Diffuse intrahepatic recurrence after percutaneous radiofrequency ablation for solitary and small hepatocellular carcinoma

Abstract

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.

Comparative study of percutaneous radiofrequency ablation and hepatic resection for small, poorly differentiated hepatocellular carcinomas

“…However, the guidelines do not address tumor differentiation. Some previous studies have shown that RFA, which is used to treat poorly differentiated HCC, is associated with a risk of tumor seeding and diffuse intrahepatic recurrence . Despite this, it remains unclear as to whether or not tumor differentiation is actually associated with prognosis.…”

Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis

“…Of the local therapies, radiofrequency ablation (RFA) is more curative than percutaneous ethanol injection, but prognosis-related issues, such as dissemination, recurrence accompanied by portal invasion, and aggressive recurrence after RFA, have been identified [12][13][14][15], and histologically poorly differentiated HCCs have been reported to be a risk factor for dissemination [16]. Since there is a high possibility that poorly differentiated HCCs, even if small, may be advanced, with vascular invasion or intrahepatic metastasis, complete cure cannot be obtained by local therapy alone, and there is a risk that such treatment may cause metastasis or dissemination [16][17][18]. Because it is extremely difficult to diagnose tiny microscopic vascular invasion or intrahepatic metastases on diagnostic imaging, it will be extremely important in the future to diagnose poorly differentiated HCCs, which have higher malignant potential, to plan the treatment of HCCs.…”

Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma

“…There have been various terminologies used in previous studies and case reports representing the phenomenon of aggressive tumor recurrence after RFA for HCC, such as “rapid intra-hepatic dissemination” [9], “aggressive recurrence” [10,11], “scattered and rapid intrahepatic recurrence” [12], “early diffuse recurrence” [13], “diffuse intrahepatic recurrence” [14], “rapid aggressive tumor progression” [15], and “aggressive intrasegmental recurrence” [8]. Among these terminologies, we restricted our search to publications that included a definition of tumor recurrences.…”

“…1). Another hypothesis is that rapid heating of a tumor may lead to a sudden increase in internal pressure of ablated tissue and cause the scattering of malignant cells around the ablation zone [14,18]. In addition, although the results were based on an animal model studies, Ahmed et al [19] recently reported that RFA of normal liver tissue can stimulate distant tumor growth mediated by the hepatocyte growth factor/c-Met pathway and vascular endothelial growth factor activation.…”

“…Although several studies have investigated the risk factors and imaging findings of aggressive tumor recurrence after RFA for HCC [9-12, 14-16], there has been only one study that directly evaluated the therapeutic outcomes of RFA for HCC according to the occurrence of aggressive tumor recurrence during follow-up. Kang et al8 reported that the occurrence of AIR during follow-up had a significant unfavorable effect on overall survival.…”