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
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).
Life cycle of Echinococcus granulosus. (Modified from Melvin DM et al. Common Blood and Tissue Parasites of Man. Life Cycle Charts. Atlanta, Georgia: Center for Disease Control, 1979.)
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.
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
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
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.
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.
Table 43-9: Symptoms, Signs, and Laboratory Data of Hydatid Liver Cysts ||Download (.pdf)
Table 43-9: Symptoms, Signs, and Laboratory Data of Hydatid Liver Cysts
|% of Hydatid Cysts|
|Fever and chills||8|
|Right upper quadrant mass||70|
|Right upper quadrant tenderness||20|
|Bilirubin >2 mg/dL||20|
|WBC count <10,000/mm3||10|
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%.
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.
Table 43-10: Differential Imaging and Character of Hepatic Cysts ||Download (.pdf)
Table 43-10: Differential Imaging and Character of Hepatic Cysts
|Number||Single or multiple||One or few||Usually single||Single or multiple||Single with loculations|
|Wall character||Uniform or multiloculated||Usually uniform||Uniform, daughter cysts; 50% calcified||Uniform||Septations common may be irregular|
|Cyst contents||Usually pus with blood||Red-brown; like anchovy paste||Clear or bilious; gelatinous||Usually clear water density||Usually green-brown mucinous|
A. CT scan demonstrating rupture of hydatid cyst through the diaphragm (arrow) into the pleural space. B. CT scan in the same patient demonstrating a heavily calcified hydatid cyst (arrow) with diaphragmatic penetration and a lightly calcified cyst on the left. C. CT scan in the same patient showing a third calcified cyst near the gallbladder fossa and a small superficial fourth cyst on the left. D. Endoscopic retrograde cholangiopancreatography (ERCP) in the same patient demonstrating biliary communication in the cyst that also penetrates the diaphragm.
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
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
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 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
A. Open-cyst evacuation demonstrating cyst aspiration (upper left), removal of daughter cysts (upper right), resection of active cyst lining (lower left), and packing with omentum (lower right).B. Pericystectomy demonstrating removal of a calcified pericyst (top right), closure of a small bile duct (middle left), and closure of the cavity over a drain (lower right). (Reproduced, with permission, from Cameron JL, Sandove C. Atlas of Surgery. Philadelphia, PA: BC Decker; 1990:215–221.)
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
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 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.
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
Table 43-11: Treatment Options for Hydatid Liver Cysts ||Download (.pdf)
Table 43-11: Treatment Options for Hydatid Liver Cysts
|Percutaneous or Laparoscopic Evacuation||Open Evacuation or Resection|
|Gharbi type I or II||Gharbi type IV or V|
|Anterior cysts||Posterior cysts|
|Peripheral cysts||Central cysts|
|One to three cysts||More than three cysts|
|Small cysts||Large cysts|
|No or minimal calcification||Heavy calcification|
|Percutaneous or Laparoscopic Evacuation||Open Evacuation or Resection|
|Infected cysts meeting above criteria||Infected cysts meeting above criteria|
|Biliary communication— not indicated||Biliary communication—indicated|
|Pulmonary communication—not indicated||Pulmonary communication—indicated|
|Peritoneal rupture—not indicated||Peritoneal rupture—indicated|
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
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.