The study protocol was approved by the ethical committee of the Beijing Ditan Hospital. All patients signed an informed consent form before the procedure. A total of 88 patients with single Barcelona clinic liver cancer (BCLC)-A HCC eligible for MWA and admitted in the Beijing Ditan Hospital, Capital Medical University from November 1, 2017 to February 28, 2019 were enrolled in the study. The diagnostic criteria of HCC were assessed according to the guidelines for the diagnosis and treatment of primary liver cancer in the BCLC Staging Classification .
The inclusion criteria were as follows: (1) patients aged 18-80 years; (2) tumor clinical stage BCLC-A1-3: diameter ≤5 cm, liver function Child-Pugh class A or B; no vascular cancer embolus, vascular and intrahepatic bile duct invasion, or distant metastases; (3) patients who did not receive any anticancer treatment such as surgery, radiotherapy, chemotherapy, ablation, or targeted drugs; and (4) the performance status score of patients was less than 2, with no serious organ dysfunction syndrome such as heart, brain, liver, or kidney problems.
The exclusion criteria were as follows: (1) severe liver malfunction (Child–Pugh score>9, serum total bilirubin level>3 mg/dl, and prothrombin time-international normalized ratio>1.5); (2) severe hepatic atrophy, expected ablated area larger than one-third of liver volume; (3) patients with esophageal or gastric variceal bleeding in the last six months; (4) active infection or intrahepatic bile duct dilation; (5) uncorrectable coagulopathy (PLT<30×109/L, PT>30 s, PTA<40%); (6) lesion adjacent to the diaphragm, gallbladder, and major vessel, or protruding liver surface; and (7) obstinate massive ascites and hepatic encephalopathy.
We used a KV2100 microwave tumor treatment device (Nanjing Kangyou Microwave Energy Sources Institute, China; frequency, 2450 MHz; needle type, internal water-cooling; electrode diameter, 15G; electrode length, 150 or 180 mm; power, 0–100 W; and distance from the aperture of the MW emission to the needle tip, 11 mm); the ultrasound machine was LOGIQ P6 (GE, USA), using a broadband convex array probe (frequency, 1-5 MHz); and the CT device was produced by Germany's Siemens AG (tube voltage, 120 kV; tube current, 200 mA; slice thickness, 5 mm; and pitch, 1).
All patients were initially treated with transcatheter arterial chemoembolization (TACE). The purpose of TACE was to interdict the tumor target artery and make the tumor easily-recognizable on CT images, and to reduce heat deposition resulting from the artery and enhance the efficiency and effects of MWA. The treatment process was as follows: hepatic artery angiography was performed using the Seldinger technique. Femoral arterial catheterization was conducted through the common hepatic artery or proper hepatic artery, and the location, number, size, and blood supply of the lesions were evaluated. Subsequently, a microcatheter was super-selectively inserted into the hepatic lobe or hepatic segmental artery branch, and mixed suspensions of iodized oil (5-10 ml) and loplatin injection (40 mg) were infused into the artery through the catheter. Finally, blank microspheres (100-300 µm) were infused to embolize the artery until the arterial blood flow supplying the tumor was completely blocked.
MWA was initiated 1 week after TACE. Patients were divided into 3 groups at random by using draw lots: the CT group, US group, and combination group. The procedure was performed under local anesthesia, and vital signs were monitored using an electrocardiogram. The patient was given a pethidine hydrochloride injection and diazepam injection 30 minutes before treatment. The microwave therapy instrument was in good working condition. Procedures were performed by one of two doctors with 10 years of experience in HCC ablation.
In the CT group, most patients were placed in the supine position, and a few patients were placed in the lateral decubitus position or prone position according to the point and direction of the embedded microwave electrode. CT scans provided clinically useful information such as the size, shape and position of the lesion, and the relationship between the lesion and adjacent structure; the distance from the lesion to the skin was measured, and the puncture path and site were confirmed. The skin around the puncture site was disinfected routinely, local anesthesia with lidocaine was used, a prepared guide pin (21G) was inserted in advance, and the position of the guide pin was dynamically adjusted according to the CT scanning image, enabling it to reach the edge of the lesion. Subsequently, the microwave electrode was inserted precisely into the lesions in the direction of the guide pin, the guide pin was removed, and the microwave electrode was adjusted slightly to the best position according to the CT scanning image. Microwave electrode placement was performed based on the expected ablation zone size described by the manufacturer, considering a sufficient (>5 mm) safety margin around the tumor. The microwave power was set at 50-60 W. The ablation time for each lesion was 5-8 minutes, and the ablation area covering the lesion and its surrounding area measured 5 mm or more. If a single treatment did not produce satisfactory results, the microwave electrode was adjusted according to the CT scanning image, and a second MWA treatment was conducted immediately until the ablation area covered the lesion. Routine ablation needle tracking was performed to prevent implantation metastasis, a pressure dressing was placed to prevent hemorrhage immediately after the procedure, and a postoperative CT scan was performed to confirm whether any complications (for example, pneumothorax, pleural effusion, subcapsular hemorrhage) required further management. After treatment, liver protection, anti-inflammatory, and sedation therapies were prescribed. A follow-up study with repeat contrast-enhanced MRI or CT was conducted, as shown in Fig 1.
In the US group, all patients were in supine or left lateral decubitus position following the principle that the lesions were more apparent in ultrasonic imaging. If necessary, artificial pleural effusion and ascites were used to treat US-invisible HCC in the hepatic dome or adjacent gastrointestinal tract before the procedure. Microwave electrodes were inserted precisely into the lesions under US guidance. The ablation power was 50-60 W, and the ablation time was 5-8 minutes. During the course of treatment, changes in the internal echoes of the lesion and manifestations of the intrahepatic and perihepatic tissues were observed by US in real time. When hyperechoic regions completely covered the targeted lesions, the therapy was stopped. The same needle track ablation and pressure dressing were performed after the procedure. Whether there were any complications such as pleural effusion and subcapsular hemorrhage were evaluated by US after treatment. Patients were regularly followed up for more than 12 months, as shown in Fig 2.
In the combination group at first, all patients underwent CT examination in a supine position. The best puncture path and site were designed according to the CT image, avoiding nearby larger blood vessels and the bile duct, pulmonary tissue and pleural cavity. Subsequently, the microwave electrode was inserted precisely into the lesions to avoid nearby larger blood vessels and the bile duct under real-time US guidance. Then, repeat CT was performed to further precisely target the position of the microwave electrode, and the relationship between the microwave electrode and the surrounding structure of the lesion when necessary, was slightly adjusted. The ablation power was 50-60 W, and the ablation time was 5-8 minutes. Internal echo changes in the lesions were observed by real-time US, and timely CT examination was performed. The therapy was stopped when the ablation area completely covered the targeted lesions and when there were no complications according to the CT image. Routine needle track ablation and pressure dressing were performed after the procedure. Regular follow-up examinations continued for more than 12 months, as shown in Fig 3.
Efficacy and safety
All patients underwent contrast-enhanced MRI or CT preoperatively as well as after 1, 3, 6, and 12 months of treatment. The treatment time, puncture time, and local recurrence rate were used to evaluate the efficacy of the three groups. During the follow-up period, if we found local recurrence, we treated the patients with a second MWA; if we found intrahepatic metastasis and distant metastasis, we treated the patients with other treatment methods such as targeted drugs.At the same time, the liver and kidney functions and AFP were recorded. The MWA-related complications including bile duct injury, gastrointestinal bleeding, hydrothorax, sepsis, liver failure, renal dysfunction, peritoneal hemorrhage, and skin burn were assessed.
Parameters were tested for normality using the Shapiro-Wilk test. The means and standard deviations (SDs) of continuous, normally distributed parameters were determined and compared using the one-way analysis of variance or independent samples t test. Patient age, lesion size, treatment time, complete ablation rate, local recurrence rate, number of punctures, and adverse events were compared between the three groups. Differences with p values <0.05 were considered significant, and p values were not adjusted for multiple comparisons. Statistical analyses were performed with SPSS 19.0 software (SPSS, IBM Company, USA).