Lesions of The Pancreas

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Lesions of The Pancreas

The pancreas originates during week 4 of gestation as dual evaginations from the foregut endoderm. The dorsal pancreatic bud gives rise to the body and tail of the pancreas, its minor duct (Santorini) and papilla, and the continuation of the major duct (Wirsung) into the body and tail. The ventral pancreatic bud arises from the biliary diverticulum and swings around the dorsal aspect of the duodenal anlage during gut rotation to give rise to the head of the pancreas as well as the proximal portion of Wirsung’s duct (Fig. 46-1).1

The two pancreatic buds fuse to form one pancreas at approximately 7 weeks’ gestation, although it appears that complete fusion of the two ducts to form the main pancreatic duct is delayed until the perinatal period.2 The endocrine component of the pancreas, the islets of Langerhans, starts to differentiate before evagination of the pancreatic buds from the wall of the foregut. The islets comprise 10% of the pancreas during early embryonic and fetal life, but this contribution decreases to less than 1% in adulthood. Pancreatic acini begin to form at 12 weeks gestation and begin to accumulate organelles and zymogen granules at this stage, but do not secrete appreciable amounts of enzyme until birth.1

The pancreas is retroperitoneal and is light pink in children. The acini can be seen under low power loupe magnification, as can the septa dividing the lobulations. The head of the pancreas lies in the C-loop of the duodenum while the uncinate process, emanating from the posteromedial portion of the head, projects under the superior mesenteric artery (SMA) and vein. The neck of the pancreas is defined as that portion of the pancreas anterior to these vessels. The body and tail, to the left of these vessels, angle sharply towards the hilum of the spleen. The main pancreatic duct runs along the posterior aspect of the gland and curves downward in the head to run alongside the common bile duct, which runs in a groove posterior to the pancreas or within the substance of the posterior gland. The main pancreatic duct and common bile duct may fuse to form a ‘common channel’ before entry into the duodenum.

The pancreas is convex and its midportion is reflected over the anterior surface of the upper lumbar vertebrae and aorta. Its lateral aspects falls posteriorly toward each kidney (Fig. 46-2). The arterial supply of the pancreas is from the celiac and SMA, which form the pancreaticoduodenal arcade. The pancreas also has anastomoses from the splenic artery.3

Congenital Anomalies

Ectopic pancreatic rests are frequently encountered along foregut derivatives such as stomach, duodenum, jejunum, and colon, but are also infrequently encountered in the thorax and other sites.4–6 These lesions are found in approximately 2% of autopsy series and represent the most common anomaly of the gastric antrum. Moreover, they may cause gastric outlet obstruction.7 Their origin is unknown, but may be the result of aberrant epithelial–mesenchymal interactions leading to the transdifferentiation of embryonic epithelium into pancreatic epithelium. Several studies have implicated defects in hedgehog signaling and Notch signaling as the cause of ectopic pancreatic rests.8 Ectopic rests are typically asymptomatic and are encountered incidentally at laparotomy or during endoscopy. They can be identified as pancreatic tissue visually, because the surface has the same granular acinar appearance as the normal pancreas. These ectopic pancreatic rests usually do not become inflamed, possibly because they contain numerous small drainage ducts that usually do not obstruct; however, they can occasionally cause intestinal obstruction or bleeding. When encountered at laparotomy, ectopic rests should probably be excised, unless the excision would entail significant risk.

An annular pancreas is thought to result from faulty rotation of the ventral pancreatic bud in its course around the posterior aspect of the duodenal anlage. The duodenum is encircled and often obstructed by normal pancreatic tissue.9 Abnormal expression patterns of endodermal hedgehog may be responsible for the formation of annular and ectopic pancreas.8 Duodenal atresia and stenosis, intestinal malrotation, and trisomy 21 can often be found in combination with an annular pancreas.10 The clinical significance relates primarily to intrinsic duodenal obstruction, typically with bilious vomiting. Radiographic studies may reveal the classic finding of the ‘double-bubble’ sign. Management consists of bypass of the obstructing lesion with a duodenoduodenostomy or gastrojejunostomy, depending on the anatomy. Resection or division of the annular pancreas should not be performed due to the variable and complex ductal drainage system. Occasionally, patients with complex ductal anatomy may require reoperation for pancreatobiliary anomalies not apparent at the time of the initial surgery.11

Cystic fibrosis (CF) is an autosomal recessive condition, seen primarily in Caucasians which occurs in about 1 of 2,500 births.12 It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a protein expressed on the apical membrane of exocrine epithelial cells. CF leads to significant pancreatic insufficiency. The pancreatic secretions generally have a reduced amount of bicarbonate, a lower pH, and a lower overall fluid volume. The inspissated secretions lead to blockage of the ducts with dilatation. This may lead to acinar cell degeneration, acute and chronic pancreatitis, and pancreatic fibrosis. The result is impaired digestion of fats and proteins from loss of these digestive enzymes.13 See Chapter 32 for more information about CF.

Pancreatitis

Acute Pancreatitis

Acute pancreatitis is an acute inflammation of the pancreas, varying in severity from mild abdominal pain to fulminant necrotizing pancreatitis and death. 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.14

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 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. 46-3). Biliary stone disease, increasing in frequency in children, may lead to pancreatitis from transient pancreatic duct obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) is safe and effective in children and is the preferred method for stone retrieval.15 Drugs that are thought to induce pancreatitis include asparaginase and valproic acid.16 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, can also cause pancreatitis.17

Pancreas divisum is an anomaly of the pancreas present in 10% of the population and is thought to result from failure of the dorsal duct to fuse with the ventral duct. In pancreas divisum, the majority of exocrine pancreatic secretions, including those from the entire body and tail, must drain through the small minor duct of Santorini. The resulting relative obstruction may 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.18

Though 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.19

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.14 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’s sign) or at the umbilicus (Cullen’s sign) (Fig. 46-4). These ecchymoses generally take 1 to 2 days to develop.

Elevated amylase levels are helpful in the diagnosis, although a normal serum amylase level does not exclude pancreatitis. Hyperamylasemia may also 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 pancreatic from salivary trauma. The degree of enzyme elevation does not correlate with disease severity.19,20

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, the so-called ‘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 ultrasonography (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 ultrasound and ultrasound 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.21

Abdominal computed tomography (CT) provides much better resolution of the pancreas than ultrasound. 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 ultrasound. If necessary, CT can be combined with interventional procedures to drain fluid collections.22

Magnetic resonance cholangiopancreatography (MRCP) is a newer, noninvasive technique for evaluating the biliary tree and pancreatic duct (Fig. 46-5). 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.21,23

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.15 ERCP was shown to be particularly useful in the diagnosis of recurrent pancreatitis, though in only 60% of patients an organic etiology was 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 towards a goal urine output of 2 mL/kg/h measured by an indwelling urinary catheter. Because of circulating cytokines, activated digestive enzymes, and other pro-inflammatory 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 (H2) 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 empirical, 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.24

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). Patients with 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 to TPN, EN has been shown to decrease length of stay, reduce the need for surgery, and reduce the risk of infection.25 When restarting a diet, conservatively determined by resolution of symptoms, there appears to be no difference between clear liquid or solid food as the initial meal.26 Unfortunately, these data come almost exclusively from the adult population as pediatric trials are lacking.17,27

Adequate analgesia is critical to minimizing the physiologic stress that develops from pain. While 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.28

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 adult respiratory distress syndrome. Hypocalcemia, hypomagnesemia, anemia from hemorrhage, hyperglycemia, renal failure, and late sepsis can also be seen in these patients. Disagreement exists regarding the use of prophylactic antibiotics in severe cases of pancreatitis. The most recent adult data suggests a trend towards decreased mortality and infection with prophylactic antibiotics, but this study failed to reach statistical significance.29 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 suggests 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 demonstrates improved mortality compared to primary necrosectomy.30,31

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. 46-6). 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 four to six weeks, allowing for drainage. Those smaller than 5 cm in diameter usually spontaneously regress. When compared to those in adults, pseudocysts in children tend to resolve more frequently with medical therapy alone.32 There are anecdotal reports of pseudocyst resolution in children after treatment with long-acting somatostatin analogs.33

The 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.34

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