Cholecystitis

Cholecystitis

Last Updated: June 17, 2004

Synonyms and related keywords: acute cholecystitis, chronic cholecystitis, acalculous cholecystitis, calculous cholecystitis, gallbladder inflammation, gall bladder inflammation, gallstones, gall stones

AUTHOR INFORMATION Section 1 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyAuthor: Andre Hebra, MD, Clinical Associate Professor, Department of Surgery, University of South Florida School of Medicine; Director, Minimally Invasive Pediatric Surgery Program, Chief of Surgery, All Children's Hospital

Coauthor(s): Melissa Miller, MD, Department of Surgery, Medical University of South Carolina

Andre Hebra, MD, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, Association for Academic Surgery, Society of Laparoendoscopic Surgeons, South Carolina Medical Association, Southeastern Surgical Congress, and Southern Medical Association

Editor(s): Jeffrey J DuBois, MD, Professor, Department of Surgery, Division of Pediatric Surgery, University of California at Davis School of Medicine; Robert Konop, PharmD, Clinical Assistant Professor, Department of Pharmacy, Section of Clinical Pharmacology, University of Minnesota; Carmen Cuffari, MD, Assistant Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University; Steven Schwarz, MD, Chairman, Department of Pediatrics, Long Island College Hospital; Professor of Pediatrics, State University of New York Downstate Medical Center; and Steven Altschuler, MD, President and CEO, Children's Hospital Foundation, Children's Hospital of Philadelphia

INTRODUCTION Section 2 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyBackground: Cholecystitis, which has long been considered an adult disease, is quickly gaining recognition in pediatric practice because of the significant documented increase in nonhemolytic cases over the last 20 years. Gallbladder disease is common throughout the adult population, affecting as many as 25 million Americans and resulting in 500,000-700,000 cholecystectomies per year. Although gallbladder disease is much more rare in children, with 1.3 pediatric cases occurring per every 1000 adult cases, pediatric patients undergo 4% of all cholecystectomies. In addition, acalculous cholecystitis, uncommon in adults, is not that unusual in children with cholecystitis. Because of the increasing incidence of gallstones and the disproportionate need for surgery in the pediatric population, consider cholecystitis and other gallbladder diseases in the differential diagnosis in any pediatric patient with jaundice or abdominal pain in the right upper quadrant, particularly if the child has a history of hemolysis.

Pathophysiology: Cholecystitis is defined as inflammation of the gallbladder and is traditionally divided into acute and chronic subtypes. These subtypes are considered to be 2 separate disease states; however, evidence suggests that the 2 conditions are closely related, especially in the pediatric population. Most gallbladders that are removed for acute cholecystitis show evidence of chronic inflammation, supporting the concept that acute cholecystitis may actually be an exacerbation of chronic distension and tissue damage. Cholecystitis may also be considered calculous or acalculous, but the inflammatory process remains the same.

Chronic cholecystitis is most often related to gallstone disease but has been documented without gallstones. Its course may be insidious or involve several acute episodes of obstruction. The initiating factor is thought to be the supersaturation of bile, often with cholesterol crystals and/or calcium bilirubinate, which contributes to stone formation and inflammation. These processes lead to chronic obstruction, decreased contractile function, and biliary stasis, which contribute to further inflammation of the gallbladder wall. Biliary stasis also permits the increased growth of bacteria, usually Escherichia coli and enterococci, which may irritate the mucosa and increase inflammatory response. Chronic acalculous cholecystitis is less understood, but it may result from a functional deficiency of the gallbladder, which leads to spasm and an inability to appropriately empty its contents, causing chronic bile stasis.

Acute calculous cholecystitis results from a more sudden obstruction of the cystic duct by gallstones, which results in distension of the sac, edema, and bile stasis with bacterial overgrowth. These events lead to inflammation and a local release of lysolecithins, which further exacerbates the inflammatory process. In addition, edema of the wall and duct reinforces obstruction and may cause ischemia of the local tissue, releasing still more inflammatory mediators. Local lymph node hypertrophy and duct torsion or congenital anomalies may further complicate the obstructive process. As obstruction and inflammatory tissue damage progress, bacteria may proliferate. Bile cultures are positive in 75% of cases, usually with E coli, enterococci, or Klebsiella species. Bacterial infection most likely follows tissue damage, but after colonization, the severity of the disease can dramatically worsen. This cascade of events quickly leads pain and, possibly, a toxic appearance.

Acute acalculous cholecystitis develops in a similar manner but from different etiologic factors than acute calculous cholecystitis. Acute acalculous cholecystitis is most often associated with systemic illness, whether chronic or critical and acute. Increased mucous production, dehydration, and increased pigment load all are factors that increase cholesterol saturation and biliary stasis, whereas hyperalimentation, assisted ventilation, intravenous narcotics, ileus, and prolonged fasting contribute to cholestatic hypofunction. These conditions allow the formation of biliary sludge and may lead to obstruction. The resulting inflammation and edema lead to compromised blood flow and bacterial infection, as in acute calculous cholecystitis; however, the compromised blood flow appears more central in acute acalculous cholecystitis because acute acalculous cholecystitis can occur in vasculitides (eg, Kawasaki disease, periarteritis nodosa) presumably because of direct vascular compromise.

Frequency: In the US: The exact frequency of acute and chronic cholecystitis in children is not known. The overall incidence appears to have increased in the last 3 decades because of the high consumption of fatty foods by young children (ie, Western diet). In children with chronic hemolysis (eg, hemolytic anemias), the incidence of cholecystitis is much more prevalent than in the general population. Biliary sludge and/or gallstones are likely to form in 1 in 5 children with hemolytic anemia before their adolescent years.

Mortality/Morbidity: Most information related to morbidity and mortality in gallstone disease is related to the adult population, although some trends can be extracted and applied to the pediatric population. In general, the mortality rate of cholecystectomy in acute cholecystitis has dropped from 6.6% in 1930 to 1.8% in 1950 to nearly 0% currently. In one study, the overall mortality rate in 42,000 patients receiving open cholecystectomy (OC) was 0.17%; the mortality rate in patients younger than 65 years was 0.03%. Children can be expected to do well, although comorbid conditions are common and may cause complications. Risk factors for morbidity and mortality in the pediatric population include associated conditions, such as cystic fibrosis (CF), obesity, hepatic disease, diabetes mellitus, sickle cell disease, and immunocompromise.

General complications, such as pulmonary, cardiac, thromboembolic, hepatic, and renal insufficiency, account for most deaths. Procedure-related complications mainly contribute to morbidity and occur with higher frequency in acute cholecystitis in which symptoms of gallstone disease have been present longer than 1 year. The most common procedure-related complications are wound infections, abscess, cholangitis or pancreatitis, ileus, hemorrhage, and bile duct complications.

Although OC is still commonly performed, the laparoscopic approach has become much more common and is now the new criterion standard. In 1994, approximately 80% of all cholecystectomies were performed laparoscopically. This approach reduces the morbidity associated with length of recovery. Patients report less pain, a shortened hospital stay, and a faster return to productivity. In addition, cosmetic results are improved. Lugo-Vicente found that the length of stay, days that pain medication is taken, and time before a regular diet can be resumed were all reduced by one half.

Laparoscopic cholecystectomy (LC) carries its own risks, however. Major complications include bleeding, pancreatitis, leakage from the duct stump, and major bile duct injury. The risk of ductal injury increases from 0.1-0.2% in OC to 0.5-1% in LC; however, Holcomb et al reported no iatrogenic injuries with LC in their first 100 patients. They believe that with conscientious surgical care, morbidity related to the laparoscopic approach can be minimized.

Acalculous cholecystitis has its own statistics for mortality and morbidity. Mortality in the adult population has been reported to be as high as 10% and, in patients with critical illness, up to 50%. The mortality rate in patients with critical illness is most likely related to the close association with severe systemic illness. Surrounding illness and risk factors should be considered when predicting morbidity and mortality in children.

Other procedures used in cholecystitis carry risks. Choledochotomy and endoscopic papillotomy may be performed independently or in conjunction with cholecystectomy to aid in the treatment of choledocholithiasis. The overall mortality rate from choledochotomy (also applied to papillotomy) was determined to be 2.1%; however, by excluding patients with preexisting cholangitis or pancreatitis, the mortality rate decreased to 1.2%. The morbidity rate with these exclusions rests at 6-8%. The most serious complications resulting from these procedures have been hemorrhage, cholangitis, and pancreatitis.

Although controversy still exists over the use of cholecystectomy versus medical management, the morbidity and mortality rates have been the same in patients receiving early surgery as in those in whom surgery was delayed more than 48 hours for stabilization of inflammation. However, because symptoms continued in 24% of patients in whom surgery was delayed, if surgery is the goal of treatment, no advantage to delay surgery exists. In general, the complication rates of cholecystitis and cholecystectomy are low in the absence of critical illness. The ability to tolerate general anesthesia and operative conditions for cholecystectomy has become the most significant indicator of outcome in cholecystitis. As a rule, children recover well once appropriate operative treatment has been established.

Race: Racial and genetic influences in the adolescent age group are similar to those of adults. African Americans (without hemolytic disease) and the African Masai are less prone to cholelithiasis, whereas Chilean women, Pimas, and whites are more predisposed to this disease. Two contributing diseases in particular have a genetic component and racial distribution. Hemolytic diseases, including sickle cell disease and hemoglobin C disease, occur almost exclusively in the black population, although thalassemia also has a Mediterranean distribution. Cystic fibrosis (CF), which occurs mainly in whites, may also contribute to the formation of biliary sludge and, possibly, acalculous cholecystitis.

Sex: No sex predilection exists in children. In adult patients, the disease is more prevalent in females than in males.

Age: The incidence of cholecystitis in the pediatric population varies mostly according to age, with some racial and cultural influences. In a review of 693 cases of cholelithiasis, 10% of gallstones were found in children younger than 6 months, 21% were found in children aged 6 months to 10 years, and 69% were found in persons aged 11-21 years. In general, the infants who had cholelithiasis tended to be patients who were ill, were receiving hyperalimentation, and had prematurity, congenital anomalies, and necrotizing enterocolitis as compounding risk factors. Children aged 1-5 years most frequently had hemolysis as the underlying condition. Adolescent risk factors included menarche, pregnancy, and use of birth control pills; sex, race, and genetic influences also contributed to risk.

Cholelithiasis in infancy is most often related to acute and chronic illness and hyperalimentation. Risk factors include abdominal surgery, sepsis, bronchopulmonary dysplasia, hemolytic disease, malabsorption, necrotizing enterocolitis, and hepatobiliary disease. Other factors implicated include CF, polycythemia, phototherapy, and distal ileal resection. The immature hepatobiliary system of infants may predispose them to stone formation. Decreased hepatobiliary flow and immature bilirubin conjugation both contribute to stasis and sludge formation. Interestingly, up to one half of infantile gallstones, especially those associated with hyperalimentation, may resolve spontaneously.

Risk factors in children include hepatobiliary disease, abdominal surgery, artificial heart valves, and malabsorption. Gallstones usually contain a mixture of calcium bilirubinate and cholesterol. Hemolysis and prolonged hyperalimentation are significant influences in this age group. In adolescents, the epidemiology more closely resembles that of adults. Major risk factors include pregnancy, hemolytic disease, obesity, abdominal surgery, hepatobiliary disease, hyperalimentation, and malabsorption. In addition, differences based on race, genetics, and sex become more evident. Adolescent girls are much more at risk than boys. The female-to-male ratio in white adults is 4:1; in adolescents, the ratio is estimated to be 14-22:1.

Pregnancy, birth control pills, dehydration, and obesity have contributory roles. Early menarche has been shown to significantly increase incidence, perhaps because of the lithogenic effect of estrogen on bile. Racial and genetic influences in the adolescent age group are similar to those in adults (see Race).

CLINICAL Section 3 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyHistory: Symptoms of cholelithiasis often precede those of cholecystitis, although patients may have acute cholecystitis on initial presentation. Cholelithiasis causes biliary colic. Patients may complain of intermittent abdominal pain of inconsistent severity in the right upper quadrant, with possible radiation to the scapular region of the back, or pain may be diffuse or localized to the epigastrium. Discomfort is more likely to be nonspecific in infants and younger children. Patients of this age group often present with irritability, jaundice, and acholic stools. The classic history of patients with gallstones is postprandial right upper quadrant pain associated with nausea and vomiting, but this is usually observed only in older children. Jaundice in pediatric cholelithiasis is much more frequent than in adults and can occur in the absence of gallstone obstruction of the common bile duct. Most likely, the stone causes inflammation of the ductal tissue, creating an edematous obstruction to bile flow.

Patients with chronic cholecystitis usually present similarly to patients with biliary colic, with an intermittent and indolent history of pain. Therefore, differentiation must be made on the basis of findings from the physical examination and diagnostic tests.

Acute cholecystitic pain resembles biliary colic but is usually more severe and constant, lasting for several days. The pain may begin as a vague discomfort; however, as inflammation spreads and affects the surrounding peritoneum, the pain localizes to the right upper quadrant. Patients often report a recent history of nausea, vomiting, anorexia, and a low-grade fever. Onset of symptoms usually occurs approximately 1 week prior to presentation, although the patient may report years of the less severe symptoms of biliary colic and chronic cholecystitis.

Physical: The physical examination in acute cholecystitis usually reveals right upper quadrant tenderness. The classic triad is right upper quadrant pain, fever, and leukocytosis. The patient may have abdominal guarding and a positive Murphy sign, ie, arrest of inspiration on deep palpation of the gallbladder in the right upper quadrant of the abdomen. Omental adherence to the inflamed gallbladder combined with distension may create a palpable mass between the 9th and 10th costal cartilages. The ductal system may become inflamed, causing cholangitis. In 50% of these cases, the examiner may find a Charcot triad.

Charcot triad: This combination of right upper quadrant pain, fever, and jaundice is indicative of obstruction to the common bile duct and the presence of acute cholangitis. The Charcot triad is considered a medical emergency, and patients require immediate intervention.

Biliary colic versus chronic cholecystitis: Performing a physical examination may be the only way to distinguish biliary colic from chronic cholecystitis. In chronic cholecystitis, the patient usually complains of tenderness to palpation in the right upper quadrant; however, the differentiation may be trivial given the high likelihood of chronic cholecystitis in the presence of recurring biliary colic.

Causes: Cholelithiasis is the most common cause of acute or chronic cholecystitis in adults and children. Three major types of gallstones may form, although most gallstones have components of more than one type. Cholesterol gallstones are radiolucent and are composed of cholesterol (>50%), calcium salts, and glycoproteins. They form within the gallbladder and migrate to the bile duct. Pigment gallstones are black, often radiopaque, and usually associated with hemolytic diseases. Radiopacity and color are related to an increased concentration of calcium bilirubinate, which interacts with mucin glycoproteins to form gallstones. These gallstones also form within the gallbladder and migrate to the ductal system. Brown gallstones, in contrast, form within the ductal system and are orange, soft, and greasy. They are composed of calcium salts of bilirubin, stearic acid, lecithin, and palmitic acid. These gallstones are more often associated with infection.

In rural Asia, infections with Opisthorchis sinensis or Ascaris lumbricoides are predisposing conditions. In the United States, these gallstones are more rare, although they have been found after cholecystectomy in which the bile was infected (most often by E coli) and in infants and children infected with Staphylococcus, Enterobacter, Citrobacter, and Salmonella species. In addition, chronic urinary tract infections may predispose individuals to the formation of these gallstones, and isolated gallstones associated with Ascaris have been recorded in the United States.

All gallstones require similar conditions to form. First, the bile must be supersaturated either by cholesterol or bilirubin. Second, chemical kinetics must favor nucleation of cholesterol. This occurs when cholesterol is no longer soluble in bile. Finally, stasis of the gallbladder allows cholesterol or calcium bilirubinate crystals to remain long enough to aggregate to form gallstones.

Many disease processes can precipitate or foster these events. Infection induces the deconjugation of bilirubin glucuronide, thereby increasing the concentration of unconjugated bilirubin in the bile. Hemolysis overwhelms the conjugation abilities of the liver, increasing the amount of unconjugated bilirubin in the bile. Hemolytic diseases include hereditary spherocytosis, sickle cell disease, thalassemia major, hemoglobin C disease, and possible uncontrolled glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Multiple blood transfusions also increase the pigment load, which predisposes the bile to the formation of biliary sludge.

Dehydration, whether primary or secondary to shock or sepsis, concentrates the bile, increasing viscosity and allowing supersaturation. CF is associated with increased mucous production and may cause a similar scenario. Gallstones remain the most common cause of cholecystitis. Although acalculous cases significantly contribute to incidence of cholecystitis, most acalculous cases are related to systemic illness and risk factors rather than epidemiologic determinants. Therefore, the discussion of epidemiology focuses on the development of cholelithiasis.

Acalculous cholecystitis

The aforementioned diseases may also contribute to the development of acalculous cholecystitis because the formation of gallstones is not necessary for the obstruction of the bile duct. In addition, acalculous cholecystitis has been heavily associated with local inflammation, endocarditis, vasculitides, and systemic infection. Implicated infections include those occurring in typhoid fever, scarlet fever, measles, and AIDS and those caused by mycoplasma, Streptococcus (groups A and B), and gram-negative organisms, such as Shigella and E coli.

Acalculous cholecystitis may also occur postoperatively. Tsakayannis et al observed acute cholecystitis occurring after open-heart surgery in 4 of their patients, although it is more commonly observed in other nonbiliary surgeries and trauma. Shock, sepsis, hyperalimentation, prolonged fasting, intravenous narcotics, and multiple transfusions were the most common risk factors for the development of acute acalculous cholecystitis. The presence of 4 or more of these risk factors is highly predisposing.

Other unusual causes

Gallstones may also be caused by medications. Furosemide, octreotide, ceftriaxone, and cyclosporine have all been associated with gallstone disease. Ceftriaxone causes a reversible pseudolithiasis through several mechanisms. Ceftriaxone displaces bilirubin on albumin, thereby increasing the blood concentration of unconjugated bilirubin. Ceftriaxone is also secreted in bile, and calcium salts of ceftriaxone have been found in biliary sludge.

Risk factors associated with gallstone formation are prolonged fasting and age older than 24 months. Lasix has also been implicated in gallbladder disease, but it usually is only a compounding factor in the presence of prematurity, sepsis, or small-bowel disease. Cyclosporine may be lithogenic, but it seems to require high drug levels and hepatotoxicity. Finally, ileal disease or resection has been correlated with cholelithiasis in adults and children, although the risks associated with resection seem to be highest after puberty. These patients have an increased cholesterol secretion and a lowered bile acid secretion, which leads to cholesterol supersaturation.

DIFFERENTIALS Section 4 of 11

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Other Problems to be Considered: The differential diagnosis of cholecystitis is based on the presenting symptoms of abdominal pain in the right upper quadrant (patients with any of the diseases listed above may present with right upper quadrant pain). In the pediatric population, consider the following conditions in addition to the ones listed above:

Biliary colicCholangitisRupture of the gallbladderPeptic ulcer diseaseRenal colicGastritisPleurisyFitz-Hugh and Curtis syndrome (gonococcal perihepatitis)Hepatic abscessAbdominal tumorPyelonephritis

WORKUP Section 5 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyLab Studies: In assessing for cholecystitis, appropriate laboratory studies include a CBC, gamma-glutamyltransferase (GGT) assessment, amylase measurement, urinalysis, direct and indirect bilirubin tests, alkaline phosphatase measurement, and transaminase levels. In acute cholecystitis, the WBC count is elevated, with a predominance of polymorphonuclear cells and bands. Bilirubin, alkaline phosphatase and GGT levels rise secondary to a blocked biliary system. The traditional cholestatic picture involves direct hyperbilirubinemia, with a direct-to-indirect ratio approaching 1:1. Amylase may be elevated even in the absence of obstructive pancreatitis. In addition, transaminases may show mild elevation but not a significant increase, unless obstruction has been severe enough to cause hepatocyte damage. Transaminase levels are more likely to rise early in patients with obstruction of the common bile duct.

Imaging Studies: Plain abdominal radiography may be used for initial screening in abdominal pain. Calcifications representing radiopaque gallstones may be observed in the gallbladder or ductal system. Radiopaque gallstones contain more calcium bilirubinate and are more common in the pediatric population, especially in infants and children. In addition, complications such as porcelain gallbladder and emphysematous cholecystitis may be visible on radiographs, although these complications are rare in children.

Abdominal ultrasonography has become the diagnostic tool of choice in evaluating cholelithiasis. The accuracy of abdominal ultrasonography in depicting gallstones is estimated to be more than 95%, but its reliability in the accurate diagnosis of acute cholecystitis is more limited. Ultrasonographic findings in acute cholecystitis include a discrete echodensity representing the gallstone, the presence of sludge, and, possibly, ductal anomalies or dilation. The gallbladder may be dilated with thickened walls. Imhof et al found gallbladder wall thickness of more than 3.5 mm to be a reliable independent diagnostic indicator of cholecystitis. Gallstones are often in a dependent position in the gallbladder and may move as the patient changes position. The reliability of ultrasonography is well established with both opaque and lucent gallstones. Results are immediate, and accessibility is usually excellent.

Oral cystography has been used in the past, but is now largely ignored because of the refinement of ultrasonography. Oral cystography involves the ingestion of contrast material that is secreted in the bile. Lack of visualization of the gallbladder indicates cholelithiasis. This procedure is limited by liver dysfunction and malabsorption. In addition, the contrast tablets have been associated with emesis and diarrhea, further complicating effectiveness.

The most accurate tool in the diagnosis of acute cholecystitis is biliary scintography, otherwise known as the hepatic 2,6-dimethyliminodiacetic acid or hepatoiminodiacetic acid (HIDA) scanning. This procedure involves the intravenous injection of substances labeled with technetium 99m, taken into the hepatocytes, and excreted into the biliary system. Normal hepatic uptake without gallbladder visualization is diagnostic, but false positive results occur with decreased biliary function secondary to prolonged fasting and the use of hyperalimentation. Morphine augmentation of this test has been shown to decrease false positive results. Induced spasm of the sphincter of Oddi increases biliary pressure and enhances gallbladder filling. This test may be unnecessary, however, because the clinical diagnosis and treatment are determined by the symptoms and presence of gallstones or sludge. Ultrasonography has proved its usefulness in depicting gallstones, does not rely on contrast, and, therefore, may be safer.

Other imaging techniques that can be used in the diagnosis of cholecystitis include MRI and CT, especially in cases in which ultrasonography is not helpful. Ultrasonographic results may be compromised by ileus, surgical incisions, and coexisting diseases, especially those found in patients who are critically ill. MRI and CT may be more sensitive than ultrasonography in detecting inflammation within and around the gallbladder. In addition, the presence of other sources of abdominal sepsis are more easily discovered and treated by means of MRI and CT.

Other Tests: Other tests associated with the diagnosis and treatment of cholecystitis include cholecystokinin (CCK) stimulation, intraoperative cholangiography, and endoscopic retrograde cholangiopancreatography (ERCP). CCK stimulation may be employed during other imaging studies, such as cholescintigraphy. Gallbladder dyskinesia after CCK administration is diagnostic of gallbladder hypofunction and may be useful in discerning acalculous or chronic cholecystitis and acute inflammation.

Intraoperative cholangiography, whether intravenous or percutaneous, is widely used for the visualization of the gallbladder and ductal system. However, cholangiography can be time-consuming and an added expense to the patient, although some data show no statistical difference in operative time with and without its use. Consider cholangiography for any risk of obstruction of the common bile duct. Indications are a history of jaundice, pancreatitis, dilated common bile duct, and the presence of small gallstones. The benefits of using cholangiography have not been proven for routine cholecystectomy, routine screening for congenital anomalies, or assessment of the common bile duct for obstruction in the absence of clinical suspicion.

If the patient displays signs and symptoms of choledocholithiasis, ERCP may also be used preoperatively for exploration of the common bile duct. This procedure is both diagnostic and therapeutic because it may be used for stent placement, basket retrieval, or papillotomy to allow passage of gallstones; however, available choledochoscopes may be too large for small patients.

Procedures: One alternative to cholecystectomy is percutaneous transhepatic cholecystostomy. In this approach, thread a catheter directly into the gallbladder and place it to allow gravity drainage. Cholecystostomy is especially useful in acalculous cholecystitis and in seriously ill patients with simple gallstones in whom obstruction of the common bile duct is ruled out. Because cholecystectomy is the standard of care for cholecystitis, cholecystostomy is usually reserved for seriously ill patients who may not tolerate surgery.

Choledocholithiasis complicates the picture of cholecystitis and usually requires adjunctive procedures to cholecystectomy. If obstruction of the common bile duct is suspected preoperatively, perform ERCP before surgery with papillotomy, stent placement, or basket retrieval. If gallstones are found intraoperatively, several techniques can be used. The common bile duct can be flushed with saline or opened and explored. Additionally, an endoscope or nephroureteroscope may be used intraoperatively for basket retrieval.

Histologic Findings: The histology of the inflamed gallbladder is fairly straightforward. Acute cholecystitis shows changes similar to that of any acute inflammation. Edema, leukocytic infiltration, and vascular congestion are prominent. Inflammation may progress to abscess formation, gangrenous necrosis, and perforation, especially in acalculous cholecystitis. Chronic cholecystitis shows long-term inflammatory changes, with lymphocytes, plasma cells, and macrophages scattered throughout the mucosa. Subserosal fibrous tissue forms and may extend into the subepithelial layer with increasing disease severity. As the mucosa proliferates, epithelium may become buried in crypts known as Rokitansky-Aschoff sinuses.

Over time, chronic obstruction and inflammation may lead to the deposit of calcium within the gallbladder wall, causing the porcelain gallbladder, which is visible on flat plate imaging of the abdomen. Another variation is xanthogranulomatous cholecystitis in which chronic inflammation leads to a shrunken nodular gallbladder with many foci of necrosis and hemorrhage. This condition may be confused with malignancy but is actually benign. Hydrops of the gallbladder may also develop with chronic obstruction. This is characterized by a distended lumen and atrophic walls. Obstruction of the common bile duct may cause histologic change in nearby organs. Ductal hyperplasia ensues from obstruction and distension, and periportal fibrosis in the liver may occur with hepatic bile flow obstruction. Gallstones may also cause transient acute pancreatitis, resulting in characteristic histologic changes in the pancreas.

TREATMENT Section 6 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyMedical Care: Medical care of the patient with acute cholecystitis centers around stabilization of the patient and preparation for surgery if the patient is a candidate. Administer IV fluids to correct any dehydration and continue as maintenance therapy. Standard regimens include 5% dextrose in 0.2% sodium chloride solution or 5% dextrose in 0.45% sodium chloride solution with 20 mEq of potassium chloride (KCl) per liter at a rate determined by standard pediatric calculations.

Patients who are at risk for vaso-occlusion, including those with sickle hemoglobinopathies, should receive hydration at 1.5 times maintenance dose. The patient should receive nothing by mouth (NPO), and a nasogastric tube should be placed to low-intermittent wall suction for evacuation of gastric contents. This step minimizes stimulation to the inflamed gallbladder and prepares the patient for general anesthesia. Administer pain medications; however, avoid morphine because of its spasmodic effects on the sphincter of Oddi.

Antibiotics with biliary excretion covering enteric pathogens may be administered to control infection. The combination of ampicillin, gentamicin, and clindamycin is a common and well-accepted regimen. In addition, cefoperazone has a broad spectrum of coverage and good biliary excretion. The use of antibiotics remains controversial. Some authors assert that antibiotics are not necessary in simple cases and should be reserved for persistent fever or worsening condition; however, Agrawal found a significant reduction in postoperative infection with the use of prophylactic preoperative antibiotic administration in elective cholecystectomy. Because of the high percentage of cases of acute cholecystitis that are complicated by bacterial colonization, clinicians should maintain a low threshold for the use of antibiotic therapy.

Removal of the gallbladder is the standard of care in patients with symptomatic gallstone disease, although some exceptions exist. Critically ill children with acute acalculous cholecystitis may not tolerate anesthesia and operative conditions. These children should receive antibiotic therapy, hyperalimentation, and gastric decompression until their conditions improve. These patients may then undergo surgery if symptoms persist; however, many cases resolve with medical therapy alone. One author reported a 75% resolution of acute acalculous cholecystitis with the use of antibiotics, nasogastric suction, and hyperalimentation. Therefore, antibiotics may be sufficient in critically ill patients who do not tolerate anesthesia and who may be assisted by other procedures, such as cholecystotomy, if gallbladder drainage is necessary.

Observation is also recommended in infants with gallstone disease, especially those with hyperalimentation-associated gallstones. These gallstones often dissolve with maturation of the hepatobiliary system. The gallbladder should be removed with any sign of common duct obstruction, pancreatitis, or cholecystitis. Cholecystectomy should also be performed if gallstones persist longer than 1 year or if long-term hyperalimentation is anticipated, as in Crohn disease, pseudo-obstruction, or short-bowel syndrome. Medical care in chronic cholecystitis or other gallbladder disease is also supportive. Cholecystectomy is recommended in most patients with gallstone disease. Treatment should be aimed at control of any underlying conditions and preparation for surgery.

Children with sickle cell disease present a unique challenge because their hemoglobinopathy may cause perioperative and postoperative complications. These patients are susceptible to vaso-occlusive crises, pneumonia, sepsis, and pulmonary infarct, most likely secondary to hypoxia, dehydration, and acidosis in response to anesthesia.

Ware et al observed no complications when preoperative transfusion of RBCs were performed to obtain a hemoglobin A (Hgb A) ratio greater than 2:1 while the hematocrit level was maintained at 35-45%. This required 2 transfusions 2 weeks apart in most patients with partial volume exchange employed for those with hemoglobin sickle cell (Hgb SC) or sickle beta-thalassemia (SB thalassemia) disease. The preparation involved with such improved outcomes suggests that planned elective surgery is beneficial to patients with sickle hemoglobinopathies.

Other medical management strategies include contact dissolution and biliary lithotripsy. Percutaneous transhepatic cholecystolitholysis involves the injection of a cholesterol solubilizer, such as methyl-tert-butyl ether, directly into the gallbladder.

The time between instillation and aspiration must be conscientiously limited to avoid leakage into the bile duct, causing abdominal pain and duodenitis. This method has been successful in a few children. Biliary lithotripsy has also been used with limited success. Similar to lithotripsy for nephrolithiasis, biliary lithotripsy uses shock waves to pulverize gallstones. Biliary lithotripsy causes fragmentation in most patients but rarely causes complete dissolution. Because fragments may still cause biliary colic and cholecystitis, additional oral therapy may be necessary. All management techniques that involve leaving the gallbladder in situ have 1-year recurrence rates of approximately 10% and 5-year recurrence rates of approximately 50%.

Surgical Care: The surgical options available are OC and LC. Although OC was considered the criterion standard, the laparoscopic approach is quickly becoming the preferred procedure and now is used in 75-80% of cases. Advantages are reduced pain and hospital stay and improved cosmetic results and patient satisfaction. Some concern remains regarding the slightly higher risk of bile duct injury and the increased difficulty of the procedure in cases of acute inflammation and in infants and children younger than 2 years. However, many authors now agree that acute cholecystitis is not a contraindication, although the surgeon must be experienced and well skilled with laparoscopic tricks. In addition, conversion to OC can be used in the face of extreme difficulty.

Some authors assert that LC is ideal in infants and children and should be the procedure of choice. In this case, surgical experience with laparoscopy and with infants is a must. Wide spacing of cannulas is helpful in small children to allow for visualization and adequate working distance. Also, with conscientious surgical technique, some authors believe that bile duct injury can be minimized. In general, OC is reserved for conversion and cases of prior major abdominal surgery. OC is accomplished through a right subcostal incision or a transverse abdominal incision if a splenectomy is also indicated. Laparoscopic entry involves 4 ports: 2 subcostal, 1 subxiphoid, and 1 umbilical.

The surgical course is usually routine. Patients can be admitted to the hospital the day of surgery and discharged within 48-72 hours. The average postsurgical hospital stay after LC is 36 hours, whereas patients undergoing OC typically need to stay in the hospital for 3 days. Continue hydration until the patient can tolerate a regular diet, usually the morning after LC. In either procedure, observe the patient postoperatively for complications, including fever, jaundice, ileus, pancreatitis, bile leak, or urinary retention. Jaundice or continued right upper quadrant pain may signify a retained common duct stone or biliary injury and should be investigated using ERCP or HIDA scanning as soon as possible.

Consultations: Use a team approach to achieve proper care of the patient with cholecystitis. Consult a pediatric gastroenterologist and surgeon early in the treatment of the patient. The assistance of a dietitian may be very useful if observation without surgery is to be used. In addition, consulting a radiologist is helpful if percutaneous cholecystotomy is considered.

Diet: Dietary recommendations in gallbladder disease differ according to the stage of disease. The 2 available strategies include acute management and preventative measures. The patient with acute cholecystitis should receive NPO and undergo nasogastric evacuation of gastric contents. The goal in this stage of disease is to eliminate unnecessary stimulation to the biliary system and to reduce infectious exposure. Additionally, preparations can be more readily made for surgery.

No widely accepted dietary therapy exists for the prevention of cholecystitis; however, the contemporary Western diet and obesity have been implicated as predisposing factors in the development of gallstone disease. Certainly, diet and exercise are influential, and the West is infamous for poor dietary and exercising habits. In the Jamaican cohort study, Walker examined a population of patients with sickle cell disease similar to that examined by Winter in the United States. The progression of biliary sludge to cholecystitis and the need for cholecystectomy was significantly decreased in the Jamaican population. Walker theorized that dietary differences in the 2 countries were causal. These cultural influences affect the adolescent and adult populations.

Presumably, a decrease in cholesterol and fatty food consumption would lower risk of disease, but no specific data supporting this have been collected. Dietary restriction to achieve weight reduction may minimize risk in children with obesity. Weight loss should be controlled and gradual because rapid reduction may increase bile cholesterol saturation and gallbladder stasis, actually promoting stone formation. Dietary management of chronic gallbladder disease in the absence of surgery also follows this preventative approach with the added goal of preventing symptoms. Although biliary colic in children is less likely to directly correspond with fatty food consumption than in adults, still advise the patient to avoid high-fat meals. Finally, in patients with hyperalimentation-associated gallstones, administer low-dose enteral feedings, which may prevent stone formation by stimulating contraction of the gallbladder and reduction bile stasis.

Activity: Cholecystitis does not directly affect activity. Children should remain as active as their condition, comfort, and development allow. Postoperatively, activity recommendations correspond with the general precautions recommended abdominal surgery. Ambulation, as soon as tolerable, improves outcomes, although patients should restrict lifting to less than 5 pounds for several weeks.

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MEDICATION Section 7 of 11

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Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures BibliographyMedical treatment of gallstones remains inadequate, especially in the pediatric population. The only treatments approved for use in children are OC, cholecystotomy, LC, and ERCP. The 2 oral medications that have been used with some success are chenodiol (chenodeoxycholic acid) and ursodiol (ursodeoxycholic acid). Both medications selectively inhibit hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), thereby decreasing bile cholesterol supersaturation and lithogenicity. Chenodiol was shown to achieve complete dissolution of pure cholesterol gallstones in 15% of adult patients and partial dissolution in 28% of adult patients. However, the medications are expensive and cause adverse effects, including diarrhea and hepatotoxicity.

Combination treatment may be more effective and allow lower doses of each medication, causing fewer adverse effects. Although ursodiol was found to be unsuccessful in dissolving radiolucent gallstones in 10 children with CF, it has been shown to increase hepatobiliary excretion and may be useful in a cytoprotective and preventative role.

Drug Category: Bile acids -- Bile acids are used for the medical dissolution of cholesterol gallstones. Ursodiol and chenodiol both are orphan drugs and FDA approved for the dissolution of gallstones.

Drug Name

Ursodiol (Actigall, Urso) -- Suppresses hepatic synthesis and secretion and intestinal absorption of cholesterol. Does not seem to significantly inhibit synthesis and secretion of endogenous bile acids or affect secretion of phospholipids into bile. Overall, increases concentration at which cholesterol saturation occurs and allows cholesterol to solubilize in an aqueous medium. Preferred over chenodiol because of its relative safety.

Adult Dose

300 mg PO bid pc

Pediatric Dose

30 mg/kg/d PO divided tid pc; not to exceed 600 mg/dAdolescents: Administer as in adults

Contraindications

Documented hypersensitivity; calcified cholesterol gallstones, radiopaque gallstones, and radiolucent bile pigment stones (because of ineffectiveness)

Interactions

Bile acid sequestrants (eg, cholestyramine, colestipol) decrease absorption of bile acids; aluminum-based antacids may decrease absorption in a similar mechanism; estrogens, oral contraceptives, and clofibrate increase hepatic synthesis of cholesterol and can counteract effects

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Hepatotoxicity not associated with ursodiol but has been related to other bile acids; monitor liver enzymes before use and during therapy; obtain ultrasonograms q6mo during therapy to monitor progress; adverse effects are rare; diarrhea is most commonly, noted in