Ann Hepatobiliary Pancreat Surg.  2021 Aug;25(3):349-357. 10.14701/ahbps.2021.25.3.349.

Conversion surgery for initially unresectable extrahepatic biliary tract cancer

Affiliations
  • 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

Abstract

Backgrounds/Aims
Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents.
Methods
Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively.
Results
Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies.
Conclusions
Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.

Keyword

Biliary tract neoplasms; Operative surgical procedures; Chemoradiotherapy

Figure

  • Fig. 1 Overall survival rates. (A) Graph shows the overall survival rates of patients undergoing surgery. Both the 3-year and 5-year survival rates were 51.6%. (B) The overall survival rates of patients from the time of first chemotherapy are shown. The 3-year and 5-year survival rates were 68.8% and 55.0%, respectively.

  • Fig. 2 Patient 6: perihilar cholangiocarcinoma with prolonged chemotherapy and long-term survival. (A) Pre-chemotherapy magnetic resonance cholangiopancreatography shows perihilar cholangiocarcinoma Bismuth type IV (arrow). (B) Pre-chemotherapy computed tomography shows metastatic lymph node (LN) invading the common hepatic artery (CHA) and the portal vein (PV) (arrow). (C) Post-chemotherapy magnetic resonance imaging shows a decrease in LN size, and no involvement of CHA and the PV (arrow).

  • Fig. 3 Patient 11: gallbladder cancer treated with multiple chemotherapy regimens. (A) Pre-chemotherapy computed tomography (CT) shows suspicious seeding nodule (red arrow) and regional and para-aortic lymph node (LN) enlargement (blue dotted arrows). (B) Pre-chemotherapy CT reveals suspicious seeding nodule (arrow). (C) Post-chemotherapy CT shows the decreased size of suspicious seeding nodule (red arrow) and the size of regional and para-aortic LNs (blue dotted arrows).


Reference

1. Benavides M, Antón A, Gallego J, Gómez MA, Jiménez-Gordo A, La Casta A, et al. 2015; Biliary tract cancers: SEOM clinical guidelines. Clin Transl Oncol. 17:982–987. DOI: 10.1007/s12094-015-1436-2. PMID: 26607930. PMCID: PMC4689747.
Article
2. Matsukuma S, Tokumitsu Y, Shindo Y, Matsui H, Nagano H. 2019; Essential updates to the surgical treatment of biliary tract cancer. Ann Gastroenterol Surg. 3:378–389. DOI: 10.1002/ags3.12266. PMID: 31346577. PMCID: PMC6635684.
Article
3. Sano T, Shimizu Y, Senda Y, Kinoshita T, Nimura Y. 2014; Assessing resectability in cholangiocarcinoma. Hepat Oncol. 1:39–51. DOI: 10.2217/hep.13.6. PMID: 30190940. PMCID: PMC6114008.
Article
4. Blechacz B, Gores GJ. 2008; Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology. 48:308–321. DOI: 10.1002/hep.22310. PMID: 18536057. PMCID: PMC2547491.
Article
5. Thongprasert S. 2005; The role of chemotherapy in cholangiocarcinoma. Ann Oncol. 16 Suppl 2:ii93–ii96. DOI: 10.1093/annonc/mdi712. PMID: 15958484.
Article
6. Lin MH, Chen JS, Chen HH, Su WC. 2003; A phase II trial of gemcitabine in the treatment of advanced bile duct and periampullary carcinomas. Chemotherapy. 49:154–158. DOI: 10.1159/000070622. PMID: 12815209.
Article
7. Creasy JM, Goldman DA, Dudeja V, Lowery MA, Cercek A, Balachandran VP, et al. 2017; Systemic chemotherapy combined with resection for locally advanced gallbladder carcinoma: surgical and survival outcomes. J Am Coll Surg. 224:906–916. DOI: 10.1016/j.jamcollsurg.2016.12.058. PMID: 28216422. PMCID: PMC5409857.
Article
8. Kato A, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, et al. 2013; Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 20:318–324. DOI: 10.1245/s10434-012-2312-8. PMID: 23149849.
Article
9. Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, et al. 2018; Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 105:839–847. DOI: 10.1002/bjs.10641. PMID: 28858392.
Article
10. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. 2004; Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 240:644–657. discussion 657–658. DOI: 10.1097/01.sla.0000141198.92114.f6. PMID: 15383792. PMCID: PMC1356466.
11. Yoshida K, Yamaguchi K, Okumura N, Tanahashi T, Kodera Y. 2016; Is conversion therapy possible in stage IV gastric cancer: the proposal of new biological categories of classification. Gastric Cancer. 19:329–338. DOI: 10.1007/s10120-015-0575-z. PMID: 26643880. PMCID: PMC4824831.
Article
12. Furuse J, Shibahara J, Sugiyama M. 2018; Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer. J Hepatobiliary Pancreat Sci. 25:261–268. DOI: 10.1002/jhbp.547. PMID: 29651809.
Article
13. Randi G, Malvezzi M, Levi F, Ferlay J, Negri E, Franceschi S, et al. 2009; Epidemiology of biliary tract cancers: an update. Ann Oncol. 20:146–159. DOI: 10.1093/annonc/mdn533. PMID: 18667395.
Article
14. GBD 2017 Causes of Death Collaborators. 2018; Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 392:1736–1788. DOI: 10.1016/S0140-6736(18)32203-7. PMID: 30496103. PMCID: PMC6227606.
15. Kim BW, Oh CM, Choi HY, Park JW, Cho H, Ki M. 2019; Incidence and overall survival of biliary tract cancers in South Korea from 2006 to 2015: using the National Health Information Database. Gut Liver. 13:104–113. DOI: 10.5009/gnl18105. PMID: 29938462. PMCID: PMC6347005.
Article
16. Shroff RT, Kennedy EB, Bachini M, Bekaii-Saab T, Crane C, Edeline J, et al. 2019; Adjuvant therapy for resected biliary tract cancer: ASCO clinical practice guideline. J Clin Oncol. 37:1015–1027. DOI: 10.1200/JCO.18.02178. PMID: 30856044.
Article
17. Thongprasert S, Napapan S, Charoentum C, Moonprakan S. 2005; Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol. 16:279–281. DOI: 10.1093/annonc/mdi046. PMID: 15668284.
Article
18. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. 2010; Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 362:1273–1281. DOI: 10.1056/NEJMoa0908721. PMID: 20375404.
Article
19. Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. 2010; Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 103:469–474. DOI: 10.1038/sj.bjc.6605779. PMID: 20628385. PMCID: PMC2939781.
Article
20. Morganti AG, Massaccesi M, La Torre G, Caravatta L, Piscopo A, Tambaro R, et al. 2010; A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 17:194–205. DOI: 10.1245/s10434-009-0762-4. PMID: 19856029.
Article
21. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, et al. 2010; Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 11:48–54. DOI: 10.1016/S1470-2045(09)70333-X. PMID: 19932054.
Article
22. Lee JK, Capanu M, O'Reilly EM, Ma J, Chou JF, Shia J, et al. 2013; A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas. Br J Cancer. 109:915–919. DOI: 10.1038/bjc.2013.432. PMID: 23900219. PMCID: PMC3749586.
Article
23. Suzuki Y, Kan M, Kimura G, Umemoto K, Watanabe K, Sasaki M, et al. 2019; Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy. J Gastroenterol. 54:281–290. DOI: 10.1007/s00535-018-1518-3. PMID: 30298469. PMCID: PMC6394712.
Article
24. McMasters KM, Tuttle TM, Leach SD, Rich T, Cleary KR, Evans DB, et al. 1997; Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma. Am J Surg. 174:605–608. discussion 608–609. DOI: 10.1016/S0002-9610(97)00203-1. PMID: 9409582.
Article
25. Nelson JW, Ghafoori AP, Willett CG, Tyler DS, Pappas TN, Clary BM, et al. 2009; Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys. 73:148–153. DOI: 10.1016/j.ijrobp.2008.07.008. PMID: 18805651. PMCID: PMC4142576.
Article
26. Tada S, Fujikawa T, Tanaka A, Abe T, Yoshimoto Y, Maekawa H, et al. 2012; [A case of unresectable hilar cholangiocarcinoma successfully treated by gemcitabine and S-1 combination chemotherapy]. Gan To Kagaku Ryoho. 39:1279–1282. Japanese. PMID: 22902459.
27. Glazer ES, Liu P, Abdalla EK, Vauthey JN, Curley SA. 2012; Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins. J Gastrointest Surg. 16:1666–1671. DOI: 10.1007/s11605-012-1935-1. PMID: 22777053. PMCID: PMC3867946.
Article
28. Kobayashi S, Gotoh K, Takahashi H, Akita H, Marubashi S, Yamada T, et al. 2016; Clinicopathological features of surgically-resected biliary tract cancer following chemo-radiation therapy. Anticancer Res. 36:335–342. PMID: 26722062.
29. Jung JH, Lee HJ, Lee HS, Jo JH, Cho IR, Chung MJ, et al. 2017; Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma. World J Gastroenterol. 23:3301–3308. DOI: 10.3748/wjg.v23.i18.3301. PMID: 28566890. PMCID: PMC5434436.
Article
30. Sumiyoshi T, Shima Y, Okabayashi T, Negoro Y, Shimada Y, Iwata J, et al. 2018; Chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. World J Surg. 42:2910–2918. DOI: 10.1007/s00268-018-4558-1. PMID: 29511872.
Article
Full Text Links
  • AHBPS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr