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
Gallstones in patients without biliary symptoms are commonly diagnosed
incidentally on ultrasonography, CT scans, 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
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
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
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, p 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
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
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
(Reprinted from Gunn A, Keddie N: Some clinical
observations on patients with gallstones. The Lancet 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 Acute Cholecystitis below) should
be suspected. An impacted stone without cholecystis 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 Ultrasonography
above).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 Natural History. 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 Acalculous
Cholecystitis section below). 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
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
A mild to moderate leukocytosis (12,000 to 15,000 cells/mm3)
is usually present. However, some patients may have a normal WBC. A
high WBC (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
Ultrasonography is the most useful radiologic test for 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 to
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, 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). 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 to 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 E. coli, Klebsiella
pneumoniae, Streptococcus faecalis, Enterobacter,
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 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