Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10‐year intention‐to‐treat analysis

Lee, Min Woo; Raman, Steven S.; Asvadi, Nazanin H.; Siripongsakun, Surachate; Hicks, Robert M.; Chen, Jeffrey; Worakitsitisatorn, Akeanong; McWilliams, J.; Tong, Myron J.; Finn, Richard S.; Agopian, Vatche G.; Busuttil, Ronald W.; Lu, David

doi:10.1002/hep.29098

Cited by 93 publications

(77 citation statements)

References 31 publications

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“…In 2004, Mazzaferro et al reported complete necrosis in 55% of 60 nodules, which increased to 63% when nodules were <3 cm . Other experiences are published, but the largest and most recent series available to date is that of Lee et al published in 2017 where histological examination of 113 HCC nodules treated with RFA revealed CPR in 71.7% of cases, somehow higher than the present results, even if similar when analyzing CPR for tumors <3 cm (78.9% in the Lee et al study). Quickly meta‐analyzing the present results and the results from Lee et al, the CPR achievable for HCCs within transplant criteria can be estimable to approximately 66.7% (95% CI, 56.8%‐76.6%, random effect model) and up to 72.7% (95% CI, 58.5%‐85.5%) for tumors <3 cm.…”

Section: Discussionsupporting

confidence: 55%

“…The presence of partial necrosis was assessed in a semiquantitative manner as the percentage of necrotic tissue divided by total tumor tissue. The complete absence of any residual vital tumor tissue defined CPR …”

Section: Methodsmentioning

confidence: 99%

“…However, some historical data are reported in regard to histological evaluation after RFA, including a relatively small number of patients and/or of treated nodules in whom necrosis was finally assessed on the explanted liver after transplant . These available data refer to the late 1990s or early 2000s, and with the refinement of ablation techniques as well as periprocedural care, it would be worthwhile to reassess the treatment success as defined by histological examination . Furthermore, the agreement between radiologic response to locoregional therapies (LRTs) and the degree of induced tumor necrosis remains to be fully ascertained .…”

mentioning

confidence: 99%

“…Furthermore, the agreement between radiologic response to locoregional therapies (LRTs) and the degree of induced tumor necrosis remains to be fully ascertained . It is well known that achieving a complete pathological response (CPR) is highly predictive of excellent longterm tumor‐free survival as well as a negligible risk of HCC recurrence after liver transplantation (LT) …”

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confidence: 99%

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Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology

Serra¹,

Cucchetti

Felicani

et al. 2019

Liver Transpl

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Radiofrequency ablation (RFA) represents a potentially curative option for early‐stage hepatocellular carcinoma (HCC). This study aims at evaluating the histologic response after RFA of small HCCs arising in cirrhosis. Data were reviewed from 78 patients with de novo HCCs who were treated with RFA and subsequently transplanted. The last radiological assessment before liver transplantation (LT) was used for comparison between modified Response Evaluation Criteria in Solid Tumors (mRECIST) and histological findings. A total of 125 de novo HCCs (median diameter, 20 mm) were treated with RFA only in 92 sessions. There were 98 nodules that did not show local recurrence during follow‐up (78.4%), and the remaining were retreated, except 1 because of subsequent LT. On explanted livers, complete pathological response (CPR) was observed in 61.6%, being 76.9% when <2 cm, 55.0% when 2‐3 cm, and 30.8% when >3 cm. Tumors near hepatic vessels had CPR in 50% of patients versus 69.3% for tumors distant from vessels (P = 0.039). Of the 125 HCCs, 114 had available radiological assessment within a median of 3 months before LT. Complete radiological response, according to mRECIST, was observed in 77.2% of nodules before LT. The Cohen κ was 0.48 (moderate agreement). The overall accuracy was 78.1%. A total of 18 complications were recorded with only 1 graded as major. In conclusion, RFA can provide high CPR for HCC, especially in smaller tumors distant from hepatic veins or portal branches. The agreement between mRECIST and histology is only moderate. Further refinements in radiological assessment are essential to accurately assess the true effectiveness of RFA.

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Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology

Serra¹,

Cucchetti

Felicani

et al. 2019

Liver Transpl

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“…Radiofrequency ablation (RFA) is a local therapy that is an alternative to surgery for HCC < 3 cm and is widely used due to its simplicity, safety, minimal invasiveness, repeatability, and short hospitalization (Lee et al 2017; Tsukamoto et al 2018). However, cases of rapidly progressing residual HCC after insufficient RFA have been reported to be on the rise, with post-RFA recurrent rates ranging from 3.2 to 26% (Lam et al 2008; Shiina et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Insufficient radiofrequency ablation promotes the metastasis of residual hepatocellular carcinoma cells via upregulating flotillin proteins

Zhang

Qin

et al. 2019

J Cancer Res Clin Oncol

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PurposeRadiofrequency ablation (RFA) therapy has proven to be effective and feasible for early-stage hepatocellular carcinoma (HCC); however, rapid progression of residual tumor cells after RFA has been confirmed, but the molecular mechanisms of this phenomenon are poorly understood. This study evaluated the effect of the lipid raft proteins known as flotillins on the invasive and metastatic potential of residual HCC.MethodsThe human HCC cell line HCCLM3 was used to establish insufficient RFA models in vivo and in vitro. Changes in cellular morphology, soft agar colony formation, motility, metastasis, and epithelial–mesenchymal transition (EMT) markers after insufficient RFA intervention in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry and transwell assays.ResultsThe results showed that flotillin-1 and flotillin-2 expression were upregulated in HCCLM3 cells following 45 °C heat treatment and in residual HCCLM3 xenografts cells after insufficient RFA. Knocking down flotillin-1 or flotillin-2 in HCCLM3 cells by shRNA significantly lowered insufficient RFA-induced tumor growth, EMT changes, and metastasis in vitro and in vivo. Furthermore, mechanism studies indicated that flotillins altered the EMT status and metastatic potential of heat-treated HCCLM3 cells by activating the Akt/Wnt/β-catenin signaling pathway.ConclusionsOur findings present new evidence that flotillins play a key role in the aggressive behaviors of residual cancer cells after insufficient RFA and provide new insights into the regulatory mechanism of Wnt/β-catenin signaling.Electronic supplementary materialThe online version of this article (10.1007/s00432-019-02852-z) contains supplementary material, which is available to authorized users.

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Current topics in the surgical treatments for hepatocellular carcinoma

Ban

Ogura

Akahoshi

et al. 2018

Annals of Gastroent Surgery

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Treatment strategy for hepatocellular carcinoma (HCC) requires optimal selection of therapies based on various factors related to tumor condition and liver functional reserve. Although several evidence‐based guidelines have been proposed for the treatment of HCC, the criteria and range of indications differ among these guidelines according to the circumstances of each country. In European nations and the USA, patients with the Barcelona Clinic Liver Cancer stage 0‐A are subjects for surgical resection, whereas in Asian countries, even those with the intermediate stage are regarded as surgical candidates. Furthermore, since the recent introduction and rapidly widely spreading use of laparoscopic liver resection, this technique has become an important treatment option for surgical resection. In this review article, we overview the current topics of treatment of HCC with a special focus on surgical therapy.

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Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10‐year intention‐to‐treat analysis

Cited by 93 publications

References 31 publications

Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology

Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology

Insufficient radiofrequency ablation promotes the metastasis of residual hepatocellular carcinoma cells via upregulating flotillin proteins

Current topics in the surgical treatments for hepatocellular carcinoma

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