Influence of Microscopically Positive Resection Margins on Long-Term (>5-Year) Survival after Resection of Pancreatic Ductal Adenocarcinoma
Context The impact of R1 resection on outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear, with most studies assessing survival for up to 5 years. Objective The aim of this study was to evaluate the prognostic influence of R1 and R0 resection on >5-year survival in patients with PDAC. Material and methods Of the 271 patients with PDAC who underwent pancreatic resection over a 26-year period, 33 had survived for ≥5 years. R1 status was defined as the presence of tumor tissue ≤1 mm from a circumferential margin surface. Patients were followed-up for 61 to 288 months. Results Of the 33 long-term survivors, 19 and 14 underwent R0 and R1 resection, respectively. The percentage of male patients was significantly higher in the R1 than in the R0 group. The R0 group tended to show a weaker relationship between R status and stage than the R1 group. Multivariate analysis showed that R status was an independent prognostic marker (P=0.0071), and Kaplan–Meier curves showed that >5-year survivors in the R1 group had significantly poorer prognoses (P=0.002). Conclusions Patients who have survived >5 years following R1 resection for PDAC can experience tumor recurrence in the resected area.
Image: Kaplan–Meier survival curves of patients with PDAC.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008; 58: 71-96. [PMID: 18287387].
Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999; 189: 1-7. [PMID: 10401733].
Verbeke CS, Leitch D, Menon KV, McMahon MJ, Guillou PJ, Anthoney A. Redefining the R1 resection in pancreatic cancer. 2006; Br J Surg 93: 1232-1237. [PMID: 16804874]
Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, Schirmacher P, Büchler MW. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008; 15: 1651-1660. [PMID: 18351300].
Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, Dooley WC, Coleman J, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995; 221: 721-731. [PMID: 7794076]
Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000; 4: 567-579. [PMID: 11307091]
Neoptolemos JP1, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, Bassi C, 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: 758-768. [PNID: 11729382].
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: 202-209.
Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006; 10: 1199-1210. [PMID: 17114007].
Bouvet M, Gamagami RA, Gilpin EA, Romeo O, Sasson A, Easter DW, Moossa AR. Factors influencing survival after resection for periampullary neoplasms. Am J Surg. 2000; 180: 13-17. [PMID: 11036132].
Schmidt CM1, Powell ES, Yiannoutsos CT, Howard TJ, Wiebke EA, Wiesenauer CA, Baumgardner JA, et al. Pancreaticoduodenectomy: a 20-year experience in 516 patients. Arch Surg. 2004; 139: 718-725. [PMID: 15249403].
Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, Hwang R, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007; 246: 52-60.[PMID: 17592291].
Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, Zheng H, Szymonifka J, Wargo JA, Thayer SP, et al. Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery. 2012; 152: S43-49. [PMID: 22763261].
Schnelldorfer T1, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008; 247: 456-462. [PMID: 18376190].
Riall TS, Cameron JL, Lillemoe KD, Winter JM, Campbell KA, Hruban RH, Chang D, Yeo CJ. Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery. 2006; 140: 764-772. [PMID: 17084719].
Cleary SP1, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, Strasberg S, et al. Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg. 2004; 198: 722-731. [PMID: 15110805].
Classification of Pancreatic carcinoma. Japan Pancreas Society Kanehara & Co. Ltd., Tokyo. 1996.
Conlon KC, Klimstra DS, Brennan MF (1996) Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223: 273-279. [PMID: 8604907].
Han SS, Jang JY, Kim SW, Kim WH, Lee KU, Park YH. Analysis of long-term survivors after surgical resection for pancreatic cancer. Pancreas. 2006; 32: 271-275. [PMID: 16628082].
Rasheed ZA1, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, et al. Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst. 2010; 102: 340-351. [PMID: 20164446].
Javle MM, Gibbs JF, Iwata KK, Pak Y, Rutledge P, Yu J, Black JD, Tan D, Khoury T. Epithelial-mesenchymal transition (EMT) and activated extracellular signal-regulated kinase (p-Erk) in surgically resected pancreatic cancer. Ann Surg Oncolo. 2007; 14: 3527-3533. [PMID: 17879119].
Krantz SB1, Shields MA, Dangi-Garimella S, Munshi HG, Bentrem DJ. Contribution of epithelial-to-mesenchymal transition and cancer stem cells to pancreatic cancer progression. J Surg Res. 2012; 173: 105-112. [PMID: 22099597].
Yachida S1, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010; 467: 1114-1117. [PMID: 20981102].
Chatelain D1, Fléjou JF. [Pancreatectomy for adenocarcinoma: prognostic factors, recommendations for pathological reports]. Ann Pathol. 2002; 22: 422-431. [PMID: 12483163].
Ishizuka J. Clinical significance of measurement of visceral fat area (in Japanese). Nippon Rinsho Naikaikaishi 2006; 21: 420-425.
Copyright (c) 2014 Yoshihiro Hamada, Kensei Maeshiro, Yoshifuku Nakayama
This work is licensed under a Creative Commons Attribution 4.0 International License.As a member of Publisher International Linking Association, PILA, iMedPub Group’s JOP follows the Creative Commons Attribution License and Scholars Open Access publishing policies. Journal of the Pancreas is the Council Contributor Member of Council of Science Editors (CSE) and following the CSE slogan Education, Ethics, and Evidence for Editors.