Are metastatic central lymph nodes (D3 volume) in right-sided colon cancer “REALLY” a sign of systemic disease?—a sub-group analysis of an ongoing multicenter trial

We would like to thank doctors Ballal and Saklani (1) for their well written, well-tempered, and kind comments on our publication in the Annals of Surgery (2). Having said that, we are required to provide some additional facts that did not come out quite clearly from the article itself. We present these thoughts to clear the water, for the sake of a better understanding to the readership of your esteemed journal.

• First, the clinical trial was started in 2010 (can be seen from the regional ethical committee approval cited, as well as the registration at clinicaltrials.gov) when most colon cancer surgery was still performed through open access, and absolutely all cases with advanced disease (3). It is also obvious that today we still operate a sizeable number of these patients through open access, especially those requiring multi organ resections (specifically cited in our manuscript). When the chronology is understood it is evident that in the later period, most of these patients were actually operated through minimally invasive access (4).
• The definition of the personalized D3 volume is based not only on the compartmentalizing of this volume but more importantly on the lymphatic clearances of the colic arteries, which define complete lymphadenectomy (5,6).
• While it is evident that right colectomy is a procedure with a low complication rate, surgery for advanced disease does bear the burden of increased complication rates. As the authors have correctly noticed there is a learning curve that has been clearly described also demonstrating improved survival through time, including lower complication rates (2). The gain in survival is important since the survival rate in the R1/2 group is depressing. All of these patients were initially operated with the intent to cure.
• We have published the quality-of-life results in patients operated with D3 extended mesenterectomy (7,8), and have documented the extent of the injury to the superior mesenteric nerve plexus (9), shedding more light on the consequences of this injury.
• The authors are correct when commenting on the quality of computed tomography (CT) detection of metastatic nodes (which according to the unpublished data from our study lies at the level of 73%) has not yet been at the required level. We strongly believe in our radiology colleagues that this can be enhanced, and that improvements in technology could well lead to the centralization of this patient group, where feasible. It seems that a 73% correct diagnosis would still lead to cure in most of these patients.
• And last, but not least, the only survivor in the R1/2 group was a patient with microsatellite instability (MSI)-positive tumor that received immunotherapy. The quality of life in patients who have received postoperative chemotherapy is, after all significantly lower in patients that have survived chemotherapy (10,11).

We, the authors, believe that all of these factors should be taken into account in the comment.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://actr.amegroups.com/article/view/10.21037/actr-24-161/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Ballal DS, Saklani AP. Can compartment-based complete mesocolic excision improve outcomes in patients with right colon cancer with metastatic D3 nodes? AME Clin Trials Rev 2024;2:51. [Crossref]
2. Banipal GS, Stimec BV, Andersen SN, et al. Are Metastatic Central Lymph Nodes (D3 volume) in right-sided Colon Cancer a Sign of Systemic Disease? A sub-group Analysis of an Ongoing Multicenter Trial. Ann Surg 2024;279:648-56. [PubMed]
3. Nesgaar JM, Stimec BV, Bakka AO, et al. Right Colectomy with Extended D3 Mesenterectomy: Anterior and Posterior to the Mesenteric Vessels. Surg Technol Int 2019;35:138-42. [PubMed]
4. Gaupset R, Nesgaard JM, Kazaryan AM, et al. Introducing Anatomically Correct CT-Guided Laparoscopic Right Colectomy with D3 Anterior Posterior Extended Mesenterectomy: Initial Experience and Technical Pitfalls. J Laparoendosc Adv Surg Tech A 2018;28:1174-82. [Crossref] [PubMed]
5. Nesgaard JM, Stimec BV, Soulie P, et al. Defining minimal clearances for adequate lymphatic resection relevant to right colectomy for cancer: a post-mortem study. Surg Endosc 2018;32:3806-12. [Crossref] [PubMed]
6. Willard CD, Kjaestad E, Stimec BV, et al. Preoperative anatomical road mapping reduces variability of operating time, estimated blood loss, and lymph node yield in right colectomy with extended D3 mesenterectomy for cancer. Int J Colorectal Dis 2019;34:151-60. [Crossref] [PubMed]
7. Thorsen Y, Stimec B, Andersen SN, et al. Bowel function and quality of life after superior mesenteric nerve plexus transection in right colectomy with D3 extended mesenterectomy. Tech Coloproctol 2016;20:445-53. [Crossref] [PubMed]
8. Thorsen Y, Stimec BV, Lindstrom JC, et al. Bowel Motility After Injury to the Superior Mesenteric Plexus During D3 Extended Mesenterectomy. J Surg Res 2019;239:115-24. [Crossref] [PubMed]
9. Luzon JA, Thorsen Y, Nogueira LP, et al. Reconstructing topography and extent of injury to the superior mesenteric artery plexus in right colectomy with extended D3 mesenterectomy: a composite multimodal 3-dimensional analysis. Surg Endosc 2022;36:7607-18. [Crossref] [PubMed]
10. Malik YG, Benth JŠ, Hamre HM, et al. Chemotherapy reduces long-term quality of life in recurrence-free colon cancer survivors (LaTE study)-a nationwide inverse probability of treatment-weighted registry-based cohort study and survey. Colorectal Dis 2024;26:22-33. [Crossref] [PubMed]
11. Malik YG, Lyckander LG, Lindstrøm JC, et al. Stratification of Stage III colon cancer may identify a patient group not requiring adjuvant chemotherapy. J Cancer Res Clin Oncol 2021;147:61-71. [Crossref] [PubMed]