Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function

Abstract

BACKGROUND

Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies.

AIM

To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.

METHODS

Clinical data from patients with liver cancer admitted to Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups.

RESULTS

One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 μmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4⁺ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8⁺ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4⁺/CD8⁺ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups.

CONCLUSION

The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

Key Words: Microwave ablation, Liver cancer, Short-term efficacy, Liver function, Immunologic function

Core Tip: Survival is prolonged by laparoscopic surgery in patients with liver cancer. However, the safe range of tumor boundaries is poorly defined and damage to adjacent normal structures can affect liver and immune functions. Our study demonstrated that the short-term efficacy and safety of medical image-guided microwave ablation is similar to laparoscopic surgery in the treatment of liver cancer, but the liver function recovered quickly after microwave ablation, which could enhance immune function.

INTRODUCTION

Liver cancer ranks third among malignant tumor deaths[1]. Surgical removal of cancer lesions can reduce the tumor load, control disease progression, and prolong survival. Thus, surgical resection of cancerous lesions is the preferred method for treating liver cancer. A variety of surgical methods are available for treating liver cancer, and the effectiveness of the different surgical methods varies. Furthermore, some patients develop postoperative complications, including pain, persistent fever, and jaundice, which adversely affect patient prognosis[2]. Due to the rapid progression of liver cancer, the location of cancer lesions is complex. Cancer lesions surrounding the middle hepatic vein, invading the left hepatic vein, or invading the left branch of the portal vein can compress the left branch of the portal vein. Radical resections are difficult to achieve when the lesions are located near the hilum of the liver, adjacent to the gallbladder, diaphragm, hepatic artery, and portal vein. Additionally, surgical procedures require anesthesia, pneumoperitoneum, cutting, suturing, and other procedures, which cause significant damage. Surgery can cause stress and inflammatory responses[3]. In addition, pain caused by the hepatectomy can induce the release of inflammatory factors. Excessive uncontrolled release of inflammatory mediators can lead to perioperative immune suppression, which affects postoperative recovery and patient prognosis[4]. Therefore, developing safer and more effective treatments for liver cancer that can enhance immune function is important for improving outcomes.

Medical image-guided percutaneous microwave ablation for the treatment of solid tumors is gaining favor among patients and physicians. Medical image-guided microwave ablation is achieved by emitting microwaves into tumor tissue. The microwaves kill tumor cells via the thermal effects of microwave magnetic fields[5,6]. The objective of this study was to compare the short-term efficacy and immune function effects of microwave ablation with hepatectomy in patients with liver cancer.

MATERIALS AND METHODS

Research objectives

Clinical data from 70 liver cancer patients who received treatment at Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed. Patients who underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group, n = 35) were compared with patients who underwent medical image-guided microwave ablation (liver cancer ablation group, n = 35). The inclusion criteria were as follows: (1) Liver cancer confirmed by computed tomography (CT), magnetic resonance imaging (MRI), and other imaging and histopathological examinations; (2) Child–Pugh classification for liver function of A or B; and (3) complete clinical data. The exclusion criteria were as follows: (1) Extrahepatic tumor metastasis or large vessel invasion; (2) other malignant tumors; (3) renal failure; (4) history of liver transplantation, (5) autoimmune disease complications; and (6) coagulation dysfunction.

Therapeutic methods

The liver cancer resection group underwent laparoscopic liver cancer resection. After general anesthesia, the relevant skin area was disinfected. A resection was performed below the navel (1 cm). After establishing the pneumoperitoneum, a trocar was placed, and a laparoscopic lens was inserted. After verifying the tumor location and size, the resection line was marked 2 cm from the edge of the tumor. The diseased tissue was removed. The abdominal cavity was rinsed with warm distilled water. Hemostatic gauze was placed on the liver wound to stop the bleeding. After confirming no active bleeding in the abdominal cavity, the laparoscopic instrument and gauze were removed and the incision was sutured.

In the liver cancer ablation group, microwave ablation was performed under the guidance of medical images. The patients fasted for 8 h before surgery. After placing the patient in the supine position, local anesthesia and intravenous assisted anesthesia at the incision site were administered. The location and size of the tumors were verified through medical imaging to clarify the extent of tumor infiltration. The parameters for the microwave ablation therapy device (Nanjing Kangyou Medical Technology Co., Ltd., model KY-2200) were set based on the patient’s condition (power: 40–50 W; time: 8–12 min). The microwave ablation was administered from deep to shallow. For tumors with a diameter of < 3 cm, single needle single point ablation was administered. For tumors with a diameter of ≥ 3 cm, multi-needle multi-point ablation was administered. For tumors adjacent to organs and blood vessels, the ablation range only extended 0.5–1.0 cm beyond the edge of the tumor. Before the end of the microwave ablation, the imaging was reviewed to confirm that the tumor was completely ablated. If the tumor was not completely ablated, the ablation was continued. After complete ablation was achieved, the device was switched to solidification mode, and the heated needle was used to coagulate the needle passage and prevent bleeding, tumor implantation, and liver surface bleeding as much as possible. For postoperative local disinfection, Fu paste was administered to protect the wound.

Observation indicators

Age, gender, number of tumors, maximum tumor diameter, Child–Pugh grade, and adjacent tumor sites were compared between the two groups of patients. Patients underwent a follow-up examination one month after treatment. Abdominal plain scans were performed using enhanced CT or MRI to detect the presence of new lesions. The efficacy was evaluated according to the International Solid Tumor Efficacy Evaluation Standard (mRECIST), which includes complete response (CR), partial response (PR), stable condition (SD), or disease progression (PD). Total effective rate = (CR + PR)/total number of cases × 100%. The incidence of complications within one month after treatment, including gastrointestinal reactions, fever, abdominal fluid accumulation, and liver pain, was determined.

Fasting peripheral venous blood was collected before and one month after treatment. Blood samples were placed in anticoagulant tubes and centrifuged to extract serum. To determine changes in liver function, serum total bilirubin (TBil) and alanine aminotransferase (ALT) levels were detected using a fully automated biochemical analyzer (Hitachi, Japan, model: 7600). To determine changes in immune function, T lymphocyte subsets (CD4⁺, CD8⁺, CD4⁺/CD8⁺) were detected in serum using flow cytometry (Beckman Coulter, CytoFLEX).

Statistical analysis

Statistical analyses were conducted using SPSS 26.0 software. Continuous data are expressed as means with standard deviations (mean ± SD) and compared using t-tests. Count data are expressed as a percentage (%) and compared using χ² tests. Rank data were compared using the rank sum test (Mann Whitney U). P value of < 0.05 was considered statistically significant.

RESULTS

Comparison of general information

As shown in Table 1, no differences in age, gender, number of tumors, maximum tumor diameter, Child–Pugh grading, and adjacent tumor sites were detected between the liver cancer ablation and the liver cancer resection groups (P > 0.05).

Table 1 Comparison of general information, n (%)/mean ± SD.

General information	Liver cancer resection group (n = 35)	Liver cancer ablation group (n = 35)	t/χ2	P value
Age (yr)	56.59 ± 5.83	56.74 ± 6.02	0.106	0.916
Gender			0.072	0.788
Male	26 (74.29)	25 (71.43)
Female	9 (25.71)	10 (28.57)
Tumor number			1.942	0.163
Single	29 (82.86)	24 (68.57)
Multiple	6 (17.14)	11 (31.43)
Maximum diameter of tumor (cm)	2.85 ± 0.74	2.91 ± 0.79	0.328	0.744
Child–Pugh classification			0.254	0.615
A-level	24 (68.57)	22 (62.86)
B-level	11 (31.43)	13 (37.14)
Adjacent site of tumor			0.516	0.915
Paracholecystic	11 (31.43)	13 (37.15)
Diaphragm	5 (14.29)	6 (17.14)
Inferior margin of the liver	12 (34.28)	10 (28.57)
Beside the hepatic vein	7 (20.00)	6 (17.14)

Comparison of recent therapeutic effects between two groups

In the liver cancer resection group, 19 patients experienced CR, 8 patients experienced PR, 6 patients experienced SD, and 2 patients experienced PD one month after the procedure. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in short-term therapeutic effects were detected between the liver cancer ablation and liver cancer resection groups (χ² = 0.850, P = 0.356) (Table 2).

Table 2 Comparison of short-term efficacy, n (%).

Short-term effects	Liver cancer resection group (n = 35)	Liver cancer ablation group (n = 35)	U/χ2	P value
CR	19 (54.29)	21 (60.00)	−0.632	0.528
PR	8 (22.86)	9 (25.71)
SD	6 (17.14)	3 (8.57)
PD	2 (5.71)	2 (5.71)
Total effective rate	27 (77.14)	30 (85.71)	0.850	0.356

CR: Complete response; PR: Partial response; SD: Stable condition; PD: Disease progression.

Comparison of complications

No significant differences in the incidence of complications within one month after treatment were detected between the two groups (χ² = 0.565, P = 0.452) (Table 3).

Table 3 Comparison of complications, n (%).

Complication	Liver cancer resection group (n = 35)	Liver cancer ablation group (n = 35)	χ2	P value
Gastrointestinal reactions	1 (2.86)	1 (2.86)
Fever	1 (2.86)	2 (5.71)
Ascites	0 (0.00)	1 (2.86)
Hepatalgia	1 (2.86)	1 (2.86)
Total incidence	3 (8.57)	5 (14.29)	0.565	0.452

Comparison of liver function before and after treatment

No significant differences in TBil and ALT indicators were detected between the two groups before treatment (P > 0.05) (Table 4). After one month of treatment, TBil and ALT were significantly reduced in both groups compared with the levels before treatment. Serum TBil and ALT levels were significantly lower in the liver cancer ablation group compared with the levels in the liver cancer resection group after treatment (both P < 0.01).

Table 4 Comparison of liver function before and after treatment, mean ± SD.

Liver function indicators	Stage	Liver cancer resection group (n = 35)	Liver cancer ablation group (n = 35)	t	P value
TBil (μmol/L)	Before treatment	58.13 ± 10.65	58.79 ± 11.54	0.249	0.804
	After one month of treatment	49.18 ± 8.64a	41.24 ± 7.35a	4.141	< 0.001
ALT (U/L)	Before treatment	48.21 ± 9.98	48.58 ± 9.37	0.159	0.873
	After one month of treatment	42.32 ± 7.56a	30.85 ± 6.23a	6.927	< 0.001

^aP < 0.05 vs before treatment.

TBil: Total bilirubin; ALT: Alanine aminotransferase.

Comparison of immune function indices before and after treatment

No significant differences in CD4⁺, CD8⁺, and CD4⁺/CD8⁺ indicators were detected between the two groups before treatment (P > 0.05) (Table 5). After one month of treatment, the CD4⁺ and CD4⁺/CD8⁺ indicators increased significantly and the CD8⁺ index decreased significantly in both groups compared with the indicators before treatment. CD4⁺ and CD4⁺/CD8⁺ levels were significantly higher in the liver cancer ablation group compared with the CD4⁺ and CD4⁺/CD8⁺ levels in the liver cancer resection group after one month of treatment (both P < 0.01). The CD8⁺ index was significantly lower in the liver cancer ablation group compared with the index in the liver cancer resection group after treatment (P < 0.05).

Table 5 Comparison of immune function indexes between the two groups, mean ± SD.

Immune function indicators	Stage	Liver cancer resection group (n = 35)	Liver cancer ablation group (n = 35)	t	P value
CD4+ (%)	Before treatment	29.75 ± 6.32	29.52 ± 6.43	0.151	0.880
	After one month of treatment	35.27 ± 5.56a	43.95 ± 5.72a	6.437	< 0.001
CD8+ (%)	Before treatment	25.09 ± 4.78	25.43 ± 4.96	0.292	0.771
	After one month of treatment	22.75 ± 4.62a	20.38 ± 3.91a	2.317	0.024
CD4+/CD8+	Before treatment	1.19 ± 0.28	1.16 ± 0.25	0.473	0.638
	After one month of treatment	1.55 ± 0.32a	2.16 ± 0.39a	7.154	< 0.001

^aP < 0.05 vs before treatment.

DISCUSSION

Liver cancer exhibits occult onset and rapid development. The specific pathogenesis of liver cancer is unclear but may be related to metabolic abnormalities, viral hepatitis, genetic factors, long-term alcohol abuse, and other factors[7-10]. The medical community generally believes that the earlier the malignant tumor is diagnosed and treated, the better the prognosis will be. Hepatectomy is the main treatment for liver cancer. Radical resection of the tumor prolongs survival time. However, the anatomical structure of the liver is complex, and safe tumor boundaries cannot always be accurately defined. Damage to adjacent normal structures and tissues or excessive tumor tissue may limit the effectiveness and safety of surgical radical resection for liver cancer[11].

The application of medical image-guided percutaneous microwave ablation has gradually entered clinical practice. Microwaves cause tumor cells to rub against each other and generate heat, leading to tumor cell necrosis and apoptosis under high-temperature conditions[12,13]. Ryu et al[14] detected no significant differences in overall survival and recurrence-free survival between liver resection and microwave ablation treatments in patients with single hepatocellular carcinoma of ≤ 5 cm. These results indicate that the overall survival rate, tumor recurrence, and efficacy of microwave ablation and liver resection in the treatment of liver cancer are comparable. In agreement with the Ryu et al[14], we detected no significant difference in the short-term efficacy between the liver cancer ablation and the liver cancer resection groups. Zhang et al[15] demonstrated similar overall survival rates, tumor recurrence rates, and efficacy in the treatment of liver cancer between microwave ablation and liver resection; however, patients who underwent microwave ablation experienced shorter operation times and less bleeding. Chong et al[16] demonstrated that liver function recovery was better in patients who underwent microwave ablation treatment compared with patients who underwent liver resection surgery. These studies suggest that microwave ablation may be superior to liver resection in the treatment of liver cancer.

In the microwave ablation procedure, the needle-shaped electrode probe punctures the predetermined center of the tumor. The microwaves release a microwave magnetic field that causes the surrounding molecules to rotate at high speed and generate friction. The resulting heat promotes cell necrosis and coagulation. Under the guidance of medical imaging, the tissue can be assessed in real time while performing the microwave ablation. Thus, the infiltration range and size of tumor lesions can be accurately assessed, enabling physicians to fully assess the intrahepatic lesions, portal vein, and various branching directions. The puncture point can be accurately placed according to the location of the lesion and damage to adjacent tissues and organs can be minimized. Therefore, microwave ablation may cause less trauma and liver dysfunction[17]. In addition, microwave ablation directly inactivates tumor tissue, to a certain extent. Thus, the risk of tumor metastasis is minimized.

Patients with multiple liver tumor lesions often only undergo palliative surgery for liver cancer resection due to the difficulty in achieving complete resection. Therefore, hepatectomy may poorly control PD in these patients. In addition, liver resection of multiple lesions can lead to multiple liver cross-sections, which adversely affect postoperative liver function recovery. When inflammation, necrosis, injury, and bile duct blockage occur in the liver, TBil and ALT levels increase, indicating impaired liver function. In our study, TBil and ALT levels in the liver cancer ablation group were significantly higher than the levels in the liver cancer resection group one month after treatment. These results demonstrate that liver function recovery after microwave ablation is better than recovery after hepatectomy. Thus, during medical image-guided microwave ablation, the puncture point is accurately selected according to the location of the lesion, and damage to adjacent tissues and organs is reduced, resulting in a faster recovery of liver function after the procedure compared with liver resection.

Decreased immune function is common in patients with liver cancer[18]. CD3⁺T lymphocytes regulate immune function, and CD4⁺T lymphocytes promote the antitumor effects of effector cells. Unbalanced CD4⁺/CD8⁺ levels lead to immune disorders. Leuchte et al[19] demonstrated that microwave ablation enhances the tumor-specific immune response in patients with hepatocellular carcinoma. Luo et al[20] demonstrated that microwave ablation enhances the expression of immune-related genes, leading to activation of CD8⁺T cells. Activation of CD8⁺T cells enhances programmed death receptor 1 inhibition in cancer tissue to induce antitumor immunity. In our study, CD4⁺T lymphocytes and the ratio of CD4⁺/CD8⁺ were significantly higher in the liver cancer ablation group compared with the liver cancer resection group one month after treatment. In addition, the proportion of CD8⁺T lymphocytes decreased in the liver cancer ablation group compared with the liver cancer resection group one month after treatment. These results confirm the regulation of immune function by microwave ablation in patients with liver cancer.

Microwave ablation kills tumor cells and alleviates immune disorders caused by tumor cells. In addition, microwave ablation can promote lesion coagulation, accelerate the clearance of immunosuppressive factors, and improve the immune response. The main mechanism for these effects is the processing of antigen-presenting cells during microwave ablation and the presentation of antigens released by tumor tissue necrosis, which enhance or induce antitumor T-cell responses[21]. Microwave ablation induces tissue damage via protein denaturation and destruction of organelles. In addition, microwave ablation decreases DNA polymerase activity, which prevents single strand-break repair, decreases RNA synthesis, destroys tumor microvasculature, and accelerates coagulation and necrosis of tumor cells[22]. The viability of necrotic tumor cells is decreased, but the tumor vaccine formed by the antigens, which can induce T-cell proliferation and differentiation, is retained. Thus, cellular immune responses are enhanced, and immunosuppressive lymphocytes are reduced.

Our study has several limitations. First, this was a single-center study with a limited sample size, which may have affected the statistical analysis. Second, this study is a retrospective analysis. Thus, bias in the selection of case information may have occurred. Therefore, multicenter, large-sample, prospective studies are needed to confirm the value of medical image-guided microwave ablation in liver cancer.

CONCLUSION

The short-term efficacy and safety of microwave ablation guided by medical imaging in the treatment of liver cancer was similar to the efficacy of laparoscopic surgery. However, microwave ablation reduced liver function damage and improved immune function compared with liver resection.