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Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer—a distinct view on lymph node yield

Abstract

Purpose

While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined.

Methods

The National Cancer Data Base 2006–2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA–IIB). Patients were dichotomized into the following two groups, those with 1–14 resected lymph nodes and those with  15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival.

Results

A total of 21,912 patients were included; median age was 66 years (IQR 59–73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10–22), 10,163 (46.4%) had 1–14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88–0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57–0.62, p < 0.001; adjusted HR 0.86, CI 0.83–0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy.

Discussion

While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.

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Acknowledgments

We thank the American College of Surgeons and the American Cancer Society for providing patient information through the NCDB used for this investigation. Furthermore, we thank the patients whose information through the NCDB allowed us to perform the investigation for this manuscript. RW holds a masters’ degree in biostatistics from the University of Heidelberg, Germany.

Funding

This study was in part supported by the Swiss Cancer Foundation.

Author information

R.W, C.T, and M.W. participated in the conceptualization of the study; R.W. and M.W. worked on the methodology; R.W. participated in formal analysis and investigation; R.W, C.T, and M.W. participated in the writing of the original draft; S.E, N. K, B.S, D.N, B.G, and S.A.M reviewed and edited the manuscript; D.N, D.B, and M.W. provided the resources; and B.S, B.G, S.A.M, and D.B. were the ones who supervised.

Correspondence to Mathias Worni.

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The authors declare that they have no conflict of interest.

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This retrospective cohort study was approved by the Duke Institutional Review Board. This article does not contain any studies with human participants performed by any of the authors.

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This paper was in part presented as a poster at the International Hepato-Pancreato-Biliary Association Conference in Geneva, Switzerland on September 4–7, 2018.

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Warschkow, R., Tsai, C., Köhn, N. et al. Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer—a distinct view on lymph node yield. Langenbecks Arch Surg 405, 43–54 (2020). https://doi.org/10.1007/s00423-020-01859-2

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Keywords

  • Pancreatic cancer
  • Lymph node
  • Mediation analysis
  • National Cancer Data Base
  • Surgery
  • Survival