Reply to comment on “Optimal extent of central lymphadenectomy for right-sided colon cancers: is lymphadenectomy beyond the superior mesenteric vein meaningful?”

Abstract

We gratefully appreciate the insightful comments from Dr. Zizzo and colleagues on our article which evaluated the therapeutic benefit of lymphadenectomy by LN area (i.e., D1, D2 and D3) among patients with right-sided colon cancers. By utilizing the metric of the therapeutic index (TI), which was calculated based on the frequency of lymph node metastasis (LNM) and the 5-year overall survival (OS) rate of patients with LNM, the results of our study suggested that, in the treatment of right-sided colon cancers, the survival benefit of D3 lymphadenectomy was lower (TI: 1.9) in comparison to D1 (TI: 22.1) and D2 (TI: 6.8) [1]. We agree with Dr. Zizzo et al. that D3 lymphadenectomy may be useful for predicting the prognosis as well as for improving the long-term outcomes. However, the aim of our study was not to determine whether D3 lymphadenectomy should be performed instead of D2 but to define whether extended central lymphadenectomy (i.e., beyond the superior mesenteric vein [SMV]) may contribute to improved survival. Complete mesocolic excision (CME) plus D3 lymphadenectomy for advanced colorectal cancers has been routinely performed at most Japanese institutions in compliance with the Japanese Classification of Colorectal Carcinoma guidelines [2]. In contrast, the optimal extent of central lymphadenectomy for right-sided colon cancers has not been well defined in Japan. In specific, Kanemitsu et al. suggested the performance of D3 lymphadenectomy extended to the left edge of the superior mesenteric artery (SMA) for right-sided colon cancers [3], whereas our institutions have utilized central lymphadenectomy extending to the left edge of the SMV. In Japan, there has long been debate about whether D3 lymphadenectomy should extend to the left edge of the SMA or to the left edge of the SMV for right-sided colon cancers; however, no consensus has been reached. In this context, the data from our study indicate that even central lymph node dissection (LND) up to the left border of the SMV had a low TI and suggest that central LND beyond the SMV may be of even less significance. Dr. Zizzo et al. referred to a meta-analysis that assessed the shortand long-term outcomes of right-sided hemicolectomy with CME + D3 LND versus classic right hemicolectomy with conventional D2 lymphadenectomy [4], which noted that the CME + D3 procedure was associated with better surgical specimen quality and an increased number of harvested LNs, as well as the improved overall survival rates [4]. More recently, two randomized control trials have been published and compared the surgical outcomes between D3 and D2 LND. The COLD trial found no difference between D2 and D3 in most of the short-term outcomes [5]. In the same manner, the RELARC trial noted similar outcomes between laparoscopic CME + D3 and D2 groups in postoperative morbidity rates, as well as in proximal and distal clearance [6]. As such, even the superiority of D3 lymphadenectomy over D2 for right-sided colon cancers remains controversial. Although D3 lymphadenectomy could be useful for right-sided colon cancers, the extended LND beyond SMV may not be beneficial to improve survival.