References

Prevalence of gallstone disease in an Italian adult female population. Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO). Am J Epidemiol 1984 119(5) 796-805. 2. The epidemiology of gallstone disease in Rome, Italy. Part I. Prevalence data in men. The Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO). Hepatology 1988 8(4) 904-6. 3. Halldestam I, Enell EL, Kullman E, et al. Development of symptoms and complications in individuals with asymptomatic...

Contents

Preface Gallbladder Disease xiii Laura M. Stinton, Robert P. Myers, and Eldon A. Shaffer Gallstones are common with prevalences as high as 60 to 70 in American Indians and 10 to 15 in white adults of developed countries. Ethnic differences abound with a reduced frequency in black Americans and those from East Asia, while being rare in sub-Saharan Africa. Certain risk factors for gallstones are immutable female gender, increasing age, and ethnicity family (genetic traits). Others are modifiable...

Keywords

Bile salts Cholesterol absorption Ezetimibe Gallbladder Nuclear receptors Statins Gallstone disease is one of the most frequent and costly digestive diseases in Western countries its prevalence in adults ranges from 10 to 15 .1-4 Despite the frequency of the condition, many patients with gallstones remain undiagnosed, although symptoms and or complications occur in approximately a third of patients. In the United States, medical expenses for the treatment of gallstones exceeded 6 billion in...

Symptomatic Patients Without Complications

Patients with symptomatic gallstones are generally offered cholecystectomy. This is based on several longitudinal studies on the natural history of symptomatic gallstones without complications (grade B). These studies assess the hospital admissions and the complications that patients with symptomatic gallstones developed. The number of hospital admissions varied from 2.5 hospital admissions per 100 patients per month to 23 hospital admissions per 100 patients per month,45-47 possibly because of...

Longterm Biliary Stenting

A practical approach to difficult stones refractory to endoscopic retrieval is to place a biliary stent as a temporizing measure to maintain biliary drainage and to prevent stone impaction, pending more definitive management.4 Alternatively, long-term biliary stenting is used in patients who have severe comorbid medical conditions that preclude surgery or have failed repeated endoscopic interventions for definitive therapy of bile duct stones.85-88 Stones may partially disintegrate or decrease...

Pathophysiology Of Cholesterol Gallstone Formation

It is not surprising, that in a polygenetic disorder as cholesterol gallstone disease, several underlying mechanisms may be involved in its pathogenesis. Nevertheless, the common theme remains excess biliary cholesterol compared with solubilizing bile salts or phospholipids. In Chilean patients (especially of Amerindian descent), increased bile salt and cholesterol synthesis have been reported.42 The defect was supposed to be secondary to increased intestinal loss of bile salts, and preceded...

Info

Gallstone disease is an important risk factor for the development of gallbladder cancer however, not all individuals with gallstones will develop gallbladder cancer. Fig. 12. NCI mortality data for White women between 1970 and 1994 in the United States. (From National Cancer Institute. Available at http www.cancer.gov .) Fig. 12. NCI mortality data for White women between 1970 and 1994 in the United States. (From National Cancer Institute. Available at http www.cancer.gov .) Moreover, having a...

Risk Factors

Traditionally, risk factors for the development of gallbladder cancer have essentially been chronic cholelithiasis and female gender. However, other factors also promote Fig. 10. SEER mortality data for African American women between 1992 and 2006 in the United States. (From National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. Available at http seer.cancer.gov .) Fig. 10. SEER mortality data for African American women between 1992 and 2006 in the United States....

Summary

The primary goal in the management of gallbladder polyps is to prevent the development of gallbladder carcinoma, which is a rare illness. Often patients with gallbladder polyps undergo cholecystectomy because of symptoms. However, asymptomatic gallbladder polyps can be a dilemma for the clinician. Polyp size has long been known to be the simplest predictor for malignant potential. However, recent studies suggest that the cut-off size should be 6 mm as opposed to the traditional 10 mm...

Diagnostic Tests

In the setting of biliary-like abdominal pain and a normal gallbladder on transcutaneous ultrasound, the diagnosis of functional gallbladder disorder requires a careful evaluation to exclude other causes of the symptoms, and, at a minimum, serologic testing of liver and pancreatic enzymes and upper endoscopy.6 Several tests have been developed in an attempt to more objectively implicate the gallbladder as the source of the symptoms. The technique of analyzing aspirated bile from the biliary...

Management

When a gallbladder polyp is identified on abdominal ultrasound, the two major questions are (1) is this causing any symptoms and (2) does this need to be removed As discussed above, most polyps are generally thought to be asymptomatic. Therefore, the main role for the clinician in managing these polyps is recommending when to proceed with surgery and when to take a watchful waiting approach, recognizing that gallbladder cancer, while quite rare, carries a poor prognosis (Fig. 2). Numerous...

Ethnicity And Gallstone Disease

The highest prevalence of gallstone disease has been described in North American Indians 64.1 of women and 29.5 of men have gallstones (Table 1).1,12 This apparent epidemic reaches a high of 73 in Pima Indian women over age 30.13 Similar high occurrences have been reported among the aboriginal populations of South America.14 In the native Mapuche of Chile, gallstone disease afflicts 49.4 of women and 12.6 of men, exceeding 60 in women in their 50s. Mexican Americans are also at an increased...

1

K Serial imaging every 6 months to one year Fig. 2. Proposed algorithm for management of gallbladder polyps. be solitary, whereas cholesterol polyps were typically multiple. If less than three polyps were noted, then the incidence of neoplasm was 37 , even in polyps 5 to 10 mm in diameter. Kwon and colleagues31 reviewed 291 patients with confirmed gallbladder polyps on cholecystectomy and found that age over 60, sessile morphology, and size of 10 mm were all clear risk factors of malignant...

Mirizzi Syndrome

Mirizzi syndrome (MS) is an atypical presentation of gallstone disease in which the impaction of a gallstone in the cystic duct or the gallbladder neck causes stenosis of the extrahepatic bile duct by extrinsic compression or fibrosis.52 Bile duct wall necrosis and subsequent cholecystobiliary fistula caused by chronic inflammation are rare sequelae of the disease. The syndrome was first described by the Argentinean surgeon Pablo Mirizzi in 1948. It is reported to occur in 0.7 to 2.5 of all US...

Evidence Against Cholecystectomy For Patients With Functional Gallbladder Disorder

Despite excellent symptom improvement after cholecystectomy for gallstone disease, the clinical improvement in patients with presumed functional biliary pain is not as good. Fenster and colleagues46 prospectively evaluated the effects of cholecystectomy on the presenting symptoms in 225 patients undergoing laparoscopic cholecystectomy. Fifteen percent of the patients were believed to have functional gallbladder disorder, while 48 described atypical pain, and 82 experienced bothersome nonpain...

Iv

Data from American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York Springer 2010. Data from American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York Springer 2010. similarly sensitive at detecting invasion into liver or other adjacent organ was with sensitivities ranging from 80 to 100 .24'25 MRI is less frequently used for staging of GBCA, but sometimes the use of magnetic resonance cholangiography (MRCP) or magnetic resonance angiography...

A

Gallstones MRI findings. (A) Coronal image from an MRCP shows a large stone with very low signal intensity (open arrow) lodged in the gallbladder neck causing acute cholecystitis associated with mural thickening of the gallbladder and high signal intensity peri-cholecystic fluid (solid arrow). Note the normal common bile duct (arrowhead). (B) Coronal T2-weighted, fat-suppressed image shows multiple small stones within the gallbladder and high signal intensity pericholecystic fluid...

Dyslipidemia Diabetes Mellitus and the Metabolic Syndrome

Given that cholesterol gallstone disease is a metabolic problem, it should correlate with lipid abnormalities, diabetes mellitus, and adiposity. Although most gallstones in the Western world consist of cholesterol, there is no definite association with hypercholesterolemia.1 Rather, a low HDL cholesterol carries an increased risk of developing stones, as does hypertriglyceridemia. The association between diabetes mellitus and gallstones is confounded by age, obesity, and a family history of...

Fxr

Nascent bile formation at the hepatocytic canalicular membrane. ABCG5-G8 transports cholesterol into bile, and is regulated by nuclear receptor LXR. ABCB11 and ABCB4 transport bile salts and phosphatidylcholine into bile, and are regulated by nuclear receptor FXR. Excess hepatic cholesterol secretion or insufficient bile salt-phosphatidylcholine secretion lead to biliary cholesterol supersaturation. Subsequently, cholesterol supersaturated vesicles may form, which is promoted by bile...

Qj

Quantitative trait loci (QTLs) for Lith genes, as well as candidate gallstone genes for cholesterol gallstone formation on chromosomes representing the entire mouse genome. A vertical line represents each chromosome, with the centromere at the top genetic distances from the centromere (horizontal black lines) are indicated to the left of the chromosomes in centimorgans (cM). Gallstone QTLs (Lith genes) and candidate gene locations are indicated by horizontal black lines with the gene...

Physicalchemical Aspects Of Biliary Cholesterol Solubilization And Cholesterol Crystallization

Although solubility of cholesterol in aqueous solutions is extremely limited, in gallbladder bile a relatively large amount (approximately 20 x 10 3 M) of the sterol can be kept in solution. This significant increase in solubility is explained by incorporation of cholesterol in mixed micelles, together with bile salts and phospholipids (mainly phosphatidylcholine). Supersaturation occurs when either too much cholesterol or not enough solubilizing bile salt and phosphatidylcholine molecules are...

Eus And Occult Cholecystolithiasis Or Microlithiasis

Gallstone disease is common in the United States, with a prevalence of approximately 10 to 15 among adults.4 The gold standard for evaluation for gallbladder stones is transabdominal US, which has been shown to have a sensitivity of 98 for the detection of cholecystolithiasis.5 However, US may miss gallstones in some patients, particularly those with small gallstones, and a high clinical suspicion for cholelithiasis may Fig. 5. Transluminal view from the duodenal bulb of the common bile and...

Diagnosis

AAC poses major diagnostic challenges.68 Most afflicted patients are critically ill and unable to communicate their symptoms. Cholecystitis is but one of many potential causes in the differential diagnosis of systemic inflammatory response syndrome or sepsis in such patients. Rapid and accurate diagnosis is essential, because gallbladder ischemia can progress rapidly to gangrene and perforation. Acalculous cholecystitis is sufficiently common that the diagnosis should be considered in every...

Surgically Altered Anatomy

ERCP may be performed for a variety of clinical indications in patients with surgically altered gastrointestinal anatomy. Such procedures can be more technically challenging, time consuming, and often require a significant level of expertise to optimize success.72 Moreover, the obesity epidemic has led to further increases in bariatric surgery and increased the patient population with difficult to access pancreaticobiliary anatomy. Several significant challenges to performance of ERCP in a...

Eus And Polypoid Lesions Of The Gallbladder

Adenomyomytosis The Gallbladder Eus

Polypoid lesions of the gallbladder are common, being found in 3 to 7 of healthy subjects undergoing US.27,28 On US, these masses have echogenicity similar to the gallbladder wall, project into the lumen, are fixed, and lack an acoustic shadow (Fig. 9).29 Most polypoid gallbladder lesions are cholesterol polyps, which appear Fig. 9. EUS image of a gallbladder polyp, seen as a small echogenic, nonshadowing, nonmobile structure adherent to the gallbladder wall. The findings are consistent with a...

Surgical Treatment of Gallstones

Gurusamy, mrcs*, Brian R. Davidson, frcs KEYWORDS Gallstones Cholelithiasis Choledocholithiasis Cholecystectomy Surgical procedures Operative Postoperative complications About 5 to 25 of the adult western population have gallstones.1-4 About 2 to 4 become symptomatic each year.3'5'6 Most common symptoms are upper abdominal pain, biliary colic, and dyspepsia.7,8 Biliary colic is defined as a steady right upper quadrant abdominal pain lasting for more than half an hour,'' which may be...

Gallbladder And Intestinal Motility

Meal ingestion induces considerable gallbladder emptying (up to 70 -80 of fasting gallbladder volumes) by releasing the hormone cholecystokinin from the upper intestine. Impaired gallbladder emptying may prolong residence of bile in the gallbladder, allowing more time for nucleation of cholesterol crystals from supersaturated bile. Furthermore, in case of adequate emptying, cholesterol crystals that have nucleated may be ejected to the duodenum, whereas in case of impaired gallbladder emptying,...

Gallbladder Sludge

Gallbladder sludge is thick viscous bile that consists of cholesterol monohydrate crystals and calcium bilirubinate granules embedded in a gel matrix of mucus glycopro-teins. It often develops in patients with prolonged fasting in intensive care units, trauma patients receiving total parenteral nutrition, and within 5 to 7 days of fasting in patients who have undergone gastrointestinal surgery. Sludge typically has a fluctuating course and may disappear and reappear over several months or...

Co 40

Cholesterol saturation of bile, UDCA might counteract the impaired contractility caused by incorporation of excessive luminal cholesterol into the plasmalemma of gallbladder smooth muscles.88-91 UDCA might also counteract the detrimental effects of the hydrophobic bile acid deoxycholate on the gallbladder smooth muscle contractility,91,92 and have an effect on local oxidative stress89,93 and risk of acute cholecystitis.71 Excess biliary cholesterol might provide the basis for stimulation of...

Guidelines For Management Of Gallstone Disease

Gall Bladder

Gallbladder stones are frequently found in asymptomatic patients during routine abdominal ultrasonography, because in most cases (60 -80 ) gallstones do not generate symptoms.43,48,49 Previous observations have shown that the average risk of developing symptomatic gallstones is 2.0 to 2.6 per year.45,50 By contrast, the presence of microstones and sludge in the gallbladder is a major risk factor for the development of biliary pain and complicated gallstone disease, and also plays a main role in...

Searching For Human Lith Genes

Because of its multifactorial pathogenesis, it is difficult to identify human gene abnormalities that are responsible for the formation of cholesterol gallstones. Monogenic predisposition for cholelithiasis has only been ascribed to mutations in the genes in specific subgroups of patients. Table 2 summarizes human LITH genes that have been identified and updated in 2008. Missense mutations in the ABCB4 gene, which encodes the phospholipid transporter in the canalicular membrane of hepatocytes,...

Clinical Patterns Of

Reports of acute cholecystitis complicating surgery, multiple trauma, or burn injury are numerous. In patients with gallstones, postoperative cholecystitis affects males and females to a similar degree. More than 80 of patients who develop non-trauma-related postoperative AAC, however, are male.6 The incidence of AAC following open abdominal aortic reconstruction is 0.7 to 0.9 ,7,8 and has also been reported to complicate endovascular aortic reconstruction.9 After cardiac surgery, the incidence...

Caveats Relating To The Use Of Cholecystokinincholescintigraphy

Cholecystokinin Disease

CCK-CS involves the intravenous administration of 99mtechnetium-labeled hepato-iminodiacetic acid, which is taken up by the liver and excreted into the biliary system, where it accumulates in the gallbladder. A GBEF then can be measured reliably after stimulating gallbladder emptying, most commonly with CCK. A low GBEF has been suggested to be indicative of gallbladder dysfunction and supportive of a diagnosis of functional gallbladder disorder however, its use is not without controversy.37...

Gallbladder Carcinoma

Gall Bladder Lesions Ultrasound

Cross-sectional imaging is needed to expedite the diagnosis and appropriate treatment of patients with gallbladder malignancies, who often present with nonspecific symptoms of right upper quadrant pain, jaundice, and weight loss.2,3,84-86 Initial assessment of patients with right upper quadrant pain should include examination by ultrasonography. The diagnostic accuracy of ultrasonography is more than 80 , but it has limitations in the diagnosis of involved lymph nodes and the staging of...

Gender and Female Sex Hormones

Female gender is one of the most powerful influences on gallstone disease, with women almost twice as likely as men to form stones.1 This is especially true for women in their fertile years, with the gap narrowing into the postmenopausal period when men catch up. Women are also more likely to undergo cholecystectomy. The basis for this finding seems related to the female sex hormones, because parity, oral contraceptive use, and estrogen replacement therapy are risk factors for gallstone...

Cholelithiasis

Cholecystography

The nature and size of a gallstone affects its imaging characteristics. Gallstones are comprised mainly of cholesterol, bilirubin, and calcium salts, with smaller amounts of protein and other materials including bile acids, fatty acids, and inorganic salts. In Western countries, cholesterol is the principal constituent of more than 75 of gallstones, with smaller amounts of calcium bilirubinate.7-9 Pure cholesterol stones contain more than 90 cholesterol and account for less than 10 of biliary...

Acute Cholecystitis

Cholecystitis Mri

Acute cholecystitis results from obstruction of the gallbladder neck or cystic duct by a gallstone in 80 to 95 of patients.34 Acute acalculous cholecystitis (AAC) composes 5 to 15 of cases of acute cholecystitis and is typically caused by diminished gallbladder emptying (eg, in patients with severe trauma surgery, burns, shock, anesthesia, diabetes) by decreased blood flow in the cystic artery because of obstruction, hypotension, or embolization or by bacterial infection.35,36 Although most...

Choledocholithiasis

Echogenic Gall Stones

Choledocholithiasis is found in 7 to 20 of patients undergoing cholecystectomy and 2 to 4 of patients after cholecystectomy.21-23 These stones are usually silent unless they obstruct the common bile duct (CBD). Small calculi may intermittently cause colicky pain as they obstruct at the ampulla of Vater but generally pass into the duodenum. Larger stones between 5 and 10 mm in size are difficult to pass and can result in intermittent long-term symptoms and sequelae such as cholangitis and...

Eus And Gallbladder Carcinoma

Gallbladder carcinoma is an uncommon disease. It is estimated that approximately 9760 cases of gallbladder and other biliary tract cancers were diagnosed in the United States in 2009 and that these were responsible for 3370 deaths.39 Because the signs and symptoms of gallbladder carcinoma (including abdominal pain, nausea, vomiting, weight loss, and anorexia) are nonspecific, the disease is often diagnosed at an advanced stage and is associated with a high mortality.40 Accurate preoperative...

Pathogenesis Of Pigment Gallstones

In the Western world, approximately 30 of gallstone carriers exhibit black pigment gallbladder stones (< 20 cholesterol content). Whereas black gallbladder pigment stones are extremely rare below age 50 years, there is a progressive relative contribution of this stone type at older age.65 In East Asia, there is a relatively high prevalence of brown pigment stones residing in the bile ducts, and causing potentially devastating cholangitis. Black pigment stones are formed in sterile bile in the...

Clinical Presentation

Gallbladder polyps are generally thought not to cause any symptoms, though most of the prevalence studies did not assess symptoms.9 Polyps are sometimes identified on transabdominal ultrasounds done for right upper quadrant pain. In the absence of other findings, the gallbladder polyp may be considered a source of biliary colic.10 Terzi and colleagues11 reported that, in a series of 74 patients undergoing cholecystectomy for gallbladder polyps, 91 had symptoms, most commonly right upper...

Chronic Cholecystitis

Gallbladders that are subjected to repeated bouts of acute cholecystitis are at risk for developing chronic cholecystitis. Chronic cholecystitis is several times more common pathologically in cholecystectomy specimens than in acute cholecystitis, and both conditions are often present simultaneously. Many cases that are pathologically diagnosed as chronic cholecystitis have the imaging diagnosis of acute cholecystitis because the findings on cross-sectional imaging may be identical. Also, from a...

Burden Of Gallstone Disease

Gallstones are an ancient entity, having occurred more than 3500 years ago according to autopsies performed on Egyptian and Chinese mummies. Gallbladder disease today is a common problem 20 to 25 million Americans harbor gallstones, representing 10 to 15 of the adult population.1 It constitutes a major health burden, with direct plus indirect costs of approximately 6.2 billion annually in the United States.4 This burden has increased more than 20 since the 1980s and accounts for an estimated...

Obstructive Jaundice

Patients with gallstones develop obstructive jaundice if stones migrate into the common bile duct. Although common bile duct stones can be removed endoscopi-cally,73 subsequent cholecystectomy is recommended based on a systematic review of randomized controlled trials in which a policy of observation after endoscopic sphincterotomy increased the risk of mortality and gallstone-related complications compared with routine cholecystectomy65 grade A . There are no studies investigating the natural...

Novel Medical Treatments

Selenoprotein

The presence of a lithogenic bile is primarily a result of a sustained hypersecretion of biliary cholesterol, which has 2 key components hepatic and intestinal.31 In principle, drugs influencing hepatic synthesis and or secretion of cholesterol ie, statins and or intestinal absorption of cholesterol ie, EZT are potentially able to influence the formation of cholesterol gallstones and to promote dissolution of gallstones. Inhibition of Hepatic Cholesterol Synthesis by Statins Statins are...

Acute Acalculous Cholecystitis

Longitudinal Scan Gallbladder

Acute gallbladder inflammation in the absence of stones, AAC, is seen in 2 to 15 of patients undergoing cholecystectomy and accounts for 47 of cases of postoperative cholecystitis and 50 of children with acute cholecystitis. It is difficult to make the diagnosis of AAC clinically and on imaging.49 AAC has a mortality rate approaching 60 and should be considered in every postoperative, posttraumatic, or coronary care patient with sepsis.50 AAC typically results from a gradual increase of bile...