Cholelithiasis (Gallstones)

Gallstones are relatively uncommon in blacks (except in sickle cell disease), exceptionally common in select groups of Native Americans and Hispanics, and a frequent occurrence in whites. Gallstones currently are being recognized in children with increased frequency. Whether this increase in diagnosis is related to an increase in frequency of the disease or an increase in recognition because of the widespread use of ultrasound for abdominal complaints is unclear. The incidence currently is reported to be 0.15% to 0.22% in children. In comparison, gallstones are found in approximately 10% of adults.

NONHEMOLYTIC CHOLELITHIASIS (Gallstones not due to breakdown of blood cells)

The gallstones in patients with nonhemolytic disease (diseases not caused by blood cell breakdown) are usually made of cholesterol. These stones result when the bile cannot dissolve all of the cholesterol and some of the cholesterol solidifies into a stone. Although cholesterol stones are often typically seen in adults as they get older, in obese patients, and in patients using estrogens or who are pregnant, these stones also can be seen in older children and adolescents. Nonhemolytic gallstones often are seen in obese children, in pregnant adolescents, in patients with a family history of gallstones, in women using oral contraceptives, and in children with other chronic illnesses such as cystic fibrosis. In some patients requiring chemotherapy for Wilms’ tumor, neuroblastoma, Hodgkin’s disease, or non-Hodgkin’s lymphoma, there also has been noted to be an increased risk for the development of gallstones.

Despite the above-described risk factors, no specific cause can be found in most patients with nonhemolytic gallstones. Although boys and girls usually are affected equally by gallstones in infancy and early childhood, gallstones are more common in girls in adolescents. This increased number of cases in older girls probably is related to the strong hormonal influences of estrogen and progesterone.

HEMOLYTIC DISEASE (Gallstones due to breakdown of blood cells)

Gallstones caused by breakdown of blood cells are usually colored black or earthy brown. Black colored stones usually are associated with a disease causing breakdown of blood cells (hemolytic disease), such as sickle cell disease, hereditary spherocytosis, thalassemia major, pyruvate kinase deficiency, autoimmune hemolytic anemia, and other hemolytic processes. The exact cause of the development of pigment stones is unclear but may in part be due to a change in the composition of bile. Poor gallbladder emptying may also play a role. Certain types of intestine removal may also play a role because of changes in the way the body absorbs bile from the gut.

Sickle Cell Anemia

Approximately 50,000 blacks have sickle cell disease. Gallstones are reported to occur in as many as 10% to 70% of patients with sickle cell anemia. The incidence of gallstones in children with sickle cell disease increases with age, with 12% affected in the 2- to 4-year age group and 42% affected in the 15- to 18-year age group.

Often, it can be difficult to tell the difference between abdominal pain due to gallstones from an abdominal crisis in the sickle cell patient. Ultrasound should be performed in all children with sickle cell disease and abdominal pain before labeling them as having a sickle crisis.

There has been an increased risk of complications related to gallstones in patients with sickle cell disease. At the same time this increased risk has been noted, laparoscopic gallbladder removal in the sickle cell patient has become much safer. For this reason removing the gallbladder (cholecystectomy) and the gallstones before problems occur has been suggested by some doctors. Of patients who have no symptoms, 50% require operation within 3 years because of significant problems or the start of symptoms of acute gallbladder disease. The child with sickle cell anemia must be carefully prepared before surgery in order to to avoid a sickle cell crisis. For elective operations, preoperative blood transfusion can be performed over 2 to 3 weeks before the operative procedure. This transfusion decreases the amount of abnormal hemoglobin in the blood. For urgent gallbladder removal, simple transfusion to a hemoglobin level of approximately 12 g/dL can allow a safe procedure. Another technique in the more urgent setting is an exchange transfusion. This involves replacing a large volume of the patient’s blood with banked blood that has normal hemoglobin.

Hereditary Spherocytosis

The incidence of gallstones in hereditary spherocytosis is 43% to 63% and is slightly more common in girls than boys. Children with hereditary spherocytosis may need their spleen removed to treat the condition. Abdominal ultrasound should be performed before elective spleen removal to detect the presence of gallstones. Laparoscopic gallbladder removal is recommended in all patients with hereditary spherocytosis and who have symptoms and in all patients with gallstones who are undergoing laparoscopic splenectomy. Although not used routinely, there have been reports of simple cholecystotomy, opening the gallbladder with removal of the stones and then sewing the gallbladder closed again, at the time of splenectomy. with no recurrence of stones after 11-year follow-up. This is generally discouraged because there is an increased risk of recurrent gallstones after removing the stones only and not the gallbladder, but with the spleen removed, the level of blood cell breakdown may be low enough to avoid new stone formation.

Thalassemia Major

The incidence of gallstones in children with thalassemia major varies from 2.3% to 23% and increases with age. Gallstones have been observed in 6% of children 6 to 10 years old and 45% of children 11 to 14 years old. The risk of gallstones in this patient population is decreasing, however, as a result of a hypertransfusion therapy. The development of the fragile blood cells by the bone marrow in patients with thalassemia major is avoided because of this therapy. For all symptomatic patients and for patients undergoing laparoscopic splenectomy in whom ultrasound shows the presence of gallstones, laparoscopic gallbladder removal is recommended.

CLINICAL PRESENTATION

Neonates and Infants

Gallstones in babies and young infants frequently result from other problems such as prematurity, surgical removal of a part of the bowel called the ileum, cystic fibrosis, long use of TPN (IV feeding), and not eating for a prolonged period of time. Other associated conditions include the use of furosemide, a medicine that helps patients get rid of extra water, phototherapy, used for babies with jaundice, polycythemia, an increased red blood cell count, and after exchange transfusion. Of children receiving long-term TPN, slightly less than half have been shown to develop gallstones. Bile thickening or sludge may be observed before stone formation. Gallstone formation in babies is probably caused by a number of problems happening in combination.

Gallstones in neonates and infants may go away on their own in about 20% of patients. It may be difficult to tell the difference between bile sludge and gallstones in premature infants, however, and in some cases that resolved, the patients may have had sludge rather than actual stones. Gallstones may go away in as little as 2 to 20 days after stopping TPN. Many neonates and infants have calcified stones, however, which do not resolve. These stones are very hard and may be seen on an X-ray. The recommended treatment for this kind of stone in this age group is not clear. Gallstones that are not calcified, are thought to be due to TPN and are causing no symptoms may be left alone for up to a year to see if they go away on their own. Babies that have stones that are causing symptoms or if the stones are calcified should probably have their gallbladder removed. Gallstones that have fallen out of the gallbladder into the main bile duct that drains the liver have what is called choledocholithiasis. Babies who have this often also have jaundice and usually will need the gallbladder removed, although on occasion this problem may get better on its own. A procedure called endoscopic retrograde cholangiopancreatography (ERCP) may performed to remove this type of gallstone but the procedure may not be possible in very small babies. If ERCP is not successful or if the child is too small for ERCP, surgery may be required.

Older Children

Most older children and adolescents with gallstones present with symptoms called biliary colic. These symptoms include abdominal pain, nausea, and vomiting. If the patient has inflammation or infection of the gallbladder, a problem called acute cholecystitis, they may have a swollen, tender gallbladder, and the pain is mostly in the right upper part of the abdomen. Younger children often have difficulty saying exactly where they hurt. Cholecystitis may be a fairly sudden condition (acute) or the pain can be present a long time and cause frequent, recurring symptoms (chronic). These symptoms often occur with eating. The pain is often difficult to pinpoint and rarely is associated with eating fatty food as is seen often in adults. In children with chronic cholecystitis and gallstones, the physical examination is often normal. Patients with acute cholecystitis may have a fever, and right upper abdominal tenderness. If there is also jaundice the patient may also have gallstones in the main bile duct from the liver. To help diagnose the condition, certain blood tests will be checked including white blood cell count, bilirubin levels, liver function tests and pancreatic enzymes.

In patients with suspected gallstones, the most accurate and useful diagnostic test is ultrasound. An abdominal x-ray may be performed and see about 30% of gallstones. For patients with suspected acute cholecystitis, a special scan called cholescintigraphy may be the most useful test to detect blockage of the cystic duct. This study may or may not be needed to diagnose the patient. Cholescintigraphy is also useful to see if the common bile duct is blocked. A CT scan is not helpful when first trying to diagnose gallstones in children but may be useful in cases complicated by gallstones in the main bile duct or when gallstones cause problems with the pancreas.