Skip to main content

Advertisement

Log in

Extended Versus Standard Lymphadenectomy for Pancreatic Head Cancer: Meta-Analysis of Randomized Controlled Trials

  • Review Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy (EPD) compared to standard pancreatoduodenectomy (SPD) in patients with carcinoma of the head of the pancreas has not been considered from only randomized controlled trials (RCTs).

Methods

The aim of this study was to conduct a systematic review and meta-analysis of the outcomes comparing SPD and EPD in RCTs. Searches were performed on MEDLINE, Embase and Cochrane databases using MeSH keyword combinations: ‘pancreatic cancer’, ‘pancreaticoduodenectomy’, ‘extended’, ‘randomized’ and ‘lymphadenectomy’. RCTs published up to 2014 were included. Overall post-operative survival, morbidity, 30-day mortality and length of hospital stay were the outcomes assessed.

Results

Five eligible RCTs with 546 participants were included (EPD = 276 and SPD = 270). EPD was associated with a significantly higher number of excised lymph nodes (LNs) compared to SPD (mean difference = 15.73, 95 % confidence interval (CI) = 9.41–22.04; P < 0.00001; I 2 = 88 %). LN metastasis was detected in 58–68 and 55–70 % of patients who had EPD and SPD, respectively. EPD did not improve overall survival (hazard ratio (HR) = 0.88, 95 % CI = 0.75–1.03; P = 0.11) but did worsen post-operative morbidity compared to SPD (risk ratio (RR) = 1.23; 95 % CI = 1.01–1.50; P = 0.004; I 2 = 9 %). There were no differences in the 30-day mortality (RR = 0.81; 95 % CI = 0.32–2.06; P = 0.66; I 2 = 0 %) or length of hospital stay (mean difference = 1.39, 95 % CI = −2.31 to 5.09; P = 0.46; I 2 = 67 %).

Conclusion

SPD is associated with reduced morbidity, but equivalent long-term benefits compared to patients undergoing EPD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW ; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.

    Article  CAS  PubMed  Google Scholar 

  2. Bogoevski D, Yekebas EF, Schurr P, Kaifi JT, Kutup A, Erbersdobler A, Pantel K, Izbicki JR. Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal adenocarcinoma: prognostic significance of nodal microinvolvement. Ann Surg. 2004;240:993–1000.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Mosca F, Giulianotti PC, Balestracci T, Di Candio G, Pietrabissa A, Sbrana F, Rossi G. Long-term survival in pancreatic cancer: pylorus-preserving versus Whipple pancreatoduodenectomy. Surgery. 1997;122:553–66.

    Article  CAS  PubMed  Google Scholar 

  4. Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211:447–58.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165:68–72.

    Article  CAS  PubMed  Google Scholar 

  6. Nitecki SS, Sarr MG, Colby T V, van Heerden JA. Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg. 1995;221:59–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. 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;10:1199–210.

    Article  PubMed  Google Scholar 

  8. Kazanjian KK, Hines OJ, Duffy JP, Yoon DY, Cortina G, Reber HA. Improved survival following pancreaticoduodenectomy to treat adenocarcinoma of the pancreas: the influence of operative blood loss. Arch Surg. 2008;143:1166–71.

    Article  PubMed  Google Scholar 

  9. 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;91:586–94.

    Article  CAS  PubMed  Google Scholar 

  10. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakashima A, Yuasa Y, Kondo N, Ohge H, Sueda T. Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg. 2010;211:196–204.

    Article  PubMed  Google Scholar 

  11. Zacharias T, Jaeck D, Oussoultzoglou E, Neuville A, Bachellier P. Impact of lymph node involvement on long-term survival after R0 pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas. J Gastrointest Surg. 2007;11:350–6.

    Article  PubMed  Google Scholar 

  12. Wind J, Lagarde SM, Ten Kate FJ, Ubbink DT, Bemelman WA, van Lanschot JJ. A systematic review on the significance of extracapsular lymph node involvement in gastrointestinal malignancies. Eur J Surg Oncol. 2007;33:401–8.

    Article  CAS  PubMed  Google Scholar 

  13. Michalski CW, Kleeff J, Wente MN, Diener MK, Büchler MW, Friess H. Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg. 2007;94:265–73.

    Article  CAS  PubMed  Google Scholar 

  14. Durczyński A, Hogendorf P, Szymański D, Grzelak P, Strzelczyk J. Sentinel lymph node mapping in tumors of the pancreatic body: preliminary report. Contemp Oncol (Pozn). 2012;16:206–9.

    PubMed Central  PubMed  Google Scholar 

  15. Ishikawa O, Ohhigashi H, Sasaki Y, Kabuto T, Fukuda I, Furukawa H, Imaoka S, Iwanaga T. Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head. Ann Surg. 1988;208:215–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Hirai I, Kimura W, Ozawa K, Kudo S, Suto K, Kuzu H, Fuse A. Perineural invasion in pancreatic cancer. Pancreas. 2002;24:15–25.

    Article  PubMed  Google Scholar 

  17. Manabe T, Ohshio G, Baba N, Miyashita T, Asano N, Tamura K, Yamaki K, Nonaka A, Tobe T. Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Cancer. 1989;64:1132–7.

    Article  CAS  PubMed  Google Scholar 

  18. Henne-Bruns D, Vogel I, Lüttges J, Klöppel G, Kremer B.. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology. 45:855–66.

  19. Pedrazzoli S, DiCarlo V, Dionigi R, Mosca F, Pederzoli P, Pasquali C, Klöppel G, Dhaene K, Michelassi F. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg. 1998;228:508–17.

    CAS  Google Scholar 

  20. Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK, Coleman JA, Abrams RA, Hruban RH. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg. 2002;236:355–66.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Nimura Y, Nagino M, Takao S, Takada T, Miyazaki K, Kawarada Y, Miyagawa S, Yamaguchi A, Ishiyama S, Takeda Y, Sakoda K, Kinoshita T, Yasui K, Shimada H, Katoh H. Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas: long-term results of a Japanese multicenter randomized controlled trial. J Hepatobiliary Pancreat Sci. 2012;19:230–41.

    Article  PubMed  Google Scholar 

  22. Farnell MB, Pearson RK, Sarr MG, DiMagno EP, Burgart LJ, Dahl TR, Foster N, Sargent DJ. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery. 2005;138:618–28.

    Article  PubMed  Google Scholar 

  23. Jang JY, Kang MJ, Heo JS, Choi SH, Choi DW, Park SJ, Han SS, Yoon DS, Yu HC, Kang KJ, Kim SG, Kim SW. A prospective randomized controlled study comparing outcomes of standard resection and extended resection, including dissection of the nerve plexus and various lymph nodes, in patients with pancreatic head cancer. Ann Surg. 2014;259:656–64.

    Article  PubMed  Google Scholar 

  24. Pedrazzoli S, Pasquali C, Sperti C. Extent of lymphadenectomy in the resection of pancreatic cancer. Analysis of the existing evidence. Rocz Akad Med w Białymstoku. 2005;50:85–90.

    CAS  Google Scholar 

  25. Iqbal N, Lovegrove RE, Tilney HS, Abraham AT, Bhattacharya S, Tekkis PP, Kocher HM. A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: a meta-analysis of 1909 patients. Eur J Surg Oncol. 2009;35:79–86.

    Article  CAS  PubMed  Google Scholar 

  26. Xu X, Zhang H, Zhou P, Chen L. Meta-analysis of the efficacy of pancreatoduodenectomy with extended lymphadenectomy in the treatment of pancreatic cancer. World J Surg Oncol. 2013;11:311.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Higgins JPT GS. Cochrane Handbook for Systematic Reviews of Interventions 501. Chichester, UK: John Wiley & Sons, Ltd

  29. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.

    Article  CAS  PubMed  Google Scholar 

  30. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.a

    Article  Google Scholar 

  31. Glimelius B, Dahl O, Cedermark B, Jakobsen A, Bentzen SM, Starkhammar H, Grönberg H, Hultborn R, Albertsson M, Påhlman L, Tveit KM; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Acta Oncol. 2005;44:904–12.

  32. Morris EJA, Maughan NJ, Forman D, Quirke P. Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology. Gut. 2007;56:1419–25.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Adjuvant Chemotherapy for Breast Cancer—30 Years Later—NEJM [Internet]. [cited 2014 Dec 1]. Available from: http://www.nejm.org/doi/full/10.1056/NEJMe068204

  34. Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.

    Article  PubMed  Google Scholar 

  35. Sultana A, Neoptolemos J, Ghaneh P. Adjuvant treatment. HPB (Oxford). 2006;8:352–64.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Neoptolemos J, Buchler M, Stocken DD, Ghaneh P, Smith D, Bassi C, Moore M, Cunningham D, Dervenis C, Goldstein D. ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. ASCO Meet Abstr. Journal of Clinical Oncology 2009;27(18S):LBA4505.

    Google Scholar 

  37. de Wilde, RF, Besselink MGH, van der Tweel I, de Hingh IHJT, van Eijck CHJ, Dejong CHC, Porte RJ, Gouma DJ, Busch ORC, Molenaar IQ and for the Dutch Pancreatic Cancer Group. Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality. Br J Surg. 2012;99:404–10.

  38. Yeo CJ, Cameron JL, Sohn TA, Coleman JA, Sauter PK, Hruban RH, Pitt HA, Lillemoe KD. Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome. Ann Surg. 1999;229:613–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Farnell MB, Aranha G V, Nimura Y, Michelassi F. The role of extended lymphadenectomy for adenocarcinoma of the head of the pancreas: strength of the evidence. J Gastrointest Surg. 2008;12:651–6.

    Article  PubMed  Google Scholar 

Download references

Funding sources

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bobby V M Dasari.

Additional information

Synopsis

Standard lymphadenectomy is associated with reduced morbidity, but equivalent long-term benefits compared to patients undergoing extended lymphadenectomy in patients undergoing pancreaticoduodenectomy for head of the pancreas cancer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dasari, B.V., Pasquali, S., Vohra, R.S. et al. Extended Versus Standard Lymphadenectomy for Pancreatic Head Cancer: Meta-Analysis of Randomized Controlled Trials. J Gastrointest Surg 19, 1725–1732 (2015). https://doi.org/10.1007/s11605-015-2859-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-015-2859-3

Keywords

Navigation