Patients
The study protocol was approved by the ethical committee of the Beijing Ditan Hospital. All patients signed an informed consent before procedure. From November 1,2017 to February 28, 2019, a total of 88 patients with single BCLC-A HCC who were candidates for MWA and admitted to Beijing Ditan Hospital, Capital Medical University, were enrolled in this study. Diagnostic criteria of HCC were performed according to the guidelines for the diagnosis and treatment of primary liver cancer in BCLC Staging Classification [7].
The eligibility criteria were: (1) patients aged 18–80 years; (2) tumor clinical stage is BCLC-A1-3: diameter ≤ 5 cm,liver function Child-Pugh class A or B; no vascular cancer embolus, vascular and intrahepatic bile duct invasion and distant metastasis; (3) patients who did not receive any anti-cancer treatment, such as surgery, radiotherapy, chemotherapy, ablation, and targeted drugs; (4) the performance status score of patients is less than 2, no serious organ dysfunction syndrome, such as heart, brain, liver, and kidney problems.
The exclusive 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 would be larger than one-third of liver volume; (3) esophageal and gastric variceal bleeding patients in the last six months; (4) active infection or intra-hepatic bile duct dilation; (5) uncorrectable coagulopathy(PLT༜30 × 109/L, PT༞30 s, PTA༜40%); and (7) obstinate massive ascites and hepatic encephalopathy.
Equipment
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; distance from the aperture of the MW emission to the needle tip, 11 mm); ultrasound machine was LOGIQ P6 (GE, USA), using broadband convex array probe(frequency,1–5 MHz);CT devices was produced by Germany's Siemens AG (tube voltage,120 kV; tube current, 200mAs; the slice thickness, 5 mm; pitch,1).
Treatment
All patients were initially treated with TACE. The purpose of TACE was to interdict tumor target artery and make tumor easier to recognize on CT images,and it could enhance the efficiency and the effect 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 microsphere (100–300 um) 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: CT group, US group and combination group. The procedure was performed under local anesthesia, and the vital signs were monitored under ECG monitor. The patient was given pethidine hydrochloride injection and diazepam injection 30 minutes before the 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.
The CT group,most patients took the supine position, a few patients took lateral decubitus position or prone position according to the point and direction of embedded microwave electrode. CT scan provided clinically useful information such as the size, shape and position of lesion and the relationship between lesion and adjacent structure, measure the distance from lesion to skin, confirm the puncture path and site. The skin around the puncture site was disinfected routinely, local anesthesia with lidocaine, inserting prepared guide pin (21G) in advance and dynamically adjusting the position of guide pin according to CT scanning image, enabling it to reach to lesion edge. Subsequently, microwave electrode was inserted precisely into lesions in the direction of guide pin, pulling out the guide pin and adjusting slightly microwave electrode to the best position according to 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, adjusted microwave electrode according to CT scanning image, a second MWA treatment was conducted immediately, until the ablation area covering the lesion. Routine ablation needle track was performed to prevent implantation metastasis, pressure dressing was performed to prevent hemorrhage immediately after the procedure, a postoperative CT scan was performed to confirmed whether it had some complications (for example, pneumothorax, pleural effusion, subcapsular hemorrhage, etc) to manage further. After treatment, liver protection, anti-inflammatory and sedation therapies were prescribed. A follow-up study by repeat contrast-enhanced magnetic resonance imaging (MRI) was conducted. As shown in Fig. 1.
The US group, all patients took the supine position or left lateral decubitus position and must follow the principle that the lesions were more apparent in ultrasonic imaging. If necessary, artificial pleural effusion and ascites were applied to treat US-invisible HCC in the hepatic dome or adjacent gastrointestinal tract before procedure. Microwave electrodes were inserted precisely into lesions under US guidance. The ablation power was 50–60 W, ablation time was 5–8 minutes. During course of treatment, internal echoes change of lesion and manifestations of intrahepatic and perihepatic tissue were observed by US in real time. When hyperechoic completely cover targeted lesions, the therapy was stopped. It would be the same as CT group, the same needle track ablation and pressure dressing were made after the procedure. Whether there were any complications, such as pleural effusion and subcapsular hemorrhage, were evaluated by US after treatment. Regular follow-up examinations would continue for greater than12 months. As shown in Fig. 2.
The combination group, at first, all patients underwent CT examination in a supine position. Designing the best puncture path and site according to CT image, avoiding nearby larger blood vessels and bile duck, pulmonary tissue and pleural cavity. Subsequently, microwave electrode was inserted precisely into lesions avoiding nearby larger blood vessels and bile duck under real-time US guidance. Then, repeat CT was performed to further precisely targeted the position of microwave electrode and the relationship between microwave electrode and around structure of the lesion, when necessary, to adjust slightly. Ablation power was 50–60 W, ablation time was 5–8 minutes. Internal echoes change of lesion was observed by real-time US, timely CT examination was performed. The therapy was stopped, when the ablation area completely covered targeted lesions and had not some complications according to CT image. Routine needle track ablation and pressure dressing were made after the procedure. Regular follow-up examinations would continue for greater than 12 months. As shown in Fig. 3.
Efficacy and safety
All patients were on preoperative contrast-enhanced MRI, after 1 month, 3 months, 6 months and 12 months of treatment. Treatment time, puncture time, local recurrence rate were used to evaluate the efficacy of the three groups. Follow-up period, if we found local recurrence and we will treat them by a second MWA; if we found intrahepatic metastasis and distant metastasis and we will treat them by other treatment methods, such as targeted drugs.
At the same time, liver and kidney functions, AFP were recorded. The MWA-related complications including bile duct injury, GI bleeding and hydrothorax, sepsis, liver failure, renal dysfunction, peritoneal hemorrhage, and skin burn were assessed.
Statistical analysis
Parameters were tested for normality using the Shapiro Wilk test. The means and standard deviations (SD) of continuous, normally distributed parameters were determined and compared using one-way analysis of variance or the independent-samples t test. Patient age, lesion size, treatment time, complete ablation rate, local recurrence rate, number of puncture 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 by an SPSS19.0 software (SPSS, IBM Company, USA).