Evaluating the short term outcome of radiofrequency ablation of hepatocellular carcinoma at Binh Dan hospital

Journal of military pharmaco-medicine no4-2018<br /> <br /> EVALUATING THE SHORT-TERM OUTCOME OF<br /> RADIOFREQUENCY ABLATION OF<br /> HEPATOCELLULAR CARCINOMA AT BINH DAN HOSPITAL<br /> Nguyen Van Xuyen*; Ngo Viet Thi**; Do Son Hai*<br /> Nguyen Hai Dang**; Pham Vinh Quang**<br /> SUMMARY<br /> Objectives: Evaluation of technical success as complete ablation rate, tumor progression,<br /> the safety and short-term outcome of radiofrequency ablation (RFA) in hepatocellular carcinoma<br /> (HCC). Subjects and methods: 30 patients with HCC were treated with radiofrequency ablation<br /> from Jun 1, 2014 to Jun 1, 2017 at Binhdan Hospital. Results: RFA was perfomed<br /> percutaneously in 30 patients with complete ablation rate 90%, recurrence rate at 3 months,<br /> 6 months and 12 months followed up was 0%, 23.33% and 30%, respectively, only one case<br /> with minor complication (3.3%) and no treatment-related deaths was recorded. Conclusions:<br /> RFA is an effective and safe method treatment for small or unresectable HCC. However, further<br /> controlled trials are needed to determine the effect of hepatic RFA on long-term survival.<br /> * Keywords: Hepatocellular carcinoma; Radiofrequency ablation; Therapy; Survival; Efficacy.<br /> <br /> INTRODUCTION<br /> Hepatocellular carcinoma is a very<br /> common disease in both sex. The risk for<br /> HCC is surprisingly high with chronic<br /> hepatitis B, C or cirrhosis.<br /> Surveillance programs addressed to<br /> the early detection of small nodular type<br /> HCC in patients with chronic liver diseases<br /> are increasing the eligibility for local or<br /> surgical treatments.<br /> Today, curative treatment for HCC<br /> including liver resection, liver transplant<br /> and local therapy. However, in Vietnam,<br /> liver transplant still got many problems<br /> due to the lack of donor organs. Liver<br /> <br /> resection brings good results but only<br /> 10 to 25% of patients are eligible to<br /> surgery because of problems such as:<br /> multi-focal tumors, not enough functional<br /> liver remnant etc… Therefore, the local<br /> therapy (especially radio frequency<br /> ablation) is strongly focused nowadays to<br /> give a better outcome for the patients.<br /> At present, radiofrequency ablation<br /> (RFA) is the best indicated for small HCC<br /> (≤ 3 cm) with no more than 3 lesions or<br /> unresectable tumor or in HCC patients<br /> who refused to undergoing liver resection<br /> with promising outcome. The advantages<br /> of RFA is the high capacity of complete<br /> <br /> * 103 Military Hospital<br /> ** Binh Dan Hospital<br /> Corresponding author: Do Son Hai (dosonhai.pr@gmail.com)<br /> Date received: 23/01/2018<br /> Date accepted: 26/03/2018<br /> <br /> 191<br /> <br /> Journal of military pharmaco-medicine no4-2018<br /> tumor destruction, it is a less invasive<br /> therapy which help to conserve the<br /> functional liver remnant with minor<br /> complications. Although RFA has been<br /> utilized throughout the world, it was not<br /> frequently applicated in Binhdan Hospital<br /> and its efficacy is still under discussion.<br /> The aim of this research is to: Investigate<br /> the efficacy and also the safety of FFA in<br /> HCC.<br /> SUBJECTS AND METHODS<br /> 1. Subjetcs.<br /> All the patients diagnosed with HCC<br /> were treated with RFA at Binhdan<br /> Hospital from June 2014 to June 2017.<br /> Diagnosis of HCC was confirmed by<br /> specific wash-out image on multi-sliced<br /> computed tomography or by core biopsy.<br /> * Inclusion criteria: The patients were<br /> indicated for radiofrequency ablation based<br /> on AASLD guidelines for HCC or patients<br /> with resectable lesion but refuse to<br /> undergoing surgery.<br /> * Exclusion criteria: Patients with 4 or<br /> more lesions, tumor diameter is more than<br /> 3 cm, portal thrombosis or progressive<br /> lesion which invade portal or hepatic vein,<br /> while relative contraindication for ablative<br /> is lesion located closely to important<br /> organs and serious coagulopathy (platelet<br /> counts less than 50,000 per mm3 or<br /> PT < 50%).<br /> 2. Methods.<br /> * Patients and HCC characteristics:<br /> From June 1st 2014 to June 1st 2017,<br /> 30 consecutive patients fulfilling the inclusion<br /> criteria were treated with RFA. Pretreatment<br /> assessment was performed before each<br /> 192<br /> <br /> treatment with ordinary liver function tests,<br /> prothrombin time and alpha-foetoprotein<br /> (AFP), platelet counts, chest X-ray,<br /> abdominal ultrasound and abdominal<br /> multi-sliced computed tomography scan.<br /> The procedures were all performed<br /> percutaneously with ultrasound guidance.<br /> The patient was followed and discharged<br /> off the hospital the day later if no<br /> complication was noticed. The surveillance<br /> protocol included early treatment response<br /> assessment by contrast-enhanced CT-scan<br /> performed 1 month after the first treatment,<br /> and a long-term response evaluation with<br /> alphafoetoprotein measurement, abdominal<br /> ultrasound every 3 months with chest/<br /> abdominal CT-scan when suspect of<br /> recurrence or distal metastasis.<br /> The aim of this monitoring was to detect<br /> signs of both local tumor progression and<br /> new lesions separated from the previously<br /> treated nodule. Complete ablation was<br /> defined as no enhancements in both<br /> peripheral or intra-nodular on arterial<br /> phase at ablative site on the 1-month<br /> CT-scan. Multicentric disease was<br /> defined as onset of more than 3 nodules<br /> or portal thrombosis or extrahepatic<br /> disease.<br /> An<br /> intra-nodular/peripheral<br /> enhancement at CT-scan after the first<br /> treatment was considered incomplete<br /> ablative and if the patient still met the<br /> inclusion criteria, RFA was repeated. An<br /> intra-nodular/peripheral enhancement at<br /> CT-scan after the lesion was completely<br /> treated (no enhancements after the first<br /> ablation at the first 1 month CT-scan) was<br /> accounted as local recurrence. New<br /> <br /> Journal of military pharmaco-medicine no4-2018<br /> lesions, or distant intrahepatic recurrence,<br /> were defined as new lesion appeared in<br /> the liver separate from the ablated area.<br /> Extrahepatic metastasis refers to any<br /> tumor recurrence out-side the liver.<br /> Continuous data were expressed as<br /> the median and the range. Groups were<br /> <br /> compared by using Chi-square test. All<br /> statistical analysis was performed by<br /> using Stata MP for Window statistical<br /> package. A p value less than 0.05 was<br /> considered<br /> to<br /> indicate<br /> statistical<br /> significance.<br /> <br /> RESULTS<br /> Patients description for sex, age, etiology, tumor characteristics, AFP, patient’s liver<br /> function values were shown in table 1.<br /> Table 1: Characteristics of patients with HCC treated with RFA.<br /> Characteristics<br /> Number of patients<br /> Sex, males<br /> <br /> 60.9 ± 8.9<br /> HBV<br /> <br /> 10 (33)<br /> <br /> HCV<br /> <br /> 14 (46)<br /> <br /> Ethanol abused<br /> <br /> 2 (4)<br /> <br /> Others<br /> <br /> 4 (13)<br /> <br /> AFP<br /> Total numbers<br /> of tumors<br /> <br /> Size of tumor<br /> <br /> 30<br /> 25 (83)<br /> <br /> Age<br /> Etiology<br /> <br /> Number (%)<br /> <br /> 185.2 ng/mL (2 - 2000 ng/mL)<br /> 1 tumor<br /> <br /> 27 (90)<br /> <br /> 2 tumors<br /> <br /> 3 (10)<br /> <br /> 3 tumors<br /> <br /> 0 (0)<br /> 2.27 ± 0.589 cm<br /> <br /> Follow-up observation time was 12 months for all the patients. During the<br /> observation time, there were 30 patients with 33 HCC lesions treated with RFA at<br /> Hepatology Department at Binhdan Hospital.<br /> On patient-basis, a complete “tumor” response rate (complete ablation ratecomplete response rate) was 90% (27/30 patients). On nodular-basis, the complete<br /> response rate was 90.9% (30/33 lesions). All 3 patients with incomplete ablative tumor<br /> were going for secondary ablation and complete tumor destruction was archived in all<br /> three based on CT-scan one month later.<br /> 193<br /> <br /> Journal of military pharmaco-medicine no4-2018<br /> Table 2: Recurrent rate after RFA.<br /> 3 months<br /> <br /> 6 months<br /> <br /> 12 months<br /> <br /> Recurrence<br /> <br /> 0<br /> <br /> 23.33%<br /> <br /> 30%<br /> <br /> Local recurrence<br /> <br /> 0<br /> <br /> 4 (13.33%)<br /> <br /> 4 (13.33%)<br /> <br /> Distant intrahepatic recurrence<br /> <br /> 0<br /> <br /> 3 (10%)<br /> <br /> 5 (16.66%)<br /> <br /> Extrahepatic metastasis<br /> <br /> 0<br /> <br /> 0 (0%)<br /> <br /> 0 (0%)<br /> <br /> Table 2 showed the progression of the<br /> tumor after ablation. Within the observation<br /> time, the recurrence rate at 3, 6 and<br /> 12 months were 0%, 23.33% and 30%,<br /> respectively. At 6 months, there were<br /> 7 patients with signs of recurrence<br /> disease (4 local recurrence and 3 new<br /> lesions). They were checked both<br /> clinically and laboratory and no signs of<br /> distal metastasis were noted, their liver<br /> function was still acceptable so they were<br /> all going for additional ablation.<br /> * Complications after RFA:<br /> Death: 0 patient (%); hemorrhage<br /> requiring surgery: 0 patient (%);<br /> pneumothorax: 0 patient (0%); pleural<br /> effusion: 0 patient (0%); hepatic<br /> insufficiency: 0 patient (0%); biloma/bile<br /> duct stricture: 0 patient (0%); abscess/<br /> wound infection: 1 patient (4.4%);<br /> colon/gastric perforation: 0 patient (0%);<br /> ascites require treatment: 0 patient (0%).<br /> During the observation period, there<br /> were no treatment-related deaths, no major<br /> complications which required surgery,<br /> only one case with minor complication<br /> accounted for 3.3%. The patient developed<br /> punction-site abscess 1 week after the<br /> first RFA treatment and was treated with<br /> 194<br /> <br /> percutaneous drainage with antibiotics, he<br /> later went well and was discharged of the<br /> hospital the day later.<br /> DISCUSSION<br /> Today, liver resection is still the best<br /> treatment method for HCC in both overall<br /> survival rate and recurrent rate. Despite<br /> the good outcome, hepatectomy carries<br /> lot of risks with high mortality rate and<br /> complications, thus HCC usually develops<br /> on liver with severe cirrhosis which made<br /> the conservation of the normal liver tissue<br /> a big problem. Luckily, RFA is an well<br /> alternative choice to treat HCC with its<br /> good result and it is now widely accepted.<br /> Moreover, RFA is a less invasive therapy<br /> and can be repeat easily to treat recurrent<br /> cases. Data strongly support RFA as an<br /> effective treatment for single HCC ≤ 2 cm<br /> even when surgical resection is possible<br /> [1, 8]. As recently report for RFA in size<br /> less than 3.5 cm, the technical efficacy<br /> (complete tumor ablation) ranged from<br /> 76% to 96% of nodules after 1 session,<br /> and could be up to 100% after 2 sessions.<br /> In our studies, we archived a complete<br /> ablation rate at 90% on patients-basis.<br /> <br /> Journal of military pharmaco-medicine no4-2018<br /> Recent evidence supported percutaneous<br /> local ablative therapy for small HCC<br /> considered as effective as liver resection<br /> [1, 6].<br /> <br /> its indications to help treat larger lesion<br /> with stronger ablative needle.<br /> <br /> In our group, survival rate at 1 year<br /> followed-up was 100%, with no treatmentrelated deaths, no major complications<br /> with only one local minor complication.<br /> <br /> 1. Andrea Salmi. Efficacy of radiofrequency<br /> ablation of hepatocellular carcinoma associated<br /> with chronic liver disease without cirrhosis.<br /> International Journal of Medical Sciences.<br /> 2008, 5 (6), pp.327-332.<br /> <br /> Local recurrence rates varies from<br /> 12% to 36% at 6 months and from 16% to<br /> 38% at 12 months follow-up after RFA [3].<br /> Our study recorded the recurrent rates at<br /> 6 and 12 months were 23.33% and 30%,<br /> respectively.<br /> <br /> 2. Bruix Jordi, Sherman Morris. Management<br /> of HCC: an update. Hepatology. 2011,<br /> pp.1020-1022.<br /> <br /> Junichi Toshimori et al studied 397 cases<br /> of HCC treated with RFA and reported<br /> that large tumor size (> 2 cm), tumor<br /> location (adjacent to major portal or<br /> hepatic vein/biliary duct or major visceral<br /> and diaphragm) and small ablated margin<br /> (< 3 mm) were independent predictor<br /> factors for local recurrence after RFA [5].<br /> In our studies, we also noticed the same<br /> results with factors which contributed to<br /> recurrence were: tumor size > 2 cm<br /> (100% of local recurrent at 6 and<br /> 12 months had lesions larger than 2 cm),<br /> tumor in the difficult location to ablate<br /> (3 on 4 local recurrent lesions at 12 months)<br /> and uneffective post RFA antiviral treatment.<br /> CONCLUSION<br /> In conclusion, RFA is a safe and<br /> effective curative treatment for early-stage<br /> HCC, alternative to liver resection. Thus,<br /> the therapy is developing a lot to expand<br /> <br /> REFERENCES<br /> <br /> 3. Courtney L. Scaife. Complication, local<br /> recurrence and survival rates after RFA<br /> for hepatic malignancies. Surg Oncol Clin N<br /> Am. 2003, vol 12, pp.243-255.<br /> 4. Josep M. Llovet. The Barcelona<br /> approach: Diagnosis, staging and treatment of<br /> HCC. Liver Transplation. 2004, 10 (2), suppl<br /> 1, pp.S115-S120.<br /> 5. Junichi Toshimori. Local recurrence<br /> and complications after percutaneous RFA<br /> of HCC: a retrospective cohort study<br /> focused on tumor location. Acta Med.<br /> Okayama. 2015, 69 (4), pp.219-226.<br /> 6. Gugliemi A, Ruzzenante A. Radiofrequency<br /> ablation versus surgical resection for the<br /> treatment of small HCC in cirrhosis. J<br /> Gastrointest Surg. 2008, 12 (1), pp.192-198.<br /> 7. Ronnie T.P. Poon. Locoregional therapies<br /> for HCC: A critical review from surgeon’s<br /> perspective. Annals of Surg. 2002, 235 (4),<br /> pp.466-486.<br /> 8. S.M Lin, C.C Lin, Lin C.J et al.<br /> Randomised controlled trial comparing<br /> percutaneous radiofrequency thermal ablation,<br /> percutaneous ethanol injection, percutaneous<br /> acetic acid injection to treat HCC of 3 cm or<br /> less. Gut. 2005, 54 (8), pp.1151-1156.<br /> <br /> 195<br /> <br />