ANATOMY AND PHYSIOLOGY
The liver is located in the right upper quadrant of the abdomen and is bounded superiorly and posteriorly by the diaphragm, laterally by the ribs, and inferiorly by the gallbladder, stomach, duodenum, colon, kidney, and right adrenal. It is covered by Glisson capsule and peritoneum. The right and left lobes of the liver are defined by the plane formed by the gallbladder fossa and the inferior vena cava. The falciform ligament between the liver and diaphragm is a landmark between the lateral and medial segments of the left lobe. The coronary ligaments continue laterally from the falciform and end at the right and left triangular ligaments. These ligaments define the bare area of the liver, an area devoid of peritoneum. The liver parenchyma is divided into eight segments on the basis of arterial and venous anatomy (see Color Plate 5). Segment 1 is also known as the caudate lobe. It is not visible from the ventral surface of the liver, being tucked behind segment 4. The caudate is juxtaposed to the inferior vena cava and has venous branches that drain directly into the cava. These branches are quite fragile and must be carefully controlled if resection of the caudate is required. Segments 2, 3, and 4 form the left lobe of the liver, whereas segments 5, 6, 7, and 8 comprise the right lobe. Segment 4 may be divided into cranial segment 4a and caudal segment 4b.
The hepatic circulation is based on a portal circulation that provides the liver with first access to all intestinal venous flow. Seventy-five percent of total hepatic blood flow is derived from the portal vein, which is formed from the confluence of the splenic and superior mesenteric veins. The remaining blood supply comes from the hepatic artery via the celiac axis. The right hepatic artery arises from the superior mesenteric artery in 15% of patients. When this occurs, the artery will run posterior to the bile duct on the right side of the hilum, and it is termed a replaced right hepatic artery. The left hepatic artery arises from the left gastric in 15% of patients, called a replaced left hepatic artery. In this instance, the artery will run in the cranial portion of the gastrohepatic ligament. Other arterial variants include a completely replaced hepatic artery, which arises from the superior mesenteric artery, and a middle hepatic artery, which occurs when the segment 4 branch arises in the hilum. Blood leaving the liver enters the inferior vena cava via the right, middle, and left hepatic veins. Often there is an accessory right hepatic vein that leaves the liver caudad to the principle right hepatic vein. This vein must be controlled separately during right hepatic lobectomy.
The hepatic hilum can be palpated by placing a finger through the foramen of Winslow (epiploic foramen) into the lesser sac (Fig. 6-1). This is an important maneuver because it provides control of the hepatic hilum (hepatoduodenal ligament), within which runs the hepatic artery, portal vein, and bile duct. A Pringle maneuver, which involves placing a clamp on the hilum, disrupts most blood flow to the liver and can greatly reduce bleeding during liver resection (Fig. 6-2). This maneuver also makes the liver ischemic and can cause arterial thrombosis. As a result, it should be used for a limited amount of time and only when necessary.
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Figure 6-1 • The lesser sac. The lesser sac is behind the hepatoduodenal and hepatogastric ligaments. Entry is through the epiploic foramen (foramen of Winslow). From Sadler T. Langman's Medical Embryology, Ninth Edition Image Bank. Baltimore: Lippincott Williams & Wilkins, 2003. |
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Figure 6-2 • Pringle maneuver. Occlusion of the porta hepatis decreases blood flow to the liver to slow bleeding during liver surgery. From Blackbourne LH. Advanced Surgical Recall. 2nd ed. Baltimore: Lippincott Williams & Wilkins, 2004. |
The liver is the site of many critical events in energy metabolism and protein synthesis. Glucose is taken up and stored as glycogen, and glycogen is broken down, as necessary, to maintain a relatively constant level of serum glucose. The liver is able to initiate gluconeogenesis during stress, and the liver can oxidize fatty acids to
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ketones, which the brain can use as an energy source. Proteins synthesized in the liver include the coagulation factors fibrinogen, prothrombin, prekallikrein, high-molecular-weight kininogen, and factors V, VII, VIII, IX, X, XI, and XII. Of these, prothrombin and factors VII, IX, and X are dependent on vitamin K. The anticoagulant warfarin (Coumadin) affects these vitamin K–dependent pathways, resulting in an increased pro- thrombin time. Albumin and alpha globulin are pro-duced solely in the liver.
The digestive functions of the liver include bile synthesis and cholesterol metabolism. Heme is used to form bilirubin, which is excreted in the bile after conjugation with glycine or taurine. Bile emulsifies fats to aid their digestion and plays a role in vitamin uptake. Bile salts excreted into the intestine are reabsorbed into the portal circulation. This cycle of bile excretion and absorption is termed the enterohepatic circulation. Total body bile circulates approximately
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10 times per day in this loop. More than 95% of excreted bile is reabsorbed, and the remainder must be resynthesized. The rate-limiting step of cholesterol synthesis involving the enzyme 3-hydroxy-3-methyl-glutaryl–coenzyme A reductase occurs in the liver, as does cholesterol metabolism to bile salts.
Detoxification occurs in the liver through two pathways. Phase I reactions involve cytochrome P450 and include oxidation, reduction, and hydrolysis. Phase II reactions consist of conjugation. These reactions are critical to destruction or renal clearance of toxins. The dosing of all oral drugs is determined only after considering the first-pass effect of the drug through the liver. The initial hydroxylation of vitamin D occurs in the liver. Immunologic functions are mediated by Kupffer cells, the resident liver macrophages.
BENIGN LIVER TUMORS
PATHOLOGY
Benign liver tumors include hepatocellular adenoma (see Color Plate 6), focal nodular hyperplasia, hemangioma, and lipoma. Hemangiomas are categorized into capillary and cavernous types, the former being of no clinical consequence and the latter capable of attaining large size and rupturing.
EPIDEMIOLOGY
Only 5% of liver tumors are benign, with hemangioma being the most common. Approximately 7% of people have a cavernous hemangioma at autopsy. The incidence of adenoma is one per million in women without a history of oral contraceptive use. These medicines increase the risk by a factor of 40. This lesion most commonly occurs in women between 30 and 50 years of age. Adenoma and focal nodular hyperplasia are five times more common in female patients.
History
Patients with adenomas and hemangiomas can be asymptomatic or present with dull pain; rupture can produce sudden onset of severe abdominal pain. These lesions can also become large enough to cause jaundice or symptoms of gastric outlet obstruction, including nausea and vomiting. Focal nodular hyperplasia is rarely symptomatic.
PHYSICAL EXAMINATION
Large lesions can be palpated. Jaundice may occur in patients if the tumor causes bile duct obstruction.
DIAGNOSTIC EVALUATION
These lesions are most often found incidentally at laparotomy or on imaging studies requested for other reasons. Laboratory evaluation is often unremarkable, although hemorrhage in an adenoma can lead to hepatocellular necrosis and a subsequent increase in transaminase levels. Hemangioma can cause a consumptive coagulopathy. Ultrasound differentiates cystic from solid lesions. Triple-phase computed tomography (CT) is the best study for distinguishing between various types of benign and malignant lesions, but in certain cases, this determination is not possible. Adenomas are typically low-density lesions; focal nodular hyperplasias may appear with a filling defect or central scar, whereas hemangiomas have early peripheral enhancement after contrast administration. Hemangiomas should not be biopsied because of the risk of bleeding.
TREATMENT
Patients with adenoma who are using oral contraceptives should stop. If the lesion does not regress, resection should be considered in otherwise healthy individuals because of the risk of malignant degeneration or hemorrhage. Relative contraindications to resection include a tumor that is technically difficult to resect or tumors of large size in which a large portion of the liver would need to be removed. Symptomatic hemangiomas should be resected, if possible. Because focal nodular hyperplasia is not malignant and rarely causes symptoms, it should not be resected unless it is found incidentally at laparotomy and is small and peripheral enough to be wedged out easily.
LIVER CANCER
PATHOLOGY
Liver cancers are hepatomas, also known as hepatocellular carcinoma, or metastases from other primaries (see Color Plate 7).
EPIDEMIOLOGY
Ninety-five percent of liver tumors are malignant. Hepatoma is one of the most common malignancies
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in the world, but rates in the United States are relatively low (approximately two per 100,000). It is more common in male than in female patients.
ETIOLOGY
Cirrhosis is a predisposing factor to hepatoma; as such, hepatitis B, the leading cause of cirrhosis, and alcoholism are associated with hepatoma development. Fungal-derived aflatoxins have been implicated as causes of hepatoma, as have hemochromatosis, smoking, vinyl chloride, and oral contraceptives.
HISTORY
Patients with hepatoma may complain of weight loss, right upper quadrant or shoulder pain, and weakness. Hepatic metastases are often indistinguishable from primary hepatocellular carcinoma.
PHYSICAL EXAMINATION
Hepatomegaly may be appreciable, and signs of portal hypertension, including splenomegaly and ascites, may be present. Jaundice occurs in approximately half of patients.
DIAGNOSTIC EVALUATION
Laboratory examination may reveal abnormal liver function tests. α-Fetoprotein is a specific marker for hepatoma but can also be elevated in embryonic tumors. Radiographic studies are used to differentiate benign and malignant lesions. Ultrasonography can distinguish cystic from solid lesions, whereas CT or magnetic resonance imaging can reveal multiple lesions and clarify anatomic relationships (Fig. 6-3). They can also demonstrate nodularity of the liver, hypersplenism, and portal hypertension, indicative of underlying liver disease. Hepatic arteriography can diagnose a hemangioma. Because most cancers occur in the setting of liver disease and cirrhosis, it is important to perform viral studies for hepatitis.
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Figure 6-3 • Hepatocellular carcinoma with portal venous thrombosis. Computed tomography image demonstrates portal vein thrombus (black arrows on thrombosed right and left portal veins). A mass (curved white arrows) is present in the right lobe of the liver. From Kelsen DP, Daly JM, Kern SE, et al. Gastrointestinal Oncology: Principles and Practice. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:10–16. |
TREATMENT
Before consideration of resection, the underlying health of the liver should be assessed using the Child-Turcotte-Pugh scoring system (Table 6-1). Patients with Child class C disease will generally not tolerate a resection; patients with Child class B disease may tolerate a limited resection.
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TABLE 6-1 Child-Turcotte-Pugh Scoring System for Cirrhosis |
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If the patient is a surgical candidate, treatment involves resection of the tumor. Survival without treatment averages 3 months; resection can extend survival to 3 years, with a 5-year survival rate of 11% to 46%.
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The decision to resect the tumor depends on comorbid disease and the location and size of the tumor. When possible, wedge resection should be performed, because formal hepatic lobectomy does not provide any additional survival benefit. Patients with small tumors who are not candidates for resection because of tumor location or concomitant cirrhosis should be considered for liver transplantation. Liver transplantation is becoming an increasingly attractive option for these patients, providing good long-term survival. Patients who meet the Milan criteria (tumor <5 cm or no more than three tumors, the largest of which is <3 cm) will receive extra points on the liver transplant list.
Metastatic disease occurs in decreasing frequency from lung, colon, pancreas, breast, and stomach. When colon cancer metastasizes to the liver, resection of up to three lesions has been shown to improve survival and should be attempted as long as the operative risk is not prohibitive. In general, liver metastases from other tumors should not be resected.
LIVER ABSCESSES
ETIOLOGY
Liver abscesses are most frequently due to bacteria, amebas, or the tapeworm Echinococcus. Bacterial abscesses usually arise from an intra-abdominal infection in the appendix, gallbladder, or intestine but may be due to trauma or a complication of a surgical procedure. Causative organisms are principally gut flora, including Escherichia coli, Klebsiella, enterococci, and anaerobes (including Bacteroides). Amebic abscesses owing to Entamoeba histolytica are an infrequent complication of gastrointestinal amebiasis.
EPIDEMIOLOGY
Pyogenic abscesses are responsible for fewer than one in 500 adult hospital admissions. Amebic abscesses occur in 3% to 25% of patients with gastrointestinal amebiasis (Fig. 6-4). Risk factors include HIV, alcohol abuse, and foreign travel. Echinococcus is most commonly seen in Eastern Europe, Greece, South Africa, South America, and Australia; although rare in the United States, it is the most common cause of liver abscesses worldwide (Fig. 6-5).
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Figure 6-4 • Amebic abscesses of the liver. The cut surface of the liver shows multiple abscesses containing "anchovy paste" material. From Rubin E, Farber JL. Pathology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:9–75. |
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Figure 6-5 • A computed tomography scan shows a multilocular cyst in the liver of a patient with hydatid disease. From Sun, Tsieh MD. Parasitic Disorders: Pathology, Diagnosis, and Management. 2nd ed. Baltimore: Lippincott Williams & Wilkins, 1999. |
HISTORY
Patients with pyogenic or amebic abscesses usually have nonspecific complaints of vague abdominal pain, weight loss, malaise, anorexia, and fever. Travel to an endemic region may suggest Echinococcus.
PHYSICAL EXAMINATION
The liver may be tender or enlarged, and jaundice may occur. Rupture of an abscess can lead to peritonitis, sepsis, and circulatory collapse.
DIAGNOSTIC EVALUATION
The white blood cell count and transaminase levels are elevated. Antibodies to ameba are found in 98% of patients with amebic abscesses but in fewer than 5% of those with pyogenic abscesses. Echinococcal infection
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produces eosinophilia and a positive heme agglutination test. Ultrasonography is approximately 90% sensitive for demonstrating a lesion; CT is slightly better. The presence of multiple cysts, or "sand," on CT is suggestive of Echinococcus. Sampling of the cyst contents with CT or ultrasound guidance reveals the causative organism in the case of pyogenic abscesses but does not usually lead to a diagnosis in amebic abscesses. Aspiration of echinococcal cysts is contraindicated because of the risk of contaminating the peritoneal cavity.
TREATMENT
Pyogenic abscesses require antibiotics alone or in combination with percutaneous or open drainage. Amebic abscesses are treated with metronidazole (Flagyl), with or without chloroquine, and surgical drainage is reserved for complications, including rupture. Echinococcal abscesses require an open procedure. Scolecoidal agents (e.g., ethanol or 20% sodium chloride) are instilled directly into the cyst, followed by drainage, with care not to spill the organisms into the peritoneum.
PORTAL HYPERTENSION
ETIOLOGY
Portal hypertension is caused by processes that impede hepatic blood flow, either at the presinusoidal, sinusoidal, or postsinusoidal levels. Presinusoidal causes include schistosomiasis and portal vein thrombosis. The principal sinusoidal cause in the United States is cirrhosis, usually caused by alcohol but also by hepatitis B and C. Cirrhosis develops in approximately 15% of alcoholics. Postsinusoidal causes of portal hypertension include Budd-Chiari syndrome (hepatic vein occlusion), pericarditis, and right-sided heart failure.
COMPLICATIONS
Bleeding varices are a life-threatening complication of portal hypertension. When portal pressures increase, flow through the hemorrhoidal, umbilical, or coronary veins becomes the low-resistance route for blood flow. The coronary vein empties into the plexus of veins draining the stomach and esophagus (Fig. 6-6). Engorgement of these veins places the patient at risk of bleeding into the esophagus or stomach.
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Figure 6-6 • Selected collateral circulation in portal hypertension. |
HISTORY
Alcoholism, hepatitis, or previous variceal hemorrhage are common.
PHYSICAL EXAMINATION
A variety of physical findings, including ascites, jaundice, "cherubic face," spider angioma, testicular atrophy, gynecomastia, and palmar erythema, may suggest the diagnosis.
DIAGNOSTIC EVALUATION
Laboratory examination may reveal increased liver enzymes, which may return to normal with advanced cirrhosis as the amount of functioning hepatic parenchyma decreases. Tests of liver synthetic function, including clotting times and serum albumin, may be abnormal.
TREATMENT
Patients with portal hypertension are placed on beta-blockers to decrease the risk of bleeding. Endoscopic surveillance and banding are useful in preventing bleed- ing episodes.
For patients with upper gastrointestinal bleeds, large-bore intravenous lines and volume resuscitation should be started immediately. A nasogastric tube should be placed to confirm the diagnosis. If the patient cannot be lavaged clear, suggesting active bleeding, emergency endoscopy is both diagnostic and therapeutic. Endoscopy is >90% effective in controlling acute bleeding from esophageal varices. Should this fail, balloon tamponade with a Sengstaken-Blakemore tube and vasopressin infusion should be considered. Use of the Sengstaken-Blakemore tube involves passing the gastric
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balloon into the stomach, exerting gentle traction on the tube, and then inflating the esophageal balloon to tamponade bleeding. Although effective in stopping life-threatening hemorrhage, the tube can produce gastric and esophageal ischemia and must be used with extreme caution. Transjugular intrahepatic portosystemic shunting has a high rate of success in controlling acute bleeding and is usually preferred to an emergent surgical shunt, although this is also an option (Fig. 6-7).
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Figure 6-7 • Transjugular intrahepatic portosystemic shunting. A metallic shunt is placed from the hepatic vein to the right portal vein via a catheter introduced through the internal jugular vein. The shunt will typically continue into the main portal vein. From Blackbourne LH. Advanced Surgical Recall. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2004. |
Approximately 40% of patients with varices will develop a bleeding complication. Seventy percent of patients with a first episode will rebleed. For this reason, a definitive procedure should be considered after the initial episode is controlled.
Patients with bleeding varices and cirrhosis will ordinarily be considered for liver transplantation. If there is no cirrhosis, or if the patient has good residual liver function, surgical shunts have better long-term patency than transjugular intrahepatic portosystemic shunting. Surgical shunts are divided into nonselective and selective shunts. Nonselective shunts divert the entire portal blood flow into the systemic circulation. An example is an end-to-side portacaval shunt, in which the portal vein is divided and drained directly into the inferior vena cava. Selective shunts divert only a portion of the portal blood away from the liver. The most common is the distal splenorenal shunt, in which portal blood is shunted through the renal vein and into the cava. Because there is still blood going to the liver to be detoxified, patients with selective shunts have less encephalopathy and equivalent success in preventing rebleeding.
As a last resort in patients with bleeding esophageal varices, a Sugiura procedure can be performed. During this procedure, the varices are disconnected from the portal circulation by complete esophageal transection and reanastomosis. This procedure also includes splenectomy, proximal gastric devascularization, vagot-comy, and pyloroplasty.
In patients with Budd-Chiari syndrome, side-to-side portacaval shunt can be life-saving.
KEY POINTS