Skip to main content

Advertisement

SpringerLink
Log in

Outcome of radical surgery for gallbladder carcinoma according to TNM stage: implications for adjuvant therapeutic strategies

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Outcomes following surgery for advanced gallbladder carcinoma remain unsatisfactory. This study aimed to determine the surgical outcome and effectiveness of adjuvant chemotherapy according to TNM stage in patients with gallbladder carcinoma.

Methods

A total of 200 patients undergoing surgery for gallbladder carcinoma were enrolled. Clinicopathological data were evaluated and surgical outcomes were compared between patients with and without adjuvant chemotherapy according to TNM stage.

Results

The 5-year overall survival (OS) after resection for patients with stage I (n = 27), IIA (n = 18), IIB (n = 28), IIIA (n = 25), IIIB (n = 43), IVA (n = 7), and IVB (n = 52) disease was 90.8%, 94.4%, 73.6%, 33.7%, 57.7%, 14.3%, and 11.8%, respectively (p < 0.001). R0 resection was performed in all patients with stage I or II disease, in 89.7% of those with stage III disease, and 69.5% of those with stage IV disease. For patients with stage III disease, adjuvant chemotherapy was associated with improved OS (5-year OS, 60.9% vs. 41.1%; p = 0.028) and was an independent prognostic factor (hazard ratio, 2.045; p = 0.039). For patients with stage IV disease, adjuvant chemotherapy appeared to affect OS (5-year OS, 25.1% vs. 5.3%; p = 0.041); R0 resection (hazard ratio, 1.882; p = 0.040) was the only independent prognostic factor.

Conclusion

TNM stage clearly predicts survival after resection of gallbladder carcinoma. R0 resection with adjuvant chemotherapy is recommended for long-term survival in the multimodal management of patients with stage III or IV gallbladder carcinoma.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Shirai Y, Yoshida K, Tsukada K, Muto T, Watanabe H (1992) Radical surgery for gallbladder carcinoma. Long-term results. Ann Surg 216:565–568

    Article  CAS  Google Scholar 

  2. Fong Y, Jarnagin W, Blumgart LH (2000) Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg 232:557–569

    Article  CAS  Google Scholar 

  3. Dixon E, Vollmer CM Jr, Sahajpal A, Cattral M, Grant D, Doig C, Hemming A, Taylor B, Langer B, Greig P, Gallinger S (2005) An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: a 12-year study at a North American center. Ann Surg 241:385–394

    Article  Google Scholar 

  4. Manterola C, Duque G, Grande L, de Aretxabala X, Conejeros R, Otzen T, García N (2019) A systematic review of the effectiveness of adjuvant therapy for patients with gallbladder cancer. HPB 21:1427–1435

    Article  Google Scholar 

  5. Aloia TA, Jarufe N, Javle M et al (2015) Gallbladder cancer: expert consensus statement. HPB 17:681–690

    Article  Google Scholar 

  6. D'Angelica M, Dalal KM, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR (2009) Analysis of the extent of resection for adenocarcinoma of the gallbladder. Ann Surg Oncol 16:806–816

    Article  Google Scholar 

  7. Tsukada K, Hatakeyama K, Kurosaki I, Uchida K, Shirai Y, Muto T, Yoshida K (1996) Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage. Surgery 120:816–822

    Article  CAS  Google Scholar 

  8. Shirai Y, Ohtani T, Tsukada K, Hatakeyama K (1997) Combined pancreaticoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results. Cancer 80:1904–1909

    Article  CAS  Google Scholar 

  9. Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R, Uemura S, Miyata T, Kato Y, Uesaka K (2016) Is combined pancreatoduodenectomy for advanced gallbladder cancer justified? Surgery 159:810–820

    Article  Google Scholar 

  10. Wakai T, Shirai Y, Sakata J, Nagahashi M, Ajioka Y, Hatakeyama K (2010) Mode of hepatic spread from gallbladder carcinoma: an immunohistochemical analysis of 42 hepatectomized specimens. Am J Surg Pathol 34:65–74

    Article  Google Scholar 

  11. Nishio H, Ebata T, Yokoyama Y, Igami T, Sugawara G, Nagino M (2011) Gallbladder cancer involving the extrahepatic bile duct is worthy of resection. Ann Surg 253:953–960

    Article  Google Scholar 

  12. Shimada K, Nara S, Esaki M, Sakamoto Y, Kosuge T, Hiraoka N (2011) Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum. Br J Surg 98:117–123

    Article  CAS  Google Scholar 

  13. Yamamoto Y, Sugiura T, Ashida R, Okamura Y, Ito T, Uesaka K (2017) Indications for major hepatectomy and combined procedures for advanced gallbladder cancer. Br J Surg 104:257–266

    Article  CAS  Google Scholar 

  14. Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T, Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95:1685–1695

    Article  Google Scholar 

  15. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Kobayashi H, Sueda T (2011) Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg 15:1007–1016

    Article  Google Scholar 

  16. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820

    Article  CAS  Google Scholar 

  17. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388:248–257

    Article  CAS  Google Scholar 

  18. Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J, Primrose JN, Fox RP, Morement H, Chan O, Rees C, Ma YT, Hickish T, Falk S, Finch-Jones M, Pope I, Corrie P, Crosby T, Sothi S, Sharkland K, Adamson D, Wall L, Evans J, Dent J, Hombaiah U, Iwuji C, Anthoney A, Bridgewater J, Cunningham D, Gillmore R, Ross P, Slater S, Wasan H, Waters J, Valle JW, Palmer D, Malik H, Neoptolemos J, Faluyi O, Sumpter K, Dernedde U, Maduhusudan S, Cogill G, Archer C, Iveson T, Wadsley J, Darby S, Peterson M, Mukhtar AA, Thorpe JG, Bateman A, Tsang D, Cummins S, Nolan L, Beaumont E, Prasad R, Mirza D, Stocken D, Praseedom R, Davidson B, Raftery J, Zhu S, Garden J, Stubbs C, Coxon F (2019) Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol 20:663–673

    Article  CAS  Google Scholar 

  19. Kobayashi S, Nagano H, Tomokuni A, Gotoh K, Sakai D, Hatano E, Seo S, Terajima H, Uchida Y, Ajiki T, Satake H, Kamei K, Tohyama T, Hirose T, Ikai I, Morita S, Ioka T, Kansai Hepato-Biliary Oncology (KHBO) Group (2019) Prospective, randomized phase II study of adjuvant gemcitabine versus S-1 after major hepatectomy for biliary tract cancer (KHBO 1208). Ann Surg 270:230–237

    Article  Google Scholar 

  20. Kim Y, Amini N, Wilson A, Margonis GA, Ethun CG, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Krasnick B, Weber SM, Salem A, Martin RCG, Scoggins C, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Cardona K, Maithel SK, Pawlik TM (2016) Impact of chemotherapy and external-beam radiation therapy on outcomes among patients with resected gallbladder cancer: a multi-institutional analysis. Ann Surg Oncol 23:2998–3008

    Article  Google Scholar 

  21. Amin MB, Edge SB, Greene FL et al (eds) (2017) AJCC cancer staging manual, 8th edn. Springer, New York

    Google Scholar 

  22. Sakata J, Shirai Y, Wakai T, Ajioka Y, Hatakeyama K (2010) Number of positive lymph nodes independently determines the prognosis after resection in patients with gallbladder carcinoma. Ann Surg Oncol 17:1831–1840

    Article  Google Scholar 

  23. Sakata J, Kobayashi T, Tajima Y, Ohashi T, Hirose Y, Takano K, Takizawa K, Miura K, Wakai T (2017) Relevance of dissection of the posterior superior pancreaticoduodenal lymph nodes in gallbladder carcinoma. Ann Surg Oncol 24:2474–2481

    Article  Google Scholar 

  24. Bergquist JR, Shah HN, Habermann EB, Hernandez MC, Ivanics T, Kendrick ML, Smoot RL, Nagorney DM, Borad MJ, McWilliams RR, Truty MJ (2018) Adjuvant systemic therapy after resection of node positive gallbladder cancer: time for a well-designed trial? (results of a US-national retrospective cohort study). Int J Surg 52:171–179

    Article  Google Scholar 

  25. Sasaki R, Itabashi H, Fujita T, Takeda Y, Hoshikawa K, Takahashi M, Funato O, Nitta H, Kanno S, Saito K (2006) Significance of extensive surgery including resection of the pancreas head for the treatment of gallbladder cancer--from the perspective of mode of lymph node involvement and surgical outcome. World J Surg 30:36–42

    Article  Google Scholar 

  26. Creasy JM, Goldman DA, Dudeja V, Lowery MA, Cercek A, Balachandran VP, Allen PJ, DeMatteo RP, Kingham TP, D'Angelica MI, Jarnagin WR (2017) Systemic chemotherapy combined with resection for locally advanced gallbladder carcinoma: surgical and survival outcomes. J Am Coll Surg 224:906–916

    Article  Google Scholar 

  27. Chaudhari VA, Ostwal V, Patkar S, Sahu A, Toshniwal A, Ramaswamy A, Shetty NS, Shrikhande SV, Goel M (2018) Outcome of neoadjuvant chemotherapy in “locally advanced/borderline resectable” gallbladder cancer: the need to define indications. HPB 20:841–847

    Article  Google Scholar 

  28. Engineer R, Goel M, Chopra S, Patil P, Purandare N, Rangarajan V, Ph R, Bal M, Shrikhande S, Shrivastava SK, Mehta S (2016) Neoadjuvant chemoradiation followed by surgery for locally advanced gallbladder cancers: a new paradigm. Ann Surg Oncol 23:3009–3015

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan

    Kizuki Yuza, Jun Sakata, Yuki Hirose, Kohei Miura, Takuya Ando, Tomohiro Katada, Kazuyasu Takizawa, Takashi Kobayashi, Hiroshi Ichikawa, Yoshifumi Shimada, Masayuki Nagahashi & Toshifumi Wakai

Authors
  1. Kizuki Yuza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Sakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuki Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kohei Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takuya Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomohiro Katada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazuyasu Takizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takashi Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Ichikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoshifumi Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masayuki Nagahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshifumi Wakai
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yuza K, Sakata J, and Wakai T participated in study conception and design. Acquisition of data was done by Yuza K, Sakata J, Hirose Y, Ando T, Katada T, and Miura K. Yuza K, Sakata J, Takizawa K, Kobayashi T, Ichikawa H, Shimada Y, and Nagahashi M participated in the analysis and interpretation of data. Drafting of manuscript was carried out by Yuza K and Sakata J. Hirose Y, Katada T, Miura K, Takizawa K, Kobayashi T, Ichikawa H, Shimada Y, Nagahashi M, and Wakai T participated in the critical revision of manuscript:

Corresponding author

Correspondence to Jun Sakata.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the institutional review board of Niigata University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with 1964 Helsinki declaration.

Informed consent

The need for informed consent was waived due to the retrospective observational nature of the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuza, K., Sakata, J., Hirose, Y. et al. Outcome of radical surgery for gallbladder carcinoma according to TNM stage: implications for adjuvant therapeutic strategies. Langenbecks Arch Surg 406, 801–811 (2021). https://doi.org/10.1007/s00423-020-02068-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-020-02068-7

Keywords

Search

Navigation