Skip to main content

Advertisement

SpringerLink
Log in

Detailed Analysis of Margin Positivity and the Site of Local Recurrence After Pancreaticoduodenectomy

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The association between a positive surgical margin and local recurrence after resection of pancreatic adenocarcinoma (PDAC) has been reported. Assessment of the location of the a positive margin and the specific site of local recurrence has not been well described.

Methods

A prospectively maintained database was queried for patients who underwent R0/R1 pancreaticoduodenectomy for PDAC between 2000 and 2015. The pancreatic, posterior, gastric/duodenal, anterior peritoneal, and bile duct margins were routinely assessed. Postoperative imaging was reviewed for the site of first recurrence, and local recurrence was defined as recurrence located in the remnant pancreas, surgical bed, or retroperitoneal site outside the surgical bed.

Results

During the study period, 891 patients underwent pancreaticoduodenectomy, and 390 patients had an initial local recurrence with or without distant metastases. The 5-year cumulative incidence of local recurrence by site included the remnant pancreas (4%; 95% confidence interval [CI], 3–5%), the surgical bed (35%; 95% CI, 32–39%), and other regional retroperitoneal site (4%; 95% CI, 3–6%). In the univariate analysis, positive posterior margin (hazard ratio [HR], 1.50; 95% CI, 1.17–1.91; p = 0.001) and positive lymph nodes (HR, 1.36; 95% CI, 1.06–1.75; p = 0.017) were associated with surgical bed recurrence, and in the multivariate analysis, positive posterior margin remained significant (HR, 1.40; 95% CI, 1.09–1.81; p = 0.009). An isolated local recurrence was found in 197 patients, and a positive posterior margin was associated with surgical bed recurrence in this subgroup (HR, 1.51; 95% CI, 1.08–2.10; p = 0.016).

Conclusion

In this study, the primary association between site of margin positivity and site of local recurrence was between the posterior margin and surgical bed recurrence. Given this association and the limited ability to modify this margin intraoperatively, preoperative assessment should be emphasized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.

    Article  CAS  Google Scholar 

  2. Gnerlich JL, Luka SR, Deshpande AD, et al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012;147:753–60.

    Article  Google Scholar 

  3. Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267:936–45.

    Article  Google Scholar 

  4. Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600–4.

    Article  Google Scholar 

  5. Sugiura T, Uesaka K, Mihara K, et al. Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 2013;154:1078–86.

    Article  Google Scholar 

  6. You Y, Choi DW, Heo JS, et al. Clinical significance of revised microscopic positive resection margin status in ductal adenocarcinoma of pancreatic head. Ann Surg Treat Res. 2019;96:19–26.

    Article  Google Scholar 

  7. Walston S, Salloum J, Grieco C, et al. Identifying clinical factors which predict for early failure patterns following resection for pancreatic adenocarcinoma in patients who received adjuvant chemotherapy without chemoradiation. Am J Clin Oncol. 2018;41:1185–92.

    Article  Google Scholar 

  8. Ghaneh P, Kleeff J, Halloran CM, et al. The impact of positive resection margins on survival and recurrence following resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Ann Surg. 2019;269:520–9.

    Article  Google Scholar 

  9. Dillhoff M, Yates R, Wall K, et al. Intraoperative assessment of pancreatic neck margin at the time of pancreaticoduodenectomy increases likelihood of margin-negative resection in patients with pancreatic cancer. J Gastrointest Surg. 2009;13:825–30.

    Article  Google Scholar 

  10. Hernandez J, Mullinax J, Clark W, et al. Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg. 2009;250:76–80.

    Article  Google Scholar 

  11. Kooby DA, Lad NL, Squires MH III, et al. Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients. Ann Surg. 2014;260:494–501; discussion 501–493.

    Article  Google Scholar 

  12. Lad NL, Squires MH, Maithel SK, et al. Is it time to stop checking frozen section neck margins during pancreaticoduodenectomy? Ann Surg Oncol. 2013;20:3626–33.

    Article  Google Scholar 

  13. Pang TC, Wilson O, Argueta MA, et al. Frozen section of the pancreatic neck margin in pancreatoduodenectomy for pancreatic adenocarcinoma is of limited utility. Pathology. 2014;46:188–92.

    Article  CAS  Google Scholar 

  14. Fatima J, Schnelldorfer T, Barton J, et al. Pancreatoduodenectomy for ductal adenocarcinoma: implications of positive margin on survival. Arch Surg. 2010;145:167–72.

    Article  Google Scholar 

  15. Nitschke P, Volk A, Welsch T, et al. Impact of intraoperative re-resection to achieve R0 status on survival in patients with pancreatic cancer: a single-center experience with 483 patients. Ann Surg. 2017;265:1219–25.

    Article  Google Scholar 

  16. Barbier L, Turrini O, Gregoire E, Viret F, Le Treut YP, Delpero JR. Pancreatic head resectable adenocarcinoma: preoperative chemoradiation improves local control but does not affect survival. HPB Oxford. 2011;13:64–9.

    Article  Google Scholar 

  17. Greer SE, Pipas JM, Sutton JE, et al. Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma. J Am Coll Surg. 2008;206:451–7.

    Article  Google Scholar 

  18. Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.

    Article  CAS  Google Scholar 

  19. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.

    Article  CAS  Google Scholar 

  20. Papavasiliou P, Hoffman JP, Cohen SJ, Meyer JE, Watson JC, Chun YS. Impact of preoperative therapy on patterns of recurrence in pancreatic cancer. HPB Oxford. 2014;16:34–9.

    Article  Google Scholar 

  21. Schorn S, Demir IE, Samm N, et al. Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma. BJS Open. 2018;2:52–61.

    Article  CAS  Google Scholar 

  22. Adsay NV, Basturk O, Saka B, et al. Whipple made simple for surgical pathologists: orientation, dissection, and sampling of pancreaticoduodenectomy specimens for a more practical and accurate evaluation of pancreatic, distal common bile duct, and ampullary tumors. Am J Surg Pathol. 2014;38:480–93.

    Article  Google Scholar 

  23. Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.

    Article  Google Scholar 

  24. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. (eds) AJCC Cancer Staging Manual. 8th ed. American Joint Commission on Cancer, Springer, New York 2017.

    Google Scholar 

  25. National Comprehensive Cancer Network. Pancreatic Adenocarcinoma (version 3.2019). https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.

  26. Bockhorn M, Burdelski C, Bogoevski D, Sgourakis G, Yekebas EF, Izbicki JR. Arterial en bloc resection for pancreatic carcinoma. Br J Surg. 2011;98:86–92.

    Article  CAS  Google Scholar 

  27. Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254:882–93.

    Article  Google Scholar 

  28. Zettervall SL, Ju T, Holzmacher JL, et al. Arterial, but not venous, reconstruction increases 30-day morbidity and mortality in pancreaticoduodenectomy. J Gastrointest Surg. 2019;24(3):578–84.

    Article  Google Scholar 

  29. Hackert T, Strobel O, Michalski CW, et al. The TRIANGLE operation: radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single arm observational study. HPB Oxford. 2017;19:1001–7.

    Article  Google Scholar 

  30. Adham M, Singhirunnusorn J. Surgical technique and results of total mesopancreas excision (TMpE) in pancreatic tumors. Eur J Surg Oncol. 2012;38:340–5.

    Article  CAS  Google Scholar 

  31. Kawabata Y, Tanaka T, Nishi T, Monma H, Yano S, Tajima Y. Appraisal of a total meso-pancreatoduodenum excision with pancreaticoduodenectomy for pancreatic head carcinoma. Eur J Surg Oncol. 2012;38:574–9.

    Article  CAS  Google Scholar 

  32. Hsu CC, Herman JM, Corsini MM, et al. Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol. 2010;17:981–90.

    Article  Google Scholar 

  33. Merrell KW, Haddock MG, Quevedo JF, et al. Predictors of locoregional failure and impact on overall survival in patients with resected exocrine pancreatic cancer. Int J Radiat Oncol Biol Phys. 2016;94:561–70.

    Article  Google Scholar 

  34. Rutter CE, Park HS, Corso CD, et al. Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: an analysis of the National Cancer Data Base. Cancer. 2015;121:4141–9.

    Article  CAS  Google Scholar 

  35. Morganti AG, Falconi M, van Stiphout RG, et al. Multi-institutional pooled analysis on adjuvant chemoradiation in pancreatic cancer. Int J Radiat Oncol Biol Phys. 2014;90:911–7.

    Article  Google Scholar 

  36. Parikh AA, Maiga A, Bentrem D, et al. Adjuvant therapy in pancreas cancer: does it influence patterns of recurrence? J Am Coll Surg. 2016;222:448–56.

    Article  Google Scholar 

  37. Osipov A, Nissen N, Rutgers J, et al. Redefining the positive margin in pancreatic cancer: impact on patterns of failure, long-term survival and adjuvant therapy. Ann Surg Oncol. 2017;24:3674–82.

    Article  Google Scholar 

  38. Strobel O, Hank T, Hinz U, et al. Pancreatic cancer surgery: the new R-status counts. Ann Surg. 2017;265:565–73.

    Article  Google Scholar 

  39. van Roessel S, Kasumova GG, Tabatabaie O, et al. Pathological margin clearance and survival after pancreaticoduodenectomy in a U.S. and European pancreatic center. Ann Surg Oncol. 2018;25:1760–7.

    Article  Google Scholar 

  40. Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA

    Caitlin A. McIntyre MD, Constantinos P. Zambirinis MD, MRes, Alessandra Pulvirenti MD, Vinod P. Balachandran MD, T. Peter Kingham MD, Michael I. D’Angelica MD, Murray F. Brennan MD, Jeffrey A. Drebin MD, PhD, William R. Jarnagin MD & Peter J. Allen MD

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, New York, NY, USA

    Joanne F. Chou MPH & Mithat Gonen PhD

  3. Department of Surgery, Hepatopancreatobiliary Service, Duke University School of Medicine, Durham, NC, USA

    Peter J. Allen MD

Authors
  1. Caitlin A. McIntyre MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Constantinos P. Zambirinis MD, MRes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Pulvirenti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joanne F. Chou MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mithat Gonen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vinod P. Balachandran MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Peter Kingham MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael I. D’Angelica MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Murray F. Brennan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeffrey A. Drebin MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. William R. Jarnagin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Peter J. Allen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Allen MD.

Ethics declarations

Disclosures

Murray F. Brennan, MD - NIH/NCI Cancer Center Support Grant P30 CA008748.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McIntyre, C.A., Zambirinis, C.P., Pulvirenti, A. et al. Detailed Analysis of Margin Positivity and the Site of Local Recurrence After Pancreaticoduodenectomy. Ann Surg Oncol 28, 539–549 (2021). https://doi.org/10.1245/s10434-020-08600-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-08600-9

Search

Navigation