Advertisement

Radiologically occult metastatic pancreatic cancer: how can we avoid unbeneficial resection?

  • Atsushi Oba
  • Yosuke InoueEmail author
  • Yoshihiro Ono
  • Shoichi Irie
  • Takafumi Sato
  • Yoshihiro Mise
  • Hiromichi Ito
  • Yu Takahashi
  • Akio Saiura
Original Article

Abstract

Purpose

This study aimed to clarify the key factors for minimizing unsuitable surgical interventions for patients with radiologically occult metastatic pancreatic cancer (ROMPC), defined as a distant metastasis detected during surgery or within 6 months after resection.

Methods

This study involved 502 patients planned to undergo curative resection for pancreatic cancer between 2008 and 2015. Patients were divided into ROMPC and non-ROMPC groups and evaluated preoperative factors associated with ROMPC.

Results

Overall survival (OS) was significantly lower in the ROMPC group (n = 145) than the non-ROMPC group (n = 357, median survival time [MST] 10.8 vs. 35.3 months, P < 0.001). In the ROMPC group, OS tended to be worse for patients who had pancreatectomies (n = 84) than those who did not (n = 61, MST 10.1 vs. 13.2 months, P = 0.057), and the next chemotherapy started significantly later in patients who had pancreatectomies (P < 0.001). Moreover, OS was significantly lower for patients with (n = 82) than without (n = 63) liver metastases (MST 9.7 vs. 13.0 months, respectively, P = 0.020). The best indicator for patients at higher risk of ROMPC was a combination of carbohydrate antigen 19-9 concentration ≥ 300 U/ml and tumor size ≥ 30 mm.

Conclusions

In the ROMPC group, patients who underwent pancreatectomy had a poorer prognosis than patients not undergoing pancreatectomy. Given that the liver was the most frequent distant metastatic site for ROMPC and had the poorest prognosis, establishing a strategy featuring new imaging modalities to detect radiologically occult liver metastases is necessary.

Keywords

Pancreatic cancer Distant metastasis Liver metastasis Staging laparoscopy CA19-9 Occult metastasis, early recurrence 

Notes

Authors’ contributions

Study conception and design: Oba, Inoue, Mise, Takahashi, Saiura. Acquisition of data: Oba, Irie, Sato, Ono, Inoue. Analysis and interpretation of data: Oba, Inoue, Saiura. Drafting of manuscript: Oba, Inoue, Ito. Critical revision: Inoue, Takahashi, Saiura. Final approval: Oba, Inoue, Ono, Irie, Sato, Mise, Ito, Takahashi, Saiura.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The present retrospective study was approved by the Institutional Review Board of the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, with a waiver of the written informed consent from all patients concerned.

References

  1. 1.
    Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921CrossRefGoogle Scholar
  2. 2.
    Neoptolemos JP, Kleeff J, Michl P, Costello E, Greenhalf W, Palmer DH (2018) Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol 15(6):333–348CrossRefGoogle Scholar
  3. 3.
    Uesaka K, Boku N, Fukutomi A et al (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet (London, England) 388(10041):248–257CrossRefGoogle Scholar
  4. 4.
    Allen VB, Gurusamy KS, Takwoingi Y, Kalia A, Davidson BR (2013) Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev 2013(11):Cd009323Google Scholar
  5. 5.
    Tamburrino D, Riviere D, Yaghoobi M, Davidson BR, Gurusamy KS (2016) Diagnostic accuracy of different imaging modalities following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev 9:Cd011515PubMedGoogle Scholar
  6. 6.
    Kim TH, Han SS, Park SJ et al (2011) CA 19-9 level as indicator of early distant metastasis and therapeutic selection in resected pancreatic cancer. Int J Radiat Oncol Biol Phys 81(5):e743–e748CrossRefGoogle Scholar
  7. 7.
    Matsumoto I, Tanaka M, Shirakawa S, Shinzeki M, Toyama H, Asari S, Goto T, Yamashita H, Ishida J, Ajiki T, Fukumoto T, Shimokawa M, Ku Y (2015) Postoperative serum albumin level is a marker of incomplete adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma. Ann Surg Oncol 22(7):2408–2415CrossRefGoogle Scholar
  8. 8.
    Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH (2013) Recent progress in pancreatic cancer. CA Cancer J Clin 63(5):318–348CrossRefGoogle Scholar
  9. 9.
    Arita J, Ono Y, Takahashi M, Inoue Y, Takahashi Y, Saiura A (2014) Usefulness of contrast-enhanced intraoperative ultrasound in identifying disappearing liver metastases from colorectal carcinoma after chemotherapy. Ann Surg Oncol 21(Suppl 3):S390–S397CrossRefGoogle Scholar
  10. 10.
    Arita J, Ono Y, Takahashi M, Inoue Y, Takahashi Y, Matsueda K, Saiura A (2015) Routine preoperative liver-specific magnetic resonance imaging does not exclude the necessity of contrast-enhanced intraoperative ultrasound in hepatic resection for colorectal liver metastasis. Ann Surg 262(6):1086–1091CrossRefGoogle Scholar
  11. 11.
    Oba A, Mise Y, Ito H, Hiratsuka M, Inoue Y, Ishizawa T, Arita J, Matsueda K, Takahashi Y, Saiura A (2018) Clinical implications of disappearing colorectal liver metastases have changed in the era of hepatocyte-specific MRI and contrast-enhanced intraoperative ultrasonography. HPB (Oxford) 20(8):708–714CrossRefGoogle Scholar
  12. 12.
    Matsumoto I, Murakami Y, Shinzeki M, Asari S, Goto T, Tani M, Motoi F, Uemura K, Sho M, Satoi S, Honda G, Yamaue H, Unno M, Akahori T, Kwon AH, Kurata M, Ajiki T, Fukumoto T, Ku Y (2015) Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: a multi-center retrospective study. Pancreatology 15(6):674–680CrossRefGoogle Scholar
  13. 13.
    Satoi S, Yanagimoto H, Toyokawa H, Inoue K, Wada K, Yamamoto T, Hirooka S, Yamaki S, Yui R, Mergental H, Kwon AH (2011) Selective use of staging laparoscopy based on carbohydrate antigen 19-9 level and tumor size in patients with radiographically defined potentially or borderline resectable pancreatic cancer. Pancreas 40(3):426–432CrossRefGoogle Scholar
  14. 14.
    Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ (2014) Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg 260(2):372–377CrossRefGoogle Scholar
  15. 15.
    Dobrila-Dintinjana R, Trivanovic D, Zelic M et al (2013) Nutritional support in patients with colorectal cancer during chemotherapy: does it work? Hepato-gastroenterology 60(123):475–480PubMedGoogle Scholar
  16. 16.
    Satoi S, Yanagimoto H, Yamamoto T, Toyokawa H, Hirooka S, Yamaki S, Opendro SS, Inoue K, Michiura T, Ryota H, Matsui Y, Kon M (2016) A clinical role of staging laparoscopy in patients with radiographically defined locally advanced pancreatic ductal adenocarcinoma. World J Surg Oncol 14(1):14CrossRefGoogle Scholar
  17. 17.
    Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, Weiss MJ, Zheng L, Wolfgang CL, He J (2018) Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg 267(5):936–945CrossRefGoogle Scholar
  18. 18.
    Fong ZV, Alvino DML, Fernandez-Del Castillo C et al (2017) Reappraisal of staging laparoscopy for patients with pancreatic adenocarcinoma: a contemporary analysis of 1001 patients. Ann Surg Oncol 24(11):3203–3211CrossRefGoogle Scholar
  19. 19.
    Mui LW, Pursell LJ, Botwinick IC, Allendorf JD, Chabot JA, Newhouse JH (2014) Routine intraoperative hepatic sonography does not affect staging or postsurgical hepatic recurrence in pancreatic adenocarcinoma. J Ultrasound Med 33(1):47–51CrossRefGoogle Scholar
  20. 20.
    Piccolboni P, Settembre A, Angelini P, Esposito F, Palladino S, Corcione F (2015) Laparoscopic ultrasound: a surgical “must” for second line intra-operative evaluation of pancreatic cancer resectability. Il Giornale di chirurgia 36(1):5–8PubMedPubMedCentralGoogle Scholar
  21. 21.
    Looijen GA, Pranger BK, de Jong KP, Pennings JP, de Meijer VE, Erdmann JI (2018) The additional value of laparoscopic ultrasound to staging laparoscopy in patients with suspected pancreatic head Cancer. J Gastrointest Surg 22(7):1186–1192CrossRefGoogle Scholar
  22. 22.
    Yokoyama N, Otani T, Hashidate H, Maeda C, Katada T, Sudo N, Manabe S, Ikeno Y, Toyoda A, Katayanagi N (2012) Real-time detection of hepatic micrometastases from pancreatic cancer by intraoperative fluorescence imaging: preliminary results of a prospective study. Cancer 118(11):2813–2819CrossRefGoogle Scholar
  23. 23.
    Alexakis N, Gomatos IP, Sbarounis S, Toutouzas K, Katsaragakis S, Zografos G, Konstandoulakis MM (2015) High serum CA 19-9 but not tumor size should select patients for staging laparoscopy in radiological resectable pancreas head and peri-ampullary cancer. Eur J Surg Oncol 41(2):265–269CrossRefGoogle Scholar
  24. 24.
    Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Sasaki K, Furukawa H, Matsunaga K, Maeda A (2012) Serum CA19-9 is a significant predictor among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma. J Gastrointest Surg 16(5):977–985CrossRefGoogle Scholar
  25. 25.
    Yamamoto Y, Ikoma H, Morimura R, Konishi H, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Kubota T, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Ochiai T, Otsuji E (2014) Optimal duration of the early and late recurrence of pancreatic cancer after pancreatectomy based on the difference in the prognosis. Pancreatology 14(6):524–529CrossRefGoogle Scholar
  26. 26.
    Groot VP, Gemenetzis G, Blair AB, Rivero-Soto RJ, Yu J, Javed AA, Burkhart RA, Rinkes IHMB, Molenaar IQ, Cameron JL, Weiss MJ, Wolfgang CL, He J (2019) Defining and predicting early recurrence in 957 patients with resected pancreatic ductal adenocarcinoma. Ann Surg 269(6):1154–1162CrossRefGoogle Scholar
  27. 27.
    Kurahara H, Shinchi H, Ohtsuka T et al (2019) Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study. Langenbeck's Arch Surg 404(2):167–174CrossRefGoogle Scholar
  28. 28.
    Nakagawa K, Akahori T, Nishiwada S et al (2018) Prognostic factors for actual long-term survival in the era of multidisciplinary treatment for pancreatic ductal adenocarcinoma. Langenbeck's Arch Surg 403(6):693–700CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Atsushi Oba
    • 1
  • Yosuke Inoue
    • 1
    Email author
  • Yoshihiro Ono
    • 1
  • Shoichi Irie
    • 1
    • 2
  • Takafumi Sato
    • 1
  • Yoshihiro Mise
    • 1
    • 2
  • Hiromichi Ito
    • 1
  • Yu Takahashi
    • 1
  • Akio Saiura
    • 1
    • 2
  1. 1.Department of Hepatobiliary Pancreatic SurgeryCancer Institute Hospital, Japanese Foundation for Cancer ResearchTokyoJapan
  2. 2.Department of Hepatobiliary-Pancreatic SurgeryJuntendo University School of MedicineTokyoJapan

Personalised recommendations