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Novel postoperative adjuvant strategy prevents early hepatic recurrence after resection of pancreatic cancer

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background/Purpose

It has been reported recently that adjuvant gemcitabine prolonged postoperative disease-free survival in patients with resectable pancreatic cancer. However, the efficacy was limited and further studies are required to improve the prognosis. In particular, postoperative hepatic recurrence often occurs even after gemcitabine treatment.

Methods

We are currently trying to evaluate the efficacy of postoperative combination therapy of high-dose 5-fluorouracil (5-FU) arterial infusion with systemic gemcitabine. Patients received weekly high-dose 5-FU through the hepatic artery using a port-catheter system (1000 mg/m2 for 5 h) plus concurrent systemic gemcitabine (1000 mg/m2).

Results

Thirty-one patients were enrolled and 29 patients (94%) completed the scheduled adjuvant chemotherapy. The toxicity was acceptable and this regimen was well feasible as an outpatient treatment. At the time of analysis, 21 patients (68%) had recurrence. Local recurrence was most frequently observed, in 43% of the patients with recurrence. On the other hand, hepatic recurrence developed in only 2 patients (10%). The 1-year disease-free rate and overall survival rate were 62.9 and 100%, respectively.

Conclusion

Our novel adjuvant strategy had a significant beneficial effect on early hepatic recurrence and may have the potential to prolong the overall survival of pancreatic cancer patients.

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References

  1. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363:1049–57.

    Article  PubMed  CAS  Google Scholar 

  2. Traverso LW. Pancreatic cancer: surgery alone is not sufficient. Surg Endosc. 2006;20(Suppl 2):S446–9.

    Article  PubMed  Google Scholar 

  3. Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456–62.

    Article  PubMed  Google Scholar 

  4. Ferrone CR, Brennan MF, Gonen M, Coit DG, Fong Y, Chung S, et al. Pancreatic adenocarcinoma: the actual 5-year survivors. J Gastrointest Surg. 2008;12:701–6.

    Article  PubMed  Google Scholar 

  5. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.

    PubMed  CAS  Google Scholar 

  6. Hochster HS, Haller DG, de Gramont A, Berlin JD, Philip PA, Moore MJ, et al. Consensus report of the International Society of Gastrointestinal Oncology on therapeutic progress in advanced pancreatic cancer. Cancer. 2006;107:676–85.

    Article  PubMed  CAS  Google Scholar 

  7. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.

    Article  PubMed  CAS  Google Scholar 

  8. Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101:908–15.

    Article  PubMed  CAS  Google Scholar 

  9. Barugola G, Falconi M, Bettini R, Boninsegna L, Casarotto A, Salvia R, et al. The determinant factors of recurrence following resection for ductal pancreatic cancer. JOP. 2007;8:132–40.

    PubMed  Google Scholar 

  10. Hirano S, Kondo S, Hara T, Ambo Y, Tanaka E, Shichinohe T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg. 2007;246:46–51.

    Article  PubMed  Google Scholar 

  11. Kosuge T, Kiuchi T, Mukai K, Kakizoe T. A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol. 2006;36:159–65.

    Article  PubMed  Google Scholar 

  12. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.

    Article  PubMed  CAS  Google Scholar 

  13. Shibata K, Matsumoto T, Yada K, Sasaki A, Ohta M, Kitano S. Factors predicting recurrence after resection of pancreatic ductal carcinoma. Pancreas. 2005;31:69–73.

    Article  PubMed  Google Scholar 

  14. Tani M, Kawai M, Miyazawa M, Hirono S, Ina S, Nishioka R, et al. Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma. Langenbecks Arch Surg. 2009;394:249–53.

    Article  PubMed  Google Scholar 

  15. Shimada K, Sakamoto Y, Sano T, Kosuge T. The role of paraaortic lymph node involvement on early recurrence and survival after macroscopic curative resection with extended lymphadenectomy for pancreatic carcinoma. J Am Coll Surg. 2006;203:345–52.

    Article  PubMed  Google Scholar 

  16. Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S. Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 2006;10:511–8.

    Article  PubMed  Google Scholar 

  17. Tanaka T, Sakaguchi H, Anai H, Yamamoto K, Morimoto K, Tamamoto T, et al. Arterial infusion of 5-fluorouracil combined with concurrent radiotherapy for unresectable pancreatic cancer: results from a pilot study. AJR Am J Roentgenol. 2007;189:421–8.

    Article  PubMed  Google Scholar 

  18. Tanaka T, Sakaguchi H, Sho M, Yamamoto K, Nishiofuku H, Nakajima Y, et al. A novel interventional radiology technique for arterial infusion chemotherapy against advanced pancreatic cancer. AJR Am J Roentgenol. 2009;192:W168–77.

    Article  PubMed  Google Scholar 

  19. Beger HG, Gansauge F, Buchler MW, Link KH. Intraarterial adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic cancer: significant reduction in occurrence of liver metastasis. World J Surg. 1999;23:946–9.

    Article  PubMed  CAS  Google Scholar 

  20. Lygidakis NJ, Sgourakis G, Georgia D, Vlachos L, Raptis S. Regional targeting chemoimmunotherapy in patients undergoing pancreatic resection in an advanced stage of their disease: a prospective randomized study. Ann Surg. 2002;236:806–13.

    Article  PubMed  Google Scholar 

  21. Kurosaki I, Kawachi Y, Nihei K, Tsuchiya Y, Aono T, Yokoyama N, et al. Liver perfusion chemotherapy with 5-fluorouracil followed by systemic gemcitabine administration for resected pancreatic cancer: preliminary results of a prospective phase 2 study. Pancreas. 2009;38:161–7.

    Article  PubMed  CAS  Google Scholar 

  22. Takeda S, Inoue S, Kaneko T, Harada A, Nakao A. The role of adjuvant therapy for pancreatic cancer. Hepatogastroenterology. 2001;48:953–6.

    PubMed  CAS  Google Scholar 

  23. Yamaue H, Tani M, Onishi H, Kinoshita H, Nakamori M, Yokoyama S, et al. Locoregional chemotherapy for patients with pancreatic cancer intra-arterial adjuvant chemotherapy after pancreatectomy with portal vein resection. Pancreas. 2002;25:366–72.

    Article  PubMed  Google Scholar 

  24. Ishikawa O, Ohigashi H, Sasaki Y, Furukawa H, Kabuto T, Kameyama M, et al. Liver perfusion chemotherapy via both the hepatic artery and portal vein to prevent hepatic metastasis after extended pancreatectomy for adenocarcinoma of the pancreas. Am J Surg. 1994;168:361–4.

    Article  PubMed  CAS  Google Scholar 

  25. Ishikawa O, Ohigashi H, Imaoka S, Sasaki Y, Kameyama M, Nakamori S, et al. Regional chemotherapy to prevent hepatic metastasis after resection of pancreatic cancer. Hepatogastroenterology. 1997;44:1541–6.

    PubMed  CAS  Google Scholar 

  26. Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, et al. Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg. 2009;250:88–95.

    Article  PubMed  Google Scholar 

  27. Rauchwerger DR, Firby PS, Hedley DW, Moore MJ. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res. 2000;60:6075–9.

    PubMed  CAS  Google Scholar 

  28. Correale P, Cerretani D, Marsili S, Pozzessere D, Petrioli R, Messinese S, et al. Gemcitabine increases systemic 5-fluorouracil exposure in advanced cancer patients. Eur J Cancer. 2003;39:1547–51.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the following individuals for their contributions to the discussion. Moderator: Tatsuya Aoki, Third Department of Surgery, Tokyo Medical University; Commentators: Koji Yamaguchi, Department of Surgery, University of Occupational and Environmental Health; Koichi Aiura, Department of Surgery, Keio University School of Medicine; and Sohei Satoi, Department of Surgery, Kansai Medical University. We thank Ms. Kumiko Yamamoto for her kind help with manuscript preparation. This work was supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer.

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Authors and Affiliations

  1. Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Masayuki Sho, Takatsugu Yamada, Takeo Nomi, Takahiro Akahori, Jin Doh, Ichiro Yamato, Daisuke Hokuto, Hiromichi Kanehiro & Yoshiyuki Nakajima

  2. Department of Radiology, Nara Medical University, Kashihara, Nara, 634-8522, Japan

    Toshihiro Tanaka, Hideyuki Nishiofuku, Nagaaki Marugami & Kimihiko Kichikawa

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  1. Masayuki Sho
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  2. Toshihiro Tanaka
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Correspondence to Masayuki Sho.

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Sho, M., Tanaka, T., Yamada, T. et al. Novel postoperative adjuvant strategy prevents early hepatic recurrence after resection of pancreatic cancer. J Hepatobiliary Pancreat Sci 18, 235–240 (2011). https://doi.org/10.1007/s00534-010-0336-7

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  • DOI: https://doi.org/10.1007/s00534-010-0336-7

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