COMPLICATIONS IN PANCREATIC SURGERY
Despite recent technical advancements, post-operative complications after pancreatic surgery (especially after pancreatic resections) remain a major issue. The principal determinant of post-operative morbidity is – paradoxically – the pancreas, a very soft and friable organ that produces digestive enzymes. An early diagnosis and the correct management of post-operative complications require a broad experience in the field, and account for a favorable postoperative outcome. Here are listed the principal complications after pancreatic surgeries. Click on the links to learn more.
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.
The origin of pancreatic fistula differs according to the type of pancreatic resection:
- 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.
Many patients with grade B and C postoperative pancreatic fistula can be discharged with drains in situ and observed in the outpatient setting.
Postoperative hemorrhage is one of the most severe complications after pancreatic resections, with an incidence between 2% to 8%. The International Study Group of Pancreatic Surgery (ISGPS) developed an objective, generally applicable definition of PPH based on 3 parameters:
- Onset (early/late)
- Location (intraluminal/extraluminal)
- Severity (mild/severe)
Postoperative hemorrhage manifests with blood loss from drains or nasogastric tube, and/or clinical signs of hypovolemia (loss of blood volume). Unless the bleeding requires emergency treatment, all patients should be initially monitored (hemoglobin, red blood cell count, hematocrit, blood pressure, pulse, urine output). A CT-scan may be able to demonstrate the bleeding site and the associated abdominal collections.
Early post-pancreatectomy hemorrhage occurs in the first 24 hours postoperatively. It is caused most likely by technical failure of appropriate hemostasis during the index operation or an underlying perioperative coagulopathy. If feasible, it can be treated by blood transfusions; otherwise, re-exploraton and hemostasis are required. Re-exploration within 24 hours from the index operation does not modify substantially the post-operative course.
Late post-pancreatectomy hemorrhage occurs typically from complications of the operation, with a usual delay of several days or even weeks (eg, after intraabdominal abscesses, erosion of a peripancreatic vessel secondary to pancreatic fistula or intraabdominal drains, ulceration at the site of an anastomosis, or in association with an arterial pseudoaneurysm that has developed). A so-called “sentinel bleeding”, a small amount of blood loss via abdominal drains or nasogastric tube several hours before massive hemorrhage, may be present (30% to 100%). Diagnostic angiography may localize the bleeding site, and embolization can be performed. Otherwise, surgical re-exploration may be needed, especially to treat a massive bleeding or to treat a concomitant complication (e.g. pancreatic fistula). Endoscopy may play a role in intraluminal bleeding. Late hemorrhage is a serious event associated with mortality rates of 15-20%.
Intraluminal bleeding occurs into the bowel lumen. In pancreaticoduodenectomy and middle segment pancreatectomy bleeding may originate suture lines of the pancreato-enteric anastomosis because of enzymatic digestion of the blood vessel wall on the pancreatic stump surface by pancreatic exocrine enzymes secondary to a pancreatic leak. Other sites of intraluminal bleeding include the gastro-enteric or the duodeno-enteric anastomosis. Such bleedings usually depend on gastric/duodenal ulcer or diffuse gastritis. Intraluminal bleeding presents with dark blood in the nasogastric tube (if present), or with hematemesis and/or melena (black stools), and/or signs of hypovolemic shock. The treatment of bleeding from the enteric anastomosis is endoscopic, while bleeding from the pancreatic anastomosis may require surgical re-exploration.
Extraluminal bleeding occurs in the abdomimal cavity, and may originate from arterial or venous vessels in the areas of resection (especially retroportal lamina), or eroded and ruptured pseudoaneurysms, that are secondary to intra-abdominal infection with involvement of peripancreatic vessels, or vascular injury during resection. Intraluminal bleeding presents withblood loss from intra-abdominal drains and/or signs of hypovolemic shock. The treatment may be either surgical or angiographic.
The severity of bleeding can be differentiated into 2 categories based on the amount of blood loss or transfusion requirements: mild bleeding involves no clinical impairment, drop of hemoglobin level by <3 g/dl, and transfusion <3 units of packed red blood cells within 24 hours. Severe bleeding involves a large volume blood loss (drop of hemoglobin level by >3 g/dl), clinically significant impairment (eg, tachycardia, hypotension, oliguria, hypovolemic shock), need for blood transfusion >3 units of packed red blood cells within 24 hours, and need for invasive treatment (interventional angiographic embolization, or relaparotomy).
Post-pancreatectomy hemorrhage remains a major complication that at least requires a careful clinical monitoring, Recognizing this event in a timely fashion may prevent severe and fatal outcomes. A multidisciplinary expert team is mandatory to ensure the best treatment 24 hours/day.
DELAYED GASTRIC EMPTYING
Delayed gastric emptying consists in a functional gastroparesis, and it is one of the most common complications after pancreatic resection (especially after pancreaticoduodenectomy). Its incidence varies widely across surgical institutions (5-25%).The definition of delayed gastric emptying encompasses different clinical items, including:
- Prolonged naso-gastric tube or necrssity of naso-gastric tube reinsertion
- Inability to tolerate a solid diet
- Vomit and gastric distension
- Use of prokinetic drugs
The causes for delayed gastric emptying are still unclear and are probably multifactorial, involving disruption of pylorus innervation, motilin deficiency due to duodenum resection, and technical aspects. Several studies have suggested a greater incidence of delayed gastric emptying after pylorus-preserving than after Whipple pancreaticoduodenectomy, whereas others found the opposite effect. Another operative factors that may impact the rate delayed gastric emptying is method of reconstruction of gastric drainage (antecolic versus retrocolic). Finally, delayed gastric emptying is often secondary to pancreatic fistula, biliary fistula and abdominal collections.
When a delayed gastric emptying is suspected, it may be necessary to exclude a gastric outlet obstruction. This can be done by a gastrografin swallow X-ray (that allows the radiologist to see the movement of the dye through the digestive anastomosis), or an upper endoscopy (that allows visualization of the digestive anastomosis and of associated problems, such as anastomotic ulcers).
Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management:
- Delayed gastric emptying grade A usually does not lead to a marked change in management other than by minor disturbances in the return to intake of solid food or reinsertion of nasogastric tube for a brief period.
- Delayed gastric emptying grade B requires treatment with prokinetic drugs and parenteral or enteral nutritional support, and usually a prolonged reinsertion of the nasogastric tube.
- Delayed gastric emptying grade C necessitates a major change in clinical management, and possibly treatment of associated postoperative complications, such as pancreatic fistula or intra-abdominal abscesses. Consequently, further diagnostic workup and radiologic or operative interventions are often needed.
Delayed gastric emptying may lead to significant patient discomfort, and its treatment may be difficult. A multidisciplinary team including experienced gastroenterologists and dietitians is necessary to provide the best care.
Post-operative pancreatitis depends on local inflammation triggered by enzymatic digestion at the level of pancreatic remnant. Patients with a soft, acinar pancreas are more prone do develop postoperative pancreatitis, despite other patient-related factors may contribute to the pathogenesis. Early postoperative pancreatitis (day 1-3) usually contributes to the formation of a pancreatic leak. The diagnosis relies on elevated serum amylase levels, a dark-brown drain fluid, and poorly controlled postoperative pain. Postoperative pancreatitis necessitates changes in clinical managemement, including artifical nutrition.
Biliary fistula is defined as the output via a drain of any measurable volume of fluid containing bile. Drain fluid is typically greenish and thick. Most of the times biliary fistula does not cause serious clinical manifestations, although in few cases 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. Bile leakage may occur after pancreaticoduodenectomy or total pancreatectomy, and represents the failure of healing/sealing of hepatico-jejunostomy. Occasionally, biliary fistula may depend on a leakage from the cystic duct remnant. The incidence of biliary fistula is 3-5%. Treatment options include fasting and artificial nutrition to allow healing of the anastomosis. It may be necessary to place a percutaneous transhepatic biliary drainage if high-output fistulas do not resolve spontaneously.
Patients undergoing pancreatic surgery are at increased risk for pulmonary complications postoperatively. Major upper abdominal surgery alters postoperative pulmonary function, and reduces the efficiency of efforts to cough for as long as one week. These mechanisms lead to a decrease in functional residual and vital capacity for many days, and subsequently to atelectasis or pneumonia. Frail, elderly patients or patients with comorbidities are at increased risk of developing pneumonia. Postoperative pulmonary complications increase hospital morbidity, and prolong hospital stay. Therefore, postoperative chest physiotherapy was implemented. Respiratory exercises during hospitalization has been shown to improve respiratory performance as well as preventing postoperative pulmonary complications.
EXOCRINE PANCREATIC INSUFFICIENCY
Exocrine pancreatic insufficiency with maldigestion is caused by a deficiency of pancreatic enzymes production due to fibrotic replacement of normal pancreatic tissue or loss of pancreatic parenchyma. This condition is major consequence of chronic pancreatitis, but may also follow pancreatic resections. In pancreatic resections, the development of exocrine insufficiency depends on the type and the extension of resection, on the associated bowel resection, and on individual factors.
Digestion is often impaired after pancreaticoduodenectomy, and patients may experience steatorrhea and weight loss. This condition is often transient, and depends more on bowel resection than on the loss of pancreatic parenchyma. The duodenum, in fact, functions as an intestinal pacemaker and activates pancreatic enzymes. Most patients return to a normal bowel and pancreatic function within few months. Long-term exocrine insufficiency may depend on anastomosis failure with subsequent pancreatic duct obstruction and secondary chronic pancreatitis. signs of exocrine insufficiency are not present until 85 to 90% of the pancreas is unable to secrete enzymes. After left pancreatectomy, exocrine isufficiency is uncommon.
Total pancreatectomy is invariably associated with exocrine insufficiency and impairment of gastrointestinal motility. However, these conditions tend to ameliorate over time (with an appropriate replacement therapy) such that the reported 1-year quality of life seems to be comparable to patients who underwent pancreaticoduodenectomy.
Symptoms of exocrine pancreatic insufficiency are mainly related to lipids and protein maldigestion, and include (in a variable degree) malabsorption, diarrhea, steatorrhea, and weight loss. Recurring abdominal pain may be present. Breakdown of carbohydrates can be partially taken over by amylase in the saliva and enzymes in the small intestine; while breakdown of proteins may be partially taken over by gastric peptidase and enteropeptidase. Deficiency of liposoluble vitamins is usually present.
Quantification of exocrine pancreatic insufficiency requires functional tests. Among them, determination of fecal elastase-1, fecal chymotripsin, and stool fat content are the most widely available.
The mainstays of exocrine pancreatic insufficiency treatment are a balanced low-fat diet, supplementation with trace elements and vitamins, and enzyme replacement therapy. A pancreatic enzyme preparation (pancreatine) contains lipases, alpha-amylase, and proteases. The strenght of the preparation is defined as the content of lipase per capsule (microspheres or minimicrospheres), where 10.000 = 10.000 lipase units. Up to 40.000 lipase units per capsule are commercially available.
The capsules must be taken with meals or immediately thereafter. Enzyme preparations are acid-resistant and become activated under basic pH, in the small intestine. Nevertheless, proton-pump inhibitors may be associated to maximize their activation, especially in the case of gastric hyperacidity. Therapeutic success is primarily determined on a clinical basis.
ENDOCRINE PANCREATIC INSUFFICIENCY
Some patients develop endocrine pancreatic insufficiency after pancreatic resection, consisting in impaired carbohydrate metabolism up to diabetes mellitus. Diabetes after pancreatic resection depends on loss of Langerhans islets and deficiency in the production of insulin.
After partial pancreatic resection, it is common to experience a temporary impairment of carbohydrate metabolism, especially in those patients who receive parenteral nutrition. This condition can be resolved with an adequate diet and a mild antidiabetic therapy. If diabetes develops, insulin is needed to control hyperglycemia and prevent long-term complications. Insulin is given subcutaneously using pre-filled pens. In some patients, diabetes may develop several years after the resection, and depends on chronic obstructive pancreatitis of the remnant.
The relationship between partial pancreatic resections and diabetes mellitus is still unclear. Patients undergoing left pancreatectomy seem to be at greater risk of developing some form of diabetes in the long term, because the bulk of Langerhans islets is naturally located in the pancreatic tail.
Total pancreatectomy results in a complete loss of pancreatic endocrine function, with full-manifestations of pancreoprival diabetes. The absence of both insulin and glucagon (that oppose one another) increases the risk for hyperglycemia and hypoglycemia. Significan glycemic fluctuations may occur, with marked post-prandial hyperglycemia and sudden hypoglycemia after insulin administration or during prolonged fasting. Therefore, it is important to provide a diabetes treatment plan that includes frequent blood sugar monitoring and flexible insulin therapy to help decrease the risk of high and low blood sugar.