Journal of Gastrointestinal Surgery

, Volume 16, Issue 10, pp 1875–1882 | Cite as

Tumor Infiltration in the Medial Resection Margin Predicts Survival After Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

  • Yaojun Zhang
  • Adam E. Frampton
  • Patrizia Cohen
  • Charis Kyriakides
  • Jan J. Bong
  • Nagy A. Habib
  • Duncan R. C. Spalding
  • Raida Ahmad
  • Long R. Jiao
Original Article

Abstract

Background

Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated.

Methods

Clinico-pathological data for 258 patients who underwent PD between 2001 and 2010 were retrieved from a prospective database. The rates of R1 resection in the circumferential resection margin (pancreatic transection, medial, posterior, and anterior surfaces) and their prognostic influence on survival were assessed.

Results

For PDAC, the R1 rate was 57.1 % (48/84) for any margin, 31.0 % (26/84) for anterior surface, 42.9 % (36/84) for posterior surface, 29.8 % (25/84) for medial margin, and 7.1 % (3/84) for pancreatic transection margin. Overall and disease-free survival for R1 resections were significantly worse than those for R0 resection (17.2 vs. 28.7 months, P = 0.007 and 12.3 vs. 21.0 months, P = 0.019, respectively). For individual margins, only medial positivity had a significant impact on survival (13.8 vs. 28.0 months, P < 0.001), as opposed to involvement in the anterior (19.7 vs. 23.3 months, P = 0.187) or posterior margin (17.5 vs. 24.2 months, P = 0.104). Multivariate analysis demonstrated R0 medial margin was an independent prognostic factor (P = 0.002, HR = 0.381; 95 % CI 0.207–0.701).

Conclusion

The medial surgical resection margin is the most important after PD for PDAC, and an R1 resection here predicts poor survival.

Keywords

Pancreatic ductal adenocarcinoma Pancreaticoduodenectomy Medial resection margin Prognostic factors Survival 

Supplementary material

11605_2012_1985_MOESM1_ESM.doc (31 kb)
Table S1Logistic regression for covariates associated with R1 medial resection margin. PPPD pylorus-preserving pancreaticoduodenectomy. (DOC 31 kb)

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60: 277-300.PubMedCrossRefGoogle Scholar
  2. 2.
    Vincent A, Herman J, Schulick R, Hruban RH, Goggins M (2011) Pancreatic cancer. Lancet 378: 607-620.PubMedCrossRefGoogle Scholar
  3. 3.
    Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, et al. (2005) Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut 54: 385-387.PubMedCrossRefGoogle Scholar
  4. 4.
    Alexakis N, Halloran C, Raraty M, Ghaneh P, Sutton R, et al. (2004) Current standards of surgery for pancreatic cancer. Br J Surg 91: 1410-1427.PubMedCrossRefGoogle Scholar
  5. 5.
    Ghaneh P, Costello E, Neoptolemos JP (2007) Biology and management of pancreatic cancer. Gut 56: 1134-1152.PubMedCrossRefGoogle Scholar
  6. 6.
    Pancreatic Section BSoG (2005) Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut 54 Suppl 5: v1-16.Google Scholar
  7. 7.
    Fatima J, Schnelldorfer T, Barton J, Wood CM, Wiste HJ, et al. (2010) Pancreatoduodenectomy for ductal adenocarcinoma: implications of positive margin on survival. Arch Surg 145: 167-172.PubMedCrossRefGoogle Scholar
  8. 8.
    Chang DK, Johns AL, Merrett ND, Gill AJ, Colvin EK, et al. (2009) Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol 27: 2855-2862.PubMedCrossRefGoogle Scholar
  9. 9.
    Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, et al. (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 10: 1199-1210; discussion 1210-1191.Google Scholar
  10. 10.
    Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, et al. (2007) Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg 246: 52-60.PubMedCrossRefGoogle Scholar
  11. 11.
    Schmidt CM, Powell ES, Yiannoutsos CT, Howard TJ, Wiebke EA, et al. (2004) Pancreaticoduodenectomy: a 20-year experience in 516 patients. Arch Surg 139: 718-725; discussion 725-717.Google Scholar
  12. 12.
    Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, et al. (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350: 1200-1210.PubMedCrossRefGoogle Scholar
  13. 13.
    Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, et al. (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304: 1073-1081.PubMedCrossRefGoogle Scholar
  14. 14.
    Verbeke CS (2008) Resection margins and R1 rates in pancreatic cancer--are we there yet? Histopathology 52: 787-796.PubMedCrossRefGoogle Scholar
  15. 15.
    Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, et al. (1995) Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221: 721-731; discussion 731-723.Google Scholar
  16. 16.
    Khalifa MA (2007) Intraoperative assessment of the Whipple resection specimen. J Clin Pathol 60: 975-980.PubMedCrossRefGoogle Scholar
  17. 17.
    Verbeke CS, Leitch D, Menon KV, McMahon MJ, Guillou PJ, et al. (2006) Redefining the R1 resection in pancreatic cancer. Br J Surg 93: 1232-1237.PubMedCrossRefGoogle Scholar
  18. 18.
    Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, et al. (2008) Most pancreatic cancer resections are R1 resections. Ann Surg Oncol 15: 1651-1660.PubMedCrossRefGoogle Scholar
  19. 19.
    (2003) Japanese Pancreatic Society: Classification of Pancreatic Cancer. Tokyo: Kanahara Publishing Co.Google Scholar
  20. 20.
    Hruban RH, Pitman MB, Klimstra DS (2007) Tumors of the pancreas. Atlas of tumor pathology. Washington DC: Armed Forces Institute of Pathology.Google Scholar
  21. 21.
    Jamieson NB, Foulis AK, Oien KA, Going JJ, Glen P, et al. (2010) Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. Ann Surg 251: 1003-1010.PubMedCrossRefGoogle Scholar
  22. 22.
    Schmidt CM, Glant J, Winter JM, Kennard J, Dixon J, et al. (2007) Total pancreatectomy (R0 resection) improves survival over subtotal pancreatectomy in isolated neck margin positive pancreatic adenocarcinoma. Surgery 142: 572-578; discussion 578-580.Google Scholar
  23. 23.
    Hernandez J, Mullinax J, Clark W, Toomey P, Villadolid D, et al. (2009) Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg 250: 76-80.PubMedCrossRefGoogle Scholar
  24. 24.
    Williamson R (1994) The pancreas. In: Keen G, Farndon J, editors. Operative surgery and management. Oxford, England: Butterworth Heinemann.Google Scholar
  25. 25.
    Sommerville CA, Limongelli P, Pai M, Ahmad R, Stamp G, et al. (2009) Survival analysis after pancreatic resection for ampullary and pancreatic head carcinoma: an analysis of clinicopathological factors. J Surg Oncol 100: 651-656.PubMedCrossRefGoogle Scholar
  26. 26.
    Pathologists TRCo (2010) Standards and Minimum Datasets for Reporting Cancers. Minimum Dataset for the Histopathological Reporting of Pancreatic, Ampulla of Vater and Bile Duct Carcinoma. London, UK.Google Scholar
  27. 27.
    Verbeke CS, Menon KV (2009) Redefining resection margin status in pancreatic cancer. HPB (Oxford) 11: 282-289.CrossRefGoogle Scholar
  28. 28.
    Angst E, Kim-Fuchs C, Kuruvilla YC, Inderbitzin D, Montani M, et al. (2012) How to counter the problem of R1 resection in duodenopancreatectomy for pancreatic cancer? J Gastrointest Surg 16: 673.PubMedCrossRefGoogle Scholar
  29. 29.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, et al. (2010) American Joint Committee on Cancer (AJCC) cancer staging manual. Chicago: Springer.Google Scholar
  30. 30.
    Howard TJ, Krug JE, Yu J, Zyromski NJ, Schmidt CM, et al. (2006) A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon’s contribution to long-term survival in pancreatic cancer. J Gastrointest Surg 10: 1338-1345; discussion 1345-1336.Google Scholar
  31. 31.
    Nagakawa T, Sanada H, Inagaki M, Sugama J, Ueno K, et al. (2004) Long-term survivors after resection of carcinoma of the head of the pancreas: significance of histologically curative resection. J Hepatobiliary Pancreat Surg 11: 402-408.PubMedCrossRefGoogle Scholar
  32. 32.
    Tsuchiya R, Noda T, Harada N, Miyamoto T, Tomioka T, et al. (1986) Collective review of small carcinomas of the pancreas. Ann Surg 203: 77-81.PubMedCrossRefGoogle Scholar
  33. 33.
    Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, et al. (2008) Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor. BMC Cancer 8: 5.PubMedCrossRefGoogle Scholar
  34. 34.
    Chua TC, Saxena A (2010) Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg 14: 1442-1452.PubMedCrossRefGoogle Scholar
  35. 35.
    Nakagohri T, Kinoshita T, Konishi M, Inoue K, Takahashi S (2003) Survival benefits of portal vein resection for pancreatic cancer. Am J Surg 186: 149-153.PubMedCrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2012

Authors and Affiliations

  • Yaojun Zhang
    • 1
  • Adam E. Frampton
    • 1
  • Patrizia Cohen
    • 2
  • Charis Kyriakides
    • 1
  • Jan J. Bong
    • 1
  • Nagy A. Habib
    • 1
  • Duncan R. C. Spalding
    • 1
  • Raida Ahmad
    • 2
  • Long R. Jiao
    • 1
  1. 1.HPB Surgical Unit, Department of Surgery and CancerImperial CollegeLondonUK
  2. 2.Department of Histopathology, Imperial College Healthcare NHS TrustHammersmith HospitalLondonUK

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