Approach Considerations
For liver cysts, a stage-specific approach should be taken, in which CE1 and CE3a cysts should be treated with either albendazole alone (if < 5 cm in diameter) or percutaneous treatment in association with medical therapy (if cysts are 5-10 cm in diameter). For cysts larger than 10 cm, continuous catheterization may be a viable option. Inactive uncomplicated cysts can be safely managed expectantly, especially if they became spontaneously inactive (ie, as opposed to treatment-induced inactivity). [25, 26, 27, 28, 29]
Medical Care
Two benzimidazolic drugs, mebendazole and albendazole, are the only anthelmintics effective against cystic echinococcosis. Albendazole and mebendazole are well tolerated but show different efficacy.
Albendazole is significantly more effective than mebendazole in the treatment of liver cysts. Benzimidazole treatment alone requires prolonged administration over many weeks, with an unpredictable outcome in terms of response rates in individuals. [30]
Treatment with albendazole in E granulosus infection can result in an apparent cure in as many as 30% of patients, with a further 40-50% of patients showing objective evidence of response when observed short term. Patients who do not show obvious initial evidence of response may be found to be cured when observed over several years.
Duration of therapy and doses are also important. Albendazole efficacy increases with courses of up to 3 months in the more common cyst sites.
Patients once received these drugs in cycles of 4 weeks separated by 1-2 weeks without drugs. This regimen is no longer advocated given the parasitostatic activity of benzimidazoles and their safety as shown by cumulative data from several retrospective studies. Continuous treatment is preferred and has been administered for periods of up to 2 years without significant side effects. [31, 13] The safety profile shows that liver function abnormalities are common, although they rarely limit treatment, while occasional hematologic changes affecting white cells may be more serious. The safety data supply the rationale for monitoring patients during treatment.
Overall, albendazole has been demonstrated to be a useful advance in the management of cystic echinococcosis when used as sole treatment or as an adjunct to surgery or other treatments.
Praziquantel has recently been suggested, administered additionally once per week in a dose of 40 mg/kg during treatment with albendazole. However, available data are limited. [32]
Radiation therapy
A 2013 case report described a patient with sternal CE that was successfully treated with radiation therapy after multiple surgical procedures and medical treatment had failed. [33] However, a recent editorial on the subject concluded that “in light of existing data, radiotherapy cannot be advocated as an alternative to surgery in osseous echinococcosis where complete excision of the affected bone is possible, and thus potentially curative. In fact, radiotherapy has to be regarded as contraindicated in such cases.” [34]
Surgical Care
Surgery was the only treatment available before the introduction of anthelmintic drugs. It is considered the first choice of treatment for echinococcosis but is associated with considerable mortality (up to 2% in some series, increasing with second and further operations), morbidity, [35] and recurrence rates (2-25%). Given the more frequent detection of early and asymptomatic E granulosus liver lesions, a widened indication for chemotherapy exists.
Several procedures have been described for the treatment of hepatic echinococcal cysts, ranging from simple puncture to liver resection and transplantation, although the most commonly used technique is total or partial cystopericystectomy.
Usually, radical surgery (total pericystectomy or partial hepatectomy) is indicated for liver cysts. Conservative surgery (open endocystectomy with or without omentoplasty) or palliative surgery (simple tube drainage of infected cysts or communicating cysts) is also an option. More radical interventions have higher intraoperative risks but less numerous relapses. With the inclusion of chemotherapy prior to or after surgery, less-aggressive surgery may be possible.
Surgery for pulmonary cysts includes extrusion of cysts using Barrett technique (intact endocystectomy without preliminary aspiration), pericystectomy, and lobectomy. [36]
Peripheral and unilobar echinococcal cysts, regardless of how complicated they are, can also be treated with laparoscopic surgery using partial cystopericystectomy and drainage. When surgery cannot be avoided, presurgical use of albendazole reduces risk of recurrence and facilitates surgery by reducing intracystic pressure.
Surgery is the treatment of choice for spinal echinococcosis, with decompression of a compromised spinal cord and stabilization of a compromised spinal column being the two primary tasks. However, the existing data on follow-up of spinal CE cases is largely insufficient to judge the long-term outcome of surgery. [37]
Percutaneous treatment
Minimally invasive treatment is discussed below.
The puncture of echinococcal cysts has long been discouraged because of risks of anaphylactic shock and spillage of the fluid; however, as experience with ultrasonography-guided interventional techniques has increased since the early 1980s, an increasing number of articles have reported its effectiveness and safety in treating abdominal, especially liver, echinococcal cysts. A recent systematic review of the literature found that the overall fatality rate due to lethal anaphylaxis from puncture of echinococcal cysts is 0.03% (2 in 5943 procedures) for procedures and 0.04% (2 in 5517 cysts) for cysts, respectively. [14]
One study of 446 patients who were treated surgically for cystic echinococcosis (CE) found an increased incidence in anaphylatic shock in younger patients (P< 0.001) and in patients with pulmonary cysts. The authors suggest taking precautions such as reducing intracystic pressure, preventing antigen from contacting other tissues where it might trigger anaphylaxis, and resecting the cyst completely when feasible. [38]
Under albendazole coverage, cysts are punctured under ultrasonographic or CT guidance either with a needle or with a catheter according to their size. The presence of an anesthesiologist who intervenes in case of allergic manifestations or anaphylactic shock is mandatory. Usually, a small quantity of fluid is first aspirated and examined by light microscope to observe for the presence of viable protoscolices. If they are present, the cyst is aspirated completely.
At this point, exclude possible connections of the cyst with the biliary tree by means of injection of contrast medium in the cavity. If no connections are evident, a scolecoidal agent, usually hypertonic sodium chloride solution or ethanol, is injected and left for a variable period (usually 5-30 min) and then reaspirated. The destruction of protoscolices can be observed in fluid sample aspirated after the injection of a scolecoidal agent. This sequence is termed PAIR (puncture, aspiration, injection, reaspiration). As happens with drug therapy, positive responses include both a decrease in cyst size and a progressive change in echo pattern (generally solidification). [39, 40, 41]
From a diagnostic standpoint, PAIR is the only method that helps provide a direct diagnosis of the parasitic nature of the cysts. Neither imaging modalities nor serology is sufficient to exclude the diagnosis. PAIR is also an effective alternative to chemotherapy alone because it has a higher efficacy and avoids the problem of drug resistance. It also shortens the time of treatment and final recovery. PAIR is a valuable alternative to surgery in terms of cost containment and hospitalization time. [42, 43, 44, 45, 46, 47] In types I and II (Gharbi classification), CE1 and CE3a (WHO-IWGE classification) echinococcal cysts with no or incomplete response to therapy, PAIR is an effective therapeutic tool in the management of human cystic echinococcosis.
Increasing evidence shows that CE2 cysts (multivesiculated, type I in Gharbi classification) and CE3b (predominantly solid with daughter vesicles) [13] tend to relapse after PAIR, [48] so other percutaneous treatments should be adopted, if indicated, for this type of cyst.
Reserve PAIR for use in highly specialized centers where teams are well prepared to deal with possible complications.
Some authors have treated CE2 and CE3b cysts with large-bore catheters, but studies on larger cohorts of patients are needed to conclude that this method is efficacious. [49, 50]
A 2017 retrospective study showed that percutaneous aspiration without injection of scolicidal agents but in combination with long-term albendazole administration is probably as effective as, simpler than, and safer than percutaneous treatments with injection of scolicidal agents. [51]
Consultations
Consult a surgeon to discuss the opportunity of surgical intervention.
Consult a radiologist for injection of contrast medium in the cyst after fluid aspiration if PAIR is scheduled. Contrast injection in the cyst allows the physician to exclude connections of the cyst with the biliary tree. Contact of scolecoidal agents, such as alcohol and hypertonic sodium chloride solution, with the biliary epithelium may lead to cholangitis. Attempts to inject albendazole directly into the cysts have yielded interesting results in animal studies but are still methodologically weak in human studies. Most recently, a glucose solution as a scolecoidal agent has been used with good results in vitro. [52] Studies in vivo should confirm the safety of this approach before it can be applied to humans.
Consult an anesthesiologist for assistance in case of anaphylactic shock or anaphylactoid reactions if PAIR is scheduled.
Prevention
In endemic areas, distribution of educational material in elementary schools regarding modes of transmission of the disease is helpful to increase knowledge about the nature and transmissibility of cystic echinococcosis.
Educational material should include information about proper disposal of sheep viscera in abattoirs and proximity to dogs and sources of transmission.
Further Outpatient Care
During treatment of patients discharged on benzimidazoles, monitor aminotransferases, WBC, RBC, and hemoglobin monthly.
Evaluate patients for ultrasonographic appearance modifications and changes in serology titers after 3 months of treatment and then for several years (at least 5).
Further Inpatient Care
Reevaluate patients for symptom resolution and determination of cure.
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WHO Informal Working Group on Echinococcosis standardized ultrasound classification of echinococcal cysts. Image courtesy of World Health Organization (WHO).
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CE1 cyst in the right segments of the liver in a young Albanian boy
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CE3a echinococcal cyst of the liver. Note the folding endocyst ("waterlily sign") typical of CE3a cysts.
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CE3b cyst in the right lobe of the liver. The cyst is predominantly solid with a few daughter cysts
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CE4 cyst in the liver. The cyst is completely solid and inactive.
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CE3b cyst in the muscles of posterior thigh (scanned with a convex ultrasound probe).
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CE4 cysts in the peritoneum in a patient with disseminated echinococcosis (longitudinal scan).
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Viable scolices (note rostellar hooklets).
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CT scan of peritoneal, disseminated echinococcosis
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MR scan of echinococcal cyst in the right psoas muscle, infiltrating the adjacent vertebral body
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Ultrasound scan of a CE3b subcutaneous cyst located in the lumbar area. The cyst was the subcutaneous extension of a cyst located in the spine that had been previously operated on.
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MR of the spine showing CE involvement of CE3,CE4,CE5 vertebral bodies, spinous processes and subcutaneous tissue (same patient as # )
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CT scan showing CE infiltration of vertebral bodies and destruction of left peduncles
