Gallbladder Disorders.

Hepatobiliary Diseases.

Gallstone Disease

• ESSENTIAL CONCEPTS

• Major risk factors for cholesterol gallstones include age > 50 years, female sex, genetic predisposition, family history, pregnancy and parity, estrogens, obesity, and the metabolic syndrome.

• Gallstones are often found incidentally during abdominal ultrasonography, which has > 95% sensitivity for cholesterol stones ≥ 1.5 mm.

• In ~80% of cases gallstones remain asymptomatic; in symptomatic patients, biliary colic is almost always present, often radiating to the right scapula or shoulder.

• Laparoscopic cholecystectomy is indicated in patients with symptomatic gallstones.

• Major complications of gallstone disease requiring treatment are acute cholecystitis, choledocholithiasis, obstructive jaundice, cholangitis and pancreatitis.

• Acute cholangitis caused by an obstructing gallstone should be treated by endoscopic removal of the stone under antibiotic coverage as soon as possible.

• General Considerations

• With a prevalence of 10–15% in adults in the United States and in Europe, it is one of the most common digestive diseases.

• The clinical manifestations of gallstones include episodic abdominal pain, acute cholecystitis, obstructive jaundice, cholangitis, and pancreatitis.

• In Western industrialized countries, about 80% of gallstones consist mainly of cholesterol.

• A. Epidemiology

• The overall prevalence of gallstones in Europe is 7.9% in men and 16.6% in women, with a progressive increase after age 20 years.

• The prevalence of gallstone disease is lower in Asians (ranging from 3% to 15%) and very low (< 5%) in Africans.

• B. Risk Factors

• The prevalence of gallstones increases with age.

• It is about twice as high in women as in men.

• Pregnancy increases the risk of gallstones becauseimpaired gallbladder emptying, caused by progesterone, combines with the influence of estrogen, which increases cholesterol hypersecretion.

• In obese persons an overproduction of cholesterol causes cholesterol hypersecretion into bile and thus predisposes to gallstone formation.

• Pathogenesis

• A. Cholesterol Stones

• Supersaturation of bile with cholesterol is the thermodynamic requirement for theformation of cholesterol gallstones.

• It can result from secretion of cholesterol into bile that exceeds the solubilizing capacity of bile acids and phospholipids.

• B. Pigment Stones

• Black pigment stones:

• They are more common in patients who have chronic hemolytic states (with increased conjugated bilirubin in bile), liver cirrhosis, Gilbert syndrome, or cystic fibrosis

• Brown pigment stones:

• Brown pigment stones are frequent in Asia, where there is a high prevalence of infection of the biliary tree.

• Clinical Findings

• A. Symptoms and Signs

• Gallstones are often discovered incidentally during abdominal ultrasonography and remain asymptomatic in nearly 80% of cases.

• The first symptom of gallstone disease almost always is biliary colic.

• Biliary colic results from obstruction of the cystic duct or common bile duct by a stone.

• There may be concomitant nausea with or without vomiting.

• B. Laboratory and Imaging Studies

• 1. Ultrasonography—Ultrasonography of the right upper quadrant is the method of choice for the diagnosis of gallbladder stones.

• Ultrasonography also offers information about the size of the gallbladder, the presence of a thickened gallbladder wall, and pericholecystic fluid (signs of acute cholecystitis).

• 2. Computed tomography (CT)—

• CT is occasionally useful for the detection or exclusion of gallstones, especially calcified stones, but it is less sensitive and more expensive thanultrasound and requires exposure to radiation.

• It is valuable for visualization of the biliary system in suspected biliary obstruction.

• It should be used if biliary pancreatitis or commonbile duct stone obstruction is suspected.

• 3. Magnetic resonance imaging (MRI) and cholangiopancreatography (MRCP)—

• Is useful for visualizing pancreatic ducts and bile ducts and has excellent sensitivity for bile duct or pancreatic duct dilations.

• Its sensitivity for detection of bile duct stones is approximately 85%.

• MRCP can be used as an alternative to ERCP to exclude bile duct stones.

• 4. Endoscopic retrograde cholangiopancreatography (ERCP)—

• ERCP is not useful for detection of gallstones in the gallbladder but is the method of choice for the detection of bile duct stones.

• In contrast to MRI, it has both diagnostic and therapeutic value for visualization and extraction of bile duct stones.

• Differential Diagnosis

• The differential diagnosis of acute right upper quadrant abdominal pain should include duodenal ulcer disease, acute pancreatitis, appendicitis, duodenal obstruction, right lower lobe pneumonia, mesenteric vascularischemia, and gastroparesis.

• Complications

• A. Acute Cholecystitis

• Acute cholecystitis is the most frequent complication of gallstone disease.

• The increased intraluminal pressure and distention of the gallbladder result in ischemia of the mucosa and the wall of the gallbladder.

• Bacterial inflammation playing a role in 50–85% of patients with acute cholecystitis and, in general, is a secondary event occurring late in the course.

• Acute cholecystitis usually begins as an attack of biliary pain that progressively worsens.

• Usually there is marked tenderness and inhibition of inspiration on deeppalpation under the right subcostal margin (Murphy sign).

• Low-grade fever is usually present.

• Mild to moderate leucocytosis is common.

• Serum bilirubin and serum liver enzymes may be mildly elevated.

• Serum amylase levels usually are normal; if substantially elevated, they suggest pancreatitis.

• In 10–30% of the patients with acute cholecystitis severecomplications, such as gallbladder gangrene, empyema, orperforation, occur.

• Mirizzi syndrome is a rare complication in which a gallstone becomes impacted in the neck of the gallbladder or cystic duct, causing compression of the common bile duct and obstructive jaundice.

• B. Choledocholithiasis

• Passage of gallstones into the common bile duct occurs in approximately 10–15% of patients with gallbladder stones.

• Most patients with common bile duct stones present with biliary pain accompanied by abnormal liver tests with or without jaundice.

• Most patients with obstruction have elevated liver enzymes (ALT, AST) in the acute phase of obstruction.

• Transcutaneous abdominal ultrasonography has only moderate diagnostic accuracy for the detection or exclusion of bile duct stones.

• If there is high suspicion of the presence of a bile duct stone, endoscopic retrograde cholangiography (ERC) is indicated because it permits simultaneous therapeutic intervention (endoscopic papillotomy and stone extraction).

• C. Cholangitis

• The characteristic presentation of cholangitis involves biliary pain, jaundice, and spiking fevers with chills (the Charcot triad).

• Leukocytosis is typical, and blood cultures are positive in about 75% of patients.

• D. Biliary Pancreatitis

• Biochemical evidence of pancreatic inflammation complicates acute cholecystitis in about 15% and choledocholithiasis in about 30% of patients.

• Treatment

• A. Surgical Therapy

• 1. Asymptomatic gallstones—Treatment of persons with asymptomatic gallstones is not recommended because the risks of biliary colic, complications, and gallbladder cancer are low.

• Prophylactic cholecystectomy is, however, indicated for asymptomatic patients with an increased risk of gallbladder cancer (eg, patients with a so-called porcelain gallbladder; patients with large stones (≥ 3 cm in diameter).

• Prophylactic cholecystectomy has been proposed for patients with small gallstones (≤ 5 mm in size) and preserved gallbladder motility, because they may have a high risk for acute pancreatitis.

• Patients with gallstones and gallbladder polyps larger than 1 cm should be cholecystectomized irrespective of symptoms.

• 2. Symptomatic gallstones—

• Elective laparoscopic cholecystectomy is the standard method of cholecystectomy in patients with symptomatic gallstones.

• Laparoscopic cholecystectomy should not be performed if advanced gallbladder carcinoma is suspected.

• B. Nonsurgical Therapy

• 1. Oral bile acid dissolution—

• In selected patients who have symptomatic gallbladder stones without complications and have mild and infrequent episodes of biliary pain, stone dissolution with UDCA may be employed.

• Complete dissolution can be achieved with UDCA inabout 50% of patients.

• In general, 6–18 months of therapy are required to achieve complete dissolution of stones 5–10 mm indiameter.

• 2. Extracorporeal shock wave lithotripsy—

• This nonsurgical therapeutic modality has been abandoned mainly because of high rates of stone recurrence (11–29% at 2 years, 60–80% at 10 years).

• Extracorporeal shock wave lithotripsy has maintained a limited role in the treatment of bile duct stones resistant to endoscopic extraction.

• 3. Medical prophylaxis of cholesterol gallstone disease—

• UDCA may prevent gallstone formation in obese patients during rapid weight loss.

• For prophylaxis of gallstone formation during rapid weight loss (> 1.5 kg/week) a minimal dose of UDCA of 500 mg/kg/day isrecommended until constant body weight is attained.

• 4. Symptomatic treatment of biliary colic—

• Combinations of analgesics with spasmolytic drugs are used for relief of pain.

• The patient should be kept NPO (nothing by mouth).

• In case of vomiting, parenteral fluid and electrolyte replacement may be indicated.

• C. Management of Complications

• 1. Cholecystitis—

• Patients with acute cholecystitis should undergo early elective laparoscopic cholecystectomy, ideally within 72 hours after diagnosis.

• Administration of broad-spectrum antibiotics early in the course is recommended, because secondary infection often supervenes in what is initially a noninfectious process.

• If a complication of cholecystitis, such as diffuse peritonitiswith suspected perforation, gangrene, or empyema, develops an emergency operation should be performed within 24 hours.

• 2. Choledocholithiasis—

• Patients with symptomatic bile duct stones who have hadcholecystectomy previously should undergo endoscopic papillotomy (EPT) and stone extraction.

• Patients with simultaneous gallbladder and bile duct stones should undergo so called therapeutic splitting.

• In this technique, ERC is performed before or after cholecystectomy.

• In centers with high expertise, laparoscopic cholecystectomy may be combined with laparoscopic revision of the common duct and removal of the stones.

• If endoscopic transpapillary therapy is not possible or fails, percutaneous, transhepatic, or surgical therapy of choledocholithiasis may be employed.

• In high-risk patients the placement of an endoprosthesis may be considered for primary therapy.

• 3. Cholangitis—

• Acute cholangitis caused by an obstructivegallstone should be treated as soon as possible (in septic patients, as an emergency procedure) by endoscopic removal of the stone.

• An accompanying systemic antibiotic therapy is indicated to prevent septic complications.

• If stone extraction fails, nasobiliary drainageor a biliary stent should be placed.

• 4. Biliary pancreatitis—

• If biliary pancreatitis is severe and is associated with choledocholithiasis and signs of cholestasis, ERC with papillotomy and stone extraction should be performed as soon aspossible, in the presence of cholangitis within 24 hours.

• Most cases of biliary pancreatitis are mild, resolve spontaneously, and may be managed expectantly.

• Incidence

2 – 4 % of all GI tumor

F/M : 2-3 / 1

0/4 % in random autopsy

1% incidentally in cholecystectomy

Carcinoma of the Gall bladder

Etiology

• 90% have gall stones

• Polypoid lesions, particulary larger than 10 mm

• Porcelain gallbladder

• Choledochal cysts

Pathology

• Adenocarcinomas is 80-90%

• histologic subtypes are papillary, nodular, and tubular.

• Cancer spreads through the lymphatics, venous drainage, and with direct invasion

Clinical Manifestations

• abdominal discomfort, right upper quadrant pain, nausea, and vomiting.

• less common: Jaundice, weight loss, anorexia, ascites, and abdominal mass

Diagnosis

• Ultrasonography

• CT scan

• ERC

• PTC

• MRCP

Treatment

• Surgery is the only curative option

• Tumors limited to the muscular layer (T1) need simple cholecystectomy

• tumor invades the perimuscular connective tissue without extension beyond the serosa or into the liver (T2 tumors)need extended cholecystectomyThat includes resection of liver segments IVB and V, and lymphadenectomy of the cystic duct, and pericholedochal,portal, right celiac, and posterior pancreatoduodenal lymph node

tumors that grow beyond the serosa

or invade the liver or other organs

(T3 and T4 tumors),need extended

right hepatectomy (segments IV, V,

VI, VII, and VIII)

Prognosis

• 5-year survival rate of all patients is less 5%

• median survival is 6 months.

• median survival in distant metastasis is only 1 to 3 months.

Primary SclerosingCholangitis

• ESSENTIALS OF DIAGNOSIS• Progressive inflammatory, sclerosing, and obliterative disease

of the extrahepatic or intrahepatic bile ducts, or both.• Disproportionate elevation of serum alkaline phosphatase (4–

10 times normal) is seen in almost all patients.• MRCP or ERCP shows multifocal stricturing of the intrahepatic

and extrahepatic bile ducts.• Small duct disease is diagnosed by liver biopsy.• Liver biopsy findings that are highly specific include fibrous

obliteration of small bile ducts with concentric replacement by connective tissue in an “onion skin” pattern.

• Patients have an 8–15% lifetime risk of developing cholangiocarcinoma, and it is often difficult to distinguish a dominant stricture from a cholangiocarcinoma.

• General Considerations• Primary sclerosing cholangitis (PSC) is a disorder of unknown

etiology characterized by a progressive, inflammatory, sclerosing, and obliterative process affecting medium sized and large extrahepatic or intrahepatic bile ducts, or both.

• A vast majority of patients (prevalence rates range from 70% to 90%) have underling inflammatory bowel disease, especially ulcerative colitis.

• The median survival of patients with PSC from time of diagnosis to death in several series has ranged from 9 to 12 years.

• Late in the course of the disease, complete biliary obstruction, secondary biliary cirrhosis, portal hypertension with bleeding varices, liver failure, and development of cholangiocarcinoma may occur.

• Clinical Findings

• A. Symptoms and Signs

• Patients with PSC are often asymptomatic at the time of diagnosis.

• The disorder is often suspected in patients with inflammatory bowel disease who have a persistent and otherwise unexplained abnormal elevation in serum alkaline phosphatase.

• Symptomatic patients who have PSC often present with signs and symptoms of chronic biliary obstruction, right upper quadrant abdominal pain, pruritus, jaundice, and acute cholangitis.

• B. Laboratory Findings

• Liver tests usually demonstrate a cholestatic pattern,with serum alkaline phosphatase elevated to levels 4–10 times normal.

• The presence of positive tests for antinuclear antibodies or smooth muscle antibodies, or both, should raise the suspicion of PSC.

• C. Imaging Studies• The diagnosis of PSC is usually established by

demonstration of the characteristic multifocal stricturing with normal and or dilated areas of intrahepatic or extrahepatic bile ducts, or both, on cholangiography.

• These abnormalities can be demonstrated by either magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP).

• Patients with small duct PSC do not demonstrate cholangiographic abnormalities.

PSC

• D. Histologic Findings

• The most characteristic histologic finding is fibrous obliteration of small bile ducts with concentric replacement by connective tissue in an “onion skin” pattern.

• Differential Diagnosis

• A. Small Duct Primary Sclerosing Cholangitis

• Small duct PSC is defined by the presents of chronic cholestasis and hepatic histologic findings consistent with PSC but with normal findings on cholangiography.

• Small duct PSC is found in about 5% of patients with PSC, and represents an earlier stage of PSC associated with a significantly better longterm prognosis.

• Patients may progress to classic PSC or end-stage liver disease, with consequent necessity of liver transplantation.

• B. Autoimmune Pancreatitis

• Patients with autoimmune pancreatitis can present with bile duct strictures, obstructive jaundice, and pancreatic duct abnormalities.

• This diagnosis should be suspected in patients with a focal mass in the head of the pancreas or narrowing of a main pancreatic duct along with an elevated serum immunoglobulin G4 value.

• C. Primary Sclerosing Cholangitis—Autoimmune Hepatitis Overlap Syndrome

• Patients with PSC-AIH overlap syndrome have cholangiographic abnormalities characteristic of PSC but serologic features of AIH.

• The overlap syndrome should be suspected in patients diagnosed with PSC who have elevated circulating levels of antinuclear antibodies or smooth muscle antibodies (titer ≥ 1:40), elevated levels of immunoglobulin G, and evidence of severe interface hepatitis on liver biopsy.

• D. Acquired Immunodeficiency Syndrome

• In patients with AIDS, cholangiopancreatography may demonstrate a broad range of biliary tract changes as well as pancreatic duct obstruction and occasionally pancreatitis.

• Biliary tract lesions in AIDS include cholangiopancreatographic changes similar to PSC.

• Treatment• A. Medical Therapy• PSC is a progressive, debilitating disease for which few

treatment options are currently available.• A major focus of medical treatment, therefore, is on managing

symptoms.• Pruritus: bile salt–sequestering agents such as

cholestyramine, as well as naltrexone and rifampin.• Ursodeoxycholic acid (UDCA) is the most extensively

evaluated treatment in patients with PSC. Doses of 20–30• mg/kg/day have shown modest improvement in liver

biochemical tests.• ERCP with balloon dilation of dominant strictures and removal

of debris may be beneficial.

• B. Liver Transplantation

• Liver transplantation is best choice for patients with advanced PSC.

• 5-year survival rates of approximately 85% and a 10-year survival rate of approximated 70% have been reported.

• Course & Prognosis

• PSC is usually a progressive disease that leads ultimately to biliary obstruction, secondary biliary cirrhosis, hepatic failure, portal hypertension with bleeding varices, and the development of cholangiocarcinoma.

• Patients with PSC are at increased risk of developing cholelithiasis and choledocholithiasis.

• Patients with PSC have an 8–15% lifetime risk of developing cholangiocarcinoma.