Background
Hepatic Alveolar Echinococcosis (HAE) is a zoonotic disease caused by the larvae of Echinococcus multilocularis. In China, Qinghai Province is considered to be endemic to this parasite, as well as Sichuan Province, Gansu Province, and the autonomous regions of Xinjiang and Tibet [
1]. HAE is also called “parasitic cancer” because of its invasiveness, which is similar to the biological characteristics of a malignant tumor [
2]. As far as we know, HAE in China and Europe does not differ much in terms of clinical symptoms. Clinical symptoms vary with the degree of organ invasion involved. Given that HAE mainly invades the liver, the symptoms are similar to the liver cancer. Most patients seek treatment in the hospital for symptoms such as abdominal pain, jaundice, and/or weight loss [
3]. Without timely diagnosis and therapy, the prognosis is worse, and approximately 95% of patients will die [
4]. Therefore, aggressive therapy is often necessary to eradicate the totality of the parasites.
At present, radically surgical resection combined with antiparasitic drug treatment has been considered the first choice for the treatment of HAE [
4]. However, radical resection has more trauma and more postoperative complications than MWA in small lesions of liver cancer [
5]. As we all know, MWA causes coagulative necrosis of the lesion tissue by generating high temperature around the lesion and has achieved good therapeutic results in the treatment of liver malignant tumor [
6]. Therefore, MWA may be a good choice for the treatment of HAE.
To date, there are few reports about MWA for the treatment of HAE [
7,
8]. The present study aimed to analyze the effectiveness and safety of MWA in the treatment of HAE.
Discussion
In order to verify the effectiveness and safety of MWA, the data of 45 patients were analyzed retrospectively. We found that MWA was characterized by short operative time, few postoperative complications, short postoperative hospital stay, and low recurrence rate. At the same time, compared to radical surgery, it was less traumatic for the patients, allowing for a higher quality of life. Finally, we believe that MWA is an effective and safe method for the treatment of HAE.
In our study, the complete ablation rate was 100%. Although the recurrence rate was 13% (6/45), we get the result is to be acceptable. Firstly, Salm et al. [
15] showed that the recurrence rate of radical surgery for HAE was between 2 and 16%; and our post-operative recurrence rate is within this range. Secondly, in a study by Joliet et al. [
16], it was noted that 2% (1/42) of patients with R0 resection had extrahepatic metastasis, and the probability of intrahepatic metastases in R1, R2 resected patients was 36% (5/14), and 66.7% (2/3), respectively. In addition, they pointed out that patients with non-R0 resection had a median recurrence time of 10 months. In contrast, the median time of recurrence was 22 months in our study, which was significantly longer than that in their study. Meanwhile, our patients did not present with extrahepatic metastases, and have a lower recurrence rate compared to non-radical resection.
In radical surgery, the common site of recurrence of HAE is at the edge of the surgical incision [
17]. Similarly, our study also shows that the site of recurrence is commonly associated with the ablation margins. When MWA is used for liver cancer, recurrence also occurred near the ablation area [
5,
18]. It’s believed to be due to the presence of an infiltrating area around the HAE lesion, which has characteristics of invasive growth similar to that of malignant tumors [
19]. The main factor leading to the recurrence of HAE is that the marginal invasion zone is not completely inactivated. Since there is uncertainty regarding the extent of the infiltrative zone, in our experience, the ablation zone should cover at least 0.5 cm of liver parenchyma surrounding the lesion. We agree with the view that Albendazole (ABZ) should be applied for 2 years after any treatment of HAE [
20].
In the study, we have shown that the efficacy of MWA is confirmed in lesions no larger than 5 cm in diameter. Since HAE is a benign disease, we also included patients with lesions larger than 5 cm in diameter, based on Wang et al.'s experience of treating giant hepatic hemangiomas with MWA [
21]. But these lesions account for only 8.8% (5/57). Data on the effectiveness of MWA in large lesions are still insufficient. Although there were no recurrence or serious complications during the follow-up, other potential benefits of MWA were not evaluated in our study. Therefore, we still recommend that these patients choosing radical resection.
As reported by the National Institute for Health and Care Excellence, MWA is a safe treatment with “no major safety concerns” [
22]. Meanwhile, two large, retrospective MWA studies showed major complication rates of 2.6% and 2.9% respectively [
23,
24]. However, previous studies have shown that the incidence of postoperative complications in patients undergoing radical resection was 14%-40% [
25,
26]. In an article exploring the surgical methods of HAE, Yang and colleagues [
27] showed that the probability of minor complication and major complication after radical resection was 18.4% (16/87) and 9.2% (8/87) respectively, and there were two deaths. In the study by Joliet and colleagues [
16], the probability of minor and major complications of the surgery was even higher, at 25% (15/59) and 9% (5/59), respectively. At the same time, a study has shown that the mortality rate of HAE patients undergoing radical surgery is 0–3.5% [
28]. But, in our study, the rate of minor complications after MWA was 11.1% (5/45), and there were no serious complications and deaths. Additionally, these minor complications are usually self-limiting and do not require any further treatment. Although our patients had an increased post-procedure aminotransferase level, this only required supportive therapy. Andreano et al. [
29] speculated that the total volume of ablation is associated with increased post-procedure aminotransferase levels. In our study, microwave ablation does not affect the patient's coagulation function. In addition, patients who underwent MWA had a faster postoperative recovery and a significantly shorter postoperative length of stay than patients undergoing radical surgery [
27]. Therefore, we believe that microwave ablation is a safe method for the treatment of HAE.
In our experience, the relationship of the lesion to the hilar and intrahepatic vessels and bile ducts is an important key in the evaluation before MWA. With this as a starting point, we have developed the appropriate exclusion criteria. Among the patients, single (80.0%) and multiple lesions (20%) were involved, and lesions smaller than 3 cm, 3–5 cm, and > 5 cm were also included. The efficacy of MWA treatment could not be determined because the sample size of > 5 cm was too small to be included. However, for patients ≤ 5 cm, our study initially showed the effectiveness of its treatment.
In our study, one of the six patients who relapsed was P3N0M0, Kodama type 3; five were P1N0M0, Kodama type 1. According to Azizi et al. [
10], Kodama type 1–3 is metabolically active. The recurrence in these six patients may be due to the failure to completely ablate the "infiltrative zone" around the lesion. However, the remaining metabolically active 44 lesions were ablated. Thus, our results suggest that MWA can be used in patients with P1N0M0 stage and Kodama type 1–3. Also, in conjunction with the study by Azizi et al. [
10], we suggest that a follow-up can be adopted for patients with Kodama type 4–5. When the lesion tends to progress, aggressive surgical or MWA treatment is then promptly undertaken. Of course, we still need more studies to investigate the appropriate population for MWA to treat HAE.
The study with the largest number of cases and the longest follow-up period to evaluate the efficacy of MWA in the treatment of HAE. However, this study also has several limitations. First, the study was descriptive. So, we did not set up a control group. But we have compared the results of other researchers and confirmed the safety and efficacy of MWA to some extent. Secondly, the number of cases with a follow-up period of more than 5 years is still relatively insufficient. We need studies in this area to confirm the long-term recurrence rate of MWA. Third, we have only confirmed the effectiveness and safety of MWA for the treatment of lesions up to 5 cm in diameter. The performances of MWA in large lesions were not assessed in our study. Finally, this is a single-centered and retrospective work, which can easily lead to selection bias. Therefore, more researches are needed to verify our findings.
In conclusion, our results show that MWA is a safe and effective way to treat HAE. Meanwhile, it provides a new option and a new way of thinking about the treatment modality for patients with lesions ≤ 5 cm in diameter, P1N0M0, and Kodama type 1–3. And it has the possibility to replace radical surgery and drugs in the treatment of early HAE.
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