Correspondence to: Anita Balakrishnan (email: ab2031@cam.ac.uk)
Department of Hepatopancreatobiliary Surgery
Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
Hills Road
Cambridge CB2 0QQ
UK
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BJS Open, https://doi.org/10.1093/bjsopen/zraf056, published 23 May 2025
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Dear Editor
We thank Benhami et al. for their interest in our OMEGA study1 and for their insightful comments regarding the OMEGA-NOPPS score and nodal management in gallbladder cancer (GBC).
We agree that the median nodal yield across the cohort (median 5, IQR 2–9) remains below the AJCC-recommended 6-node threshold, reflecting real-world challenges in lymphadenectomy during GBC resection, especially in low-incidence regions. Our multivariable analysis accounted for country as a frailty variable to adjust for potential staging bias. Nonetheless, this is an important area for improvement and we would certainly continue to emphasise the importance of thorough regional lymphadenectomy, as per the discussion section of the manuscript.
We appreciate the opportunity to clarify our findings regarding nodal involvement in patients undergoing extrahepatic bile duct resection. In our dataset, 976 patients underwent extrahepatic bile duct resection (not 43 patients as mentioned in the comment), of whom 41% had N1 disease and 14% had N2 disease, as per the data presented in Table 1 of our manuscript.
We agree that a 2.6% N+ rate for patients with T1a disease might be considered surprising; however, this may be explained by two important points. Firstly, it must be remembered that it is not possible to confirm that the whole gallbladder was sectioned for all cases in this study. This is imperative to definitively exclude more advanced tumours, and we therefore cannot exclude the possibility that some of these cases might have harboured undiagnosed T1b or T2 disease with attendant node positivity. Secondly, it is also the case that some true T1a tumours, particularly those with lymphovascular or perineural invasion or poorly differentiated tumours, may be more aggressive and thus associated with positive nodes, which highlights the importance of our OMEGA-NOPPS score.
We have not been overly prescriptive in dictating how clinicians worldwide should treat patients with a high OMEGA-NOPPS score, as this is subject to nuances often specific to individual patient fitness or willingness for further surgery or chemotherapy. We believe this score highlights the likelihood of node positivity, allowing clinicians to then proceed with either confirmatory further surgery or chemotherapy on a personalised basis in patients with high scores. PET-CT may be useful, but in the context of incidental GBC (depending on the timing) is often limited by post-surgical changes and thus may not provide more confirmatory evidence than the score alone. We would anticipate that incidental GBC patients with early stage disease (T1a or T1b) and low scores are unlikely to benefit from further surgery for the purposes of lymphadenectomy. Benhami et al. suggest a possible role for therapeutic extended lymphadenectomy based on findings from registry datasets, however our more granular dataset demonstrated that while resection of non-regional lymph nodes increased the nodal yield, this was not associated with a survival benefit.
In summary, we thank Benhami et al. for their interest in our publication and comments on our paper and fully concur with the importance of appropriate nodal staging in GBC. In pre-operatively diagnosed GBC regional nodal dissection is essential, while in incidental early stage GBC, a high OMEGA-NOPPS score allows clinicians to identify those patients more likely to need further treatment.
References
Balakrishnan A, Barmpounakis P, Demiris N et al. Assessment of nodal staging and risk factors for nodal involvement in gallbladder cancer: an international, multicentre retrospective study. BJS Open 2025;9. doi:10.1093/bjsopen/zraf056.
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