Study design and ethics statement
This is a prospective randomized study to compare microwave ablation (MWA) to liver resection in treating early-stage HCC. The protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and its later amendments. An opt-out approach was used to obtain informed consent from the patients, and personal information was protected during data collection.
Patients
Seventy-two Egyptian patients attending the Hepatocellular Carcinoma Multidisciplinary clinic in Kasr Alainy Hospital, Cairo University, were enrolled in this study during the period from March 2018 to September 2020. Patients were divided into two groups where Group 1 included 31 patients who were treated through liver resection while group 2 included 41 patients who got their tumor ablated by microwave therapy. Choice of treatment modality was made through the HCC multi-disciplinary team of Kasr Alainy Hospital according to the location of the lesions, fitness for surgery as well as the liver status and portal pressure.
Exclusion criteria were as follows:
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i)
Decompensated liver disease (Child–Pugh score > 7)
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ii)
Advanced tumor stage (vascular invasion and/or extrahepatic spread)
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iii)
Patients who refused to sign the consent
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iv)
Pregnancy
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v)
ECOG performance status > 2
Data collection
Hepatocellular carcinoma was diagnosed based on imaging modalities, such as dynamic computed tomography (CT) and/or dynamic magnetic resonance imaging (MRI).
The following items of categorical data were collected at the time of HCC diagnosis:
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i)
Demographics, namely age, sex, body mass index, and chronic medical illnesses
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ii)
Assessment of liver functions through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, and prothrombin activity
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iii)
Other laboratory investigations include complete blood picture, urea & creatinine, and viral markers (HCV Ab, HBsAg, HBcAb)
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iv)
Tumor factors, namely size and number of HCCs, clinical staging according to BCLC staging system, and alpha-fetoprotein levels.
The performance status was assessed using the Eastern Cooperative Oncology Group (ECOG) performance status scale [a scale of 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead)] [6].
Treatment applied
Group 1: liver resection
Preoperative assessment: with the aforementioned clinical and laboratory investigations.
Anesthetic assessment: of the fitness for surgery.
A written informed consent was obtained from all patients prior to surgery.
Surgical set up:
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All the hepatic resection procedures were undertaken by experienced hepatobiliary surgeons through an inverted L-shaped incision in the right upper quadrant of the abdomen.
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Hepatic mobilization was performed first.
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Liver resection was then carried out on the basis of the segmental anatomy of the liver after delineation of the proper hepatic transection plane using intraoperative ultrasound. Planning the parenchymal transection first was important, not only to help achieve an adequate tumor-free margin, but also to avoid injury of major intrahepatic vessels or bile duct pedicles.
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Tissue dissection was carried out using the monopolar diathermy, the ultracision Harmonic scalpel and/or the Ligasure electrothermal bipolar vessel sealing device (Covidien–Valleylab, Boulder, CO, USA).
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Intraoperative incidents were recorded, e.g., intraoperative bleeding, any other surgical or anesthetic complications.
Group 2: microwave ablation
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The procedures were performed under ultrasound guidance using a Hitashi EUB-5500 machine with a 3.5–5-MHz probe. We used an HS AMICA microwave machine (HS Hospital service S.P.A. Roma, Italy), so-called AMICA GEM machine. It operated at a frequency of 2450 MHz, and 14-gauge (150 mm and 200 mm) cooled shift electrodes (AMICA-probes) were used to deliver the microwave energy into the liver tissue [7].
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A single microwave antenna, connected to a generator, was inserted directly into the tumor or tissue to be ablated.
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High-frequency microwaves emitted by the antenna agitate water molecules, create friction, and therefore generate heat, thus resulting in coagulative tissue necrosis.
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The size and the shape of the hyperechoic zone caused by gas microbubbles appearing in the ablated zone during the MWA procedure were monitored by US to assess the completeness of therapy.
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Treatment was stopped when the entire target was completely hyperechoic and the determined time and power according to the size of the lesion were reached.
Follow-up
All patients were followed up till the end of the study, with a minimum follow-up period of 6 months. They were assessed early after the procedure (hepatic resection or microwave ablation) for complications and liver decompensation where follow up of liver functions was carried on days 0, 3, and 7 post-procedure, as well as one month after the procedure by assessment of serum ALT, total bilirubin, and INR. Assessment of serum AFP was done 3 months post-procedure in all patients during their regular follow-up visits. Triphasic CT was performed 4 weeks post-treatment and every 6 months during the follow-up period to exclude recurrence. The treatment response was assessed in all patients based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria [8].
Overall survival
The overall survival was calculated from the date of the patients’ first visits to the multidisciplinary HCC clinic till the patients’ death or the end of the study. Survival curves were plotted by the Kaplan–Meier method and compared using the log-rank test. Independent prognostic factors were estimated by the Cox proportional hazards in univariate and multivariate regression models [9].
Statistical analysis
Data were coded and entered using the statistical package for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY, USA). Data were summarized using mean, standard deviation, median, minimum, and maximum in quantitative data; and using frequency (count) and relative frequency (percentage) for categorical data. Comparisons between quantitative variables were done using the non-parametric Mann–Whitney U test [10]. For comparing categorical data, Chi-square \(\left({}_\chi2\right)\) test was performed. Fisher’s exact test was used instead when the expected frequency was less than 5 [11]. P values less than 0.05 were considered statistically significant.