Advertisement

Preoperative prediction model of microvascular invasion in patients with hepatocellular carcinoma

Published:August 19, 2022DOI:https://doi.org/10.1016/j.hpb.2022.08.007

      Abstract

      Background

      Microvascular invasion (MVI) is an adverse factor for the prognosis of patients with hepatocellular carcinoma (HCC). We aimed to construct a preoperative prediction model for MVI, thereby providing a reference for clinicians in formulating treatment options for HCC.

      Methods

      A total of 360 patients with non-metastatic HCC were retrospectively enrolled. We used logistic regression analysis to screen out independent risk factors for MVI and further constructed a predictive model for MVI. The performance of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

      Results

      Logistic regression analysis revealed that fibrinogen (>4 g/L) (OR: 6.529), alpha-fetoprotein (≥ 400 ng/mL) (OR: 2.676), cirrhosis (OR: 2.25), tumor size (OR: 1.239), and poor tumor border (OR: 3.126) were independent risk factors of MVI. The prediction model of MVI had C-index of 0.746 and 0.772 in the training and validation cohorts, respectively. The calibration curves showed good agreement between actual and predicted MVI risk. Finally, DCA reveals that this model has good clinical utility.

      Conclusion

      The nomogram-based model we established can predict the preoperative MVI well and provides reference for surgeons to make clinical treatment decisions.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to HPB
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • Laversanne M.
        • Soerjomataram I.
        • Jemal A.
        • et al.
        Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2021; 71 (2021-05-01): 209-249https://doi.org/10.3322/caac.21660
        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • Siegel R.L.
        • Torre L.A.
        • Jemal A.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2018; 68 (2018-11-01): 394-424https://doi.org/10.3322/caac.21492
        • Akoad M.E.
        • Pomfret E.A.
        Surgical resection and liver transplantation for hepatocellular carcinoma.
        Clin Liver Dis. 2015; 19 (2015-05-01): 381-399https://doi.org/10.1016/j.cld.2015.01.007
        • Bruix J.
        • Gores G.J.
        • Mazzaferro V.
        Hepatocellular carcinoma: clinical frontiers and perspectives.
        GUT. 2014; 63 (2014-05-01): 844-855https://doi.org/10.1136/gutjnl-2013-306627
        • Qi Y.P.
        • Zhong J.H.
        • Liang Z.Y.
        • Zhang J.
        • Chen B.
        • Chen C.Z.
        • et al.
        Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion.
        Am J Surg. 2019; 217 (2019-04-01): 739-744https://doi.org/10.1016/j.amjsurg.2018.07.054
        • Song T.
        • Wang C.
        • Guo C.
        • Liu Q.
        • Zheng X.
        Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition.
        J Cancer. 2018; 9 (2018-01-20): 2650-2658https://doi.org/10.7150/jca.25188
        • Zhang X.
        • Li J.
        • Shen F.
        • Lau W.Y.
        Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma.
        J Gastroenterol Hepatol. 2018; 33 (2018-02-01): 347-354https://doi.org/10.1111/jgh.13843
        • Zhao H.
        • Chen C.
        • Gu S.
        • Yan X.
        • Jia W.
        • Mao L.
        • et al.
        Anatomical versus non-anatomical resection for solitary hepatocellular carcinoma without macroscopic vascular invasion: a propensity score matching analysis.
        J Gastroenterol Hepatol. 2017; 32 (2017-04-01): 870-878https://doi.org/10.1111/jgh.13603
        • Cucchetti A.
        • Qiao G.L.
        • Cescon M.
        • Li J.
        • Xia Y.
        • Ercolani G.
        • et al.
        Anatomic versus nonanatomic resection in cirrhotic patients with early hepatocellular carcinoma.
        Surgery. 2014; 155 (2014-03-01): 512-521https://doi.org/10.1016/j.surg.2013.10.009
        • Han J.
        • Li Z.L.
        • Xing H.
        • Wu H.
        • Zhu P.
        • Lau W.Y.
        • et al.
        The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study.
        HPB (Oxford). 2019; 21 (2019-08-01): 962-971https://doi.org/10.1016/j.hpb.2018.11.005
        • Vitale A.
        • Cucchetti A.
        • Qiao G.L.
        • Cescon M.
        • Li J.
        • Ramirez M.R.
        • et al.
        Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on "number of patients needed to transplant" as measure of transplant benefit.
        J Hepatol. 2014; 60 (2014-06-01): 1165-1171https://doi.org/10.1016/j.jhep.2014.01.022
        • Feng S.T.
        • Jia Y.
        • Liao B.
        • Huang B.
        • Zhou Q.
        • Li X.
        • et al.
        Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI.
        Eur Radiol. 2019; 29 (2019-09-01): 4648-4659https://doi.org/10.1007/s00330-018-5935-8
        • Zhao W.
        • Liu W.
        • Liu H.
        • Yi X.
        • Hou J.
        • Pei Y.
        • et al.
        Preoperative prediction of microvascular invasion of hepatocellular carcinoma with IVIM diffusion-weighted MR imaging and Gd-EOB-DTPA-enhanced MR imaging.
        PLoS ONE. 2018; 13 (2018-01-20)e197488https://doi.org/10.1371/journal.pone.0197488
        • Ni M.
        • Zhou X.
        • Lv Q.
        • Li Z.
        • Gao Y.
        • Tan Y.
        • et al.
        Radiomics models for diagnosing microvascular invasion in hepatocellular carcinoma: which model is the best model?.
        Cancer Imaging. 2019; 19 (2019-08-28): 60https://doi.org/10.1186/s40644-019-0249-x
        • Xu X.
        • Zhang H.L.
        • Liu Q.P.
        • Sun S.W.
        • Zhang J.
        • Zhu F.P.
        • et al.
        Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma.
        J Hepatol. 2019; 70 (2019-06-01): 1133-1144https://doi.org/10.1016/j.jhep.2019.02.023
        • Liu S.
        • Li H.
        • Guo L.
        • Zhang B.
        • Zhou B.
        • Zhang W.
        • et al.
        Tumor size affects efficacy of adjuvant transarterial chemoembolization in patients with hepatocellular carcinoma and microvascular invasion.
        Oncologist. 2019; 24 (2019-04-01): 513-520https://doi.org/10.1634/theoncologist.2018-0305
        • Nitta H.
        • Allard M.A.
        • Sebagh M.
        • Ciacio O.
        • Pittau G.
        • Vibert E.
        • et al.
        Prognostic value and prediction of extratumoral microvascular invasion for hepatocellular carcinoma.
        Ann Surg Oncol. 2019; 26 (2019-08-01): 2568-2576https://doi.org/10.1245/s10434-019-07365-0
        • Imura S.
        • Teraoku H.
        • Yoshikawa M.
        • Ishikawa D.
        • Yamada S.
        • Saito Y.
        • et al.
        Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria.
        Int J Clin Oncol. 2018; 23 (2018-02-01): 98-103https://doi.org/10.1007/s10147-017-1189-8
        • Hyun S.H.
        • Eo J.S.
        • Song B.I.
        • Lee J.W.
        • Na S.J.
        • Hong I.K.
        • et al.
        Preoperative prediction of microvascular invasion of hepatocellular carcinoma using (18)F-FDG PET/CT: a multicenter retrospective cohort study.
        Eur J Nucl Med Mol Imaging. 2018; 45 (2018-05-01): 720-726https://doi.org/10.1007/s00259-017-3880-4
        • Hu H.T.
        • Wang Z.
        • Huang X.W.
        • Chen S.L.
        • Zheng X.
        • Ruan S.M.
        • et al.
        Ultrasound-based radiomics score: a potential biomarker for the prediction of microvascular invasion in hepatocellular carcinoma.
        Eur Radiol. 2019; 29 (2019-06-01): 2890-2901https://doi.org/10.1007/s00330-018-5797-0
        • Mosesson M.W.
        Fibrinogen and fibrin structure and functions.
        J Thromb Haemost. 2005; 3 (2005-08-01): 1894-1904https://doi.org/10.1111/j.1538-7836.2005.01365.x
        • Tennent G.A.
        • Brennan S.O.
        • Stangou A.J.
        • O'Grady J.
        • Hawkins P.N.
        • Pepys M.B.
        Human plasma fibrinogen is synthesized in the liver.
        Blood. 2007; 109 (2007-03-01): 1971-1974https://doi.org/10.1182/blood-2006-08-040956
        • Vilar R.
        • Fish R.J.
        • Casini A.
        • Neerman-Arbez M.
        Fibrin(ogen) in human disease: both friend and foe.
        Haematologica. 2020; 105 (2020-01-20): 284-296https://doi.org/10.3324/haematol.2019.236901
        • Kattula S.
        • Byrnes J.R.
        • Wolberg A.S.
        Fibrinogen and fibrin in hemostasis and thrombosis.
        Arterioscler Thromb Vasc Biol. 2017; 37 (2017-03-01): e13-e21https://doi.org/10.1161/ATVBAHA.117.308564
        • Merlini M.
        • Rafalski V.A.
        • Rios C.P.
        • Gill T.M.
        • Ellisman M.
        • Muthukumar G.
        • et al.
        Fibrinogen induces microglia-mediated spine elimination and cognitive impairment in an Alzheimer's disease model.
        Neuron. 2019; 101 (2019-03-20): 1099-1108https://doi.org/10.1016/j.neuron.2019.01.014
        • Jiang N.
        • Zeng K.N.
        • Dou K.F.
        • Lv Y.
        • Zhou J.
        • Li H.B.
        • et al.
        Preoperative Alfa-fetoprotein and fibrinogen predict hepatocellular carcinoma recurrence after liver transplantation regardless of the milan criteria: model development with external validation.
        Cell Physiol Biochem. 2018; 48 (2018-01-20): 317-327https://doi.org/10.1159/000491731
        • He X.
        • Huang T.
        • Xue Y.
        • Zhang M.
        • Liu Q.
        • Wang Y.
        • et al.
        Association of preoperative plasma D-dimmer and fibrinogen and renal cell carcinoma outcome.
        J Cancer. 2019; 10 (2019-01-20): 4096-4105https://doi.org/10.7150/jca.31173
        • Lin Y.
        • Liu Z.
        • Qiu Y.
        • Zhang J.
        • Wu H.
        • Liang R.
        • et al.
        Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: a systematic review and meta-analysis.
        Eur J Surg Oncol. 2018; 44 (2018-10-01): 1494-1503https://doi.org/10.1016/j.ejso.2018.07.052
        • Wen J.
        • Yang Y.
        • Ye F.
        • Huang X.
        • Li S.
        • Wang Q.
        • et al.
        The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.
        Breast. 2015; 24 (2015-12-01): 745-750https://doi.org/10.1016/j.breast.2015.09.007
        • Zhong H.
        • Qian Y.
        • Fang S.
        • Wang Y.
        • Tang Y.
        • Gu W.
        Prognostic value of plasma fibrinogen in lung cancer patients: a meta-analysis.
        J Cancer. 2018; 9 (2018-01-20): 3904-3911https://doi.org/10.7150/jca.26360
        • Yang J.
        • Ma J.
        • Cheng S.
        • Wang Y.
        The combination of plasma fibrinogen concentration and neutrophil lymphocyte ratio (F-NLR) as a prognostic factor of epithelial ovarian cancer.
        Onco Targets Ther. 2020; 13 (2020-01-20): 7283-7293https://doi.org/10.2147/OTT.S264118
        • Tosi P.
        • Luzi P.
        • Leoncini L.
        • Rivano M.T.
        • Barbini P.
        • Pileri S.
        Mantle zone lymphoma: a morphometric comparison with centrocytic and immunocytic lymphomas and reactive secondary follicles.
        Hum Pathol. 1988; 19 (1988-11-01): 1293-1300https://doi.org/10.1016/s0046-8177(88)80284-3
        • Weisel J.W.
        • Litvinov R.I.
        Fibrin formation, structure and properties.
        Subcell Biochem. 2017; 82 (2017-01-20): 405-456https://doi.org/10.1007/978-3-319-49674-0_13
        • Sahni A.
        • Francis C.W.
        Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation.
        Blood. 2000; 96 (2000-12-01. PMID:11090059): 3772-3778
        • Zheng S.
        • Shen J.
        • Jiao Y.
        • Liu Y.
        • Zhang C.
        • Wei M.
        • et al.
        Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity.
        Cancer Sci. 2009; 100 (2009-05-01): 859-865https://doi.org/10.1111/j.1349-7006.2009.01115.x
        • Kinoshita A.
        • Onoda H.
        • Imai N.
        • Iwaku A.
        • Oishi M.
        • Tanaka K.
        • et al.
        Elevated plasma fibrinogen levels are associated with a poor prognosis in patients with hepatocellular carcinoma.
        Oncology. 2013; 85 (2013-01-20): 269-277https://doi.org/10.1159/000355502