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Percutaneous Radiofrequency Ablation for Hepatoblastoma in a 2-Year-Old Child

Sharoev TA*1234,Grachev NS1,Rokhoev MA56,Potapova EI5,Rybakova KS1,Skоbееv DA7 and Ivanova NV25

1Federal research center of pediatric hematology, oncology and immunology named after Dmitry Rogachev of the Ministry of Heath of the Russian Federation;
2Research Clinical Institute of Childhood of the Moscow Region;
3Federal State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Continuous Professional Education” of the
Ministry of Healthcare of the Russian Federation;
4Moscow Regional Research and Clinical Institute “MONIKI”;
5V.Y. Voyno-Yasenetsky Scientific and Practical Center of Specialized Medical Care for Children
6State Budgetary Public Health Institution «N.F. Filatov Children’s City Hospital of Moscow Healthcare Ministry»
7State budgetary healthcare institution «Мorozovskaya Children’s City Clinical Hospital of the department of health of the city of Moscow»

*Corresponding author

*Sharoev TA, Federal research center of pediatric hematology, oncology and immunology named after Dmitry Rogachev of the Ministry of Heath of the Russian Federation, Russia

Abstract

Introduction: Malignant liver tumors account for 1.5% of all malignant neoplasms and 3.0% of solid tumors in children. Among malignant liver tumors in children under 4, hepatoblastoma is registered in 80%. The surgical stage is the most important in the treatment of hepatoblastoma. Liver surgeries are often accompanied by intra- and postoperative complications, including those that are life-threatening for the child. One of the promising areas in pediatric liver oncology surgery is radiofrequency ablation (RFA) - a method of local action on the tumor focus, causing coagulation necrosis of the tumor under the action of high-frequency current. RFA is not yet widely used in hepatoblastoma surgery in children. In this regard, the presented clinical case is of unconditional interest to pediatric oncologists, pediatric oncologists, pediatricians and all those interested in the problems of tumors in children.
Aim: demonstration of the possibilities of using percutaneous radiofrequency ablation for hepatoblastoma in a young child.
Clinical observation: A 2-year-old child has been ill since the beginning of August 2024, when after an abdominal injury as a result of a fall, after ultrasound and CT of the abdominal organs, a multinodular tumor of the right lobe of the liver was detected with damage to the segments: S5 (31x32x30 mm), S6 -S7 (14x36x27 mm) and contrast defects in S4. (29x40x20 mm). Conclusion: tumor of the right, damage to the left lobe of the liver is not excluded, possibly malignant in nature. The AFP level is increased to - 1050 ng / ml. Hepatoblastoma was diagnosed (PRETEXT 3). The patient underwent preoperative chemotherapy (CT) according to the clinical guidelines of the Russian Federation. Against the background of CT, the tumor size decreased and the AFP level decreased to 36.5 ng / ml. On October 10, 2024, an operation was performed: video-assisted percutaneous radiofrequency ablation of a liver tumor. There were no intra- and postoperative complications. Histological analysis of tumor areas taken for biopsy after RFA revealed a picture of complete therapeutic pathomorphism. After the operation, the child received chemotherapy according to clinical recommendations. AFP indicators completely normalized after the operation and remain normal during the dynamic monitoring of the patient. The patient has no signs of relapse of the disease.
Conclusion: The presented clinical case of RFA of hepatoblastoma of the right lobe of the liver in a two-year-old child demonstrates that minimally invasive percutaneous RFA is a good alternative to classical anatomical liver resection, a low-traumatic organ-preserving method capable of achieving complete destruction of the tumor (complete therapeutic pathomorphosis) in the absence of intra- and postoperative complications.

Keywords: Radiofrequency ablation, Tumors in children, Hepatoblastoma, Minimally invasive surgery

Introduction

According to statistical analysis, solid tumors in children under 15 years of age occurred in 51.6% of cases in Russia in 2023. The most common localizations of solid tumors in childhood are malignant neoplasms of the brain and other parts of the nervous system, the proportion of which was 14.9% of all neoplasms and 28.9% of solid tumors. Malignant neoplasms of the liver accounted for 1.5% of all malignant neoplasms and 3.0% of solid tumors [1]. Among malignant liver tumors in children, hepatoblastoma is the most common, accounting for up to 80% of all liver neoplasms in patients under 4 years of age [2]. Hepatoblastoma is a tumor that produces the embryonic protein alpha-fetoprotein (AFP), an important but non-specific marker, since it can also increase in other malignant tumors. An increase in AFP is initially recorded in 90% of cases in patients with hepatoblastoma. Very high AFP values ​​are associated with local or metastatic spread of the tumor and reflect its large mass [3]. AFP is not only a diagnostic marker for hepatoblastoma, but also a reliable predictor of treatment results, and requires regular monitoring during therapy [4].

Surgical and medicinal methods and their combinations are used to treat hepatoblastoma. The surgical stage is the most important, and sometimes the only method in the treatment of hepatoblastoma. The scope of the operation depends on the prevalence of the tumor process in the liver: from atypical resection, segmentectomy, to extended lobectomy. Any operation on the liver is a highly traumatic surgical intervention capable of causing both intra- and postoperative complications, including those that are life-threatening for the patient. Based on this, medical researchers and engineers working in the field of surgery are searching for new technologies to influence liver tumors.

The surgical stage is the most important, and sometimes the only method in the treatment of hepatoblastoma. The scope of the operation depends on the prevalence of the tumor process in the liver: from atypical resection, segmentectomy, to extended lobectomy. Any operation on the liver is a highly traumatic surgical intervention capable of causing both intra- and postoperative complications, including those dangerous to the life of the patient. Based on this, doctors, researchers, engineers working in the field of surgery are looking for new technologies to influence liver tumors. One of the promising areas that is gaining popularity in pediatric oncological practice is radiofrequency ablation (RFA). Being a method of local action on the tumor focus, causing coagulation necrosis under the influence of high-frequency current, it can be a full-fledged method of tumor removal with minimal invasiveness [5, 6]. It should be noted that in pediatric oncological surgery, in contrast to adult oncological surgery, the RFA method has become widespread relatively recently. This is due to the low number of studies and publications on the possibilities, risks and complications of RFA in pediatric oncological surgery practice [7,8].

Meanwhile, RFA can be a full-fledged method of treating liver tumors in children, especially in situations with multiple, difficult-to-remove or recurrent foci, with limited functional reserves of the liver [5, 8]. Thus, in the article by Long H. et al., 2023, the successful use of RFA in children with recurrent hepatocellular carcinoma was confirmed. In the study, complete ablation was achieved in 93.3% of cases in the absence of serious complications [6]. Despite its advantages in the form of low invasiveness, relative safety and parenchyma-preserving direction, RFA has a number of possible complications. The most common ones include the risk of bleeding as a result of vascular damage during the passage of electrodes and thermal effects, infections, including abscesses in the ablation area, as well as damage to adjacent organs if they are located close to the tumor. Specific complications include the formation of biloma as a result of damage to the bile ducts and the development of liver failure in case of extensive ablation zones of foci in the liver [7]. However, high-precision navigation allows to reduce the risks of complications, expand indications, increase the possibility of optimization and application of RFA for liver tumors in young children [5,9,10]. There are several types of RFA depending on the access method: percutaneous ablation, performed by puncture through the skin under ultrasound or CT control; laparoscopic, performed under endoscope control, allowing for more precise visual control, especially in hard-to-reach areas; open (laparotomic), most often used in combination with other interventions, allowing for more radical and safe ablation of foci under visual and palpation control [5,7].

Among the above-mentioned types of RFA, percutaneous thermoablation is of particular interest as the least invasive method. An important aspect of this method is navigation control during the manipulation. In this regard, our clinical observation of RFA of hepatoblastoma of the right lobe of the liver in a two-year-old child is of unconditional interest to pediatric oncosurgeons, pediatric oncologists, radiation diagnosticians and all those interested in the issues of diagnostics and treatment of childhood tumors.

Aim: demonstration of the possibilities of using percutaneous radiofrequency ablation for hepatoblastoma in a young child.

Clinical observation. According to the mother, in early August 2024, in the evening, while in the bathroom, the child fell on the sink and hit his chest and stomach, and after falling on the floor, also hit the back of his head. He did not lose consciousness, but nausea and four-fold vomiting were noted. That same evening, the parents sought help at the emergency room of one of the Moscow children's city clinical hospitals. The boy was examined by a traumatologist. After an X-ray of the chest and skull, a contusion of soft tissues of the above-mentioned areas was diagnosed.

During an ultrasound examination (US) of the abdominal organs (08.08.2024) in the projection of the V and VI segments of the liver, a neoplasm of a heterogeneous structure measuring 44x24x45 mm with a polycyclic contour, areas of increased and decreased echogenicity and small anechoic inclusions (10x4.5 mm) was found. The neoplasm deformed the contour of the liver, while the size of the organ was not increased. On 08.08.24 the child underwent computed tomography (CT) of the abdominal cavity with contrast enhancement. In S5 of the liver, a multinodular neoplasm was detected, measuring 31x32x30 mm, with a thin capsule, actively accumulating contrast in the arterial and venous phases, with rapid washout of the contrast agent in the early delayed phase. In S6-7 and S4, defects in contrasting the liver parenchyma were determined measuring 14x36x27 mm and 29x40x20 mm, respectively (Figure 1a, b).

Conclusion: CT picture of a multinodular neoplasm of the right lobe of the liver. The malignant nature of the pathological process cannot be excluded. Contrast defects S6-7 and S4 are possibly post-traumatic in nature.

Blood was taken for tumor markers. AFP level = 1050 ng/ml. Considering the above, the child was transferred for further examination and treatment to the specialized pediatric oncology department No. 1 of the State Budgetary Healthcare Institution "Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Health Department". After a comprehensive examination of the patient, the diagnosis was established: hepatoblastoma, damage to the right and left lobes of the liver, Pretext 3. standard risk group. After discussing the child at a council of pediatric oncologists, oncosurgeons, and radiation diagnosticians, a decision was made to administer preoperative chemotherapy (CT) to the patient with Cisplatin, in accordance with the existing clinical guidelines of the Russian Ministry of Health. The course of therapy was uneventful. During the treatment, a decrease in AFP to 36.5 ng/ml was noted. After a control CT scan of the liver, a significant reduction in the size of the primary tumor was noted, which at the time of the study was localized in the VI segment of the organ. Considering the positive results obtained after neoadjuvant chemotherapy in the form of a decrease in AFP levels and a reduction in tumor size, after discussing the patient at a council of doctors, a decision was made to perform percutaneous RFA on the child.

 October 10, 2024 surgery: video-assisted percutaneous radiofrequency ablation of liver tumor.

Description of the operation: the patient is positioned on the operating table on his back. Open cannulation of the abdominal cavity was performed through an infraumbilical incision of 0.5 cm with the installation of a 5 mm port for the camera. Pneumoperitoneum CO2 -8 - mm Hg. One additional working port was installed under direct visual control, 5 mm along the midclavicular line on the right. During the revision of the organs and tissues of the abdominal cavity, no pathology was revealed, additional pathological volumetric masses were not determined. During liver revision in the right lobe of the S6 segment, a tumor node up to 3 cm in diameter with a bumpy surface, whitish in color, is determined. Considering the size of the neoplasm, comparison of the visual intraoperative assessment with ultrasound and CT data, after consultation in the operating room, a decision was made to perform RFA of the liver tumor.

Under visual control of an endoscope using the Cool-Tip™ Covidien (RFA system (Medtronic), a needle with a working surface of 2 cm was inserted percutaneously into the tumor under its base. Exposure time was 15 min. RFA of the tumor node was performed. The temperature in the tumor reached - 710C. A needle was inserted into the base of the tumor from the opposite side in a similar manner. The duration of RFA was 15 min. The temperature in the tumor reached 710C.

Two more similar procedures were performed with vertical insertion of the needle into the tumor with reaching a temperature of -670 C. The exposure time in all cases was 15 minutes (Figure 3). Biopsy material was taken from the scab formed on the surface of the tumor node for morphological analysis. The port placement sites were sutured with Vicryl (4-0). Alcohol, aseptic patch. There were no complications during RFA. The postoperative period was uneventful.

Results of histological examination No. O15316_24: taking into account the clinical data, the morphological picture corresponds to fragments of liver tissue with signs of complete therapeutic pathomorphosis (Figure 4).

IHC study with antibodies to AFP, Beta-catenin, CD163, CD68, Glypican 3, Hepatocyte, Ki-67, Oct 3/4, PanCK, PLAP, Sall4 was performed - phenotype anomalies were not revealed. Expression of CD68 and CD163 in macrophages. No anomalies were revealed. Final morphological diagnosis: hepatoblastoma. AFP levels 1 week after surgery were 3.7 ng/ml (normal). AFP levels 4 months after surgery (in February 2025) dropped to 2.11 ng/ml. According to imaging studies (ultrasound, MRI), there is no evidence of relapse of the disease in the child.

Figure 1: a, b Computed tomography of the liver with contrast enhancement.

1a (axial section) - in S5 of the liver a neoplasm is determined, measuring 31x32x30 mm, with a thin capsule, actively accumulating contrast

1b (reconstruction) – in S6-7 and S4, defects in contrasting the liver parenchyma with dimensions of 14x36x27 mm and 29x40x20 mm were determined

Figure 2: Stage of radiofrequency ablation. Under visual control of an endoscope using the Cool-tip™ RF Ablation System E Series /Medtronic (UK), a needle with a working surface of 2 cm is inserted percutaneously into the tumor under its base.

Figure 3: Stage of radiofrequency ablation. A needle with a working surface of 2 cm is inserted percutaneously into the tumor in a vertical direction (perpendicular to the neoplasm).

Figure 4:Liver tissue fragments with therapeutically induced changes represented by clusters of foamy macrophages. Hepatocytes are polygonal in shape with optically “empty cytoplasm”.

Discussion

It has been reported that children without any underlying diseases who undergo mechanical ventilation for bronchiolitis caused by RSV infection have increased transaminase levels in 19% [2]. In this previous study, AST was increased the most, and ALT was less increased, and increased mortality was associated with longer duration of respiratory management and longer hospital stays. Another retrospective review of the medical records of 161 hospitalized children with acute bronchiolitis also demonstrated that 14 of the children (8.7%) had increased ALT levels. Fifteen patients (32.6%) had high prothrombin times, 3 patients (6.5%) had greatly increased partial thromboplastin times, and 5 patients (21.7%) had hepatomegaly. In addition, a high ALT level was significantly associated with a long hospital stay and positive urine culture [4]. These studies demonstrated that an increase in transaminase level is often observed in patients with severe disease, which is assumed to be caused by a combination of infections, heart failure, and overload of respiratory muscle, rather than by the hepatitis itself. However, owing to the presence of RSV in the liver tissue and successful viral culture in some cases, RSV hepatitis can be diagnosed in patients [5].

In this study, we reported RSV-associated metabolic encephalopathy in a patient with CHARGE syndrome, who had extreme hypertransaminasemia and carnitine deficiency (case 1). CHARGE syndrome has been reported to be associated with T-cell immunodeficiency, from the results of lymphocyte subset analysis [6]. Therefore, virus load is assumed to be increased in patients with CHARGE syndrome. His pathological findings revealed mitochondrial dysfunction. Recently, mitochondrial dysfunction has been reported to occur in the livers of patients with RSV infection. Hu et al. reported the staged redistribution of mitochondria in RSV-infected cells, resulting in compromised respiratory activities and increased reactive oxygen species generation. Mitochondrial complex I is the key to this effect on host cells, and mitochondrial complex I subunit knock-out cells show increased levels of RSV production [7]. The 2 nonstructural (NS) proteins, NS1 and NS2, of RSV suppress the type I interferon-mediated innate immunity of host cells by degrading or inhibiting multiple cellular factors. Goswami et al. provided evidence for the existence of a large and heterogeneous degradative complex assembled by the NS protein. They demonstrated that the majority of NS proteins and their substrates inside a cell translocated to the mitochondria upon infection [8]. Fujiogi et al. reported the association between respiratory viruses and the systemic metabolism of the host. Among 63 infants with bronchiolitis caused by RSV infection, they found significant differences in 30 discriminatory metabolites, which were predominantly metabolites of lipid metabolism pathways (e.g., sphingolipids and carnitines) [9]. They reported that higher lignoceroylcarnitine intensity is associated with a significantly lower risk of positive pressure ventilation use (OR 0.20; 95% CI: 0.08–0.48; P < 0.001).

Hu et al. aimed to clarify the effects of RSV on host mitochondria, such as RSV-induced microtubule/dynein-dependent mitochondrial perinuclear clustering, and translocation towards the microtubule-organizing center, using high-resolution quantitative imaging, bioenergetics measurements, and mitochondrial membrane potential- and redox-sensitive dyes [10]. Their study showed that RSV infection is involved in impaired mitochondrial respiration, and the loss of mitochondrial membrane potential. In this study, the patient of case 1 improved gradually, and his AST, ALT, CK, and carnitine levels normalized upon L-carnitine treatment. Case 2 involved a CHARGE syndrome patient who was regularly receiving L-carnitine supplementation. Despite presenting with similar increases in transaminase levels as patient 1, this patient recovered uneventfully without any sequelae. These observations support the hypothesis that carnitine supplementation may mitigate RSV-induced hepatic and metabolic dysfunction, potentially by preserving mitochondrial function and reducing oxidative stress. Many studies have reported the use of L-carnitine when diseases involve mitochondrial dysfunction. According to the report by Abbasnezhad et al., a systematic review and meta-analysis demonstrated that L-carnitine supplementation significantly reduced blood levels of ammonia, bilirubin, AST, BUN, and Cr in hepatic encephalopathy patients [11]. In the studies of the hepatoprotective effects of L-carnitine against lead acetate-induced hepatocellular injury using Wistar rats, L-carnitine caused a decrease in hepatic damage with minimal vascular alterations in the central vein. L-carnitine has also been reported to show significant protective effects against hepatocellular apoptosis and inflammation induced by Pb acetate[12].

An alternative explanation for the differences observed between the 2 cases may involve the thermolability of the protein product of CHD7, which is a causative gene of CHARGE syndrome. CHD7 encodes a DNA helicase, which may be thermolabile and vulnerable to stress-induced dysfunction. It is conceivable that febrile illness exacerbates mitochondrial impairment in CHARGE syndrome patients, making them more susceptible to RSV-induced metabolic derangements. A limitation of this study is that we were unable to establish a definitive association between carnitine deficiency and RSV severity owing to the small sample size. Further research is hence needed to evaluate whether the association between CHARGE syndrome and low carnitine levels is confounded by other risk factors.

Conclusion

The presented clinical case of RFA of hepatoblastoma of the right lobe of the liver (PRETEXT 3) in a two-year-old child demonstrates that minimally invasive percutaneous RFA is a good alternative to classical anatomical liver resection, a low-traumatic organ-preserving method capable of achieving complete destruction of the tumor (complete therapeutic pathomorphosis) in a short surgical period in the absence of intra- and postoperative complications. When choosing a method of local action on a tumor, including RFA, it is necessary to take into account the size and location of the neoplasm, age and general somatic condition of the patient. An important component in determining the operation plan is the experience of the surgical team in liver operations in children.

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