreatic fistula depends upon the texture of the gland, underlying pathology, diameter of the pancreatic duct, underlying carcinoma involving the pancreatic duct, intraoperative blood loss and other risk factors such as male gender, obesity, malnutrition, increase gland remnant volume, fasting blood glucose level <108 mg/dl and excessive fluid administration during surgery.

According to Fistula Risk Scoring (FRS) system, the risk factors for the development of pancreatic fistula depends upon:

• Texture of the gland: Soft texture of the gland is identified as a predictive risk factor.
• Pathology: Carcinoma of the duodenum, ampulla, cystic duct and islet cell carries high risk for fistula development compared to the glandular carcinoma such as pancreatic ductal adenocarcinoma or chronic pancreatitis.
• Diameter of the pancreatic duct: Small pancreatic duct diameter <3mm is identified as a risk factor for the development of fistula formation, specifically a diameter of <1mm carries a high risk.
• Intraoperative blood loss: >1000ml is associated with a high risk of fistula formation.^[1]

• Less common risk factors in the development of pancreatic fistula include:
  • Male gender
  • Excessive fluid administration during surgery,
  • Fasting blood glucose <108 mg/dl and an increase remnant gland volume.
  • Some studies have reported both malnutrition and obesity as risk factors for the development of pancreatic cancer.^[2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clinical presentation may range from being asymptomatic to showing a variety of signs and symptoms such as nausea, vomiting, hypotension, infection, tachycardia, pain, weight loss, ileus and severe symptoms such as unrelenting pain and sepsis. Complications following a pancreatic fistula may include Wound infection and sepsis, Hemorrhage, Internal and/or external fistula, Pancreatic pseudocyst, Delayed gastric emptying, Walled off pancreatic necrosis, Prolongation of the hospital stay, Pancreatic ascites, High amylase pleural effusion, Disconnected duct syndrome, Multisystem involvement eventually leading to multiorgan failure and/or death. Pancreatic fistula that are less severe are reported to heal in a duration of 4-6 weeks with conservative management only. Surgical intervention provides resolution of the fistula with a 90-92% success rate.

History and clinical presentation depends upon the size, location and connection of the pancreatic fistula with the involved organ or cavity.^[1][2]

Clinical presentation may range from being asymptomatic to showing a variety of signs and symptoms resulting from fluid accumulation such as nausea, vomiting, hypotension, infection, tachycardia, pain, weight loss, ileus and severe symptoms such as unrelenting pain and sepsis.

• External pancreatic fistula presents with pancreatic fluid accumulation noticeable on the skin surface.^[3]
• Internal pancreatic fistula may present with ascites or pleural effusion as fluid accumulates within the abdominal or thoracic cavity.^[2]

• Anterior disruption of a pseudocyst or a pancreatic duct leads to leakage of pancreatic secretions into the free peritoneal cavity, leading to pancreatic ascites. If the duct is disrupted posteriorly, the secretions leak through the retroperitoneum into the mediastinum via the aortic or esophageal hiatus.^[4][5]
• Once in the mediastinum, the secretions can either be contained in a mediastinal pseudocyst, lead to enzymatic mediastinitis, or, more commonly, leak through the pleura to enter the chest and form a chronic pancreatic pleural effusion.^[6][7]
• Complications arising from a pancreatic fistula are due to the undrained pancreatic fluid accumulation and erosions caused by the enzymatically active substances of the fluid which affects the surrounding tissues. The most commonly observed complications are:^[8][9]

1. Wound infection and sepsis
2. Hemorrhage
3. Internal and/or external fistula
4. Pancreatic pseudocyst
5. Delayed gastric emptying
6. Walled off pancreatic necrosis
7. Prolongation of the hospital stay
8. Pancreatic ascites
9. High amylase pleural effusion
10. Disconnected duct syndrome
11. Multisystem involvement eventually leading to multiorgan failure and/or death.

• Pancreatic fistula that are less severe are reported to heal in a duration of 4-6 weeks with conservative management only.
• 80% of the external fistula and 50-65% of the internal fistula are reported to close eventually with conservative measures which involve stabilization of the patient with supportive therapies. However, pancreatic fistula can lead to significant morbidity if not addressed on time.
• Surgical intervention provides resolution of the fistula with a 90-92% success rate.^[10][11]

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