INTRODUCTION — A pancreatic fistula is characterized by leakage of pancreatic fluid as a result of disruption of pancreatic ducts. Disruption of pancreatic ducts can occur following acute or chronic pancreatitis, pancreatic resection, or trauma. Leakage of pancreatic secretions can cause significant morbidity due to malnutrition, skin excoriation, and infection. Successful management of pancreatic fistulas requires a multidisciplinary approach [1-3].

This topic will review the management of pancreatic fistulas. The clinical features, diagnosis, and prevention of pancreatic fistulas and the management of walled-off pancreatic fluid collections, infected pancreatic necrosis, and pancreatic trauma are discussed separately. (See "Pancreatic fistulas: Clinical manifestations and diagnosis" and "Approach to walled-off pancreatic fluid collections in adults" and "Endoscopic interventions for walled-off pancreatic fluid collections" and "Pancreatic debridement" and "Management of duodenal trauma in adults".)

DEFINITION AND CLASSIFICATION — A pancreatic fistula (PF) is defined as an abnormal connection between the pancreas and adjacent or distant organs, structures, or spaces (image 1).

PFs are classified as internal if the pancreatic duct communicates with the peritoneal or pleural cavity or another hollow viscus and external if the pancreatic duct communicates with the skin (table 1). PFs can also be classified based upon the underlying disease process and the immediate predisposing cause. (See "Pancreatic fistulas: Clinical manifestations and diagnosis", section on 'Definition and classification'.)

INITIAL MANAGEMENT — The management of pancreatic fistulas (PFs) depends on the presence of symptoms (eg, abdominal pain, fever, chills, jaundice, or early satiety), the characteristics and location of the fluid collection on imaging (eg, presence of pancreatic necrosis, proximity to the bowel lumen), and the presence of associated complications (eg, infection of pancreatic fluid). (See "Pancreatic fistulas: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)

In the absence of significant symptoms or coexisting infected pancreatic necrosis, initial management of PFs consists of supportive care. The management of infected pancreatic necrosis and walled-off pancreatic fluid collections are discussed in detail, separately. (See "Approach to walled-off pancreatic fluid collections in adults", section on 'Management' and "Pancreatic debridement", section on 'Infected pancreatic necrosis'.)

Supportive care for PFs includes the following measures:

●Reduction of pancreatic stimulation by maintaining patients nil by mouth (NPO) and nasojejunal feeding to correct malnutrition. Enteral nutrition is associated with a lower incidence of infection, higher 30-day fistula closure rates, and shorter time to closure of postoperative pancreatic fistula as compared with total parenteral nutrition [4,5]. (See "Nutrition support in critically ill patients: An overview", section on 'Enteral versus parenteral'.)

●Correction of fluid and electrolyte disturbances.

●Skin care for the excoriation due to external PFs.

●Somatostatin analogues, such as octreotide (100 micrograms subcutaneously three times a day) in patients with high-output PFs or those that result in electrolyte abnormalities or skin breakdown. Somatostatin preparations may be effective in the reduction of fistula output but not the rate of fistula closure. In a 2012 meta-analysis of seven randomized trials that included 297 patients of which 102 had pancreatic fistulas, closure rates were not significantly higher in patients treated with somatostatin analogues as compared with controls [6].

With supportive care, case series have reported fistula closure in approximately 80 percent of external and 50 to 65 percent of internal fistulas over four to six weeks [7]. We obtain follow-up abdominal imaging with an abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) in six to eight weeks to evaluate the size of peripancreatic fluid collections. Imaging should be repeated sooner if the patient develops abdominal pain, fever, chills, jaundice, or early satiety. In patients with clinical symptoms, sepsis physiology, or increasing white blood cell count, pancreatic fluid should be sent for Gram stain and culture to rule out an infection. Systemic antibiotics should be administered in patients with evidence of infected pancreatic fluid collections.

SUBSEQUENT MANAGEMENT — For patients who are symptomatic or those with persistent or enlarging fluid collections on follow-up abdominal imaging after six to eight weeks of supportive care, additional intervention is required. Management options include endoscopic therapy, percutaneous drainage, and surgery. Prior to intervention, we further characterize the pancreatic fistula (PF) with secretin-enhanced magnetic resonance cholangiopancreatography (MRCP) (image 2).

Endoscopic therapy — Endoscopic therapy is the preferred approach for management of most PFs. The goal of endoscopic therapy is to promote internal drainage of pancreatic secretions, thereby reducing flow through the fistula tract. This is typically accomplished by placement of a pancreatic stent and/or pancreatic sphincterotomy. Transpapillary stent placement is performed during endoscopic retrograde cholangiopancreatography (ERCP). To avoid the theoretical risk of transient biliary obstruction due to pancreatic sphincterotomy, we perform a biliary sphincterotomy prior to stent placement. We then place a stent, preferably bridging the ductal disruption. Although transpapillary passage of a stent through the pancreatic sphincter reduces ductal pressure to promote flow toward the duodenum and away from the fistula tract, the passage of a stent through the disruption may be somewhat more effective than transpapillary stenting alone [8-10]. Pancreatic duct drainage can also be accomplished by placement of a nasopancreatic stent. In case series, endoscopic therapy for pancreatic fistulas has been associated with success rates of 85 to 100 percent [7]. (See 'Percutaneous drainage' below.)

Complications of pancreatic duct stenting include acute pancreatitis, pain, and, much less commonly, perforation and cholangitis. Late complications include pancreatic ductal and parenchymal changes that resemble chronic pancreatitis, and stent malfunction, which is principally due to occlusion [11]. (See "Pancreatic stenting at endoscopic retrograde cholangiopancreatography (ERCP): Indications, techniques, and complications".)

Endoscopic transgastric or transduodenal drainage is performed in patients who have a large, symptomatic walled-off pancreatic fluid collection that is compressing the stomach or duodenum when there is close apposition of the fluid collection to the bowel lumen. While endoscopic drainage procedures may be possible in patients with disconnected pancreatic duct syndrome, they are associated with a high rate of recurrent symptoms, requiring repeat intervention or surgery [12,13]. (See "Endoscopic interventions for walled-off pancreatic fluid collections", section on 'EUS-guided transmural drainage'.)

Percutaneous drainage — For PFs occurring after elective pancreatic resection, prophylactic percutaneous drains placed at operation may control the existing PF with possible need for repositioning or exchange. When these drains omitted at operation or are remote from a collection, postoperative image-guided percutaneous drainage is recommended for management of symptomatic, persistent, or enlarging collections [14-16]. With percutaneous drainage, the majority of postoperative PFs resolve over three to six weeks. For all other PFs, percutaneous drainage should be considered only when endoscopic and surgical drainage are not feasible or have failed, as percutaneous drainage of an internal PF may lead to the development of an external PF in 5 to 10 percent of cases [17,18].

Surgical therapy — Surgery for a persistent PF is indicated when endoscopic management fails or is technically unfeasible. The operative approach depends on the location of the disruption, status of the pancreatic remnant "upstream" from the ductal disruption, presence of necrosis, vascular thrombosis, and prior interventions (figure 1). In patients with chronic PFs, surgical options include enteric drainage of an associated pseudocyst, pancreatic ductal decompression with a pancreatojejunostomy, partial pancreatic resection, and fistulojejunostomy. For a fistulojejunostomy, the fistula tract must be mature and the anastomosis performed close to the pancreas, since long-term failure has been attributed to obliteration of the fistula track with time. Although there are limited data to guide the timing of surgical intervention, we wait three to six months for the development of a very fibrotic tract. Enteric drainage of chronic external PFs is generally effective, although it may be associated with fistula recurrence, particularly if cystenterostomy is performed [19]. Surgical treatment of PFs in patients who have failed all other treatments has a success rate of approximately 90 percent and an associated mortality rate of 6 to 9 percent [7].

In the acute setting of pancreatic anastomotic disruption, oversewing of the pancreatic stump and, in some cases, completion pancreatectomy may be necessary [20,21]. Strategies for prevention of postoperative pancreatic fistula are discussed in detail, separately. (See "Surgical resection of lesions of the head of the pancreas", section on 'Prevention'.)

Other approaches — Endoscopic sealants have been used to close PFs in small series, but additional data are needed before they can be routinely recommended [22,23]. N-butyl-2-cyanoacrylate is delivered as a stable monomer in liquid state, but polymerizes into a solid on contact with body fluids at neutral pH. In one series in which 12 patients with peripancreatic or external PFs underwent endoscopic injection of N-butyl-2-cyanoacrylate into the fistulous tract, complete fistula closure was achieved in 8 of 12 patients [22].

SUMMARY AND RECOMMENDATIONS

●A pancreatic fistula (PF) is an abnormal connection between the pancreas and adjacent or distant organs, structures, or spaces. PFs are classified as internal if the pancreatic duct communicates with the peritoneal or pleural cavity or another hollow viscus and external if the pancreatic duct communicates with the skin (table 1). The main cause is leakage of pancreatic secretions from disrupted pancreatic ducts due to pancreatic disease, trauma, or surgery. PFs can cause significant morbidity due to malnutrition, skin excoriation, and infection. (See 'Definition and classification' above.)

●In patients with a PF and minimal or no symptoms and no infected pancreatic necrosis, we suggest initial supportive care rather than a drainage procedure (Grade 2C). With supportive care, approximately 80 percent of external and 50 to 65 percent of internal PFs resolve within four to six weeks. (See "Pancreatic fistulas: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation' and 'Initial management' above.)

●We obtain follow-up abdominal imaging with an abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) after six to eight weeks of supportive care. Imaging should be repeated sooner if the patient develops abdominal pain, nausea, vomiting, jaundice, early satiety, fever, or chills. In patients with clinical symptoms, sepsis physiology, or increasing white blood cell count, pancreatic fluid should be sent for Gram stain and culture to rule out an infection. Systemic antibiotics should be administered in patients with evidence of infected pancreatic fluid collections. (See 'Initial management' above.)

●For patients who are symptomatic or those with persistent or enlarging fluid collections on follow-up abdominal imaging, we suggest endoscopic therapy rather than continued supportive care (Grade 2C). Endoscopic therapy promotes internal drainage of pancreatic secretions, thereby reducing flow through the fistula tract. This is typically accomplished by transpapillary stent placement, preferably across the leak/disruption during endoscopic retrograde cholangiopancreatography (ERCP). (See 'Endoscopic therapy' above.)

●If pancreatic fluid leakage persists following endoscopic drainage, or if endoscopic drainage is not feasible due to technical reasons, surgical intervention should be considered. Depending upon the underlying anatomy, surgical options include enteric drainage of associated pseudocyst(s), pancreatic ductal decompression with a pancreatojejunostomy, fistulojejunostomy, partial pancreatic resection, and, in rare cases, a completion pancreatectomy. (See 'Surgical therapy' above.)

●We reserve percutaneous drainage of peripancreatic fluid collections for management of postoperative PFs and for all other PFs provided endoscopic and surgical drainage are unfeasible or have failed. (See 'Percutaneous drainage' above.)