Lesions of the Pancreas

Acute Pancreatitis

Acute pancreatitis is an acute inflammation of the pancreas, varying in severity from mild abdominal pain to fulminant necrotizing pancreatitis and death. A histopathologic specimen of fulminant necrotizing pancreatitis shows diffuse stippled necrosis of the pancreatic parenchyma and peripancreatic fat ( Fig. 46.3 ). It has an incidence between 3.6 and 13.2 cases per 100,000 children. If episodes of acute inflammation completely resolve and then recur, it is termed acute recurrent pancreatitis. It is thought that complete interval resolution of morphology and function occurs between episodes, unlike in cases of chronic pancreatitis.

The causes of acute pancreatitis include trauma, biliary tract stone disease, choledochal cyst, ductal developmental anomalies, drugs, metabolic derangements, and infections. Most commonly, the cause is not apparent and is termed idiopathic. As the pancreas is fixed against the lumbar spine, trauma to the upper abdomen can fracture the pancreas or injure the major duct at that point ( Fig. 46.4 ). Biliary stone disease, increasing in frequency in children, may lead to pancreatitis from transient pancreatic duct obstruction. ERCP is safe and effective in children and is the preferred method for stone retrieval. Drugs that are thought to induce pancreatitis include asparaginase and valproic acid. Systemic illnesses and metabolic conditions, such as CF, Reye syndrome, Kawasaki disease, hyperlipidemias, and hypercalcemia, as well as viral infections (e.g., coxsackievirus and rotavirus) and generalized bacterial sepsis, also can cause pancreatitis.

As discussed previously, the relative obstruction found in pancreas divisum also can cause recurring episodes of pancreatitis. Symptomatic patients should undergo sphincteroplasty of the minor papilla. Endoscopic stenting, with or without sphincterotomy, is the preferred treatment, with operation reserved for recurrent cases. Choledochal cysts produce pancreatitis by pancreatic duct compression or bile reflux resulting from a long common biliary–pancreatic duct within the head of the pancreas. Other rare ductal anomalies may result in obstruction and recurring bouts of pancreatitis.

Although acute pancreatitis has many etiologies, they all appear to share a common pathway of nonphysiologic calcium signaling in the pancreas, followed by the premature activation of acinar proenzymes. These enzymes, especially trypsin, lead to acinar cell injury and cytokine release. The cytokines, along with vascular dissemination of activated enzymes, free radical formation, and release of vasoactive substances, such as kallikreins and histamine, together mediate extrapancreatic inflammation.

Diagnostic criteria for acute pancreatitis include at least two of the following: acute abdominal pain (especially in the epigastric region), serum amylase or lipase more than three times the upper limit of normal, and imaging findings characteristic or compatible with acute pancreatitis. The abdomen is diffusely tender with signs of peritonitis, and distention occurs with a paucity of bowel sounds. In severe cases of necrotizing or hemorrhagic pancreatitis, hemorrhage may spread away from the pancreas along tissue planes, appearing as ecchymosis either in the flanks (Grey Turner sign) or at the umbilicus (Cullen sign) ( Fig. 46.5 ). These ecchymoses generally take 1–2 days to develop.

Elevated amylase levels are helpful in the diagnosis, although a normal serum amylase level does not exclude pancreatitis. Hyperamylasemia also may be caused by salivary inflammation/trauma, intestinal disease (such as perforation, ischemia, necrosis, or inflammation), and macroamylasemia. Lipase has been suggested as an alternative marker, but can be falsely elevated in pancreatic cancer, macrolipasemia, renal insufficiency, cholecystitis, esophagitis, intestinal perforation, and hypertriglyceridemia. Elevated lipase tends to be more sensitive in infants and toddlers and may also help differentiate pancreatitis from salivary trauma. The degree of enzyme elevation does not correlate with disease severity.

Imaging the abdomen is important as part of the evaluation of the patient with abdominal pain. In the patient with pancreatitis, plain abdominal radiographs may reveal an isolated loop of intestine in the vicinity of the inflamed pancreas, termed the sentinel loop. Pancreatic calcifications suggest chronic pancreatitis. Plain chest radiographs should be performed in all patients with acute pancreatitis to look for evidence of pleural effusion and pulmonary edema.

Abdominal ultrasound (US) is useful in the evaluation of the patient with pancreatitis, but has limited applications. It is well established in the evaluation of biliary stone disease as the etiology for pancreatitis and can detect choledochal cysts and pancreatic pseudocysts as well. Advanced techniques such as contrast-enhanced US and US elastography have also been shown to be useful in the diagnosis of pancreatitis and its complications, but their availability is limited to a few experienced centers.

Abdominal computed tomography (CT) provides much better resolution of the pancreas than US. Its primary role is in the detection of early and late complications, such as pancreatic necrosis, pseudocysts, and fluid collections, and should be reserved for patients with more severe pathology or recurrent symptomatology with an equivocal US. If necessary, CT can be combined with interventional procedures to drain fluid collections.

MRCP is a newer, noninvasive technique for evaluating the biliary tree and pancreatic duct ( Fig. 46.6 ). It is the initial imaging study of choice for the evaluation of pancreatic ductal anatomy in children with recurrent or unexplained pancreatitis. Studies comparing MRCP and ERCP show high concordance in diagnoses. Its disadvantages are that it does not allow for therapeutic intervention (though it may direct the type of intervention necessary), its poor spatial resolution limits the visualization of ducts in smaller children, and it usually requires anesthesia in the pediatric age group.

The most frequent indication for ERCP in children is in the diagnosis or treatment of acute, recurrent, or chronic pancreatitis. A large single-institution retrospective study found a low rate of post-ERCP complications and a high therapeutic success rate. In that study, ERCP was shown to be particularly useful in the diagnosis of recurrent pancreatitis, though in only 60% of patients was an organic etiology found. Sphincter of Oddi manometry was particularly useful in establishing a diagnosis when no anatomic abnormalities were present.

The treatment for pancreatitis has remained unchanged for decades. The mainstays of therapy are pain control, intravenous fluid resuscitation, pancreatic rest, and monitoring for complications. Fluid resuscitation and maintenance should be guided toward a goal urine output of 2 mL/kg/h measured by an indwelling urinary catheter. Because of circulating cytokines, activated digestive enzymes, and other proinflammatory molecules, extracellular fluid losses can be enormous. Constant monitoring is necessary to avoid the development of severe hypovolemia. Patients with severe acute pancreatitis may require nasogastric decompression. Most patients receive histamine-2 (H ₂ ) receptor antagonists to reduce exposure of the duodenal secretin-producing cells to gastric acid, a potent stimulator of pancreatic secretion. This therapeutic regimen is logical but empiric, because no studies have shown improvement in outcomes with these interventions. The effectiveness of somatostatin in the treatment of pancreatitis is equivocal and probably serves more to mitigate complications of pancreatitis rather than to treat the disease itself. Further studies are needed to clearly define its role in both adults and children.

Nutrition is critically important in patients with pancreatitis. The past decade has seen a paradigm shift in the nutritional management of patients with pancreatitis. Early nutrition, within the first 72 hours, is still recommended. However, enteral nutrition (EN) has become the preferred method over total parenteral nutrition (TPN). Mild to moderate cases of acute pancreatitis often resolve prior to requiring EN or TPN. More severe cases should be treated with EN via a nasojejunal tube, though studies have demonstrated tolerance of nasogastric feeding in severe pancreatitis as well. TPN use, especially early in the disease course during the peak inflammatory response, has been associated with increased length of stay and delayed advancement of diet. When EN is contraindicated, some advocate waiting as long as 5 days prior to starting TPN. Compared with TPN, EN has been shown to decrease length of stay, reduce the need for surgery, and reduce the risk of infection. When restarting a diet, conservatively determined by resolution of symptoms, there appears to be no difference between clear liquids and solid food as the initial meal. Unfortunately, these data come almost exclusively from the adult population as pediatric trials are lacking.

Adequate analgesia is critical to minimizing the physiologic stress that develops from pain. Although meperidine (Demerol) was once advocated because morphine was thought to cause spasm of the Sphincter of Oddi, no clinical trials have shown superiority of meperidine over other narcotic analgesics. Large doses of meperidine, however, are associated with the risk of seizure, euphoria, and drug interactions, suggesting other narcotics such as morphine and fentanyl may be safer alternatives. The diagnosis of pancreatitis must be certain prior to initiating treatment with high doses of narcotics as these may mask signs of serious nonpancreatic pathology, such as intestinal or gastric perforations.

As pancreatitis progresses in severity, patients need to be monitored closely for signs of multisystem organ failure. Pleural effusions, pulmonary edema, and tense abdominal distention may lead to hypoxia requiring intubation and acute respiratory distress syndrome. Hypocalcemia, hypomagnesemia, anemia from hemorrhage, hyperglycemia, renal failure, and late sepsis also can be seen in these patients. Disagreement exists regarding the use of prophylactic antibiotics in severe cases of pancreatitis. The most recent adult data suggest a trend toward decreased mortality and infection with prophylactic antibiotics, but this study failed to reach statistical significance. Imipenem is the antibiotic therapy of choice when necessary.

Operative exploration is usually not necessary in acute pancreatitis. However, exploration is needed in patients with infected necrotic pancreatitis or a pancreatic abscess. Infected pancreatic necrosis increases mortality significantly. Diagnosis is typically by CT pancreatography, with confirmation of infection by fine-needle aspiration, clinical deterioration, or positive cultures. The latest adult data suggest that infected necrosis or peripancreatic abscesses are best treated in a stepwise manner from least to most invasive. When feasible, percutaneous drainage should be followed by minimally invasive necrosectomy if the patient fails to improve. Delayed operative therapy has been shown to improve mortality when compared with the rate in primary necrosectomy.

Pancreatic pseudocyst is a complication of trauma or pancreatitis that forms after injury to the pancreatic ductal system. The extravasated pancreatic enzymes and digested tissue are contained by the formation of a cavity composed from a fibroblastic reaction and inflammation that lacks an epithelial lining. The acute pseudocyst has an irregular wall on CT scan, is tender, and usually develops shortly after an episode of acute pancreatitis or trauma ( Fig. 46.7 ). Chronic pseudocysts are usually spherical with a thick wall and are commonly seen in patients with chronic pancreatitis. The distinction is important because half of acute pseudocysts resolve without treatment, while chronic pseudocysts rarely spontaneously resolve. An acute pseudocyst matures and forms a thick fibrous wall in 4–6 weeks, allowing for drainage. Those smaller than 5 cm in diameter usually spontaneously regress. When compared with those in adults, pseudocysts in children tend to resolve more frequently with medical therapy alone. There are anecdotal reports of pseudocyst resolution in children after treatment with long-acting somatostatin analogs.

Pancreatic pseudocysts that persist or are symptomatic require either a drainage procedure or excision. Endoscopic treatment, well established in adults, has been reported to be safe and efficacious in children as well. This should be performed only at centers with sufficient experience with these techniques. Other options include laparoscopic transgastric and intragastric drainage into the stomach or jejunum ( Fig. 46.8 ). Percutaneous drainage is the preferred approach for an infected pseudocyst because these cysts typically have thin, weak walls that are not amenable to internal drainage.

The three major complications of pancreatic pseudocysts are hemorrhage, rupture, and infection. Hemorrhage is the most serious complication and usually results from pressure and erosion of the cyst into a nearby visceral vessel. These patients require emergency angiography with embolization. Rupture or infection of a pseudocyst is uncommon. In both cases, external drainage is indicated.

Ascites in children can follow pancreatic trauma or pancreatic surgery. Free fluid results from the uncontained leakage from a major pancreatic ductal injury. When suspected, CT, ERCP, or MRCP should be performed to assess for a ductal injury. Nonoperative management initially consists of bowel rest with hyperalimentation and the use of long-acting somatostatin analogs. In many cases, the ascites resolves spontaneously with this treatment. The recent literature is full of controversy regarding optimal management for pancreatic trauma with a ductal injury. More complications, a longer time to goal feeds, and a higher rate of pseudocyst formation were found with nonoperative management in two recent retrospective reviews. On the other hand, other recent studies support nonoperative management of pancreatic trauma in children even in the presence of a ductal injury. When operative treatment is needed, depending on the nature and site of the injury, drainage alone may be sufficient. Distal ductal injuries can be treated with distal pancreatic resection, and recent experience has shown that the laparoscopic approach is safe and feasible. Proximal injuries require a Roux-en-Y jejunal onlay anastomosis to preserve pancreatic tissue. Pseudocyst formation is common in this patient population.

A pancreatic fistula can develop postoperatively or from nonoperative management. Most low-output fistulas close spontaneously but can drain for several months. Long-acting somatostatin analogs decrease fistula output and accelerate the rate of closure, but do not appear to induce closure of fistulas that would not otherwise have closed. Managing a pancreatic fistula centers around maintaining nutrition, with hyperalimentation necessary if enteral feeding increases fistula output, and ensuring the fistula tract does not become obstructed. Operative intervention with a Roux-en-Y jejunostomy anastomosed to the fistula site is usually curative if the fistula fails conservative management. Please see Chapter 16 for more information about pancreatic trauma.

Chronic Pancreatitis

Chronic pancreatitis is distinguished from acute pancreatitis by the irreversibility of the changes associated with the inflammation. Chronic pancreatitis remains a substantial clinical problem, afflicting roughly 140,000 individuals in the United States alone. The disease entails several clinical problems: (1) severe and intractable pain typically requiring narcotics; (2) malabsorption due to loss of pancreatic digestive enzymes from the exocrine pancreas, requiring chronic enzyme replacement for life; (3) life-threatening complications such as pancreatic pseudocyst, pancreatic ascites, biliary obstruction, etc.; (4) a 13-fold increased risk of pancreatic cancer ; and (5) the development of insulinopenia and overt diabetes mellitus in over half of patients (and probably most patients if they live long enough). Diabetes is likely due to the proximity of the endocrine pancreas to the inflamed exocrine pancreas.

Chronic pancreatitis can be classified as either calcifying or noncalcifying. The calcifying form, most common in hereditary or idiopathic pancreatitis, is more prevalent than the obstructive form in children and is associated with intraductal pancreatic stones, pseudocysts, and more aggressive scar formation. The obstructive type of chronic pancreatitis, which is associated with an anatomic or functional obstruction, is generally less severe with less scarring than calcifying pancreatitis. Single institutional experiences vary as to distributions in etiology, though the predominant causes are hereditary/genetic, obstructive, or idiopathic.

The discovery of a genetic basis for certain forms of chronic pancreatitis represents a major breakthrough in our understanding of its pathogenesis. Current thinking is that familial pancreatitis results from a combination of environmental triggers, genetic susceptibility, and an inappropriate immune response leading to chronic inflammation and fibrosis. Hereditary pancreatitis, the most common genetic cause of pancreatitis, can result from abnormalities in the cationic trypsinogen gene PRSS1 . This autosomal dominant condition most commonly results from one of two mutations that either prevent degradation of prematurely activated trypsin or make trypsin resistant to inactivation. Penetrance in this condition is approximately 80%. Other gene mutations implicated in chronic pancreatitis are SPINK1 and CFTR . Genetic testing is recommended for children with recurrent, idiopathic pancreatitis, with or without a family history of pancreatitis. Notably, patients with hereditary pancreatitis have a markedly increased risk of pancreatic cancer after age 50 years.

Obstructive pancreatitis is most often due to an anatomic or functional obstruction of the pancreatic duct. The most common anatomic causes are pancreas divisum followed by choledochal cysts. Uncertainty exists as to why a minority of patients with pancreas divisum develop chronic pancreatitis while most do not. The literature suggests that potential causes are the anatomic variant, structural narrowing of the minor papilla, sphincter of Oddi dysfunction, or the relatively high association with CFTR mutations. Many patients with ductal dilatation and anatomic or functional obstruction clearly improve with endoscopic sphincterotomy and/or stents. Pancreatic dyskinesia, though not well studied in children, may be improved by endoscopic sphincterotomy and sometimes temporary stent placement. For those in whom endoscopic treatment is not feasible or fails, individualized surgical treatment is reasonable based on the patient’s ductal anatomy, level of obstruction, and severity of pancreatic fibrosis.

Chronic pancreatitis can manifest with a characteristic pain, diminished pancreatic function, and radiographic abnormalities. Increased stool fat, diabetes, and steatorrhea are signs of pancreatic insufficiency. Frequently on a CT scan, the pancreas has microcalcifications throughout the parenchyma and calcified stones in the duct ( Fig. 46.9 ). Additionally, pancreatic pseudocysts or inflammation may be seen on the CT scan. ERCP and MRCP can evaluate the ductal anatomy and identify anatomic causes of chronic pancreatitis. Only ERCP provides a means for evaluating sphincter pressure measurements for functional obstruction.

Therapy for chronic pancreatitis is directed toward palliation of symptoms. Initial management for acute exacerbations is pain control and hydration. Steatorrhea indicates the need for pancreatic enzyme replacement. In general, these patients respond better with small, frequent meals. The diabetes that results from chronic pancreatitis tends to be unusually brittle, with a propensity for severe hypoglycemic episodes after even low doses of insulin. This hypersensitivity to insulin may be due to the loss of entire islets, which includes the glucagon-producing alpha cells that normally oppose the glucose-lowering effect of insulin.

In patients with chronic pancreatitis who have severe, intractable pain, ERCP or MRCP may help locate correctable problems such as large stones or a stricture with distal duct dilatation. Surgical options in chronic pancreatitis include sphincteroplasty, excision of localized pancreatitis, subtotal pancreatectomy, lateral pancreaticojejunostomy (modified Puestow procedure), and the duodenum or pylorus-preserving Whipple. Individualization of the operative approach and maximization of pancreatic ductal drainage are key. Patients failing more conservative surgical management may require a more definitive procedure to achieve symptomatic relief. Although the operative results in patients with hereditary pancreatitis are generally disappointing, evidence exists that complicated patients treated with a modified Puestow procedure may experience an improved quality of life (QOL), with subsequent improvement in pancreatic function and nutritional status ( Fig. 46.10 ). Unlike adults with hereditary pancreatitis, some reversal of the steatorrhea may be seen in children.