Lesions of the Pancreas Flashcards

Question

What is pancreas divisum?

Answer 1

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. It is the most common congenital anomaly of the pancreas. 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. Endoscopic retrograde cholangiopancreatography (ERCP) is regarded as the most definitive and reliable diagnostic method for revealing pancreas divisum. However, the ERCP sometimes can induce pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive and accurate method in the diagnosis of pancreas divisum. The clinical relevance of pancreas divisum remains controversial. A relative obstruction to pancreatic exocrine secretory flow through the duct of Santorini and minor papilla could result in pancreatitis in a small number of patients with pancreas divisum.

Answer 2

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. 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. Their origin is unknown, but may be the result of aberrant epithelial–mesenchymal interactions that lead 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. 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 of complications.

Answer 3

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 can be obstructed by normal pancreatic tissue. Abnormal expression patterns of endodermal hedgehog may be responsible for the formation of annular and ectopic pancreas. Duodenal atresia and stenosis, intestinal malrotation, and trisomy 21 often can be found in combination with an annular pancreas. The clinical significance relates primarily to an 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 operation.

Answer 4

Cystic fibrosis (CF) is an autosomal recessive condition, seen primarily in Caucasians, and occurs in about 1 of 2500 births. It is caused by mutations in the CF 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.

Answer 5

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. 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. 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 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.

Answer 6

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). 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. 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.

Answer 7

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. 1) Fluid resuscitation 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. 2) Pancreatic rest 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 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. 3) Nutrition 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. 4) Pain control 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. 5) Monitoring and indications for operation 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.

Answer 8

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. 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. 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. — Pancreatic tumors in children are quite rare. The most commonly encountered lesion of the pancreas in pediatric surgical practice is a pancreatic fluid collection or pseudocyst following pancreatic trauma or an episode of pancreatitis. In fact, one of the challenges of a pediatric surgeon is to decide when a lesion is not likely to be a pseudocyst. History is extremely critical in arriving at the correct diagnosis of a pancreatic cystic lesion. Fluid collections and pseudocysts are more likely to occur following an episode of severe pancreatitis in children than in adults. However, they also tend to behave in a less-aggressive manner in the pediatric age group. A pseudocyst is defined as a pancreatic fluid collection that has been present for 4 weeks or more. As mentioned in the index case, multiple treatment modalities now exist for the treatment of these lesions. In the past, internal drainage to the stomach or a small intestinal loop was the most commonly practiced treatment. Typically, pseudocysts had to reach a size of 6 cm and have a wall at least 6-mm thick to be amenable to internal drainage. However, the treatment paradigm has changed to one based upon symptoms. Asymptomatic pseudocysts of any size, etiology, and location within the pancreas may be observed. The fear of pseudocyst rupture or hemorrhage is unfounded. The surgical dictum of “putting the pancreas to rest” is no longer applicable and enteral feedings by any route have been found to be associated with better outcomes. Sherif

Answer 9

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.

Answer 10

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.

Answer 11

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 cancer48 ; 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.

Answer 12

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.

Answer 13

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.

Answer 14

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.

Answer 15

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. 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.

Answer 16

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 glucoselowering 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. Unlike adults with hereditary pancreatitis, some reversal of the steatorrhea may be seen in children.

Answer 17

In newborns and young infants, the major causes are: (1) congenital hyperinsulinism of infancy, previously called nesidioblastosis; (2) a lack of substrate for gluconeogenesis (e.g., glycogen storage disease); and (3) inadequate gluconeogenic hormones (e.g., hypothyroidism or growth hormone deficiency). In children with the onset of hypoglycemia after 1 year of age, the causes are different, with insulinoma being the most common.

Answer 18

Nesidioblastosis, the original term for what is now called congenital hyperinsulinism of infancy (CHI), comes from the Greek nesidio, meaning “island,” and blast, meaning “new formation.” Nesidioblasts were originally thought to be progenitor cells in the wall of the pancreatic ducts, which overproliferate in patients with this condition. With the advent of genetic analysis, this pathogenesis is now known to be incorrect. Mutations in seven genes are currently known to cause CHI, though roughly half of cases are caused by genetic malformations not yet understood. Initially discovered was the loss-of-function mutations in the SUR1 and Kir6.2 components of the ATP-sensitive potassium channel (KATP) found in the cell membrane of the pancreatic β-cell. These mutations either impair the ability of Mg-adenosine diphosphate (ADP) to stimulate channel activity or affect the expression of the KATP channels at the surface membrane, resulting in continuous depolarization of the β-cell membrane and dysregulated insulin secretion. Heterozygous gain-of-function mutations in GULD1, the mitochondrial gene encoding glutamate dehydrogenase, leads to CHI caused by the insensitivity of the enzyme to inhibition by guanosine-5′-triphosphate. This gain-of-function mutation results in a milder form of CHI, which may be diagnosed later in childhood, and is associated with hyperammonemia and occasionally epilepsy. Heterozygous loss-of-function mutations in HNF4A, an islet transcription factor gene, are also associated with CHI through unknown mechanisms. More rare are cases of CHI caused by mutations in glucokinase (GCK), hydroxyacyl-coenzyme A dehydrogenase (HADH), and the solute carrier SLC16A1. — The earliest indication for pancreatic resection due to symptomatic lesions occurs in hypoglycemic neonates. Formerly called nesidioblastosis, the condition is now referred to as congenital hyperinsulinism or persistent hyperinsulinemic hypoglycemia of infancy. Significant advances have occurred in the diagnosis and treatment of these lesions over the last two decades, leading to important changes in the treatment paradigm. It is now recognized that the disease consists of two forms, a diffuse and a focal form. Differentiation between the two is essential prior to surgical treatment and relies on genetic testing and 18 fluorodihydroxyphenylalanine positron emission tomography/computed tomography scan (18 F-DOPA PET/CT). At least half the patients have focal disease and are cured by segmental pancreatectomy. The diffuse form of the disease represents a spectrum of severity based on the amount of glucose infusion necessary to maintain euglycemia. Medical management with diazoxide, octreotide, and other agents may be able to control less severe cases. Patients who do not respond to maximal medical management require a 95% pancreatectomy, leaving a small pancreatic rim along the duodenum. The outcomes of these patients are inferior to those with focal disease. Congenital hyperinsulinism is exceedingly rare and several centers around the world have developed enhanced medical and surgical expertise in both its diagnosis and treatment. Strong consideration should be given to referral of these patients to one of these centers if local expertise is unavailable. Sherif

Answer 19

CHI occurs in a focal and diffuse type, the differentiation of which is critical for operative management. Unfortunately, however, the clinical presentation is identical. Patients with SUR1 mutations often have the focal type. The focal type is actually a focal adenomatous hyperplasia, different from an adenoma. Histologically, it is seen as a confluence of hyperplastic but otherwise normalappearing islets. There is little insulin present within the lesion due to excess secretion, while uninvolved islets outside are small with high insulin content. — The diffuse type is macroscopically normal, but careful evaluation of the islets reveals enlarged β-cells with abnormally large nuclei, a large Golgi apparatus, and weak insulin staining due to hypersecretion.

Answer 20

CHI patients typically develop hypoglycemia shortly after birth, though it may manifest at a later age. Infants with CHI are often macrosomic. Symptoms may be subtle, such as lethargy and irritability, or severe with apnea, seizures, and coma. Simultaneous insulin and glucose measurements show a high ratio of insulin to glucose, keeping in mind that insulin levels may be normal but inappropriate in the presence of hypoglycemia. These patients differ from insulinoma patients, who usually have high absolute insulin levels. Another powerful indicator of CHI is a glucose requirement greater than 8 mg/kg/min. Owing to the much higher incidence of insulinoma, patients older than 1 year at the onset of hypoglycemia should be evaluated for both conditions.

Answer 21

Stabilization of the CHI patient includes frequent intermittent or continuous feeding, with the addition of intravenous glucose as needed. Central venous access is advised because adequate venous access is lifesaving and high concentrations of intravenous glucose may be necessary. Maintaining normoglycemia is key to preventing potentially disabling hypoglycemic brain injury. Intramuscular glucagon can be used as a temporizing measure until definitive venous access is obtained. Treatment of CHI begins with medical management. Diazoxide remains a mainstay of therapy. Diazoxide binds the SUR1 component of the KATP channel and maintains it in a persistently open state, preventing insulin secretion. Patients with diazoxide-sensitive CHI who can tolerate fasting can be managed medically until they outgrow their condition. Those unresponsive to diazoxide should be managed with frequent feedings, glucose infusions, and somatostatin analogs. Somatostatin analogs inhibit pancreatic insulin secretion and can be administered subcutaneously either intermittently or continuously by a pump. Somatostatin analogs are associated with gallstones and biliary sludge, and have been implicated in cases of necrotizing enterocolitis. Medical failure to control hypoglycemia necessitates surgical intervention. Distinguishing diffuse versus focal CHI is critical for operative planning. The development of a fluoro-18-Ldihydroxyphenylalanine (18 F-DOPA) positron emission tomography–CT (PET-CT) scanner has replaced pancreatic venous sampling as the optimal method for delineating focal versus diffuse disease with a sensitivity of 94% and specificity of 100%. Intraoperative US can provide additional anatomic detail to help avoid injury to the biliary tree. For the focal type, resection of the hypermetabolic focus is curative. Focal lesions in the head may require duodenum-preserving pancreatic head resection and distal pancreaticojejunostomy with excision of distal lesions via spleen-preserving distal pancreatectomy. In patients with diffuse disease, a near-total pancreatectomy is needed, leaving only a rim of pancreatic tissue along the common bile duct. The laparoscopic approach for both procedures has been reported, but data are limited. Operative complications include bile duct injury, pancreatic insufficiency, and the need for repeat pancreatic resection due to persistent hypoglycemia. Alternative forms of hyperinsulinemic hypoglycemia can arise secondary to maternal diabetes, birth asphyxia, or intrauterine growth restriction (IUGR). In these patients, the condition is transient, resolving for most patients within several days. A subgroup of patients with IUGR and prenatal asphyxia will have a prolonged condition that requires diazoxide for several months prior to resolution. Approximately 50% of children with Beckwith–Wiedemann syndrome have a CHI-like condition that tends to resolve spontaneously, but 5% will eventually require pancreatectomy.

Answer 22

The long-term outlook for these patients depends primarily on the age at onset, which reflects severity of disease, and on an expeditious diagnosis because a late diagnosis results in a higher incidence of neurologic sequelae. Most patients seem to grow out of the disease after several years, implying diminished activity of the β-cells. Near-total pancreatectomy in one series was associated with a 91% incidence of insulin-dependent diabetes by age 14; however, no patient with focal resection required long-term insulin therapy, emphasizing the need for a conservative operative approach when possible.

Answer 23

Glycogen storage disease type Ia (GSD Ia) and Ib classically appear as severe hypoglycemia in infants caused by the inability to dephosphorylate hepatic glycogen subunits into glucose. GSD Ia is caused by inactivating mutations of the glucose-6-phosphatase enzyme itself, whereas GSD Ib results from inactivating mutations of the glucose6-phosphate transporter. Hypoglycemia becomes apparent when the time between feedings increases and the liver fails to generate glucose from glycogen stores. It is clinically diagnosed by hypoglycemia, hypoinsulinemia, hepatomegaly, nephromegaly, ketosis, and hyperlipidemia. Central venous access is required for continuous infusion of highly concentrated glucose. Survivors into adulthood have an increased incidence of hepatic adenoma after age 25 and have a 10% risk of malignant transformation. Liver transplantation ultimately becomes necessary in these patients.

Answer 24

The only pancreatic endocrine tumors seen in infants and children are insulinomas, gastrinomas, and VIPomas. VIPoma is a tumor of vasoactive intestinal peptide (VIP) producing cells and only case reports exist in children. Insulinoma is the most common of the three, though still quite rare among pediatric tumors in general. Only 10% of insulinomas are malignant, and these tend to spread to the liver and peripancreatic lymph nodes. Insulinomas cause symptoms of hypoglycemia, including dizziness, headaches, confusion, sweating, and seizures. The classic Whipple triad was described in patients with insulinoma and consists of symptoms of hypoglycemia with fasting, glucose levels less than half of normal when fasting, and relief of symptoms with glucose administration. Patients are typically in their adolescence, though younger children have been described with insulinoma. The lesions are usually solitary, except in multiple endocrine neoplasia type I (MEN I), in which multiple insulinomas may be found.

Answer 25

The gold standard test for insulinoma is the 72-hour fast, though studies have shown that a positive result is achieved in 80–90% of patients with insulinoma after a shorter 24or 48-hour fast, respectively. While fasting, periodic blood glucose levels are obtained. When the patient’s blood glucose falls below 50 mg/dL and symptoms are present, blood is drawn for plasma glucose, C-peptide, proinsulin, insulin, β-hydroxybutyrate, and sulfonylureas. Administration of exogenous insulin, followed by measurement of the Cpeptide level, can be suggestive of an insulinoma, but is not completely reliable. Measuring the insulin-to-glucose ratio is no longer needed. Preoperative localization is challenging but can be extremely helpful. Extrapancreatic insulinomas are rare. Most experts advocate for both transabdominal US and CT for initial localization, which identifies more than half of the tumors. Centers experienced with endoscopic US also have reported good success in detecting insulinomas, but this expertise is not widely available. Magnetic resonance imaging (MRI) is most useful for detecting liver metastases. If noninvasive studies fail to identify the tumor, intra-arterial calcium stimulation via a catheter in several visceral arteries with parallel venous sampling from the right hepatic vein has been reported to regionally localize insulinomas in 80–94% of cases. Intraoperative US is strongly advocated for identification of adjacent biliary and vascular structures, and as a method of last resort if nonoperative localization fails.

Answer 26

All patients with insulinoma should undergo resection. Insulinomas are pink, firm, encapsulated, and usually amenable to enucleation. In most cases, through preoperative and intraoperative analysis, the tumors can be localized, but in patients in whom they cannot be localized, blind distal pancreatic resection is no longer advised. The distinction between benign and malignant lesions is difficult and is based on tumor size (<2 cm tend to be benign) and the presence of metastases. Insulinomas that are hard, cause puckering of surrounding tissues, appear infiltrating, or cause distal pancreatic duct dilation should be assumed malignant and resected with a margin instead of enucleated. Malignant tumors can be treated with chemotherapy, biotherapy (such as octreotide), hepatic artery embolization/chemoembolization, radiation therapy, or radiofrequency ablation.

Answer 27

Fetal gastrin-producing cells in the pancreas are believed to give rise to pancreatic gastrinoma. In the fetus, the primary source of gastrin is the pancreas. After birth, the gastric antrum becomes the principal source. Zollinger-Ellison syndrome (ZES) consists of gastric hypersecretion with severe peptic ulcer disease and a gastrin-producing tumor, classically in the pancreas. ZES may occur as part of the MEN I syndrome or sporadically. Gastrinomas are now understood to be frequently malignant, especially with spread to the liver, and their removal is strongly advocated. The diagnosis of a gastrinoma is based on hypergastrinemia and gastric hypersecretion. Fasting gastrin levels are usually elevated but can be normal. Patients suspected of having ZES should undergo a secretin stimulation test, which is considered positive if the gastrin level increases by 200 pg/mL or more. Localization can be challenging because the tumors are often small and may be extrapancreatic, but CT, MRI, endoscopic US, and indium-111 octreotide scintigraphy have been utilized to localize the tumors. Extrapancreatic tumors are often found in the duodenal wall.

Answer 28

Medically, patients should initially be treated with omeprazole to control peptic ulcer disease and prevent bleeding. All disease should be excised if possible to control symptoms and help prevent metastases. Patients cured by resection should be followed closely as recurrence is common. Medical treatment for unresectable disease includes proton pump inhibitors and octreotide. Tumor debulking in unresectable cases is recommended to improve patient QOL and increase life expectancy. Chemotherapy has been utilized in a few cases with good results. There is a report of a patient with multiple gastrinomas managed medically who survived 26 years before succumbing to unrelated causes.

Answer 29

Although most cystic lesions of the pancreas are pseudocysts and are acquired, congenital cysts may be seen at an early age as a symptomatic mass with compression of surrounding structures. Alternatively, these congenital cysts may be noted incidentally on physical examination or radiographic studies. Congenital cysts contain cloudy, straw-colored fluid. The cysts are most often found in the distal pancreas and are amenable to local resection with a rim of normal pancreas. Lesions in the pancreatic head should be internally drained with a Roux-en-Y cystjejunostomy. Congenital duplications of the foregut also may present as pancreatic cysts. They have a gastric or intestinal mucosal lining and maintain pancreatic ductal communication. Gastric acid secretion from the cyst may cause episodes of pancreatitis. Surgical resection is necessary, in the form of enucleation, distal pancreatectomy, or even pancreaticoduodenectomy. Acquired non-neoplastic cysts of the pancreas are called retention cysts and appear to result from obstruction of the smaller pancreatic ducts. The preoperative distinction of a retention cyst from other types of cysts or pseudocysts may be difficult but is supported by finding a small cystic lesion in communication with the pancreatic duct that has a proximal stricture. These can be excised if symptomatic or otherwise observed. However, they are often confused with neoplastic cysts and are resected for this reason.

Answer 30

The pancreatic exocrine system includes the pancreatic ducts, centroacinar cells, and acini. Tumors from this system include pseudopapillary tumors, ductal adenocarcinomas, acinar cell carcinomas, and pancreatoblastomas. Cystic tumors of the pancreas, including serous and mucinous cystadenomas and cystadenocarcinoma, are well described in adults but are exceedingly rare in the pediatric population. Several case reports exist of serous and mucinous cystadenomas, but one review suggests that no confirmed reports of cystadenocarcinoma in children exist in the literature. Management of serous cystadenoma is debated based on its benign nature, but excision appears curative.

Answer 31

Exocrine pancreatic cancers account for roughly half of pancreatic neoplasms in children. Whereas ductal adenocarcinoma is most common in adults, its embryonic counterpart pancreatoblastoma is more common in children. Pancreatoblastoma is believed to result from the persistence of embryonic pancreatic progenitor cells beyond the eighth week of gestation. It tends to be diagnosed in early childhood and is more common in boys and those of Asian descent. An allelic loss on 11p is often associated and suggests a similar pathogenesis with Beckwith–Wiedemann syndrome and other embryonic tumors. A large multicenter review demonstrated that the tumor distribution was homogenous throughout the pancreas, most were larger than 5 cm at presentation, and over half had distant metastases. Elevation of serum α-fetoprotein was an inconsistent feature. The prognosis is relatively good with complete resection and with appropriate neoadjuvant and/or adjuvant chemotherapy and radiation therapy. Relapse is common, so continued monitoring is essential. — Acinar cell carcinoma and ductal adenocarcinoma are less common pancreatic exocrine tumors. Ductal adenocarcinoma is infrequently reported in the pediatric literature, and no definitive recommendations are possible. Acinar cell carcinoma is comparatively more common. Complete resection for both tumor types appears necessary with appropriate provision of neoadjuvant or adjuvant chemotherapy based on pretreatment staging. Long-term survival improves with an earlier stage at presentation. — Occurring slightly less frequently than pancreatoblastoma is the solid pseudopapillary tumor, also known as a papillary-cystic tumor or Frantz tumor. It has a female preponderance and is derived from exocrine cells but without acinar or ductal structures. Presenting symptoms often include a palpable abdominal mass and abdominal pain. These tumors can be very large at the time of diagnosis. They are very slow growing, and there are reports of patients surviving 20 years after diagnosis without treatment. Although these tumors are rarely metastatic, excision of regional and distal metastases greatly improves survival. Even with its indolent nature, an aggressive approach with complete resection is recommended as one retrospective study of patients with incomplete resections showed poor long-term survival.

Answer 32

E Dorsal bud forms most of pancreas. Normally, ventral bud rotates backward; if it does not occur, the condition is called annular pancreas. Normally duct of Wirsung becomes the major duct in the end. If two-duct system fails to fuse, condition is called pancreatic divisum. In this condition, dorsal duct (duct of Santorini) becomes the main duct. Dorsal bud forms most of head, body and tail of pancreas. Ventral bud forms posterior and inferior part of the head. Syed/MCQ

Answer 33

B Head is at the level of L2, body is at the level of L1 and tail is at the level of T12. Anatomical continuity is through peritoneal reflection from transverse mesocolon, small intestinal mesentery, lienorenal and splenocolic ligament. Venous drainage is through superior mesenteric vein. Syed/MCQ

Answer 34

D Mumps, ERCP, and choledochal cyst are all causes of pancreatitis. Syed/MCQ

Answer 35

A Serum amylase is nonspecific, as it also increases in intestinal perforation, intestinal obstruction, and acute cholecystitis. ERCP is rarely indicated but is helpful in relapsing pancreatitis associated with pancreaticobiliary malunion. Syed/MCQ

Answer 36

D Meperidine is better than morphine because the latter produces spasms of the ampulla of Vater. TPN is part of the treatment and helpful. Glucagon, somatostatin and anticholinergics are all part of the treatment. Surgical intervention is required when diagnosis is uncertain, when there are complications like pseudocyst or abscess or when the cause is surgically correctable pancreaticobiliary disease. Syed/MCQ

Answer 37

A Chronic relapsing pancreatitis is characterised by recurrent episodes of upper abdominal pain. Syed/MCQ

Answer 38

C Pseudo-pancreatic cyst does not have epithelial lining. Cyst lies mostly in lesser sac, surrounded by fibrous capsule, formed by stomach, duodenum, small intestine, colon and omentum. Syed/MCQ

Answer 39

D Medical management is supportive therapy, which is generally required for 6 weeks if no improvement surgical therapy is required. Syed/MCQ

Answer 40

C Diazoxide helps by inhibiting glucose stimulated insulin secretion. Mesoxalyl urea is the beta cell cytotoxic agent. In surgery, 95 percent resection of the pancreas is required, leaving a rim of tissue on duodenum and bile duct. Syed/MCQ

Answer 41

A Rise in white cell count is a feature of Ranson criteria on admission, not during first 48 hours. Syed/MCQ

Answer 42

D The dorsal pancreatic bud arises from the dorsum of the foregut just distal to the stomach and the ventral pancreas arises from the biliary diverticulum. Fusion of the parenchyma of the two buds is typically complete by 7 weeks’ gestation but duct fusion is delayed until the perinatal period. The major arterial blood supply is from the coeliac axis and the SmA, which gives rise to the superior and inferior pancreaticoduodenal vessels. SPSE 1

Answer 43

B Duodenal atresia or stenosis is seen in as many as 50% of patients with annular pancreas. Trisomy 21 and malrotation occurs in about 20% of patients each. Complex congenital heart disease and tracheo-oesophageal fistula are also associated with annular pancreas. SPSE 1

Answer 44

E In annular pancreas, frequently a thin, flat band of pancreatic tissue arising from the head of the pancreas surrounds the second portion of the duodenum. Typically there is coexisting duodenal stenosis or atresia and the pancreatic tissue may penetrate the duodenal muscularis. Bypass of the duodenal obstruction should be performed without mobilising the annular pancreas because injury to the pancreas could result in production of a chronic fistula. SPSE 1

Answer 45

B The frequency of PD in the general population is between 5% and 10%. The majority of patients with PD are asymptomatic. Endoscopic retrograde cholangiopancreatography (ERCP) is the most helpful preoperative imaging study in patients with PD. For symptomatic patients, operative sphincteroplasty seems to have the greatest benefit. There is little data to support endoscopic sphincterotomy in children. SPSE 1

Answer 46

D CF results from a defect in a cAmP-induced transmembrane chloride channel. Although rectal prolapse may be seen in up to 30% of patients with CF it is rarely the presenting symptom (<3%). Neonatal presentation rarely includes glucose intolerance. male patients with CF are typically infertile and may have bilateral absence of the vas deferens noted at diagnostic laparoscopy. Fertility in women is reduced only slightly. SPSE 1

Answer 47

B Fibrosing colonopathy (FC) is a sequela of prolonged exposure to high-dose pancreatic exocrine supplementation. Fusiform segmental colonic narrowing with submucosal fibrosis presents with symptoms of distal colonic obstruction. Initial management includes reduction in supplemental enzyme dose. most cases eventually require surgical therapy. Children should be maintained on less than 10 000 units/kg/day of pancreatic enzyme. The coating and manufacturer are not independently associated with the risk of FC. Gastrograffin enema and polyethylene glycol are effective therapies for distal intestinal obstruction syndrome. SPSE 1

Answer 48

A Congenital hyperinsulinism, or persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), is a rare disorder of glucose metabolism. most patients have a disorder of the sulfonylurea receptor (SuR) gene or the Kir6.2 gene regulating the associated potassium channel. manifestations include severe hypoglycaemia with detectable insulin levels and maintenance glucose requirements greater than maximal hepatic production. Hypoglycaemia may occur in patients with Beckwith–Wiedemann’s syndrome or in those with glycogen storage disease, which are separate disorders from PHHI. SPSE 1

Answer 49

A Initial therapy of PHHI is directed at correcting hypoglycaemia including intravenous glucose administration, frequent oral feedings and medical therapy to control insulin secretion. First-line medications include diazoxide (activates potassium adenosine triphosphate channel through sulfonylurea receptor-1 to inhibit insulin secretion) and octreotide (activates beta-cell potassium channels to inhibit insulin secretion). Alternative therapies include glucocorticoids (promotes insulin resistance), streptozotocin (beta-cell toxin), nifedipine, and glucagon. SPSE 1

Answer 50

E Because of the risk of brain injury, most clinicians believe pancreatic resection, rather than medical management and high-glucose diet, is necessary in patients with PHHI. Patients with a sulfonylurea receptor defect typically have a more severe, diffuse form of PHHI and require more extensive resection. Islet cell preservation with autotransplantation is an evolving therapy which has not yet been tested in paediatric cases. limited resection with image guidance is an excellent option in focal cases with a discrete pancreatic nodule. SPSE 1

Answer 51

D True congenital epithelium-lined cysts of the pancreas are rare and typically asymptomatic. When present they are typically found in infancy and are commonly seen in the body and tail of the pancreas. Pseudocysts account for more than 75% of cystic pancreatic lesions, are typically post-traumatic and are most commonly located in the lesser sac. SPSE 1

Answer 52

B Pancreaticoblastoma is the most common pancreatic tumour of small children with a mean age of presentation at 4.5 years. more than half of the reported cases are in Asians who typically present with an asymptomatic, large mass and non-specific abdominal complaints. These tumours are often very large at presentation, compressing adjacent structures without invasion, and often the organ of origin is unclear on preoperative imaging. In the majority of cases the mass is heterogeneous with internal cystic areas reflecting necrosis and the tumour is multiloculated with enhancing septa. SPSE 1

Answer 53

A Solid-pseudopapillary tumours most commonly affect females of reproductive age and have low malignant potential. The imaging features reflect the mixed cystic and solid nature of the lesion with encapsulation and intratumoural haemorrhage. SPSE 1

Answer 54

A Insulinoma is the most common endocrine tumour of the pancreas. most patients have Whipple’s triad of fasting hypoglycaemia, symptoms of hypoglycaemia, and resolution of symptoms with intravenous glucose administration. Gastrinoma is the second most common. All other functioning islet cell tumours are extremely rare in children. SPSE 1

Answer 55

B Gastrinoma is the most common islet cell tumour seen in mEN1 (seen in up to 50% of patients) and causes Zollinger–Ellison’s (ZE) syndrome. Patients frequently have multiple or recurrent peptic ulcers, classically in uncommon locations. Approximately 75% of gastrinomas are sporadic and 25% are associated with mEN1. The mean age of presentation of ZE syndrome is 50 years old. Gastrinomas associated with mEN are more often benign, multicentric, and extrapancreatic. Insulinoma is seen in 10%–30% of patients with mEN1. SPSE 1

Answer 56

E Insulinomas are typically benign (90%), solitary, and less than 2 cm in size. Insulinomas are found with relatively similar frequency in the head, body, and tail of the pancreas so intraoperative imaging is an important part of tumour localisation. SPSE 1

Answer 57

D The most reliable method for diagnosing an insulinoma is the 72-hour supervised fast with blood glucose and insulin levels measured every 4–6 hours. The presence of hypoglycaemia with concurrent serum insulin elevation during a monitored fast is diagnostic. Insulin-to-glucose ratio of more than 0.3 is common; however, up to 20% of patients with insulinoma do not have an elevated insulinto-glucose ratio. measurement of C-peptide and proinsulin levels are helpful as these are typically increased in patients with insulinoma. Commercial insulin does not contain these products. Somatostatin receptor scintigraphy is of limited benefit in patients with insulinoma as they rarely have somatostatin receptors. SPSE 1

Answer 58

B The classic description of gastrinoma location is within the ‘gastrinoma triangle’ which is bounded by the pancreatic body/neck, the third part of the duodenum and the cystic duct/common bile duct junction. overall, 55% of gastrinomas are found in the pancreas, most commonly in the head. The most common extrapancreatic site is the proximal duodenum and these are typically microadenomas in the 2 mm size range. oesophagogastroduodenoscopy and endoscopic ultrasound are important adjuncts to localising extrapancreatic gastrinomas. Evaluation of the liver and peripancreatic lymph nodes is an important part of the staging of pancreatic gastrinomas which are metastatic at least 50% of the time. SPSE 1

Answer 59

E A fasting serum gastrin level greater than 1000 pg/ml is usually diagnostic of gastrinoma. most gastrinomas have more moderate gastrin level elevation. Gastric pH <2.5 excludes a physiologic response as the cause of hypergastrinaemia. Typically patients have a basal acid output of greater than 15 mEq/hr. Secretin provocative testing (administration of 2 u/kg of secretin following an overnight fast) showing paradoxical increase in serum gastrin levels by more than 200 pg/ml, is required to diagnose gastrinoma. The urea breath test is used to evaluate patients for Helicobacter pylori infection. SPSE 1

Answer 60

E Somatostatin receptor scintigraphy (SRS) is both sensitive and specific for localising gastrinomas, more so than other conventional modalities. Small duodenal gastrinomas may be missed and endoscopic ultrasound is an excellent complementary diagnostic tool to SRS. SPSE 1

Answer 61

D CT scan is an excellent technique to evaluate stable paediatric trauma patients in whom a reliable physical examination cannot be performed and there is suspicion for significant abdominal trauma as in this patient with a seat-belt contusion. CT provides information relative to specific organ injury and extent and allows better evaluation of pelvic and retroperitoneal structures which are difficult to assess by physical exam, FAST scan, and DPl. Abdominal CT also provides information about the lower thoracic and lumbar spine which should be evaluated in this patient with a seat-belt contusion. Some gastrointestinal and pancreatic injuries may be missed on initial CT so close clinical follow-up is required. SPSE 1

Answer 62

C management of traumatic injuries to the pancreas remains an area of controversy. Several studies have demonstrated that early operative intervention in a child with a major pancreatic ductal injury results in shorter hospitalisation, less total parenteral nutrition (TPN) dependence and fewer complications than in those initially managed non-operatively. Pseudocyst formation occurs in greater than 45% of patients managed non-operatively, many of whom require drainage procedures, resulting in a prolonged return to normal health. Early distal pancreatectomy avoids pancreatic fistula and pseudocyst formation. SPSE 1

Answer 63

E In two large series evaluating the aetiology of acute pancreatitis in children, idiopathic and post-traumatic were the most commonly identified causes accounting for 34% and 14% of all cases, respectively, in the largest series. SPSE 1

Answer 64

E most pancreatic pseudocysts in children are the result of blunt abdominal trauma (60%–75%). Complications from untreated large pseudocysts can include mechanical obstruction, haemorrhage, perforation and infection. While more than 50% of acute peripancreatic fluid collections resolve, cysts larger than 4–6 cm with a well-defined thick wall and present for greater than 6 weeks are unlikely to resolve spontaneously. Internal drainage is the most effective option for large, persistent pseudocysts. Cysts which communicate with the main pancreatic duct have a high rate of recurrence following percutaneous aspiration. Endoscopic cyst-enteric drainage has been described in limited reports from a few experienced endoscopists. SPSE 1

Answer 65

E For symptomatic children with pancreatic duct obstruction with calculi, longitudinal pancreaticojejunostomy has demonstrated durable long-term results. SPSE 1

Answer 66

The diagnosis of acute pancreatitis is based on the clinical history, physical examination, laboratory test results, and findingsofdiagnosticimaging investigations. Determination of amylase isoenzymes has also been used to increase diagnostic accuracy by identifying the tissue from which the amylase originates. Serum lipase levels may also complement pancreatitis testing and increase the yield of positive diagnoses. A new scoring system for acute pancreatitis in children has been proposed that has better sensitivity than the Ranson and Glasgow scores. The parameters are: age (<7 years), weight (<23 kg), admission white blood cell count (>18,500), admission lactate dehydrogenase level (>2000), 48-hour trough Ca2+ level (<8.3 mg/dL), 48-hour trough albumin level (<2.6 g/dL), 48-hour fluid sequestration (>75 mL/kg/48 hr), and 48-hour rise in blood urea nitrogen (>5 mg/dL). Plain radiographs of the chest and abdomen are obtained to exclude intestinal perforation. Occasionally radiopaque gallstones, a gas-filled right colon, or a distended loop of small intestine (sentinel loop) may be seen. Left basal pleural effusion is relatively common, and mottling of the lung fields is a sign of systemic cytokine release. Radiographic studies enhanced by water-soluble contrast of the upper gastrointestinal tract are occasionally useful, particularly in cases of trauma when injury to the duodenum or small intestine is suspected. Ultrasonography (US) and computed tomography (CT) are useful for detecting pancreatic abnormalities. Trauma-induced injuries to abdominal organs, particularly the pancreas, are readily detected on CT. ERCP is rarely indicated for acute pancreatitis, but it eventually becomes essential in any child who has pancreatitis with an unclear cause. This technique is useful in cases of relapsing pancreatitis associated with pancreaticobiliary malunion. ERCP is an invasive method that can aggravate pancreatitis and is often not an option during the acute phase of pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method of obtaining images of the pancreaticobiliary tract. MRCP images the common bile duct in more than 96% of patients and detects common bile duct stones with a sensitivity of 71% to 100%, thus exceeding the sensitivity of US (20% to 65%) and CT (45% to 85%). Visualization of the smaller pancreatic duct is successful in more than 80% of patients. Miyano and colleagues 38 have previously evaluated the efficacy of MRCP in pediatric patients with acute pancreatitis. Patients were divided into two groups. Group 1 consisted of seven patients in whom choledochal cysts were sonographically diagnosed, and group 2 consisted of nine patients with no obvious cause of acute pancreatitis. Pancreaticobiliary malunion was detected in six of seven in group 1 and in one of nine in group 2. Pancreatic divisum was detected in one patient in group 1 but could not be confirmed in any of the group 2 patients. Dilatation of the main pancreatic duct was detected in one in group 1 and in three in group 2. These findings indicate that MRCP is a potentially useful method for identifying and ruling out structural abnormalities of the pancreaticobiliary tract in children. Coran

Answer 67

Treatment of acute pancreatitis has two primary goals: (1) to minimize any causative factors and (2) to provide meticulous supportive care including liberal use of analgesics, administration of parenteral fluids, maintenance of nutrition, prevention of infection, and inhibition of endocrine and exocrine activity. Parenteral analgesia with narcotics or nonsteroidal antiinflammatory agents is generally required, even in mild cases of pancreatitis, because the pain can be extreme. It is traditional to administer meperidine rather than morphine because the latter produces ampullary spasm. Although nasogastric suction is usually initiated to reduce vomiting and abdominal distention, the value of nasogastric decompression is questionable, unless the patient is vomiting. Aspiration of gastric acid may reduce pancreatic exocrine secretion by limiting the release of secretin. Oral feeding must be withheld to reduce pancreatic stimulation. Total parenteral nutrition should be initiated early to avoid malnutrition. In addition, early placement of a central venous catheter in patients with severe disease will provide access for aggressive intravascular volume support and nutrition. The hematocrit and serum levels of glucose and calcium should be measured, and hourly urine output should be monitored carefully. Although the advantages of prophylactic antibiotics have not been proved, patients with necrotizing pancreatitis may benefit. Other treatment strategies involving somatostatin, glucagon, anticholinergics, histamine blockers, and protease inhibitors have been recommended, but to date they have not shown conclusive benefit. Standard medical treatment must be used in patients with acute pancreatitis in an attempt to control the disorder before surgical intervention, which is rarely required in children but is occasionally performed if the diagnosis is uncertain or a complication develops after an acute episode such as a pseudocyst or an abscess. Patients with acute pancreatitis associated with underlying pancreaticobiliary disease generally require surgical correction of the underlying condition before cure can be expected. In the management of severe acute pancreatitis, a major decision is whether and when surgery for pancreatic necrosis or infection is necessary. Infection of necrotic pancreatic tissue is the major risk factor for mortality in severe acute pancreatitis and is an indication for surgery. On the other hand, there is support for nonsurgical conservative management of sterile pancreatic necrosis including antibiotic treatment. The reported death rate is 1.8% with sterile pancreatic necrosis and 24% with infected necrosis. Early surgery has been associated with increased mortality and should be delayed, if not avoided. Coran

Answer 68

Chronic relapsing pancreatitis is characterized by recurrent episodes of upper abdominal pain associated with varying degrees of pancreatic exocrine and endocrine dysfunction. Relatively few case series of chronic relapsing pancreatitis in childhood exist, although it is more frequently being suspected in children with recurrent episodes of abdominal pain. The disease produces a wide variation of progressive and irreversible structural changes in the pancreas. At present, the most controversial aspect of treatment of this disorder is the choice of an appropriate surgical procedure. Causes and Pathophysiology In children the most common causes of chronic relapsing pancreatitis are trauma, heredity, systemic disease, and malformations of the pancreaticobiliary duct such as pancreas divisum, annular pancreas, and choledocholithiasis. In addition, various unusual conditions including metabolic disease, endocrine disorders, and inflammatory bowel disease may cause the disorder. Certain congenital anomalies affect the pancreas and surrounding tissue, several of which are associated with chronic relapsing pancreatitis. Obstruction of pancreatic flow caused by a stenotic papilla of Vater and bile reflux resulting from a common channel are believed to be responsible for the resultant inflammation, which may be reversible if the obstruction is relieved. A relatively common cause of relapsing pancreatitis is pancreas divisum, in which most of the pancreatic fluid flows through the minor duct of Santorini, with the possibility of a relative obstruction to flow because of anatomy and flow dynamics. Some series have reported an increased incidence of pancreas divisum in patients with idiopathic chronic pancreatitis. Annular pancreas, which results from an error of rotation or fixation of the embryologic pancreatic primordium, has also been associated with chronic pancreatitis. Pancreaticobiliary malunion with or without choledocholithiasis may likewise result in relapsing chronic pancreatitis. In the past few years, several genes have been identified as being associated with hereditary and idiopathic chronic pancreatitis: PRSS1, CFTR, and SPINK1. SPINK1 mutations were found predominantly in patients without a family history. These mutations were most common in those with idiopathic chronic pancreatitis, whereas patients with hereditary chronic pancreatitis predominantly had PRSS1 mutations. Coran

Answer 69

The degree of permanent damage to the pancreas may be assessed by blood tests (pancreatic enzymes), stool tests (pancreatic enzymes, fecal fat), and noninvasive tests of pancreatic function such as the pancreatic stimulation (secretin) test. In 30% to 50% of adolescents and adults with chronic pancreatitis, plain radiographs of the abdomen reveal pancreatic calcification. Calcification is diagnostic of chronic pancreatitis, even if clinical evidence of pancreatic disease is absent. However, the incidence of calcification in children with chronic relapsing pancreatitis is low, except in younger children with hereditary pancreatitis, in whom the incidence is high. US is ideal for examining the pancreas in children. Dilatation of the pancreatic or biliary tracts may be noted, and calcification and complications such as pseudocysts, abscesses, calculi, and ascites can be seen. CT is useful for visualizing the size of the pancreas and its ducts and for detecting small calculi that may be missed on plain radiographs and US. ERCP is an important tool in the diagnosis and management of chronic relapsing pancreatitis in adults and children. Pancreaticobiliary malunion with or without dilatation of the bile duct may be detected. ERCP is up to 90% accurate in diagnosing ductal abnormalities. However, as described earlier, MRCP has been greatly refined in the past decade. MRCP is considered to be equivalent to ERCP for the diagnosis of many pancreatic and biliary conditions and is preferable because it is noninvasive and safer. Coran

Answer 70

Surgery for chronic relapsing pancreatitis is done to relieve pain, treat complications, or both. Surgery on the pancreas is generally of three types: (1) sphincteroplasty; (2) pancreatic drainage via longitudinal pancreaticojejunostomy (Puestow), end-to-end pancreaticojejunostomy (Duval), or the Frey procedure; or (3) partial or total pancreatectomy. Several groups of investigators have attested to the success of sphincteroplasty in controlling the symptoms of chronic pancreatitis in carefully selected patients. Correct use of this procedure, however, demands that intrapancreatic ductal obstruction be ruled out by pancreatography. O’Neill and colleagues reported good results in six of seven children who underwent sphincteroplasty for chronic pancreatitis. The general indication for the use of a direct ductal decompression procedure is evidence of pancreatic ductal ectasia with multiple intrapancreatic duct strictures. An important secondary feature of drainage procedures is preservation of existing endocrine function by avoiding major pancreatic resection. Longitudinal pancreaticojejunostomy (Puestow technique) in adults has been successful in eliminating or ameliorating pain from chronic pancreatitis in 70% to 97% of patients in series reported 3 decades ago. In children, several authors have shown that either the Puestow procedure or the Frey procedure improves pancreatic function, decreases hospitalization, and increases body weight toward ideal. Others have reported that distal pancreatectomy and pancreaticojejunostomy are effective. Tailored organ-preserving resective pancreatectomy can also be performed with low morbidity and mortality in pediatric patients with chronic pancreatitis and not responding to medical management. Total pancreatectomy is not generally indicated in children. The individual procedure for chronic pancreatitis should be tailored to the pancreatic ductal anatomy. Coran

Answer 71

The embryology of this entity was described in the first section of this chapter. Pancreas divisum is suspected on MRCP or ERCP when the duct of Wirsung fails to be visualized after injection of the major papilla or when it is attenuated and rudimentary. MRCP is a useful and noninvasive diagnostic tool for pancreas divisum, but ERCP can provide detailed information on the pancreatic duct. If pancreas divisum is suspected after injection of the papilla of Vater, an attempt should be made to find and cannulate the minor papilla, but this is possible in less than half the cases because of its small size and the angle at which it meets the duodenum. If the minor papilla can be entered, ERCP will demonstrate that the duct of Santorini is the dominant duct and that it extends the entire length of the body and tail of the pancreas. Imaging of the duct of Santorini occasionally demonstrates dilatation, irregularity, or stricture suggestive of chronic pancreatitis. Autopsy studies have suggested that pancreas divisum, which is found in 4% to 11% of patients, is the most common congenital anomaly of the pancreas. When absence of the duct of Wirsung is associated with pancreas divisum, approximately 10% of affected patients have anomalous anatomy resulting in most or all of the pancreatic secretions draining by means of the accessory papilla. Pancreas divisum should not be regarded as a disease. However, if the orifice of the accessory papilla is stenotic, pancreatitis can result. Stenosis of the minor papilla is probably developmental because the orifice is usually small with no evidence of inflammation. The incidence of pancreas divisum may be significantly higher in patients with unexplained recurrent pancreatitis, and it was detected in up to 25% of patients. Neblett and O’Neill reported that pancreas divisum was identified in 7.4% of all children with pancreatitis and 19.2% of children with relapsing or chronic pancreatitis. In 10 patients with pancreas divisum, 8 had complete pancreas divisum and 2 had incomplete variants. The primary goal of treatment of pancreas divisum associated with pancreatitis is to establish adequate drainage of the duct of Santorini. The progression of disease to pancreatic insufficiency can be arrested when the obstruction is relieved early. Correction may not only preserve pancreatic function but may also help ensure that normal growth and development occur. Several reports have shown that adequate drainage of the duct of Santorini can be achieved with accessory papilla sphincteroplasty. A report by Adzick and colleagues delineated the technical details of the operative procedure. Endoscopic sphincterotomy has been performed, but restenosis and recurrence of symptoms have been reported. If chronic pancreatitis has developed in the presence of a dilated duct, longitudinal pancreaticojejunostomy should be considered. Neblett and O’Neill 61 reported that 8 of 10 patients with pancreas divisum underwent surgery: 7 underwent transduodenal sphincteroplasty of the accessory papilla, along with sphincteroplasty of the major papilla in 2 (plus septoplasty in 1). Three patients underwent longitudinal pancreaticojejunostomy, as a primary procedure in one patient with mid-ductal stenosis and in two because of recurring pancreatitis after sphincteroplasty without endocrine and exocrine pancreatic insufficiency. Surgical intervention is directed toward relief of ductal obstruction and may involve accessory duct sphincteroplasty alone or in conjunction with major sphincteroplasty and septoplasty. Patients with more distal ductal obstruction or ductal ectasia may benefit from pancreaticojejunostomy. In an extremely rare case, Miyano and colleagues treated a patient with coexistence of pancreas divisum, choledochal cyst, and pancreaticobiliary malunion. This patient underwent complete excision of the choledochal cyst with a Roux-en-Y hepaticojejunostomy, followed by transduodenal papilloplasty to allow complete drainage of the common channel. Coran

Answer 72

Congenital and developmental cysts of the pancreas are rare and may be encountered in a fetus, infant, child, or adult. Only 25 cases have been reported in the pediatric literature to date. These cysts have a female preponderance. They are most common in the body and tail of the pancreas, are more often unilocular than multilocular, and are lined with epithelium. The cysts are usually filled with a cloudy, yellow sterile fluid that has no enzyme activity, and they are remarkably free of adhesions and infection. They have been reported to occur simultaneously in other organs; for example, von Hippel-Lindau disease is characterized by hereditary cerebellar cysts, retinal hemangiomas, and cysts of the pancreas and other organs. The cysts that occur with cystic fibrosis are not considered pancreatic pseudocysts and are not discussed in this chapter. Clinically, congenital and developmental cysts are detected in the prenatal period as an incidental sonographic finding or as a cause of polyhydramnios. After birth, they may be manifested as asymptomatic abdominal distention, as vomiting or jaundice caused by extrinsic pressure on neighboring organs, or as an asymptomatic mass. Surgical treatment consists of total excision of cysts located in the pancreatic body or tail and either internal drainage or complete resection of those in the pancreatic head. Coran

Answer 73

Retention cysts of the pancreas are rare and believed to result from chronic obstruction of the gland. They contain cloudy fluid composed of pancreatic exocrine secretions and a high concentration of pancreatic enzymes. Such cysts are lined with ductal epithelium unless it has been destroyed by chronic dilatation or inflammation from enzyme exposure. Coran

Answer 74

Enteric duplication involving the pancreas is rare and usually associated with gastric duplication. This duplication is most likely to result from failure of regression of an enteric diverticulum formed from the pancreatic duct. Many of the reported cases of enteric duplication involving the pancreas communicate with the pancreatic duct, are lined with gastric-type epithelium, and contain ectopic pancreatic tissue in their walls. Pancreatic duplication cysts have been noted on fetal US. The most common symptom in these patients is recurrent abdominal pain, often postprandial. Pancreatitis associated with enteric duplication cysts is believed to be caused by obstruction of the pancreatic ducts by viscous secretions from the cyst or by blood and debris from peptic ulceration within the cyst. In patients without pancreatitis, pain may be caused by tension on the wall of the cyst as a result of accumulation of secretions and muscular contraction. CT may help identify the location and size of duplication cysts, as well as any edema of the pancreatic head. ERCP or MRCP is useful to outline ductal anatomy and demonstrate any communication between the duplication cyst and the pancreatic duct to aid in planning the surgical approach. To date, virtually all duplication cysts reported in the literature have been treated by extirpation, and some have required pancreaticoduodenectomy. Coran

Answer 75

Pancreatic pseudocysts are localized collections of pancreatic secretions that do not have an epithelial lining and develop after pancreatic injury, inflammation, or duct obstruction. The most common causes of pseudocysts in children are trauma and infection. Drug-induced acute pancreatitis such as with valproic acid is also a rare cause of pancreatic pseudocyst. These cysts typically lie in the lesser sac behind the stomach and are composed of a fibrous capsule surrounded by inflamed connective tissue. The capsule of the cyst may also be formed by neighboring tissue such as the stomach, duodenum, colon, small intestine, or omentum. Pseudocyst fluid is clear or straw colored in most cases and may contain toothpaste-like debris. The amylase level of cyst fluid is typically higher than 50,000 Somogyi U/mL. Diagnosis The presence of a pancreatic pseudocyst is suggested by a history of blunt abdominal trauma; an illness resembling pancreatitis, possibly followed by a symptom-free interval of weeks to months; or palpation of a mass in the epigastrium or left upper quadrant. Abdominal pain is the most common symptom, with jaundice, chest pain, signs of gastric obstruction, vomiting, gastrointestinal hemorrhage, weight loss, fever, and ascites also being features. US, CT, and magnetic resonance imaging (MRI) are helpful and accurate in diagnosis. These studies are also invaluable for evaluating the thickness of the cyst wall and for observing changes in the cyst during the ensuing period of treatment. ERCP is often useful because it can definitively determine the status of the pancreatic duct and thus guide surgical interventions. Rarely, pancreatic pseudocysts can extend into the mediastinum in children. Coran

Answer 76

Optimal management of a pancreatic pseudocyst remains controversial. Treatment options range from conservative medical management to surgical drainage. Conventional management involves supportive therapy over a 6-week waiting period, during which time either the cyst resolves spontaneously or the cyst wall undergoes fibrous maturation, thereby permitting internal surgical drainage to the stomach or jejunum. This 6-week interval is what has traditionally been accepted, but CT may demonstrate thickening of the cyst wall sufficient to hold sutures as early as 3 to 4 weeks. Surgical drainage is usually performed in adults when necessary but is controversial in children because some pancreatic pseudocysts in this group resolve without surgical intervention and have a low risk for recurrence. Pseudocysts from nontraumatic etiologies are more likely to require surgical intervention, whereas traumatic pseudocysts are more amenable to nonoperative treatment. Octreotide acetate, a long-acting analogue of somatostatin, may facilitate medical management of pancreatic pseudocysts. A significant risk for complications such as infection or major hemorrhage in untreated pseudocysts or persistence of severe symptoms may be an indication for earlier intervention. If the patient cannot withstand major surgery, external drainage is preferred. There is significant evidence indicating that internal drainage, especially transgastric cystogastrostomy or Roux-en-Y cystojejunostomy, is effective in the treatment of pancreatic pseudocyst. Roux-en-Y cystojejunostomy is the most widely used internal drainage procedure for this problem and is associated with the lowest rate of complications and recurrence. In contrast to this approach, others have reported that percutaneous drainage and endoscopic transmural drainage are safe and efficient procedures. However, it is generally recognized that external drainage carries a higher risk for complications such as fistula formation and a higher recurrence rate than internal drainage does. Internal drainage procedures cannot be accomplished until the wall of the pseudocyst has matured. Recent studies have shown that internal drainage should be performed in patients with pseudocysts that are more than 6 weeks old and have a diameter larger than 5 cm because a large proportion of pseudocysts regress during the first 6 weeks after diagnosis and the risks associated with managing the pseudocyst are reduced. Cystogastrostomy has been performed laparoscopically. Though less commonly used than drainage procedures into the stomach or jejunum, cystoduodenostomy is effective when a cyst is closely adherent to the duodenum. Either pancreaticoduodenectomy or distal pancreatectomy, as indicated by anatomy, is effective in treating patients with pseudocysts under ideal circumstances. Distal pancreatic resection is indicated in patients with a pseudocyst in the body or tail of the pancreas, particularly if associated with multiple small cysts. Pseudocysts involving the head and uncinate process of the pancreas that are not amenable to internal drainage are rare and may require proximal pancreatic resection, but such resection should be done only as a last resort. Coran

Answer 77

Molecular biologic studies have shown that abnormalities of the K ATP channel, which are encoded by the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes, are responsible for altered control of insulin secretion. In response to elevated glucose levels, the K ATP channel closes, depolarizing the beta-cell membrane and initiating calcium-dependent release of insulin from the beta-cell storage granules. Uncontrolled insulin secretion may occur if either the SUR1 or Kir6.2 proteins are defective. The SUR1/Kir6.2 form of HI may not be controlled with medical therapy such as diazoxide, which acts on SUR1 to suppress insulin secretion, and pancreatectomy is often necessary. In contrast, surgery is not usually necessary in other genetic forms of HI that result from mutations of glucokinase or glutamate dehydrogenase genes that are responsive to diazoxide treatment. Neonates with HI may have either diffuse involvement of the pancreatic beta-cells or focal adenomatous islet cell hyperplasia. Mutations of the SUR1/Kir6.2 complex are involved in both of these types. Recessive mutations cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation causes focal adenomatous HI. Patients with diffuse disease have recessively inherited mutations of the SUR1/Kir6.2 complex, whereas patients with focal disease have normal beta cells, as well as a focal clone of abnormal beta cells that are homozygous for the SUR1/Kir6.2 mutation. The focal lesions arise by a two-hit loss-of-heterozygosity mechanism. First, there is a specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells from the focal lesion but not in the surrounding normal pancreatic cells. Second, there is a transmission of a mutation of SUR1/Kir6.2 in the paternal chromosome 11p; focal lesions have been linked to non-Mendelian expression of paternally transmitted SUR1 mutation in which there is duplication and reduction to homozygosity of the mutant paternal allele. In the future, molecular biology testing of peripheral leukocytes may help differentiate focal from diffuse disease. However, the search for mutations is currently of limited use in clinical practice because the process takes many weeks and not all mutations are known. One of the big challenges in diagnosis has been that the diffuse and focal forms of HI are clinically identical. Patients with either focal or diffuse disease are usually large for gestational age, reflecting the effects of HI on fetal growth. We have found that approximately 55% of our patients have focal disease, and about 45% have diffuse disease. Distinguishing focal from diffuse disease is of importance in guiding the extent of surgical resection. Patients with diffuse disease often require near-total pancreatectomy, which has the long-term risk of diabetes mellitus. Conversely, babies with focal disease can be cured with a selective partial pancreatectomy with little risk of subsequent diabetes. Coran

Answer 78

Babies with HI present with severe and persistent hypoglycemia manifested by seizures, lethargy, apnea, and other symptoms resulting from neuroglucopenia. The diagnosis of congenital HI is established if fasting hypoglycemia (glucose < 50 mg/dL) occurs simultaneously with: an inappropriately elevated plasma insulin (>2 mU/mL), low plasma beta-hydroxybutyrate (<2 mmol/L) and free fatty acids (<1.5 mmol/L), and an inappropriate glycemic response to intravenous glucagon (>30 mg/dL rise in serum glucose level). Medical therapy to maintain euglycemia is standardized and involves high continuous intravenous infusions of glucose as measured by the Glucose Infusion Rate (which is the amount of glucose infused in mg/kg/min), frequent oral feedings, and administration of diazoxide, glucagon, and octreotide. Early efforts to distinguish focal from diffuse disease involved the injection of intravenous calcium and tolbutamide (a sulfonylurea) to elicit different types of insulin responses by focal and diffuse disease, but the results were not predictive enough to be clinically useful. Preoperative assessment of babies with HI reveals that they are large, are often fluid overloaded due to high intravenous glucose requirements, have hepatic enlargement due to steatosis, may be anemic due to frequent blood sampling, and have oral aversion. They are predisposed to central venous line sepsis both preoperatively and postoperatively. Octreotide is the mainstay of medical therapy for HI but can rarely lead to necrotizing enterocolitis because octreotide reduces splanchnic blood flow in a dose-dependent manner. Coran

Answer 79

Diagnostic radiology tests such as US (both preoperative and intraoperative), MRI, CT, contrast angiography, and radiolabeled octreotide scans have all been unsuccessful in identifying focal lesions. For insulinoma localization in adults, intraoperative saline injection into the pancreas followed by tissue aspiration with rapid insulin measurements has been helpful, but this localization technique is untenable in the fragile neonatal pancreas. Two interventional radiology tests have been used in an attempt to differentiate focal from diffuse disease. The Arterial Stimulation with Venous Sampling (ASVS) technique involves selective pancreatic angiographic stimulation and venous sampling using intra-arterial calcium, which stimulates abnormal islet cells to release insulin. An immediate rise in insulin from stimulation in only one artery suggests focal HI in the corresponding area of the pancreas (gastroduodenal artery—pancreatic head; superior mesenteric arteryuncinate process and neck; splenic artery—pancreatic body or tail), whereas an insulin rise in all three areas suggests diffuse HI. We and others have also used transhepatic portal venous catheterization and selective sampling of the pancreatic veins (THPVS). Both techniques require that the patient be off all glycemic medications (5 days for diazoxide, 1 to 2 days for octreotide) before catheterization under general anesthesia. THPVS requires that glucose levels be maintained at 50 mg/dL during the procedure as compared with 60 to 80 mg/dL for ASVS. For THPVS, the pancreatic venous insulin levels are compared with simultaneously drawn plasma levels of insulin and glucose. Both ASVS and THPVS are technically demanding and have limited specificity and sensitivity for distinguishing between focal and diffuse disease. These techniques are being replaced by a new PET-CT scan technique using 18-Fluoro-L-DOPA. Neuroendocrine cells have an affinity for taking up and decarboxylating amino acid precursors such as L-dihydroxyphenylalanine (L-DOPA). Decarboxylation of the L-DOPA to dopamine in islet cells allows meaningful localization by means of PET scanning, using the radioactive isomer 18Fluoro-L-DOPA. The isotope is manufactured by the Cyclotron Facility at the University of Pennsylvania on the day of the PET scan because of the isotope’s short half-life, and it is administered to patients under an Investigational New Drug (IND) program approved by the U.S. Food and Drug Administration. Hopefully, 18-Fluoro-L-DOPA will become commercially available in the future so that it can be used in other medical centers. The PET results are dramatic and visually spectacular for preoperative localization of a focal lesion. In more than 140 PET scans for HI, we have found that PET-CT scans read as showing a focal lesion have been 100% accurate in localizing a lesion. However, in about 20% of PETscans that were interpreted as showing diffuse disease, the patient at operative exploration will prove to have a focal lesion that was usually small. This false-negative rate should decrease with greater clinical experience. Coran

Answer 80

A focal lesion is characterized by a tumor-like proliferation of islet cells that push exocrine elements aside or haphazardly incorporate them. Unlike insulinomas, the focal lesion retains the lobular architecture of the normal pancreas, and exocrine elements usually remain within the lesion. The lesions often have irregular borders, and the endocrine cells frequently have enlarged nuclei. Islets outside the lesion appear normal. Patients with diffuse disease have abnormal islets containing 5% to 10% of cells with enlarged nuclei present throughout the pancreas. After the surgery, all frozen samples are processed for routine histology and confirmation of findings on the basis of paraffin-embedded sections and insulin immunohistochemistry. Coran

Answer 81

Open operations are approached in a similar manner using a transverse supraumbilical laparotomy. The pancreas is exposed by an extended Kocher maneuver, entry into the lesser sac, and mobilization of the inferior border of the pancreas. It is not necessary to mobilize the spleen. The pancreas is inspected under 3.5Â loupe magnification in an attempt to visualize a focal lesion, and the pancreas is palpated. If no focal lesion is seen, then 2- to 3-mm-diameter biopsies are taken each from the pancreatic head, body, and tail. Patients with suspected diffuse HI have intraoperative biopsies to confirm the diagnosis and then undergo near-total pancreatectomy. Near-total pancreatectomy (95% to 98%) involves resection of the entire pancreas leaving only a tiny residual piece of the pancreas between the common bile duct and the duodenum. The intrapancreatic course of the common bile duct should be completely dissected for an adequate near-total pancreatectomy to be performed. For children with diffuse disease treated by near-total pancreatectomy, a gastrostomy tube is also placed to make it easier to administer supplemental glucose or night-time feedings if necessary. When the biopsies demonstrate normal pancreatic histology, a further search for the focal lesion using the preoperative localization data is conducted. Additional biopsies of suspicious areas are obtained until the focal lesion is diagnosed by frozen section. Expert pediatric pathologic interpretation is vitally important. Focal lesions tend to be less than 10 mm in size (although they can be much larger) and are frequently irregularly shaped. Some lesions have octopus-like tentacles that make imperative the intraoperative confirmation of clear margins by frozen section analysis. Although focal lesions may maintain a lobular structure similar to that of the normal pancreas, subtle visual clues (ranging from a slightly reddish color to a marble-like appearance) may permit visual detection of the lesion intraoperatively and accurate preoperative localization studies greatly facilitate the visual search for a focal lesion. In some cases the lesion will feel firmer than the surrounding normal pancreas. However, a tiny focal lesion can be buried within the pancreas and be impossible to see or feel. Greater operative experience has led to more frequent intraoperative visualization or palpation of a focal lesion. Insulinomas differ from focal lesions because they are usually straightforward to identify intraoperatively and occur in older children. Once the focal lesion is identified, a partial pancreatectomy is performed using frozen sections of margins to ensure a complete resection. For periductal lesions in the body and tail, a distal pancreatectomy is performed. With pancreatic head lesions close to the common bile duct or pancreatic duct, it can be tricky to excise all of the lesion, particularly if there are tentacles of diseased tissue that emanate from the lesion. To ensure complete lesion resection in these challenging cases, the surgeon should remove most or all of the pancreatic head followed by Roux-en-Y pancreaticojejunostomy to drain the remaining pancreatic body and tail. In this way, the endocrine and exocrine function of the remaining normal pancreas is saved. In babies the pancreatic duct on the cut surface of the transected pancreatic body is not visible, so the end of the Roux-en-Y jejunal limb is meticulously anastomosed to the capsule of the pancreatic body with fine interrupted monofilament suture to effectively dunk the cut end of the pancreas into the small bowel lumen. Rarely, a focal lesion in the head will extend into the duodenal wall in which case a Whipple procedure may be necessary. Because PET scan localization of focal lesions has proven to be so accurate, focal lesions in the body and tail are now resected using laparoscopic techniques. The drawback to the laparoscopic approach is that there is little tactile feedback to help locate a nonvisible focal lesion. Because more than 50% of focal lesions involve the pancreatic head, subtotal (50% to 75%) distal pancreatectomy is inadequate therapy in many of these cases. Our experience with several referrals who underwent subtotal pancreatectomy elsewhere with the focal lesion remaining within the residual pancreas are good examples of this potential pitfall. Coran

Answer 82

Postoperative management has been standardized by a clinical care pathway including the use of the Glucose Infusion Rate to quantitate the patient’s glucose requirement. Glucose Infusion Rate (GIR) is calculated as % dextrose x IV rate x 0.169/Wt in kilograms. For the initial postoperative period, blood glucose values are determined hourly. The GIR begins at 2 mg/kg/min immediately postoperatively, is increased to a GIR of 5 on the morning of postoperative day 1, and then usually advances to a GIR of 8 by the evening of the first postoperative day. It is not unusual for an intravenous insulin infusion to be necessary for the first few postoperative days. After hospital discharge, a complete response at follow-up is defined as no requirement for glycemic medications, no continuous tube feedings, no diabetes mellitus, and the ability to tolerate an 18-hour fast without hypoglycemia. In our entire experience, 95% of babies with the focal form of HI are cured after limited pancreatectomy. The vast majority had a less than 50% pancreatectomy. For babies with diffuse HI treated with near-total pancreatectomy (95% to 98%), about one third require no glycemic medications, one third require insulin to treat diabetes, and one third require a glycemic medication (usually octreotide). Long-term follow-up is necessary for all of these children, particularly with regard to neurodevelopmental issues. Coran

Answer 83

Cystic neoplasms of the pancreas are relatively rare. Howard 100 classified these lesions into: (1) cystadenoma and cystadenocarcinoma, which include benign (microcystic) cystadenoma, benign and malignant mucinous (macrocystic) cystadenoma and cystadenocarcinoma, papillary-cystic epithelial neoplasm, and acinar cell cystadenocarcinoma (not reported in children) and (2) teratomatous cysts. 1) Cystadenoma and Cystadenocarcinoma Cystadenoma of the pancreas is rare in children and adults. Only six cases including one in a newborn have been reported in the pediatric population to date. Cystadenoma and cystadenocarcinoma should be divided into two groups. Because large mucinous cystic adenomas have considerable malignant potential, these tumors should be distinguished from serous cystadenomas, which are benign; the latter tumors are rich in glycogen and contain little or no mucin. Serous Cystadenoma and Cystadenocarcinoma Serous cystic neoplasms of the pancreas are rare in children and adults, are more often observed in females, and are found mainly in the body and tail of the pancreas. These tumors consist predominantly of small cysts (microcystic adenomas). Calcification is often demonstrated on CTand US. Serous cysts do not need to be excised unless they create a mechanical obstruction because nearly all of them are benign with no malignant potential. Biopsy is required. Serous cystadenocarcinoma is virtually nonexistent in children, and only a few cases have been reported in adults. Mucinous Cystadenoma and Cystadenocarcinoma Mucinous cystic neoplasms of the pancreas are usually large and often multilocular. They form papilla lined with columnar, mucin-producing epithelium; are more often observed in females; and are found mainly in the body and tail of the pancreas. Other features are the association of large blood vessels within the capsule and the presence of subepithelial hemorrhage. A common differential diagnosis is pancreatitis with pseudocyst formation. Mucinous cystadenocarcinoma of the pancreas represents 1% of all malignant conditions of the pancreas, occurs at an earlier age than conventional solid pancreatic tumors do, and seems to be approximately half as common as cystadenoma. The clinical and radiologic manifestations of mucinous cystadenocarcinoma are similar to those of mucinous cystadenoma. It is not always possible to differentiate mucinous cystadenoma from cystadenocarcinoma pathologically. It is also common to find apparently benign epithelium in the same tumors as malignant epithelium, thus suggesting that a malignant focus may develop within a mucinous cystadenoma. Therefore mucinous cystadenoma should be considered a premalignant lesion that should be completely excised after incomplete excision or marsupialization. However, the prognosis for this form of pancreatic malignancy is significantly better than that for the common typical solid ductal adenocarcinoma because of its slow growth and lack of metastatic potential. Papillary-Cystic Epithelial Neoplasm The first cases of papillary-cystic endothelial tumors of the pancreas were reported by Franz in 1959. Since these tumors were described as solid and cystic acinar cell tumors of the pancreas by Kloppel and colleagues, increasing numbers have been reported in children. They occur predominantly in girls and young women and are manifested as large, encapsulated masses, usually with extensive necrosis and varying amounts of cystic change. Histologically, they are composed of solid areas of rather small cells with pseudorosette formation reminiscent of endocrine tumors and cystic areas with papillary structures. Immunohistochemically, the tumor cells of solid and cystic pancreatic neoplasms contain periodic acid-Schiff-positive granules and often have progesterone receptors. Immunologic hallmarks are immunoreactivity with alpha-antitrypsin, alpha-antichymotrypsin, phospholipase A2 , and neuroendocrine markers such as neuron-specific enolase and synaptophysin. However, they are generally free of the usual markers of pancreatic carcinoma such as carcinoembryonic antigen, CA19-9, and tissue peptide antigen. These tumors seem to be associated with a much better prognosis than the usual type of pancreatic carcinoma but still have malignant potential. The tumor follows a benign course after resection in most cases. Metastasis or recurrence has occurred in 5% of cases in Japan. Thus complete extirpation is necessary because of the slow tumor progression associated with metastatic disease. L Liver metastases have been treated with resection and liver transplantation. 2) Other Cystic Neoplasms in Children In 1992 Flaherty and Benjamin 115 reported a case of multicystic pancreatic hamartoma in a 20-month-old girl. In 1990 Mester and colleagues reviewed 10 cases of cystic teratoma of the pancreas including one of their own. Cystic teratomas were usually seen as benign extragonadal germ cell tumors in younger patients; 5 of 10 patients were younger than 11 years. Coran

Answer 84

Endocrinologically active tumors are usually identified by their symptoms, and most of them originate in the islet cells. Beta-cell tumors secrete insulin; alpha cell tumors, glucagon; gamma cell tumors, gastrin; delta cell tumors, somatostatin; and delta 1 cell tumors, vasoactive intestinal polypeptide (VIP) and possibly substance P and secretin. Glucagonomas and somatostatinomas have not been identified in children. Insulinoma Insulinomas are the most common tumor arising from islet cells and are usually benign (>90%), solitary (80%) lesions that occur in children older than 4 years. A plasma insulinto-glucose ratio greater than 1 is diagnostic (<0.4 is normal), and the ratio increases with fasting. Concomitant measurement of C peptide levels may be used to exclude factitious hypoglycemia. CT, US, arteriography, and transhepatic portal venous sampling can be used to localize an insulinoma. The tumor is usually discrete and well encapsulated, and most can be enucleated. The introduction of endoscopic and intraoperative US has allowed obscure lesions to be identified. If all methods of tumor localization are unsuccessful, distal pancreatectomy with careful sectioning of the gland is advisable. In that circumstance, measurement of intraoperative insulin levels is recommended to avoid missing lesions. Virtually all infants and children with insulinoma can be cured. Multiple endocrine neoplasia type I (MEN-I) is characterized by endocrine tissues in the gut and pancreas including insulin-secreting tumors, but expression is usually delayed beyond the first decade of life. MEN-I is rare, with a frequency not exceeding approximately 1 in 10,000. The gene for MEN-I has been localized to the long arm of chromosome 11 and functions as a tumor suppressor gene, unrelated to the functional alterations in the SUR1/Kir6.2 components of K ATP on the short arm of chromosome 11.118 Gastrinoma The second most commonly reported pancreatic hormonal tumor is the gamma cell tumor. The clinical syndrome related to gastrinoma is often referred to as Zollinger-Ellison syndrome, a condition characterized by hypergastrinemia with severe peptic ulcer disease. This syndrome is rare in children. Gastrinoma is part of the MEN-I syndrome and is commonly malignant, multicentric, and metastatic at discovery. The diagnosis is usually made after recurrent episodes of peptic ulceration associated with an elevated gastrin level (>500 pg/mL). Calcium infusion and secretin simulation tests are used for diagnosis. CT, percutaneous transhepatic venous sampling, and gastrin assay have been useful for localization. Although total gastrectomy was originally the most common method of treatment, the development of inhibitors of gastric acid secretion such as H2 blockers and omeprazole has changed the direction of treatment of gastrinoma substantially. Children with gastrinoma generally require lifelong medical treatment, and somatostatin, although beneficial because it decreases gastric acid secretion, also inhibits growth hormone secretion, so it cannot be used long-term. Surgical treatment should thus be aggressive, especially if a solitary tumor is found with no evidence of metastasis at the time of laparotomy. However, total gastrectomy may still be required for patients in whom medical treatment has failed or those with residual tumor or metastatic disease. VIPoma VIPoma in children is far more commonly related to other neurogenic neoplasms such as neuroblastoma or ganglioneuroma than to tumors of primary pancreatic origin. Only a few cases of VIPoma in children have been reported. The VIP that is produced by a pancreatic VIPoma probably originates from neural cells in the islets. Patients have profuse, watery diarrhea associated with hypokalemia and hypochlorhydria (WDHA syndrome), and metabolic acidosis and prerenal azotemia secondary to dehydration are often present. Although medical therapy includes the use of streptozotocin and somatostatin, long-term use of somatostatin is undesirable. Surgical extirpation of the tumor-bearing gland is recommended whenever possible because 50% of pancreatic VIPomas are malignant. Coran

Answer 85

Carcinoma of the pancreas is common in adults but rare in children. The clinical features are different in that obstructive jaundice is the primary finding in adults, whereas an abdominal mass is usually the initial feature in children. Pancreatic carcinoma in children can be divided into four groups: islet cell carcinoma, adenocarcinoma, pancreatoblastoma, and miscellaneous lesions. Islet Cell Carcinoma Islet cell carcinoma in children may or may not be functional. Functioning beta-cell and non–beta-cell islet cell carcinoma occurs in infants and children with hypoglycemia in conjunction with Zollinger-Ellison syndrome, but it is not associated with a palpable mass. A beta-cell carcinoma is usually discovered during laparotomy for insulinoma. Four functional islet cell carcinomas have been described in children; all were treated by surgical extirpation, with good long-term survival. Seven of the eight children with Zollinger-Ellison syndrome described by Wilson had non–beta-cell carcinoma with metastatic disease. Nonfunctioning islet cell carcinomas are more common in children than adults. Because these tumors are usually discovered by palpation of an abdominal mass, they are often diagnosed late, and many affected infants and children have distant metastatic disease at the time of diagnosis. Most nonfunctional tumors are large, solitary lesions that can appear in any location within the gland. In general, although most of these tumors grow slowly, aggressive surgical therapy is warranted because of their malignant potential. Adenocarcinoma Adenocarcinoma of the pancreas is rare in children. Vejcho reviewed 37 cases of adenocarcinoma in 1993. The clinical manifestations differ from those of adults in that the incidence of pain with jaundice is lower. Abdominal pain and a palpable epigastric mass are the primary findings in children. Classification is still controversial and is based on tumor activity and histopathologic and immunohistochemical findings. Kloppel classified adenocarcinoma into three types: acinar cell carcinoma, solid and cystic tumor (papillary cystic tumor), and pancreatoblastoma. Acinar cell tumors are proportionately more common in children. It seems that children with an acinar cell tumor have a somewhat better prognosis than do those with an adenocarcinoma of the duct cell type. The prognosis for children with adenocarcinoma of the duct cell type is discouraging and similar to that for adults. CT and sonography are useful for diagnosis. For localized lesions, pancreaticoduodenectomy seems to be associated with a favorable prognosis. Infants and children tolerate radical resection of the pancreas somewhat better than adults do and have a lower mortality rate and better long-term survival. Pancreatoblastoma In 1977 Horie reported two cases of pancreatic carcinoma, which they termed pancreatoblastoma, an infantile type of pancreatic carcinoma. In 1984 Buchino reviewed eight patients with pancreatoblastoma, six of whom survived after surgical extirpation. Pancreatoblastoma is the most common pancreatic neoplasm in young children. Pancreatoblastomas have a better prognosis than adenocarcinoma because they have an encapsulated organoid structure that does not directly interfere with the main duct system. The criteria for diagnosing pancreatoblastoma have been described. Although there is no agreement on the pathology of these rare lesions, terminology based on recognizable lines of differentiation seems preferable (e.g., islet cell, duct cell, acinar cell, undifferentiated lesions). The recurrence risk after resection is high. These tumors can be responsive to chemotherapy and radiation, but the appropriate role for these modalities is unknown. Miscellaneous Carcinomas The following miscellaneous carcinomas in children have been reported in the literature: one case of carcinoma simplex; one case of medullary carcinoma ; six cases of sarcoma (two lymphosarcomas, two with sarcomatous degeneration from cystadenoma, and two rhabdomyosarcomas93 ); four cases of undifferentiated carcinoma; and two cases of cylindrical cell adenocarcinoma. Coran

Answer 86

Accessory spleens represent the most common anatomic abnormality and are present in 15% to 30% of children. They most likely originate from mesenchymal remnants that do not fuse with the main splenic mass. The majority (75%) are located near the splenic hilum or adjacent to the tail of the pancreas; a few are found along the splenic artery, in the omentum, mesentery, and retroperitoneum and have even been noted in the scrotum. Of those with accessory spleens, 86% have one, 11% have two, and 3% have three or more, with the hilum the most common site of multiple accessory spleens. Surgeons must be cognizant of these locations and routinely check for their presence because a missed accessory spleen can be a cause of recurrence of immune thrombocytopenic purpura (ITP) or hereditary spherocytosis. Recurrence with ITP is frequently early, whereas recurrence with hereditary spherocytosis has been reported as long as 31 years later. Coran

Answer 87

Wandering spleen is characterized by lack of ligamentous attachments to the diaphragm, colon, and retroperitoneum. The embryologic basis of this is probably related to failure of development of the splenic ligaments from the dorsal mesentery. Children with this condition most often present with diffuse abdominal pain secondary to torsion and infarction, although they may also present with episodic pain and an abdominal mass. Although splenectomy is required for infarction, splenopexy is preferred in nonischemic and incidentally detected cases. Splenopexy has been performed with various techniques including placement in an extraperitoneal pocket, use of Dexon mesh basket, suture splenopexy, and colonic displacement with gastropexy. Laparoscopic detorsion and splenopexy can be performed with the use of an absorbable mesh bag that is closed around the splenic hilum and then tacked to the diaphragm and posterolateral abdominal wall. Coran

Answer 88

Primary splenic cysts have an epithelial lining, frequently with a trabeculated internal appearance. They most likely originate from inclusion of the surface mesothelium into the splenic parenchyma. They may be asymptomatic or may present as pain, rupture, abscess, or symptoms due to gastric compression. Symptomatic cysts are usually greater than 8 cm. Small (<5 cm) simple cysts can be observed; however, larger, enlarging, or symptomatic cysts require definitive treatment. Percutaneous aspiration and sclerosis have been used, but recurrence is common and partial splenectomy has been required. Alcohol sclerosis of a congenital cyst has been reported with success, although the length of follow-up was not specified. Marsupialization can be associated with recurrence if an adequate segment of cyst is not removed. Laparoscopic partial cyst excision and cyst resection with partial splenectomy have been reported but are accompanied with a 64% to 88% recurrence rate. Partial splenectomy with excision of the cyst at the margin with the spleen can be performed with an electrosurgical device or with the use of stapling devices in an open or laparoscopic approach. Use of cautery, sutures, and omental packing of the defect may also be useful. Splenic pseudocysts lack an epithelial lining and most frequently occur after trauma. Enlarging cysts and symptomatic cysts should be excised. Coran

Answer 89

Asplenia and polysplenia syndromes have many similar features. Congenital asplenia is usually noted with complex congenital heart disease, as well as bilateral “right-sidedness” including bilateral three-lobed lungs, right-sided stomach, and a central liver. Intestinal malrotation has also been observed. Howell-Jolly bodies are noted on peripheral smear, and infants have the risk of overwhelming infection. Polysplenia in which the spleen is divided into multiple splenic masses is often associated with biliary atresia. Other associated features included preduodenal portal vein, situs inversus, malrotation, and cardiac defects. These children have adequate splenic immune function. Coran

Answer 90

Splenogonadal fusion occurs as a result of early fusion between the spleen and left gonad. The remnant may be continuous with a fibrous band or discontinuous with splenic tissue attached to the gonad. Another abnormality identified has been ectopic splenic tissue in the scrotum apart from a gonadal fusion. Coran

Answer 91

Hereditary spherocytosis is the most common inherited red cell disorder among northern European descendants. Approximately 75% of affected children have an autosomal dominant inheritance pattern; the remainder are new mutations or autosomal recessive. The attendant membrane defects in ankyrin or spectrin proteins result in poorly deformable spherocytes. The degree of splenic hemolysis can range from mild to severe. Most children are noted to have anemia, an elevated reticulocyte count, and a mild elevation of bilirubin. The presence of spherocytes along with a positive osmotic fragility test confirms the diagnosis. In affected children, an aplastic crisis can occur secondary to parvovirus B19 infection, with suppression of red cell production and a resultant low hematocrit due to ongoing destruction. Splenectomy is usually required for moderate to severe anemia. Gallstones are common, increasing in frequency with the age of the child and degree of hemolysis, and thus a gallbladder ultrasound is required before splenectomy. Hereditary elliptocytosis is a similar disorder associated with spectrin defects, but most patients are asymptomatic and without significant hemolysis. Coran

Answer 92

ITP occurs when antiplatelet autoantibodies, usually IgG, bind with platelets, leading to destruction in the reticuloendothelial system. The thrombocytopenia can be transient or can persist in a chronic phase. The decision to treat a patient with ITP is based primarily on bleeding complications, not on an absolute platelet count. Childhood ITP is usually a selflimited, acute disorder, and splenectomy is only required in chronic cases. First-line therapies include short-course corticosteroids, which may function by inhibiting the reticuloendothelial binding of platelet-antibody complexes; intravenous immunoglobulin (IVIG), which competitively inhibits the Fc receptor binding of platelets by macrophages; and Rho (D) immunoglobulin in Rh-positive children, which binds to red cells that then saturate the splenic capacity and spares the antibody-coated platelets. Second-line therapies include rituximab, which binds the CD20 antigen on B lymphocytes and is presumed to decrease autoantibody production, and splenectomy. With poor long-term response and concerning drug toxicities associated with rituximab, children with chronic ITP (with bleeding complications) resistant to first-line therapies are often referred for splenectomy. Unfortunately, predicting a response to splenectomy has been difficult. In one study, response to corticosteroids, IVIG, or both predicted a 97% response to splenectomy, whereas failure to respond to either predicted a 70% failure rate to splenectomy. Another study noted the response to IVIG to be a better predictor of response to splenectomy than corticosteroids. The most recent study directly challenged these findings with a 100% response rate among children who were nonresponsive to corticosteroids, with postsplenectomy platelet counts inversely related to peak platelet response to steroids. Despite the widely disparate literature, there is a sustained response rate as high as 80% for children with chronic ITP treated with splenectomy. Coran

Answer 93

Sickle cell disease occurs as the result of a substitution of valine for glutamic acid in the b chain of normal hemoglobin A, resulting in hemoglobin S. These red cells become rigid when oxygen saturation decreases, with subsequent capillary occlusion and shortened red cell life. Children with homozygous sickle cell anemia and with hemoglobin sickle cell disease have significant rates of painful crisis and acute chest syndrome. Splenic sequestration with rapid drop in hemoglobin and platelet counts can occur and, if severe or recurrent, merit splenectomy to reduce the chance of further episodes. Postoperatively, children with sickle cell disease are at risk for acute chest syndrome (ACS). ACS is characterized by basilar pulmonary infiltrates and is thought to be secondary to polymerized deoxygenated sickle hemoglobin, causing local tissue infarction in the lung. Treatment is supportive. Coran

Answer 94

The thalassemias are a group of disorders characterized by abnormal production of a or b chains of hemoglobin. Thalassemia major (Cooley anemia; b-thalassemia) results in the most severe clinical anemia among this group of disorders. Some children develop significant splenomegaly with sequestration. Splenectomy has been used to decrease the need for transfusions in children with severe anemia and those with significant splenomegaly and platelet or white cell sequestration. Coran

Answer 95

Gaucher disease is a metabolic disorder characterized by deficiency of the enzyme b-glucocerebrosidase, which results in excessive glucocerebroside in macrophages of the spleen, liver, bone marrow, and lungs. It is an autosomal recessive disorder found most commonly in Ashkenazi Jews. Splenomegaly can be severe, and both partial and total splenectomy have been used to alleviate the hypersplenism and increase the red cell, leukocyte, and platelet counts. However, recurrence has been reported after partial splenectomy. Coran

Answer 96

Splenic abscesses are rare but have been noted with increasing frequency with the increase in the number of immunocompromised children. Organisms are frequently fungal or mycobacterial. Children present with fever, pain, and positive blood cultures. An isolated splenic abscess may be treated with percutaneous drainage and intravenous antibiotics. However, diffuse or multifocal abscesses may be better served by splenectomy. Coran

Answer 97

The risk of postsplenectomy sepsis remains a concern for any asplenic individual. Preoperative immunization has become the standard of care for all patients being considered for elective splenectomy. In case of emergent splenectomy, postoperative immunization is still strongly encouraged. Current recommendations include polysaccharide pneumococcal, conjugate Haemophilus influenzae type b, and polysaccharide meningococcal vaccinations. All vaccinations should be completed at least 2 weeks before planned splenectomy. In addition, yearly influenza vaccination is strongly recommended to reduce the incidence of secondary bacterial pneumonia. Coran

Answer 98

A left upper quadrant subcostal incision provides excellent exposure for most spleens even in cases of splenomegaly. The spleen is retracted medially, and the splenorenal, splenophrenic, and splenocolic ligaments are divided. This can usually be accomplished with a relatively small incision, and the spleen is removed from the abdominal cavity by delivering the lower pole first, taking advantage of the concave medial surface of the spleen. The gastrosplenic ligament and short gastric vessels are divided, followed by the hilar vessels. If the pancreas is close to the hilum, it may be necessary to divide the segmental vessels. A careful search is made for accessory spleens, and, if present, they are removed. An alternative open approach uses a lateral muscle-splitting incision, which has been associated with a 2.7-day length of stay, comparable with some laparoscopic series. Coran

Answer 99

Total splenectomy with removal of accessory spleens eliminates splenic hemolysis and sequestration for congenital hemolytic anemias. However, concerns of overwhelming postsplenectomy sepsis, particularly in children younger than 5 years of age, have led to the exploration of partial splenectomy. This has primarily been used for hemolytic anemias such as hereditary spherocytosis but has also been used for Gaucher disease, Hodgkin disease staging, trauma, hypersplenism with cystic fibrosis, as well as excision of splenic cysts, hamartomas, and hemangiomas. When this technique is used for splenic volume reduction, 85% to 95% of the disease-affected splenic mass is removed, leaving approximately 10% to 25% of a normal splenic remnant. Anatomic studies of the splenic blood supply indicate that 86% of spleens have two lobar vessels and 12% have three lobar arteries. In addition, 77% have either four or five segmental vessels, thus allowing preservation of either an upper or lower pole segmental vessel supplying 20% to 25% of the spleen. The spleen is divided with either a stapling device, cautery, or the Harmonic scalpel, and hemostasis is achieved with cautery, argon beam coagulation, or topical agents as needed. If the spleen is totally mobilized, the remnant can be fixed to the retroperitoneum to prevent torsion. This procedure can be performed laparoscopically using the Harmonic scalpel to both divide the spleen and provide hemostasis. Long-term follow-up has noted increased red blood cell half-life, higher hemoglobin level, and lower transfusion requirement, reticulocyte count, and bilirubin levels. Preservation of splenic phagocytic function has been demonstrated by elimination of Howell-Jolly bodies on peripheral smear and decreased numbers of pitted red cells. Other parameters have included normal IgM and IgG levels of specific antibody titers to Streptococcus pneumoniae. Splenic regrowth occurs in all patients with hemolytic anemias, although the degree of regrowth does not correlate with hemolysis. Laparoscopic partial splenectomy has higher intraoperative blood loss,morphine use, and longer times to full oral intake, with longer hospital stays when compared with laparoscopic total splenectomy inthesame institution. Complications of post partial splenectomy hemolysis can include ongoing development of cholelithiasis (7% to 22%), recurrent anemia with need for transfusion, or subsequent total splenectomy. Caution must be exercised in the assumption of normal splenic function because one patient with evidence of residual splenic function by scan after partial splenectomy for trauma died of an S. pneumoniae infection 13 years later. This patient had not received pneumococcal vaccine. Preoperative immunization is recommended for all partial splenectomy candidates, and postoperative antibiotics are administered at least until splenic immunologic competence is noted. Coran

Answer 100

Complications are relatively rare after splenectomy. Thrombosis of the splenic, portal, and mesenteric veins has occurred after splenectomy, with a reported incidence of 1.6% to 11%. Symptoms include fever, vomiting, and/or abdominal pain as early as 2 days postoperatively. The diagnosis can be made by Doppler ultrasonography or contrastenhanced CT of the abdomen. Treatment consists of antiplatelet and antithrombotic therapy. Recannulization of the portal vein can occur with prompt diagnosis and treatment of the thrombus, but long-term complications of portal hypertension have also been described. Antibiotic prophylaxis is recommended for all asplenic individuals in the immediate postoperative period. Penicillin prophylaxis is given to all children, except for those who are penicillin allergic. In penicillin-allergic children, options are limited. Trimethoprim-sulfamethoxazole can be used, recognizing higher pneumococcal resistance with this antibiotic. There are no universal recommendations on the duration of antibiotic prophylaxis, but most recommend prophylaxis for at least 2 years after splenectomy. Coran

Answer 101

The occurrence of overwhelming postsplenectomy infection (OPSI) was first reported by King and Shumacker in 1951 in a series of five infants younger than 6 months of age undergoing splenectomy for hereditary spherocytosis. All five developed serious infections, and two died. Since then numerous reports have documented this risk and the increased risk (60- to 100-fold) in children younger than 5 years of age, as well as during the first few years after splenectomy. The etiology is probably related to decreased clearance of encapsulated bacteria and decreased immunoglobulin levels. The spleen is particularly important in infancy and childhood because the phagocytic function in infection occurs almost exclusively in the spleen. A cumulative review of the literature reported in the 1970s identified the incidence of OPSI at 3.75%, with a mortality of 1.7%. The rate in pediatric cases was 4.1% compared with 1.9% in adults and a mortality rate of 1.8% in children compared with 1.1% identified in adults. Other studies in the 1980s and 1990s had a wide range of OPSI, and as of the mid-1990s the overall incidence of OPSI ranged from 0.13% to 8.1% in children younger than 15 years of age compared with 0.28% to 1.9% in adults. S. pneumoniae was causative in 50% to 90% of all infections and is responsible for 60% of all fatal infections. H. influenzae accounted for 32% of mortality, and the meningococcus and group A Streptococcus were also significant pathogens. The risk of late infectious mortality also varied with the disease state with a rate of 0.51% for spherocytosis and 2.67% for ITP. Others also noted a higher mortality in children younger than 4 years of age (mortality: 8.1% in those younger than 4 years of age, 3.3% in older patients) with most deaths within 4 years of splenectomy. In view of this, penicillin prophylaxis was advocated. The increased risk in children relative to adults was documented with an incidence of fatal OPSI of 3.77% in children compared with 0.39% in adults. Many of these early reports were performed before widespread vaccination and use of prophylactic antibiotics, and more recent studies have somewhat lower rates of OPSI of 3.5% to 3.8%. Vaccination has been shown to decrease the risk of bacteremia. A more recent population-based study out of Denmark determined that among all patients undergoing splenectomy (adults and children), excess risk of bacteremia was greatest in the first 90 days after splenectomy, occurring in 10% of all patients. The risk remained higher than the general population for the first year. Different than previous studies, the Denmark study found enteric rods to be the predominant organism isolated from the blood in early and late postsplenectomy infections. A comparison study of an early era of splenectomy with no immunizations or prophylactic antibiotics compared with a later era with a 70% immunization and a 100% prophylaxis rate noted a decrease in the infection rate (6% to 3.8%) and mortality (3.9% to 0.9%). Even in this more recent study the rate of infection was related to age at splenectomy (birth to 5 years, 13.8%; >5 years, 0.5%). The historical mortality associated with OPSI has been 50% to 70%, but more recently a mortality of around 10% has been observed. Coran

Answer 102

A triad of hypoglycemia, low blood glucose during symptoms, and improvement of symptoms with glucose administration. While this classic triad is often present in patients with insulinoma, it is neither specific nor diagnostic of the disease. Sherif

Answer 103

As with all secreting endocrine tumors, a biochemical diagnosis should be established followed by localization of the tumor. The biochemical diagnosis of insulinoma requires a monitored fast with serial checks of glucose level every 6 hours until glucose drops below normal, then hourly. Although this fast was traditionally planned for 72 hours, shorter durations are usually sufficient for diagnosis. Once the glucose level drops below normal, insulin, C-peptide, proinsulin, and B-hydroxybutyrate levels are checked. Normally, low glucose levels are associated with low insulin levels and high levels of ketone bodies. In insulinoma, insulin levels are inappropriately elevated. In the past, an insulin (µU/mL) / glucose (mg/dL) ratio >0.3 was sought, but the ratio is now considered less important than the actual values. C-peptide and proinsulin, indicative of endogenous insulin secretion, are found elevated. Since the elevated insulin inhibits ketogenesis, B-hydroxybutyrate is inappropriately low. Sherif

Answer 104

Most insulinomas in children are sporadic but 10%–15% arise in the context of multiple endocrine neoplasia (MEN) type 1 syndrome. MEN1 includes pituitary tumors, hyperparathyroidism, and pancreatic endocrine tumors. Screening and testing for MEN1 should be performed. Screening includes: 1) a prolactin level to detect the most common pituitary adenoma, 2) calcium level to detect hyperparathyroidism, and 3) gastrin level to detect the rare possibility of other pancreatic endocrine tumors. 4) Genetic testing for MEN1 is currently available and can identify patients before endocrine abnormalities manifest. This should also be completed. Localization of the tumor does not need to await the results of this test. Sherif

Answer 105

Pancreatic endocrine tumors arising in the setting of MEN1 syndrome are much more likely to be gastrinomas. Insulinomas arising in the context of MEN1 are more likely to be multifocal, as well as malignant. Recurrence is also higher in the presence of the syndrome. Imaging evaluation for metastatic disease and multifocality is therefore necessary. Careful postoperative monitoring for recurrence, as well as development of pituitary and parathyroid lesions, is necessary. Screening of other family members may also be indicated. Sherif

Answer 106

Diazoxide has been used for the treatment of insulinoma. However, it appears to be effective in controlling hypoglycemia in only approximately 50% of patients and has been used mostly as a temporizing maneuver while awaiting surgical intervention. Resection is the standard of care and is curative in the great majority of patients. Sherif

Answer 107

Like many endocrine tumors, behavior, not pathology, will determine the malignant potential. Pancreatic endocrine tumors may be focal or multifocal. so thin sectioning, and careful examination of the specimen is required. The tumor generally has a pushing border and does not invade surrounding pancreas. It is composed of monomorphic cells with a salt and pepper chromatin pattern arranged in a gyriform (replicating islets), trabecular, glandular, or solid sheet pattern. The cells are positive for neuroendocrine markers such as chromogranin and synaptophysin and may demonstrate specific hormone expression (e.g., insulin). The tumors are classified as either “nonfunctioning” or “functioning,” depending on whether they secrete hormones related to a specific clinical syndrome. Even nonfunctioning tumors may express immunohistochemically detectable hormone products, so specific immunohistochemical typing is not necessary. Certain findings may be associated with more aggressive behavior, including large size (>3 cm), necrosis, local and vascular invasion, and high proliferation index, but the only certain indictor of malignancy is the presence of metastasis. Well-differentiated neuroendocrine tumors are graded from G1 to G3 based on their mitotic index. Although the tumor in this case showed mild nuclear atypia, the tumor was small and had a low mitotic index. Sherif

Answer 108

Multiple other benign and malignant exocrine tumors of the pancreas have been reported in children. All are exceedingly rare. Benign cystic tumors include serous and mucinous cystadenomas. As mentioned above, the main challenge is to differentiate these tumors from pseudocysts through thorough history-taking and adequate crosssectional imaging with CT scan or MRI. While there have been rare reports of mucinous cystadenocarcinoma in children, no cases of serous cystadenocarcinoma have been reported. Pancreatoblastoma is a malignant tumor occurring in young children. This is a rare, frankly malignant tumor, presenting with metastases at diagnosis in up to one-third of cases. Alpha fetoprotein is elevated in approximately 50% of cases and may be used as a tumor marker in such patients. Surgical resection is again the mainstay of treatment. Unresectable tumors, and those that present with metastatic disease, are treated with neoadjuvant chemotherapy followed by surgical resection. Long-term survival is dependent on complete resection of disease limited to the pancreas. Ductal adenocarcinoma is exceedingly rare in children, but presents similar to adults, i.e., with obstructive jaundice. Most occur in syndromic settings, such as Peutz–Jeghers or familial adenomatous polyposis. Complete resection is possible in a minority of patients. Autoimmune pancreatitis may occur in children, particularly teenagers and mimic ductal adenocarcinoma in presentation and on imaging. An elevated level of IgG4 is a sensitive and specific finding in this disease. Biopsy can be guided by endoscopic ultrasound and will demonstrate typical lymphoplasmacytic infiltration and obliterative phlebitis. The disease manifests a dramatic response to steroids, which is both diagnostic and therapeutic. Surgeons should be aware of this entity as it may lead to an incorrect diagnosis of adenocarcinoma followed by an unnecessary Whipple procedure. Any pediatric patient presenting with obstructive jaundice and a mass or enlargement of the head of the pancreas should undergo work-up for autoimmune pancreatitis. Sherif