Because of mostly asymptomatic cyst growth and often-neglected nonspecific low-grade symptoms, many cases of cystic echinococcosis (CE) caused by Echinococcus granulosus in the pediatric population are diagnosed at school age, in an advanced and even complicated stage. In 2003, after 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old boy was diagnosed with massive liver CE, with ∼20 round-shaped double-walled medium-sized infective cysts, which permeated the whole liver. Because of their wide distribution across the liver tissue and the risky superficial position of some cysts, liver transplantation emerged as the optimal therapeutic option. Despite being described as only an exceptionally used method for CE, we subjected our patient on 4 occasions to a radiofrequency energy thermoablation (RFT) procedure similar to the one used for malignant neoplasms. In total, 9 superficially situated cysts were initially treated with RFT by using a 14-gauge outer needle and a temperature of 70°C for 8 minutes per cyst, and the remaining cysts were treated with the puncture-aspiration-instillation-reaspiration procedure, along with albendazole (15 mg/kg per day) therapy, for a period of 20 months. After 2 years of follow-up, 4 residual small-sized semisolidified cysts were seen in the liver, and the patient showed no signs of relapse. Although not routinely used, RFT, along with puncture-aspiration-instillation-reaspiration and prolonged albendazole therapy, has shown good tolerability and long-term efficacy in the treatment of multiple infective CE, which could suggest the usefulness of the RFT method beyond salvage situations in pediatric patients.
Cystic echinococcosis (CE) is a worldwide distributed anthropozoonosis, caused by larvae of E granulosus. Living in the canine intestine, the adult parasite sheds its eggs, which, after feco-oral transmission, can cause the development of parasitic cyst(s) in humans in virtually any part of the body, with the liver being affected in >65% of cases; however, 20% to 40% of individuals develop multiple cysts.1 According to the World Health Organization (WHO) classification, cystic echinococcosis stage 1 (CE1) and cystic echinococcosis stage 2 (CE2) cysts are considered infective, CE stage 3a and cystic echinococcosis stage 3b (CE3b) are considered transitional, and CE stage 4 and CE stage 5 are considered noninfective.2 Because of playful and intimate contact with dogs, combined with often insufficient hand hygiene, children are at an increased risk for infection, particularly in rural endemic areas.3 Because of mostly asymptomatic growth of the cyst and infrequent use of preventive imaging diagnostics, only 10% to 20% of patients <16 years of age are diagnosed during the asymptomatic stage, with the rest being diagnosed in the symptomatic and complicated phase of the disease, usually at school age.3,–7
Among 4 current therapeutic options for the treatment of CE (percutaneous, surgical, medicamentous, and “watch and wait”), the percutaneous treatment modalities are rarely used in children, and data about their outcomes are scarce.5,–8
Since the first description of its use in this setting,9 radiofrequency energy thermoablation (RFT) was only exceptionally used for the treatment of CE in adults, and recently a successful use of the new radiofrequency electrode in the treatment of a liver hydatid cyst in a pediatric patient has been published.10 Optimal indications, safety, and long-term efficacy of RFT for the treatment of CE in children still remain unexplored.
After 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old, previously healthy pupil from a rural area was admitted to our tertiary care university hospital in March 2003 because of massive hepatic CE diagnosed by ultrasound, multislice computed tomography (MSCT), and positive serology blood test results.
The initial MSCT scan of the abdomen revealed ∼20 round-shaped double-walled infective cysts (according to WHO,2 CE1 and sporadically CE2 cysts), up to 5.92 × 8.76 cm, that permeated the whole liver (Fig 1).
At admission, the patient’s body temperature was normal, and his liver was tender and palpable for 4 cm; however, other clinical findings were unremarkable. Erythrocyte sedimentation rate was 32 mm per h, C-reactive protein was 3 mg per L, and leukocyte count was 9.4 × 109 per L with 968 eosinophils (EOs) per µL of peripheral blood; other routine laboratory findings were normal. As initial treatment, albendazole therapy was started in a daily dose of 15 mg per kg, divided in 3 daily doses. Ten days after admission, the patient became subfebrile, and the rise in erythrocyte sedimentation rate (92 mm/h) and leukocyte count (13.9 × 109/L) with 2641 EOs per µL of peripheral blood was found. Blood culture and urine culture remained sterile, but empirical treatment with amoxicillin-clavulanic acid was applied for 3 weeks, resulting in fever and leukocytosis resolution, while eosinophilia with 2321 EOs per µL remained. After obtaining verbal consent from the patient’s parents and a 28-day course of albendazole therapy, the first percutaneous RFT with local anesthesia was performed by an expert radiologist under ultrasound guidance, using a 14-gauge outer needle (LeVeen Needle Electrode; RadioTherapeutics, Mountain View, CA). In contrast to the previously described index procedure by Brunetti and Filice,9 in our patient, the superficially lying cysts were approached by the RFT method. The 4 most critical cysts were treated by using a temperature of 70°C for 8 minutes per cyst. Parasitological examination of the aspirated cyst fluid revealed well-preserved E granulosus elements before the procedure and destructed E granulosus elements after the procedure. In the postprocedure samples after incubation with sodium taurocholate in Hanks’ buffer for 48 hours at 37°C (“stimulation”),11 protoscolices revealed no signs of viability, and 75% of them showed signs of destruction.
The following 3 RFT procedures were further performed on 5 cysts, in intervals of 2 to 3 weeks, accompanied by the development of a clinically silent rise of transaminases, with highest levels of aspartate aminotransferase at 125 U per L, alanine aminotransferase at 193 U per L, and γ-glutamyl transferase at 90 U per L, without improvement after halving the daily dose of albendazole. Liver damage caused by RFT was suspected, the daily dose of albendazole was returned to 15 mg per kg after 2 weeks of the reduced-dose regimen, and further percutaneous treatments were continued by 7 puncture-aspiration-instillation-reaspiration (PAIR) procedures until October 2004, whereby an 18-gauge needle was used, and instillation of scolicidal 95% ethanol was performed, according to the recommended WHO protocol.12
One to 4 cysts were treated with each procedure. During the treatment with PAIR, gradual normalization of transaminases and levels of EO in blood followed, and our patient tolerated percutaneous procedures well. Therapy with albendazole, lasting for 20 months, was also tolerated without any unwanted reactions.
After 11 percutaneous treatments, the follow-up MSCT scan of the abdomen revealed partial regression of some treated liver cysts in the sense of decreased size, changed shape, and partial solidification. Two years later, the ultrasound follow-up examination revealed 1 cyst in the left hepatic lobe and 3 cysts in the right hepatic lobe, all semisolidified and with a maximal diameter of 22 mm. Further annual ultrasound controls in the local county hospital were recommended, and parents were strongly advised to return with the patient to our hospital if the signs of disease recurrence appeared, but until today, 15 years after the treatment, that did not happen.
According to rare pediatric cohorts described, it seems that in comparison with adult populations with CE, children are more prone to present with multiple cysts, multiple organ involvement, and with lungs being affected more frequently.5,13,–17 Moreover, lung affection in a child as young as 6 months has been described.18 A disease prevalence rate as high as 2.1% among school children from Golog, Qinghai, west China, has been reported.3
In select inoperable cases, in patients with peritoneal cysts or cysts in multiple organs, the continuous, indefinitely long treatment with 10 to 15 mg per kg per day of albendazole is recommended as the first choice,19 whereby reported efficacy after 3 to 6 months of continuous therapy reached 30%.21 Little is known about the safety of the long-term albendazole therapy in the pediatric population19; however, our experience in the described case speaks in favor of good tolerability of the 20-month albendazole therapy in a child who ended the therapy without subjective complaints and with transaminase levels within normal values.
In described pediatric cohorts, surgical excision was the most frequently used procedure, which was applied in 98.3% and 98.0% of patients with CE, respectively,5,7 but solely medicamentous treatment of abdominal CE in children, applied in 54% of the patients with a mean duration of 142.5 days, was reported being highly effective.6
Since first reported as a successful and safe procedure in 1985,22 the percutaneous treatment of CE experienced many modifications, from the PAIR protocol recommended by WHO for CE1 and CE stage 3a cysts,12 continuous catheter drainage for cysts larger than 10 cm,19 Örmeci et al23 modification of PAIR (outpatient basis, without albendazole prophylaxis, smaller needle of 22 gauge, procedure lasts 5 minutes), and puncture-aspiration-instillation (PAIR without the reaspiration step, applicable for CE1 through CE stage 5 cysts)24 to a variety of procedures aimed to remove the entire endocyst and daughter cysts from CE2 and CE3b cysts (eg, percutaneous evacuation).25 During percutaneous procedures, the longest possible transhepatic needle approach to the cyst is advised, to reduce the risk of intraperitoneal leakage of the infective material.
Because of symptomatic disease progression, and superficial location of medium-sized cysts, neither surgical resection nor solely medicamentous treatment were options in our patient. To avoid liver transplantation and patient stigmatization by lifelong immunosuppression and urged to act by febrility and rise of eosinophilia, we considered percutaneous approaches under albendazole therapy as the most appropriate therapeutic option. Given the fact that only superficially situated cysts were initially accessible in our patient, because of the risk of shedding an aggressive scolicidal agent into the abdominal cavity if using PAIR, and inspired by a pioneer report of RFT use in adult patients with CE3b cysts,9 we decided to try the RFT method in our patient. Although there have been some doubts regarding the safety of RFT in patients with cysts in the early, infective stage with plentiful fluid content,26 after a 2-year follow-up period in our hospital, there were no signs of relapse in our patient to date, which is in accordance with the previously reported adult patient case report.27 The first experiences with RFT in 6 patients with stage CE3b cysts were rather disappointing, due to cyst relapse in 4 patients, which was speculated to be caused by the complex structure of the cyst, which prevented the full ablation of all daughter vesicles.28 However, the method was also considered as unsuitable for the treatment of superficial or peritoneal lesions, and RFT was abandoned with time.28
On the contrary, with our experience, we relativize the danger of rupture in superficial liver hydatid cysts treated by RFT and suggest the possibility of increased efficacy of this method in managing simply structured, watery CE1 cysts. Recent advances in technology, with the development of a new radiofrequency electrode capable of simultaneous drainage and ablation, yielded an effective and safe treatment of CE, as it has been reported in a case of a 7-year-old boy with a 4-cm hepatic CE1 cyst.10
Regarding the benefit of the procedure, a transient rise in liver enzymes was an acceptable disadvantage in our patient, and the used method could be considered being safe. It remains unclear whether enzymatic liver damage could be prevented by manipulating the applied temperature level and/or duration of each procedure, which should be further investigated in appropriate cases.
Hereby, we report the efficacy and good tolerability of RFT, PAIR, and prolonged albendazole therapy in the treatment of numerous CE1 and CE2 superficial and deep-liver cysts in a pediatric patient, which could also suggest the usefulness of the RFT method beyond salvage situations.
Dr Balen Topić conceptualized and drafted the initial manuscript and reviewed the literature; Drs Skuhala and Desnica reviewed the available literature and critically read the manuscript; Dr Višković analyzed and interpreted the patient’s images; Dr Drinković analyzed and described percutaneous therapeutic approaches; and all authors participated in the conceptualization and design, analysis and interpretation of data, drafting and revision of the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.