Gallstone disease is one of the most common problems affecting the digestive tract. Autopsy reports have shown a prevalence of gallstones from 11% to 36%.24 The prevalence of gallstones is related to many factors, including age, gender, and ethnic background. Certain conditions predispose to the development of gallstones. Obesity, pregnancy, dietary factors, Crohn’s disease, terminal ileal resection, gastric surgery, hereditary spherocytosis, sickle cell disease, and thalassemia are all associated with an increased risk of developing gallstones.8 Women are three times more likely to develop gallstones than men, and first-degree relatives of patients with gallstones have a twofold greater prevalence.25
Most patients will remain asymptomatic from their gallstones throughout life. For unknown reasons, some patients progress to a symptomatic stage, with biliary colic caused by a stone obstructing the cystic duct. Symptomatic gallstone disease may progress to complications related to the gallstones.26 These include acute cholecystitis, choledocholithiasis with or without cholangitis, gallstone pancreatitis, cholecystocholedochal fistula, cholecystoduodenal or cholecystoenteric fistula leading to gallstone ileus, and gallbladder carcinoma. Rarely, complication of gallstones is the presenting picture.
Gallstones in patients without biliary symptoms are commonly diagnosed incidentally on ultrasonography, CT scans, or abdominal radiography or at laparotomy. Several studies have examined the likelihood of developing biliary colic or developing significant complications of gallstone disease. Approximately 3% of asymptomatic individuals become symptomatic per year (i.e., develop biliary colic). Once symptomatic, patients tend to have recurring bouts of biliary colic. Complicated gallstone disease develops in 3% to 5% of symptomatic patients per year. Over a 20-year period, about two thirds of asymptomatic patients with gallstones remain symptom free.27
Because few patients develop complications without previous biliary symptoms, prophylactic cholecystectomy in asymptomatic persons with gallstones is rarely indicated. For elderly patients with diabetes, for individuals who will be isolated from medical care for extended periods of time, and in populations with increased risk of gallbladder cancer, a prophylactic cholecystectomy may be advisable. Porcelain gallbladder, a rare premalignant condition in which the wall of the gallbladder becomes calcified, is an absolute indication for cholecystectomy.
Gallstones form as a result of solids settling out of solution. The major organic solutes in bile are bilirubin, bile salts, phospholipids, and cholesterol. Gallstones are classified by their cholesterol content as either cholesterol stones or pigment stones. Pigment stones can be further classified as either black or brown. In Western countries, about 80% of gallstones are cholesterol stones and about 15% to 20% are black pigment stones.28 Brown pigment stones account for only a small percentage. Both types of pigment stones are more common in Asia.
Pure cholesterol stones are uncommon and account for <10% of all stones. They usually occur as single large stones with smooth surfaces. Most other cholesterol stones contain variable amounts of bile pigments and calcium, but are always >70% cholesterol by weight. These stones are usually multiple, of variable size, and may be hard and faceted or irregular, mulberry-shaped, and soft (Fig. 32-11). Colors range from whitish yellow and green to black. Most cholesterol stones are radiolucent; <10% are radiopaque. Whether pure or of mixed nature, the common primary event in the formation of cholesterol stones is supersaturation of bile with cholesterol. Therefore, high bile cholesterol levels and cholesterol gallstones are considered as one disease. Cholesterol is highly nonpolar and insoluble in water and bile. Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and lecithin (the main phospholipid in bile). Supersaturation almost always is caused by cholesterol hypersecretion rather than by a reduced secretion of phospholipid or bile salts.2
Gallbladder with cholesterol stones. Note the different shapes and sizes.
Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. Cholesterol is held in solution by micelles, a conjugated bile salt-phospholipid-cholesterol complex, as well as by the cholesterol-phospholipid vesicles. The presence of vesicles and micelles in the same aqueous compartment allows the movement of lipids between the two. Vesicular maturation occurs when vesicular lipids are incorporated into micelles. Vesicular phospholipids are incorporated into micelles more readily than vesicular cholesterol. Therefore, vesicles may become enriched in cholesterol, become unstable, and then nucleate cholesterol crystals. In unsaturated bile, cholesterol enrichment of vesicles is inconsequential. In the supersaturated bile, cholesterol-dense zones develop on the surface of the cholesterol-enriched vesicles, leading to the appearance of cholesterol crystals. About one third of biliary cholesterol is transported in micelles, but the cholesterol-phospholipid vesicles carry the majority of biliary cholesterol29 (Fig. 32-12).
The three major components of bile plotted on triangular coordinates. A given point represents the relative molar ratios of bile salts, lecithin, and cholesterol. The area labeled “micellar liquid” shows the range of concentrations found consistent with a clear micellar solution (single phase), where cholesterol is fully solubilized. The shaded area directly above this region corresponds to a metastable zone, supersaturated with cholesterol. Bile with a composition that falls above the shaded area has exceeded the solubilization capacity of cholesterol and precipitation of cholesterol crystals occurs. (Reproduced with permission from Holzbach RT. Pathogenesis and medical treatment of gallstones. In: Slesinger MH, Fordtran JS, eds. Gastrointestinal Diseases. Philadelphia: WB Saunders; 1989:1672.)
Pigment stones contain <20% cholesterol and are dark because of the presence of calcium bilirubinate. Otherwise, black and brown pigment stones have little in common and should be considered as separate entities.
Black pigment stones are usually small, brittle, black, and sometimes spiculated. They are formed by supersaturation of calcium bilirubinate, carbonate, and phosphate, most often secondary to hemolytic disorders such as hereditary spherocytosis and sickle cell disease, and in those with cirrhosis. Like cholesterol stones, they almost always form in the gallbladder. Unconjugated bilirubin is much less soluble than conjugated bilirubin in bile. Deconjugation of bilirubin occurs normally in bile at a slow rate. Excessive levels of conjugated bilirubin, as in hemolytic states, lead to an increased rate of production of unconjugated bilirubin. Cirrhosis may lead to increased secretion of unconjugated bilirubin. When altered conditions lead to increased levels of deconjugated bilirubin in bile, precipitation with calcium occurs. In Asian countries such as Japan, black stones account for a much higher percentage of gallstones than in the Western hemisphere.
Brown stones are usually <1 cm in diameter, brownish-yellow, soft, and often mushy. They may form either in the gallbladder or in the bile ducts, usually secondary to bacterial infection caused by bile stasis. Precipitated calcium bilirubinate and bacterial cell bodies compose the major part of the stone. Bacteria such as Escherichia coli secrete β-glucuronidase that enzymatically cleaves bilirubin glucuronide to produce the insoluble unconjugated bilirubin. It precipitates with calcium, and along with dead bacterial cell bodies, forms soft brown stones in the biliary tree.
Brown stones are typically found in the biliary tree of Asian populations and are associated with stasis secondary to parasite infection. In Western populations, brown stones occur as primary bile duct stones in patients with biliary strictures or other common bile duct stones that cause stasis and bacterial contamination.2,30
Chronic Cholecystitis (Biliary Colic)
About two thirds of patients with gallstone disease present with chronic cholecystitis characterized by recurrent attacks of pain, often inaccurately labeled biliary colic. The pain develops when a stone obstructs the cystic duct, resulting in a progressive increase of tension in the gallbladder wall. The pathologic changes, which often do not correlate well with symptoms, vary from an apparently normal gallbladder with minor chronic inflammation in the mucosa, to a shrunken, nonfunctioning gallbladder with gross transmural fibrosis and adhesions to nearby structures. The mucosa is initially normal or hypertrophied, but later becomes atrophied, with the epithelium protruding into the muscle coat, leading to the formation of the so-called Aschoff-Rokitansky sinuses.
The chief symptom associated with symptomatic gallstones is pain. The pain is constant and increases in severity over the first half hour or so and typically lasts 1 to 5 hours. It is located in the epigastrium or right upper quadrant and frequently radiates to the right upper back or between the scapulae (Fig. 32-13). The pain is severe and comes on abruptly, typically during the night or after a fatty meal. It often is associated with nausea and sometimes vomiting. The pain is episodic. The patient suffers discrete attacks of pain, between which they feel well. Physical examination may reveal mild right upper quadrant tenderness during an episode of pain. If the patient is pain free, the physical examination is usually unremarkable. Laboratory values, such as WBC count and liver function tests, are usually normal in patients with uncomplicated gallstones.
A. Sites of the most severe pain during an episode of biliary pain in 107 patients with gallstones (% values add up to >100% because of multiple responses). The subxiphoid and right subcostal areas were the most common sites; note that the left subcostal area was not an unusual site of pain. B. Sites of pain radiation (%) during an episode of biliary pain in the same group of patients. (Reprinted from Gunn A, Keddie N. Some clinical observations on patients with gallstones. Lancet. 1972;300(7771):239-241, Copyright 1972, with permission from Elsevier.)
Atypical presentation of gallstone disease is common. Association with meals is present in only about 50% of patients. Some patients report milder attacks of pain, but relate it to meals. The pain may be located primarily in the back or the left upper or lower right quadrant. Bloating and belching may be present and associated with the attacks of pain. In patients with atypical presentation, other conditions with upper abdominal pain should be sought out, even in the presence of gallstones. These include peptic ulcer disease, gastroesophageal reflux disease, abdominal wall hernias, irritable bowel disease, diverticular disease, liver diseases, renal calculi, pleuritic pain, and myocardial pain. Many patients with other conditions have gallstones.
When the pain lasts >24 hours, an impacted stone in the cystic duct or acute cholecystitis (see later Acute Cholecystitis section) should be suspected. An impacted stone without cholecystitis will result in what is called hydrops of the gallbladder. The bile gets absorbed, but the gallbladder epithelium continues to secrete mucus, and the gallbladder becomes distended with mucinous material. The gallbladder may be palpable but usually is not tender. Hydrops of the gallbladder may result in edema of the gallbladder wall, inflammation, infection, and perforation. Although hydrops may persist with few consequences, early cholecystectomy is generally indicated to avoid complications.
The diagnosis of symptomatic gallstones or chronic calculous cholecystitis depends on the presence of typical symptoms and the demonstration of stones on diagnostic imaging. An abdominal ultrasound is the standard diagnostic test for gallstones (see earlier Ultrasonography section).31 Gallstones are occasionally identified on abdominal radiographs or CT scans. In these cases, if the patient has typical symptoms, an ultrasound of the gallbladder and the biliary tree should be added before surgical intervention. Stones diagnosed incidentally in patients without symptoms should be left in place as discussed previously in the Natural History section. Occasionally, patients with typical attacks of biliary pain have no evidence of stones on ultrasonography. Sometimes only sludge in the gallbladder is demonstrated on ultrasonography. If the patient has recurrent attacks of typical biliary pain and sludge is detected on two or more occasions, cholecystectomy is warranted. In addition to sludge and stones, cholesterolosis and adenomyomatosis of the gallbladder may cause typical biliary symptoms and may be detected on ultrasonography. Cholesterolosis is caused by the accumulation of cholesterol in macrophages in the gallbladder mucosa, either locally or as polyps. It produces the classic macroscopic appearance of a “strawberry gallbladder.” Adenomyomatosis or cholecystitis glandularis proliferans is characterized on microscopy by hypertrophic smooth muscle bundles and by the ingrowths of mucosal glands into the muscle layer (epithelial sinus formation). Granulomatous polyps develop in the lumen at the fundus, and the gallbladder wall is thickened and septae or strictures may be seen in the gallbladder. In symptomatic patients, cholecystectomy is the treatment of choice for patients with these conditions.32
Patients with symptomatic gallstones should be advised to have elective laparoscopic cholecystectomy. While waiting for surgery, or if surgery has to be postponed, the patient should be advised to avoid dietary fats and large meals. Diabetic patients with symptomatic gallstones should have a cholecystectomy promptly, as they are more prone to develop acute cholecystitis that is often severe. Pregnant women with symptomatic gallstones who cannot be managed expectantly with diet modifications can safely undergo laparoscopic cholecystectomy during the second trimester. Laparoscopic cholecystectomy is safe and effective in children as well as in the elderly.33,34 Cholecystectomy, open or laparoscopic, for patients with symptomatic gallstones offers excellent long-term results. About 90% of patients with typical biliary symptoms and stones are rendered symptom free after cholecystectomy. For patients with atypical symptoms or dyspepsia (flatulence, belching, bloating, and dietary fat intolerance), the results are not as favorable.
Acute cholecystitis is secondary to gallstones in 90% to 95% of cases. Acute acalculous cholecystitis is a condition that typically occurs in patients with other acute systemic diseases (see later Acalculous Cholecystitis section). In <1% of acute cholecystitis, the cause is a tumor obstructing the cystic duct. Obstruction of the cystic duct by a gallstone is the initiating event that leads to gallbladder distention, inflammation, and edema of the gallbladder wall. Why inflammation develops only occasionally with cystic duct obstruction is unknown. It is probably related to the duration of obstruction of the cystic duct. Initially, acute cholecystitis is an inflammatory process, probably mediated by the mucosal toxin lysolecithin, a product of lecithin, as well as bile salts and platelet-activating factor. Increase in prostaglandin synthesis amplifies the inflammatory response. Secondary bacterial contamination is documented in 15% to 30% of patients undergoing cholecystectomy for acute uncomplicated cholecystitis. In acute cholecystitis, the gallbladder wall becomes grossly thickened and reddish with subserosal hemorrhages. Pericholecystic fluid often is present. The mucosa may show hyperemia and patchy necrosis. In severe cases, about 5% to 10%, the inflammatory process progresses and leads to ischemia and necrosis of the gallbladder wall. More frequently, the gallstone is dislodged and the inflammation resolves.35
When the gallbladder remains obstructed and secondary bacterial infection supervenes, an acute gangrenous cholecystitis develops, and an abscess or empyema forms within the gallbladder. Rarely, perforation of ischemic areas occurs. The perforation is usually contained in the subhepatic space by the omentum and adjacent organs. However, free perforation with peritonitis, intrahepatic perforation with intrahepatic abscesses, and perforation into adjacent organs (duodenum or colon) with cholecystoenteric fistula occur. When gas-forming organisms are part of the secondary bacterial infection, gas may be seen in the gallbladder lumen and in the wall of the gallbladder on abdominal radiographs and CT scans, an entity called an emphysematous gallbladder.
About 80% of patients with acute cholecystitis give a history compatible with chronic cholecystitis. Acute cholecystitis begins as an attack of biliary colic, but in contrast to biliary colic, the pain does not subside; it is unremitting and may persist for several days. The pain is typically in the right upper quadrant or epigastrium and may radiate to the right upper part of the back or the interscapular area. It is usually more severe than the pain associated with uncomplicated biliary colic. The patient is often febrile, complains of anorexia, nausea, and vomiting, and is reluctant to move, as the inflammatory process affects the parietal peritoneum. On physical examination, focal tenderness and guarding are usually present in the right upper quadrant. A mass, the gallbladder and adherent omentum, is occasionally palpable; however, guarding may prevent this. A Murphy’s sign, an inspiratory arrest with deep palpation in the right subcostal area, is characteristic of acute cholecystitis.
A mild to moderate leukocytosis (12,000–15,000 cells/mm3) is usually present. However, some patients may have a normal WBC. A high WBC count (above 20,000) is suggestive of a complicated form of cholecystitis such as gangrenous cholecystitis, perforation, or associated cholangitis. Serum liver chemistries are usually normal, but a mild elevation of serum bilirubin, <4 mg/mL, may be present along with mild elevation of alkaline phosphatase, transaminases, and amylase.31 Severe jaundice is suggestive of common bile duct stones or obstruction of the bile ducts by severe pericholecystic inflammation secondary to impaction of a stone in the infundibulum of the gallbladder that mechanically obstructs the bile duct (Mirizzi’s syndrome). In elderly patients and in those with diabetes mellitus, acute cholecystitis may have a subtle presentation resulting in a delay in diagnosis. The incidence of complications is higher in these patients, who also have approximately 10-fold the mortality rate compared to that of younger and healthier patients.
The differential diagnosis for acute cholecystitis includes a peptic ulcer with or without perforation, pancreatitis, appendicitis, hepatitis, perihepatitis (Fitz-Hugh–Curtis syndrome), myocardial ischemia, pneumonia, pleuritis, and herpes zoster involving the intercostal nerve.
Ultrasonography is the most useful radiologic testfor diagnosing acute cholecystitis. It has a sensitivity and specificity of 95%. In addition to being a sensitive test for documenting the presence or absence of stones, it will show the thickening of the gallbladder wall and the pericholecystic fluid (Fig. 32-14). Focal tenderness over the gallbladder when compressed by the sonographic probe (sonographic Murphy’s sign) also is suggestive of acute cholecystitis. Biliary radionuclide scanning (HIDA scan) may be of help in the atypical case. Lack of filling of the gallbladder after 4 hours indicates an obstructed cystic duct and, in the clinical setting of acute cholecystitis, is highly sensitive and specific for acute cholecystitis. A normal HIDA scan excludes acute cholecystitis. CT scan is frequently performed on patients with acute abdominal pain. It demonstrates thickening of the gallbladder wall, pericholecystic fluid, and the presence of gallstones as well as air in the gallbladder wall, but is less sensitive than ultrasonography.
Ultrasonography from a patient with acute cholecystitis. The arrowheads indicate the thickened gallbladder wall. There are several stones in the gallbladder (arrows) throwing acoustic shadows.
Patients who present with acute cholecystitis will need IV fluids, antibiotics, and analgesia. The antibiotics should cover gram-negative aerobes as well as anaerobes. A third-generation cephalosporin with good anaerobic coverage or a second-generation cephalosporin combined with metronidazole is a typical regimen. For patients with allergies to cephalosporins, an aminoglycoside with metronidazole is appropriate. Although the inflammation in acute cholecystitis may be sterile in some patients, more than one half will have positive cultures from the gallbladder bile. It is difficult to know who is secondarily infected; therefore, antibiotics have become a part of the management in most medical centers.
Cholecystectomy is the definitive treatment for acute cholecystitis.36 In the past, the timing of cholecystectomy has been a matter of debate. Early cholecystectomy performed within 2 to 3 days of the illness is preferred over interval or delayed cholecystectomy that is performed 6 to 10 weeks after initial medical treatment and recuperation. Several studies have shown that unless the patient is unfit for surgery, early cholecystectomy should be recommended, as it offers the patient a definitive solution in one hospital admission, quicker recovery times, and an earlier return to work.37
Laparoscopic cholecystectomy is the procedure of choice for acute cholecystitis. The conversion rate to an open cholecystectomy is higher (10%–15%) in the setting of acute cholecystitis than with chronic cholecystitis. The procedure is more tedious and takes longer than in the elective setting. However, when compared to the delayed operation, early operation carries a similar complication rate.
When patients present late, after 3 to 4 days of illness, or if they are unfit for surgery, they can be treated with antibiotics with laparoscopic cholecystectomy scheduled for approximately 2 months later. Approximately 20% of patients will fail to respond to initial medical therapy and require an intervention. Laparoscopic cholecystectomy could be attempted, but the conversion rate is high and some prefer to go directly for an open cholecystectomy. For those unfit for surgery, a percutaneous cholecystostomy or an open cholecystostomy under local analgesia can be performed. Failure to improve after cholecystostomy usually is due to gangrene of the gallbladder or perforation. For these patients, surgery is unavoidable. For those who respond after cholecystostomy, the tube can be removed once cholangiography through it shows a patent ductus cysticus. Laparoscopic cholecystectomy may then be scheduled in the near future.38 For the rare patients who can’t tolerate surgery, the stones can be extracted via the cholecystostomy tube before its removal.39
Common bile duct stones may be small or large and single or multiple, and are found in 6% to 12% of patients with stones in the gallbladder. The incidence increases with age. About 20% to 25% of patients above the age of 60 with symptomatic gallstones have stones in the common bile duct as well as in the gallbladder.40 The vast majority of ductal stones in Western countries are formed within the gallbladder and migrate down the cystic duct to the common bile duct. These are classified as secondary common bile duct stones, in contrast to the primary stones that form in the bile ducts. The secondary stones are usually cholesterol stones, whereas the primary stones are usually of the brown pigment type. The primary stones are associated with biliary stasis and infection and are more commonly seen in Asian populations. The causes of biliary stasis that lead to the development of primary stones include biliary stricture, papillary stenosis, tumors, or other (secondary) stones.
Choledochal stones may be silent and often are discovered incidentally. They may cause obstruction, complete or incomplete, or they may manifest with cholangitis or gallstone pancreatitis. The pain caused by a stone in the bile duct is very similar to that of biliary colic caused by impaction of a stone in the cystic duct. Nausea and vomiting are common. Physical examination may be normal, but mild epigastric or right upper quadrant tenderness as well as mild icterus are common. The symptoms may also be intermittent, such as pain and transient jaundice caused by a stone that temporarily impacts the ampulla but subsequently moves away, acting as a ball valve. A small stone may pass through the ampulla spontaneously with resolution of symptoms. Finally, the stones may become completely impacted, causing severe progressive jaundice. Elevation of serum bilirubin, alkaline phosphatase, and transaminases are commonly seen in patients with bile duct stones. However, in about one third of patients with common bile duct stones, the liver chemistries are normal.
Commonly, the first test, ultrasonography, is useful for documenting stones in the gallbladder (if still present), as well as determining the size of the common bile duct. As stones in the bile ducts tend to move down to the distal part of the common duct, bowel gas can preclude their demonstration on ultrasonography. A dilated common bile duct (>8 mm in diameter) on ultrasonography in a patient with gallstones, jaundice, and biliary pain is highly suggestive of common bile duct stones. Magnetic resonance cholangiography (MRC) provides excellent anatomic detail and has a sensitivity and specificity of 95% and 89%, respectively, at detecting choledocholithiasis >5 mm in diameter.18 Endoscopic cholangiography is the gold standard for diagnosing common bile duct stones. It has the distinct advantage of providing a therapeutic option at the time of diagnosis. In experienced hands, cannulation of the ampulla of Vater and diagnostic cholangiography are achieved in >90% of cases, with associated morbidity of <5% (mainly cholangitis and pancreatitis). Endoscopic ultrasound has been demonstrated to be as good as ERCP for detecting common bile duct stones (sensitivity of 91% and specificity of 100%), but it lacks therapeutic intervention and requires expertise, making it less available.41 PTC is rarely needed in patients with secondary common bile duct stones but is frequently performed for both diagnostic and therapeutic reasons in patients with primary bile duct stones.
For patients with symptomatic gallstones and suspected common bile duct stones, either preoperative endoscopic cholangiography or an intraoperative cholangiogram will document the bile duct stones.42 If an endoscopic cholangiogram reveals stones, sphincterotomy and ductal clearance of the stones is appropriate, followed by a laparoscopic cholecystectomy. An intraoperative cholangiogram at the time of cholecystectomy will also document the presence or absence of bile duct stones43 (Fig. 32-15). Laparoscopic common bile duct exploration via the cystic duct or with formal choledochotomy allows the stones to be retrieved in the same setting (see Choledochal Exploration section). If the expertise and/or the instrumentation for laparoscopic common bile duct exploration are not available, a drain should be left adjacent to the cystic duct and the patient scheduled for endoscopic sphincterotomy the following day. An open common bile duct exploration is an option if the endoscopic method has already been tried or is, for some reason, not feasible. If a choledochotomy is performed, a T tube is left in place. Stones impacted in the ampulla may be difficult for both endoscopic ductal clearance as well as common bile duct exploration (open or laparoscopic). In these cases the common bile duct is usually quite dilated (about 2 cm in diameter). A choledochoduodenostomy or a Roux-en-Y choledochojejunostomy may be the best option under this circumstance.44
An endoscopic sphincterotomy. A. The sphincterotome in place. B. Completed sphincterotomy. C. Endoscopic picture of completed sphincterotomy.
Retained or recurrent stones following cholecystectomy are best treated endoscopically (Fig. 32-16). If the stones were deliberately left in place at the time of surgery or diagnosed shortly after the cholecystectomy, they are classified as retained; those diagnosed months or years later are termed recurrent. If a common bile duct exploration was performed and a T tube left in place, a T-tube cholangiogram is obtained before its removal. Retained stones can be retrieved either endoscopically or via the T-tube tract once it has matured (2–4 weeks). The T tube is then removed and a catheter passed through the tract into the common bile duct. Under fluoroscopic guidance, the stones are retrieved with baskets or balloons. Recurrent stones may be multiple and large. A generous endoscopic sphincterotomy will allow stone retrieval as well as spontaneous passage of retained and recurrent stones. Patients >70 years old presenting with bile duct stones should have their ductal stones cleared endoscopically. Studies comparing surgery to endoscopic treatment have documented less morbidity and mortality for endoscopic treatment in this group of patients.45 They do not need to be submitted for a cholecystectomy, as only about 15% will become symptomatic from their gallbladder stones, and such patients can be treated as the need arises by a cholecystectomy.46
Retained common bile duct stones. The patient presented 3 weeks after laparoscopic cholecystectomy. A. An ultrasound shows a normal or mildly dilated common bile duct with a stone. Note the location of the right hepatic artery anterior to the common hepatic duct (an anatomic variation). B. An endoscopic retrograde cholangiography from the same patient shows multiple stones in the common bile duct. Only the top one showed on ultrasound as the other stones lie in the distal common bile duct behind the duodenum.
Cholangitis is one of the two main complications of choledochal stones, the other being gallstone pancreatitis. Acute cholangitis is an ascending bacterial infection in association with partial or complete obstruction of the bile ducts. Hepatic bile is sterile, and bile in the bile ducts is kept sterile by continuous bile flow and by the presence of antibacterial substances in bile, such as immunoglobulin. Mechanical hindrance to bile flow facilitates bacterial contamination. Positive bile cultures are common in the presence of bile duct stones as well as with other causes of obstruction. Biliary bacterial contamination alone does not lead to clinical cholangitis; the combination of both significant bacterial contamination and biliary obstruction is required for its development. Gallstones are the most common cause of obstruction in cholangitis; other causes are benign and malignant strictures, parasites, instrumentation of the ducts and indwelling stents, and partially obstructed biliary-enteric anastomosis. The most common organisms cultured from bile in patients with cholangitis include Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, Enterobacter, and Bacteroides fragilis.47
Cholangitis may present as anything from a mild, intermittent, and self-limited disease to a fulminant, potentially life-threatening septicemia. The patient with gallstone-induced cholangitis is typically older and female. The most common presentation is fever, epigastric or right upper quadrant pain, and jaundice. These classic symptoms, well known as Charcot’s triad, are present in about two thirds of patients. The illness may progress rapidly with septicemia and disorientation, known as Reynolds’ pentad (e.g., fever, jaundice, right upper quadrant pain, septic shock, and mental status changes). However, the presentation may be atypical, with little if any fever, jaundice, or pain. This occurs most commonly in the elderly, who may have unremarkable symptoms until they collapse with septicemia. Patients with indwelling stents rarely become jaundiced. On abdominal examination, the findings are indistinguishable from those of acute cholecystitis.48
Leukocytosis, hyperbilirubinemia, and elevation of alkaline phosphatase and transaminases are common and, when present, support the clinical diagnosis of cholangitis. Ultrasonography is helpful, as it will document the presence of gallbladder stones, demonstrate dilated ducts, and possibly pinpoint the site of obstruction; however, rarely will it elucidate the exact cause. The definitive diagnostic test is ERC. In cases in which ERC is not available, PTC is indicated. Both ERC and PTC will show the level and the reason for the obstruction, allow culture of the bile, possibly allow the removal of stones if present, and allow drainage of the bile ducts with drainage catheters or stents. CT scanning and MRI will show pancreatic and periampullary masses, if present, in addition to the ductal dilatation.
The initial treatment of patients with cholangitis includes IV antibiotics and fluid resuscitation. These patients may require intensive care unit monitoring and vasopressor support. Most patients will respond to these measures. However, the obstructed bile duct must be drained as soon as the patient has been stabilized. About 15% of patients will not respond to antibiotics and fluid resuscitation, and an emergency biliary decompression may be required. Biliary decompression may be accomplished endoscopically, via the percutaneous transhepatic route, or surgically. The selection of procedure should be based on the level and the nature of the biliary obstruction. Patients with choledocholithiasis or periampullary malignancies are best approached endoscopically, with sphincterotomy and stone removal, or by placement of an endoscopic biliary stent.49 In patients in whom the obstruction is more proximal or perihilar, or when a stricture in a biliary-enteric anastomosis is the cause or the endoscopic route has failed, percutaneous transhepatic drainage is used. When neither ERC nor PTC is available, an emergent operation for decompression of the common bile duct with a T tube may be necessary and lifesaving. Definitive operative therapy should be deferred until the cholangitis has been treated and the proper diagnosis established. Patients with indwelling stents and cholangitis usually require repeated imaging and exchange of the stent over a guidewire.
Acute cholangitis is associated with an overall mortality rate of approximately 5%. When associated with renal failure, cardiac impairment, hepatic abscesses, and malignancies, the morbidity and mortality rates are much higher.
Gallstones in the common bile duct are associated with acute pancreatitis. Obstruction of the pancreatic duct by an impacted stone or temporary obstruction by a stone passing through the ampulla may lead to pancreatitis. The exact mechanism by which the obstruction of the pancreatic duct leads to pancreatitis is still not clear. An ultrasonogram of the biliary tree in patients with pancreatitis is essential. If gallstones are present and the pancreatitis is severe, an ERC with sphincterotomy and stone extraction may abort the episode of pancreatitis. Once the pancreatitis has subsided, the gallbladder should be removed during the same admission. When gallstones are present and the pancreatitis is mild and self-limited, the stone has probably passed. For these patients, a cholecystectomy and an intraoperative cholangiogram or a preoperative ERC is indicated.
Cholangiohepatitis, also known as recurrent pyogenic cholangitis, is endemic to the Orient. It also has been encountered in the Chinese population in the United States, as well as in Europe and Australia. It affects both sexes equally and occurs most frequently in the third and fourth decades of life. Cholangiohepatitis is caused by bacterial contamination (commonly E. coli, Klebsiella species, Bacteroides species, or Enterococcus faecalis) of the biliary tree, and often is associated with biliary parasites such as Clonorchis sinensis, Opisthorchis viverrini, and Ascaris lumbricoides. Bacterial enzymes cause deconjugation of bilirubin, which precipitates as bile sludge. The sludge and dead bacterial cell bodies form brown pigment stones. The nucleus of the stone may contain an adult Clonorchis worm, an ovum, or an ascarid. These stones are formed throughout the biliary tree and cause partial obstruction that contributes to the repeated bouts of cholangitis. Biliary strictures form as a result of recurrent cholangitis and lead to further stone formation, infection, hepatic abscesses, and liver failure (secondary biliary cirrhosis).50
The patient usually presents with pain in the right upper quadrant and epigastrium, fever, and jaundice. Recurrence of symptoms is one of the most characteristic features of the disease. The episodes may vary in severity but, without intervention, will gradually lead to malnutrition and hepatic insufficiency. An ultrasound will detect stones in the biliary tree, pneumobilia from infection due to gas-forming organisms, liver abscesses, and, occasionally, strictures. The gallbladder may be thickened but is inflamed in about 20% of patients and rarely contains stones. MRCP and PTC are the mainstays of biliary imaging for cholangiohepatitis. They can detect obstructions, define strictures and stones, and allow emergent decompression of the biliary tree in the septic patient. Hepatic abscesses may be drained percutaneously. The long-term goal of therapy is to extract stones and debris and relieve strictures. It may take several procedures and require a Roux-en-Y hepaticojejunostomy to establish biliary-enteric continuity. Occasionally, resection of involved areas of the liver may offer the best form of treatment. Recurrences are common and the prognosis is poor once hepatic insufficiency has developed.51