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Pathology Reporting of Resected Pancreatic/Periampullary Cancer Specimen

  • María Carmen Gómez-Mateo
  • Luis Sabater-Ortí
  • Inmaculada Ruiz-Montesinos
  • Antonio Ferrández-Izquierdo
Chapter

Abstract

Pancreatic specimens have always been a great challenge for surgical pathologists due to their anatomic complexity and the difficulty of becoming familiar with these specimens. However, pancreatic specimens are becoming more and more common in many hospitals because of the improvements in surgical techniques and perioperative care that have dramatically reduced the postoperative mortality rate.

Pathological aspects are highly relevant for the management of cancer patients. However, in pancreatic cancer the discrepancies in the published data in terms of relevance have obscured their real value. This variability is mainly due to the different pathological approaches, not only in specimen handling and slicing but also in defining what should be considered as “margin” or “surface,” the nomenclature of these margins, and when we should consider that a margin is involved (0 mm versus 1 mm rule).

In the last decade, the use of standardized pathological protocols for macroscopic handling and reporting has proved to be essential for obtaining robust and reproducible data, emphasizing the fact that a good quality pathological report is required because of its prognostic relevance and implications in oncological treatment. However, some disagreements still exist regarding the most important guidelines, and this continues to be an obstacle for homogenizing and comparing studies.

Keywords

Pancreatic cancer Duodenopancreatectomy Resection margins Pathology protocols 

Abbreviations

AJCC

American Joint Committee on Cancer

BDM

Bile duct margin

CAP

College of American Pathologists

CDP

Cephalic duodenopancreatectomy

CRM

Circumferential resection margin

DBDC

Distal bile duct carcinoma

DP

Distal pancreatectomy

IPMN

Intraductal papillary mucinous neoplasm

ISGPS

International Study Group of Pancreatic Surgery

ITPN

Intraductal tubulopapillary neoplasm

JPS

Japan Pancreas Society

LN

Lymph node

LNR

Lymph node ratio

PanIN

Pancreatic intraepithelial neoplasia

PDAC

Pancreatic ductal adenocarcinoma

PNM

Pancreatic neck margin

PUPM

Posterior surface of the uncinate process margin

PV-SMVM

Portal vein-superior mesenteric vein margin

RCPA

Royal College of Pathologists of Australasia

RCPUK

Royal College of Pathologists of the United Kingdom

SMA

Superior mesenteric artery

SMAM

Superior mesenteric artery margin

SMV

Superior mesenteric vein

SMVM

Superior mesenteric vein margin

TP

Total pancreatectomy

WHO

World Health Organization

Notes

Acknowledgments

The authors thank Ms. Landy Menzies for her review of the manuscript. The authors also thank A. Juaristi, M.J. Silva, M.C. Caballero, and M. Larzabal, specialized pathologists at the Department of Pathology, Hospital Universitario Donostia, for their collaboration.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Silvestris N, Longo V, Cellini F, Reni M, Bittoni A, Cataldo I, et al. Neoadjuvant multimodal treatment of pancreatic ductal adenocarcinoma. Crit Rev Oncol Hematol. 2016;98:309–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2014;155(6):977–88.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 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(6):600–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, Zheng H, Szymonifka J, Wargo JA, et al. Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery. 2012;152(3 Suppl 1):S43–9.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Allema JH, Reinders ME, van Gulik TM, Koelemay MJ, Van Leeuwen DJ, de Wit LT, et al. Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region. Cancer. 1995;75(8):2069–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Lillemoe KD, Pitt HA. Periampullary adenocarcinoma: analysis of 5-year survivors. Ann Surg. 1998;227(6):821–31.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–79.PubMedCrossRefGoogle Scholar
  9. 9.
    Jarufe NP, Coldham C, Mayer AD, Mirza DF, Buckels JA, Bramhall SR. Favourable prognostic factors in a large UK experience of adenocarcinoma of the head of the pancreas and periampullary region. Dig Surg. 2004;21(3):202–9.PubMedCrossRefGoogle Scholar
  10. 10.
    van Geenen RC, van Gulik TM, Offerhaus GJ, de Wit LT, Busch OR, Obertop H, Gouma DJ. Survival after pancreaticoduodenectomy for periampullary adenocarcinoma: an update. Eur J Surg Oncol. 2001;27(6):549–57.PubMedCrossRefGoogle Scholar
  11. 11.
    Schmidt CM, Powell ES, Yiannoutsos CT, Howard TJ, Wiebke EA, Wiesenauer CA, et al. Pancreaticoduodenectomy: a 20-year experience in 516 patients. Arch Surg. 2004;139(7):718–25. discussion 725-7PubMedCrossRefGoogle Scholar
  12. 12.
    Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Büchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91(5):586–94.PubMedCrossRefGoogle Scholar
  13. 13.
    Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10(9):1199–210. discussion 1210-1PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    van Roest MH, Gouw AS, Peeters PM, Porte RJ, Slooff MJ, Fidler V, et al. Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization. Ann Surg. 2008;248(1):97–103.PubMedCrossRefGoogle Scholar
  15. 15.
    Chang DK, Johns AL, Merrett ND, Gill AJ, Colvin EK, Scarlett CJ, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol. 2009;27(17):2855–62.PubMedCrossRefGoogle Scholar
  16. 16.
    Hatzaras I, George N, Muscarella P, Melvin WS, Ellison EC, Bloomston M. Predictors of survival in periampullary cancers following pancreaticoduodenectomy. Ann Surg Oncol. 2010;17(4):991–7.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Verbeke CS, Leitch D, Menon KV, McMahon MJ, Guillou PJ, Anthoney A. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93(10):1232–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15(6):1651–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Verbeke CS. Resection margins and R1 rates in pancreatic cancer—are we there yet? Histopathology. 2008;52(7):787–96.PubMedCrossRefGoogle Scholar
  20. 20.
    Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford). 2009;11(4):282–9.CrossRefGoogle Scholar
  21. 21.
    Campbell F, Smith RA, Whelan P, Sutton R, Raraty M, Neoptolemos JP, et al. Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin. Histopathology. 2009;55(3):277–83.PubMedCrossRefGoogle Scholar
  22. 22.
    Menon KV, Gomez D, Smith AM, Anthoney A, Verbeke CS. Impact of margin status on survival following pancreatoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP). HPB (Oxford). 2009;11(1):18–24.CrossRefGoogle Scholar
  23. 23.
    Liszka Ł, Pajak J, Zielińska-Pajak E, Gołka D, Mrowiec S, Lampe P. Different approaches to assessment of lymph nodes and surgical margin status in patients with ductal adenocarcinoma of the pancreas treated with pancreaticoduodenectomy. Pathology. 2010;42(2):138–46.PubMedCrossRefGoogle Scholar
  24. 24.
    Jamieson NB, Foulis AK, Oien KA, Going JJ, Glen P, Dickson EJ, et al. Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2010;251(6):1003–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Sabater L, Gómez-Mateo Mdel C, López-Sebastián J, Muñoz-Forner E, Morera-Ocón F, Cervantes A, et al. Prognostic implications of the standardized study of resection margins in pancreatic cancers. Cir Esp. 2014;92(8):532–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Delpero JR, Bachellier P, Regenet N, Le Treut YP, Paye F, Carrere N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB (Oxford). 2014;16(1):20–33.CrossRefGoogle Scholar
  27. 27.
    Staley CA, Cleary KR, Abbruzzese JL, Lee JE, Ames FC, Fenoglio CJ, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996;12(4):373–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Verbeke CS. Resection margins in pancreatic cancer: are we entering a new era? HPB (Oxford). 2014;16(1):1–2.CrossRefGoogle Scholar
  29. 29.
    Verbeke CS, Gladhaug IP. Resection margin involvement and tumour origin in pancreatic head cancer. Br J Surg. 2012;99(8):1036–49.PubMedCrossRefGoogle Scholar
  30. 30.
    Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, et al. Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor. BMC Cancer. 2008;8:5.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Khalifa MA, Maksymov V, Rowsell C. Retroperitoneal margin of the pancreaticoduodenectomy specimen: anatomic mapping for the surgical pathologist. Virchows Arch. 2009;454(2):125–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Gaedcke J, Gunawan B, Grade M, Szöke R, Liersch T, Becker H, et al. The mesopancreas is the primary site for R1 resection in pancreatic head cancer: relevance for clinical trials. Langenbeck’s Arch Surg. 2010;395(4):451–8.CrossRefGoogle Scholar
  33. 33.
    Rau BM, Moritz K, Schuschan S, Alsfasser G, Prall F, Klar E. R1 resection in pancreatic cancer has significant impact on long-term outcome in standardized pathology modified for routine use. Surgery. 2012;152(3 Suppl 1):S103–11.PubMedCrossRefGoogle Scholar
  34. 34.
    Maksymov V, Hogan M, Khalifa MA. An anatomical-based mapping analysis of the pancreaticoduodenectomy retroperitoneal margin highlights the urgent need for standardized assessment. HPB (Oxford). 2013;15(3):218–23.CrossRefGoogle Scholar
  35. 35.
    Gómez-Mateo Mdel C, Sabater-Ortí L, Ferrández-Izquierdo A. Pathology handling of pancreatoduodenectomy specimens: approaches and controversies. World J Gastrointest Oncol. 2014;6(9):351–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Adsay NV, Basturk O, Saka B, Bagci P, Ozdemir D, Balci S, 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(4):480–93.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Ethun CG, Kooby DA. The importance of surgical margins in pancreatic cancer. J Surg Oncol. 2016;113(3):283–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Campbell F, Foulis AK, Verbeke CS. Dataset for the histopathological reporting of carcinomas of the pancreas, ampulla of Vater and common bile duct. In “Standards and datasets for reporting cancers.”. London: The Royal College of Pathologists; 2010. https://www.rcpath.org Google Scholar
  39. 39.
    Chai SM, Brown I, de Boer B, Epari K, Gill A, Jasas K, et al. Cancer of the exocrine pancreas, ampulla of Vater and distal common bile duct. Structured reporting protocol. 1st ed. Australia: Royal College of Pathologists of Australasia; 2014. http://www.rcpa.edu.au Google Scholar
  40. 40.
    Washington K, Berlin J, Branton P, Burgart LJ, Carter DK, Compton CC, et al. Protocol for the examination of specimens from patients with carcinoma of the exocrine pancreas: protocol applies to all endocrine tumors of the pancreas. Northfield: College of American Pathologists; 2016. http://www.cap.org Google Scholar
  41. 41.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. Cancer staging manual. American Joint Committee on Cancer (AJCC). 7th ed. New York: Springer; 2010.Google Scholar
  42. 42.
    Gill AJ, Johns AL, Eckstein R, Samra JS, Kaufman A, Chang DK, et al. Synoptic reporting improves histopathological assessment of pancreatic resection specimens. Pathology. 2009;41(2):161–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Katz MH, Merchant NB, Brower S, Branda M, Posner MC, William Traverso L, et al. Standardization of surgical and pathologic variables is needed in multicenter trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031 trial. Ann Surg Oncol. 2011;18(2):337–44.PubMedCrossRefGoogle Scholar
  44. 44.
    Lüttges J, Zamboni G, Klöppel G. Recommendation for the examination of pancreaticoduodenectomy specimens removed from patients with carcinoma of the exocrine pancreas. A proposal for a standardized pathological staging of pancreaticoduodenectomy specimens including a checklist. Dig Surg. 1999;16(4):291–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Howard TJ, Krug JE, Yu J, Zyromski NJ, Schmidt CM, Jacobson LE, et al. 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. 2006;10(10):1338–45. discussion 1345-6PubMedCrossRefGoogle Scholar
  46. 46.
    Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246(1):52–60.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Jamieson NB, Chan NI, Foulis AK, Dickson EJ, McKay CJ, Carter CR. The prognostic influence of resection margin clearance following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2013;17(3):511–21.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Gnerlich JL, Luka SR, Deshpande AD, Dubray BJ, Weir JS, Carpenter DH, Brunt EM, Strasberg SM, Hawkins WG, Linehan DC. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012;147(8):753–60.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    John BJ, Naik P, Ironside A, Davidson BR, Fusai G, Gillmore R, et al. Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival. HPB (Oxford). 2013;15(9):674–80.CrossRefGoogle Scholar
  50. 50.
    Kimbrough CW, St Hill CR, Martin RC, McMasters KM, Scoggins CR. Tumor-positive resection margins reflect an aggressive tumor biology in pancreatic cancer. J Surg Oncol. 2013;107(6):602–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Konstantinidis IT, Warshaw AL, Allen JN, Blaszkowsky LS, Castillo CF, Deshpande V, et al. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg. 2013;257(4):731–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Sugiura T, Uesaka K, Mihara K, Sasaki K, Kanemoto H, Mizuno T, et al. Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 2013;154:1078–86.PubMedCrossRefGoogle Scholar
  53. 53.
    Mathur A, Ross SB, Luberice K, Kurian T, Vice M, Toomey P, Rosemurgy AS. Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued. Am Surg. 2014;80(4):353–60.PubMedGoogle Scholar
  54. 54.
    Pang TC, Wilson O, Argueta MA, Hugh TJ, Chou A, Samra JS, et al. Frozen section of the pancreatic neck margin in pancreatoduodenectomy for pancreatic adenocarcinoma is of limited utility. Pathology. 2014;46(3):188–92.PubMedCrossRefGoogle Scholar
  55. 55.
    Gebauer F, Tachezy M, Vashist YK, Marx AH, Yekebas E, Izbicki JR, et al. Resection margin clearance in pancreatic cancer after implementation of the Leeds Pathology Protocol (LEEPP): clinically relevant or just academic? World J Surg. 2015;39(2):493–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Japan Pancreas Society. Classification of pancreatic cancer. 2nd ed. Tokyo: Kanehara; 2003.Google Scholar
  57. 57.
    Matsuno S, Egawa S, Fukuyama S, Motoi F, Sunamura M, Isaji S, et al. Pancreatic cancer registry in Japan: 20 years of experience. Pancreas. 2004;28(3):219–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Nagakawa T, Nagamori M, Futakami F, Tsukioka Y, Kayahara M, Ohta T, et al. Results of extensive surgery for pancreatic carcinoma. Cancer. 1996;77(4):640–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Nagakawa T, Sanada H, Inagaki M, Sugama J, Ueno K, Konishi I, et al. Long-term survivors after resection of carcinoma of the head of the pancreas: significance of histologically curative resection. J Hepato-Biliary-Pancreat Surg. 2004;11(6):402–8.CrossRefGoogle Scholar
  60. 60.
    Hruban RH, Bishop Pitman M, Klimstra DS. Tumors of the pancreas. In AFIP atlas of tumor pathology, 4th series, fascicle 6. Washington, DC: Armed Force Institute of Pathology; 2007.Google Scholar
  61. 61.
    Verbeke CS. Resection margins in pancreatic cancer. Surg Clin North Am. 2013;93(3):647–62.PubMedCrossRefGoogle Scholar
  62. 62.
    Katz MH, Bouvet M, Al-Refaie W, Gilpin EA, Moossa AR. Non-pancreatic periampullary adenocarcinomas: an explanation for favorable prognosis. Hepato-Gastroenterology. 2004;51(57):842–6.PubMedGoogle Scholar
  63. 63.
    Kamsposioras K, Anthoney DA, Ferentinos G, Smith AM, Menon KM, Cairns A, et al. Distal bile duct cancer – clinicopathological features and prognostic factors. Pancreatology. 2010;10:361.Google Scholar
  64. 64.
    Verbeke CS, Knapp J, Gladhaug IP. Tumour growth is more dispersed in pancreatic head cancers than in rectal cancer: implications for resection margin assessment. Histopathology. 2011;59(6):1111–21.PubMedCrossRefGoogle Scholar
  65. 65.
    Solcia E, Capella C, Kloppel G. Tumors of the endocrine pancreas. In AFIP atlas of tumor pathology, 3rd series, fascicle 20. Washington, DC: Armed Forces Institute of Pathology; 1997.Google Scholar
  66. 66.
    Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234(6):758–68.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Pingpank JF, Hoffman JP, Ross EA, Cooper HS, Meropol NJ, Freedman G, et al. Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg. 2001;5(2):121–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Kuhlmann KF, de Castro SM, Wesseling JG, ten Kate FJ, Offerhaus GJ, Busch OR, et al. Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer. 2004;40(4):549–58.PubMedCrossRefGoogle Scholar
  69. 69.
    Bilimoria KY, Talamonti MS, Sener SF, Bilimoria MM, Stewart AK, Winchester DP, et al. Effect of hospital volume on margin status after pancreaticoduodenectomy for cancer. J Am Coll Surg. 2008;207(4):510–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Fatima J, Schnelldorfer T, Barton J, Wood CM, Wiste HJ, Smyrk TC, et al. Pancreatoduodenectomy for ductal adenocarcinoma: implications of positive margin on survival. Arch Surg. 2010;145(2):167–72.PubMedCrossRefGoogle Scholar
  71. 71.
    Butturini G, Stocken DD, Wente MN, Jeekel H, Klinkenbijl JH, Bakkevold KE, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg. 2008;143(1):75–83. discussion 83PubMedCrossRefGoogle Scholar
  72. 72.
    Willett CG, Lewandrowski K, Warshaw AL, Efird J, Compton CC. Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann Surg. 1993;217(2):144–8.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 1997;225(5):621–33. discussion 633-6PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Millikan KW, Deziel DJ, Silverstein JC, Kanjo TM, Christein JD, Doolas A, et al. Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg. 1999;65(7):618–23. discussion 623-4PubMedGoogle Scholar
  75. 75.
    Benassai G, Mastrorilli M, Quarto G, Cappiello A, Giani U, Forestieri P, et al. Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas. J Surg Oncol. 2000;73(4):212–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Hsu CC, Herman JM, Corsini MM, Winter JM, Callister MD, Haddock MG, et al. Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol. 2010;17(4):981–90.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Kooby DA, Lad NL, Squires MH 3rd, Maithel SK, Sarmiento JM, Staley CA, et al. Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients. Ann Surg. 2014;260(3):494–501. discussion 501-3PubMedCrossRefGoogle Scholar
  78. 78.
    Schlitter AM, Esposito I. Definition of microscopic tumor clearance (r0) in pancreatic cancer resections. Cancers (Basel) 2010;2(4):2001–10.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer. 2002;94(9):2511–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Shimada K, Sakamoto Y, Sano T, Kosuge T. Prognostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancreatic adenocarcinoma of the body and tail. Surgery. 2006;139(3):288–95.PubMedCrossRefGoogle Scholar
  81. 81.
    Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237(1):74–85.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Moon HJ, An JY, Heo JS, Choi SH, Joh JW, Kim YI. Predicting survival after surgical resection for pancreatic ductal adenocarcinoma. Pancreas. 2006;32(1):37–43.PubMedCrossRefGoogle Scholar
  83. 83.
    House MG, Gönen M, Jarnagin WR, D’Angelica M, DeMatteo RP, Fong Y, et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007;11(11):1549–55.PubMedCrossRefGoogle Scholar
  84. 84.
    Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247(3):456–62.PubMedCrossRefGoogle Scholar
  85. 85.
    Garcea G, Dennison AR, Ong SL, Pattenden CJ, Neal CP, Sutton CD, et al. Tumour characteristics predictive of survival following resection for ductal adenocarcinoma of the head of pancreas. Eur J Surg Oncol. 2007;33(7):892–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Berger AC, Watson JC, Ross EA, Hoffman JP. The metastatic/examined lymph node ratio is an important prognostic factor after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am Surg. 2004;70(3):235–40. discussion 240PubMedGoogle Scholar
  87. 87.
    Tomlinson JS, Jain S, Bentrem DJ, Sekeris EG, Maggard MA, Hines OJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007;142(8):767–23. discussion 773-4PubMedCrossRefGoogle Scholar
  88. 88.
    Falconi M, Crippa S, Domínguez I, Barugola G, Capelli P, Marcucci S, et al. Prognostic relevance of lymph node ratio and number of resected nodes after curative resection of ampulla of Vater carcinoma. Ann Surg Oncol. 2008;15(11):3178–86.PubMedCrossRefGoogle Scholar
  89. 89.
    Lahat G, Lubezky N, Gerstenhaber F, Nizri E, Gysi M, Rozenek M, et al. Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome? World J Surg Oncol. 2016;14(1):254.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Elshaer M, Gravante G, Kosmin M, Riaz A, Al-Bahrani A. A systematic review of the prognostic value of lymph node ratio, number of positive nodes and total nodes examined in pancreatic ductal adenocarcinoma. Ann R Coll Surg Engl. 2017;99(2):101–6.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Sabater L, García-Granero A, Escrig-Sos J, Gómez-Mateo Mdel C, Sastre J, Ferrández A, et al. Outcome quality standards in pancreatic oncologic surgery. Ann Surg Oncol. 2014;21(4):1138–46.PubMedCrossRefGoogle Scholar
  92. 92.
    Sierzega M, Popiela T, Kulig J, Nowak K. The ratio of metastatic/resected lymph nodes is an independent prognostic factor in patients with node-positive pancreatic head cancer. Pancreas. 2006;33(3):240–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141(5):610–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Gomez D, Menon KV, Smith AM, Verbeke CS. Tumour location and number of positive lymph nodes are independent prognostic factors in distal bile duct cancer. HPB (Oxford). 2008;10(Suppl 1):227.Google Scholar
  95. 95.
    Robinson SM, Rahman A, Haugk B, French JJ, Manas DM, Jaques BC, et al. Metastatic lymph node ratio as an important prognostic factor in pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2012;38(4):333–9.PubMedCrossRefGoogle Scholar
  96. 96.
    La Torre M, Cavallini M, Ramacciato G, Cosenza G, Rossi Del Monte S, Nigri G, et al. Role of the lymph node ratio in pancreatic ductal adenocarcinoma. Impact on patient stratification and prognosis. J Surg Oncol. 2011;104(6):629–33.PubMedCrossRefGoogle Scholar
  97. 97.
    Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. 4th ed. Geneva, Switzerland: WHO Press; 2010.Google Scholar
  98. 98.
    Sobin LH, Gospodarowicz MK, Wittekind CH. International Union against cancer TNM classification of malignant tumours. 7th ed. Hoboken: Wiley/Blackwell; 2009.Google Scholar
  99. 99.
    Bogoevski D, Yekebas EF, Schurr P, Kaifi JT, Kutup A, Erbersdobler A, et al. Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal adenocarcinoma: prognostic significance of nodal microinvolvement. Ann Surg. 2004;240(6):993–1000. discussion 1000-1PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Allen PJ, Kuk D, Castillo CF, Basturk O, Wolfgang CL, Cameron JL, et al. Multi-institutional Validation Study of the American Joint Commission on cancer (8th edition) changes for T and N staging in patients with pancreatic adenocarcinoma. Ann Surg. 2017;265(1):185–91.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Adsay NV, Bagci P, Tajiri T, Oliva I, Ohike N, Balci S, et al. Pathologic staging of pancreatic, ampullary, biliary, and gallbladder cancers: pitfalls and practical limitations of the current AJCC/UICC TNM staging system and opportunities for improvement. Semin Diagn Pathol. 2012;29(3):127–41.PubMedCrossRefGoogle Scholar
  102. 102.
    Nelson DW, Blanchard TH, Causey MW, Homann JF, Brown TA. Examining the accuracy and clinical usefulness of intraoperative frozen section analysis in the management of pancreatic lesions. Am J Surg. 2013;205(5):613–7; discussion 617.PubMedCrossRefGoogle Scholar
  103. 103.
    Doucas H, Neal CP, O'Reilly K, Dennison AR, Berry DP. Frozen section diagnosis of pancreatic malignancy: a sensitive diagnostic technique. Pancreatology. 2006;6(3):210–3; discussion 214.PubMedCrossRefGoogle Scholar
  104. 104.
    Campanale RP 2nd, Frey CF, Farias LR, Twomey PL, Guernsey JM, Keehn R, Higgins G. Reliability and sensitivity of frozen-section pancreatic biopsy. Arch Surg. 1985;120(3):283–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Catalano C, Laghi A, Fraioli F, Pediconi F, Napoli A, Danti M, et al. Pancreatic carcinoma: the role of high-resolution multislice spiral CT in the diagnosis and assessment of resectability. Eur Radiol. 2003;13(1):149–56.PubMedGoogle Scholar
  106. 106.
    Raut CP, Grau AM, Staerkel GA, Kaw M, Tamm EP, Wolff RA, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer. J Gastrointest Surg. 2003;7(1):118–26. discussion 127-8PubMedCrossRefGoogle Scholar
  107. 107.
    Dillhoff M, Yates R, Wall K, Muscarella P, Melvin WS, Ellison EC, Bloomston M. 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(5):825–30.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Pessaux P, Varma D, Arnaud JP. Pancreaticoduodenectomy: superior mesenteric artery first approach. J Gastrointest Surg. 2006;10(4):607–11.PubMedCrossRefGoogle Scholar
  109. 109.
    Dumitrascu T, David L, Popescu I. Posterior versus standard approach in pancreatoduodenectomy: a case-match study. Langenbeck’s Arch Surg. 2010;395(6):677–84.CrossRefGoogle Scholar
  110. 110.
    Shrikhande SV, Barreto SG, Bodhankar YD, Suradkar K, Shetty G, Hawaldar R, et al. Superior mesenteric artery first combined with uncinated process approach versus uncinate process first approach in pancreatoduodenectomy: a comparative study evaluating perioperative outcomes. Langenbeck’s Arch Surg. 2011;396(8):1205–12.CrossRefGoogle Scholar
  111. 111.
    Sanjay P, Takaori K, Govil S, Shrikhande SV, Windsor JA. ‘Artery-first’ approaches to pancreatoduodenectomy. Br J Surg. 2012;99(8):1027–35.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Pallisera A, Morales R, Ramia JM. Tricks and tips in pancreatoduodenectomy. World J Gastrointest Oncol. 2014;6(9):344–50.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Inoue Y, Saiura A, Yoshioka R, Ono Y, Takahashi M, Arita J, et al. Pancreatoduodenectomy with systematic mesopancreas dissection using a supracolic anterior artery-first approach. Ann Surg. 2015;262:1092.PubMedCrossRefGoogle Scholar
  114. 114.
    Zhang Y, Frampton AE, Cohen P, Kyriakides C, Bong JJ, Habib NA, et al. Tumor infiltration in the medial resection margin predicts survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2012;16(10):1875–82.PubMedCrossRefGoogle Scholar
  115. 115.
    Schmidt CM, Glant J, Winter JM, Kennard J, Dixon J, Zhao Q, et al. Total pancreatectomy (R0 resection) improves survival over subtotal pancreatectomy in isolated neck margin positive pancreatic adenocarcinoma. Surgery. 2007;142(4):572–8. discussion 578-80PubMedCrossRefGoogle Scholar
  116. 116.
    Hernandez J, Mullinax J, Clark W, Toomey P, Villadolid D, Morton C, et al. Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg. 2009;250(1):76–80.PubMedCrossRefGoogle Scholar
  117. 117.
    Lad NL, Squires MH, Maithel SK, Fisher SB, Mehta VV, Cardona K, et al. Is it time to stop checking frozen section neck margins during pancreaticoduodenectomy? Ann Surg Oncol. 2013;20(11):3626–33.PubMedCrossRefGoogle Scholar
  118. 118.
    Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, et al. Members of Verona consensus meeting, 2013. Pathologic evaluation and reporting of intraductal papillary mucinous neoplasms of the pancreas and other tumoral intraepithelial neoplasms of pancreatobiliary tract: recommendations of Verona consensus meeting. Ann Surg. 2016;263(1):162–77.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, et al. Baltimore consensus meeting. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 2015;39(12):1730–41.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Matthaei H, Hong SM, Mayo SC, dal Molin M, Olino K, Venkat R, et al. Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. Ann Surg Oncol. 2011;18(12):3493–9.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    McCarthy DM, Brat DJ, Wilentz RE, Yeo CJ, Cameron JL, Kern SE, Hruban RH. Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labeling. Hum Pathol. 2001;32(6):638–42.PubMedCrossRefGoogle Scholar
  122. 122.
    Nara S, Shimada K, Sakamoto Y, Esaki M, Kosuge T, Hiraoka N. Clinical significance of frozen section analysis during resection of intraductal papillary mucinous neoplasm: should a positive pancreatic margin for adenoma or borderline lesion be resected additionally? J Am Coll Surg. 2009;209(5):614–21.PubMedCrossRefGoogle Scholar
  123. 123.
    Fujii T, Kato K, Kodera Y, Kanda M, Nagai S, Yamada S, et al. Prognostic impact of pancreatic margin status in the intraductal papillary mucinous neoplasms of the pancreas. Surgery. 2010;148(2):285–90.PubMedCrossRefGoogle Scholar
  124. 124.
    Sauvanet A, Couvelard A, Belghiti J. Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas. World J Gastrointest Surg. 2010;2(10):352–8.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Chun YS, Cooper HS, Cohen SJ, Konski A, Burtness B, Denlinger CS, et al. Significance of pathologic response to preoperative therapy in pancreatic cancer. Ann Surg Oncol. 2011;18(13):3601–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg. 2002;6(5):763–9.PubMedCrossRefGoogle Scholar
  127. 127.
    Kang CM, Chung YE, Park JY, Sung JS, Hwang HK, Choi HJ, et al. Potential contribution of preoperative neoadjuvant concurrent chemoradiation therapy on margin-negative resection in borderline resectable pancreatic cancer. J Gastrointest Surg. 2012;16(3):509–17.PubMedCrossRefGoogle Scholar
  128. 128.
    Casadei R, Di Marco M, Ricci C, Santini D, Serra C, Calculli L, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg. 2015;19(10):1802–12.PubMedCrossRefGoogle Scholar
  129. 129.
    Hartman DJ, Krasinskas AM. Assessing treatment effect in pancreatic cancer. Arch Pathol Lab Med. 2012;136(1):100–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Katz MH, Wang H, Balachandran A, Bhosale P, Crane CH, Wang X, et al. Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. J Gastrointest Surg. 2012;16(1):68–78. discussion 78-9PubMedCrossRefGoogle Scholar
  131. 131.
    Spitz FR, Abbruzzese JL, Lee JE, Pisters PW, Lowy AM, Fenoglio CJ, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15(3):928–37.PubMedCrossRefGoogle Scholar
  132. 132.
    Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127(11):1335–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Verbeke C, Löhr M, Karlsson JS, Del Chiaro M. Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. Cancer Treat Rev. 2015;41(1):17–26.PubMedCrossRefGoogle Scholar
  134. 134.
    Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–6.PubMedCrossRefGoogle Scholar
  135. 135.
    Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Color Dis. 1997;12(1):19–23.CrossRefGoogle Scholar
  136. 136.
    Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141–6.PubMedCrossRefGoogle Scholar
  137. 137.
    White RR, Xie HB, Gottfried MR, Czito BG, Hurwitz HI, Morse MA, et al. Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol. 2005;12(3):214–21.PubMedCrossRefGoogle Scholar
  138. 138.
    Ishikawa O, Ohhigashi H, Teshima T, Chatani M, Inoue T, Tanaka S, et al. Clinical and histopathological appraisal of preoperative irradiation for adenocarcinoma of the pancreatoduodenal region. J Surg Oncol. 1989;40(3):143–51.PubMedCrossRefGoogle Scholar
  139. 139.
    Pendurthi TK, Cooper HS, Young NA, Hoffman JP, Litwin S, Watts P, et al. Histopathologic effects of preoperative chemoradiotherapy on pancreatic carcinoma. Gastroenterology. 1996;110(4):1410.Google Scholar
  140. 140.
    Chatterjee D, Katz MH, Rashid A, Varadhachary GR, Wolff RA, Wang H, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118(12):3182–90.PubMedCrossRefGoogle Scholar
  141. 141.
    Lüttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Klöppel G. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000;191(2):154–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • María Carmen Gómez-Mateo
    • 1
  • Luis Sabater-Ortí
    • 2
  • Inmaculada Ruiz-Montesinos
    • 3
  • Antonio Ferrández-Izquierdo
    • 4
  1. 1.Department of PathologyHospital Universitario DonostiaDonostiaSpain
  2. 2.Department of SurgeryHospital Clínico, University of ValenciaValenciaSpain
  3. 3.Department of SurgeryHospital Universitario DonostiaDonostiaSpain
  4. 4.Department of PathologyHospital Clínico, University of ValenciaValenciaSpain

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