Surgical management of intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICCA) is a rare tumor with a poor prognosis that arises from the intrahepatic biliary tract. Patients who present with locally advanced or metastatic ICCA are generally treated with first-line gemcitabine/cisplatin and/or liver-directed therapy with the hope of downstaging/downsizing the disease. Patients who present with resectable ICCA may be treated with upfront surgery and postoperative adjuvant capecitabine. Staging laparoscopy should be considered to evaluate for occult metastatic disease and laparoscopic ultrasound can be used to better evaluate the liver parenchyma. Resection with the goal of achieving an R0 margin, along with lymphadenectomy to adequately stage patients, should be the standard operative approach. Unfortunately, the surgical technique cannot overcome poor tumor biology, and ICCA has a high incidence of recurrence, with many patients developing metastatic disease. Targeted therapy with IDH and FGFR inhibitors has had promising results in early clinical trials. Future endeavors should strive to identify more effective systemic and targeted therapies, which will hopefully improve survival for patients with ICCA.

Keywords

Surgery / intrahepatic cholangiocarcinoma / margin status / lymphadenectomy

References

[1] Goyal L,Crolley VE.Targeting FGFR inhibition in cholangiocarcinoma.Cancer Treat Rev2021;95:102170

[2] Cardinale V,Torrice A.Intra-hepatic and extra-hepatic cholangiocarcinoma: new insight into epidemiology and risk factors.World J Gastrointest Oncol2010;2:407-16 PMCID:PMC3000454

[3] Primrose JN,Palmer DH.BILCAP study groupCapecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study.Lancet Oncol2019;20:663-73

[4] Buettner S,IJzermans JN.Intrahepatic cholangiocarcinoma: current perspectives.Onco Targets Ther2017;10:1131-42 PMCID:PMC5328612

[5] Squires MH,Dillhoff M,Pawlik TM.Challenges of surgical management of intrahepatic cholangiocarcinoma.Expert Rev Gastroenterol Hepatol2018;12:671-81

[6] Valle J,Palmer DH.ABC-02 Trial InvestigatorsCisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.N Engl J Med2010;362:1273-81

[7] Rizvi S,Hallemeier CL,Gores GJ.Cholangiocarcinoma - evolving concepts and therapeutic strategies.Nat Rev Clin Oncol2018;15:95-111 PMCID:PMC5819599

[8] Brown ZJ,Pawlik TM.Developments in FGFR and IDH inhibitors for cholangiocarcinoma therapy.Expert Rev Anticancer Ther2023;23:257-64

[9] Doherty B,Palmer WC.Update on the diagnosis and treatment of cholangiocarcinoma.Curr Gastroenterol Rep2017;19:2

[10] Masarone M.Hepatitis c virus infection and non-hepatocellular malignancies in the daa era: a systematic review and meta-analysis.Liver Int2019;39:1292-306

[11] Tanaka M,Tsukuma H,Oshima A.Risk factors for intrahepatic cholangiocarcinoma: a possible role of hepatitis B virus.J Viral Hepat2010;17:742-8 PMCID:PMC3020326

[12] Kubo S,Tanaka S.Occupational cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane.Ann Gastroenterol Surg2018;2:99-105 PMCID:PMC5881298

[13] Tao LY,He XD.Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma.Am Surg2010.76:p. 1210-3

[14] Moro A,Sahara K.The impact of preoperative CA19-9 and CEA on outcomes of patients with intrahepatic cholangiocarcinoma.Ann Surg Oncol2020;27:2888-901

[15] Valls C,Puig I.Intrahepatic peripheral cholangiocarcinoma: CT evaluation.Abdom Imaging2000;25:490-6

[16] Seo N,Choi JY.Cross-sectional imaging of intrahepatic cholangiocarcinoma: development, growth, spread, and prognosis.AJR Am J Roentgenol2017;209:W64-75

[17] Blechacz B.Cholangiocarcinoma: current knowledge and new developments.Gut Liver2017;11:13-26 PMCID:PMC5221857

[18] Fábrega-Foster K,Pawlik TM.Multimodality imaging of intrahepatic cholangiocarcinoma.Hepatobiliary Surg Nutr2017;6:67-78 PMCID:PMC5411278

[19] Fujita N,Nishie A.Mass-forming intrahepatic cholangiocarcinoma: enhancement patterns in the arterial phase of dynamic hepatic CT - correlation with clinicopathological findings.Eur Radiol2017;27:498-506

[20] Hewitt DB,Pawlik TM.Surgical management of intrahepatic cholangiocarcinoma.Expert Rev Anticancer Ther2022;22:27-38

[21] Lamarca A,Chander A.¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET) for patients with biliary tract cancer: Systematic review and meta-analysis.J Hepatol2019;71:115-29

[22] Spolverato G,Cucchetti A.Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma?.Cancer2015;121:3998-4006

[23] Lamarca A,McNamara MG.Current standards and future perspectives in adjuvant treatment for biliary tract cancers.Cancer Treat Rev2020;84:101936

[24] Zhang XF,Chakedis J.Perioperative and long-term outcome for intrahepatic cholangiocarcinoma: impact of major versus minor hepatectomy.J Gastrointest Surg2017;21:1841-50

[25] Le Roy B,Pittau G.Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma.Br J Surg2018;105:839-47

[26] Kato A,Ohtsuka M.Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study.Ann Surg Oncol2013;20:318-24

[27] Moris D,Kim C,Morse MA.Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians.CA Cancer J Clin2023;73:198-222

[28] D'Angelica M,Weber S.The role of staging laparoscopy in hepatobiliary malignancy: prospective analysis of 401 cases.Ann Surg Oncol2003;10:183-9

[29] Goere D,Pessaux P.Utility of staging laparoscopy in subsets of biliary cancers: laparoscopy is a powerful diagnostic tool in patients with intrahepatic and gallbladder carcinoma.Surg Endosc2006;20:721-5

[30] Weber SM,O'Reilly EM,Miyazaki M.Intrahepatic cholangiocarcinoma: expert consensus statement.HPB2015;17:669-80 PMCID:PMC4527852

[31] Shindoh J,Aloia TA.Optimal future liver remnant in patients treated with extensive preoperative chemotherapy for colorectal liver metastases.Ann Surg Oncol2013;20:2493-500 PMCID:PMC3855465

[32] Zorzi D,Pawlik TM,Vauthey JN.Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases.Br J Surg2007;94:274-86

[33] Abdalla EK,Doherty D,Vauthey JN.Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization.Arch Surg2002;137:675-80; discussion 680

[34] Abdalla EK.Resection of colorectal liver metastases.J Gastrointest Surg2011;15:416-9

[35] Vauthey JN,Do KA.Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.Surgery2000;127:512-9

[36] Kubota K,Kusaka K.Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors.Hepatology1997;26:1176-81

[37] Thirunavukarasu P.Preoperative assessment and optimization of the future liver remnant.Surg Clin North Am2016;96:197-205

[38] Rassam F,van Lienden KP.Comparison of functional and volumetric increase of the future remnant liver and postoperative outcomes after portal vein embolization and complete or partial associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).Ann Transl Med2020;8:436 PMCID:PMC7210209

[39] Li M,Song J.Preoperative ICG test to predict posthepatectomy liver failure and postoperative outcomes in hilar cholangiocarcinoma.Biomed Res Int2021;2021:8298737 PMCID:PMC7925035

[40] Owen ML.Minimally invasive surgery for intrahepatic cholangiocarcinoma: patient selection and special considerations.Hepat Med2021;13:137-43 PMCID:PMC8866996

[41] Lee W,Kim JY.Comparison of perioperative and oncologic outcomes between open and laparoscopic liver resection for intrahepatic cholangiocarcinoma.Surg Endosc2016;30:4835-40

[42] Wei F,Cai L,Liang X.Can laparoscopic liver resection provide a favorable option for patients with large or multiple intrahepatic cholangiocarcinomas?.Surg Endosc2017;31:3646-55

[43] Uy BJ,Yoon YS.Laparoscopic liver resection for intrahepatic cholangiocarcinoma.J Laparoendosc Adv Surg Tech A2015;25:272-7

[44] Ratti F,Ariotti R.Safety and feasibility of laparoscopic liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma: a propensity score-based case-matched analysis from a single institution.Surg Endosc2016;30:1999-2010

[45] Neoptolemos JP,Cox TF.European Study Group for Pancreatic CancerEffect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.JAMA2012;308:147-56

[46] Spolverato G,Kim Y.The impact of surgical margin status on long-term outcome after resection for intrahepatic cholangiocarcinoma.Ann Surg Oncol2015;22:4020-8

[47] de Jong MC,Sotiropoulos GC.Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment.J Clin Oncol2011;29:3140-5

[48] Endo Y,Moazzam Z.Higher tumor burden status dictates the impact of surgical margin status on overall survival in patients undergoing resection of intrahepatic cholangiocarcinoma.Ann Surg Oncol2023;30:2023-32

[49] NCCN guidelines version: hepatobiliary cancers. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1438 [Last accessed on 12 May 2023]

[50] Cloyd JM,Pawlik TM.The landmark series: intrahepatic cholangiocarcinoma.Ann Surg Oncol2020;27:2859-65

[51] Zhang XF,Kimbrough CW.Lymphadenectomy for intrahepatic cholangiocarcinoma: has nodal evaluation been increasingly adopted by surgeons over time? a national database analysis.J Gastrointest Surg2018;22:668-75

[52] Zhang XF,Dong DH.Number and station of lymph node metastasis after curative-intent resection of intrahepatic cholangiocarcinoma impact prognosis.Ann Surg2021;274:e1187-95

[53] Reames BN,Koerkamp BG.Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis.J Surg Oncol2017;116:133-9

[54] Conci S,Ercolani G.Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma.Eur J Surg Oncol2020;46:1727-33

[55] Ali SM,Zaydfudim VM,Nagorney DM.Role of major vascular resection in patients with intrahepatic cholangiocarcinoma.Ann Surg Oncol2013;20:2023-8

[56] Franssen S,Jolissaint JS.Comparison of hepatic arterial infusion pump chemotherapy vs resection for patients with multifocal intrahepatic cholangiocarcinoma.JAMA Surg2022;157:590-6 PMCID:PMC9096688

[57] Wright GP,Jones H.Surgical resection does not improve survival in multifocal intrahepatic cholangiocarcinoma: a comparison of surgical resection with intra-arterial therapies.Ann Surg Oncol2018;25:83-90

[58] Cercek A,Tan BR.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 Oncol2020;6:60-7 PMCID:PMC6824231

[59] Bekki Y,Takahashi H,Gunasekaran G.Recurrent intrahepatic cholangiocarcinoma - review.Front Oncol2021;11:776863 PMCID:PMC8567135

[60] Zhang XF,Bagante F.Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.Br J Surg2018;105:848-56

[61] Hu LS,Weiss M.Recurrence patterns and timing courses following curative-intent resection for intrahepatic cholangiocarcinoma.Ann Surg Oncol2019;26:2549-57

[62] Spolverato G,Alexandrescu S.Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative-intent surgical resection.Ann Surg Oncol2016;23:235-43

[63] Bartsch F,Rückert F.German ICC Collaboration GroupRepeated resection for recurrent intrahepatic cholangiocarcinoma: a retrospective German multicentre study.Liver Int2021;41:180-91

[64] Gani F,Kim Y.Program death 1 immune checkpoint and tumor microenvironment: implications for patients with intrahepatic cholangiocarcinoma.Ann Surg Oncol2016;23:2610-7

[65] Oh D,Qin S.A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1.JCO2022;40:378-378

[66] Zhu AX,Kim Y.Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets.Ann Surg Oncol2014;21:3827-34 PMCID:PMC4324507

[67] Chmiel P,Rawicz-Pruszyński K,Skórzewska M.FGFR inhibitors in cholangiocarcinoma-a novel yet primary approach: where do we stand now and where to head next in targeting this axis?.Cells2022;11:3929 PMCID:PMC9737583

[68] Lowery MA,Jordan E.Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention.Clin Cancer Res2018;24:4154-61 PMCID:PMC6642361

[69] Javle MM,Macarulla T.Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: interim results from the phase 2 study FIDES-01.JCO2022;40:427-427

[70] Kim SH,Choi GH,Kim KS.Extent of lymph node dissection for accurate staging in intrahepatic cholangiocarcinoma.J Gastrointest Surg2022;26:70-6