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Indian Journal of Surgical Oncology logoLink to Indian Journal of Surgical Oncology
. 2011 Jun 30;2(1):9–15. doi: 10.1007/s13193-011-0073-7

Presence of Pancreatic Intraepithelial Neoplasia in the Pancreatic Transection Margin does not Influence Outcome in Patients with R0 Resected Pancreatic Cancer

Hanno Matthaei 1,2, Seung-Mo Hong 1,2, Skye C Mayo 1,3, Marco dal Molin 1,2, Kelly Olino 3, Raghunandan Venkat 3, Michael Goggins 1,2,4,5, Joseph M Herman 6, Barish H Edil 1,3, Christopher L Wolfgang 1,3, John L Cameron 1,3, Richard D Schulick 1,3,4, Anirban Maitra 1,2,4, Ralph H Hruban 1,2,4,✉
PMCID: PMC3373004  PMID: 22696140

Abstract

Background.

Margin status is one of the strongest prognosticators after resection of pancreatic ductal adenocarcinoma (PDAC). The clinical significance of pancreatic intraepithelial neoplasia (PanIN) at a surgical margin has not been established.

Methods.

A total of 208 patients who underwent R0 resection for PDAC between 2004 and 2008 were selected. Intraoperative frozen section slides containing the final pancreatic parenchymal transection margin were evaluated for presence or absence, number, and grade of PanINs. Data were compared to clinicopathologic factors, including patient survival.

Results.

PanIN lesions were present in margins in 107 of 208 patients (51.4%). Median number of PanINs per pancreatic resection margin was 1 (range, 1–11). A total of 72 patients had PanIN-1 (34.6%), 44 had PanIN-2 (21.1%), and 16 had PanIN-3 (7.2%) at their margin. Overall median survival was 17.9 (95% confidence interval, 14–21.9) months. Neither the presence nor absence of PanIN nor histological grade had any significant correlation with important clinicopathologic characteristics. There were no significant survival differences between patients with or without PanIN lesions at the resection margin or among patients with PanIN-3 (carcinoma in situ) versus lower PanIN grades. However, patients with R1 resection had a significantly worse outcome compared with patients without invasive cancer at a margin irrespective of the presence of PanIN (P = 0.02).

Conclusions.

The presence of PanINs at a resection margin does not affect survival in patients who undergo R0 resection for PDAC. These results have significant clinical implications for surgeons, because no additional resection seems to be indicated when intraoperative frozen sections reveal even high-grade PanIN lesions.

Footnotes

Hanno Matthaei and Seung-Mo Hong contributed equally to this article.

References

  • 1.Society AC. Available at: http://www.cancer.org/cancer/pancreaticcancer/overviewguide/pancreatic-cancer-overview-key-statistics. Accessed 21 Dec 2010.
  • 2.Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol. 2008;3:157–188. doi: 10.1146/annurev.pathmechdis.3.121806.154305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.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(5):825–830. doi: 10.1007/s11605-009-0845-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Schmidt CM, Glant J, Winter JM, et al. Total pancreatectomy (R0 resection) improves survival over subtotal pancreatectomy in isolated neck margin positive pancreatic adenocarcinoma. Surgery. 2007;142(4):572–578. doi: 10.1016/j.surg.2007.07.016. [DOI] [PubMed] [Google Scholar]
  • 5.Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91(5):586–594. doi: 10.1002/bjs.4484. [DOI] [PubMed] [Google Scholar]
  • 6.Neoptolemos JP, Stocken DD, Dunn JA, 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):758–768. doi: 10.1097/00000658-200112000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–579. doi: 10.1016/S1091-255X(00)80105-5. [DOI] [PubMed] [Google Scholar]
  • 8.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):144–148. doi: 10.1097/00000658-199302000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Jamieson NB, Foulis AK, Oien KA, et al. Positive mobilization margins alone do not influence survival following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2010;251(6):1003–1010. doi: 10.1097/SLA.0b013e3181d77369. [DOI] [PubMed] [Google Scholar]
  • 10.Howard TJ, Krug JE, Yu J, et al. 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):1338–1345. doi: 10.1016/j.gassur.2006.09.008. [DOI] [PubMed] [Google Scholar]
  • 11.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(12):1200–1210. doi: 10.1056/NEJMoa032295. [DOI] [PubMed] [Google Scholar]
  • 12.Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–277. doi: 10.1001/jama.297.3.267. [DOI] [PubMed] [Google Scholar]
  • 13.Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15(6):1651–1660. doi: 10.1245/s10434-008-9839-8. [DOI] [PubMed] [Google Scholar]
  • 14.Pawlik TM, Gleisner AL, Cameron JL, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141(5):610–618. doi: 10.1016/j.surg.2006.12.013. [DOI] [PubMed] [Google Scholar]
  • 15.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(1):52–60. doi: 10.1097/01.sla.0000259391.84304.2b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10(9):1199–1210. doi: 10.1016/j.gassur.2006.08.018. [DOI] [PubMed] [Google Scholar]
  • 17.Kim J, Reber HA, Dry SM, et al. Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut. 2006;55(11):1598–1605. doi: 10.1136/gut.2005.083063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. New York: Springer; 2010. [Google Scholar]
  • 19.Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28(8):977–987. doi: 10.1097/01.pas.0000126675.59108.80. [DOI] [PubMed] [Google Scholar]
  • 20.Matthaei H, Maitra A. Precursor lesions of pancreatic cancer. In: Fitzgerald RC, editor. Pre-invasive disease: pathogenesis and clinical management. New York: Springer; 2011. pp. 395–420. [Google Scholar]
  • 21.Mayo SC, Austin DF, Sheppard BC, Mori M, Shipley DK, Billingsley KG. Adjuvant therapy and survival after resection of pancreatic adenocarcinoma: a population-based analysis. Cancer. 2010;116(12):2932–2940. doi: 10.1002/cncr.25082. [DOI] [PubMed] [Google Scholar]
  • 22.Kozuka S, Sassa R, Taki T, et al. Relation of pancreatic duct hyperplasia to carcinoma. Cancer. 1979;43(4):1418–1428. doi: 10.1002/1097-0142(197904)43:4<1418::AID-CNCR2820430431>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  • 23.Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467(7319):1114–1117. doi: 10.1038/nature09515. [DOI] [PMC free article] [PubMed] [Google Scholar]

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