Evaluating the short-term outcome of radiofrequency ablation of hepatocellular carcinoma at binh dan hospital – Nguyen Van Xuyen

Journal of military pharmaco-medicine n o 4-2018 191 EVALUATING THE SHORT-TERM OUTCOME OF RADIOFREQUENCY ABLATION OF HEPATOCELLULAR CARCINOMA AT BINH DAN HOSPITAL Nguyen Van Xuyen*; Ngo Viet Thi**; Do Son Hai* Nguyen Hai Dang**; Pham Vinh Quang** SUMMARY Objectives: Evaluation of technical success as complete ablation rate, tumor progression, the safety and short-term outcome of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). Subjects and methods: 30 patients with HCC were treated with radiofrequency ablation from Jun 1, 2014 to Jun 1, 2017 at Binhdan Hospital. Results: RFA was perfomed percutaneously in 30 patients with complete ablation rate 90%, recurrence rate at 3 months, 6 months and 12 months followed up was 0%, 23.33% and 30%, respectively, only one case with minor complication (3.3%) and no treatment-related deaths was recorded. Conclusions: RFA is an effective and safe method treatment for small or unresectable HCC. However, further controlled trials are needed to determine the effect of hepatic RFA on long-term survival. * Keywords: Hepatocellular carcinoma; Radiofrequency ablation; Therapy; Survival; Efficacy. INTRODUCTION Hepatocellular carcinoma is a very common disease in both sex. The risk for HCC is surprisingly high with chronic hepatitis B, C or cirrhosis. Surveillance programs addressed to the early detection of small nodular type HCC in patients with chronic liver diseases are increasing the eligibility for local or surgical treatments. Today, curative treatment for HCC including liver resection, liver transplant and local therapy. However, in Vietnam, liver transplant still got many problems due to the lack of donor organs. Liver resection brings good results but only 10 to 25% of patients are eligible to surgery because of problems such as: multi-focal tumors, not enough functional liver remnant etc Therefore, the local therapy (especially radio frequency ablation) is strongly focused nowadays to give a better outcome for the patients. At present, radiofrequency ablation (RFA) is the best indicated for small HCC (≤ 3 cm) with no more than 3 lesions or unresectable tumor or in HCC patients who refused to undergoing liver resection with promising outcome. The advantages of RFA is the high capacity of complete * 103 Military Hospital ** Binh Dan Hospital Corresponding author: Do Son Hai (dosonhai.pr@gmail.com) Date received: 23/01/2018 Date accepted: 26/03/2018 Journal of military pharmaco-medicine n o 4-2018 192 tumor destruction, it is a less invasive therapy which help to conserve the functional liver remnant with minor complications. Although RFA has been utilized throughout the world, it was not frequently applicated in Binhdan Hospital and its efficacy is still under discussion. The aim of this research is to: Investigate the efficacy and also the safety of FFA in HCC. SUBJECTS AND METHODS 1. Subjetcs. All the patients diagnosed with HCC were treated with RFA at Binhdan Hospital from June 2014 to June 2017. Diagnosis of HCC was confirmed by specific wash-out image on multi-sliced computed tomography or by core biopsy. * Inclusion criteria: The patients were indicated for radiofrequency ablation based on AASLD guidelines for HCC or patients with resectable lesion but refuse to undergoing surgery. * Exclusion criteria: Patients with 4 or more lesions, tumor diameter is more than 3 cm, portal thrombosis or progressive lesion which invade portal or hepatic vein, while relative contraindication for ablative is lesion located closely to important organs and serious coagulopathy (platelet counts less than 50,000 per mm3 or PT < 50%). 2. Methods. * Patients and HCC characteristics: From June 1st 2014 to June 1st 2017, 30 consecutive patients fulfilling the inclusion criteria were treated with RFA. Pretreatment assessment was performed before each treatment with ordinary liver function tests, prothrombin time and alpha-foetoprotein (AFP), platelet counts, chest X-ray, abdominal ultrasound and abdominal multi-sliced computed tomography scan. The procedures were all performed percutaneously with ultrasound guidance. The patient was followed and discharged off the hospital the day later if no complication was noticed. The surveillance protocol included early treatment response assessment by contrast-enhanced CT-scan performed 1 month after the first treatment, and a long-term response evaluation with alphafoetoprotein measurement, abdominal ultrasound every 3 months with chest/ abdominal CT-scan when suspect of recurrence or distal metastasis. The aim of this monitoring was to detect signs of both local tumor progression and new lesions separated from the previously treated nodule. Complete ablation was defined as no enhancements in both peripheral or intra-nodular on arterial phase at ablative site on the 1-month CT-scan. Multicentric disease was defined as onset of more than 3 nodules or portal thrombosis or extrahepatic disease. An intra-nodular/peripheral enhancement at CT-scan after the first treatment was considered incomplete ablative and if the patient still met the inclusion criteria, RFA was repeated. An intra-nodular/peripheral enhancement at CT-scan after the lesion was completely treated (no enhancements after the first ablation at the first 1 month CT-scan) was accounted as local recurrence. New Journal of military pharmaco-medicine n o 4-2018 193 lesions, or distant intrahepatic recurrence, were defined as new lesion appeared in the liver separate from the ablated area. Extrahepatic metastasis refers to any tumor recurrence out-side the liver. Continuous data were expressed as the median and the range. Groups were compared by using Chi-square test. All statistical analysis was performed by using Stata MP for Window statistical package. A p value less than 0.05 was considered to indicate statistical significance. RESULTS Patients description for sex, age, etiology, tumor characteristics, AFP, patient’s liver function values were shown in table 1. Table 1: Characteristics of patients with HCC treated with RFA. Characteristics Number (%) Number of patients 30 Sex, males 25 (83) Age 60.9 ± 8.9 HBV 10 (33) HCV 14 (46) Ethanol abused 2 (4) Etiology Others 4 (13) AFP 185.2 ng/mL (2 - 2000 ng/mL) 1 tumor 27 (90) 2 tumors 3 (10) Total numbers of tumors 3 tumors 0 (0) Size of tumor 2.27 ± 0.589 cm Follow-up observation time was 12 months for all the patients. During the observation time, there were 30 patients with 33 HCC lesions treated with RFA at Hepatology Department at Binhdan Hospital. On patient-basis, a complete “tumor” response rate (complete ablation rate- complete response rate) was 90% (27/30 patients). On nodular-basis, the complete response rate was 90.9% (30/33 lesions). All 3 patients with incomplete ablative tumor were going for secondary ablation and complete tumor destruction was archived in all three based on CT-scan one month later. Journal of military pharmaco-medicine n o 4-2018 194 Table 2: Recurrent rate after RFA. 3 months 6 months 12 months Recurrence 0 23.33% 30% Local recurrence 0 4 (13.33%) 4 (13.33%) Distant intrahepatic recurrence 0 3 (10%) 5 (16.66%) Extrahepatic metastasis 0 0 (0%) 0 (0%) Table 2 showed the progression of the tumor after ablation. Within the observation time, the recurrence rate at 3, 6 and 12 months were 0%, 23.33% and 30%, respectively. At 6 months, there were 7 patients with signs of recurrence disease (4 local recurrence and 3 new lesions). They were checked both clinically and laboratory and no signs of distal metastasis were noted, their liver function was still acceptable so they were all going for additional ablation. * Complications after RFA: Death: 0 patient (%); hemorrhage requiring surgery: 0 patient (%); pneumothorax: 0 patient (0%); pleural effusion: 0 patient (0%); hepatic insufficiency: 0 patient (0%); biloma/bile duct stricture: 0 patient (0%); abscess/ wound infection: 1 patient (4.4%); colon/gastric perforation: 0 patient (0%); ascites require treatment: 0 patient (0%). During the observation period, there were no treatment-related deaths, no major complications which required surgery, only one case with minor complication accounted for 3.3%. The patient developed punction-site abscess 1 week after the first RFA treatment and was treated with percutaneous drainage with antibiotics, he later went well and was discharged of the hospital the day later. DISCUSSION Today, liver resection is still the best treatment method for HCC in both overall survival rate and recurrent rate. Despite the good outcome, hepatectomy carries lot of risks with high mortality rate and complications, thus HCC usually develops on liver with severe cirrhosis which made the conservation of the normal liver tissue a big problem. Luckily, RFA is an well alternative choice to treat HCC with its good result and it is now widely accepted. Moreover, RFA is a less invasive therapy and can be repeat easily to treat recurrent cases. Data strongly support RFA as an effective treatment for single HCC ≤ 2 cm even when surgical resection is possible [1, 8]. As recently report for RFA in size less than 3.5 cm, the technical efficacy (complete tumor ablation) ranged from 76% to 96% of nodules after 1 session, and could be up to 100% after 2 sessions. In our studies, we archived a complete ablation rate at 90% on patients-basis. Journal of military pharmaco-medicine n o 4-2018 195 Recent evidence supported percutaneous local ablative therapy for small HCC considered as effective as liver resection [1, 6]. In our group, survival rate at 1 year followed-up was 100%, with no treatment- related deaths, no major complications with only one local minor complication. Local recurrence rates varies from 12% to 36% at 6 months and from 16% to 38% at 12 months follow-up after RFA [3]. Our study recorded the recurrent rates at 6 and 12 months were 23.33% and 30%, respectively. Junichi Toshimori et al studied 397 cases of HCC treated with RFA and reported that large tumor size (> 2 cm), tumor location (adjacent to major portal or hepatic vein/biliary duct or major visceral and diaphragm) and small ablated margin (< 3 mm) were independent predictor factors for local recurrence after RFA [5]. In our studies, we also noticed the same results with factors which contributed to recurrence were: tumor size > 2 cm (100% of local recurrent at 6 and 12 months had lesions larger than 2 cm), tumor in the difficult location to ablate (3 on 4 local recurrent lesions at 12 months) and uneffective post RFA antiviral treatment. CONCLUSION In conclusion, RFA is a safe and effective curative treatment for early-stage HCC, alternative to liver resection. Thus, the therapy is developing a lot to expand its indications to help treat larger lesion with stronger ablative needle. REFERENCES 1. Andrea Salmi. Efficacy of radiofrequency ablation of hepatocellular carcinoma associated with chronic liver disease without cirrhosis. International Journal of Medical Sciences. 2008, 5 (6), pp.327-332. 2. Bruix Jordi, Sherman Morris. Management of HCC: an update. Hepatology. 2011, pp.1020-1022. 3. Courtney L. Scaife. Complication, local recurrence and survival rates after RFA for hepatic malignancies. Surg Oncol Clin N Am. 2003, vol 12, pp.243-255. 4. Josep M. Llovet. The Barcelona approach: Diagnosis, staging and treatment of HCC. Liver Transplation. 2004, 10 (2), suppl 1, pp.S115-S120. 5. Junichi Toshimori. Local recurrence and complications after percutaneous RFA of HCC: a retrospective cohort study focused on tumor location. Acta Med. Okayama. 2015, 69 (4), pp.219-226. 6. Gugliemi A, Ruzzenante A. Radiofrequency ablation versus surgical resection for the treatment of small HCC in cirrhosis. J Gastrointest Surg. 2008, 12 (1), pp.192-198. 7. Ronnie T.P. Poon. Locoregional therapies for HCC: A critical review from surgeon’s perspective. Annals of Surg. 2002, 235 (4), pp.466-486. 8. S.M Lin, C.C Lin, Lin C.J et al. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, percutaneous acetic acid injection to treat HCC of 3 cm or less. Gut. 2005, 54 (8), pp.1151-1156.