Pancreatic fistula is the leading complication after pancreatic resections. It is defined as the output via a drain, a drain track, or a surgical wound (on or after postoperative day 3) of any measurable volume of fluid containing pancreatic juice (amylase content greater than 3 times the upper normal serum value). Drain fluid could have a ‘‘sinister appearance’’ that may vary from a dark brown to greenish fluid to milky water to clear ‘‘spring water’’ that looks like pancreatic juice. Associated clinical findings may include abdominal pain and distention with impaired bowel function, delayed gastric emptying, fever, elevated serum leukocyte count, and increased C-reactive protein.   

• In pancreaticoduodenectomy, pancreatic fistula represents the failure of healing/sealing of pancreaticojejunostomy or pancreatico-gastrostomy. Incidence is between 10% and 20%.
• In left pancreatectomy, pancreatic fistula represents a parenchymal leak not directly related to an anastomosis. The leak originates from the raw pancreatic surface (closed with sutures or with a stapler). Incidence is 20-25%.
• In middle segment pancreatectomy pancreatic fistula derives from a failure of healing/sealing of the pancreatic-enteric anastomosis performed on the distal stump, and/or it may represent a parenchymal leak originating from the raw pancreatic surface of the proximal stump. Incidence is 40-50%.
• In enucleation pancreatic fistula represents a parenchymal leak form the resection bed, often because of inadvertent damage of a secondary duct or, less commonly, because of damage to the main pancreatic duct. Its incidence is 35-40%.

The most widely recognized risk factors for pancreatic fistula are directly linked to state and disease of the pancreas and or/periampullary region. Principal among them is a soft pancreatic parenchyma. The normal pancreas texture is soft and friable, and remains unaltered when small and benign/borderline neoplasms develop. On the other hand, ductal adenocarcinoma and – especially – chronic pancreatitis cause duct obstruction and fibrotic replacement of the normal pancreatic tissue. It has been widely accepted that a fibrotic pancreatic remnant facilitates the pancreatico-enteric anastomosis, whereas a soft and friable pancreatic parenchyma makes the anastomosis difficult to perform and prone to inflammatory injury (due to the unaltered acinar component), and leak.

The size of the main pancreatic duct has been also implicated as a major predictor of fistula. Small non-dilated pancreatic ducts, typically defined as less than or equal to 3 mm in diameter, predispose patients to pancreatic fistulae. Small pancreatic duct and soft parenchyma often coexist, making the risk of postoperative fistula greater.

Despite refinements in surgical technique and postoperative care, pancreatic fistula remains a major issue. Variations in surgical technique (modification of pancreatic anastomosis technique in pancreaticoduodenectomy or management of the pancreatic stump in distal pancreatectomy) or in postoperative management did not modify the incidence of fistula appreciably.

Clinically, pancreatic fistula can be associated with abdominal collections, abscesses, infection, fever, abdominal distension and bowel impairment, bleeding. A clinical grading system for postoperative pancreatic fistula (A,B,C) has been proposed, by the International Study Group of Pancreatic Fistula (ISGPF) and is summarized below:

• Pancreatic fistula grade A has no clinical impact and requires little change in management or deviation from the normal clinical pathway. 
• Pancreatic fistula grade B requires a change in management or adjustment in the clinical pathway. Often the patient is supported with artificial nutrition. The peripancreatic drains are usually maintained in place or repositioned. Antibiotics are usually required, somatostatin analogues may also be used. Grade B fistula usually leads to a delay in discharge, or readmission after a previous discharge may be required. 
• Pancreatic fistula grade C requires a major change in clinical management. An invasive procedure is required, including percutaneous drain placement of surgical re-exploration. The patient typically requires an extended hospital stay with a major delay in hospital discharge. There are often associated complications and the possibility of post- operative mortality. 

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Bassi C, et. al. Surgery. 2005 Jul;138(1):8-13.