Olivier Sutter

Comparison of no-touch multi-bipolar vs. monopolar radiofrequency ablation for small HCC

BACKGROUND & AIMS The primary aim of this study was to compare the rate of global radiofrequency ablation (RFA) failure between monopolar RFA (MonoRFA) vs. no-touch multi-bipolar RFA (NTmbpRFA) for small hepatocellular carcinoma (HCC) ⩽5cm in cirrhotic patients. METHODS A total of 362 cirrhotic patients were included retrospectively across four French centres (181 per treatment group). Global RFA failure (primary RFA failure or local tumour progression) was analysed using the Kaplan-Meier method after coarsened exact matching. Cox regression models were used to identify factors associated with global RFA failure and overall survival (OS). RESULTS Patients were well matched according to tumour size (⩽30/>30mm); tumour number (one/several); tumour location (subcapsular and near large vessel); serum AFP (<10; 10-100; >100ng/ml); Child-Pugh score (A/B) and platelet count (</⩾100G/L), p=1 for all. One case of perioperative mortality was observed in the NTmbpRFA group and the rate of major complications was 7.2% in both groups (p=1). The cumulative rates of global RFA failure at 1, 3 and 5years were respectively 13.3%, 31% and 36.7% for MonoRFA vs. 0.02%, 7.9% and 9.2% for NTmbpRFA, p<0.001. Monopolar RFA, tumour size >30mm and HCC near large vessel were independent factors associated with global RFA failure. Five-year OS was 37.2% following MonoRFA vs. 46.4% following NTmbpRFA p=0.378. CONCLUSIONS This large multicentre case-matched study showed that NTmbpRFA provided better primary RFA success and sustained local tumour response without increasing severe complications rates, for HCC ⩽5cm. LAY SUMMARY Using no-touch multi-bipolar radiofrequency ablation for hepatocellular carcinoma ⩽5cm provide a better sustained local tumour control compared to monopolar radiofrequency ablation.

Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series.

Purpose To assess the safety and efficacy of irreversible electroporation (IRE) in the treatment of patients with inoperable hepatocellular carcinoma (HCC) who are ineligible for thermal ablative techniques. Materials and Methods This retrospective study was approved by an ethics review board, and the requirement to obtain informed written consent was waived. From March 2012 to June 2015, 58 patients (median age, 65.4 years; range 41.6-90 years) with cirrhosis received IRE for the treatment of 75 HCC tumors. The median tumor diameter was 24 mm (range, 6-90 mm). IRE was selected because of tumor location (48 patients) or the patients poor general condition (10 patients). Treatment response was assessed with magnetic resonance (MR) imaging 1 month after treatment and every 3 months thereafter. Overall local tumor progression-free survival (PFS) per nodule (including initial treatment failures) was assessed by using the Kaplan-Meier method. The marginal Cox proportional hazards model was used to assess the factors associated with overall local tumor PFS. Complications were recorded and graded according to the Clavien-Dindo classification. Results Of 75 tumors, 58 (77.3%), 67 (89.3%), and 69 (92%) were completely ablated after one, two, and three IRE procedures, respectively. After a median follow-up of 9 months (range, 3 days to 31 months), the 6- and 12-month overall local tumor PFS rates for the 75 treated nodules were 87% (95% confidence interval [CI]: 77%, 93%) and 70% (95% CI: 56%, 81%), respectively. A preablative serum α-fetoprotein level higher than 200 ng/mL (hazard ratio: 9.94 [95% CI: 2.82, 35.06], P = .0004) was the only factor linked with overall local tumor PFS. Complications occurred in 11 of the 58 patients (19%) and were classified as grade I in three patients, grade II in five patients, grade IV in two patients, and grade V in one patient. The three (5.2%) complications classified as grade III or higher were liver failures occurring in patients with Child-Pugh class B disease; one led to death. Conclusion IRE offers safe, complete ablation of HCC tumors in patients with contraindications to other commonly used ablative techniques.

RE: Should We Use a Monopolar or Bipolar Mode for Performing No-Touch Radiofrequency Ablation of Liver Tumors? Clinical Practice Might have Already Resolved the Matter Once and for All

Copyright

Real-Time 3D Virtual Target Fluoroscopic Display for Challenging Hepatocellular Carcinoma Ablations Using Cone Beam CT

Three-dimensional virtual target fluoroscopic display is a new guidance tool that can facilitate challenging percutaneous ablation. The purpose of this study was to assess the feasibility, local efficacy, and safety of liver ablation assisted by three-dimensional virtual target fluoroscopic display. Sixty-seven hepatocellular carcinomas (mean diameter: 31 mm, range: 9-90 mm, 24 ≥ 30 mm, 16 of an infiltrative form) in 53 consecutive patients were ablated using irreversible electroporation (n = 39), multibipolar radiofrequency (n = 25), or microwave (n = 3) under a combination of ultrasound and three-dimensional virtual target fluoroscopic display guidance because the procedures were considered to be unfeasible under ultrasound alone. This guidance technology consisted of real-time fluoroscopic three-dimensional visualization of the tumor previously segmented from cone beam computed tomography images acquired at the start of the procedure. The results were assessed by cross-sectional imaging performed at 1 month and then every 3 months in the event of complete ablation. Factors associated with overall local tumor progression (initial treatment failure and subsequent local tumor progression) were assessed using a logistic regression model. Sixty-one (91%) tumors were completely ablated after 1 (n = 53) or 2 (n = 8) procedures. After a median follow-up of 12.75 months (1-23.2) of the 61 tumors displaying imaging characteristics consistent with complete ablation at 1 month, local tumor progression was observed in 9, so the overall local tumor progression rate was 22.3% (15 of 67). Under multivariate analysis, dome locations and infiltrative forms were associated with local tumor progression. No major complications occurred. Three-dimensional virtual target fluoroscopic display is a feasible and efficient image guidance tool to facilitate challenging ablations that are generally considered as infeasible using ultrasound alone.

Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results

Aims and Background: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. Methods: Eighty-three consecutive patients with cirrhosis (median age 70 years [37–93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1–9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. Results: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1–112 months), in naive patients the 3- and 5-year OS was 51% (38–62) and 24% (13–36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33–4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32–6.21], p = 0.008), multinodular form (HR: 2.74 [1.4–5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67–7.01], p = 0.0007) were independent RFS predictors. Conclusions: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.

Molecular classification of hepatocellular adenomas: impact on clinical practice

Hepatocellular adenomas are rare benign liver tumors usually developing in young women using oral contraception. The two main complications are hemorrhage (10–20%) and malignant transformation into hepatocellular carcinoma (<5%). A molecular classification has been recently updated in six major subgroups, linked to risk factors, histology, imaging and clinical features: adenomas inactivated for HNF1A, inflammatory adenomas, β-catenin-activated adenomas mutated in exon 3, β-catenin-activated adenomas mutated in exon 7–8, sonic hedgehog adenomas, and unclassified adenomas. Indeed, β-catenin-mutated adenomas in exon 3 are associated with malignant transformation, and sonic hedgehog adenomas with bleeding. This new nosology of hepatocellular adenomas will help to stratify patients according to risk of complications and will guide therapeutics in the future.

Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis

BACKGROUND We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis. METHODS Cirrhotic patients treated by RFA for HCC within Milan criteria were included. Associations between patient features and events were estimated by the Kaplan-Meier method with the log rank test and using uni/multivariate Cox models. RESULTS 389 cirrhotic patients (Child-Pugh A 86.6%, 473 tumors) were included. OS was 79.8%, 42.4% and 16%, and overall tumor recurrence 45%, 78% and 88% at 2, 5 and 10 years, respectively. In multivariate analysis, age, Child-Pugh, GGT, HCC near major vessels, esophageal varices, alkaline phosphatase and HBV predicted OS. Gender, ALT, AFP and alcohol intake were associated with tumor recurrence. Multinodular HCC (19.5%) was associated with risk of tumor recurrence outside Milan criteria. HBV patients had longer OS than other patients (P = 0.0059); negative HBV PCR at RFA was associated with decreased tumor recurrence (P = 0.0157). Using time-dependent analysis in HCV patients, a sustained virologic response was associated with increased OS (124.5 months) compared to other patients (49.2 months, P < 0.001). CONCLUSION Virologic response and severity of underlying liver disease were the main determinants of long-term OS after RFA for HCC developing on cirrhosis.

Could Monopolar Mode be a Suitable Strategy of Energy Deposition for Performing No-Touch Radiofrequency Ablation of Liver Tumor ≤ 5 cm?

Dear Editor, We read with great interest the study by Chang et al. [1]. Pursuing their considerable efforts in bringing scientific evidence of usefulness of no-touch ablation concept for the treatment of liver tumors [2, 3], they compared no-touch radiofrequency ablation (RFA) of patients bearing hepatocellular carcinoma up 5 cm in size, using multimonopolar (mM) versus multi-bipolar (mB) modes. While multi-bipolar mode required less number of ablations within shorter overall ablation times, they concluded that either mode could be favorably used for no-touch ablation of HCCs B 5 cm because local tumor progression (LTP)free survival rates were comparable in both groups. In our opinion, this apparent cautious conclusion is questionable regarding their results of preclinical and clinical studies. Although difference of LTP rates between the two groups was not statically significant, as authors mentioned, due to retrospective design of the study they did not emitted hypothesis and proper calculation of sample size. Thus, regarding the small number of patients recruited, the trend to achieve with mB better sustained local tumor control in shorter time with less electrodes repositioning would support a conclusion a little bit more favorable to this mode for applying no-touch ablation concept. In fact, as the authors have already nicely demonstrated in their previous experimental study [2], the centripetal energy deposition allowed by a given multi-straight-needle RF device working in mB mode is a strong physical rational for choosing it instead of mM mode [4]. Moreover, although authors did not use the same device in the two arms, the mB mode had again far better efficiency in delivering energy at the tumors since with less electrodes repositioning, and energy produced, it induced comparable volume of ablation within shorter time. It is of interest to point out that authors produced approximately twofolds more energy in mM than in mB arm for the treatment of comparable nodules in size. This apparently paradoxical result seems contradict the relationship existing between the amount of energy delivered at the tissue and the volume of ablation induced [5]. In reality, because half of energy produced with mM mode is delivered at ground pads, the energetic efficiency of such device is divided by 2 in comparison with mB mode. Thus, not surprisingly the volumes of tissue ablated were comparable between the two technics on condition to produce with mM mode twice more RF energy than with mB mode. A last technical point which calling some comments is the authors’ claim that internally cooled wet (ICW) electrode devices for performing mB procedures were mandatory because the internally cooled dry method (ICD) & Olivier Seror olivier.seror@aphp.fr

Irreversible Electroporation: Disappearance of Observable Changes at Imaging Does Not Always Imply Complete Reversibility of the Underlying Causal Tissue Changes

Irreversible Electroporation: Disappearance of Observable Changes at Imaging Does Not Always Imply Complete Reversibility of the Underlying Causal Tissue Changes