“Local recurrence” is not equal to “Local dissemination” after resection for hepatocellular carcinoma

Abstract

Complete removal of the tumor-bearing portal territory decreases local tumor recurrence and improves disease-specific survival of patients with hepatocellular carcinomaJournal of HepatologyVol. 64Issue 3PreviewLiver resection is now accepted as the first line treatment for hepatocellular carcinoma (HCC) in patients with preserved hepatic function [1,2]. A recent retrospective study has reported that surgical resection may have a prognostic advantage over the radiofrequency ablation (RFA) especially in patients with solitary HCC [3]. However, the high incidence of postoperative recurrence remains a major issue even after curative resection of HCC [4–9]. Full-Text PDF Reply to: ““Local recurrence” is not equal to “Local dissemination” after resection for hepatocellular carcinoma”Journal of HepatologyVol. 65Issue 5PreviewWe appreciate that Marubashi et al. had interest in our recent article and gave us a great opportunity to clarify major concerns in similar analyses looking at the efficacy of anatomic resection (AR) for hepatocellular carcinoma (HCC). In their letter to the editor, Marubashi et al. pointed out three “serious” issues in interpretation of the data in our recent work. Unfortunately, however, there seem to be critical misunderstandings on the design and results of the current study. Full-Text PDF We read with great interest the recent article by Shindoh et al. [[1]Shindoh J. Makuuchi M. Matsuyama Y. Mise Y. Arita J. Sakamoto Y. et al.Complete removal of the tumor-bearing portal territory decreases local tumor recurrence and improves disease-specific survival of patients with hepatocellular carcinoma.J Hepatol. 2016; 64: 594-600Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar] Their study analyzed the recurrence-free and overall survival outcomes between anatomical resection (AR) and non-anatomical resection (non-AR) for primary, solitary, and small (<5 cm) hepatocellular carcinoma. Their conclusion, that the disease-free survival rate was better in the AR group, differs from our previous report [[2]Marubashi S. Gotoh K. Akita H. Takahashi H. Ito Y. Yano M. et al.Anatomical versus non-anatomical resection for hepatocellular carcinoma.Br J Surg. 2015; 102: 776-784Crossref PubMed Scopus (90) Google Scholar]. After reading this article carefully, we found that there were three serious issues underlying the interpretation of this study. Firstly, the authors stated, “A clear prognostic advantage of AR was observed in DFS” (Fig. 2) with a p value of 0.046 between the AR group and the non-AR group. But this conclusion cannot be reliably derived from the data presented, because this analysis mixed intrahepatic metastasis with de novo (i.e., multicentric) hepatocellular carcinoma (HCC). Intrahepatic metastasis is the main cause of HCC recurrence in the residual liver within 2 years after surgery, while de novo HCC takes over it 4 years after hepatectomy and later, accounting for about half of all intrahepatic recurrences [[3]Sakon M. Umeshita K. Nagano H. Eguchi H. Kishimoto S. Miyamoto A. et al.Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves.Arch Surg. 2000; 135: 1456-1459Crossref PubMed Scopus (124) Google Scholar]. Therefore, it is easy to consider that the inclusion of these late follow-up periods in the statistical analysis could result in an overestimation of the differences in the incidence of local dissemination between the two groups. Secondly, the authors defined the AR procedure but did not define the non-AR procedure, which was only described as “a reduced extent of resection”. This could include a wide variety of resection methods, from enucleation to wide resection with a sufficient surgical margin. They seemed to disregard the importance of an appropriate resection margin based on tumor hemodynamics, i.e., the mechanism of local spread of HCC, in non-AR resection for HCC [[4]Sakon M. Nagano H. Nakamori S. Dono K. Umeshita K. Murakami T. et al.Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics.Arch Surg. 2002; 137: 94-99Crossref PubMed Google Scholar]. Heterogeneous procedures in the non-AR group would result in substantial bias, which should not be overlooked in such a comparative study of surgical procedures. Thirdly, the definition of “local recurrence” in this article is confusing. The authors stated, “Local recurrence was defined as any recurrence observed in the residual part of the tumor-bearing 3rd-order branches after non-AR or recurrence adjacent to the cut surface of the liver at the time of the initial tumor recurrence”. There was insufficient information describing the patterns of recurrence in this article. Judging from the description “the average number of recurrent nodules at the initial recurrence” was 7.9 nodules “in the patients of the non-AR group who developed local recurrences”, many instances of “local recurrence” in the non-AR group included multiple intrahepatic HCC recurrence scattered over the adjacent area or the same portal territory of the primary tumor, which should be considered as “systemic dissemination”. In other words, “local recurrence” should be clearly distinguished from “local dissemination”, which is the most important indicator of surgical outcome. The incidence of local recurrence in this study was 25 (12.0%) of 209 patients, which was too high when compared with our result of 6 (1.4%) local disseminations out of 424 patients [[5]Marubashi S. Gotoh K. Akita H. Takahashi H. Sugimura K. Miyoshi N. et al.Analysis of recurrence patterns after anatomical or non-anatomical resection for hepatocellular carcinoma.Ann Surg Oncol. 2015; 22: 2243-2252Crossref PubMed Scopus (35) Google Scholar]. We previously proposed a diagram of local, systemic dissemination and de novo HCC as the patterns of HCC recurrence after liver resection for HCC [[5]Marubashi S. Gotoh K. Akita H. Takahashi H. Sugimura K. Miyoshi N. et al.Analysis of recurrence patterns after anatomical or non-anatomical resection for hepatocellular carcinoma.Ann Surg Oncol. 2015; 22: 2243-2252Crossref PubMed Scopus (35) Google Scholar]. Most HCC recurrences after liver resection occur due to either systemic dissemination or as de novo HCC. Local dissemination is very rare, regardless of whether the procedure was AR or non-AR. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.