This document describes the anatomy of the gallbladder and extrahepatic biliary system. It discusses the structure and positioning of the gallbladder, cystic duct, common hepatic duct, common bile duct, and sphincter of Oddi. It notes the blood supply, lymphatic drainage, innervation, and histology of these structures. Variations in anatomy are also described.
The gall bladder is located in the junction of the right ninth costal cartilage and lateral border of the rectus abdominis.
It is a pear shaped sac lying on the inferior surface of the liver in a fossa between the right and quadrate lobes with a capacity of about 30 to 50 mL.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
The gall bladder is located in the junction of the right ninth costal cartilage and lateral border of the rectus abdominis.
It is a pear shaped sac lying on the inferior surface of the liver in a fossa between the right and quadrate lobes with a capacity of about 30 to 50 mL.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
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Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Gallbladder and the Extrahepatic Biliary System.docx
1. Gallbladder and the Extrahepatic Biliary System
ANATOMY Gallbladder The gallbladder is a pear-shaped sac that measures around 7 to 10 cm long, with
an average capacity of 30 to 50 mL. When obstructed, the gallbladder can distend markedly and contain
up to 300 mL of fluid. The gallbladder is located in an anatomic fossa on the inferior surface of the liver.
Cantle’s line, a vertical plane running from the gallbladder fossa anteriorly to the inferior vena cava (IVC)
posteriorly divides the liver into right and left lobes. The gallbladder itself is divided into four anatomic
areas: the fundus, the body, the infundibulum, and the neck. The fundus is the rounded, blind end that
normally extends 1 to 2 cm beyond the liver’s margin and contains most of the smooth muscle of the
organ. The body functions as the main storage area and contains most of the elastic tissue allowing for
distention. As the body tapers towards the neck of the gallbladder, a mucosal outpouching is present at
the junction of the neck and the cystic duct, known as the infundibulum or Hartmann’s pouch. Beyond
this, the neck of the gallbladder lies in the deepest part of the gallbladder fossa and can extend slightly
into the free portion of the hepatoduodenal ligament, where it connects with the cystic duct (Fig. 32-1).1
The same peritoneal lining that covers the liver extends to cover the fundus and the inferior surface of
the gallbladder. Occasionally, part or all of the gallbladder is embedded deep inside the liver parenchyma
(an intrahepatic gallbladder). Rarely, the gallbladder has a complete peritoneal covering on all sides and
is suspended in a mesentery off the inferior surface of the liver. The mucosal lining of the gallbladder is
formed by a single, highly redundant, simple columnar epithelium that contains cholesterol and fat
globules. The mucus secreted into the gallbladder originates in tubuloalveolar glands that are found in the
mucosal lining of the infundibulum and neck of the gallbladder, but are absent from the body and fundus.
The epithelial lining of the gallbladder is supported by a lamina propria. The gallbladder differs
histologically from the rest of the gastrointestinal (GI) tract in that it lacks a muscularis mucosa and
submucosa. The muscular layer has circular, longitudinal, and oblique fibers, but without well-defined
layers. The adventitia contains connective tissue, nerves, vessels, lymphatics, and adipocytes. The
gallbladder is covered by serosa except where the gallbladder is embedded in the liver. The cystic artery
that supplies the gallbladder is usually a branch of the right hepatic artery (>90% of the time). The course
of the cystic artery may vary, but it nearly always is found within the hepatocystic triangle (triangle of
Calot), the area bound by the cystic duct, common hepatic duct, and the inferior edge of the liver. When
the cystic artery reaches the neck of the gallbladder, it divides into anterior and posterior divisions.
Venous return is carried either through small veins that enter directly into the liver or, rarely, to a large
cystic vein that carries blood back to the portal vein. Gallbladder lymphatics drain into nodes Anatomy
1393 Gallbladder / 1393 Bile Ducts / 1394 Anatomic Variants / 1396 Physiology 1396 Bile Formation and
Composition / 1396 Gallbladder Function / 1397 Sphincter of Oddi / 1397 Diagnostic Studies 1398 Blood
Tests / 1398 Transabdominal Ultrasonography / 1398 Computed Tomography / 1398 Hepatobiliary
Scintigraphy / 1399 Magnetic Resonance Imaging / 1399 Endoscopic Retrograde
Cholangiopancreatography / 1400 Endoscopic Choledochoscopy / 1400 Endoscopic Ultrasound / 1401
Percutaneous Transhepatic Cholangiography / 1401 Gallstone Disease 1401 Prevalence and Incidence /
1401 Natural History / 1401 Gallstone Formation / 1402 Symptomatic Gallstones / 1404
Cholangiohepatitis / 1410 Procedural Interventions for Gallstone Disease 1410 Percutaneous
Transhepatic Cholecystostomy Tubes / 1410 Endoscopic Interventions / 1410 Cholecystectomy / 1410
Common Bile Duct Exploration / 1413 Common Bile Duct Drainage Procedures / 1414 Other Benign
Diseases and Lesions 1414 Biliary Dyskinesia and Sphincter of Oddi Dysfunction / 1414 Acalculous
Cholecystitis / 1415 Choledochal (Biliary) Cysts / 1417 Primary Sclerosing Cholangitis / 1417 Bile Duct
Strictures / 1418 Injury to the Biliary Tract 1419 Gallbladder / 1419 Extrahepatic Bile Ducts / 1419 Tumors
2. 1421 Carcinoma of the Gallbladder / 1421 Cholangiocarcinoma / 1423 Brunicardi_Ch32_p1393-
p1428.indd 1393 11/02/19 2:42 PM 1394 at the neck of the gallbladder. Frequently, a visible lymph node
(Lund’s or Mascagni’s node, often referred to as Calot’s node) overlies the insertion of the cystic artery
into the gallbladder wall. The gallbladder receives parasympathetic, sympathetic and sensory innervation
through nerve fibers running largely through the gastro hepatic ligament. Parasympathetic (cholinergic)
fibers arise from the hepatic branches of the vagus nerve to stimulate activity in the gallbladder, bile ducts,
and liver. These vagal branches also have peptide-containing nerves containing agents such as substance
P, somatostatin, enkephalins, and vasoactive intestinal polypeptide (VIP).2 The sympathetic and sensory
braches of the gallbladder, liver, and bile ducts pass through the celiac plexus and control gallbladder
relaxation and mediate the pain of biliary colic. Bile Ducts The extrahepatic biliary tree consists of the right
and left hepatic ducts, the common hepatic duct, the cystic duct, and the common bile duct. Exiting the
liver, the left hepatic duct is longer than the right and has a greater propensity for dilatation as a
consequence of distal obstruction. The two ducts join close to their emergence from the liver to form the
common hepatic duct. The common hepatic duct typically extends 1 to 4 cm, has a diameter of
approximately 4 mm, and lies anterior to the portal vein and to the right of the hepatic artery. The cystic
duct exits the gallbladder and joins the common hepatic duct at an acute angle to form the common bile
duct. The segment of the cystic duct immediately adjacent to the gallbladder neck bears a variable number
of mucosal folds called the spiral valves of Heister. While they do not have any valvular function, they can
make cannulation of the cystic duct difficult. The length and course of the cystic duct can be quite variable.
It may be short or absent and have a high union with the hepatic duct, or it may be long and running
parallel to, behind, or spiraling around to the common hepatic duct before joining it, sometimes as far
distally as at the duodenum. Variations of the cystic duct and its point of union with the common hepatic
duct are surgically important and misidentification can lead to bile duct injuries (Fig. 32-2). The union of
the cystic duct and the common hepatic duct marks the start of the common bile duct. This segment is
typically about 7 to 11 cm in length and 5 to 10 mm in diameter, i j o k l m a b d e f g c h q r p t n s Figure
32-1. Anterior aspect of the biliary anatomy. a = right hepatic duct; b = left hepatic duct; c = common
hepatic duct; d = portal vein; e = proper hepatic artery; f = gastroduodenal artery; g = right gastroepiploic
artery; h = common bile duct; i = fundus of the gallbladder; j = body of gallbladder; k = infundibulum of
the gallbladder; l = cystic duct; m = cystic artery; n = superior pancreaticoduodenal artery; o = neck of the
gallbladder; p = pancreatic duct; q = common hepatic artery; r = right gastric artery; s = ampulla of Vater;
t = supraduodenal artery. Note the situation of the hepatic bile duct confluence anterior to the right
branch of the portal vein, and the posterior course of the right hepatic artery behind the common hepatic
duct. Key Points 1 The physiology of the gallbladder, biliary tree, and sphincter of Oddi are regulated by a
complex interplay of hormones and neuronal inputs designed to coordinate bile release with food
consumption. Dysfunctions related to this activity are linked to the development of gallbladder
pathologies as described in this chapter. 2 In Western countries, the most common type of gallstones are
cholesterol stones. The pathogenesis of these stones relates to supersaturation of bile with cholesterol
and subsequent precipitation. 3 Laparoscopic cholecystectomy has been demonstrated to be safe and
effective, and it has become the treatment of choice for symptomatic gallstones. Knowledge of the various
anatomic anomalies of the cystic duct and artery is critical in guiding the dissection of these structures
and avoiding injury to the common bile duct during cholecystectomy. 4 Common bile duct injuries,
although uncommon, can be devastating to patients. Proper exposure of the hepatocystic (Calot’s)
triangle to obtain the critical view of safety and careful identification of the anatomic structures are keys
to avoiding these injuries. Once a bile duct injury is diagnosed, the best outcomes are seen at large referral
3. centers with experienced biliary surgeons, and patient transfer may be required. 5 The main risk factor
for gallbladder disease in Western countries is cholelithiasis. The main complications include cholecystitis,
choledocholithiasis, cholangitis, and biliary pancreatitis. Cholelithiasis is also the major risk factor for the
development of gallbladder cancer. 6 Carcinomas of the gallbladder or bile ducts generally have a poor
prognosis because patients usually present late in the disease process and have poor response to
chemotherapy and radiation. Surgery offers the best chance for survival and has good long-term
outcomes in patients with early-stage disease. Brunicardi_Ch32_p1393-p1428.indd 1394 11/02/19 2:42
PM 1395 GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 though its diameter can
increase slightly with age and following cholecystectomy. The upper third (supraduodenal portion) passes
downward in the free edge of the hepatoduodenal ligament, to the right of the hepatic artery and anterior
to the portal vein. The middle third (retroduodenal portion) of the common bile duct curves behind the
first portion of the duodenum and diverges laterally from the portal vein and the hepatic arteries. The
lower third (pancreatic portion) can curve behind the head of the pancreas in a groove, or traverse
through it to enter the wall of the second portion of the duodenum. The duct then runs obliquely
downward within the wall of the duodenum for 1 to 2 cm before opening on a papilla of mucous
membrane (ampulla of Vater), about 10 cm distal to the pylorus. The union of the common bile duct and
the main pancreatic duct follows one of three configurations. In about 70% of people, these ducts unite
outside the duodenal wall and traverse the duodenal wall as a single duct. In about 20%, they join within
the duodenal wall and have a short or no common duct, but open through the same opening into the
duodenum. In about 10%, they exit via separate openings into the duodenum, termed pancreas divisum.
The sphincter of Oddi, a thick coat of circular smooth muscle, surrounds the common bile duct at the
ampulla of Vater (Fig. 32-3). It controls the flow of bile, and in some cases pancreatic juice, into the
duodenum. The extrahepatic bile ducts are lined by a columnar mucosa with numerous mucous glands
that are concentrated in the common bile duct. A fibro areolar tissue containing scant smooth muscle
cells surrounds the mucosa. A distinct muscle layer is not present in the human common bile duct. The
arterial supply to the bile ducts is derived from the gastroduodenal and the right hepatic arteries, with
major trunks running along the medial and lateral walls of the common duct (sometimes referred to as 3
o’clock and 9 o’clock). The nerve supply to the common bile duct is the same as for the gallbladder, with
the density of nerve fibers and ganglia increasing near the sphincter of Oddi.1,2 A B C D E F G H Figure 32-
2. Variations of the cystic duct anatomy. A. Low junction between the cystic duct and common hepatic
duct. B. Cystic duct adherent to the common hepatic duct. C. High junction between the cystic and the
common hepatic duct. D. Cystic duct drains into right hepatic duct. E. Long cystic duct that joins common
hepatic duct behind the duodenum. F. Absence of cystic duct. G. Cystic duct crosses posterior to common
hepatic duct and joins it anteriorly. H. Cystic duct courses anterior to common hepatic duct and joins it
posteriorly. Pancreatic duct Common bile duct Sphincter of Oddi Duodenum Ampulla of Vater Duodenal
wall Figure 32-3. The sphincter of Oddi. Brunicardi_Ch32_p1393-p1428.indd 1395 11/02/19 2:43 PM 1396
SPECIFIC CONSIDERATIONS PART II A B C D E F Figure 32-5. Variations in the arterial supply to the
gallbladder. A. Cystic artery from right hepatic artery, about 80% to 90%. B. Cystic artery off the right
hepatic artery arising from the superior mesenteric artery (accessory or replaced), about 10%. C. Two
cystic arteries, one from the right hepatic, the other from the common hepatic artery, rare. D. Two cystic
arteries, one from the right hepatic, the other from the left hepatic artery, rare. E. The cystic artery
branching from the right hepatic artery and running anterior to the common hepatic duct, rare. F. Two
cystic arteries arising from the right hepatic artery, rare. Anatomic Variants The classic description of the
extrahepatic biliary tree and its arteries applies only in about one-third of patients.3 The gallbladder may
4. have abnormal positions, be intrahepatic, be rudimentary (a small, nonfunctional hypoplastic remnant),
or have anomalous forms or duplications. A partially or completely intrahepatic gallbladder is associated
with an increased incidence of cholelithiasis, and may be encountered at the time of cholecystectomy.
Isolated congenital absence of the gallbladder is very rare, with a reported incidence of 0.03%. Before the
diagnosis is made, the presence of an intrahepatic gallbladder or anomalous position must first be ruled
out. Duplication of the gallbladder with two separate cavities and two separate cystic ducts has an
incidence of about one in every 4000 persons. This occurs in two major varieties: the more common form
in which each gallbladder has its own cystic duct that empties independently into the same or different
parts of the extrahepatic biliary tree, and the less common variant in which the two cystic ducts merge
before they enter the common bile duct. Duplication is only clinically important when some pathologic
process affects one or both organs. Even rarer variants include a left-sided gallbladder (often with a cystic
duct that empties into the left hepatic or common bile duct), retrodisplacement of the gallbladder at the
posterior-inferior surface of the liver, transverse positioning of the gallbladder, or a floating gallbladder
in which the gallbladder is hanging by a mesentery (Fig. 32-4). Additional small bile ducts (of Luschka) may
drain directly from the liver fossa into the body of the gallbladder. If present, but not recognized at the
time of a cholecystectomy, a bile leak and subsequent accumulation of bile (biloma) may occur in the
abdomen. An accessory right hepatic duct occurs in about 5% of cases. Variations in how the common bile
duct enters the duodenum are described earlier, in the “Bile Ducts” section. Anomalies of the hepatic
artery and the cystic artery are quite common, occurring in as many as 50% of cases. While the right
hepatic artery usually originates from the proper hepatic branch of the celiac trunk, up to 20% of patients
will have a replaced right hepatic artery coming off the superior mesenteric artery. In about 5% of cases,
there are two right hepatic arteries, one from the proper hepatic artery and the other from the superior
mesenteric artery (accessory right hepatic artery). While the right hepatic artery typically runs posterior
to the bile ducts, variations may allow it to course anterior to the common duct, making it vulnerable
during surgical procedures, particularly if it runs parallel to the cystic duct or in the mesentery of the
gallbladder. The cystic artery arises from the right hepatic artery in about 90% of cases, but it may arise
from the left hepatic, common hepatic, gastroduodenal, or superior mesenteric arteries (Fig. 32-5).3
Figure 32-4. Floating gallbladder suspended on mesentery PHYSIOLOGY Bile Formation and Composition
The liver produces bile continuously and excretes it into the bile canaliculi. Bile leaves the liver through
the right and left hepatic ducts, into the common hepatic duct and then the common bile duct. With an
intact sphincter of Oddi, tonic contraction diverts bile flow into the gallbladder for storage, while mealtime
stimulation allows for its passage into the duodenum. The normal adult consuming an average diet
produces 500 to 1000 mL of bile a day. The secretion of bile is responsive to neurogenic, hormonal, and
chemical stimuli. Parasympathetic stimulation from the hepatic branches of the vagus nerve increases
secretion of bile, whereas sympathetic nerve stimulation via the celiac plexus results in decreased bile
flow. Hydrochloric acid, partly digested proteins, and fatty acids entering the duodenum from the stomach
after a meal stimulate the release of secretin from the S-cells of the duodenum, and increases bile
production and flow. Bile is mainly composed of water, mixed with bile salts and acids, cholesterol,
phospholipids (lecithin), proteins, and bilirubin. It also contains several minor components such as
Brunicardi_Ch32_p1393-p1428.indd 1396 11/02/19 2:43 PM 1397 GALLBLADDER AND THE
EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 electrolytes and vitamins. Sodium, potassium, calcium, and
chlorine have the same concentration in bile as in plasma or extracellular fluid. The pH of hepatic bile is
usually neutral or slightly alkaline, though a high protein diet will shift the bile to a more acidic ph. The
primary bile salts, cholate and chenodeoxycholate, are synthesized in the liver from cholesterol
5. metabolism. They are conjugated there with taurine and glycine and act within the bile as anions (bile
acids) that are balanced by sodium. These bile acids are then excreted into the bile by hepatocytes and
aid in the digestion and absorption of fats in the intestines.4 About 80% of the secreted conjugated bile
acids are reabsorbed in the terminal ileum. The remainder is dehydroxylated (deconjugated) by gut
bacteria, forming the secondary bile acids deoxycholate and lithocholate. These are absorbed in the colon
and can then be transported back to the liver. Eventually, about 95% of the bile acid pool is reabsorbed,
the so-called enterohepatic circulation. Only a small amount (5%) is excreted in the stool, allowing the
relatively small quantity of bile acids produced to have maximal effect. The color of the bile is due to the
presence of the pigment bilirubin (orange or yellow) and its oxidized form, biliverdin (green), which are
the metabolic products of the breakdown of hemoglobin, and are present in bile in concentrations 100
times greater than in plasma. Bilirubin conjugated in the liver can be excreted through the urine as
urobilinogen (yellow). Remaining excess bile pigment passes into the intestines where bacteria convert it
into stercobilinogen (brown), which is excreted through the stool. Gallbladder Function The gallbladder,
bile ducts, and the sphincter of Oddi act together to store and regulate the flow of bile. The main function
of the gallbladder is to concentrate and store hepatic bile in order to deliver it in a coordinated fashion to
the duodenum in response to a meal. Absorption and Secretion. In the fasting state, approximately 80%
of the bile secreted by the liver is stored in the gallbladder. This storage is made possible by the fact that
the gallbladder mucosa has the greatest absorptive power per unit area of any structure in the body. It
rapidly absorbs sodium, chloride, and water against significant gradients, concentrating the bile as much
as 10-fold and leading to a marked change in bile composition. This rapid absorptive capacity is one of the
protective mechanisms that prevent a potentially dangerous rise in pressure within the biliary system as
bile is produced and stored. In addition, gradual relaxation of the gallbladder as well as routine emptying
of the gallbladder’s excess bile stores during the fasting period also play a role in maintaining a low resting
intraluminal pressure in the biliary tree. The mucosal cells of the gallbladder itself secrete at least two
important products into the gallbladder lumen: glycoproteins and hydrogen ions. The mucosal glands in
the infundibulum and the neck of the gallbladder secrete mucus glycoproteins that are believed to protect
the mucosa from the corrosive action of bile and to facilitate the passage of bile through the cystic duct.
This same mucus creates the colorless “white bile” seen in hydrops of the gallbladder as a result of cystic
duct obstruction blocking the entry of bile pigments into the gallbladder. The transport of hydrogen ions
by the gallbladder epithelium also plays an important role in decreasing the pH of stored bile. This
acidification helps prevent the precipitation of calcium salts, which can act as a nidus for stone formation.4
Motor Activity. Normal gallbladder filling is facilitated by tonic contraction of the sphincter of Oddi, which
creates a small but effective pressure gradient between the bile ducts and the gallbladder. In association
with phase II of the interdigestive migrating myenteric motor complex (MMC) in the gut, the gallbladder
repeatedly empties small volumes of bile into the duodenum. This process is mediated at least in part by
the hormone motilin. In response to a meal, the gallbladder delivers larger volumes to the intestine by a
combination of gallbladder contraction and synchronized sphincter of Oddi relaxation. One of the main
stimuli to this coordinated effort of gallbladder emptying is the hormone cholecystokinin (CCK). CCK is
released endogenously from the enteroendocrine cells in the duodenum in response to a meal.5 When
stimulated by eating, the gallbladder empties 50% to 70% of its contents within 30 to 40 minutes. Over
the following 60 to 90 minutes, the gallbladder gradually refills as CCK levels drop. Other minor hormonal
and neural pathways also are involved in the coordinated action of the gallbladder and the sphincter of
Oddi. Defects in the motor activity of the gallbladder that inhibit correct emptying are thought to play a
role in cholesterol nucleation and gallstone formation. Neurohormonal Regulation. Neurally mediated
6. reflexes are very important in maintaining the functions of the gallbladder, sphincter of Oddi, stomach,
and duodenum to coordinate the flow of bile into the intestines at the correct times. The vagus nerve
stimulates contraction of the gallbladder by parasympathetic innervation while splanchnic sympathetic
nerves from the celiac plexus are inhibitory to its motor activity. For this reason, parasympathomimetic
or cholinergic drugs, including nicotine and caffeine, contract the gallbladder. Conversely, anticholinergic
drugs such as atropine lead to gallbladder relaxation. Antral distention of the stomach causes both
gallbladder contraction and relaxation of the sphincter of Oddi. In addition to neural inputs, hormonal
receptors are located on the smooth muscles, vessels, nerves, and epithelium of the gallbladder and biliary
tree. CCK is a peptide that comes from the enteroendocrine cells of the duodenum and proximal jejunum.
CCK is released into the bloodstream in response to the presence of hydrochloric acid, fat, and amino
acids in the duodenum.6 CCK has a plasma half-life of 2 to 3 minutes and is metabolized by both the liver
and the kidneys. CCK acts directly on smooth muscle receptors of the gallbladder and stimulates
gallbladder contraction. It also relaxes the terminal bile duct, the sphincter of Oddi, and the duodenum to
allow forward bile flow. CCK stimulation of the gallbladder and biliary tree is also mediated by cholinergic
vagal neurons. For this reason, patients who have had a vagotomy may have a diminished response to
CCK stimulation, resulting in an increase in the size and volume of the gallbladder. Hormones such as
vasoactive intestinal polypeptide (VIP) and somatostatin are potent inhibitors of gallbladder contraction.
Patients treated with somatostatin analogues and those with somatostatinomas have a high incidence of
gallstones, presumably due to the inhibition of gallbladder contraction and emptying. Other hormones
such as substance P and enkephalin affect gallbladder motility, but their exact physiologic role is less
clear.5 Sphincter of Oddi The sphincter of Oddi regulates the flow of bile and pancreatic juice into the
duodenum, prevents the regurgitation of duodenal contents into the biliary tree, and diverts bile into 1
Brunicardi_Ch32_p1393-p1428.indd 1397 11/02/19 2:43 PM 1398 SPECIFIC CONSIDERATIONS PART II the
gallbladder. It is a complex structure that is functionally independent from the duodenal musculature and
creates a highpressure zone between the bile duct and the duodenum. The sphincter of Oddi spans
approximately 4 to 6 mm in length and has a basal resting pressure of about 13 mmHg above the duodenal
pressure. On manometry, the sphincter shows phasic contractions with a frequency of about four per
minute and amplitude of 12 to 140 mmHg. The spontaneous motility of the sphincter of Oddi is regulated
by the interstitial cells of Cajal through intrinsic and extrinsic inputs from hormones and neurons acting
on the smooth muscle cells.7 Relaxation occurs in response to raising levels of the gastrointestinal
hormones CCK, glucagon, and secretin. This leads to diminished amplitude of phasic contractions and
reduced basal pressure of the sphincter, allowing increased flow of bile into the duodenum. During
fasting, the sphincter of Oddi activity is coordinated with the periodic partial gallbladder emptying that
occurs during phase II of the migrating myoelectric motor complexes.8 Pharmacologic administration of
certain gastrointestinal hormones, such as glucagon, can temporarily decrease sphincter of Oddi baseline
pressure and facilitate diagnostic studies.7 DIAGNOSTIC STUDIES A variety of diagnostic modalities are
available for the patient with suspected disease of the gallbladder or bile ducts. In 1924, the diagnosis of
gallstones was revolutionized by the introduction of oral cholecystography by Graham and Cole. For
decades, it was the mainstay of investigation for gallstones. It involved oral administration of a radiopaque
compound that is absorbed, excreted by the liver, and passed into the gallbladder. Stones are noted on a
film as filling defects in a visualized, pacified gallbladder. In the later half of the 20th century, biliary
imaging improved dramatically with the development of hepatobiliary scintigraphy (radionucleotide
scanning), as well as transhepatic and endoscopic retrograde cholangiography (ERCP), which allowed for
more detailed imaging of the biliary tree. Later, ultrasonography, computed tomography (CT), and
7. magnetic resonance imaging (MRI) would further improve the ability to image the biliary tract. Blood Tests
When patients with suspected diseases of the gallbladder or the extrahepatic biliary tree are evaluated, a
complete blood count and liver function tests are routinely requested. An elevated white blood cell (WBC)
count may indicate or raise suspicion of acute cholecystitis (infection within the gallbladder). If associated
with an elevation of bilirubin, alkaline phosphatase, and transaminases, cholangitis (infection within the
biliary tree) should be suspected. Cholestasis (an obstruction to bile flow) is generally characterized by an
elevation of conjugated bilirubin and a rise in alkaline phosphatase, but it may have no transaminitis. Such
a pattern may suggest choledocholithiasis (stones in the common bile duct) or an obstructing lesion such
as a stricture or cholangiocarcinoma. In patients with simple symptomatic cholelithiasis, biliary colic, or
chronic cholecystitis (a chronic inflammatory state of the gallbladder without infection), blood tests will
often be normal. Transabdominal Ultrasonography Transabdominal ultrasound is the initial investigation
of any patient suspected to have disease of the biliary tree.9 It is noninvasive, painless, does not submit
the patient to radiation, and can be performed on critically ill patients. Adjacent organs can also frequently
be examined at the same time. However, its reliability and interpretation are dependent upon the skills
and experience of the operator. In addition, obese patients, patients with ascites, and patients with
distended bowel may be difficult to examine with ultrasound as the quality of the images obtained in
these situations can be poor. Ultrasound will show stones in the gallbladder with sensitivity and specificity
of >90%, and can also reliably detect other pathologies of the biliary tree. Stones are acoustically dense
and reflect the ultrasound waves back to the ultrasonic transducer. Because stones block the passage of
sound waves to the region behind them, they also produce an acoustic shadow (Fig. 32-6). Stones move
with changes in position. Polyps, on the other hand, may be calcified and reflect shadows, but they do not
move with change in posture. Some stones form a layer in the gallbladder; others a form sediment or
sludge. A thickened gallbladder wall, pericholecystic fluid, and local tenderness with direct pressure by
the ultrasound probe over the fundus of the gallbladder (sonographic Murphy’s sign) may indicate acute
cholecystitis. When a stone obstructs the neck of the gallbladder, the gallbladder may become very large,
but thin walled. A contracted, thick-walled gallbladder can be indicative of chronic cholecystitis. The
extrahepatic bile ducts are also well visualized by transabdominal ultrasound, with the exception of the
retroduodenal portion. Dilation of the biliary tree in a patient with jaundice suggests an extrahepatic
obstruction as the cause for the jaundice. Frequently, the site and, sometimes, the cause of the
obstruction can be determined by ultrasound. Small stones in the common bile duct frequently get lodged
at the distal end of it, behind the duodenum, and are, therefore, difficult to detect. A dilated common bile
duct on ultrasound, small stones in the gallbladder, and a classic clinical presentation allows one to
assume that a stone or stones are causing the obstruction. Periampullary tumors can be difficult to
diagnose on ultrasound, but above the retroduodenal portion, the level of obstruction and the cause may
be visualized quite well. Ultrasound can also be helpful in evaluating tumor invasion and flow in the portal
vein, an important guideline for resectability of periampullary tumors.10 Computed Tomography
Abdominal CT scans are frequently used in the workup of undifferentiated abdominal pain and thus often
diagnose gallbladder Figure 32-6. An ultrasonography of the gallbladder. White arrows indicate stones
within the gallbladder; black arrowheads show acoustic shadows from stones. Brunicardi_Ch32_p1393-
p1428.indd 1398 11/02/19 2:43 PM 1399 GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM
CHAPTER 32 disease. CT scanning is inferior to ultrasonography in diagnosing gallstones but is similar in
sensitivity for acute cholecystitis. The major application of CT scan, however, is to define the course and
status of the extrahepatic biliary tree and adjacent structures, and to evaluate for alternate causes of a
patients clinical presentation.11 CT is also the initial test of choice in evaluating patients with suspected
8. malignancy of the gallbladder, the extrahepatic biliary system, or nearby organs such as the head of the
pancreas. Use of CT scan is an integral part of the differential diagnosis of obstructive jaundice of unknown
origin (Fig. 32-7). Hepatobiliary Scintigraphy Hepatobiliary scintigraphy, or hepatobiliary iminodiacetic
acid (HIDA) scanning, is another option for noninvasive evaluation of the liver, gallbladder, bile ducts, and
duodenum that provides both anatomic and functional information. 99mTechnetium-labeled derivatives
of iminodiacetic acid are injected intravenously, taken up by the Kupffer cells in the liver, and excreted in
the bile. Uptake by the liver is usually detected within 10 minutes, and the gallbladder, bile ducts, and
duodenum are typically visualized within 60 minutes in fasting subjects. The primary use of biliary
scintigraphy is in the diagnosis of acute cholecystitis, which appears as a nonvisualized gallbladder, with
prompt filling of the common bile duct and duodenum. The lack of gallbladder filling is due to
inflammatory closure of the cystic duct preventing bile backflow into the gallbladder (Fig. 32-8). Evidence
of cystic duct obstruction on biliary scintigraphy is highly diagnostic for acute cholecystitis. The sensitivity
and specificity for the diagnosis are about 95% each. False-positive results can occur in patients in the
nonfasting state, those receiving parenteral nutrition, or in the setting of gallbladder stasis, recent
narcotic use, or alcoholism. Filling of the gallbladder and common bile duct with delayed or absent filling
of the duodenum indicates an obstruction at the ampulla. Biliary leaks as a complication of surgery of the
gallbladder or the biliary tree can be confirmed and frequently localized by biliary scintigraphy.12 HIDA
scanning with evaluation of the gallbladder ejection fraction with or without CCK provocation may also be
helpful in diagnosing chronic biliary dyskinesia in patients with atypical symptoms. While an ejection
fraction of 90%. Notable complications of diagnostic ERCP include pancreatitis, which occurs in
approximately 3.5% of patients, as well as rare occurrences of bleeding, perforation, or infection
(cholangitis).16,17 Endoscopic Choledochoscopy The development of small fiber-optic cameras that can
be threaded through endoscopes used for endoscopic retrograde cholangiopancreatography (ERCP) has
facilitated the development of intraductal endoscopy. By providing direct visualization of the biliary and
pancreatic ducts, this technology has been shown to increase the effectiveness of ERCP in the diagnosis
of certain biliary diseases.18 Intraductal endoscopy has been shown to have therapeutic applications that
include biliary stone lithotripsy and directed stone extraction in high-risk surgical patients.19 It can also
allow for direct visualization and sampling of concerning lesions in order to evaluate for malignancy (Fig.
32-11). Studies have thus far shown intraductal endoscopy to be safe and effective, though complications
such as bile duct perforation, minor bleeding, and cholangitis have Figure 32-9. Magnetic resonance
cholangiopancreatography. This view shows the course of the extrahepatic bile ducts (arrow) and the
pancreatic duct (arrowheads). A B Figure 32-10. Endoscopic retrograde cholangiography. A. A schematic
picture showing the side-viewing endoscope in the duodenum and a catheter in the common bile duct. B.
An endoscopic cholangiogram showing stones in the common bile duct. The catheter has been placed
through the ampulla of Vater into the distal common bile duct (arrow). Note the duodenal shadow
indicated with arrowheads. Brunicardi_Ch32_p1393-p1428.indd 1400 11/02/19 2:43 PM 1401
GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 been described.20 Further
refinement of this technology will likely enhance ERCP as a diagnostic and therapeutic tool. Endoscopic
Ultrasound Endoscopic ultrasound (EUS) has improved significantly in recent years and offers additional
diagnostic utility to the workup of biliary disease. It requires a specialized 30° endoscope with either a
radial or linear ultrasound transducer at its tip. The results are operator dependent and require a skilled
endoscopist but offer noninvasive imaging of the bile ducts and adjacent structures. Endoscopic
ultrasound can also be used to identify choledocholithiasis. It is useful for evaluation of the retroduodenal
potion of the bile duct, which is difficult to visualize with transabdominal ultrasonography. Although EUS
9. is less sensitive than ERCP for biliary stones, the technique is less invasive as it does not require
cannulation of the sphincter of Oddi. EUS is also of particular value in the evaluation of tumors near or
behind the duodenum and their resectability. Using a linear EUS scope that has a biopsy channel, fine-
needle aspiration (FNA) of tumors or lymph nodes, therapeutic injections, or drainage procedures under
direct ultrasonic guidance can be performed.21 Percutaneous Transhepatic Cholangiography In settings
in which the biliary tree cannot be accessed endoscopically, antegrade cholangiography can be performed
by accessing the intrahepatic bile ducts percutaneously with a small needle under fluoroscopic guidance.
Once the position in a bile duct has been confirmed, a guidewire is inserted and a catheter is passed over
the wire (Fig. 32-12). Through the catheter, an antegrade cholangiogram can be obtained and therapeutic
interventions such as tissue sampling, biliary drain insertions, or stent placements performed.
Percutaneous transhepatic cholangiography (PTC) can also be performed through previously placed
percutaneous biliary drainage tubes, if present. PTC has little role in the management of patients with
uncomplicated gallstone disease but can be useful in patients with bile duct strictures or tumors, as it can
define the anatomy of the biliary tree proximal to the affected segment. As with any invasive procedure,
there are potential risks. For PTC, these are mainly bleeding, cholangitis, bile leak, and other catheter-
related problems.12 GALLSTONE DISEASE Prevalence and Incidence Gallstone disease (cholelithiasis) is
one of the most common afflictions of the digestive tract. Autopsy reports show that gallstones are
present in between 10% and 15% of adults.22 The prevalence of gallstones is related to many factors,
including diet, age, gender, BMI, and ethnic background with increased prevalence in patients of Native
American and Latin American descent. Certain conditions also predispose to the development of
gallstones including pregnancy, non-HDL hyperlipidemia, Crohn’s disease, and certain blood disorders
such as hereditary spherocytosis, sickle cell disease, and thalassemia. Surgeries that alter the normal
neural or hormonal regulation of the biliary tree including terminal ileal resection and gastric or duodenal
surgery increase the risk of cholelithiasis. Rapid weight loss following bariatric surgery or lifestyle changes
can also precipitate gallstone formation by creating an imbalance in bile composition. Medications such
as somatostatin analogues and estrogen-containing oral contraceptives are also associated with an
increased risk of developing gallstones.22 Women are three times more likely to develop gallstones than
men, and first-degree relatives of patients with gallstones have a twofold greater prevalence, possibly
indicating a genetic predisposition.23 Natural History Despite the high prevalence of cholelithiasis, most
patients will remain asymptomatic from their gallstones throughout life. For unknown reasons, some
patients progress to a symptomatic stage, with typical symptoms of postprandial right upper quadrant
pain (biliary colic) caused by a stone obstructing the cystic duct. In addition to pain, gallstones may
progress to cause complications such as acute cholecystitis, choledocholithiasis, cholangitis, gallstone
pancreatitis, gallstone ileus, and gallbladder cancer. Rarely, one of these complications of gallstones may
be the initial presenting picture. Gallstones in patients without biliary symptoms are commonly diagnosed
incidentally during unrelated abdominal imaging or at the time of surgery for an unrelated diagnosis.
Several studies have examined the likelihood of developing biliary colic or developing significant
complications of gallstone disease after incidental diagnosis in the asymptomatic patient. About 80% of
these patients will remain symptom free.24 However, 2% to 3% will become symptomatic per year (i.e.,
develop biliary colic). Once symptomatic, patients tend to have recurring bouts of biliary colic.
Complicated gallstone disease (cholecystitis, choledocholithiasis, gallstone pancreatitis, etc.) develops in
3% to 5% of symptomatic patients per year.25 Because few patients develop complications without
previous biliary symptoms, prophylactic cholecystectomy in asymptomatic persons with gallstones is
rarely indicated.24 Exceptions exist for individuals who will be isolated from medical care for extended
10. periods of time, or in populations with increased risk of gallbladder cancer, in which case a prophylactic
cholecystectomy may be advisable. The presence of porcelain gallbladder, marked by significant
calcifications thought to be related to Figure 32-11. A view from the choledochoscope showing
cholangiocarcinoma. Brunicardi_Ch32_p1393-p1428.indd 1401 11/02/19 2:43 PM 1402 SPECIFIC
CONSIDERATIONS PART II gallstones, is a rare premalignant condition and is an absolute indication for
cholecystectomy, even when asymptomatic. Gallstone Formation 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.22 Brown
pigment stones account for only a small percentage. Both types of pigment stones are more common in
Asia. Cholesterol Stones. Pure cholesterol stones are uncommon and account for 90%) are radiolucent,
though some have a high calcium carbonate component and become radioopaque. The primary event in
the formation of cholesterol stones is supersaturation of bile with cholesterol. Cholesterol is highly
nonpolar and its solubility in water and bile depends on the relative concentration of cholesterol, bile
salts, and lecithin (the main phospholipid in bile). Cholesterol is secreted into bile and is surrounded by
bile salts and phospholipids to form a soluble vesicle complex. When cholesterol hypersecretion is
present, either through increased intake or dysfunctional processing, supersaturation occurs. When
cholesterol concentrations exceed the ability of the bile salts and phospholipid to maintain solubility, the
cholesterol precipitates out of solution into a solid, forming a cholesterol stone (Fig. 32-14).26 Cholesterol
hypersecretion is almost always the cause of supersaturation rather than reduced secretion of
phospholipid or bile salts.2 Pigmented Stones. Pigmented stones contain 24 hours without resolving, 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.
Bile will be unable to enter the gallbladder due to the obstructed cystic duct, but the gallbladder
epithelium will continue to secrete mucus, and the gallbladder will become distended with clear-white
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.
Diagnosis The diagnosis of symptomatic cholelithiasis or chronic 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 as it is noninvasive and highly sensitive (see earlier
“Ultrasonography” section).28 Gallstones are occasionally identified on abdominal CT scans that were
obtained as part of a broader workup of abdominal pain. In these cases, if the patient has typical
symptoms, it is reasonable to proceed with intervention. Stones diagnosed incidentally on CT or plain
radiographs in patients without symptoms should be left in place. Occasionally, patients with typical
attacks of biliary pain have no evidence of stones on ultrasound but have evidence of sludge in the
gallbladder. If a patient has attacks of typical biliary pain and sludge is detected, 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 ultrasound or CT. Cholesterolosis is caused by the
accumulation of cholesterol in macrophages in the 2 2 15 14 7 64 50 13 5 244 4 1 2 9 6 1 4 3 9 6 3 2 2 15
19 11 2 5 2 3 11 35 33 2 3 A B Figure 32-15. A. Sites of the most severe pain during an episode of biliary
colic 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
11. not an unusual site of pain. B. Sites of pain radiation (%) during an episode of biliary colic in the same
group of patients. Brunicardi_Ch32_p1393-p1428.indd 1404 11/02/19 2:43 PM 1405 GALLBLADDER AND
THE EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 gallbladder lamina propria, either locally or as polyps. It
produces the classic studded macroscopic appearance of a “strawberry gallbladder.” Adenomyomatosis
(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. Septae
or strictures may be seen within the gallbladder. In symptomatic patients, cholecystectomy is the
treatment of choice for patients with these conditions.29 Treatment Nonsurgical management of
gallstone disease using medications or lithotripsy has had disappointing longterm results. These
modalities are not considered to be part of the primary treatment algorithm for gallstone disease.30
Surgical cholecystectomy offers the best long-term results for patients with symptomatic gallstones.
About 90% of patients with typical biliary symptoms and stones are rendered symptom free after
cholecystectomy. For patients with atypical symptoms such as dyspepsia, flatulence, belching, bloating,
and dietary fat intolerance, the results are not as favorable. The laparoscopic approach has been proven
to be safe and effective and has become the standard of care for symptomatic gallstone disease, replacing
open cholecystectomy in routine cases.29,31 3 Due to the possibility of developing complications related
to gallstone disease, patients with symptomatic cholelithiasis should be offered elective 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 be encouraged to have a
cholecystectomy promptly, as they are more prone to developing severe acute cholecystitis. Pregnant
women with symptomatic gallstones who cannot be managed expectantly with diet modifications can
safely undergo laparoscopic cholecystectomy. The operation should be performed during the second
trimester if possible. Acute Cholecystitis. Acute cholecystitis, or infection of the gallbladder, is associated
with gallstones in 90% to 95% of cases. Rarely, acalculous cholecystitis can occur, usually in patients with
other acute systemic diseases (see later “Acalculous Cholecystitis” section). Obstruction of the cystic duct
by a gallstone is the initiating event that leads to gallbladder distention, inflammation, and edema of the
gallbladder wall. In 20,000 cells/mm3 ) suggests a complicated form of cholecystitis such as gangrenous
cholecystitis, perforation, or associated cholangitis. In uncomplicated acute cholecystitis, serum liver
chemistries are usually normal, but a mild elevation of serum bilirubin (8 mm in diameter) on
ultrasonography in a patient with gallstones, jaundice, and biliary pain is highly suggestive of common bile
duct stones. If the presence of bile duct stones is in question, magnetic resonance
cholangiopancreatography (MRCP) provides excellent anatomic detail and has a sensitivity and specificity
of 95% and 89%, respectively, for detecting choledocholithiasis.14 Endoscopic retrograde
cholangiopancreatography (ERCP) is highly effective at diagnosing choledocholithiasis and in experienced
hands, cannulation of the ampulla of Vater and diagnostic cholangiography are achieved in >90% of cases.
However, due to the risks associated with the procedure, it is rarely used as a purely diagnostic modality,
rather being reserved for cases in which a therapeutic intervention such as stone extraction or
sphincterotomy is planned. Endoscopic ultrasound has been demonstrated to be as good as ERCP for
detecting common bile duct stones (sensitivity of 95% and specificity of 97%). However, EUS has fewer
therapeutic capabilities and requires endoscopic expertise, making it less desirable except in specific
clinical senarios.39 Percutaneous transhepatic cholangiography (PTC) is rarely needed in patients with
common bile duct stones but can be performed for both diagnostic and therapeutic reasons in patients
with contraindications to endoscopic or surgical approaches. Treatment For patients with symptomatic
12. gallstones and suspected common bile duct stones, bile duct clearance and cholecystectomy are
indicated. This may be safely achieved either with preoperative ERCP followed by surgery or by going
directly to surgery with intraoperative cholangiogram and common bile duct exploration to address
retained stones. Both approaches are considered safe and effective, and no formal recommendation
exists to definitively support one over the other.40,41 If upfront laparoscopic cholecystectomy is pursued,
the surgery should include an intraoperative cholangiogram to document the presence or absence of bile
duct stones. If stones are identified, 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 instrumentation for laparoscopic common bile duct
exploration are not available, the patient can be awoken and scheduled for ERCP with sphincterotomy the
following day. An open common bile duct exploration is an option if the endoscopic and laparoscopic
methods are not feasible. If a choledochotomy is performed, primary repair can be considered in large
ducts, while smaller ducts should be repaired over a T-tube. To do this, a standard T-tube should be
modified by cutting the ends short enough to allow placement within the duct and dividing the T
longitudinally to facilitate easy removal from the duct later on (Fig. 32-18). If a common Figure 32-18. T-
tube placement. A. A standard T-tube that has been cut and modified for use in the biliary tract. B. The T-
tube is placed through a ductotomy in the common bile duct with the defect closed over the tube. The
opposite end is brought out through the abdominal wall for decompression of the A B bile ducts.
Brunicardi_Ch32_p1393-p1428.indd 1407 11/02/19 2:43 PM 1408 SPECIFIC CONSIDERATIONS PART II bile
duct exploration was performed and a T tube left in place, a T-tube cholangiogram should be obtained
before its removal, at least several weeks after its placement. In very severe cases, stones impacted in the
ampulla may be unable to be cleared by endoscopic approaches or common bile duct exploration (open
or laparoscopic). In these cases, transduodenal sphincterotomy can be considered. If one is entirely unable
to disimpact the duct, choledochoduodenostomy or Roux-en-Y choledochojejunostomy may be the only
option to restore biliary continuity.42 If the stones were 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 (Fig. 32-19). Retained or recurrent stones following cholecystectomy are best
treated endoscopically. A generous sphincterotomy will allow for stone retrieval as well as spontaneous
passage of stones. Alternately, retained stones can be cleared via a mature T-tube tract (4 weeks) if one
was placed at the time of surgery. To do this, the T-tube is removed and a catheter passed through the
tract into the common bile duct. Under fluoroscopic guidance, the stones can be retrieved with baskets
or balloons. A similar approach will allow for stone clearance by percutaneous transhepatic
cholecystostomy (PTC) if there is no other way to reach the duct. Repeat surgery should be a last resort if
other interventions have failed. Cholangitis. Cholangitis is one of the main complications of choledochal
stones. Acute cholangitis is an ascending bacterial infection associated with partial or complete
obstruction of the bile ducts.43 Hepatic bile is sterile, and bile in the bile ducts is kept sterile by continuous
antegrade bile flow and by the presence of antibacterial substances in bile, such as immunoglobulin.
Mechanical hindrance to bile flow facilitates ascending bacterial contamination from the bowel. 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 include primary sclerosing cholangitis,
benign and malignant strictures, parasites, instrumentation of the ducts, and indwelling stents, as well as
partially obstructed biliary-enteric anastomoses. The most common organisms cultured from bile in
13. patients with cholangitis include E coli, Klebsiella pneumoniae, Streptococcus faecalis, Enterobacter, and
Bacteroides fragilis. 43 Clinical Manifestations Cholangitis may present as anything from a mild, self-
limited episode to a fulminant, potentially life-threatening septicemia. Patients with gallstone-induced
cholangitis are most commonly older and female. The most common presentation is fever, epigastric or
right upper quadrant pain, and jaundice. These classic symptoms, known as Charcot’s triad, are present
in about two-thirds of patients. The illness can progress rapidly with the development of shock and altered
mental status, 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 the
process is already quite advanced. Patients with indwelling stents are at particularly high risk for
cholangitis, though rarely become jaundiced as a patent stent will prevent the obstruction of bile flow. On
abdominal examination, the findings are indistinguishable from those of acute cholecystitis.44 Diagnosis
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 a site of
obstruction. CT scanning and MRI can show pancreatic and periampullary masses, if present, in addition
to the ductal dilatation. However, abdominal imaging will rarely elucidate the exact cause of cholangitis,
and the initial diagnosis is generally made clinically. Treatment The initial treatment of patients with
cholangitis includes broad-spectrum IV antibiotics to cover enteric organisms and anaerobes, fluid
resuscitation, and rapid biliary A B Figure 32-19. 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. Brunicardi_Ch32_p1393-p1428.indd 1408 11/02/19
2:43 PM 1409 GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 decompression. This
is most often accomplished through ERCP and sphincterotomy. ERCP will show the level and the reason
for the obstruction, allow for culture of the bile, permit the removal of stones if present, and accomplish
drainage of the bile ducts. Placement of drainage catheters or stents can also be performed if needed. In
cases in which ERCP is not available, PTC, EUS, or surgical drainage can be utilized. The selection of the
appropriate approach will depend on the type and location of the suspected obstruction as well as the
availability of local resources and expertise. Cholecystostomy tubes are not indicated in the acute
management of cholangitis as the primary source of the infection is extrinsic to the gallbladder. Patients
with cholangitis can deteriorate rapidly and may require intensive care unit monitoring and vasopressor
support. However, most patients will respond to biliary decompression and supportive measures. In the
current era, 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. Patients who have suffered an episode of acute cholangitis related to
gallstone disease should be recommended to undergo elective cholecystectomy approximately 6 weeks
after the resolution of their cholangitis.45 Those whose cholangitis was related to another cause of biliary
obstruction should be followed and treated for the specific etiology of their obstruction but do not
necessarily require cholecystectomy if gallstones were not the causative etiology of their cholangitis.
Patients with indwelling stents and cholangitis usually require repeated imaging and stent exchange to
mitigate the risk of recurrent infections. Gallstone Pancreatitis. Gallstones in the common bile duct can
14. provoke attacks of acute pancreatitis through transient or persistent obstruction of the pancreatic duct
by a stone passing through or impacted in the ampulla. The exact mechanism by which obstruction of the
pancreatic duct leads to pancreatitis is unclear, but it may be related to increased ductal pressures causing
leakage of pancreatic enzymes into the glandular tissue. The initial management of gallstone pancreatitis
is supportive, including admission for bowel rest, IV hydration, and pain control. Antibiotics are not
indicated in the absence of signs of infected pancreatic necrosis. Imaging of the biliary tree with
ultrasound, CT, or MRCP is essential to confirm the diagnosis. When gallstones are present and the
pancreatitis is mild and self-limited, the stone has probably passed. For these patients, a cholecystectomy
with intraoperative cholangiogram is indicated as soon as the pancreatitis has clinically resolved. It is
strongly recommended that cholecystectomy be performed during the same admission whenever
possible due to the high rate of recurrence and increased morbidity of subsequent attacks of
pancreatitis.46 If gallstones are present obstructing the duct and the pancreatitis is severe, an ERCP with
sphincterotomy and stone extraction may be necessary. This must be balanced with the risk of ERCP-
induced pancreatitis and thus is usually only employed if supportive measures are failing. Gallstone Ileus.
Gallstone ileus can occur when a large gallstone erodes through the wall of the gallbladder directly into
the intestine via a choledochoenteric fistula (Fig. 32-20A). These stones can then pass through the
intestinal tract until they reach an area of fixed obstruction. Proximal stones can become impacted in the
pylorus or proximal duodenum causing gastric outlet obstruction (Bouveret syndrome). Those that travel
distally may become lodged at surgical anastomoses or the ileocecal valve, where they can become
impacted and cause small bowel obstruction. Gallstone ileus is responsible for less than 1% of all intestinal
obstructions.47 These patients present with symptoms of obstipation, nausea, and abdominal pain. Plain
films may show an obstructive bowel gas pattern but may fail to identify a radiolucent stone. Ultrasound
evaluation may be limited by extensive bowel gas. CT is highly sensitive and specific for gallstone ileus and
will help to determine the location of the obstruction. Management of gallstone ileus focuses on relieving
the intestinal obstruction and removing the stone. In cases of very proximal obstructions in the stomach
or duodenum, endoscopic retrieval can be effective. For more distal stones, surgical enterolithotomy can
be accomplished either laparoscopically or open. This procedure entails the removal of the stone through
A B Figure 32-20. Gallstone Ileus. A. A choledochoenteric fistula has formed between the gallbladder and
the duodenum, allowing a gallstone to pass into the intestinal tract. B. Intraoperative photo showing a
longitudinal enterotomy and extraction of an impacted stone from the distal small bowel.
Brunicardi_Ch32_p1393-p1428.indd 1409 11/02/19 2:43 PM 1410 SPECIFIC CONSIDERATIONS PART II an
enterotomy that is then either repaired or resected depending on its size (Fig. 32-20B). Stones that have
successfully traversed the ileocecal valve are likely to pass without further intervention. The role of
pursuing cholecystectomy and/or choledochoenteric fistula closure at the time of enterolithotomy or
addressing it at a later time remains a topic of debate, but it should be considered to reduce the risk of
recurrence.47 Cholangiohepatitis Cholangiohepatitis, also known as recurrent pyogenic cholangitis, is
endemic to the Orient. It also has been encountered in Asian population in the United States, 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 it is associated with biliary parasites such
as Clonorchis sinensis, Opisthorchis viverrini, and A 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 which may contain an adult Clonorchis worm, an ovum, or an ascarid.
These stones can form throughout the biliary tree and cause partial obstructions that contribute to
15. repeated bouts of cholangitis, biliary strictures, further stone formation, infection, hepatic abscesses, or
liver failure (secondary biliary cirrhosis).48 Patients with cholangiohepatitis usually present with pain in
the right upper quadrant or epigastrium, fever, and jaundice. Relapsing symptoms are 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 may detect stones in the biliary
tree, pneumobilia from infection by gas-forming organisms, liver abscesses, and, occasionally, strictures.
The gallbladder may be thickened and inflamed in about 20% of patients but rarely contains gallstones.
ERCP or MRCP can be utilized for biliary imaging for cholangiohepatitis. They can detect obstructions and
define strictures and stones. ERCP (or PTC if necessary) has the additional benefit of allowing for 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 in severe, refractory cases in which stones and strictures cannot be relieved, it may
require a hepaticojejunostomy to reestablish 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.49 PROCEDURAL INTERVENTIONS FOR
GALLSTONE DISEASE Percutaneous Transhepatic Cholecystostomy Tubes In cases in which a patient with
cholecystitis is deemed to be too ill to safely undergo cholecystectomy, a cholecystostomy tube may be
placed into the gallbladder to decompress and drain a distended, inflamed, hydropic, or purulent
gallbladder.36 Surgical cholecystostomy with a large catheter placed under local anesthesia is rarely
required today. Rather, percutaneous transhepatic cholecystostomy (PTC) tubes are most often pigtail
catheters inserted percutaneously under ultrasound guidance.50 The catheter is inserted over a guidewire
that has been passed through the abdominal wall, the liver, and into the gallbladder (Fig. 32-21). By
passing the catheter through the liver, the risk of uncontrolled bile leak around the catheter and into the
peritoneal cavity is minimized. The catheter can be removed when the inflammation has resolved and the
patient’s condition has improved. A patent cystic duct should be confirmed by a tube cholangiogram prior
to its removal. Interval cholecystectomy should be considered if the patient’s fitness has improved,
particularly in individuals whose etiology of cholecystitis was gallstones. Endoscopic Interventions
Endoscopic advances in the last few decades have made endoscopy and ERCP a valuable therapeutic tool
in the management of gallstone disease, particularly in the setting of common bile duct stones or
abnormalities. Using a 90-degree side-viewing endoscope, the duodenum can be entered and the ampulla
of Vater on the medial wall of the second portion of the duodenum visualized. This can then be cannulated
to allow wire and catheter access to the biliary tree, facilitating retrograde cholangiogram, diagnostic
brushings, stenting, dilations, or fluoroscopically guided basket or balloon retrieval of common bile duct
stones. When CBD stones are present, endoscopic sphincterotomy should be performed, which will allow
for passage of larger stones both at the time of bile duct clearance and in the case of any ongoing
choledocholithiasis (Fig. 32-22). In the hands of experts, ERCP has high rates of successful cannulation and
bile duct clearance, and it is a safe and tolerable procedure. Debate remains when comparing ERCP to
surgical common bile duct exploration in terms of timing and outcomes for choledocholithiasis, but both
are considered acceptable treatments.41 In special cases, such as the presence of Roux-en-Y anatomy or
a previous hepaticojejunostomy, ERCP can be difficult. However, such anatomy does not preclude the
option for endoscopic intervention. Laparoscopic-assisted ERCP (in which the remnant stomach is
accessed surgically and the endoscope passed into the duodenum) or double-balloon ERCP can be utilized
to reach the biliary tree. Cholecystectomy Cholecystectomy is one of the most common abdominal
surgeries performed in Western countries, with over 750,000 Figure 32-21. Percutaneous
16. cholecystostomy. A pigtail catheter has been placed through the abdominal wall, the right lobe of the
liver, and into the gallbladder. Brunicardi_Ch32_p1393-p1428.indd 1410 11/02/19 2:43 PM 1411
GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 being performed each year in the
United States alone.51 Carl Langenbuch performed the first successful open cholecystectomy in 1882, and
for >100 years, it was the standard treatment for symptomatic gallbladder stones. In 1987, laparoscopic
cholecystectomy was introduced by Philippe Mouret in France and quickly revolutionized the treatment
of gallstone disease. It not only supplanted open cholecystectomy, but it also more or less ended attempts
for noninvasive management of gallstones (such as extracorporeal shock wave or cholangioscopic
lithotripsy) or medical therapies (such as bile salts). Laparoscopic cholecystectomy offers a cure for
gallstones with a minimally invasive procedure, minor pain and scarring, and early return to full activity.
Today, laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones and the
complications of gallstone disease. Few absolute contraindications exist to laparoscopic cholecystectomy,
but they include hemodynamic instability, uncontrolled coagulopathy, or frank peritonitis. In addition,
patients with severe obstructive pulmonary disease (COPD) or congestive heart failure (e.g., cardiac
ejection fraction 1.5 cm). This may allow free reflux of pancreatic secretions into the biliary tract, leading
to inflammatory changes, increased biliary pressure, and cyst formation. The cysts are lined with cuboidal
epithelium and can vary in size from small dilations to giant cystic masses. The typical clinical triad of
biliary cysts includes abdominal pain, jaundice, and a palpable mass, though this constellation is seen in
less than one-half of patients. Adults may present with cholangitis. Blood tests will often be normal though
elevations of transaminases can be seen in cases of infection or obstruction. Ultrasonography or CT
scanning will confirm the diagnosis, but ERCP or MRCP are essential to formally assess the biliary anatomy
and to plan the appropriate surgical treatment. The risk of cholangiocarcinoma in patients with
choledochal cysts is 20- to 30-fold higher than in the general population and varies with the patient’s age
and type of cyst. For this reason, excision is recommended whenever possible when high-risk choledochal
cysts are diagnosed. Choledochal cysts are classified into five types depending on the location and
structure of the cysts. The subcategories of choledochal cysts are defined in Fig. 32-27. Type I cysts
(fusiform CBD dilations) are the most common form, accounting for approximately 50% of cases, and have
the highest risk of malignancy (>60%). For types I and II (saccular diverticula of the common bile duct),
excision of the cystic dilations in the extrahepatic biliary tree, including cholecystectomy, with either
simple cyst excision or duct resection with Roux-en-Y hepaticojejunostomy is ideal. Type III cysts
(intraduodenal) create a treatment challenge as full resection would require pancreaticoduodenectomy.
Given that type III cyst are associated with the lowest malignancy risk of any choledochal cyst (~2%),
sphincterotomy and surveillance is generally recommended over formal excision.66 In Type IV (multiple
cysts), excision of all cystic tissue and reconstruction is again recommended. For type IVa, which is
characterized by multiple cysts with intrahepatic involvement, additional segmental resection of the liver
may be required if intrahepatic stones, strictures, or abscesses are present. Type V choledochal cysts
(Caroli disease) are very rare and account for less than 1% of patients with choledochal cysts. These cysts
are multiple and can affect the entire liver. In advanced stages, this may result in cirrhosis and liver failure
necessitating liver transplantation. Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is
an uncommon disease characterized by inflammatory strictures involving the intrahepatic and
extrahepatic biliary tree. It is a progressive disease that eventually results in secondary biliary cirrhosis.
Sometimes, biliary strictures are clearly secondary to bile duct stones, acute cholangitis, previous biliary
surgery, or toxic agents, and are termed secondary sclerosing cholangitis. However, primary sclerosing
cholangitis is a disease entity of its own, with no clear attributing cause. Autoimmune reaction, chronic
17. low-grade bacterial or viral infection, toxic reaction, and genetic factors have all been suggested to play a
role in its pathogenesis. PSC is commonly associated with other autoimmune diseases including ulcerative
colitis in about two-thirds of patients, Riedel’s thyroiditis, and retroperitoneal fibrosis. The human
leukocyte antigen haplotypes HLA-B8, DR3, DQ2, and DRw52A, commonly found in patients with
autoimmune diseases, also are more frequently seen in patients with primary sclerosing cholangitis than
in controls. The mean age of presentation for PSC is 30 to 45 years, and men are affected twice as often
as women. Most patients are symptomatic when diagnosed, and may complain of intermittent jaundice,
fatigue, weight loss, pruritus, or abdominal pain. Initial presentation with acute cholangitis is rare without
preceding biliary tract intervention or surgery. A minority of patients are diagnosed incidentally by
elevated liver function tests, particular when found in a patient with ulcerative colitis. While the clinical
presentation and laboratory results may suggest the PSC, ERCP revealing multiple dilatations and
strictures (beading) of the intra- and extrahepatic biliary tree confirms the diagnosis. The hepatic duct
bifurcation is often the most severely affected segment. A liver biopsy may not be diagnostic, but it is
important to determine the degree of hepatic fibrosis and the presence of cirrhosis. The clinical course in
sclerosing cholangitis is highly variable, but cyclic remissions and exacerbations are typical. Some patients
will remain asymptomatic for years, while others progress rapidly with the obliterative inflammatory
changes leading to secondary biliary cirrhosis and liver failure. In patients with associated ulcerative
colitis, the course of each disease seems independent of the other and colectomy has no effect on the
Brunicardi_Ch32_p1393-p1428.indd 1417 11/02/19 2:43 PM 1418 SPECIFIC CONSIDERATIONS PART II
course of primary sclerosing cholangitis. Of the patients with sclerosing cholangitis, 10% to 15% will
develop cholangiocarcinoma, which can present at any time during the disease process and does not
necessarily correlate with the extent of the sclerosing cholangitis or the development of liver failure.67
Cholangiocarcinoma in the setting of PSC frequently follows an aggressive course. Patients need to be
followed by serial ERCP and liver biopsies to evaluate for the development of complications such as
strictures, cancers, or cirrhosis. There is no known curative treatment for primary sclerosing cholangitis
and medical management is largely supportive. Corticosteroids, immunosuppressants, ursodeoxycholic
acid, and antibiotics have been attempted with disappointing results. If biliary strictures occur, they can
be dilated and stented either endoscopically or percutaneously. These measures have given short-term
improvements in symptoms and serum bilirubin levels but provide long-term results in less than half of
patients. Surgical management with resection of the extrahepatic biliary tree and hepaticojejunostomy
has produced reasonable results in patients with extrahepatic and bifurcation strictures, but without
cirrhosis or significant hepatic fibrosis.68 In patients with primary sclerosing cholangitis and advanced
liver disease, liver transplantation is the only option. It offers excellent results, with overall 5-year survival
as high as 85%. Unfortunately, recurrence of PSC can occur in 10% to 20% of patients and may require
retransplantation.68 Bile Duct Strictures Benign bile duct strictures can have numerous causes. However,
the vast majority are related to operative injury, most commonly during cholecystectomy. Other causes
include fibrosis due to chronic pancreatitis, common bile duct stones, acute cholangitis, biliary obstruction
due to cholecystolithiasis (Mirizzi’s syndrome), sclerosing cholangitis, cholangiohepatitis, and strictures of
a biliary-enteric anastomosis. Bile duct strictures that go unrecognized or are improperly managed can
lead to severe complications such as recurrent cholangitis, secondary biliary cirrhosis, and portal
hypertension.69 Bile duct strictures most commonly result in recurrent episodes of cholangitis but may
present with isolated jaundice without infection. Liver function tests usually show evidence of cholestasis
with elevations of bilirubin and alkaline phosphatase. Imaging with ultrasound or CT can show dilated bile
ducts proximal to the stricture, as well as provide information about the level of the stenosis. MRCP gives
18. more detailed anatomic information about the location and the degree of dilatation. If the diagnosis
remains in question, cholangiography (endoscopic or more rarely percutaneous) will outline the biliary
tree, define the stricture and its location, and allow for therapeutic interventions (Fig. 32-28). The
treatment of biliary strictures depends on the location and the cause of the stricture. Percutaneous or
endoscopic dilatation and/or stent placement will provide good results in more than one half of Type I
Type II Type III Type IVa Type IVb Type V Figure 32-27. Classification of choledochal cysts. Type I, fusiform
or cystic dilations of the extrahepatic biliary tree, is the most common type, making up >50% of the
choledochal cysts. Type II, saccular diverticulum of an extrahepatic bile duct. Rare, 3 cm) are associated
with a 10-fold increased risk of cancer.81 The risk of developing cancer of the gallbladder is higher in
patients with symptomatic than asymptomatic gallstones, and it is more commonly seen in the setting of
cholesterol stones. Polypoid lesions of the gallbladder, which are present in as many as 5% of adults, are
also associated with increased risk of cancer. This is particularly true for polyps measuring >10 mm, which
carry a 25% risk of malignancy.82 Solitary or sessile polys, or those showing rapid growth on serial imaging,
particularly if in the presence of gallstones or age >50 are also concerning for malignancy. When such
findings are identified, the patient should have their gallbladder removed, even if they are asymptomatic.
Polyps that are not removed should be monitored on serial imaging. The finding of a “Porcelain”
gallbladder, or dense circumferential calcifications of the gallbladder wall, is associated with an
approximately 10% risk of gallbladder carcinoma. While this condition was previously considered to be an
absolute indication for cholecystectomy, more recent studies suggest that given the low rate of
malignancy, observation is safe and acceptable. Nevertheless, resection remains a reasonable option,
particularly if the patient is symptomatic, and the decision should ultimately be made only after discussing
risks and benefits of each approach with the patient.97 Patients with certain types of choledochal cysts
also have an increased risk of developing cancer anywhere in the biliary tree, but the incidence is highest
in the gallbladder and cholecystectomy should be performed with any surgical intervention on the
choledochal cyst. Primary sclerosing cholangitis, anomalous pancreaticobiliary duct junction, and
exposure to carcinogens (azotoluene, nitrosamines) also are associated with cancer of the gallbladder,
and screening with abdominal ultrasound should be considered in these patients. Pathology. Between
80% and 90% of gallbladder cancers are adenocarcinomas. Squamous cell, adenosquamous, oat cell, and
other anaplastic lesions rarely occur. The histologic subtypes of gallbladder adenocarcinomas include
papillary, nodular, and tubular. Less than 10% are of the papillary type, but these are associated with an
overall better outcome, as they are most commonly diagnosed while localized to the gallbladder. Cancer
of the gallbladder can spread through lymphatics, venous drainage, or by direct invasion into the liver
parenchyma. Lymphatic flow from the gallbladder drains first to the cystic duct node (Lund’s node or
Calot’s node), then pericholedochal and hilar nodes, and finally to the peripancreatic, duodenal,
periportal, celiac, and superior mesenteric artery nodes. The gallbladder veins drain directly into the
adjacent liver, usually segments IVb and V, where tumor invasion is common (Fig. 32-30). The gallbladder
wall differs histologically from the intestines in that it lacks a muscularis mucosa and submucosa.
Lymphatics are present in the subserosal layer only. Therefore, cancers that have not grown through the
muscular layer have minimal risk of nodal disease. Unfortunately, only a small portion of gallbladder
cancers (10–25%) are identified while they are still localized to the gallbladder. The majority will already
have nodal involvement, extension into adjacent liver, or distant metastasis at the time of diagnosis.80,83
Clinical Manifestations and Diagnosis. Signs and symptoms of carcinoma of the gallbladder are generally
indistinguishable from those associated with cholecystitis and cholelithiasis, and this can lead to delays in
treatment or misdiagnosis. These include abdominal discomfort, right upper quadrant pain, nausea, and
19. vomiting. Jaundice, weight loss, anorexia, ascites, 5 Brunicardi_Ch32_p1393-p1428.indd 1421 11/02/19
2:44 PM 1422 SPECIFIC CONSIDERATIONS PART II and abdominal masses are less common presenting
symptoms. Common misdiagnoses include chronic cholecystitis, acute cholecystitis, choledocholithiasis,
hydrops of the gallbladder, and pancreatic cancer. Laboratory findings, if abnormal, are most often
consistent with biliary obstruction. Ultrasonography often reveals a thickened, irregular gallbladder wall
(>3mm) with hypervascularity or a mass replacing the gallbladder. It may also visualize tumor invasion of
the liver, lymphadenopathy, or a dilated biliary tree. The sensitivity of ultrasonography in detecting
gallbladder cancer ranges from 70% to 100%. A CT scan may be helpful in identifying a gallbladder mass
and evaluating for nodal spread or local invasion into adjacent organs or vasculature. If questions about
local invasion remain, MRCP allows for complete assessment of biliary, vascular, nodal, hepatic, and
adjacent organ involvement.84 Endoscopic ultrasound (EUS) can be a useful tool in staging and evaluating
for local invasion, as well as obtaining tissue diagnosis through fine needle aspiration (FNA). Tissue
diagnosis can also be obtained by CT or ultrasound-guided biopsy of the tumor, though this is not required
prior to cholecystectomy if the tumor appears resectable on imaging. In jaundiced patients, a
percutaneous transhepatic or endoscopic cholangiogram may be helpful to delineate the extent of biliary
tree involvement. The role of PET scanning in gallbladder cancer is yet to be fully defined but can be
utilized in both staging and surveillance. Treatment. Surgical resection remains the only curative option
for gallbladder cancer. While most patients are unresectable at the time of diagnosis, if preoperative
staging suggests a potentially resectable tumor, exploration for tissue diagnosis, formal pathologic
staging, and possible curative resection are warranted. Tumors limited to the lamina propria or muscular
layer of the gallbladder (T1) are usually identified incidentally, after laparoscopic cholecystectomy for
gallstone disease. There is near universal agreement that simple laparoscopic cholecystectomy is an
adequate treatment for T1 lesions and results in a near 100% overall 5-year survival rate. When the tumor
invades the perimuscular connective tissue without extension beyond the serosa or into the liver (T2
tumors), an extended cholecystectomy should be performed.85 This includes additional resection of liver
segments IVb and V, as well as lymphadenectomy of the cystic duct and pericholedochal, portal, right
celiac, and posterior pancreatoduodenal lymph nodes. Given the extent of this operation, an open
approach is standard. One-half of patients with T2 tumors are found to have nodal disease on pathologic
examination, highlighting the importance of regional lymphadenectomy as part of surgery for T2
cancers.86 For tumors that grow beyond the serosa, or invade the liver or other adjacent organs (T3),
there is a higher likelihood of intraperitoneal or distant spread. However, if no peritoneal or nodal
involvement is found, complete tumor excision with an extended right hepatectomy and possible caudate
lobectomy with lymphadenectomy must be performed for adequate tumor clearance. In addition, if a T2
or T3 tumor is identified incidentally after laparoscopic cholecystectomy, and the patient is returning to
the OR for liver resection and lymphadenectomy, the previous laparoscopic port sites must also be excised
due to the high risk of recurrence in these locations. T4 tumors are those that have grown into major
blood vessels or two or more structures outside the liver, and they are typically considered unresectable.
Due to the high frequency of late diagnosis, palliative procedures for unresectable cancer, jaundice, or
duodenal obstructions remain the most frequently performed surgery for gallbladder cancers. Today,
patients with obstructive jaundice can frequently be managed with either endoscopic or percutaneously
placed biliary stents. Various regimens of neoadjuvant, adjuvant, and definitive chemoradiotherapy have
been trialed in gallbladder cancer. Overall, benefits have been marginal, but treatment may improve
survival time by several months. These therapies can be offered to patients in conjunction with resection
for curative intent or as definitive therapy, but no standard recommendation exists for their use.85-87
20. Prognosis. Most patients with gallbladder cancer have unresectable disease at the time of diagnosis. The
overall 5-year survival rate of all patients with gallbladder cancer is 70% compared to 25% to 40% for T2
patients treated with simple cholecystectomy. Patients with advanced (T3 or T4) but resectable
gallbladder cancer are reported to have 5-year survival rates of 20% to 50%, supporting aggressive
resection in those patients who can tolerate surgery. The median survival for patients with distant
metastasis at the time of presentation is only 1 to 3 months. Recurrence after resection of gallbladder
cancer occurs most commonly in the liver or in the celiac or retropancreatic nodes. The prognosis for
recurrent disease is very poor, and the main goal of follow-up is to provide palliative care. The most
common problems are pruritus and cholangitis associated with obstructive jaundice, bowel obstruction
secondary to carcinomatosis, and pain. Death occurs most commonly secondary to biliary sepsis or liver
failure.
Cholangiocarcinoma Cholangiocarcinoma is a rare tumor arising from the biliary epithelium and
may occur anywhere along the biliary tree. About half are located at the hepatic duct bifurcation (Klatskin
tumors), with 40% occurring more distally and 10% being intrahepatic.88 Surgical resection offers the only
chance for cure, but unfortunately many patients have advanced disease at the time of diagnosis.
Therefore, palliative procedures aimed to provide biliary drainage and prevent liver failure and cholangitis
are often the only therapeutic possibilities available. Incidence. The autopsy incidence of bile duct
carcinoma is about 0.3%. The overall incidence of cholangiocarcinoma in the United States is about 1 per
100,000 people per year, with approximately 2500 new cases diagnosed annually. The disease has a slight
male predominance and an average age of presentation between 50 and 70 years.88 Etiology. Most cases
of extrahepatic cholangiocarcinoma develop de novo with no identifiable risk factors. However, there is
an increased risk of cholangiocarcinoma in patients with choledochal cysts, ulcerative colitis,
hepatolithiasis, biliary-enteric anastomoses, hepatitis B and C, cirrhosis, biliary tract infections with
Clonorchis (liver flukes), and chronic typhoid carriers. Exposure to dietary nitrosamines, Thorotrast, or
dioxin also puts patients at increased risk for cholangiocarcinoma.88 Patients with primary sclerosing
cholangitis have a 5% to 10% lifetime risk of developing cholangiocarcinoma with typical disease onset in
their 40s. For this reason, these patients require regular screening.67 Features common to most risk
factors include biliary stasis, bile duct stones, and infection. Pathology. Over 95% of bile duct cancers are
ductal adenocarcinomas with the vast majority occurring in the extrahepatic biliary tree. Morphologically,
they are divided into nodular (the most common type), scirrhous, diffusely infiltrating, or papillary.
Anatomically, they are divided into distal, perihilar or intrahepatic tumors. Intrahepatic
cholangiocarcinomas make up approximately 10% of cases and are typically treated like hepatocellular
carcinoma, with hepatectomy when possible and transplant when unresectable. About half of all
cholangiocarcinomas are located in the perihilar region with the remaining 40% occurring more distally in
the common bile duct. Perihilar cholangiocarcinomas, also referred to as Klatskin tumors, are further
classified based on anatomic location by the Bismuth-Corlette classification (Fig. 32-31). Type I tumors are
confined to the common hepatic duct, but type II tumors involve the bifurcation without involvement of
the secondary intrahepatic ducts. Type IIIa and IIIb tumors extend into the right and left secondary
intrahepatic ducts, respectively. Type IV tumors involve both the right and left secondary intrahepatic
ducts. Clinical Manifestations and Diagnosis. Painless jaundice is the most common initial presentation in
patients with cholangiocarcinoma. Pruritus, mild right upper quadrant pain, anorexia, fatigue, and weight
loss may also be present. Cholangitis is the presenting symptom in about 10% of patients. Except for
jaundice, physical examination is usually normal in patients with cholangiocarcinoma. Occasionally,
asymptomatic patients are found to have cholangiocarcinoma while being evaluated for elevated liver
21. function tests. Tumor markers, such as CA 125 and carcinoembryonic antigen (CEA), can be elevated in
cholangiocarcinoma but tend to be nonspecific because they also increase in other GI and gynecologic
malignancies. The tumor marker most commonly used to aid the diagnosis of cholangiocarcinoma is CA
19-9, which has a sensitivity of 79% and specificity of 98% if the serum value is >129 U/mL.89 However,
mild elevations in CA 19-9 can also be seen in cholangitis, biliary obstruction, other GI and gynecologic
neoplasms, and patients who lack the Lewis blood type antigen.90 The initial workup for suspected
cholangiocarcinoma includes abdominal imaging with ultrasound or CT scanning. Perihilar tumors will
cause dilatation of the intrahepatic biliary tree, but a normal or collapsed gallbladder and extrahepatic
bile ducts distal to the tumor. Distal bile duct cancer will lead to dilatation of the extra- and intrahepatic
bile ducts as well as the gallbladder. Initial imaging is important to determine the level of obstruction and
to rule out the presence of bile duct stones as the cause of the obstructive jaundice (Fig. 32-32). It is
usually difficult to visualize the tumor itself on ultrasound, CT, or even MRCP, but any of these modalities
can provide an outline of biliary anatomy, an estimate of the level of obstruction, evaluation of portal vein
patency, and screening for nearby lymphadenopathy. Detailed evaluation of the biliary anatomy and
tumor itself is best completed through cholangiography. ERCP is generally adequate, but in cases where
the proximal extent of the tumor remains in question, PTC may be required to determine resectability.
Tissue diagnosis may be difficult to obtain. Current diagnostic techniques including fine-needle aspiration
(percutaneous or endoscopic), and biliary brushings have been shown to have a low sensitivity in detecting
malignancy, anywhere between 15% and 60%. Choledochoscopy with direct visualization and sampling of
intraluminal masses may be able to improve diagnosis rates but is only available in specialized centers
(see Fig. 32-10). Patients with potentially resectable disease should, therefore, be offered surgical
exploration based on radiographic findings and clinical suspicion.91 Type IIIb Type I Type II Type IIIa Type
IV Figure 32-31. Bismuth-Corlette classification of perihilar bile duct tumors (Klatskin tumors).
Brunicardi_Ch32_p1393-p1428.indd 1423 11/02/19 2:44 PM 1424 SPECIFIC CONSIDERATIONS PART II
Treatment. Surgical excision is the only potentially curative treatment for cholangiocarcinoma. In the past
one to two decades, improvements in surgical techniques have resulted in lower mortality and better
outcomes for patients undergoing aggressive surgical excision for cholangiocarcinoma.92 Despite
improvements in ultrasonography, CT scanning, and MRI, more than one-half of patients who are explored
are found to have peritoneal implants, nodal or hepatic metastasis, or locally advanced disease that
precludes resection. Patients suspected of having resectable disease should first undergo diagnostic
laparoscopy. Those who are found to have previously unidentified metastatic disease should undergo
cholecystectomy and surgical bypass for biliary decompression.93 For curative resection, the location and
local extension of the tumor dictates the extent of the surgery required. Distal bile duct tumors are often
resectable but may require pancreaticoduodenectomy (Whipple procedure). For patients with distal bile
duct cancer found to be unresectable on surgical exploration, Roux-en-Y hepaticojejunostomy,
cholecystectomy, and gastrojejunostomy to prevent gastric outlet obstruction should be performed.
Perihilar tumors involving the bifurcation or proximal common hepatic duct (BismuthCorlette type I or II)
with no signs of vascular involvement are candidates for local tumor excision with portal
lymphadenectomy, cholecystectomy, common bile duct excision, and bilateral Roux-en-Y
hepaticojejunostomies. If the tumor involves the right or left hepatic duct (Bismuth-Corlette type IIIa or
IIIb), right or left hepatic lobectomy, respectively, should also be performed. Frequently, resection of the
adjacent caudate lobe is required because of direct extension into caudate biliary radicals or
parenchyma.91 Type IV Klatskin tumors, those with more extensive involvement of both hepatic ducts
and intrahepatic spread, are often considered unresectable or only treatable with liver transplantation.
22. The best outcomes in perihilar cholangiocarcinoma are seen in patients who undergo neoadjuvant
chemoradiation followed by liver transplantation. However, there are very strict inclusion criteria for
transplantation, and few patients qualify.88 Patients with primary sclerosing cholangitis who develop
cholangiocarcinoma should be treated with liver transplant whenever possible. Nonoperative biliary
decompression can be performed for patients with unresectable disease on initial presentation.
Endoscopic placement of expandable metal stents is often the preferred approach. For very proximal or
intrahepatic tumors, percutaneous drainage catheters may be necessary to fully decompress the biliary
tree (see Fig. 32-12). There is a significantly higher risk of cholangitis in patients with drainage catheters
or stents compared to those with surgical bypasses. In addition, stent occlusion is not uncommon.
Nevertheless, operative intervention is not warranted in patients with metastatic disease.94 There is no
proven role for adjuvant chemotherapy in the treatment of cholangiocarcinoma. Adjuvant radiation
therapy has also not been shown to increase either quality of life or survival in resected patients. Patients
with unresectable disease can be offered palliative chemotherapy, typically with gemcitabine and
cisplatin, but the response rates are low (10–20%), and the survival benefit is marginal. The combination
of radiation and chemotherapy may be more effective than either treatment alone for unresectable
disease, but no data from randomized trials are available. Giving chemoradiation to these patients can be
difficult because of the high incidence of cholangitis. External-beam radiation has not been shown to be
an effective treatment for unresected disease. The use of interstitial (intraoperative) radiation,
brachytherapy with iridium-192 via percutaneous or endoscopic stents, and combined interstitial and
external-beam radiation for unresectable cholangiocarcinoma has been reported with some encouraging
results. However, no randomized, prospective trials have been reported.91 Photodynamic therapy has
been proposed as a palliative measure for patients with unresectable disease and A B Figure 32-32. A. An
endoscopic retrograde cholangiogram in a patient with cancer of the common hepatic duct (arrowheads).
The common bile duct is of normal size, as is the cystic duct (arrow), but the proximal biliary tree is dilated.
The gallbladder is not visualized because of tumor obstructing its neck. B. An ultrasound from the same
patient showing dilated ducts and tumor obstructing the common hepatic duct (arrow). The walls of the
bile ducts adjacent to the obstruction are thickened by tumor infiltration (arrowheads).
Brunicardi_Ch32_p1393-p1428.indd 1424 11/02/19 2:44 PM 1425 GALLBLADDER AND THE
EXTRAHEPATIC BILIARY SYSTEM CHAPTER 32 has been found to prolong survival and improve quality of
life in patients with biliary stents.95,96 Prognosis. Most patients with perihilar cholangiocarcinoma
present with advanced, unresectable disease. Median survival in this population is between 5 and 8
months. The most common causes of death are hepatic failure and cholangitis. The overall 5-year survival
rate for patients with resectable perihilar cholangiocarcinoma is between 10% and 30%, but for patients
with negative margins, it may be as high as 40%. The operative mortality for perihilar cholangiocarcinoma
is 6% to 8%. Patients with distal cholangiocarcinoma are more likely to have resectable disease and
improved prognosis compared to perihilar cholangiocarcinoma. The overall 5-year survival rate for
resectable distal disease is 30% to 50%, and the median survival is 32 to 38 months. Patients who receive
liver transplantation for cholangiocarcinoma can experience 5-year disease free survival rates as high as
68%. The greatest risk factors for recurrence after resection are the presence of positive margins and
lymph node–positive tumors. Therapy for recurrent disease concentrates on palliation of symptoms and
additional surgery is not recommended for patients with recurrent disease. REFERENCES Entries
highlighted in bright blue are key references. 1. Clemente CD. Gray’s Anatomy. Philadelphia: Lea &
Febiger; 1985:132. 2. Klein AS, Lillemoe KD, Yeo CJ, et al. Liver, biliary tract, and pancreas. In: O’Leary JP,
ed. Physiologic Basis of Surgery. Baltimore: Williams & Wilkins; 1996:441. 3. Molmenti EP, Pinto PA, Klein