Introduction

The incidence of acute pancreatitis immediately after cephalic pancreaticoduodenectomy (CPD), a conditioning factor for the development of pancreatic fistula, is underestimated

and has been reported to be 55.8% in the international literature¹. Most patients with pancreatitis after CPD have symptoms due to inflammation of the remnant pancreas; the diagnosis is difficult because the symptoms can often be confused with usual postoperative pain. However, in some cases pancreatitis can cause severe local complications and even death.

The aim of this study is to report three cases of acute pancreatitis after CPD with local complications with review of the literature.

Material and methods

The information about pancreatic resections was retrieved from a prospective database. Patients who developed acute pancreatitis with local lesions immediately after open or laparoscopic CPD were identified. Pancreatic fistula was defined according to the International Study Group on Pancreatic Fistula (ISGPF) Definition². The definition of pancreatitis was based on serum amylase or lipase >3x upper limit of normal associated with abdominal pain or imaging criteria³.

Results

A total of 260 pancreaticoduodenectomies performed by the authors of the study in their public (2008-2014) and private (2008-2019) practice were analyzed. During that period, three of those 260 patients (1.15%) developed postoperative acute pancreatitis with local complications.

CASE 1: A 62-year-old female patient with a diagnosis of duodenal tumor made by upper gastrointestinal videoendoscopy underwent fully laparoscopic CPD with Child’s reconstruction. The neck of the pancreas was sectioned using electric scalpel and the pancreatic duct could be identified. The pancreaticojejunostomy was performed with duct-to-mucosa anastomosis and a probe was inserted in the pancreatic duct, following Blumgart technique. The hepaticojejunostomy was sutured with separate stitches because the bile duct was thin. The operative time was 6:30 hours. During the immediate postoperative period, the patient presented mild abdominal pain which was relieved by nonsteroidal anti-inflammatory drugs. On postoperative day three, the intensity of the abdominal pain increased, and serum amylase was three times above the upper limit of normal. For this reason, a computed tomography (CT) scan was performed, which showed enlarged pancreatic remnant and a small peripancreatic fluid collection (Figure 1). With these findings, the patient continued with the administration of intravenous fluids and analgesia. Oral feeding was initiated on postoperative day five when the patient recovered bowel motility. On postoperative day eight, the patient presented fever and leukocytosis. A new CT scan (Figure 2) showed fluid collection in the pancreas tail that extended anteriorly to the left kidney, and absence of free peritoneal fluid. A sample of the collection was obtained percutaneously and was sent for culture. Antibiotics were prescribed according to the results of the antibiogram. A drain output of 300 mL/day evidenced a pancreatic fistula. Watchful waiting was decided; on postoperative day 15, drain output was made of biliary and pancreatic fluid and on day 23 it was made only of biliary fluid. The patient was discharged on postoperative day 25 with the drains in place; on day 35, drainage ceased. The pathology report revealed a duodenal adenocarcinoma.

CASE 2: A 54-year-old female patient sought medical advice due to upper gastrointestinal bleeding. A tumor in the second part of the duodenum was detected by endoscopy. The patient underwent laparoscopic CPD with Child’s reconstruction. The neck of the pancreas was sectioned using electric scalpel. The pancreaticojejunostomy was performed with duct-to-mucosa anastomosis and a K-35 probe was inserted and left in the pancreatic duct (as in all the three cases) following the Blumgart technique. The immediate postoperative period was uneventful. On postoperative day two the patient presented tachycardia. abdominal pain and elevated serum amylase. A CT scan was requested (Figure 3) which showed peripancreatic fluid collection with thickening of the left anterior renal fascia, and free fluid in the Douglas’ pouch and interposed between bowel loops. On the next day, as the patient continued with generalized abdominal pain, guarding and drain output with pancreatic fluid content surgery was then decided. During exploration, free fluid and foci of cytosteatonecrosis were found (Figure 4). The cavity was washed, the drains were again placed and a feeding jejunostomy was created. The patient evolved with favorable outcome and was discharged on postoperative day 20. The pathology examination reported a 3-cm gastrointestinal stromal tumor (GIST) with low mitotic rate.

CASE 3: The last case is a 70-year-old obese female patient with a history of hypertension who presented jaundice. An abrupt amputation of the intrapancreatic common bile duct was observed in the CT scan and magnetic resonance imaging, but a tumor was not detected. An endoscopic ultrasound showed a small tumor obstructing the bile duct. The patient underwent conventional CPD with Child’s reconstruction. The neck of the pancreas was sectioned using electric scalpel as in all the patients of the series operated through laparotomy. The pancreaticojejunostomy was performed with duct-to-mucosa anastomosis (Blumgart technique). Six hours after surgery, the patient presented acute abdominal pain with shock requiring inotropic support. Hypovolemic shock was ruled out because of the absence of free fluid on ultrasound, the serohematic characteristics of drain output and the absence of fall in hemoglobin on laboratory tests. Other findings included metabolic acidosis and elevated amylase. The ultrasound also showed an enlarged pancreas remnant. The patient was transferred to the intensive care unit, where she was stabilized. The pain was relieved with opioids and non-steroidal anti-inflammatory drugs. Parenteral feeding was initiated. On postoperative day five the patient repeated acute abdominal pain. A CT scan was requested, which showed scarce free fluid in the Douglas’ pouch and Morrison’s pouch, thickening of the left anterior renal fascia and enlarged pancreatic remnant with hypoperfused areas (Figure 5). A gastrointestinal anastomosis leak was observed during reoperation, with multiple foci of cytosteatonecrosis. A gastrostomy was placed through the anastomotic fistula; a feeding jejunostomy was performed, drains were repositioned, and a polypropylene mesh was placed to close the wall. After the reoperation, the drain output had the characteristics of pancreatic fluid. On postoperative day 13, the patient required a new laparotomy due to hemorraghic drain output and drop in the hematocrit, but there was no evidence of active bleeding and areas of necrosis of the pancreatic remnant were observed. The cavity was washed, and drains were placed again. Five days later she presented fever and tachycardia; the inotropic support was increased, and a new CT scan show pancreatic and peripancreatic fluid collections. Vacuum-assisted closure (VAC) therapy was initiated. Yet, the patients died on postoperative day 35 due to multiple organ failure.

The pathology examination reported an undifferentiated adenocarcinoma of the bile duct.

Discussion

Cephalic pancreaticoduodenectomy is a procedure with high morbidity. Postoperative acute pancreatitis is one of its complications probably underestimated. As we have previously mentioned, it occurs in 55% of the cases according to the international literature and should be suspected in the presence of postoperative pain after CPD.

In most cases, mild pancreatitis occur without local or systemic involvement. In fact, most episodes of acute postoperative pancreatitis are not diagnosed and are treated as nonspecific abdominal pain. In any case, this inflammation is associated with postoperative pancreatic fistula. Winter⁵ made a retrospective analysis of 2323 pancreaticoduodenectomies and found hyperamylasemia in 1142 patients (49%). Of these patients, 16% (179 patients) developed pancreatic fistula, while only 41 patients (4%) of 1181 presented fistula with normal serum amylase.

While most postoperative pancreatitis are mild, some patients may develop local complications or more serious forms of pancreatitis. Postoperative acute pancreatitis is diagnosed by serum amylase levels and by CT scan, ultrasound or MRI showing enlargement of the pancreatic remnant. The three patients in our series with hyperamylasemia underwent imaging tests to evaluate the pancreatic remnant. The CT scan or MRI can show peripancreatic fluid collections, thickening of the renal fascia and even perfusion defects of the pancreatic remnant.

The causes of postoperative acute pancreatitis are difficult to determine. According to Banone¹, pancreatic duct diameter, soft pancreatic texture, exocrine insufficiency, additional resection of the pancreatic remnant and neoadjuvant therapy are independent predictors of postoperative acute pancreatitis. The type of approach, either by laparoscopy or open surgery, is not considered a risk factor for postoperative acute pancreatitis. It is important to emphasize that most publications consider the main etiology of acute pancreatitis is ischemia secondary to the section of the pancreas. The neck of the pancreas is irrigated by the dorsal pancreatic artery and its anastomoses with the branches of the pancreaticoduodenal arcade. When the neck of the pancreas is sectioned, the irrigation of the dorsal pancreatic artery and its anastomoses is interrupted, and ischemia of the entire pancreatic remnant may occur. Ischemia can also be due to section of the veins draining in the portal vein. Transient ischemia is sufficient to induce the cascade of changes associated with acute pancreatitis⁶. Changes in the microcirculation are the main problem. Vasoconstriction reduces the proportion of capillaries that are perfused exacerbating ischemia, and the endothelial disruption that occurs increases capillary permeability causing fluid extravasation and passage of activated proteases into the adjacent tissue. This process produces tissue damage with subsequent multiple organ failure⁷.

The administration of intravenous fluids during surgery prevents this impact on the remnant pancreas. Banone¹ demonstrated that in patients with a soft pancreatic remnant, a restrictive fluid balance was associated with a significantly increased risk of postoperative acute pancreatitis. Therefore, the intensive intraoperative hydration avoids the reduction in blood flow to the pancreas and thus prevents pancreatitis.

The moment when acute pancreatitis develops is variable. In our experience, two patients presented pancreatitis on the second and third postoperative day, without systemic involvement. The third patient presented acute pain in the immediate postoperative period, with significant systemic involvement and pancreatic necrosis. If the pathophysiology described above is analyzed, probably pancreatitis in the third patient is more directly related to an intraoperative event, while in the other two patients (with pancreatitis on the second and third postoperative day, respectively), the pathophysiology may respond to some other mechanism not yet described.

Treatment of mild acute pancreatitis include intravenous hydration, appropriate nutrition and pain management. In fact, as previously mentioned, many episodes of pancreatitis are not diagnosed, and the usual postoperative treatment after pancreaticoduodenectomy is adequate. Pancreatitis is associated with the development of pancreatic fistula and the management of the fistula determines the patient’s outcome.

Managing local complications that require treatment is more difficult as the associated pancreatic fistula increases the complexity. The infected peripancreatic collections can be drained percutaneously since reoperation will undoubtedly predispose to the leakage of any of the other anastomoses. In our experience, the three patients treated presented pancreatic fistula. One of the patients presented a dehiscence of the hepaticojejunostomy and the other developed gastrointestinal anastomosis leak. The biliary fistula did not require surgery and resolved spontaneously. The patient with the gastrointestinal anastomosis leak required surgery on postoperative day five and presented necrosis of the remnant pancreas and hemorrhage. In these cases with glandular necrosis, necrosectomy is a therapeutic option; the other option is to complete the left pancreatectomy, to be determined according to the amount of necrosis. The need for reoperation after acute postoperative pancreatitis is probably due to the complications of fistulas caused by pancreatitis. The adequate management should be individualized.

Conclusion

Postoperative acute pancreatitis is probable more common than expected. The analysis of the published literature suggests that most episodes are mild and resolve spontaneously; only a small percentage of patients will present local complications that may require percutaneous or surgical treatment, which may predispose to the development of fistulas that are sometimes difficult to manage.

Once pancreatitis has developed, there is no way to prevent pancreatic fistulas. Local complications will be treated according to their occurrence and impact, and may require a variety of procedures, ranging from percutaneous drainage to total pancreatectomy.