Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer

  • Daisuke Hashimoto
  • Kota Arima
  • Shigeki Nakagawa
  • Yuji Negoro
  • Toshihiko Hirata
  • Masahiko Hirota
  • Masafumi Inomata
  • Kengo Fukuzawa
  • Takefumi Ohga
  • Hiroshi Saeki
  • Eiji Oki
  • Yo-ichi Yamashita
  • Akira Chikamoto
  • Hideo BabaEmail author
  • Yoshihiko Maehara
Original Article—Liver, Pancreas, and Biliary Tract



After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC.


A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases.


The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17–0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC.


This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.


Pancreatic cancer RAS Local recurrence Operation Complication 



The authors thank the following institutions and investigators who participated in this study: Miyake K (Kumamoto University), Yonemura A (Kumamoto University), Yoshida M (Kumamoto University), Utsunomiya T (Oita Prefectural Hospital), Eguchi S (Nagasaki University Hospital), Kawanaka H (Beppu Medical Center), Kusumoto T (Kyusyu Medical Cnter), Okumura H (Kagoshima Koseiren Hospital). We also thank Sakamoto S and the staff at the Clinical Research Support Center Kyushu (CReS Kyushu) for their excellent data collection, management, and secretarial assistance. This work was supported by CReS Kyushu with no funding. We thank Maki S for grammatical editing of a draft of this manuscript.


No financial support or funding was received for this study.

Compliance with ethical standards

Conflict to interest

Hashimoto D and all co-authors have no conflict to interest.

Supplementary material

535_2018_1535_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 16 kb)
535_2018_1535_MOESM2_ESM.docx (48 kb)
Supplementary material 2 (DOCX 48 kb)


  1. 1.
    Miyata H, Gotoh M, Hirai I, et al. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg. 2014;259:773–80.CrossRefGoogle Scholar
  2. 2.
    Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.CrossRefGoogle Scholar
  3. 3.
    Otsubo T, Kobayashi S, Sano K, et al. Safety-related outcomes of the Japanese Society of Hepato-Biliary-Pancreatic Surgery board certification system for expert surgeons. J Hepatobiliary Pancreat Sci. 2017;24:252–61.CrossRefGoogle Scholar
  4. 4.
    Garcea G, Dennison AR, Pattenden CJ, et al. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP. 2008;9:99–132.Google Scholar
  5. 5.
    Smeenk HG, Incrocci L, Kazemier G, et al. Adjuvant 5-FU-based chemoradiotherapy for patients undergoing R-1/R-2 resections for pancreatic cancer. Dig Surg. 2005;22:321–8.CrossRefGoogle Scholar
  6. 6.
    Smeenk HG, Tran TC, Erdmann J, et al. Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist? Langenbecks Arch Surg. 2005;390:94–103.CrossRefGoogle Scholar
  7. 7.
    Kleeff J, Reiser C, Hinz U, et al. Surgery for recurrent pancreatic ductal adenocarcinoma. Ann Surg. 2007;245:566–72.CrossRefGoogle Scholar
  8. 8.
    Hashimoto D, Chikamoto A, Masuda T, et al. Pancreatic cancer arising from the remnant pancreas: is it a local recurrence or new primary lesion? Pancreas. 2017;46:1083–90.CrossRefGoogle Scholar
  9. 9.
    Hashimoto D, Chikamoto A, Ohmuraya M, et al. Pancreatic cancer in the remnant pancreas following primary pancreatic resection. Surg Today. 2014;44:1313–20.CrossRefGoogle Scholar
  10. 10.
    Müller MW, Friess H, Kleeff J, et al. Is there still a role for total pancreatectomy? Ann Surg. 2007;246:966–74 (discussion#).CrossRefGoogle Scholar
  11. 11.
    Thomas RM, Truty MJ, Nogueras-Gonzalez GM, et al. Selective reoperation for locally recurrent or metastatic pancreatic ductal adenocarcinoma following primary pancreatic resection. J Gastrointest Surg. 2012;16:1696–704.CrossRefGoogle Scholar
  12. 12.
    Strobel O, Hartwig W, Hackert T, et al. Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol. 2013;20:964–72.CrossRefGoogle Scholar
  13. 13.
    Miyazaki M, Yoshitomi H, Shimizu H, et al. Repeat pancreatectomy for pancreatic ductal cancer recurrence in the remnant pancreas after initial pancreatectomy: is it worthwhile? Surgery. 2014;155:58–66.CrossRefGoogle Scholar
  14. 14.
    Shima Y, Okabayashi T, Kozuki A, et al. Completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas: report of six cases and a review of the literature. Langenbecks Arch Surg. 2015;400:973–8.CrossRefGoogle Scholar
  15. 15.
    Nakagawa M, Choi YY, An JY, et al. Staging for remnant gastric cancer: the metastatic lymph node ratio vs the UICC 7th edition system. Ann Surg Oncol. 2016;23:4322–31.CrossRefGoogle Scholar
  16. 16.
    Qi X, Zhao Y, Li H, et al. Management of hepatocellular carcinoma: an overview of major findings from meta-analyses. Oncotarget. 2016;7:34703–51.Google Scholar
  17. 17.
    Renehan AG, Egger M, Saunders MP, et al. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ. 2002;324:813.CrossRefGoogle Scholar
  18. 18.
    Nakata M, Sawada S, Yamashita M, et al. Surgical treatments for multiple primary adenocarcinoma of the lung. Ann Thorac Surg. 2004;78:1194–9.CrossRefGoogle Scholar
  19. 19.
    Miura F, Takada T, Amano H, et al. Repeated pancreatectomy after pancreatoduodenectomy. J Gastrointest Surg. 2007;11:179–86.CrossRefGoogle Scholar
  20. 20.
    Ishida J, Toyama H, Matsumoto I, et al. Second primary pancreatic ductal carcinoma in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma: high cumulative incidence rates at 5 years after pancreatectomy. Pancreatology. 2016;16:615–20.CrossRefGoogle Scholar
  21. 21.
    Lavu H, Nowcid LJ, Klinge MJ, et al. Reoperative completion pancreatectomy for suspected malignant disease of the pancreas. J Surg Res. 2011;170:89–95.CrossRefGoogle Scholar
  22. 22.
    Hashimoto D, Arima K, Yokoyama N, et al. Heterogeneity of KRAS mutations in pancreatic ductal adenocarcinoma. Pancreas. 2016;45:1111–4.CrossRefGoogle Scholar
  23. 23.
    Yamada S, Kobayashi A, Nakamori S, et al. Resection for recurrent pancreatic cancer in the remnant pancreas after pancreatectomy is clinically promising: results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Surgery. 2018;164:1049–56.CrossRefGoogle Scholar
  24. 24.
    Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–91.CrossRefGoogle Scholar
  25. 25.
    Cancer IUA: TNM Classification of Malignant Tumours. 7th ed. New York: Wiley-Blackwell; 2009.Google Scholar
  26. 26.
    Oettle H, Post S, Neuhaus P, 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.CrossRefGoogle Scholar
  27. 27.
    Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefGoogle Scholar
  28. 28.
    Ueno H, Kosuge T, Matsuyama Y, 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.CrossRefGoogle Scholar
  29. 29.
    Yamaguchi K, Okusaka T, Shimizu K, et al. Clinical practice guidelines for pancreatic cancer 2016 from the Japan Pancreas Society: a synopsis. Pancreas. 2017;46:595–604.CrossRefGoogle Scholar
  30. 30.
    Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefGoogle Scholar
  31. 31.
    Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRefGoogle Scholar
  32. 32.
    Brune K, Abe T, Canto M, et al. Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol. 2006;30:1067–76.Google Scholar
  33. 33.
    Matsuda Y, Furukawa T, Yachida S, et al. The prevalence and Clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia: Autopsy Study evaluating the entire pancreatic parenchyma. Pancreas. 2017;46:658–64.CrossRefGoogle Scholar
  34. 34.
    Tempero M, Malafa M, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15:1028–61.CrossRefGoogle Scholar
  35. 35.
    Heinrich S, Pestalozzi B, Lesurtel M, et al. Adjuvant gemcitabine versus neoadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011;11:346.CrossRefGoogle Scholar
  36. 36.
    Billings BJ, Christein JD, Harmsen WS, et al. Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up? J Gastrointest Surg. 2005;9:1059–66 (discussion#).CrossRefGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Daisuke Hashimoto
    • 1
    • 2
  • Kota Arima
    • 1
  • Shigeki Nakagawa
    • 1
  • Yuji Negoro
    • 3
  • Toshihiko Hirata
    • 4
  • Masahiko Hirota
    • 5
  • Masafumi Inomata
    • 6
  • Kengo Fukuzawa
    • 7
  • Takefumi Ohga
    • 8
  • Hiroshi Saeki
    • 9
  • Eiji Oki
    • 9
  • Yo-ichi Yamashita
    • 1
  • Akira Chikamoto
    • 1
  • Hideo Baba
    • 1
    Email author
  • Yoshihiko Maehara
    • 9
  1. 1.Department of Gastroenterological SurgeryKumamoto University Graduate School of Medical SciencesKumamotoJapan
  2. 2.Department of Gastroenterological SurgeryOmuta Tenryo HospitalOmutaJapan
  3. 3.Department of GastroenterologyKochi Health Sciences CenterKochiJapan
  4. 4.Department of SurgeryJapanese Red Cross Kumamoto HospitalKumamotoJapan
  5. 5.Department of SurgeryKumamoto Regional Medical CenterKumamotoJapan
  6. 6.Department of Gastroenterological and Pediatric SurgeryOita University, Faculty of MedicineOitaJapan
  7. 7.Department of SurgeryOita Red Cross HospitalOitaJapan
  8. 8.Department of SurgeryFukuoka Higashi Medical CenterKogaJapan
  9. 9.Department of Surgery and ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan

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