Top

Published in:

Open Access 01-12-2008 | Research article

Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor

Authors: Arne Westgaard, Svetlana Tafjord, Inger N Farstad, Milada Cvancarova, Tor J Eide, Oystein Mathisen, Ole Petter F Clausen, Ivar P Gladhaug

Published in: BMC Cancer | Issue 1/2008

Abstract

Background

The retroperitoneal margin is frequently microscopically tumour positive in non-curative periampullary adenocarcinoma resections. This margin should be evaluated by serial perpendicular sectioning. The aim of the study was to determine whether retroperitoneal margin involvement independently predicts survival after pancreaticoduodenectomy within a framework of standardized assessment of the resected specimens.

Methods

114 consecutive macroscopically margin-free periampullary adenocarcinomas were examined according to a prospective standardized protocol for histopathologic evaluation. The retroperitoneal margin was assessed by serial perpendicular sectioning. The periampullary cancer origin (pancreas, ampulla, distal bile duct or duodenum) was registered prospectively and reevaluated retrospectively. Associations between histopathologic factors were evaluated by Chi-square test, Fisher's exact test, Kruskal-Wallis test, and Mann-Whitney test, as appropriate. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Associations between histopathologic factors and survival were also evaluated by unadjusted and adjusted Cox regression analysis, including stepwise variable selection, in order to identify factors that independently predict a poor prognosis after periampullary adenocarcinoma resections.

Results

Microscopic resection margin involvement (R1 resection) was present in 40 tumours, of which 32 involved the retroperitoneal margin. Involvement of the retroperitoneal margin independently predicted a poor prognosis (p = 0.010; HR 1.89; CI 1.16–3.08) after presumed curative (R0 and R1) resection. In microscopically curative (R0) resections (n = 74), pancreatic tumour origin was the only factor that independently predicted a poor prognosis (p < 0.001; HR 4.71 for pancreatic versus ampullary; CI 2.13–10.4).

Conclusion

Serial perpendicular sectioning of the retroperitoneal resection margin demonstrates that tumour involvement of this margin independently predicts survival after pancreaticoduodenectomy for adenocarcinoma. Periampullary tumour origin is the only histopathologic factor that independently predicts survival in microscopically curative (R0) resections.

Available only for authorised users

Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Lillemoe KD, Pitt HA: Periampullary adenocarcinoma: analysis of 5-year survivors. Ann Surg. 1998, 227: 821-831. 10.1097/00000658-199806000-00005.CrossRefPubMedPubMedCentral

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: 549-557. 10.1053/ejso.2001.1162.CrossRefPubMed

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. 10.1016/j.surg.2006.04.006.CrossRefPubMed

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: 586-594. 10.1002/bjs.4484.CrossRefPubMed

Kuhlmann KF, de Castro SM, Wesseling JG, ten Kate FJ, Offerhaus GJ, Busch OR, van Gulik TM, Obertop H, Gouma DJ: Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer. 2004, 40: 549-558. 10.1016/j.ejca.2003.10.026.CrossRefPubMed

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. 10.1016/S0002-9610(00)00405-0.CrossRefPubMed

Allema JH, Reinders ME, van Gulik TM, Koelemay MJ, Van Leeuwen DJ, de Wit LT, Gouma DJ, Obertop H: Prognostic factors for survival after pancreaticoduodenectomy for patients with carcinoma of the pancreatic head region. Cancer. 1995, 75: 2069-2076. 10.1002/1097-0142(19950415)75:8<2069::AID-CNCR2820750807>3.0.CO;2-7.CrossRefPubMed

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. 10.1159/000079346.CrossRefPubMed

Verbeke CS, Leitch D, Menon KV, McMahon MJ, Guillou PJ, Anthoney A: Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006, 93: 1232-1237. 10.1002/bjs.5397.CrossRefPubMed

10.

Katz MH, Bouvet M, Al Refaie W, Gilpin EA, Moossa AR: Non-pancreatic periampullary adenocarcinomas: an explanation for favorable prognosis. Hepatogastroenterology. 2004, 51: 842-846.PubMed

11.

Luttges J, Vogel I, Menke M, Henne-Bruns D, Kremer B, Kloppel G: The retroperitoneal resection margin and vessel involvement are important factors determining survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas. Virchows Arch. 1998, 433: 237-242. 10.1007/s004280050242.CrossRefPubMed

12.

Pingpank JF, Hoffman JP, Ross EA, Cooper HS, Meropol NJ, Freedman G, Pinover WH, LeVoyer TE, Sasson AR, Eisenberg BL: Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg. 2001, 5: 121-130. 10.1016/S1091-255X(01)80023-8.CrossRefPubMed

13.

Luttges J, Zamboni G, Kloppel 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: 291-296. 10.1159/000018738.CrossRefPubMed

14.

Albores-Saavedra J, Heffess C, Hruban RH, Klimstra D, Longnecker D: Recommendations for the reporting of pancreatic specimens containing malignant tumors. The Association of Directors of Anatomic and Surgical Pathology. Am J Clin Pathol. 1999, 111: 304-307.CrossRefPubMed

15.

Standards and Minimum Datasets for Reporting Cancers. Minimum Dataset for the Histopathological Reporting of Pancreatic, Ampulla of Vater and Bile Duct Carcinoma. 2002, London, The Royal College of Pathologists, [http://www.rcpath.org/resources/pdf/pancreas_dataset2802.pdf]

16.

AJCC cancer staging manual. Edited by: Greene FL. 2002, New York, Springer

17.

Demetter P, Cuvelier CA: Guidelines for adequate histopathological reporting of pancreatic ductal adenocarcinoma resection specimens. Acta Gastroenterol Belg. 2004, 67: 46-49.PubMed

18.

Surgical pathology dissection. Edited by: Hruban RH, Westra WH, Phelps TH and Isacson C. 1996, New York, Springer-Verlag Telos

19.

Staley CA, Cleary KR, Abbruzzese JL, Lee JE, Ames FC, Fenoglio CJ, Evans DB: The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas. 1996, 12: 373-380. 10.1097/00006676-199605000-00009.CrossRefPubMed

20.

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: 144-148. 10.1097/00000658-199302000-00008.CrossRefPubMedPubMedCentral

21.

Nagakawa T, Konishi I, Ueno K, Ohta T, Akiyama T, Kanno M, Kayahara M, Miyazaki I: The results and problems of extensive radical surgery for carcinoma of the head of the pancreas. Jpn J Surg. 1991, 21: 262-267. 10.1007/BF02470944.CrossRefPubMed

22.

Schmidt CM, Powell ES, Yiannoutsos CT, Howard TJ, Wiebke EA, Wiesenauer CA, Baumgardner JA, Cummings OW, Jacobson LE, Broadie TA, Canal DF, Goulet RJ, Curie EA, Cardenes H, Watkins JM, Loehrer PJ, Lillemoe KD, Madura JA: Pancreaticoduodenectomy: A 20-Year Experience in 516 Patients. Arch Surg. 2004, 139: 718-727. 10.1001/archsurg.139.7.718.CrossRefPubMed

23.

Khan AW, Dhillon AP, Hutchins R, Abraham A, Shah SR, Snooks S, Davidson BR: Prognostic significance of intratumoural microvessel density (IMD) in resected pancreatic and ampullary cancers to standard histopathological variables and survival. Eur J Surg Oncol. 2002, 28: 637-644. 10.1053/ejso.2002.1307.CrossRefPubMed

24.

Moon HJ, An JY, Heo JS, Choi SH, Joh JW, Kim YI: Predicting Survival After Surgical Resection for Pancreatic Ductal Adenocarcinoma. Pancreas. 2006, 32: 37-43. 10.1097/01.mpa.0000194609.24606.4b.CrossRefPubMed

25.

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H: Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007, 297: 267-277. 10.1001/jama.297.3.267.CrossRefPubMed

26.

Frierson HF: The gross anatomy and histology of the gallbladder, extrahepatic bile ducts, Vaterian system, and minor papilla. Am J Surg Pathol. 1989, 13: 146-162.CrossRefPubMed

27.

Howe JR, Klimstra DS, Moccia RD, Conlon KC, Brennan MF: Factors predictive of survival in ampullary carcinoma. Ann Surg. 1998, 228: 87-94. 10.1097/00000658-199807000-00013.CrossRefPubMedPubMedCentral

28.

Ampulla of Vater. AJCC cancer staging manual. Edited by: Greene FL. 2002, New York, Springer, 151-156.

29.

Albores-Saavedra J, Henson DE, Klimstra DS: Tumors of the gallbladder, extrahepatic bile ducts, and ampulla of Vater. Edited by: Rosai J. 2000, Washington, D.C., Armed Forces Institute of Pathology, 259-316. [http://www.afip.org] Malignant epithelial tumors of the ampulla, Atlas of tumor pathology,

30.

Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G, Haglund C: Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut. 2005, 54: 385-387. 10.1136/gut.2004.047191.CrossRefPubMedPubMedCentral

31.

Cox DR: Regression Models and Life-Tables. Journal of the Royal Statistical Society Series B-Statistical Methodology. 1972, 34: 187-220.

32.

Luttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Kloppel 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: 154-161. 10.1002/(SICI)1096-9896(200006)191:2<154::AID-PATH603>3.0.CO;2-C.CrossRefPubMed

33.

Albores-Saavedra J, Menck HR, Scoazec JC, Soehendra N, Wittekind C, Sriram PVJ, Sripa B: Pathology and genetics of tumours of the digestive system. 2000, Lyon, IARC Press, 206-213. Carcinoma of the gallbladder and extrahepatic bile ducts, Hamilton SR and Aaltonen LA, World Health Organization Classification of Tumours, Hamilton SR,

34.

Riediger H, Makowiec F, Fischer E, Adam U, Hopt UT: Postoperative Morbidity and Long-term Survival After Pancreaticoduodenectomy With Superior Mesenterico-Portal Vein Resection. J Gastrointest Surg. 2006, 10: 1106-1115. 10.1016/j.gassur.2006.04.002.CrossRefPubMed

35.

Nagakawa T, Sanada H, Inagaki M, Sugama J, Ueno K, Konishi I, Ohta T, Kayahara M, Kitagawa H: Long-term survivors after resection of carcinoma of the head of the pancreas: significance of histologically curative resection. J Hepatobiliary Pancreat Surg. 2004, 11: 402-408. 10.1007/s00534-004-0917-4.CrossRefPubMed

36.

Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, Bassi C, Dervenis C, Fernandez-Cruz L, Lacaine F, Buckels J, Deakin M, Adab FA, Sutton R, Imrie C, Ihse I, Tihanyi T, Olah A, Pedrazzoli S, Spooner D, Kerr DJ, Friess H, Buchler MW: 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. 10.1097/00000658-200112000-00007.CrossRefPubMedPubMedCentral

37.

Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA, Evans DB: Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004, 8: 935-949. 10.1016/j.gassur.2004.09.046.CrossRefPubMed

38.

Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, Sauter PK, Hruban RH, Riall TS, Schulick RD, Choti MA, Lillemoe KD, Yeo CJ: 1423 Pancreaticoduodenectomies for Pancreatic Cancer: A Single-Institution Experience. J Gastrointest Surg. 2006, 10: 1199-1211. 10.1016/j.gassur.2006.08.018.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/8/5/prepub

Title: Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor
Authors: Arne Westgaard
Svetlana Tafjord
Inger N Farstad
Milada Cvancarova
Tor J Eide
Oystein Mathisen
Ole Petter F Clausen
Ivar P Gladhaug
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-8-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2008

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

Biomonitoring of complex occupational exposures to carcinogens: The case of sewage workers in Paris

Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

MDM2 gene SNP309 T/G and p53gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

Validation of putative reference genes for gene expression studies in human hepatocellular carcinoma using real-time quantitative RT-PCR

Prognostic parameters for recurrence of papillary thyroid microcarcinoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer