The symptom of right upper quadrant (RUQ) pain is not specific for biliary and liver disease, although hepatobiliary disease must be entertained in any patient presenting with pain in this quadrant. Patients presenting with RUQ pain and hemodynamic instability must be considered to have a ruptured liver malignancy, ruptured adenoma, or a ruptured liver from trauma. In parts of the world where hepatitis and cirrhosis are endemic, hepatocellular carcinoma (HCC) can present as rupture and abdominal catastrophe in as many as 10% of patients. Rapid history and physical examination should be directed at eliciting symptoms, signs, or history of hepatitis and cirrhosis. Along with urgent resuscitation, imaging by US or CT should be obtained to look for hemoperitoneum and liver mass. An emergent angiogram can be diagnostic and allow for arterial embolization as the definitive life-saving procedure.

RUQ pain and sepsis can be associated with stone disease complicated by infection. However, the differential diagnosis includes peptic ulcer disease, biliary dyskinesia, colonic diverticulitis, pancreatitis, hepatitis, appendicitis, gallbladder malignancy, or hepatic malignancy. We will discuss the workup and treatment of gallstones, segregating the algorithms according to the presence of jaundice, sepsis, and other symptoms.

Jaundice is the only symptom that is pathognomonic for biliary or hepatic disease. The color of the skin is accompanied usually by acholic stool and dark urine with pruritus occurring in one-third of patients. The causes of jaundice can be prehepatic, hepatic, or posthepatic. Most prehepatic and hepatic causes of jaundice such as hemolysis or acute hepatitis are not surgical diseases and lack signs of biliary dilatation on imaging. The causes of jaundice that are surgical diseases are generally those with biliary obstruction and ductal dilatation. We will discuss in detail the workup of obstructive jaundice.

The majority of patients who present to a surgeon with a hepatobiliary problem have already undergone a partial workup including imaging for their chief complaint. Following are the common clinical scenarios and their workups.

Cholelithiasis affects more than 20 million Americans. Common risk factors include the five Fs: fat, female, forty, fecund, and family history. Most patients with gallstones remain asymptomatic, but 20% percent of patients will develop symptoms after 15 years of follow-up. Gallstones may cause biliary colic or acute cholecystitis, obstructive jaundice due to choledocholithiasis, pancreatitis, cholangitis, and gallbladder carcinoma.

Biliary colic is characterized as moderately severe, steady, crescendo-type crampy RUQ pain that can radiate to the right shoulder, subscapular region, or the back, and often follows a meal high in fat content when the gallbladder contracts against a stone, obstructing the cystic duct. The pain can persist from several minutes to several hours, and may be accompanied by nausea, vomiting, and anorexia; if it lasts >4 hours, one should consider the development of acute cholecystitis.

Acute cholecystitis most commonly occurs in women ages 30 to 60 years. A diagnosis of acute cholecystitis is based on the history, physical examination, and laboratory tests. Patients complain of fever and RUQ pain, with radiation to the right shoulder or back, associated with nausea, vomiting, and anorexia, often after eating a fatty meal. The pain usually lasts for more than 4 to 6 hours. The most accurate physical finding is a positive Murphy’s sign: inspiratory arrest during RUQ palpation; yet, the sensitivity of this sign may be diminished in the elderly.

In contrast to biliary colic, acute cholecystitis is not fully explained by cystic duct obstruction. Acute cholecystitis may result from irritation of the gallbladder mucosa from lecithin, a normal component of bile, which propagates inflammation through release of additional inflammatory mediators. The majority of patients have infected bile, usually involving Escherichia coli, Enterococcus, Klebsiella, and Enterobacter.

The most common complication of acute cholecystitis is the development of gallbladder gangrene (20%) and perforation (2%). Emphysematous cholecystitis is identified in 1% of cases of acute cholecystitis and is associated with significant morbidity. It more commonly occurs in men in their fifth to seventh decade, and half of these patients are diabetic. This complication is caused by secondary infection of the gallbladder wall with gas-forming Clostridium, E. coli, Pseudomonas, or Klebsiella species. Crepitus in the abdominal wall adjacent to the gallbladder is an important clue to the diagnosis but is rarely detected. There may be mild to moderate unconjugated hyperbilirubinemia. Emphysematous cholecystitis heralds the development of a gangrenous gallbladder and subsequent perforation.

Gangrenous cholecystitis is the most common complication of acute cholecystitis, particularly in older patients, diabetic patients, or those who delay seeking treatment. Perforation occurs after a gangrenous, ischemic region of the gallbladder wall becomes necrotic. The perforation may be walled off by omentum or adjacent organs and be localized as a pericholecystic abscess; at times the perforation occurs into the peritoneum, leading to generalized peritonitis and a high mortality. The inflamed gallbladder may become adherent to the small or large bowel, forming a cholecystoenteric fistula, and leading to gallstone ileus.

Along with fever, RUQ pain, and Murphy’s sign, patients with acute cholecystitis may have a slightly elevated alkaline phosphatase and white blood cell count with a left shift. Elevations in the serum total bilirubin and alkaline phosphatase are not usually seen, and when present should raise suspicion for acute cholangitis, choledocholithiasis, or Mirizzi syndrome, a condition in which a gallstone impacted in the distal cystic duct causes extrinsic compression of the common bile duct (CBD). There may also be an elevation of transaminases.

If a patient has RUQ pain and fever, but US does not reveal stones or sludge, one must suspect acalculous cholecystitis. Acalculous cholecystitis accounts for 10% of cholecystitis in adults but 30% in children. In the critically ill who may be intubated and sedated, fever, vague abdominal discomfort, and leukocytosis warrant high suspicion for this entity. Risk factors in adults include acquired immunodeficiency syndrome (AIDS), major
trauma or burns, mechanical ventilation, total parenteral nutrition (TPN), recent episode of sepsis, multiple transfusions, childbirth, or hemodynamic instability. Significant vascular disease has been observed in 72% of outpatients diagnosed with acalculous cholecystitis. In children, risk factors include hemolytic disorders such as sickle cell anemia, congenital cystic duct stenosis, acute streptococcal infection, and Borrelia recurrentis. The pathogenesis is multifactorial, including gallbladder stasis and ischemia.

On physical examination, one may elicit exquisite RUQ tenderness or palpate a mass. Up to 20% of patients will be jaundiced due to partial biliary obstruction induced by inflammation extending into the CBD. Leukocytosis with a left shift and elevated liver function tests are more common than in acute calculous cholecystitis.

Chronic cholecystitis is associated with gallstones and results from the mechanical irritation or recurrent attacks of acute cholecystitis, which leads to fibrosis and gallbladder wall thickening. Symptoms do not correlate with its presence.

US is the best initial imaging examination for gallstones due to its availability, low cost, and lack of ionizing radiation. US can be used in pregnant women, patients with contrast allergies, or those in whom MRI is contraindicated. Routine US has a >95% sensitivity for detecting gallstones, and is 88% sensitive and 80% specific for differentiating symptomatic cholelithiasis from acute cholecystitis. Under ideal conditions, stones 3 mm in size may be identified, and intrahepatic ductal dilatation may be ascertained. Characteristic findings of acute cholecystitis include gallbladder wall thickening (>4 to 5 mm) or edema (double-wall sign), pericholecystic fluid, impacted stone or biliary sludge, and a sonographic Murphy’s sign. US may erroneously note the presence of overlying bowel gas, but this gas may be in the gallbladder wall and is worrisome for gangrenous cholecystitis.

US findings that may suggest acalculous cholecystitis include absence of gallstones or sludge, >5-mm thickness of the gallbladder wall with pericholecystic fluid, a positive Murphy’s sign, failure to visualize the gallbladder, emphysematous cholecystitis with gas bubbles in the fundus of the gallbladder (champagne sign), or frank perforation of the gallbladder with associated abscess formation. An edematous gallbladder wall, however, may be visualized on US in patients with congestive heart failure, ascites, hypoalbuminemia, or nephrotic syndrome.

CT of the abdomen is often obtained when a patient presents with abdominal pain and other diagnoses are considered, or if there is evidence of intrahepatic ductal dilatation. CT is unnecessary in the diagnosis of acute cholecystitis, although it can demonstrate gallbladder wall edema, pericholecystic stranding, and high-attenuation bile.

Cholescintigraphy, which uses a technetium-labeled hepatic iminodiacetic acid, is often referred to as a hydroxy iminodiacetic acid (HIDA) scan, and is obtained if the US is indeterminate. HIDA is injected intravenously, taken up by hepatocytes, and secreted into bile. If the cystic duct is patent, the agent leads to visualization of the gallbladder. The contrast should then be visualized in the CBD and small bowel within 30 to 60 minutes. The test is “positive” if the gallbladder does not visualize, which signifies cystic duct obstruction secondary to edema with acute cholecystitis or an obstructing stone. The HIDA scan has 97% sensitivity and 90% specificity rates. False-positive results can result from cystic duct obstruction with a stone or tumor, severe liver disease, fasting patients receiving TPN, biliary sphincterotomy, and hyperbilirubinemia. False-negative results are uncommon and may be due to incomplete cystic duct obstruction. The HIDA scan is not helpful in intensive care unit patients due to bile stasis or poor gallbladder contractility and is also not recommended to assess acalculous cholecystitis as delay in therapy may prove fatal. HIDA scan is also useful in demonstrating biliary dyskinesia, defined as a gallbladder ejection fraction <40%, especially when pain occurs during cholecystokinin injection.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique for evaluating the intrahepatic and extrahepatic bile ducts. Although the sensitivity of MRCP for detecting choledocholithiasis is 100%, specificity for gallbladder wall thickening is only 69%, compared with US (96%). MRCP is much more expensive than US and should not be used to diagnose acute cholecystitis.

Choledocholithiasis is present in 10% to 20% of patients with cholelithiasis. Indicators of choledocholithiasis include evidence of CBD stones on imaging, persistent jaundice (total bilirubin >3 mg/dL) especially in the setting of CBD duct dilatation (>6 mm), a history of jaundice or gallstone pancreatitis, or modest elevation of transaminases or alkaline phosphatase. If US detects intrahepatic and extrahepatic ductal dilatation in the setting of biliary colic, the most likely diagnosis is choledocholithiasis.

Acute cholangitis is a clinical syndrome characterized by fever, RUQ pain, and jaundice, called Charcot’s triad. When associated with altered mental status and hypotension, known as Reynolds’ pentad, it can be life-threatening. In the elderly or those on corticosteroids, hypotension may be the only presenting symptom. In the setting of biliary obstruction and stasis due to biliary calculi or a stricture, high pressure facilitates bacteria (having ascended from the duodenum) to proliferate and migrate into the biliary tract and the circulation causing septicemia.

Biliary stones most commonly cause noniatrogenic cholangitis. Other causes include infected choledochal cysts, primary sclerosing cholangitis (PSC), hemobilia, and Mirizzi syndrome. Mirizzi syndrome refers to common hepatic duct obstruction caused by extrinsic compression from an impacted gallstone in the cystic duct. Iatrogenic conditions account for half of all episodes of acute cholangitis, especially in tertiary referral centers, due to the increasing numbers of biliary stents and complex biliary procedures involving biliary–biliary or biliary–enteric anastomosis, which may lead to biliary strictures.

Laboratory tests reveal elevated white blood count with a left shift and a cholestatic pattern of elevated total bilirubin, transaminases, and alkaline phosphatase. Blood cultures should be performed.

Patients with dilated intrahepatic ducts but with no extrahepatic ductal dilatation have obstruction in the liver or high in the porta hepatis. The etiology of high biliary obstruction is stones, mass lesions, cystic lesions, or PSC. Stones can cause common duct obstruction or intrahepatic ductal obstruction. Mass lesions may be identified either as parenchymal lesions in the liver impinging on the bile duct or as masses growing from the biliary tree; the workup of the hepatic parenchymal lesion is discussed further later in this chapter. The most common neoplastic cause of biliary obstruction and jaundice is HCC, which can produce jaundice both by extrinsic compression and by intraductal extension. Jaundice from high biliary obstruction can also result from cholangiocarcinoma, either a small one occurring at the hilus of the liver (Klatskin tumor) or a large one extending to involve the hilus (intrahepatic cholangiocarcinoma). Cystic lesions, both benign and malignant, may also cause jaundice. Benign simple cysts that are large can obstruct the biliary tree, although the most common reason is rapid expansion from a spontaneous bleed into the cyst. Complex cysts resulting from infection (e.g., echinococcal) or malignancy (cystadenocarcinoma) can also cause jaundice. Finally, high biliary stricture can be caused by multifocal or unifocal sclerosing cholangitis. The multifocal form will usually be suspected because of multiple strictures seen on imaging and confirmed by liver biopsy. The unifocal form is often diagnosed only after an extensive liver and biliary resection for presumed cholangiocarcinoma.

A finding of extrahepatic ductal dilatation indicates distal bile duct obstruction.

Figure 7 illustrates an algorithm for workup and treatment of patients with gallbladder polyps and masses. It is based on longitudinal follow-up studies in which small (<1 cm) gallbladder polyps followed by imaging had a low rate of subsequent diagnosis of cancer. Abdominal US is the study of choice due to its >90% sensitivity and specificity rates in diagnosing small polyps. CT is most useful in patients with suspected gallbladder cancer as it can provide staging information such as liver involvement or metastasis.