Chapter 43. Hepatic Abscess and Cystic Disease of the Liver

The differential diagnosis of cystic lesions of the liver includes bilomas, abscesses, parasitic disease, simple cysts, polycystic liver disease (PCLD), biliary cystadenoma, and cystadenocarcinoma.1 The disease spectrum includes infectious, traumatic, congenital, and neoplastic hepatic lesions that are relatively uncommon. While significant improvements have been made in the diagnosis, treatment, and outcome of many of these cystic hepatic lesions, controversy continues regarding the best treatment option. Many classification systems exist for these lesions; however, the one used in this chapter is presented in Table 43-1.

The first description of a hepatic abscess is credited to Hippocrates in the year 4000 BC. Ochsner's classic 1938 paper2 described this disease as one that occurred in young males with pylephlebitis, usually due to appendicitis, and resulting in liver abscess. At that time, pyogenic liver abscesses carried a case-fatality rate of 77%2 and open surgical drainage remained the treatment of choice for many years. In 1953, McFadzean and associates3 in Hong Kong advocated closed aspiration and antibiotics for treatment of solitary pyogenic liver abscess; however, this treatment did not gain widespread acceptance until imaging advancements in the 1980s allowed for precise localization and a percutaneous approach to treatment. In recent decades, the predominant etiology of pyogenic liver abscess has changed from pylephlebitis to a biliary origin, and more recent reports from Asia and the United States have noted an increase in incidence of cryptogenic liver abscesses. Fortunately, advanced imaging techniques and improved therapeutic modalities have decreased the case-fatality rate for this disease to 6–26%.4,5

Etiology

Kupffer cells act as a filter for the clearance of microorganisms in the liver. These organisms reach the liver through the bloodstream, biliary tree, or direct extension. Abscesses occur when normal hepatic clearance mechanisms fail or the system is overwhelmed. Parenchymal necrosis and hematoma secondary to trauma, obstructive biliary processes, ischemia, and malignancy also promote invasion of microorganisms.

In order to appropriately treat the abscess, source control is required. Six distinct categories have been identified as potential sources: (1) bile ducts, causing ascending cholangitis; (2) portal vein, causing pylephlebitis from appendicitis or diverticulitis; (3) direct extension from a contiguous disease; (4) trauma due to blunt or penetrating injuries; (5) hepatic artery due to septicemia; and (6) cryptogenic6,7 (Fig. 43-1).

Biliary disease accounts for 35–40% of all pyogenic liver abscesses, and 40% of pyogenic liver abscesses of biliary origin are related to an underlying malignancy.6 Obstruction of the biliary tree is the norm, and cholangitis is present in up to one-half of these patients.8 Intrahepatic stones and related biliary stricture are predominant in Eastern series whereas malignant biliary obstruction is more common in the West.7 Any manipulation of the biliary tree—namely cholangiography, percutaneous transhepatic stents, endoscopic stent placement, and biliary-enteric anastomoses—also predispose patients to cholangitis and pyogenic liver abscess. Malignancy contributes to poor nutrition and immunosuppression, potentiating the whole process.

Intestinal pathology is responsible for 20% of all pyogenic liver abscesses. Transient bacteremia due to bacterial translocation or frank gastrointestinal perforation causes overwhelming numbers of microorganisms to spread via the portal venous system to the liver. In the preantibiotic era, 43% of Ochsner's 622 patients seeded the liver through the portal vein, and appendicitis was the most common source (34%).2 Today, appendicitis accounts for only 2% of all pyogenic liver abscesses. Diverticulitis, perforated colon cancers, and abscesses elsewhere in the abdomen and pelvis remain common causes of pyogenic liver abscesses. Primary and metastatic liver tumors may also become colonized with enteric flora.

Contiguous extension of gangrenous cholecystitis, perforated ulcers, and subphrenic abscesses is also a reported source for pyogenic liver abscess. In addition, liver trauma causes parenchymal necrosis and clot, which creates an ideal milieu for the seeding and proliferation of microorganisms and subsequent abscess formation. Ablative procedures for tumors can create this same environment. Microorganisms can then seed these areas of necrosis through intraoperative contamination, biliary-enteric anastomoses, external drains involving the biliary tree, or percutaneous drains placed near the site of trauma or ablation.

Arterial embolization of bacteria via the hepatic artery causes approximately 12% of pyogenic liver abscesses. Intravenous drug abuse accounts for most of these cases, but hepatic artery chemoembolization and umbilical artery catheterization have also been cited. Arterial embolization can also occur from distant infection in the heart, lungs, kidneys, bones, ears, and teeth.9

Cryptogenic abscesses occur in 10–45% of patients, depending on the aggressiveness of investigation used to define the source.9,10 Patients with cryptogenic abscesses usually have comorbidities such as diabetes, immunosuppression, or malignancy. Abscesses in these patients tend to be solitary and usually contain a single anaerobe.

Incidence

Pyogenic liver abscess affected 5–13 patients per 100,000 admissions before 1970 and accounts for approximately 15 cases per 100,000 admissions today. Seeto and Rocky11 reported an incidence nearly twofold that of earlier reports (22 per 100,000). This rising incidence is attributed to a more aggressive management approach to hepatobiliary and pancreatic cancers as well as major improvements in diagnostic imaging.7,12

Predisposing Factors

Pyogenic liver abscesses occur more frequently in adults with comorbid conditions, including diabetes mellitus, cirrhosis, pancreatitis, inflammatory bowel disease, pyelonephritis, and peptic ulcer disease. Solid-organ cancers as well as lymphoma and leukemia are present in 17–36% of patients with liver abscesses.9 Branum and associates reported an increased incidence in patients with underlying malignancy and immunosuppression.13 Civardi and colleagues14 as well as Lambiase and coworkers15 have reported series of patients with liver abscesses and underlying acquired immune deficiency. The combination of chemotherapy and steroid use is thought to be responsible in these cases.

In addition to comorbidities, age plays a role in the development of pyogenic liver abscess. The age of pyogenic liver abscess patients has increased since 1938. This disease has now become one of the middle-aged and elderly with a reported mean age of 47–65 years. Older patients are more likely to have a biliary etiology or underlying malignancy, whereas younger patients are more likely to be alcoholic males with a cryptogenic origin. Polymicrobial or anaerobic infections with multidrug-resistant organisms, a pleural effusion, inappropriate initial antibiotic selection, and a greater severity of illness on admission occur more frequently in older patients. Underlying malignancy is more prevalent in older patients and is a risk factor for developing anaerobic infections. Age and an APACHE II (Acute Physiology and Chronic Health Evaluation II) score of greater than 15 on admission are risk factors for case fatality in older patients. The case-fatality rate in older patients is related to host conditions, rather than characteristics of the abscess itself. Clinicians should apply an aggressive approach for older patients exhibiting a poor response to primary treatment, particularly in those with a greater severity of illness on admission.16

In children, pyogenic liver abscesses tend to occur in the setting of host-defense abnormalities or immune disorders. Complement deficiencies, chronic granulomatous disease, leukemia, and other malignancies place these children at increased risk for liver abscess. Hepatic abscesses are also seen in sickle cell anemia, congenital hepatic fibrosis, PCLD, and after liver transplant (Table 43-2).9

Pathology

The source of the liver abscess is predictive of the number, location, and size of the abscess affecting a given patient. In general, portal, traumatic, and cryptogenic hepatic abscesses are solitary and large, while biliary and arterial abscesses are multiple and small. Huang and associates7 reported that 63% of patients had abscesses involving the right lobe, 14% had abscesses involving the left lobe, and 22% had bilobar disease. The number of bilateral and multiple abscesses have increased as more patients present with a biliary etiology. Bilateral disease may be seen in 90% of patients with an arterial or biliary source. In contrast, those with intra-abdominal infections frequently present with right lobe abscesses due to preferential flow from the superior mesenteric vein. Fungal abscesses are usually multiple, bilateral, and miliary.9

Bacteriology

Diagnostic confirmation of a pyogenic liver abscess involves aspiration of the abscess itself and obtaining blood cultures that are positive. Abscess cultures are positive for growth in the majority (80–97%), whereas blood cultures are positive in only 50–60% of cases.11,14Escherichia coli, Klebsiella species, enterococci, and Pseudomonas species are the most common aerobic organisms cultured in recent series, whereas Bacteroides species, anaerobic streptococci, and Fusobacterium species are the most common anaerobes.12 Huang and colleagues7 cited the increased use of indwelling biliary stents as the cause of an increasing incidence of Klebsiella, streptococcal, staphylococcal, and pseudomonal species in liver abscesses. They also noted the presence of fungi in 22% of cultures taken between 1973 and 1993 compared to only 1% between 1952 and 1972. Broad-spectrum antibiotic use in the treatment of cholangitis was thought to be the causative factor. Candida fungal abscesses are also found in cancer patients who have undergone cytotoxic chemotherapy. Mycobacterium tuberculosis is a common infecting organism in the acquired immune deficiency syndrome8 (Table 43-3).

The species of microorganism found in a hepatic abscess is related to the source. The biliary tree gives rise to abscesses predominantly composed of E. coli and Klebsiella. E. coli, enterococci, and anaerobes are the main organisms recovered from abscesses related to the intestinal tract. Anaerobes are the usual microorganisms found in cryptogenic liver abscesses in Western countries. Negative cultures may relate to poor anaerobic culture technique or the use of broad-spectrum antibiotics prior to abscess drainage. In series where careful attention is paid to anaerobic organism recovery, anaerobes may be detected in 10–17%, most often B. fragilis.17 If suspected bacterial cultures are repeatedly negative, amebic and parasitic organisms must be considered because they are difficult to identify by routine staining and culture techniques.9

Klebsiella pneumoniae is the number one pathogen found in pyogenic liver abscesses in Taiwan and Korea and usually occurs in a monobacterial as opposed to mixed bacterial setting. Investigation into the K antigen serotype revealed that the K1 serotype accounts for 60% of K. pneumoniae strains causing liver abscess in these countries. The reason why liver abscess caused by K1 serotype K. pneumoniae strains has been emerging has not been elucidated. In contrast, this particular serotype is rarely found in clinical isolates from Western countries. In Taiwan and Korea, the average age to develop a K. pneumoniae liver abscess is 55–60 years. These abscesses are twice as likely to be diagnosed in men than in women and are much more likely to be cryptogenic in origin (64%). Diabetes is a known risk factor for developing K. pneumoniae liver abscess and is a significant risk factor for embolic complications, especially endophthalmitis.17,18

Diagnosis

The clinical presentation of pyogenic liver abscess is usually subacute and nonspecific, leading to delays in presentation, diagnosis, and treatment. In Seeto and Rocky's review11 of 142 patients with pyogenic liver abscesses, the classic triad of fever, jaundice, and right upper quadrant (RUQ) tenderness was present in fewer than 10% of patients overall.

Clinical Presentation

Most patients have fever (92%) and 50% have abdominal pain, but only half have pain in the right upper quadrant. Diarrhea occurs in less than 10% of patients. The liver may be tender (65%) and enlarged (48%), and the patient may appear jaundiced (54%). Other nonspecific complaints include malaise, anorexia, and nausea. If the diaphragm is involved, pleuritic chest pain, cough, or dyspnea may occur. If the abscess ruptures, peritonitis and sepsis may be presenting features 7,8,11 (Table 43-4).

Laboratory Evaluation

Leukocytosis is present in 70–90%, an elevated alkaline phosphatase in 80%, and an elevated bilirubin and transaminases in 50–67% of patients. Anemia, hypoalbuminemia, and prolonged prothrombin time are seen in 60–75% of patients.7,8,11,12

Radiology

Plain films such as chest radiographs are abnormal in 50% of patients. Findings may include an elevated right hemidiaphragm, a right pleural effusion, and/or right lower lobe atelectasis. Abdominal films may show hepatomegaly, air-fluid levels in the presence of gas-forming organisms, or portal venous gas if pylephlebitis is the source (Fig. 43-2). Ultrasound (US) will distinguish solid from cystic lesions and is cost-effective and portable. US is 80–95% sensitive but has limited utility in the morbidly obese and in lesions that are located under the ribs or located in an inhomogeneous liver.

Computed tomography (CT) is more sensitive (95–100%) than US in detecting hepatic abscesses. On CT examination, an abscess is of lower attenuation than the surrounding liver, and the wall of the abscess may enhance with intravenous contrast administration. Lesions are detectable to around 0.5 cm with CT and are not limited by shadowing from ribs or air. CT and US may be used to evaluate and potentially treat the source of infection by percutaneous drainage (Figs. 43-3A and B; Figs. 43-4A through 4-4C). Radionuclide scanning with technetium 99m (99mTc) is no longer used and has been completely replaced by CT and US. On the other hand, cholangiography, usually through an indwelling biliary stent, may visualize the abscess (Fig. 43-5).

Treatment

The appropriate treatment for pyogenic liver abscesses requires treatment of the abscess itself and concomitant treatment of the source. Drainage of a pyogenic abscess is essential for cure in most cases. Although antibiotics alone may be curative, patients sustain higher risk of failure and complications such as abscess rupture. Percutaneous transhepatic drainage is relatively low-risk and successful treatment method for both polymicrobial liver abscesses and K. pneumoniae liver abscesses.17 Steps in management include antibiotic administration, radiologic confirmation by US or CT, and drainage. Exceptions to this strategy include multiple small abscesses and miliary fungal abscesses. These abscesses are treated with intravenous antibiotics and antifungals respectively, without a drainage procedure.

Antibiotics

After confirmatory imaging with US or CT, abscesses are aspirated, blood cultures are drawn, and broad-spectrum intravenous antibiotics are administered until sensitivities allow a more selective antibiotic choice. Serologic testing should also be performed if an amebic abscess is suspected.8

Classic antibiotic regimens include an aminoglycoside, clindamycin, and either ampicillin or vancomycin. Fluoroquinolones can replace aminoglycosides, and metronidazole can be used instead of clindamycin, especially if an amebic source is suspected. Single-agent therapy with ticarcillin-clavulanate, imipenem-cilastatin, or piperacillin-tazobactam is also acceptable.12 Treatment used to be given for 4–6 weeks; however, many studies now document success with only 2 weeks of antibiotic therapy.9 Empiric antibiotics should include anaerobic coverage in older pyogenic liver abscess patients, particularly in the setting of malignancy.16

K. pneumoniae is intrinsically resistant to ampicillin. Metronidazole is ineffective against aerobic organisms, and regimens containing first-generation cephalosporins have been shown to be inferior in treatment of K. pneumoniae liver abscess. A combination of an aminoglycoside and either an extended spectrum β-lactam, such as piperacillin, or second- or third-generation cephalosporin is preferred for patients with K. pneumoniae liver abscess.17

In the setting of multiple abscesses of less than 1.5 cm and no concurrent surgical disease, patients may be treated with IV antibiotics alone. However, multiple small abscesses frequently imply biliary tract disease and may require biliary drainage for source control. Similarly, fungal abscesses are miliary in nature and not amenable to percutaneous or surgical drainage.

Antifungals

Candidal liver abscess is a rare disease reported most commonly in patients with hematologic malignancies during periods of neutropenia resolution. Most of the candidal liver abscesses in patients with hematologic malignancies are a manifestation of disseminated candidiasis and have high mortality rates. They can also be acquired by fungemia from the portal vein or an ascending retrograde infection from the biliary tree. In patients with hematologic malignancies, the yield of positive culture is often less than 50% with the diagnosis usually based on microscopic examination or histopathology from deep tissues. Higher doses of amphotericin B (2–9 g) are recommended by most experts because a cumulative dose of less than 2 g correlated with residual lesions at autopsy. Cases of hepatosplenic candidiasis have been successfully treated with fluconazole. Symptoms improved at 3–8 weeks, but resolution of the lesions on CT scan was noted after at least 1 month of fluconazole.19

Candida glabrata often has reduced susceptibility to both azoles and amphotericin B, and opinions on best therapy are divided. Both C. Krusei and C. glabrata appear susceptible to caspofungin, and this agent appears to be a good alternative. Although fungemia due to C. glabrata has been treated successfully with fluconazole (6 mg/kg/d), many experts prefer amphotericin B deoxycholate (>0.7 mg/kg/d). On the basis of pharmacokinetics predictions, fluconazole (12 mg/kg/d; 800 mg/d for the 70-kg patient) may be a suitable alternative, particularly in less critically ill patients.20

Aspiration and Percutaneous Catheter Drainage

Needle aspiration and percutaneous catheter drainage of liver abscesses have similar mortality rates; however, recurrence rates and the requirement for surgical intervention may be greater in those who undergo aspiration alone.11 Needle aspiration is less invasive, less expensive, and avoids all of the complications associated with catheter care. Giorgio and colleagues21 reported a series of 115 patients with a 98.3% success rate for needle aspiration, no mortality, and no procedure-related morbidity. A randomized controlled trial by Rajak et al22 in 1998 compared percutaneous needle aspiration to catheter drainage and also found no major complications and no deaths. They did, however, report only 60% success with needle aspiration versus a 100% success rate with catheter drainage.22 The highest rate of recurrence (15%) occurred in patients with biliary tract disease and obstructive lesions, whereas the recurrence rate with cryptogenic abscesses was less than 2%. This observation suggests that the underlying lesion should influence the type of therapy chosen.11

Patients in whom percutaneous drainage is not appropriate include those with (1) multiple large abscesses; (2) a known intra-abdominal source that requires surgery; (3) an abscess of unknown etiology; (4) ascites; and (5) abscesses that would require transpleural drainage.6 An example of a patient managed by percutaneous drainage is provided in Figs. 43-6A through 43-6D.

Surgical Drainage

Surgical drainage was the widely accepted treatment for liver abscesses for many years following Ochsner's 1938 report.2 Abscesses were drained extraperitoneally via a 12th rib resection to avoid contamination of the peritoneal cavity. With the advent of systemic antibiotics, transperitoneal surgical exploration also was considered a safe surgical approach. The transperitoneal approach advantages include the ability to: (1) treat the inciting pathology in the remainder of the abdomen/pelvis; (2) gain access and exposure of the entire liver for evaluation and treatment; and (3) access the biliary tree for cholangiography and bile duct exploration.

Since the 1980s, treatment has shifted to a less invasive approach using percutaneous needle aspiration or catheter drainage to treat pyogenic abscesses. Surgical drainage is currently reserved for patients who have failed nonoperative therapy, those who need surgical treatment of the underlying source, those with multiple macroscopic abscesses, those on steroids, or those with concomitant ascites.7

Complications

Up to 40% of patients develop complications from pyogenic liver abscesses, with the most common being generalized sepsis. In addition to sepsis, morbidity can include pleural effusions, empyema, and pneumonia. Abscesses may also rupture intraperitoneally, which is frequently fatal. Usually, however, the abscess does not rupture but develops a controlled leak, resulting in a perihepatic abscess. Pyogenic abscesses may also cause hemobilia and hepatic vein thrombosis.9

Bacteremia is extremely common (95%) in K. pneumoniae liver abscess as opposed to other types of pyogenic liver abscesses (50%). As a result, end-organ seeding and distant abscesses are common. Extrahepatic abscesses occur in 7–12% of patient with K. pneumoniae liver abscesses with the most commonly reported organ being the eye. Endophthalmitis occurs in to 6–61% of cases and commonly occurs after liver abscess drainage. Disseminated intravascular coagulation (DIC), septic pulmonary emboli, and acute renal failure are also well-accepted complications of K. pneumoniae liver abscess.17

Outcome

Between the 1950s and 1990, mortality rates varied from as low as 11% to as high as 88%.6 High mortality rates came from delay or failure to diagnose the abscess, failure to detect smaller intrahepatic abscesses, ineffective surgical drainage, lack of source control, associated malignancy, immune insufficiency, or other major comorbid conditions. No general consensus has been reached regarding risk factors due to the variability of the patient population being studied (Table 43-5).

The prognosis for K. pneumoniae is better than that for other pyogenic liver abscesses regarding mortality (6–17%) and disease relapse. Prognosticators for mortality in K. pneumoniae liver abscess include abscess more than 5 cm, concomitant sepsis, intrahepatic gas formation, APACHE III score of more than 40, delayed/inadequate abscess drainage, use of antimicrobials alone, thrombocytopenia, and diabetes.17 The main concern in this type of liver abscess is no longer mortality but catastrophic disability due to irreversible ocular or neurological complications. The K. pneumoniae genotype K1 is an emerging pathogen capable of causing septic ocular or central nervous system (CNS) complications from pyogenic liver abscess independent of host underlying diseases.18 The outcome for patients who develop endophthalmitis is grim because despite rapid intervention, visual acuity outcome is poor.17

Amebic liver abscess is caused by the parasitic protozoan Entamoeba histolytica. The disease was described in association with blood and mucus diarrheal stools in the fifth century BC by Hippocrates and other practitioners. In 1890, Sir William Osier described the first North American case when, after an attack of dysentery while in Panama, a physician's stool and abscess fluid were both found to contain amebae. Councilman and LaFleur of Johns Hopkins Hospital went on to detail the pathogenic role of amebae and coined the terms “amebic dysentery” and “amebic liver abscess” in 1891.23 Amebic liver abscess is the most common extraintestinal form of invasive amebiasis and an estimated 100,000 people succumb to this disease each year.24

Etiology

Two species of ameba infect humans. Entamoeba dispar is associated with an asymptomatic carrier state and not with disease. E. histolytica is responsible for all forms of invasive disease. The life cycle involves cysts, invasive trophozoites, and fecally contaminated food or water to initiate the infection.25,26 Fecal-oral transmission occurs; the cyst passes through the stomach into the intestine unscathed, and pancreatic enzymes start to digest the outer cyst wall. The trophozoite is then released into the intestine and multiplies there. Normally, no invasion occurs, and the patient develops amebic dysentery or becomes an asymptomatic carrier. In a small number of cases, the trophozoite invades through the intestinal mucosa, travels through the mesenteric lymphatics and veins, and begins to accumulate in the hepatic parenchyma, forming an abscess cavity. Liquefied hepatic parenchyma with blood and debris gives a characteristic “anchovy paste” appearance to the abscess.12

Incidence

Worldwide, an estimated 500 million people are carriers of E. histolytica or E. dispar, 50 million people have active disease and 50,000–100,000 die annually. The vast majority of these infections are acquired in the developing world. Amebiasis is common in Africa, Indochina, and Central and South America. Up to 5% of diarrheal illness in Mexico is due to Entamoeba disease.25 The overall prevalence in the United States is 4% per year. High-risk groups in the United States include sexually active homosexual men, immigrants, tourists who travel to endemic areas, institutionalized people, and those with human immunodeficiency virus (HIV).27 Children also have been known to infect entire families. Amebiasis follows a bimodal age distribution. One peak is at age 2–3 years, with a case-fatality rate of 20%, and the second peak is at over the age of 40 years, with a case-fatality rate of 70%.25 Those living in developing countries have a greater risk and an earlier age of infection than those in developed regions. Low socioeconomic status and unsanitary conditions are significant independent risk factors for infection.27 Amebic liver abscess is 10 times as common in men as in women and is a rare disease in children.26

Pathology

Roughly 90% of people who become infected with E. histolytica are asymptomatically colonized, and factors that control the invasiveness of this organism are not completely understood. E. histolytica cysts can last for days in a dried state at temperatures of 30°C. These cysts are resistant to the effects of gastric acid pH but become stimulated to form trophozoites in the alkaline pH of the bowel. Trophozoites are found in the colon and in the feces of humans and mammals. Humans become reservoirs, and transmission occurs by ingesting food and water contaminated with amebic cysts, or occasionally through person-to-person contact. Incubation takes 1–4 weeks. Left untreated, asymptomatic individuals may shed cysts for many years.

Invasive amebiasis can include anything from amebic dysentery to metastatic abscesses. The most common form of the invasive disease is colitis. The majority (70–80%) of patients experience a gradual onset of symptoms with worsening diarrhea, abdominal pain, weight loss, and stools containing blood and mucus. Trophozoites invade and induce apoptosis in colonic mucosa, resulting in “buttonhole” ulcers with undermined edges. Trophozoites are actually found in the edge of the ulcers.

The most common extraintestinal site of amebiasis is the liver, occurring in 1–7% of children and 50% of adults (usually males) with invasive disease.25 Trophozoites reach the liver through the portal system, causing focal necrosis of hepatocytes and multiple microabscesses that coalesce into a single abscess. The central cavity of the lesion contains a homogenous thick liquid that is typically red-brown and yellow in color and similar to anchovy paste in consistency.28

Diagnosis

The definitive diagnosis of amebic liver abscess is by detection of E. histolytica trophozoites in the pus and by finding serum antibodies to the ameba.28 The differential diagnosis should include pyogenic liver abscess, necrotic adenoma, and echinococcal cyst.

Clinical Presentation

Ninety percent of amebic liver abscesses occur in young adult males. The presentation may be acute, with fever and RUQ pain, or subacute, with weight loss and, less frequently, fever and abdominal pain. The usual case of amebic liver abscess does not present with concurrent colitis, but patients may have had dysentery within the last year. Alcohol abuse is common.29 Eighty percent of patients with amebic liver abscess present with symptoms that develop within 2–4 weeks, including fever, cough, and a dull aching pain in the RUQ or epigastrium. Diaphragmatic involvement causes right-sided pleural pain or pain referred to the shoulder. Gastrointestinal symptoms of nausea, vomiting, abdominal cramping, abdominal distention, diarrhea, and constipation occur in 10–35%. Hepatomegaly with point tenderness over the liver or subcostal region is common26 (Table 43-6). In contrast to pyogenic liver abscesses, amebic liver abscesses are more likely to occur in males younger than 50 years who have immigrated or traveled to a country where the disease is endemic. The patient will also not be jaundiced or have biliary disease or diabetes mellitus26 (Table 43-7).

Laboratory Evaluation

Patients may present with a mild to moderate elevation of the white blood cell count and anemia. Acutely, alkaline phosphatase will be normal and alanine aminotransferase levels will be elevated. The opposite is true in patients with chronic disease.26 Jaundice is rare. Because amebic abscesses involve destruction of liver parenchyma and are often larger than pyogenic liver abscesses, patients may have an elevated prothrombin time.9 If colitis is present, wet mount preps of stool samples contain trophozoites 30% of the time in one sample and 70% of the time if three samples are tested. Liver abscesses are associated with positive stool samples in 40–50% of cases.25

Radiology

Chest radiographs are abnormal in two-thirds of patients with amebic liver abscess and frequently show pleural effusion, infiltrates, or an elevated hemidiaphragm.9 Ultrasound, CT, and magnetic resonance imaging (MRI) are all excellent methods for detecting amebic liver abscesses but are nonspecific.26

In 75–80% of cases, only a single abscess is present and located in the right lobe. Ten percent are in the left lobe and the rest are multiple. Six percent may present as a caudate lobe abscess. Only 40% have typical sonographic features of amebic liver abscess, and serial scanning shows no change in the ultrasound features despite adequate treatment. The mean time to resolution is 7 months, and 70% have findings that persist for more than 6 months. Eventually, resolution may be complete or result in a small residual cystic cavity that resembles a simple cyst of the liver.30

Serology

Serum antibodies are positive in 85% of patients with invasive colitis and 99% with liver abscesses.31 Countries with a high prevalence of amebiasis also have a high prevalence of positive serologies in asymptomatic individuals. Therefore serologies help exclude the diagnosis only in appropriately chosen populations. Patients with E. dispar infection will have negative serologies. Biopsies of the edge of an ulcer or the wall of an abscess reveal trophozoites with periodic acid-Schiff stain.25

Diagnostic Aspiration

Serologic data are usually available within 24–48 hours; therefore the need to aspirate a suspected amebic abscess is questionable. Diagnostic aspirations are usually done when amebic serologies are negative and a pyogenic cause needs to be ruled out. The fluid of an amebic abscess is odorless, and Gram stain and cultures are negative. Amebae are recovered in 33–90% of aspirates, and wall scrapings increase the yield.

The diagnosis of invasive amebiasis is most commonly attempted by a combination of stool testing for ova and parasites (O&P) and serologic testing, possibly coupled with colonoscopy and biopsy of intestinal lesions or drainage of liver abscesses. Numerous studies have demonstrated the inadequacies of microscopic examination for E. histolytica for the diagnosis of both amebic colitis and liver abscess. Antigen detection or polymerase chain reaction (PCR) to detect E. histolytica in the stool is a better approach than O&P but requires fresh or frozen stool specimens (vs preserved), and PCR is impractical in the developing world. The detection of amebic markers in the sera of patients with amebic colitis and liver abscess remains only a research tool at the present time.27

Treatment

Since the introduction of metronidazole in the 1960s, surgical drainage of amebic liver abscesses has become virtually unnecessary. Drainage procedures, regardless of the approach, are reserved for those cases in which the diagnosis is questionable or when complications occur.

Antibiotics

Noninvasive infections can be treated with paromomycin. Nitroimidazoles, especially metronidazole, are the mainstays of treatment for invasive amebiasis. Nitroimidazoles with longer half-lives (secnidazole, tinidazole, and ornidazole) are better tolerated and can be given for shorter periods, but these are not available in the United States.26 Metronidazole reaches high concentrations in the liver, stomach, intestine, and kidneys. This antibiotic crosses the placenta and blood-brain barrier and is contraindicated in the first trimester of pregnancy. The drug is also excreted in milk; thus breast-feeding should be discontinued during use. Serious side effects are rare. Positive responses to metronidazole should be seen by the third day of treatment. At 5 days, an 85% cure rate is achieved, and this response may be increased to 95% by 10 days. Approximately 5–15% of patients with amebic liver abscess may be resistant to metronidazole.30 Parasites persist in the intestine in up to 40–60% of patients who get a nitroimidazole; thus nitroimidazole treatment should be followed with paromomycin or diloxanide furoate to cure luminal infection or risk relapse from residual infection in the intestine.26

In summary, amebic liver abscess is usually managed by the administration of metronidazole or tinidazole, followed by treatment with a luminal amoebicide (paromomycin or diloxanide furoate).24

Therapeutic Aspiration

Blessmann and colleagues32 reported a prospective, randomized trial of patients with amebic abscesses that were treated with metronidazole alone or with US-guided aspiration of the fluid plus medication. Fever, RUQ pain, liver tenderness, and laboratory studies such as erythrocyte sedimentation rate, white blood cell count, hemoglobin, C-reactive protein, and abscess size were obtained on admission and daily thereafter. Abscess aspiration resulted in improved liver tenderness within the first 3 days, but no other difference was demonstrable between the two groups. The authors concluded that this minor benefit was insufficient to justify routine needle aspiration. They advocated drug treatment alone for uncomplicated abscesses with a diameter up to 10 cm and located in the right lobe of the liver.

Therapeutic aspiration may occasionally be required as an adjunct to antiparasitic treatment. Drainage should be considered in patients who have no clinical response to drug therapy within 5–7 days or those with a high risk of abscess rupture defined as having a cavity diameter of greater than 5 cm or lesions located in the left lobe.33 A 2009 Cochrane Review34 attempted to lay to rest the controversy surrounding percutaneous needle aspiration of uncomplicated amebic liver abscesses. The authors found that percutaneous needle aspiration did not help patients with uncomplicated amebic liver abscess. Benefits were observed in resolution time of pain and tenderness, but no additional benefit was found with percutaneous needle aspiration plus metronidazole versus metronidazole alone for uncomplicated amebic liver abscesses in hastening clinical and radiologic resolution.34 Bacterial coinfection of amebic liver abscess has been observed; therefore addition of antibiotics, drainage, or a combination of both, to nitroimidazole therapy may be necessary.26

Drainage

Percutaneous or surgical drainage should be reserved for cases in which the diagnosis of amebic liver abscess is in question or when complications occur.

Percutaneous.

Image-guided percutaneous catheter drainage has replaced surgical intervention as the procedure of choice for decreasing the size of an abscess. Percutaneous drainage remains most useful for treating pulmonary, peritoneal, and pericardial complications. The high viscosity of amebic abscess fluid, however, requires a large-diameter catheter for adequate drainage, and this may cause more discomfort for the patient. Secondary infections related to the indwelling catheter are always a risk of this intervention.9

Surgical.

Surgical drainage of amebic liver abscesses has largely been replaced by antibiotic therapy. The most common indication for surgical intervention is to manage abscesses that have failed to respond to more conservative therapy. Laparotomy is indicated for life-threatening hemorrhage that may or may not be related to abscess rupture, or when the amebic abscess erodes into a neighboring viscus and control of the involved viscus is necessary. Sepsis due to a secondarily infected amebic abscess also warrants operative intervention if percutaneous treatment fails.9

Complications

Complications from amebic abscesses occur secondary to rupture of the abscess into the peritoneum, pleural cavity, or pericardium (Fig. 43-7). Extrahepatic sites also have been described in the lungs, brain, skin, and genitourinary tract, presumably from hematogenous spread.26 Ruptured amebic liver abscesses occur in 2–17% of patients and are associated with mortality rates between 12 and 50%.30

Peritonitis associated with amebiasis is due to rupture in the majority (78%) and less commonly secondary to necrotizing or perforated amebic colitis (22%). The liver abscess usually adheres to the diaphragm and the anterior abdominal wall, or the omentum and bowel tend to wall it off. Rupture into the colon or stomach also may occur. Free rupture into the peritoneal cavity is uncommon and occurs in moribund patients or those with poor nutrition.30

Thoracic amebiasis (empyema, bronchohepatic fistulas, and pleuropulmonary abscess) is the most common complication, followed by pericardial amebiasis (acute pericarditis with tamponade).25 Transdiaphragmatic involvement manifests as dyspnea and dry cough. On examination, right basilar crackles and a pleural rub may be heard. Plain films show atelectasis and blunting of the costophrenic angle. If the abscess ruptures into the pleural cavity, it usually occurs suddenly, collapsing the lung, filling up the pleural space, and whiting out the lung on chest x-ray. Treatment requires drainage of the pleural cavity with tube thoracostomy. If the abscess ruptures into the bronchi, this complication causes sudden onset of coughing with expectoration of copious brown sputum. Surgical intervention is not required, as the abscess is usually walled off from the pleural and peritoneal cavities. Postural drainage, bronchodilators, and antiamebic drugs may suffice.

Left lobe abscesses are more likely to involve the pericardium. Complications range from asymptomatic effusions, to cardiac tamponade, to intrapericardial rupture. If pericardial thickening or effusion is noted on imaging, some experts believe that this is an indication for aspiration of a left lobe liver abscess. When tamponade develops, aspiration of the pericardium, drainage of the liver abscess, and antiamebic drugs are indicated.30 Cerebral amebiasis is seen in up to 8% of autopsies. These patients are severely ill from sepsis and may experience seizures.25

Outcome

The majority of patients with amebic liver abscess defervesce within 3–4 days of treatment29; however, if left untreated, amebic liver abscesses are often fatal. Mortality rates of 0–18% are reported, with higher rates occurring secondary to a delay in diagnosis, or when secondary bacterial infection or complications (abscess rupture) occur. Independent risk factors for mortality include serum bilirubin greater than 3.5 mg/dL, encephalopathy, hypoalbuminemia defined as less than 2.0 g/ dL, and the presence of multiple abscess cavities.35 Abscess aspiration is a risk factor for secondary bacterial infection; however in recent reports, secondary bacterial infection rates have decreased from 10–20% to 0–4% (Table 43-8).

Echinococcosis (hydatid disease) is a zoonosis caused by the larval stage of Echinococcus granulosus (also known as Taenia echinococcus). Humans are accidental intermediate hosts, whereas animals can be both intermediate and definitive hosts. The two main types of hydatid disease are caused by E. granulosus and E. multilocularis. The former is commonly seen in the Mediterranean, South America, the Middle East, Australia, and New Zealand, and is the most common type of hydatid disease in humans.36 In humans, 50–75% of the cysts occur in the liver, 25% are located in the lungs, and 5–10% distribute along the arterial system. Infection with echinococcal organisms is the most common cause of liver cysts in the world.37

Etiology

The life cycle of E. granulosus has two hosts. The definitive host is usually a dog or some other carnivore. The adult worm of the parasite lives in the proximal small bowel of the definitive host attached by hooklets to the mucosa. Eggs are released into the host's intestine and excreted in the feces. Sheep are the most common intermediate host, and these animals ingest the ovum while grazing. The ovum loses the protective chitinous layer and is digested in the duodenum. The released hexacanth embryo (oncosphere) passes through the intestinal wall into the portal circulation and develops into cysts within the liver. The definitive host eats the viscera of the intermediate host to complete the cycle (Fig. 43-8).

Humans may become intermediate hosts through contact with the definitive host (usually a dog) or by ingestion of contaminated water or vegetables. Once in the liver, cysts grow to 1 cm in the first 6 months and 2–3 cm annually thereafter. Once the parasite passes through the intestinal wall into the portal venous or lymphatic system, the liver is the first line of defense and thus is the most frequently involved organ.

Incidence

The incidence of hydatid liver cysts in the United States is approximately 200 cases per year, with an increased frequency in immigrant populations. Hydatid liver disease affects all age groups, both sexes equally, and no predisposing pathologic conditions are associated with infection. Public education about the life cycle and transmission of the disease has helped decrease the incidence. Washing hands after contact with canines, eliminating the consumption of vegetables grown at ground level from the diet, and stopping the practice of feeding entrails of slaughtered animals to dogs have all aided in decreasing the incidence of the disease.9

Pathology

Hydatid liver cysts tend to expand slowly and without symptoms and are thus frequently very large on presentation. Single lesions are noted in 75% and are predominantly located within the right lobe (80%).36 Even though the lesion is single, half contain daughter cysts and are multilocular.

The typical hydatid cyst has a three-layer wall surrounding a fluid cavity. The outer layer is the pericyst, a thin, indistinct fibrous tissue layer representing an adventitial reaction to the parasitic infection. The pericyst acts as a mechanical support for the hydatid cyst and is the metabolic interface between the host and the parasite. As the cyst grows, bile ducts and blood vessels stretch and become incorporated within this structure. This explains the biliary and hemorrhagic complications of cyst growth and difficulties with resection. Over time, the pericyst calcifies.9

The outer layer of the cyst itself is the ectocyst or laminated membrane and is bluish-white, gelatinous, and about 0.5 cm thick. This membrane is a cuticular chitinous structure without nuclei and acts as a barrier for bacteria and an ultrafilter for protein molecules.

The inner layer or endocyst is the germinal membrane, responsible for the production of clear hydatid fluid, the ectocyst, brood capsules, scoleces, and daughter cysts. The endocyst is 10–25 μm thick and attached tenuously to the laminated membrane. The absorptive function of the inner layer is important for cyst nutrition. The inner layer also has a proliferative function producing the ectocyst and scoleces.38 This germinal layer forms small cellular masses that give rise to brood capsules, in which future worm heads develop. They enlarge and develop into invaginated protoscoleces with four suckers and a double row of hooks—a protoscolex. The protoscolex fully differentiates and matures attached by a pedicle to the capsule wall. Brood capsules and freed protoscoleces are released into the fluid of the original cyst and together with calcareous bodies, form hydatid sand.

Hydatid sand is made up of around 400,000 scoleces per milliliter of fluid. The protoscolex can differentiate in two directions. In the definitive host, the scolex becomes an adult tapeworm. In the intermediate host, including humans, each of the released protoscoleces is capable of differentiating into a new hydatid cyst. Development of brood capsules from the germinal layer indicates complete biologic development of the cyst, which occurs after 6 months of growth.

Daughter cyst formation is a defense reaction. Hydatid cysts in humans are long-standing, large, and liable to injury. Any injury may cause daughter cyst formation. Daughter cysts are replicas of the mother cyst, and their size and number are variable. In uncomplicated cysts, the cyst cavity is filled with sterile, colorless, antigenic fluid containing salt, enzymes, proteins, and toxic substances.38 The formation of daughter cysts is called endogenic vesiculation.

Ectogenic vesiculation occurs when a small rupture or defect in the laminated membrane occurs and the germinal layer passes through and creates a satellite hydatid cyst. This process is uncommon in E. granulosus but is characteristic for the larval stage of E. multilocularis. Because the liver parenchyma in humans cannot sequester E. multilocularis and the process of ectogenic vesiculation is fulminant, multiple vesicles are formed in all directions. The infected parenchyma has a multilocular appearance, and the center becomes necrotic, spongy, and filled with a gelatinous fluid similar to that of a mucoid liver carcinoma. Hepatic insufficiency is common and the disease is often lethal.38

Diagnosis

The diagnosis of uncomplicated hydatid liver cyst depends on the index of clinical suspicion. Most uncomplicated cysts are asymptomatic. Symptoms may arise due to a toxic reaction from the presence of the parasite or local mechanical effects.

Clinical Presentation

The clinical features of hydatid liver disease depend on the site, size, stage of development, whether the cyst is alive or dead, and whether the cyst is infected.38 Pain in the RUQ or epigastrium is the most common symptom, whereas hepatomegaly and a palpable mass are the most common signs. Nonspecific fever, fatigue, nausea, and dyspepsia may also be present39 (Table 43-9). Approximately one-third of patients will have eosinophilia, and only 20% will present with jaundice and hyperbilirubinemia.

Serology

No single biochemical test definitively establishes the diagnosis. The Casoni and Weinberg tests are no longer used owing to their low sensitivities. Determination of specific antigens and immune complexes of the cyst with enzyme-linked immunosorbent assay (ELISA) give a positive result in more than 90% of patients. Specific IgE antibodies are demonstrated with ELISA and radioallergosorbent test (RAST) if active disease is present. The arc 5 antibody test involves precipitation during immunoelectrophoresis of the blood of patients with the antigen. Positivity for this test is 91%. Sbihi and colleagues40 reported that purified fractions enriched in antigens 5 and B and glycoproteins from hydatid fluid yielded a sensitivity of 95% with a specificity of 100%.

Radiology

Chest radiographs may show an elevated diaphragm and concentric calcifications in the cyst wall, but they are of limited value. Ultrasound and CT are considered the first choice for imaging (Figs. 43-9A through 43-9D). Classic findings of hydatid cysts are calcified thick walls, often with daughter cysts.41 Ultrasound defines the internal structure, number, and location of the cysts and the presence of complications. The specificity of ultrasound in hydatid disease is around 90%.39 The classification proposed by Gharbi and associates42 provides a morphologic description. Type I has a pure fluid collection. Type II has a fluid collection with a split wall (floating membrane). Type III reveals a fluid collection with septa (honeycomb image). Type IV has heterogenous echographic patterns and type V has reflecting thick walls. Differential imaging characteristics of hepatic cysts is presented in Table 43-10.

CT gives similar information to ultrasound, but more specific information about the location and depth of the cyst within the liver. Daughter cysts and exogenous cysts are also clearly visualized, and cyst volume can be estimated. CT is imperative for operative management, especially when a laparoscopic approach is used.39 MRI provides structural details of the hydatid cyst, but adds little more than ultrasound or CT, and is more expensive. Endoscopic retrograde cholangiopancreatography (ERCP) may show communication between the cysts and bile ducts and can be used to drain the biliary tree before surgery. The routine use of ERCP is advocated by some to completely define the bile duct anatomy and to visualize any clinically silent connections between the bile ducts and cysts.41

Treatment

Most echinococcal cysts are asymptomatic on presentation, but potential complications such as pulmonary infection, cholangitis, rupture, and anaphylaxis give good reason to consider treatment for all. Medical, surgical, and percutaneous approaches may be part of the treatment armamentarium.41 Small cysts (<4 cm) located deep in the parenchyma of the liver, if uncomplicated, can be managed conservatively.39 Basic principles include (1) eradication of the parasite within the cyst, (2) protection of the host against spillage of scoleces, and (3) management of complications.41

Antihelmintics

Medical therapy for echinococcosis is limited to the benzimidazoles (mebendazole and albendazole) and used alone is only 30% successful. Albendazole is readily absorbed from the intestine and metabolized by the liver to an active form. Mebendazole is poorly absorbed and is inactivated by the liver. Albendazole is thus the drug of choice for medical therapy. Greater success rates may be seen in extrahepatic manifestations of the disease and with the alveolar form caused by E. multilocularis. Given for at least 3 months preoperatively, albendazole reduces the recurrence rate when cyst spillage, partial cyst removal, or biliary rupture has occurred. Duration of therapy in these instances is at least 1 month.41

Percutaneous Aspiration and Drainage

Surgical dictum has stated that percutaneous puncture of a hydatid cyst is a dangerous and contraindicated activity. It was believed that the risk of anaphylaxis, communication with the biliary tree, and spillage outweighed any potential advantages. In 1983, Fornage43 challenged this axiom and reported an accidental puncture of a hydatid cyst by US that had no clinical consequences. Many successful reports followed thereafter.38,44 The most frequently used protoscolecidal agents for percutaneous treatment are 15–20% saline, 95% ethanol, a combination of 30% saline and 95% ethanol, and mebendazole solution. PAIR technique stands for puncture of the cyst wall, aspiration of cyst content, injection, and re-aspiration of a scolecoidal agent. PAIR involves initial puncture of the cyst under ultrasound or CT guidance, aspiration of cyst content, injection of contrast material to opacify the cyst, infusion of scolecoidal drug, followed by povidone-iodine infusion. The catheter stays clamped for 30 minutes, and then povidone-iodine is infused again. The catheter is preserved for drainage. Except in the case of povidone-iodine infusion, aspiration can be followed by sclerotherapy or infusion of alcohol or a scolecidal such as albendazole. Recently, a modified PAIR technique was created to introduce concomitant evacuation of cyst contents while infusing scolicidal agent via a specially designed coaxial catheter system. The simultaneous aspiration/infusion process allows almost complete washout of cyst content, reducing chances of any scoleces surviving, and the maintenance of the intracystic pressure minimizes risk of biliary fistula formation.45 The PAIR technique has been combined with albendazole therapy with 70% success rates and a low rate of recurrence. In 1997 Filice and Brunetti46 reported a series of 163 patients with 231 cysts treated percutaneously. No complications were reported and long-term results were good.

Indications for percutaneous treatment of liver hydatid cysts include types I and II cysts; types III and IV cysts with drainable material; suspected fluid collections; infected hydatid cysts; inoperable patients; pregnant women; and patients with multiple, disseminated, or symptomatic cysts. Contraindications include subgroups of types III and IV (hydatid cysts with heterogeneous echo pattern), ruptured liver cysts into the biliary system or peritoneum, cysts inaccessible to puncture, and children younger than 3 years. Type V cysts are not eligible for any intervention other than simple follow-up. Recurrence rates vary between 0 and 4%. Overall complication rates in percutaneous drainage range from 15 to 40%. Major complications (anaphylactic shock) are rare (0.1–0.2%). Minor complications (urticaria, itching, hypotension, fever, infection, fistula, rupture into the biliary system) range from 10 to 30%. Cyst-biliary complications after PAIR and caused by cyst decompression can be handled endoscopically or by cyanoacrylate infusion. Cholangiography or ERCP is recommended before any attempt for percutaneous drainage to inject contrast material and make any communication visible. Overall mortality rates are as low as 0.1%.45

Despite these reports, percutaneous treatment is not benign. Spillage, anaphylaxis, and recurrence can be life threatening. Complete aspiration of all cyst contents, especially multivesicular disease, is difficult, and complete sterilization with protoscolecidal agents is uncertain. If the protoscolecidal agent enters the biliary tree, serious damage also can occur within the liver. Exogenous vesiculation may also go undiscovered. Long-term results are unknown.38

Surgery

Surgery remains the treatment of choice for uncomplicated hydatid disease of the liver, although there is much debate about the most appropriate surgical technique that can offer total extirpation of the parasites with minimal postoperative complications.45 The objectives of surgical treatment are to (1) inactivate the scoleces, (2) prevent spillage of cyst contents, (3) eliminate all viable elements of the cyst, and (4) manage the residual cyst cavity. The surgical procedure varies from a radical resective open approach (pericystectomy or hepatic resection) to a conservative approach (drainage or obliteration of the cavity or both) that can potentially even be done laparoscopically39 (Fig. 43-10). One of the most important end points of hydatid cyst surgery may be recurrence. Dissemination of protoscoleces-rich fluid during surgery and incomplete removal of the germinative membrane from the cyst cavity is a major cause of recurrence (8.5–25%) of postoperative cases.47

Scolicidal Agents.

Early on, surgical management of hydatid cysts via cyst evacuation resulted in a high rate of peritoneal implantation. This problem prompted the use of scolicidal agents for injection into the cyst and for use in the surrounding peritoneum. Formalin, hypertonic saline, chlorhexidine, cetrimide, hydrogen peroxide, polyvinylpyrrolidone-iodine, silver nitrate, and ethyl alcohol are among some of the many agents that have been used.39,41,45 However, formalin caused sclerosing cholangitis when it entered the biliary tract. Hypertonic saline has to be used carefully to avoid biliary injection and hypernatremia. The safety of the other agents in the biliary tree has not been established. No agent should be injected pre-evacuation due to high intracyst pressure. The World Health Organization (WHO) regards the use of scolicidal agents for intraoperative killing of infectious material as questionable, as there is no agent that is both effective and safe. According to WHO, ethanol (70–95%), hypertonic saline (15–20%), and cetrimide solution (0.5%) are deemed substances with relatively low risk.47 Recently, chlorhexidine gluconate 0.04% (Chx-Glu) was found to be nontoxic, without harmful effects on the biliary tract, and is not affected by dilution in the cyst fluid. In addition, Chx-Glu is commonly available, easily prepared, inexpensive, and was 100% effective on protoscoleces and germinative membrane, and may become the preferred scolicidal in the future.47

Open-Cyst Evacuation.

The safest surgical approach is open-cyst evacuation. Peripherally located cysts are the most easily treated, and either abdominal or flank approaches may be used depending on cyst location. Before opening the cyst, the field is lined with hypertonic (20%) saline-soaked gauze to guard against spillage. The cyst is then opened, and the contents are aspirated with a suction device that is capable of generating high negative pressures. The cyst is then opened completely, and any remaining debris is meticulously cleared. The cavity may then be irrigated with a scolicidal agent.41 Recurrence rate of this procedure is 10–30%.45

Laparoscopic Cyst Evacuation.

Peripherally located echinococcal hepatic cysts may be safely managed by laparoscopic cyst evacuation.48 The lesions best suited for this approach are situated anteriorly and do not have thick calcified walls. A right lateral approach also works for cysts in segments VI and VII. A trocar (11 mm) is inserted just above the cyst, and 10% povidone-iodine–soaked sponges are placed as the scolicidal agent. The cyst is aspirated with a 14-gauge needle. The endocyst then shrinks back from the wall and rests at the bottom of the cyst. The 11-mm trocar is then exchanged for an 18-mm trocar, and the germinal membrane is aspirated. The laparoscopic camera is inserted directly into the cyst to explore for residual daughter cysts or biliary fistulae. The remaining cavity is irrigated with 20% saline solution, and the cyst wall is excised. The cavity may be plugged with omentum or closed over a closed-suction drain.48

The most difficult part of the laparoscopic approach is the initial cyst puncture and aspiration of the cyst fluid. Indications for laparoscopic excision of liver echinococcosis have changed over the years. Currently, the only excluding criteria for laparoscopic intervention include deep intraparenchymal cysts or posteriorly situated cysts, more than three cysts, and cysts with thick and calcified walls. Postoperative morbidity ranges from 8 to 25% and morality in most series is 0% with recurrence rates of 0–9% (vs 12–63% morbidity, 0–3% mortality, and 0–30% recurrence in open series). Major complications (ie, anaphylaxis) are, however, more common in laparoscopic interventions as a result of peritoneal spillage during debridement and removal of cyst contents. Major drawbacks to the comparison of laparoscopic versus open procedures include the small studies, lack of randomization, and bias related to careful selection of laparoscopic candidates.45

Pericystectomy.

Pericystectomy involves complete resection of the cyst wall without entering the cyst cavity. This procedure is done through a plane outside of the pericyst or along the cyst wall itself. Preoperative localization of the bile ducts and vascular system is imperative. If a bile duct connection is suspected, preoperative ERCP should be obtained. Intraoperative ultrasound should be used. Pericystectomy decreases the risk of spillage of cyst contents into the peritoneal cavity and also lowers the risk of recurrence. The disadvantage to this approach is the potential for bleeding and/or damage to bile ducts in proximity to the cyst wall.41 Gunay and associates37 reported 0% recurrence rates, a lower incidence of biliary fistulae, and shorter hospitalization compared with more conservative procedures. The procedure also precludes management of the cavity and facilitates detection of recurrence.

Liver Resection/Transplantation.

Some experts have argued that formal resection for benign disease is excessive and unnecessary, whereas others have stressed that resection is very safe. Multiple cysts within proximity to a major blood supply or to each other, or a cyst in a relatively safe location (ie, segments II/III) are candidates for resection provided a complete resection can be achieved. E. multilocularis infection may also lead to fulminant hepatic failure from sclerosing cholangitis, biliary sclerosis, or Budd-Chiari syndrome, and in these rare cases orthotopic liver transplant may be necessary.41 Among these various treatment options, criteria for uncomplicated and complicated patients are presented in Table 43-11. A recent study also discovered lymphatic spread of larval E. multilocularis from the liver to regional lymph nodes and suggests the routine removal of regional nodes to reduce the risk of persistent infection.49

Complications

Complications from hydatid cysts are seen in one-third of patients. Most commonly, the cyst ruptures internally or externally, followed by secondary infection, anaphylactic shock, and liver replacement, in order of decreasing frequency.37 Viable hydatid cysts are space-occupying lesions with a tendency to grow. In confined areas such as the CNS, even small cysts can cause severe symptoms. In less confined areas, symptoms depend on the site and size of the cyst. Symptoms result from direct pressure or distortion of neighboring structures or viscera. Compressive atrophy of the surrounding hepatocytes and fibrosis occurs, and these cysts may grow to such an enormous size that they replace an entire lobe.

As the cysts enlarge, they may also rupture. If rupture of only the endocyst occurs, the content is retained within the pericyst. A communicating rupture is a rupture into the biliary or bronchial tree.38 Hydatid liver cysts cause compression of the biliary system leading to decubitus lesions and biliary communication in up to 80% of cases. This communication may be very difficult to find and result in biliary leakage/fistulae postoperatively. Bile leakage is the main source of cavity-related complications in conservative surgery. If not properly drained, this may result in abscess or bile peritonitis. If drained effectively, an external biliary fistula may develop. From 12 to 33.3% with biliary fistulae require biliary drainage postoperatively and rates are higher in conservative versus radical surgery. The complication rates for radical surgery range from 17 to 20%. Retention cysts in conservative surgery may lead to misdiagnosis of early recurrence and result in unnecessary operations.50

A free rupture occurs when hydatid contents rupture throughout the peritoneal, pleural, or pericardial cavity. Acute symptomatic rupture into the peritoneal cavity occurs in 1–4% of patients and may precipitate anaphylactic shock.38

Outcome

Medical therapy alone results in recurrence rates of 70–80% and is not recommended. Medical treatment is used in combination with a drainage procedure or in patients who are not surgical candidates. Uncomplicated cases that undergo open surgical, laparoscopic, and percutaneous drainage have recurrence rates around 10%. Early local recurrence and cavity-related complications are the main problems affecting the success of the surgical management of hydatid liver disease. These problems are rare for complete resections due to complete removal of the cyst wall containing the germinal epithelium and daughter cyst. Conservative operations are easier and safer but are associated with a high incidence of local recurrence (10%) and cavity-related complications (37%). Older cysts have an increased risk of exogenic daughter cyst formation, which is an important risk factor for early local recurrence. Another important risk factor for early local recurrence, especially in conservative surgery, is pre- and intraoperative undetected satellite cysts that exist around pericysts or exogenic vesiculations. Because the disease is endemic to many locations, the potential for reinfestation remains, so long-term serologic and imaging studies are necessary. Rupture into the pleural or peritoneal cavity portends a recurrence rate of up to 25%.41

Uncomplicated cases undergoing elective procedures such as laparoscopic or percutaneous cyst aspiration should have morbidity rates between 15 and 30% and essentially no mortality. In patients with complicated disease that requires open evacuation, pericystectomy, or resection, morbidity is as high as 50%; however, mortality should still remain less than 5%. Septic shock, peritoneal rupture, and comorbid conditions (ie, malnutrition) play a major role in increasing mortality rates.

Simple

The incidence of simple hepatic cysts in 1695 patients referred for abdominal or pelvic ultrasound was 2.5% with a sharp increase noted at the age of over 60 years.51 In a separate European study52 of more than 26,000 patients undergoing upper abdominal ultrasound, simple cysts were found in 2.8%, and most (>92 %) were over the age of 40. The female to male ratio was 1.5:1.

Solitary benign cysts are believed to be congenital and thought to arise from abnormal development of intrahepatic bile ducts in utero. The aberrant ducts enlarge slowly and may result in symptoms later in life. In a study from the Mayo Clinic53 from 1907 through 1971, only 24% of simple cysts were symptomatic, and they usually became symptomatic in the fourth or fifth decade of life. Abdominal pain and mass were noted most frequently and were present in more than 50%. Less commonly, symptoms were related to mass effect, resulting in nausea, vomiting, early satiety, and jaundice. Physical examination revealed hepatomegaly or a palpable abdominal mass. Laboratory values should be normal, but occasionally hyperbilirubinemia may be seen. Simple solitary cysts are bluish in color, and contain clear, straw-colored fluid. Echinococcal disease should be ruled out by serology.54

Ultrasound is the most accurate imaging modality, with greater than 90% sensitivity and specificity. On ultrasound, the cysts appear as anechoic masses with smooth margins and thin, imperceptible walls. Ultrasound also differentiates between cystic and solid lesions and can assess for intra- and extrahepatic biliary dilation in the jaundiced patient. CT imaging reveals nonenhancing, fluid (water) density lesions with a thin, uniform wall (Fig. 43-11). On MRI, simple cysts are well-circumscribed lesions that are hypointense on T1-weighted images and hyperintense on T2-weighted images.52

Most simple cysts are found incidentally and are asymptomatic, and 80–95% remain asymptomatic. In the setting of symptoms, percutaneous aspiration can aid in diagnosis but is associated with 100% recurrence within a 2-year period. If sclerosants are added, a 17% recurrence rate can be achieved.54

Success of surgical treatment for cystic liver disease is judged by relief of symptoms rather than by complete disappearance of the cystic lesion on imaging studies. Once the benign nature of the cyst is established, a permanent internal cyst “drain” is the mainstay of surgical therapy and complete cyst excision is not necessary.55 If the cyst protrudes from the liver and no biliary connection is demonstrated, the accessible wall on the liver surface may be excised and the remaining cyst lining allowed to drain freely into the peritoneal cavity. If the cyst has a biliary connection, suspicion should be high that the lesion is a biliary cystadenoma rather than a simple cyst. In general, cyst excision or unroofing and resection have a 0–20% recurrence rate and a mortality rate of 0–5% (Table 43-12).54

Unroofing the cyst by a laparoscopic approach can also be done with an overall success rate of more than 90% and a 10% rate of symptomatic cyst recurrence. Proponents of the laparoscopic approach report excellent exposure, less postoperative pain, and success rates similar to those of cases done open.54 Gamblin et al reported the largest series of laparoscopic liver resections for cystic lesions that included 51 patients. The authors routinely left the back wall of the cyst behind and untreated. Patients experienced minimal postoperative pain, short hospital stays (median 2 days, range 1–11) resolution of symptoms (pain resolved in all), had a low recurrence rate (2 of 51 required reoperation), and no 90-day mortalities. Median follow-up was 13 months. A growing body of literature supports the equivalency of many laparoscopic and open procedures regarding outcomes and advantages in avoiding a laparotomy, especially in benign disease. These authors proposed minimally invasive cyst excision as the standard of care for management of these benign hepatic cysts.56

Polycystic

Polycystic liver disease (PCLD) is an autosomal dominant disorder, often found in association with polycystic renal disease (40%).57 PCLD is the most frequent extrarenal manifestation of autosomal dominant polycystic kidney disease. It also exists in an autosomal dominant pattern that is not associated with polycystic renal disease, but may have cysts that develop in other organs in addition to the kidneys.

Cysts in PCLD are epithelial-lined growths arising from biliary epithelium that usually do not communicate with the biliary tree. The majority of patients are asymptomatic and do not require treatment. Their prognosis is directly related to the severity of the accompanying renal disease.58

If PCLD becomes symptomatic, it is usually secondary to hepatomegaly. Symptoms may include abdominal fullness, distention and pain, or bowel and biliary obstruction. Complications such as bleeding, infection, rupture, portal hypertension, and Budd-Chiari syndrome have been reported, but they are rare. Malignant transformation has been reported, but it infrequently occurs. Hepatic function is typically preserved, so progression to liver failure is uncommon.58

Routine imaging of cysts in PCLD is similar to that of simple cysts. Unenhanced CTs show multiple, homogenous, hypoattenuating lesions with a regular outline (Fig. 43-12). Contrast-enhanced CT images have no cyst wall or enhancement of cyst contents. MRI demonstrates very low-signal intensity on T1-weighted images and does not enhance after administration of gadolinium. Because the cyst content is purely fluid and homogeneous, high-signal intensity is demonstrated on T2-weighted images.57

Development of symptoms in PCLD is most often due to hepatomegaly, and therefore treatment needs to result in a reduction in liver size. Percutaneous aspiration with sclerotherapy may be used in those who are not surgical candidates or in lesions that are not surgically accessible, but long-term results of this approach are poor.

If a small number of large cysts exist, laparoscopic unroofing with the aid of intraoperative ultrasound may be successful. Deeper cysts may be accessed and unroofed through the back wall of more superficially located cysts. However, because the rigid architecture is found in PCLD, unroofing alone may not be enough to provide hepatic collapse and relief of symptoms. In addition, if too many cysts are unroofed, the peritoneum's absorptive capacity may be exceeded and cause ascites. Unroofing is not useful in patients with a large number of smaller cysts because it cannot be adequately performed.

A combination of cyst unroofing and liver resection may achieve the best results in terms of reducing liver volume. Resection should include the most cysts with the least loss of hepatic function. Morbidity for this approach is greater, but long-term results are improved. Orthotopic liver transplant is occasionally indicated if symptoms are disabling or hepatic function is compromised. If patients have associated renal failure, the liver transplant may be combined with renal transplant.58

Neoplastic cysts are acquired cysts that occur less commonly than simple cysts, usually in females, in the fifth decade of life. Their etiology is unknown. Cystic neoplasms are frequently large, resulting in abdominal discomfort and a palpable mass on examination. Cystic neoplasms appear as multiloculated lesions with papillary projections inside the cyst cavity. Invasion of the surrounding tissue suggests malignancy, as does the presence of a predominantly solid (vs cystic) component. Ten percent of neoplastic cysts are malignant. Definitive diagnosis requires intraoperative biopsy of the cyst wall. Incomplete resection will result in nearly 100% recurrence.54

Laboratory investigation is normal in most, although some patients present with elevated liver enzymes. Serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels are usually normal. In some patients, CA 19-9 has been found to be elevated fivefold. In general, hemorrhagic cyst fluid suggests cystadenocarcinoma, whereas bilious or mucinous fluid suggests cystadenoma.59

Cystadenoma

Cystadenomas comprise less than 5% of all intrahepatic cysts of biliary origin.60 Hepatobiliary cystadenoma with mesenchymal stroma occurs exclusively in young and middle-aged women and has potential to transform into cystadenocarcinoma. In contrast, hepatobiliary cystadenoma without mesenchymal stroma occurs in both sexes equally, at a mean age of 50, and has no clear association with cystadenocarcinoma.59 These tumors are lined with columnar epithelium and frequently have papillary infoldings60 (Fig. 43-13, negative path). If symptoms are present, they may include abdominal pain (60–80%), jaundice, cholangitis, fullness, or bloating.1

Cystadenomas have a septated, multilocular appearance on US and CT (see Figs. 43-13A through 43-13C).54 CT will reveal well-demarcated cystic lesions, usually with internal septations; the walls are rarely calcified, and the presence of polypoid protrusions or wall excrescences should trigger the concern for cystadenocarcinoma.1 MRI shows typical features for a fluid-containing loculated mass with homogeneous low-signal intensity on T1-weighted images and homogeneous high-signal intensity on T2-weighted images. However, signal intensity of mucinous fluids varies depending on protein concentration. On T1-weighted images, the signal intensity may change from hypointense to hyperintense as protein concentration increases. On T2-weighted images signal intensity of mucinous fluids can decrease from hyperintense to highly hypointense with increasing protein concentration and viscosity. Blood products also have different signal characteristics on MRI. The distinction between cystadenoma and cystadenocarcinoma remains difficult on the basis of imaging findings alone as the presence/absence of septae, mural nodules, and papillary projections are variable between lesions. Magnetic resonance cholangiopancreatography (MRCP) does, however, appear helpful in evaluating the relationship of the lesion to bile ducts.61 ERCP will usually demonstrate communication with the biliary tree, often at the proximal left hepatic duct.

Serum CEA and CA 19-9 levels are usually within normal ranges and cannot be considered as significant parameters to discriminate between malignant and benign liver tumors.61 The diagnosis of intrahepatic biliary cystadenoma can be suggested on the basis of cyst fluid analysis (CFA), but this relies on adequate sampling and correlation with clinical and radiologic findings. CA 19-9 and CEA have been shown to be elevated in intrahepatic biliary cystadenoma and normal in simple cysts. Immunohistochemical analysis of intrahepatic biliary cystadenoma has shown the presence of CA 19-9 and CEA in the epithelium; however, the premalignant progression is based on the histologic presence of intestinal metaplasia characterized by the presence of numerous goblet cells. This has led to the recommendation that patients with suspected intrahepatic biliary cystadenoma based on CFA should undergo cyst wall sampling to determine whether a premalignant (intestinal metaplasia + atypia) or malignant diagnosis requiring resection exists.62 Other authors, however, believe that percutaneous biopsy for preoperative diagnosis rarely produces a definitive diagnosis and the risk of peritoneal dissemination in the case of malignancy is prohibitive.

Neoplastic cysts with no signs of malignancy may be enucleated. This technique requires removal of the entire cyst, the cyst's surrounding wall, and a small rim of liver parenchyma.54 Formal hepatic resection also is an appropriate treatment. Aspiration, sclerosis, marsupialization, and internal drainage must be avoided. Inadequate excision leads to recurrence in all cases60 (Table 43-13).

Cystadenocarcinoma

Devaney and colleagues63 divided cystadenocarcinoma (Fig. 43-14, positive path) into three subtypes: (1) cystadenocarcinoma with mesenchymal stroma arising from cystadenoma with mesenchymal stroma, occurring exclusively in females and following a relatively indolent course; (2) cystadenocarcinoma without mesenchymal stroma not associated with cystadenoma, occurring in males and following an extremely aggressive course; and (3) cystadenocarcinoma without mesenchymal stroma, occurring in females and with a poorly understood clinical course.64 Resection is the only appropriate treatment for malignant biliary cystadenocarcinoma.54 With complete resection, the clinical course for cystadenocarcinoma is better than that for hepatocellular carcinoma or cholangiocarcinoma.64 In the rare patient with a symptomatic cystadenocarcinoma with peritoneal metastasis, palliative unroofing of the cyst may be indicated.

In recent years, the management of hepatic trauma has undergone major changes. The frequent use of dual-phase CT imaging to assess patients with abdominal trauma has resulted in the detection of even the most minor of liver injuries. In the hemodynamically unstable patient, damage control laparotomy—the control of bleeding and contamination with packing off of the abdomen to postpone definitive treatment—has gained popularity, while formal anatomic hepatic resection has fallen out of favor. More and more American Association for the Surgery of Trauma grades IV and V liver injuries are also being managed nonoperatively. Mortality rates have fallen to 7–12%,65 but a different set of management problems is being created. One such problem is the traumatic cyst.

Traumatic cysts are acquired cysts that occur from continued bile leakage from an injured intrahepatic bile duct after abdominal trauma. When an injured biliary structure continues to leak into a hematoma cavity, a cyst containing bile and blood may form.54 These cysts lack a true epithelial lining and are considered pseudocysts (Fig. 43-15). Some traumatic cysts may resolve spontaneously,58 while others may grow until compressive symptoms are caused. Presentation is typically delayed, and abdominal pain or fullness may occur months or sometimes years after the trauma.54

Because of the proximity of the right hepatic artery to the cystic duct, this artery is vulnerable to injury when the critical view of safety is not achieved during laparoscopic cholecystectomy. Combined injury to the bile duct and hepatic artery during laparoscopic cholecystectomy may result in development of intrahepatic abscess, recurrent cholangitis with secondary biliary cirrhosis or ischemic necrosis, and atrophy of the liver.66 The incidence of liver necrosis with or without abscess is reported as high as 75% in patients with combined biliary and arterial injury.67 Patients with bile duct injuries after cholecystectomy should be evaluated for concomitant hepatic arterial injury and will frequently require hepatic resection to treat secondary biliary cirrhosis. An intact portal circulation is mandatory for oxygenation of the hepatic parenchyma when the hepatic artery has been injured; therefore portal blood flow must also be examined in any case of combined bile duct and hepatic artery injury following cholecystectomy. These combined portal and arterial injuries in the setting of bile duct injury tend to present earlier and often require formal hepatectomy.68

Treatment is reserved for those who are symptomatic. Options include aspiration, unroofing, and excision. Bile leaks must be sought and controlled.58 Small bilomas may be observed, whereas larger collections usually require percutaneous drainage at the time of diagnosis. Once the cavity is collapsed, spontaneous closure of the fistula is the rule.