Pediatric Gallbladder Disease Surgery 

Although gallbladder disease is relatively uncommon in the pediatric population, pediatric patients comprise a disproportionate number of cholecystectomies; this rate has been rising in recent years. Pediatric gallbladder disease is most commonly associated with hemolytic diseases or hemoglobinopathies; however, other risk factors are recognized. Extended administration of total parenteral nutritional support or prior extensive bowel resection increase the risk of gallbladder disease, a cause that will likely continue to increase as survival rates improve in extremely low birth weight infants. Sadly, as childhood obesity reaches near epidemic proportions in the United States, gallbladder disease related to dietary factors is becoming more prominent.^{[1, 2]}

Gallbladder and biliary tract disease should be in the differential diagnosis of any pediatric patient who presents with right upper quadrant pain, jaundice, or unremitting dyspepsia with normal endoscopic gastric findings. Asymptomatic gallstones and symptomatic pigment gallstones in children are common indications for surgery. Noncalcified gallstones due to long-term cholestasis or total parenteral nutrition may respond to medical therapy such as ursodeoxycholic acid (Actigall).^[3] See the image below.

As in adults, laparoscopic cholecystectomy is the most feasible option for most patients.^[4] See the image below.

Aside from gallstones, cholestasis, and biliary dyskinesia, the pediatric population can experience congenital abnormalities of the gallbladder, including gallbladder perforation, hydrops of the gallbladder, gallbladder atresia, and choledochal cysts.

The introduction of laparoscopy revolutionized the practice of surgery. Trocars have been described since 25 BC, when these devices were used to drain "bad humors" from the abdomen. The first endoscopic examination was performed in 1901 by a German gynecologist. This technique was further developed in the early part of the 20th century but remained prohibitively dangerous due to uncontrolled increases in abdominal pressure and an inability to maintain internal temperature.

By 1970, laparoscopy was commonly used by gynecologists. In 1987, the French physician Mouret performed the first human laparoscopic cholecystectomy. While performing laparoscopy for a gynecologic procedure on a woman known to have biliary colic, he tilted his camera upwards and found that he was able to remove her gallbladder without making additional incisions. This forever changed the treatment of gallbladder disease. In 1992, a National Institutes of Health (NIH) consensus conference concluded that laparoscopy was the treatment of choice for cholecystectomy.^[5]

With the development of the laparoscopic cholecystectomy, the annual number of cholecystectomies has increased from 500,000 to 700,000.^[6] Few true contraindications to a laparoscopic technique are recognized; the leading contraindication is unclear anatomy. Open cholecystectomy remains a safe and viable alternative when laparoscopy is not feasible and is commonly performed in infants and children with more uncommon diseases of the biliary tree.

Gallbladder disease in the pediatric population causes pain and results in significant morbidity. The diagnosis is frequently delayed in the pediatric population because of its relative infrequency compared with disease in adults; this results in additional illness, pain, and missed school days for the child and missed work for the parent. More serious complications may develop, such as acute cholecystitis, choledocholithiasis, cholangitis, and pancreatitis.

Frequency

Congenital abnormalities of the gallbladder are rare. On the other hand, cholelithiasis has an incidence rate of 0.15-0.22% in the pediatric population. The number of children with cholelithiasis who have hemolytic disease has decreased over the past decade, reflecting either an increase in the incidence of cholesterol cholelithiasis and biliary dyskinesia or an increase in the recognition and willingness to treat these diseases in children.^[7] The increased willingness to treat these diseases may be due to the widespread use of laparoscopy in children over the last decade. The incidence of pediatric cholelithiasis has tripled over the past decade.

Possible reasons for a rise in gallbladder disease incidence include improved availability of ultrasonography to assess abdominal pain, high teenage pregnancy rates, and an increased prevalence of childhood obesity. Although historically gallbladder disease in pediatric populations was a sign of an underlying hemolytic disease, cholesterol stones in children with obesity are currently the most common cause of gallbladder disease. Female adolescents are 11-22 times more likely to have gallbladder disease than male adolescents.

One study reported that, of 224 pediatric patients who underwent cholecystectomy, the mean weight was 58 kg.^[8] Surgery was performed secondary to symptomatic cholelithiasis in 166 patients, secondary to gallbladder dyskinesia in 35 patients, secondary to pancreatitis in 7 patients, in combination with splenectomy in 6 patients, secondary to cholecystitis in 5 patients, secondary to choledocholithiasis in 1 patient, and secondary to acalculous cholecystitis or polyp in the remaining 2 patients. Gallstone formation is seen in 20% of patients with sickle cell disease prior to adolescence.^[9]

Pediatric gallbladder disease stems from numerous causes. Some of the best described include partial or complete obstruction of the biliary ductal system, hemolytic disease, estrogen effect, increased triglycerides, obesity, familial predisposition, and metabolic-related and stress-related causes (eg, short bowel syndrome with reduced bile salt absorption).^[10] However, numerous less defined causes have been recognized, including the association between previous abdominal or renal surgery and gallstones or the development of acalculous cholelithiasis.

Acquired disorders of the gallbladder include hydrops of the gallbladder, acalculous cholecystitis, cholestasis, cholelithiasis, acute and chronic cholecystitis, choledocholithiasis, and cholangitis. Hydrops or acute distention of the gallbladder with edema but without inflammation of the gallbladder wall may be a symptom of severe sepsis or shocklike states. Acute hydrops has been associated with Kawasaki disease and Henoch-Schönlein purpura.

Acalculous cholecystitis is uncommon in children but may arise following successful resuscitation from sepsis or shock when a previously unrecognized hydrops of the gallbladder becomes infected. This is confirmed by ultrasonographic findings that reveal a nonfunctioning, distended gallbladder without gallstones. Cholestasis is defined as a failure of bile to move through the biliary system and may lead to liver disease. Symptoms and treatment depend on the primary disease process but generally include jaundice, pruritus, xanthomata, hepatomegaly, dark urine, hypopigmented stools, and, possibly, splenomegaly. In neonates, this disorder is also known as neonatal direct hyperbilirubinemia or neonatal hepatitis. Causes of cholestasis in pediatric patients include congenital anomalies, prolonged dependence on parenteral nutrition, cholangitis, hepatitis, pregnancy, and prolonged illness.^[7]

In the pediatric population, cholelithiasis most commonly presents at the time of puberty but can occur at any point in development. Underlying medical causes for gallstones are present in more than 50% of patients with calculous cholecystitis. In infants, the presence of gallstones is generally related to an extended period of fasting, required parenteral nutrition, or abdominal surgery. These gallstones are generally mixed cholesterol-calcium bilirubinate stones. Cholesterol stones have surpassed hemolytic stones as the principle type of gallstones in pediatric patients. The etiology and risk factors remain similar to those seen in adults; a high-fat diet is the primary predisposing factor.

Hemolytic processes that result in gallstones in pediatric patients include sickle cell anemia, hereditary spherocytosis, and thalassemia. Stones found in these diseases are black-pigment stones predominantly composed of calcium bilirubinate. Medications such as ceftriaxone, furosemide, octreotide, ceftriaxone, and cyclosporin have been linked to gallstone formation.

Cholecystitis refers to inflammation of the gallbladder. Acute cholecystitis occurs secondary to an obstructing stone in the cystic duct that results in bile stasis and bacterial overgrowth. Chronic cholecystitis occurs as a result of several attacks of acute cholecystitis and results in an ulcerated and scarred gallbladder epithelium. Although gallstones are the most common cause of cholecystitis in adults and children, acalculous cholecystitis may occur following local inflammation or infection. Typhoid fever, scarlet fever, measles, and acquired immunodeficiency syndrome (AIDS) have been associated with acalculous cholecystitis, as have mycoplasma, Streptococcus group A and B, Shigella, and Escherichia coli infections. Shock, sepsis, hyperalimentation, fasting, intravenous narcotics, and transfusions are risk factors in the development of acute acalculous cholecystitis following surgery.

Cholangitis is caused by an ascending infection of the biliary tract and usually occurs after a gallstone blocks the common bile duct. The most commonly involved organisms include E coli and Klebsiella, Pseudomonas, and Enterococcus species.

Choledocholithiasis occurs in 11% of children with cholelithiasis and almost 20% of pediatric patients with gallstone pancreatitis. This condition is caused by the passage of stones through the cystic duct with entrapment at the papilla of Vater.

Clinical findings may include the following^[11] :

• Hydrops: Hydrops or acute distention of the gallbladder generally presents following severe sepsis or shocklike states. Acute hydrops has been associated with Kawasaki disease and Henoch-Schönlein purpura.
• Acalculous cholecystitis: This is uncommon in children but may arise following successful resuscitation from sepsis or shock when previously unrecognized hydrops of the gallbladder becomes infected. Presentation includes abdominal pain, vomiting, fever, and laboratory findings that may mimic acute cholecystitis.
• Cholestasis: Cholestasis generally presents with jaundice, pruritus, xanthomata, hepatomegaly, dark urine, hypopigmented stools, and, possibly, splenomegaly.
• Cholelithiasis: Cholelithiasis symptoms usually include vague abdominal pain in a child with obesity. Fatty food intolerance less common in pediatric patients than in adults. Some children may present with classic symptoms of biliary colic, including severe, intermittent, colicky right upper quadrant or epigastric pain following ingestion of fatty foods.
• Cholecystitis: Unlike the other processes, cholecystitis presents with persistent pain (generally >8 h) in the right upper quadrant or epigastric region, nausea and vomiting, fever, anorexia, and mild elevation of liver function test findings, particularly alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. When associated with cholesterol stones, the presentation is generally mild. In patients with sickle cell disease or diabetes, cholecystitis may present as a much more severe illness, resulting in sickle cell crisis, sepsis, or diabetic ketoacidosis.
• Cholangitis:The presentation of cholangitis in the pediatric population is similar to that seen in adults. The classic triad of symptoms (ie, the Charcot triad) includes fever, right upper quadrant pain, and jaundice. Without treatment, these symptoms advance to include confusion, hypotension, and sepsis. This condition presents with symptoms that mimic cholecystitis, only with the additional symptoms of jaundice and pain that radiates through to the back.

In the event of congenital anomalies, most surgeons recommend a liver biopsy and cholangiography if the diagnosis or anatomy cannot be clearly discerned by preoperative imaging.

Indications in patients with acquired biliary disease can be slightly more complex. Some patients, such as those with total parenteral nutrition–induced cholestasis and those with associated noncalcified cholelithiasis, can be medically treated; however, most gallstone disease in pediatric patients is treated in a manner similar to treatment in adults.

Cholecystectomy is the treatment of choice for symptomatic gallbladder disease. Preoperatively, based on laboratory and radiology study findings, the surgeon should determine whether the patient is at high risk for choledocholithiasis. Elevation of liver function test findings or dilation of the common bile duct should raise clinical suspicion. These patients should undergo preoperative endoscopic retrograde cholangiopancreatography (ERCP) to evaluate and clear the common bile duct, if needed. In centers where this procedure is not available for pediatric patients or in pregnant patients (in whom radiation is not feasible), magnetic resonance cholangiopancreatography (MRCP) can be performed to confirm the presence of choledocholithiasis before performing a more invasive procedure.

Once the patient has had the common bile duct cleared (if possible) or once the patient is deemed low risk for choledocholithiasis, a laparoscopic cholecystectomy is performed. This procedure is usually performed laparoscopically and may be safely performed in infants and children.^[12] Intraoperative procedures such as cholangiography and common duct exploration may be necessary if a stone persists in the biliary tract or if preoperative ERCP was unavailable.^{[13, 14]}

In healthy, asymptomatic patients with gallstones, cholecystectomy is not necessary; however, it may be performed at the same time as another procedure if an associated underlying disorder is present. Patients with hereditary spherocytosis and asymptomatic gallstones may benefit from a combined cholecystectomy and splenectomy. If no stones are present, a cholecystectomy is unnecessary because the risk of developing biliary disease after a splenectomy is low. Similarly, in patients with sickle cell disease or diabetes mellitus, a high morbidity and mortality rate is associated with emergency cholecystectomy and cholecystitis; therefore, elective cholecystectomy is recommended upon recognition of gallstone disease regardless of symptoms.^[15] Choledocholithiasis is reported in more than 10% of patients with sickle cell disease and should be considered during the preoperative evaluation.

In otherwise healthy pediatric patients with symptomatic gallstones, conservation therapy with diet control should be initiated, followed by elective cholecystectomy. Repeated episodes of biliary colic or admission for cholecystitis should prompt more urgent therapy.

Open cholecystectomy is reserved for patients who underwent failed laparoscopic cholecystectomy (most commonly due to either anatomic variation or adhesive disease due to a prior operation) or rare patients with preoperative contraindications to laparoscopy. These preoperative contraindications may include hostile abdomen due to severe adhesive disease, severe cardiopulmonary compromise, or known aberrant anatomy deemed by the surgeon as unsafe for laparoscopic intervention. Rarely, instead of cholecystectomy, a cholecystostomy is performed as a bridge to cholecystectomy in critically ill children with sepsis. Indications for cholecystostomy include critical illness due to cholecystitis in an unstable child who is unsuitable for operative intervention.

Bile secretion begins in the bile canaliculus in the liver. From here, bile enters the terminal channels (the canals of Hering), which gradually enlarge as they approach the portal canal. Bile flows from the centrilobular cells in zone 3 toward the portal triads in zone 1. These ducts anastomose to form hilar, intrahepatic ducts, which, in turn, become the main hepatic ducts.

The porta hepatis and the right and left hepatic duct join to form the common hepatic duct. Generally, the right and left hepatic ducts join outside the liver; however, in 5% of the population, this occurs inside the liver or at the location where the cystic duct joins the right hepatic duct. In 70% of the population, the cystic duct directly enters the common hepatic duct. Other possibilities include a cystic duct that runs parallel to the common hepatic duct or a cystic duct that runs anterior or posterior to the bile duct before medially joining the bile duct.

The common bile duct lays inside layers of the lesser omentum and is anterior to the portal vein and to the right of the hepatic artery. The common bile duct passes retroperitoneally behind the first portion of the duodenum, behind the head of the pancreas, and enters into the second part of the duodenum. This duct then passes through the duodenal wall to join the main pancreatic duct, thus forming the ampulla of Vater and resulting in the duodenal papilla on the duodenal side. The sphincter of Oddi surrounds the bile and pancreatic ducts while they are inside the duodenal wall.

Arterial supply of the bile ducts is mostly from the right hepatic artery. The common bile duct’s blood supply arises from branches of the hepatic and gastroduodenal arteries. Injury to these vessels may lead to stricture of the bile ducts.

Lymphatics from the lower portion of the common bile duct drain into glands near the head of the pancreas. Lymphatic drainage from the rest of the biliary tree empties into the hilum of the liver.

The gallbladder serves to store bile created by the liver. This system allows for the controlled release of bile into the duodenum as needed for lipid solubilization. The gallbladder sits below the right lobe of the liver. It is divided into a fundus that lies between the transverse colon and the musculus rectus abdominis and ninth costal cartilage, a body that lies close to the duodenum, an infundibulum, and a neck. The Hartmann pouch is an outpouching of the infundibulum that lies close to the neck of the gallbladder. When gallstones are impacted in this area, they obstruct the cystic duct and produce cholecystitis or obstruction of the adjacent common hepatic duct, which may lead to Mirizzi syndrome.

The neck of the gallbladder is connected to the cystic duct, which then empties into the common bile duct. The spiral valve of Heister, formed by the mucous membrane of the neck, regulates the flow of bile.

Arterial supply to the gallbladder comes from the cystic artery, which is usually a branch of the right hepatic artery. Venous drainage is provided by the cystic vein, which usually empties into the portal vein or directly into the hepatic sinusoids. Lymph drainage empties into a lymph gland near the neck of the gallbladder. The celiac axis supplies sympathetic innervation of the gallbladder; visceral pain is conducted through this and is frequently referred to the right subcostal, epigastric, and scapular regions. Parasympathetic innervation arises from both branches of the vagus nerve.

Tubuloalveolar glands aid in the production of mucus in the neck of the gallbladder. Rokitansky-Aschoff sinuses are invaginations of the surface epithelium that may extend through the muscularis and may be a source of inflammation secondary to bacterial stasis and proliferation within the sinuses. The ducts of Luschka sit along the hepatic surface of the gallbladder and directly open into the intrahepatic bile ducts. These may be a source of bile leak after cholecystectomy.

Importantly, anatomic variations are common and are likely related to injury to the common bile duct. Care must be taken to properly identify the anatomy of each individual patient; when the anatomy is unclear, intraoperative cholangiography should be performed to avoid potential serious duct injury.

Very few contraindications to surgical intervention are recognized in patients with gallstone disease. Patients with medical comorbidities should be preoperatively optimized to ensure safe operative intervention. For example, patients with sickle cell disease should be transfused to a preoperative hemoglobin level of 10 g. Acute gallstone pancreatitis should delay surgery until clinically resolved. Additionally, patients should be screened for a family history of anesthetic complications such as malignant hyperthermia. Some patients are not optimal candidates for laparoscopic surgery; however, in those patients, open cholecystectomy can usually be safely performed.