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Extended versus standard lymphadenectomy in patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective randomized single center trial

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Summary

Background

Although randomized studies investigated the benefit of extended lymphadenectomy (ELA) compared to standard lymphadenectomy (SLA) for periampullary adenocarcinoma, these analyses failed to show overall advantage for ELA due to high heterogeneity of lymphadenectomy protocols. Therefore, the present single-center trial was designed using a standardized protocol for SLA with en bloc technique.

Methods

Patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma were randomized to either SLA or ELA. Primary study endpoint was recurrence-free survival. Secondary endpoints were overall survival as well as peri- and postoperative morbidity and mortality.

Results

Sixty-six out of 103 randomized patients were treated by SLA (n = 34) or ELA (n = 32) and included into final data analysis. ELA compared to SLA resulted in a higher number of removed lymph nodes (25 ± 12 vs. 14 ± 8; p < 0.001) with a comparable number of lymph node metastases (3 ± 5 vs. 2 ± 3). Median recurrence-free survival was comparable between SLA (18.7 months) and ELA (11.3 months) p = 0.445. Median overall survival was 22.1 months in the SLA group and 15.5 months in the ELA group. Overall survival rates after 9 and 18 months for SLA were 76.5 and 55.6 % and for ELA 68.8 and 46.9 %, respectively.

Conclusion

ELA for periampullary carcinomas resulted in a higher number of resected lymph nodes. This radical approach showed no benefit in terms of median recurrence-free and overall survival and therefore cannot be recommended in general.

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References

  1. Ouaissi M, Giger U, Louis G, Sielezneff I, Farges O, Sastre B. Ductal adenocarcinoma of the pancreatic head: a focus on current diagnostic and surgical concepts. World J Gastroenterol. 2012;18(24):3058–69.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Birk D, Fortnagel G, Formentini A, Beger HG. Small carcinoma of the pancreas. Factors of prognostic relevance. J Hepatobiliary Pancreat Surg. 1998;5(4):450–4.

    Article  CAS  PubMed  Google Scholar 

  3. Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223(3):273–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Delcore R, Rodriguez FJ, Forster J, Hermreck AS, Thomas JH. Significance of lymph node metastases in patients with pancreatic cancer undergoing curative resection. Am J Surg. 1996;172(5):463–8. (discussion 468–9).

    Article  CAS  PubMed  Google Scholar 

  5. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72. (discussion 72–3).

    Article  CAS  PubMed  Google Scholar 

  6. 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; European Study Group for Pancreatic Cancer. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, Dooley WC, Coleman J, Pitt HA. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995;221(6):721–31. (discussion 731–3).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hartel M, Wente MN, Di Sebastiano P, Friess H, Buchler MW. The role of extended resection in pancreatic adenocarcinoma: is there good evidence-based justification? Pancreatology. 2004;4(6):561–6.

    Article  PubMed  Google Scholar 

  9. Michalski CW, Kleeff J, Wente MN, Diener MK, Buchler MW, Friess H. Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg. 2007;94(3):265–73.

    Article  CAS  PubMed  Google Scholar 

  10. 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(2):215–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. 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(5):1132–7.

    Article  CAS  PubMed  Google Scholar 

  12. Nagakawa T, Nagamori M, Futakami F, Tsukioka Y, Kayahara M, Ohta T, Ueno K, Miyazaki I. Results of extensive surgery for pancreatic carcinoma. Cancer. 1996;77(4):640–5.

    Article  CAS  PubMed  Google Scholar 

  13. Satake K, Nishiwaki H, Yokomatsu H, Kawazoe Y, Kim K, Haku A, Umeyama K, Miyazaki I. Surgical curability and prognosis for standard versus extended resection for T1 carcinoma of the pancreas. Surg Gynecol Obstet. 1992;175(3):259–65.

    CAS  PubMed  Google Scholar 

  14. Sindelar WF. Clinical experience with regional pancreatectomy for adenocarcinoma of the pancreas. Arch Surg. 1989;124(1):127–32.

    Article  CAS  PubMed  Google Scholar 

  15. Henne-Bruns D, Vogel I, Luttges J, Kloppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology. 1998;45(21):855–66.

    CAS  PubMed  Google Scholar 

  16. Farnell MB, Pearson RK, Sarr MG, DiMagno EP, Burgart LJ, Dahl TR, Foster N, Sargent DJ; Pancreas Cancer Working Group. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery. 2005;138(4):618–28. (discussion 628–30).

    Article  PubMed  Google Scholar 

  17. 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(3):230–41.

    Article  PubMed  Google Scholar 

  18. Pedrazzoli S, DiCarlo V, Dionigi R, Mosca F, Pederzoli P, Pasquali C, Kloppel 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(4):508–17.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK, Coleman J, 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(3):355–66. (discussion 366–8).

    Article  PubMed Central  PubMed  Google Scholar 

  20. Yeo CJ, Cameron JL, Sohn TA, Coleman J, 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(5):613–22.(discussion 622–4).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Kollmar O, Sperling J, Moussavian MR, Kubulus D, Richter S, Schilling MK. Delayed gastric emptying after pancreaticoduodenectomy: influence of the orthotopic technique of reconstruction and intestinal motilin receptor expression. J Gastrointest Surg. 2011;15(7):1158–67.

    Article  PubMed  Google Scholar 

  22. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma—2nd English edition. Gastric Cancer. 1998;1(1):10–24.

    Article  PubMed  Google Scholar 

  23. Tol JA, Gouma DJ, Bassi C, Dervenis C, Montorsi M, Adham M, Andren-Sandberg A, Asbun HJ, Bockhorn M, Buchler MW, Conlon KC, Fernandez-Cruz L, Fingerhut A, Friess H, Hartwig W, Izbicki JR, Lillemoe KD, Milicevic MN, Neoptolemos JP, Shrikhande SV, Vollmer CM, Yeo CJ, Charnley RM; International. Study Group on Pancreatic Surgery. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2014;156(3):591–600.

    Article  PubMed  Google Scholar 

  24. Iacono C, Accordini S, Bortolasi L, Facci E, Zamboni G, Montresor E, Marinello PD, Serio G. Results of pancreaticoduodenectomy for pancreatic cancer: extended versus standard procedure. World J Surg. 2002;26(11):1309–14.

    Article  PubMed  Google Scholar 

  25. Badger SA, Brant JL, Jones C, McClements J, Loughrey MB, Taylor MA, Diamond T, McKie LD. The role of surgery for pancreatic cancer: a 12-year review of patient outcome. Ulster Med J. 2010;79(2):70–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Bhatti I, Peacock O, Awan AK, Semeraro D, Larvin M, Hall RI. Lymph node ratio versus number of affected lymph nodes as predictors of survival for resected pancreatic adenocarcinoma. World J Surg. 2010;34(4):768–75.

    Article  PubMed  Google Scholar 

  27. Konstantinidis IT, Deshpande V, Zheng H, Wargo JA, Fernandez-del Castillo C, Thayer SP, Androutsopoulos V, Lauwers GY, Warshaw AL, Ferrone CR. Does the mechanism of lymph node invasion affect survival in patients with pancreatic ductal adenocarcinoma? J Gastrointest Surg. 2010;14(2):261–7.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, Makowiec F. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg. 2009;13(7):1337–44.

    Article  PubMed  Google Scholar 

  29. Sahin TT, Fujii T, Kanda M, Nagai S, Kodera Y, Kanzaki A, Yamamura K, Sugimoto H, Kasuya H, Nomoto S, Takeda S, Morita S, Nakao A. Prognostic implications of lymph node metastases in carcinoma of the body and tail of the pancreas. Pancreas. 40(7):1029–33.

  30. Capussotti L, Massucco P, Ribero D, Vigano L, Muratore A, Calgaro M. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg. 2003;138(12):1316–22.

    Article  PubMed  Google Scholar 

  31. Albagli RO, Carvalho GS, Mali Junior J, Eulalio JM, de Melo EL. Comparative study of the radical and standard lymphadenectomy in the surgical treatment of adenocarcinoma of the ampula of Vater. Rev Col Bras Cir. 2010;37(6):420–5.

    PubMed  Google Scholar 

  32. 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 

  33. 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(4):656–64.

    Article  PubMed  Google Scholar 

  34. Pedrazzoli S, Beger HG, Obertop H, Andren-Sandberg A, Fernandez-Cruz L, Henne-Bruns D, Luttges J, Neoptolemos JP. A surgical and pathological based classification of resective treatment of pancreatic cancer. Summary of an international workshop on surgical procedures in pancreatic cancer. Dig Surg. 1999;16(4):337–45.

    Article  CAS  PubMed  Google Scholar 

  35. Svoronos C, Tsoulfas G, Katsourakis A, Noussios G, Chatzitheoklitos E, Marakis NG. Role of extended lymphadenectomy in the treatment of pancreatic head adenocarcinoma: review and meta-analysis. ANZ J Surg. 2014;84(10):706–11.

    Article  PubMed  Google Scholar 

  36. Justinger C, Schuld J, Sperling J, Kollmar O, Richter S, Schilling MK. Triclosan-coated sutures reduce wound infections after hepatobiliary surgery—a prospective non-randomized clinical pathway driven study. Langenbecks Arch Surg. 2011;396(6):845–50.

    Article  PubMed  Google Scholar 

  37. 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.

    Article  PubMed  Google Scholar 

  38. Massucco P, Ribero D, Sgotto E, Mellano A, Muratore A, Capussotti L. Prognostic significance of lymph node metastases in pancreatic head cancer treated with extended lymphadenectomy: not just a matter of numbers. Ann Surg Oncol. 2009;16(12):3323–32.

    Article  PubMed  Google Scholar 

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Acknowledgments

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Funding

All authors have substantially contributed to the work and have approved the final version of the manuscript.

Conflict of interest

None of the authors has any conflict of interest related to the data presented in the current work.

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Author notes

  1. J. Sperling MD

    Present address: Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany

  2. J. E. Slotta MD

    Present address: Department of General and Visceral Surgery, Kreiskrankenhaus St. Ingbert, St. Ingbert, Germany

  3. O. Kollmar MD

    Present address: Department of General and Visceral Surgery, Dr. Horst Schmidt Kliniken, Wiesbaden, Germany

Authors and Affiliations

  1. Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, 66421, Homburg/Saar, Germany

    J. Sperling MD,  J. Schuld MD, A. M. Hechler, J. E. Slotta MD & O. Kollmar MD

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  1. J. Sperling MD
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Correspondence to J. Schuld MD.

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Jens Sperling MD and Dr. Jochen Schuld MD contributed equally to the article.

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Sperling, J., Schuld, J., Hechler, A.M. et al. Extended versus standard lymphadenectomy in patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective randomized single center trial. Eur Surg 48, 26–33 (2016). https://doi.org/10.1007/s10353-015-0371-3

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  • DOI: https://doi.org/10.1007/s10353-015-0371-3

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