General Considerations

Approximately 10%-20% of the population have gallstones, making biliary pathology an increasing consideration in a patient with abdominal pain. Females are twice as likely to have gallstones. Gallstones are more frequently seen with increasing age, in the obese, and are more common in Caucasians and native Americans than African Americans. Most with cholelithiasis remain asymptomatic and never require surgery, but the sequelae of biliary disease remain significant: symptomatic cholelithiasis, gallstone pancreatitis, acute cholecystitis, chronic cholecystitis, choledocholithiasis, and ascending cholangitis. Understanding the basic pathophysiology of each of these conditions is an essential to appropriately diagnose and treat these conditions.

A basic understanding of biliary disease requires a vocabulary of terms used in describing them. Many have similar sounding names and can be confusing. A summary of the definitions can be found in Table 32-1. Although, the treatment of most biliary diseases ultimately requires cholecystectomy, each condition must be evaluated and treated in a unique fashion.

Cholelithiasis

Asymptomatic Cholelithiasis

A landmark study from the University of Michigan followed the course of 123 faculty members identified as having asymptomatic gallstones during a routine health examination. After over two decades of follow-up, 14 (11%) patients went on to develop complications requiring surgery. Subsequent studies have not demonstrated a survival advantage with prophylactic cholecystectomy. As a result of these studies, prophylactic cholecystectomy for asymptomatic cholelithiasis is generally not indicated.

Symptomatic Cholelithiasis

Essentials of Diagnosis

• Episodic RUQ pain.
  
• Ultrasound evidence of gallstones.

Unlike asymptomatic cholelithiasis, symptomatic cholelithiasis will generally necessitate operative intervention. The typical patient presentation will include right upper quadrant abdominal pain, usually following a fatty meal and frequently associated with nausea (biliary colic). The pain can be severe and debilitating, and a trip to the emergency room is not an infrequent occurence. Symptoms are related to transient obstruction of the gallbladder neck or infundibulum by stones or biliary sludge. As the gallbladder attempts to contract in response to cholecystokinin, the obstructed cystic duct prevents the egress of bile from the gallbladder into the biliary system, resulting in acute right upper quadrant pain. In addition to right upper quadrant pain, the character of biliary colic is often described as a colicky or crampy pain which may radiate to the back or shoulder. The pain is generally postprandial in nature and typically resolves within 1-2 hours. Persistence of pain beyond this time should prompt the clinician to suspect acute cholecystitis or other disorders discussed later.

In most circumstances, the patient with symptomatic cholelithiasis will have no abnormalities of their liver function tests or complete blood count. An abdominal ultrasound will reveal the presence of cholelithiasis without gallbladder wall thickening or pericholecystic fluid. The treatment of symptomatic cholelithiasis remains elective cholecystectomy in patients suitable to undergo a general anesthetic.

Laparoscopic cholecystectomy has replaced the open operation as the gold standard for removing the gallbladder. Many studies have documented the improved recovery time, decreased postoperative ileus, and decreased pain along with improved aesthetics associated with laparoscopy. The most feared complication of laparoscopic cholecystectomy is injury to the common bile duct. The reported incidence of bile duct injuries varies from 0% to 3% depending on the underlying pathology necessitating cholecystectomy, but is generally less than 1% in the setting of symptomatic cholelithiasis. Minor biliary injuries include cystic duct leaks and biliary leaks from the hepatic parenchyma. These injuries may be managed with percutaneous drain placement or endoscopic retrograde cholangiopancreatography (ERCP) to facilitate drainage into the duodenum. Major biliary injuries include clipping or transection of the common hepatic or common bile duct. When identified intraoperatively, these injuries are best managed with immediate repair if a skilled surgeon is available. Those biliary injuries identified in the postoperative setting are best treated with externalization of the bile flow (percutaneous transhepatic biliary drainage) and definitive repair at a later date, generally 2-3 months following the initial injury. In most circumstances, a Roux-en-Y hepaticojejunostomy is required to reconstruct the biliary tree.

Although associated with less morbidity, laparoscopic cholecystectomy does require pneumoperitoneum (insufflation of carbon dioxide gas into the abdomen) and may not be feasible in patients with other comorbid conditions (eg, the morbidly obese, severe congestive heart failure, advanced pulmonary disease, uncontrolled coagulopathy). If operation is required, open cholecystectomy remains the only viable option for these patients.

Following cholecystectomy, almost all patients (95%) with symptomatic cholelithiasis will have no further sequela of biliary diseases.

Chronic Cholecystitis

Chronic cholecystitis is a term used often synonymously with symptomatic cholelithiasis. It may also be a result of multiple episodes of untreated acute cholecystitis. The gallbladder will become scarred from multiple episodes of inflammation. Pathologic examination will demonstrate Rokitansky-Aschoff sinuses. The patient will usually describe multiple episodes of biliary colic. Ultrasound will demonstrate cholelithiasis and occasionally gallbladder wall thickening (from the scarring).

The treatment of chronic cholecystitis is cholecystectomy. Following cholecystectomy, most patients recover with no adverse effects.

Acute Cholecystitis

Essentials of Diagnosis

• Persistent severe RUQ pain (>4-6 hours).
  
• RUQ tenderness.
  
• Fever, leukocytosis.
  
• Ultrasound evidence of gallstones.

Acute cholecystitis is caused most commonly by obstruction of the cystic duct, resulting in localized edema and inflammation. Biliary cultures of most patients reveal bacteria. Women are three times as likely to develop acute cholecystitis as men. Over 90% of cases of acute cholecystitis are related to gallstones causing obstruction (calculous cholecystitis). The remaining cases are classified as acalculous cholecystitis. Here other comorbid conditions result in gallbladder wall ischemia or biliary stasis.

Acute cholecystitis is defined by the triad of right upper quadrant pain, fever, and leukocytosis. Abdominal ultrasound will demonstrate gallbladder wall thickening (>3 mm) with pericholecystic fluid. Symptoms typically begin after a meal. The pain is similar to, but far more severe, that of symptomatic cholelithiasis. In cases where acalculous cholecystitis is suspected or when ultrasound is inconclusive, radionucleotide scanning (ie, hepatobiliary iminodiacetic acid [HIDA]) may be used. Presence of radionucleotide in the extrahepatic biliary tree without filling the gallbladder is diagnostic of acute cholecystitis.

The treatment of acute cholecystitis is cholecystectomy. The timing of the operation is a controversial subject matter for general surgeons. Localized edema and subsequent scar formation after an episode of acute cholecystitis can make laparoscopic cholecystectomy difficult. Traditional teaching has been that cholecystectomy should be performed within 3 or 4 days of onset of symptoms—before myoepthelial changes can occur in the right upper quadrant. The localized edema associated with acute cholecystitis aides with dissection of tissue planes and facilitates cholecystectomy. Compared to delayed cholecystectomy (after 7 days of symptoms), this approach is associated with a decreased conversion rate to open operation (2% vs 30%) and decreased recovery time (12 vs 28 days). Many patients present, however, outside the initial 72-hour window. With each passing day of symptoms, the conversion rate to open operation increases. Many surgeons advocate a course of intravenous and (later) oral antibiotics with a plan to perform cholecystectomy in a delayed fashion approximately 6 weeks following the sentinel event. This delay will allow the scarring in the right upper quadrant to subside allowing for safer and easier dissection during laparoscopy. If the patient has continued pain or recurrence of cholecystitis during this waiting period, laparoscopic cholecystectomy should be attempted immediately. The patient should be counseled regarding the increased probability of conversion to an open operation. Alternatively, patients who are not operative candidates may undergo percutaneous tube cholecystostomy to drain the biliary tree. Percutaneous cholecystostomy serves as a bridge to elective cholecystectomy once the patient has stabilized.

Untreated cholecystitis can lead to gallbladder ischemia, necrosis, or perforation, resulting in biliary leak or fistula formation to surrounding structures. Those undergoing successful immediate cholecystectomy will generally have no further sequela of biliary disease. Consideration must be given for choledocholithiasis and common bile duct injury in a patient presenting with jaundice after cholecystectomy.

Choledocholithiasis

Choledocholithiasis or common bile duct stones are present in up to 10% of patients undergoing cholecystectomy. The treatment is cholecystectomy with evaluation of the biliary tree and clearance of all stones within the ductal system. Choledocholithiasis should be suspected in any patient with biliary ductal dilatation seen on imaging, the presence of elevated bilirubin levels (conjugated), elevated alkaline phosphatase levels, or elevated amylase and lipase levels. Patients presenting with choledocholithiasis may develop symptoms related to obstruction of the bile duct, pancreatic duct, or both.

Gallstone Pancreatitis

Essentials of Diagnosis

• RUQ or epigastric pain.
  
• Elevated serum amylase and lipase.
  
• Ultrasound evidence of gallstones.

Gallstones, small enough to pass through the biliary tree, may obstruct at the level of the ampulla of Vater. These stones will then cause obstruction of the pancreatic ductal system and resultant pancreatitis. Gallstones are associated with approximately 45%-50% of all cases of pancreatitis in the United States.

Patients presenting with pancreatitis typically have varying degrees of abdominal pain—usually located in the epigastrium or right upper quadrant. The pain may radiate to the back or shoulders. Nausea and vomiting are common. Laboratory studies will reveal elevation of serum lipase and amylase levels. If gallstones are obstructing the bile duct as well, then liver transaminases, alkaline phosphatase, and bilirubin may also be elevated. Although ultrasound is useful to confirm presence of gallstones, CT scanning is useful in delineating the severity of pancreatitis.

The treatment of gallstone pancreatitis is eventual cholecystectomy. As the gallbladder is the source of the stones, cholecystectomy will prevent subsequent episodes of pancreatitis. Cholecystectomy should not be attempted until following the resolution of the pancreatitis. Treatment for pancreatitis involves bowel rest with intravenous hydration. Severe cases of pancreatitis may require ICU admission with cardiovascular and respiratory support. Regardless of the patient’s condition, cholecystectomy should be reserved until after the pancreatitis has resolved. It has been suggested that the morbidity and mortality associated with pancreatitis is improved when patients undergo ERCP within 2 days of onset of symptoms. ERCP may be able to remove an impacted stone and thus allow for pancreatic decompression. This approach is generally considered in patients with moderate or severe pancreatitis.

Consideration as to the presence of a persistent bile duct stone should be made prior to proceeding with cholecystectomy. In most circumstances, normalization of serum lipase, amylase, and liver function tests (if originally elevated) occurs rapidly. In these circumstances, no imaging of the biliary tree is required due to the low probability of a persistent bile duct stone. However, patients with persistent abnormalities of their liver functions, amylase, or lipase should be evaluated for the presence of common bile duct stones. Biliary imaging may be obtained by means of intraoperative cholangiography at the time of cholecystectomy, perioperative ERCP, or magnetic resonance cholangiopancreatography (MRCP). MRCP is least invasive of the modalities but is only diagnostic. ERCP allows for both visualization and extraction of stones up to 1.5 cm in size. ERCP may be utilized to extract common bile duct stones either antecedent or subsequent to cholecystectomy. Common bile duct stones not amenable to endoscopic removal are generally removed operatively by performing a common bile duct exploration.

The overall long-term outcome of pancreatitis is related to the severity of the disease. Localized morbidity includes pancreatic necrosis, splenic vein thrombosis with gastric varices, hemorrhagic pancreatitis, and pancreatic abscess formation. Systemic morbidity can involve multisystem organ failure or even death.

Cholangitis

Essentials of Diagnosis

• Persistent RUQ pain.
  
• Jaundice.
  
• Fever.
  
• Hypotension, mental status changes (acute suppurative cholangitis).

Cholangitis is defined as inflammation of the biliary system. It is most commonly caused by an impacted gallstone at the ampulla of Vater preventing bile drainage into the duodenum, though other etiologies such as extrinsic compression from an adjacent mass or inflammatory process or a primary tumor of the ampulla, duodenum, or bile duct should also be considered. Cholangitis is considered a medical emergency.

Patients with cholangitis may present with Charcot’s triad (fever, right upper quadrant pain, and jaundice) or with Reynolds’ pentad (the addition of hypotension or mental status changes). Laboratory studies will show hyperbilirubinemia and leukocytosis. Ultrasound will likely show biliary ductal dilatation.

With clinical suspicion of cholangitis, patients should immediately be intravenously resuscitated and given broad-spectrum antibiotics. Biliary decompression should be urgently performed by ERCP. If ERCP fails to resolve the obstruction or is not available, percutaneous transhepatic cholangiography (PTC) with drainage may be performed. In the presence of stones, once biliary decompression has been performed, cholecystectomy should be performed electively following resolution of the cholangitis. In rare circumstances in which percutaneous or endoscopic biliary drainage is not possible, urgent cholecystectomy with common bile duct exploration should be performed.

The mortality associated with cholangitis varies widely and is related to the underlying etiology of the cholangitis. Cholangitis secondary to stones is associated with a low overall mortality provided the patient can be successfully supported through the infectious period. Cholangitis related to an underlying periampullary malignancy requires careful oncologic consideration prior to surgical intervention. This may require a more involved oncologic resection (such as a pancreaticoduodenectomy or extrahepatic biliary resection) or palliative care, depending on the extent of the malignancy. In the event of an unresectable periampullary tumor, a biliary bypass (hepaticojejunostomy) may be considered. Most periampullary malignancies are associated with poor 5-year survival even with complete extirpation of the tumor.

Biliary Tumor

Gallbladder Polyps

Gallbladder polyps are present in about 5% of the population and are commonly found incidentally during abdominal ultrasonography. The different types of polyps include cholesterolosis, adenomyomatosis, hyperplastic cholecystosis, and adenocarcinomatosis. The goal of surgical management is to identify which polyps are cancerous (adenocarcinoma) or at risk to develop cancer (adenomyomatosis) and select these patients for cholecystectomy.

Unfortunately, short of cholecystectomy, there is currently no way to distinguish among the different types of gallbladder polyps. With the relative safety of laparoscopic cholecystectomy, some advocate cholecystectomy for all gallbladder polyps. This strategy will result in the removal of many benign asymptomatic polyps. Retrospective studies have suggested that young patients (<50 years old) with small asymptomatic polyps (<1cm in size) and without associated gallstones may be observed with serial ultrasound examinations. Patients who have polyps with associated gallstones or are older than 50 years should be referred for cholecystectomy. Polyps larger than 1 cm should also warrant cholecystectomy. In the event of gallbladder cancer in the surgical specimen, the depth of invasion dictates the next course of therapy.

Gallbladder Cancer

Patients with gallbladder cancer may have similar presentations to those with symptomatic cholelithiasis or chronic cholecystitis. As most gallbladder cancer presents late in the disease progression, systemic complaints including gradual weight loss and loss of appetite may also be apparent. Since presentation is often thought to be related to gallstone disease, ultrasound is usually the initial diagnostic modality used. Ultrasound findings of a mass larger than 1 cm, a calcified gallbladder wall, discontinuity of gallbladder wall layers, and loss of interface between the gallbladder wall and the liver should raise suspicion of gallbladder cancer. Computed tomography is useful in these circumstances to delineate anatomic structures for resectability, as well as evidence of metastatic disease.

Presence of para-aortic or peripancreatic lymphadenopathy is deemed unresectable disease. This can be confirmed with endoscopic ultrasound with biopsies. Cancers that are limited to the mucosa or muscular layer of the gallbladder can be treated with cholecystectomy with negative margins alone. Tumors that invade the pericholecystic connective tissue require resection of the gallbladder fossa with en bloc cholecystectomy. Tumors that invade the liver require formal resection of the involved segments. Tumors that invade the cystic duct into the common bile duct also require en bloc extra hepatic biliary resection. Unfortunately, 15%-50% of tumors that penetrate the muscular wall of the gallbladder have nodal disease that will make them unresectable. The 5-year survival of early tumors (those confined to the muscular or mucosal layer) is excellent (90%-100%). The survival for more advanced tumors is measured in terms of weeks or months.

Choledochal Cyst

Classically, choledochal cysts are described as a palpable right upper quadrant mass in a young female with jaundice. Most choledochal cysts are described in Asian populations but are increasingly seen in the United States, males, and in older patients. Choledochal cysts are classified by their anatomic location with most being solitary fusiform dilatation of the extrahepatic biliary tree. Their presentation in Western series is similar to symptomatic cholelithiasis. They can be easily seen on ultrasound provided the ultrasonagrapher evaluates the biliary tree in addition to the gallbladder.

Choledochal cysts are associated with a seventy-fold increased incidence of cholangiocarcinoma, so surgical resection is indicated when discovered. Operative treatment involves resection of the entire extra-hepatic biliary tree, cholecystectomy, and reconstruction with a Roux-en-Y hepaticojejunostomy. Surgical resection is considered curative; a recent study reported no subsequent malignancy over 30 years in patients without cancer at the time of cyst excision.

Cholangiocarcinoma

For a variety of reasons, cholangiocarcinomas along with other right upper quadrant malignancies are associated with very poor survival. (1) These lesions often present late and are not amenable to resection. (2) Their biological activity is not well understood and systemic therapy offers little benefit. (3) Operative resection is technically difficult and patients need to be seen in specialized centers.

The vast majority of cholangiocarcinomas present with jaundice, sometimes in the setting of cholangitis. Ultrasound will often show a dilated proximal biliary tree. ERCP and endoscopic ultrasound are useful to delineate the anatomy of the tumor. Preoperative endoscopic brushings are often nondiagnostic and should not be aggressively pursued in patients with resectable disease on cross-sectional imaging. While most proximal cholangiocarcinomas (70%) are not amenable to resection, approximately half of distal tumors may be resected. Resection involves pancreaticoduodenectomy for distal tumors whereas cholangiocarcinoma of the proximal system requires an extrahepatic biliary resection with Roux-en-Y hepaticojejunostomy. Five-year survival remains poor even after complete resection (20%-25%). For patients with unresectable disease, survival is again measured in weeks or months.

Viral Hepatitis

Essentials of Diagnosis

• Variable prodromal signs and symptoms.
  
• Positive specific viral hepatitis tests.
  
• Elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

Acute viral hepatitis is a worldwide problem, and in the United States alone there are probably between 200,000 and 700,000 cases per year according to the Centers for Disease Control and Prevention (CDC). Over 32% of cases are caused by hepatitis A virus (HAV), 43% by hepatitis B virus (HBV), 21% by hepatitis C virus (HCV), and the remainder are not identified. Although few deaths (~250) are reported yearly from acute hepatitis, considerable morbidity can result from chronic hepatitis caused by HBV and HCV infections, and mortality from complications can be pronounced for years to come.

Hepatitis A

General Considerations

Hepatitis A, first identified in 1973, is the prototype for the former diagnosis of infectious hepatitis. Over the past several decades, the incidence of HAV infection has varied considerably, and a high number of cases are unreported. HAV is a very small viral particle that is its own unique genus (hepatovirus).

Most individuals infected worldwide are children. In general, there are four patterns of HAV distribution (high, moderate, low, and very low), which roughly correspond to differing socioeconomic and hygienic conditions. Countries with poor sanitation have the highest rates of infection. Most children younger than 9 years in these countries have evidence of HAV infection. Countries with moderate rates of infection have the highest incidence in later childhood; food and waterborne outbreaks are more common. In countries with low endemicity, the peak age of infection is likely to be at early adulthood, and, in very low endemic countries, outbreaks are uncommon.