European Journal of Cardiovascular Medicine

Hepatocellular Carcinoma (HCC) is a malignant tumor that is sixth most prevalent in the world, accounting for between 500,000 and a million new cases annually. Of the approximately 6,00,000 cases of HCC reported annually worldwide, over 78% are found in Asia.^[1] HCC has a poor prognosis, with a 1-4% 5-year survival rate. Four population-based registries in India show that the mean incidence of HCC is 1.38% for females and 2.77% for males. In India, the prevalence of HCC ranges from 0.2% to 1.6%.^[2,3,4] The only curative treatment is surgical excision of the HCC. About 80–90% of patients having hepatic resection obtain successful excision with negative tumor margins.

Multiple lesions, tumors in inoperable sites and other medical factors that put the patient at low candidate for surgery are all contraindications for hepatic resection . Only 5–15% of HCC patients are candidates for resection,^[5] according to estimates. Patients who have hepatic resection face a number of challenges, including significant postoperative morbidity, a slight risk of mortality and high cost. Another surgical option is liver transplantation.  However, in addition to the difficulties associated with open surgery, there is a scarcity of donors. Given these drawbacks, treating HCC requires an efficient, minimally invasive method that may be repeated as needed to treat recurrent tumors.

A relatively new minimally invasive and relatively low-cost percutaneous thermal ablation like RFA is thought to be the best choice for those with early-stage, small-sized HCC, for whom surgical resection is contraindicated. The principle of RFA is based on converting electrical radiofrequency current into heat, creating a zone of thermal necrosis. A volume of tissue is devitalized under imaging guidance without removing it from the body, resulting in a similar effect to surgery. It is evident that RFA has a wide range of reported effectiveness for complete tumor ablation and lower recurrence rates.

Therefore, this study was conducted with the purpose of identifying the factors leading to better treatment outcomes and the study hopes to achieve this by analyzing preprocedural tumor morphology, Child-Pugh score the technical parameters and correlating them with treatment outcome at follow-up.

To study the correlation of preprocedural tumor morphology (size of the lesion on contrast imaging) with the outcome of RFA (successful ablation or local tumor progression) and to study the correlation of Child-Pugh score and technical parameters with the outcome of RFA.

This was a prospective study conducted over a period from June 2010 to June 2012. The study was approved by the local review board. A written informed consent was obtained from all patients before the procedure. 35 males and 5 females satisfying the aforementioned criteria underwent radiofrequency ablation. Based on the results on the correlation of size of the lesion, Child-Pugh score and technical parameters with the outcome of RFA, from the earlier publication ^[15] and with 95% confidence and 80% power, the minimum sample size came to 30 in each group (successful ablation -30 and local tumor progression - 30). However, during my study period, I could get only 29 cases of successful ablation and 11 cases of local tumor progression.

Inclusion Criteria and Exclusion Criteria

Inclusion criteria were single nodular HCC ≤5cm in maximum diameter, 3 lesions, each ≤3 cm in diameter and Child-Pugh class A or B liver cirrhosis.

Exclusion criteria for the study include lesions >5 cm, main portal venous thrombosis, extrahepatic metastases and Child-Pugh class C liver cirrhosis.

Study Procedure

These patients were diagnosed with hepatocellular carcinoma by different imaging modalities (CT, MRI, and CEUS) and biopsy. The average age of the patient was 63.72 years (45-78 years). None of the patients were seropositive for hepatitis B or C. 25 patients were in Child A score and 15 in Child B.36 HCCs were due to alcohol-induced cirrhosis, and 4 cases were cryptogenic. The mean tumor size of HCCs was 2.83±1.06 cm (range: 1.2 cm ± 5 cm). RFA was done only in proven HCC cases, either with typical imaging features or confirmed with FNAC/liver biopsy. 33 patients were diagnosed with HCC by CT, 3 by MRI, and 3 by CEUS. One case was confirmed with FNAC, which had a doubtful washout in CE-MRI and CEUS. FNA and biopsy were done in 1 and 3 patients, respectively, with doubtful imaging interpretation. HCC most commonly involved the right lobe. Twenty seven  HCCs were located in the right lobe and 12 cases in the left lobe. One case showed bilobar HCC. Serum AFP was elevated in 18 patients, normal in 14 and was not obtained in 8 cases. The inclusion criteria were strictly followed during the entire period of the study, which was based on Milan criteria.

All patients had laboratory tests performed prior to therapy, including hematocrit, white blood cell count, blood coagulation tests, hepatic function values, and levels of a-fetoprotein. An INR (International Normalized Ratio) of greater than 1.3 or a platelet count of less than 50,000/ml is contraindicated. The aspirin has to be stopped for atleast three days prior to the procedure. Ascites was controlled before the procedure. Our institutional review board approved this study, and each patient or family member provided written and informed consent.

Radio Frequency Ablation Procedure

Patients had radiofrequency ablation following a 4-hour fast, and the procedure was done on an out-patient basis with post-procedure observation. The terminology standardization and reporting guidelines put forward by the International Working Group on Image-Guided Tumor Ablation and the Society of Interventional Radiology Technology Assessment Committee,^[6] served as the foundation for our explanations of the radiofrequency ablation techniques and data evaluation. For all processes, we employed an internally cooled electrode system (Cool-tip, Valleylab). The size, location, and configuration of the index tumor as well as the electrode stock availability determined the type of electrode that the operators chose.

At the time of the trial, five experienced radiologists, each with more than ten years of experience performed the ablation. By fastening one pad to the back and one to the thigh, grounding was accomplished. Following the iodine and alcohol sterilization of the skin, a lancet was used to puncture the skin and local anesthetic 1% lidocaine was injected subcutaneously. Patients also received analgesia by IV injection of 50-100 g of fentanyl citrate (Fentanyl, Mengun) and sedation with 1-2 mg of midazolam (Dormicum, Roche).Six patients had the procedure done under CT guidance, while thirty-four patients had it done under sonographic guidance. Radiofrequency ablation was done in all patients using internally cooled 17-gauge electrodes (Cool-Tip, Valleylab) with an exposed tip of 3.0 cm. The electrode was inserted into the lesion under CT guidance when the lesion was in the hepatic dome or was not apparent on sonography. A Somatom Sensation 64 slice MDCT scanner (Siemens Medical Solutions) was utilized for the CT-guided technique with 110 kVp scanning parameters. 200 mA, 5 mm collimation, and 7 mm/sec table speed. The most likely site of the tumor and the best path to it were determined using the pretreatment diagnostic-workup pictures. A 3.5-MHz convex probe (Sonosite Micromax portable) was utilized for sonographic guidance.

After CT or sonography had verified that the electrodes were properly positioned in the tumor, the electrodes were attached to a 500-KHz monopolar radiofrequency generator (CC-1, Valleylab) that could produce 200W. Circuitry built into the generator monitored tissue impedance using an automated pulsed-radiofrequency method that was regulated by impedance. Vital signs were continually tracked throughout the process.

Normal saline solution at 0°C was infused into the radiofrequency electrode lumen at a pace sufficient to maintain a temperature of 0–20°C using a Watson–Marlow peristaltic pump. When treating tumor nodules with a diameter of less than 3 cm, radiofrequency treatment was administered for 10 to 12 minutes, based on the size of the tumor, using a single electrode placed in the tumor's center. A single radiofrequency electrode was used in the overlap approach (two to four overlaps) for tumors larger than 3 cm. Depending on the size of the tumor, radiofrequency was used for 12 minutes at first and 6 to 12 minutes for successive ablations.

Assessment of Therapeutic Efficacy and Follow-Up Studies

Patients underwent contrast-enhanced CT within 24 hours of the procedure to assess the ablation zone. By comparing the results with pre-treatment CT or MRI, the two skilled radiologists evaluated the therapeutic effectiveness of radiofrequency ablation on posttreatment CT. When a non-enhancing area that was at least as large as the original tumor was observed, tumor necrosis was deemed to be complete. ^[7,8,9] A further ablation session was carried out within three days if persistent tumor was detected on the post-treatment CT scan. After then, an MRI or CT scan was done every three months. All patients underwent blood tests to assess liver function and was monitored for potential procedure-related complications immediately following treatment and during follow-up. We compared the aminotransferase level, bilirubin level, and Child-Pugh score prior to treatment with those during the first three weeks following treatment in order to assess the impact of radiofrequency ablation on hepatic function. The mean follow-up period was 13 months. Recurrence-free survival was defined as the time interval between the date of the initial RFA treatment and the date of a local or distant recurrence.

Statistical Analysis

Statistical Computer software SPSS (Statistical Package for Social Sciences) version 20 and Microsoft Excel 2007 were used for the statistical analysis in this study. The Kaplan-Meier technique was used to determine the median patient survival periods. The Chi-square test served as the foundation for the statistical analysis. A p-value of less than 0.05 is regarded as significant.

There were 35 males and 5 females in this study. The highest number in age group criteria was within 60 to 70 years old. A statistically significant association was observed in the size of the lesion with the outcome. <3 cm lesions showed 89.66% complete response. >3 cm lesions showed 63.64% CR. >3 cm lesions showed 36.36% local tumor progression. <3 cm lesions showed 10.34% LTP. No association was noted with other variables like Child-Pugh criteria, technical parameters like size of the needle, fresh or reused needle, and the time of ablation on outcome (Table). The median follow-up period was 5 months (range: 1–22 months). The median recurrence-free survival period was 6 months.

Figure shows median recurrence free survival curve plotted by Kaplan-Meier method. The median follow-up period was 5 months(range of 1 to 22 months). The  overall median reccurrence free survival period was 6 months.