Review Article| Volume 32, ISSUE 1, P83-99, January 2023

Past, Present, and Future Management of Localized Biliary Tract Malignancies

  • Janet Li
    Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, 3181 Southwest. Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA
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  • Flavio G. Rocha
    Department of Surgery, Knight Cancer Institute at Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA
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  • Skye C. Mayo
    Corresponding author.
    Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute at Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA
    Search for articles by this author
Published:November 03, 2022DOI:


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        • Siegel R.L.
        • Miller K.D.
        • Fuchs H.E.
        • et al.
        Cancer statistics, 2022.
        CA Cancer J Clin. 2022; 72: 7-33
        • Mosele F.
        • Stefanovska B.
        • Lusque A.
        • et al.
        Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer.
        Ann Oncol. 2020; 31: 377-386
      1. National Comprehensive Cancer Network. Hepatobiliary Cancers.(Version 1.2022).
        (Available at:) (Accessed May 23, 2022)
        • Hundal R.
        • Shaffer E.A.
        Gallbladder cancer: epidemiology and outcome.
        Clin Epidemiol. 2014; 6: 99-109
        • Henley S.J.
        • Weir H.K.
        • Jim M.A.
        • et al.
        Gallbladder Cancer Incidence and Mortality, United States 1999-2011.
        Cancer Epidemiol biomarkers Prev. 2015; 24: 1319-1326
        • Varshney S.
        • Butturini G.
        • Gupta R.
        Incidental carcinoma of the gallbladder.
        Eur J Surg Oncol. 2002; 28: 4-10
        • Duffy A.
        • Capanu M.
        • Abou-Alfa G.K.
        • et al.
        Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC).
        J Surg Oncol. 2008; 98: 485-489
        • Misra M.C.
        • Guleria S.
        Management of cancer gallbladder found as a surprise on a resected gallbladder specimen.
        J Surg Oncol. 2006; 93: 690-698
        • Patel N.
        • Benipal B.
        Incidence of Cholangiocarcinoma in the USA from 2001 to 2015: A US Cancer Statistics Analysis of 50 States.
        Cureus. 2019; 11: e3962
        • Shaib Y.H.
        • Davila J.A.
        • McGlynn K.
        • et al.
        Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?.
        J Hepatol. 2004; 40: 472-477
        • Klatskin G.
        Adenocarcinoma of the Hepatic Duct at Its Bifurcation within the Porta Hepatis. An Unusual Tumor with Distinctive Clinical and Pathological Features.
        Am J Med. 1965; 38: 241-256
        • Sutton T.L.
        • Walker B.S.
        • Radu S.
        • et al.
        Degree of biliary tract violation during treatment of gallbladder adenocarcinoma is independently associated with development of peritoneal carcinomatosis.
        J Surg Oncol. 2021; 124: 581-588
        • Benson A.B.
        • D'Angelica M.I.
        • Abbott D.E.
        • et al.
        Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.
        J Natl Compr Canc Netw. 2021; 19: 541-565
        • Okami J.
        • Dono K.
        • Sakon M.
        • et al.
        Patterns of regional lymph node involvement in intrahepatic cholangiocarcinoma of the left lobe.
        J Gastrointest Surg. 2003; 7: 850-856
        • Bismuth H.
        • Nakache R.
        • Diamond T.
        Management strategies in resection for hilar cholangiocarcinoma.
        Ann Surg. 1992; 215: 31-38
        • Aloia T.A.
        • Jarufe N.
        • Javle M.
        • et al.
        Gallbladder cancer: expert consensus statement.
        HPB (Oxford). 2015; 17: 681-690
        • Agarwal A.K.
        • Kalayarasan R.
        • Javed A.
        • et al.
        The role of staging laparoscopy in primary gall bladder cancer--an analysis of 409 patients: a prospective study to evaluate the role of staging laparoscopy in the management of gallbladder cancer.
        Ann Surg. 2013; 258: 318-323
        • Fuks D.
        • Regimbeau J.M.
        • Le Treut Y.P.
        • et al.
        Incidental gallbladder cancer by the AFC-GBC-2009 Study Group.
        World J Surg. 2011; 35: 1887-1897
        • Araida T.
        • Higuchi R.
        • Hamano M.
        • et al.
        Hepatic resection in 485 R0 pT2 and pT3 cases of advanced carcinoma of the gallbladder: results of a Japanese Society of Biliary Surgery survey--a multicenter study.
        J Hepatobiliary Pancreat Surg. 2009; 16: 204-215
        • D'Angelica M.
        • Dalal K.M.
        • DeMatteo R.P.
        • et al.
        Analysis of the extent of resection for adenocarcinoma of the gallbladder.
        Ann Surg Oncol. 2009; 16: 806-816
        • Maker A.V.
        • Butte J.M.
        • Oxenberg J.
        • et al.
        Is port site resection necessary in the surgical management of gallbladder cancer?.
        Ann Surg Oncol. 2012; 19: 409-417
        • Edge S.B.M.B.
        • Frederick L.G.
        American Joint Committee on cancer (AJCC) staging Handbook: from the AJCC cancer staging Manual.
        8th edition. American Cancer Society, Cham, Switzerland2016
        • Ito H.
        • Ito K.
        • D'Angelica M.
        • et al.
        Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment.
        Ann Surg. 2011; 254: 320-325
        • de Jong M.C.
        • Nathan H.
        • Sotiropoulos G.C.
        • et al.
        Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment.
        J Clin Oncol. 2011; 29: 3140-3145
        • Spolverato G.
        • Yakoob M.Y.
        • Kim Y.
        • et al.
        The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma.
        Ann Surg Oncol. 2015; 22: 4020-4028
        • Zhang X.F.
        • Pawlik T.M.
        Response to the Comment on "Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis.
        Ann Surg. 2021; 274: e743
        • Zhang X.F.
        • Xue F.
        • Dong D.H.
        • et al.
        Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis.
        Ann Surg. 2021; 274: e1187-e1195
        • Jarnagin W.R.
        • Fong Y.
        • DeMatteo R.P.
        • et al.
        Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma.
        Ann Surg. 2001; 234 ([discussion: 517–9]): 507-517
        • Jain V.
        • Krishnamurthy G.
        • Kumar H.
        • et al.
        Anatomical Basis of Routine Caudate Lobe Resections in Hilar Cholangiocarcinoma.
        J Gastrointest Surg. 2021; 25: 2114-2115
        • Wahab M.A.
        • Sultan A.M.
        • Salah T.
        • et al.
        Caudate lobe resection with major hepatectomy for central cholangiocarcinoma: is it of value?.
        Hepatogastroenterology. 2012; 59: 321-324
        • Birgin E.
        • Rasbach E.
        • Reissfelder C.
        • et al.
        A systematic review and meta-analysis of caudate lobectomy for treatment of hilar cholangiocarcinoma.
        Eur J Surg Oncol. 2020; 46: 747-753
        • Lamarca A.
        • Barriuso J.
        • McNamara M.G.
        • et al.
        Molecular targeted therapies: Ready for "prime time" in biliary tract cancer.
        J Hepatol. 2020; 73: 170-185
        • Valle J.W.
        • Kelley R.K.
        • Nervi B.
        • et al.
        Biliary tract cancer.
        Lancet. 2021; 397: 428-444
        • Zhu A.X.
        • Macarulla T.
        • Javle M.M.
        • et al.
        Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial.
        JAMA Oncol. 2021; 7: 1669-1677
        • Abou-Alfa G.K.
        • Sahai V.
        • Hollebecque A.
        • et al.
        Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study.
        Lancet Oncol. 2020; 21: 671-684
        • Bekaii-Saab T.S.
        • Valle J.W.
        • Van Cutsem E.
        • et al.
        FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements.
        Future Oncol. 2020; 16: 2385-2399
        • Jarnagin W.R.
        • Ruo L.
        • Little S.A.
        • et al.
        Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.
        Cancer. 2003; 98: 1689-1700
        • Doussot A.
        • Gonen M.
        • Wiggers J.K.
        • et al.
        Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models.
        J Am Coll Surg. 2016; 223: 493-505 e2
        • Valle J.
        • Wasan H.
        • Palmer D.H.
        • et al.
        Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.
        N Engl J Med. 2010; 362: 1273-1281
        • Edeline J.
        • Benabdelghani M.
        • Bertaut A.
        • et al.
        Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study.
        J Clin Oncol. 2019; 37: 658-667
        • Primrose J.N.
        • Fox R.P.
        • Palmer D.H.
        • et al.
        Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study.
        Lancet Oncol. 2019; 20: 663-673
        • Ebata T.
        • Hirano S.
        • Konishi M.
        • et al.
        Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.
        Br J Surg. 2018; 105: 192-202
        • Ben-Josef E.
        • Guthrie K.A.
        • El-Khoueiry A.B.
        • et al.
        SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma.
        J Clin Oncol. 2015; 33: 2617-2622
        • Saluja S.S.
        • Nekarakanti P.K.
        • Mishra P.K.
        • et al.
        Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection.
        J Gastrointest Surg. 2022; 26: 398-407
        • Nakachi K.
        • Konishi M.
        • Ikeda M.
        • et al.
        A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202, ASCOT).
        Jpn J Clin Oncol. 2018; 48: 392-395
        • Ikeda M.
        • Nakachi K.
        • Konishi M.
        • et al.
        Adjuvant S-1 versus observation in curatively resected biliary tract cancer: A phase III trial (JCOG1202: ASCOT).
        J Clin Oncol. 2022; 40
      2. Deutsche Krebshilfe E.V. BGCRUAG-ITGDHC, (DHCG) CCG. Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After CurativeIntent Resection of Biliary Tract Cancer (ACTICCA-1).
        (Available at:) (Accessed April 20, 2022)
        • SK M.
        Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer (OPT-IN EA2197).
        (Available at:) (Accessed April 20, 2022)
        • Maithel S.K.
        • Javle M.M.
        • Mahipal A.
        • et al.
        NEO-GAP: A phase II single-arm prospective feasibility study of neoadjuvant gemcitabine/cisplatin/nab-paclitaxel for resectable high-risk intrahepatic cholangiocarcinoma.
        J Clin Oncol. 2022; : 4097
        • Cercek A.
        • Boerner T.
        • Tan B.R.
        • et al.
        Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.
        JAMA Oncol. 2020; 6: 60-67