Letter regarding ‘Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node negative intrahepatic cholangiocarcinoma’

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinomaJournal of HepatologyVol. 78Issue 2PreviewLymph-nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (iCCA), but the need to perform lymphadenectomy in patients with clinically node-negative (cN0) iCCA is still under debate. The aim of this study was to determine whether adequate lymphadenectomy improves long-term outcomes in patients undergoing liver resection for cN0 iCCA. Full-Text PDF Reply to: “Letter regarding ‘Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node negative intrahepatic cholangiocarcinoma’ ”Journal of HepatologyVol. 78Issue 5PreviewRegional lymphadenectomy (LND) is an essential part of the surgical procedure for many cancers. According to the different histotypes, retrieval of an adequate number of regional lymph-nodes (LNs) determines the correct staging of the disease. A correct nodal staging allows for prognostic prediction and often dictates whether adjuvant treatment will be offered. In terms of long-term oncologic outcomes, the beneficial effect of regional LND is more controversial and strongly depends on the primary disease. Full-Text PDF To the Editor: It was with great interest that we read the Italian multicenter retrospective cohort study by Sposito et al. on adequate lymphadenectomy in patients with clinically node negative intrahepatic cholangiocarcinoma.[1]Sposito C. Ratti F. Cucchetti A. Ardito F. Ruzzenente A. Di Sandro S. et al.Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node negative intrahepatic cholangiocarcinoma.J Hepatol. 2023; 78: P356-P363https://doi.org/10.1016/j.jhep.2022.10.021Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar The study was able to demonstrate that in 45% of the patients with radiologically negative lymph nodes, cancer cells were found in histological workup in the lymph nodes. Several questions arise with regard to the current multicenter study and we would like to emphasize the following points: We would like to challenge that the study is potentially flawed for several reasons. The occurrence of the major oncological outcome manifests itself after the median follow-up (FU) period (overall survival median 39 months; follow-up duration median 33 months) and therefore the study is not sufficiently powered. Neither type nor duration of (adjuvant) chemotherapy was described. As the cohort encompasses a 20-year study period, systemic treatment options are likely to have evolved over time. Details on the frequency at which radiological screening tools (computed tomography [CT] vs. magnetic resonance imaging [MRI] vs. positron emission tomography [PET]) were used are not provided for the preoperative diagnostics phase nor the FU period. This might have contributed to an ascertainment bias. Additionally, a relevant Hawthorne-effect might be possible due to a (most likely) increase of use of PET and/or (liver-specific) MRI over time. Relevant surgical details (laparoscopic vs. open resection) and postoperative treatment and complication rates were not mentioned/considered in this study. Surgical technique has developed and changed during the past 20 years, and the superiority of a laparoscopic approach has previously been shown.[2]Sahakyan M.A. Aghayan D.L. Edwin B. Alikhanov R. Britskaia N. Brudvik K.W. et al.Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: a multicenter propensity score-matched study.Scand J Gastroenterol. 2022; : 1-8https://doi.org/10.1080/00365521.2022.2143724Crossref PubMed Scopus (2) Google Scholar,[3]Brustia R. Laurent A. Goumard C. Langella S. Cherqui D. Kawai T. et al.Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: report of an international multicenter cohort study with propensity score matching.Surgery. 2022; 171: 1290-1302https://doi.org/10.1016/J.SURG.2021.08.015Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Brustia et al. were able to show that severe postoperative complications are predictors of overall survival (hazard ratio 10.5; 95% CI 1.01–109; p = 0.049) and tumor recurrence alike (hazard ratio 4.07; 95% CI 1.15–14.4; p = 0.030).[3]Brustia R. Laurent A. Goumard C. Langella S. Cherqui D. Kawai T. et al.Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: report of an international multicenter cohort study with propensity score matching.Surgery. 2022; 171: 1290-1302https://doi.org/10.1016/J.SURG.2021.08.015Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Moreover, 54.1% of recurrences in the adequate lymphadenectomy (AD-LND) group occurred in the liver only. No explanation on how additional extrahepatic surgical resection impacts intrahepatic oncology was given. This might be partially due to the R1 resection status, but further discussion and possible explanations need to be sought. The necessity of using stabilized inverse probability of treatment weights is questionable, as only a few cases (0.96% [n = 4] in AD-LND and 1.73% [n = 5] in NAD-LND) were excluded from further analysis and these few patients may be fundamentally surgically or biologically different from the rest of the cohort. This corresponds to the possible limitation of a retrospective cohort study as discussed by Sposito and colleagues. Moreover, some discrepancies exist in numbers between text, tables and figures (e.g. Table S1 adequate group n = 191 vs. text n = 195; Table S1 103/191 = 53.9% and not 54.1%). In conclusion, we would like to commend the authors on addressing a clinically relevant issue. At the same time the readers need to consider the still limited scientific evidence that would be required to routinely perform D2 lymph node dissection for clinically node negative intrahepatic cholangiocarcinoma. Future studies are warranted in which the aforementioned (possible) co-factors and biases are considered and adjusted for accordingly. The authors received no financial support to produce this manuscript. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. CTJM: data interpretation, wrote the manuscript; GB: data interpretation, critical revision; VB: data interpretation, critical revision. The following are the supplementary data to this article: Download .pdf (.17 MB) Help with pdf files Multimedia component 1