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      Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

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          Abstract

          Background

          To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status.

          Methods

          In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA).

          Results

          About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients ( P < 0.01). In Child‐Pugh B/C patients, this survival difference became nonsignificant ( P = 0.22). Increased NLR and SII were associated with decreased survival ( P < 0.01), while dichotomized PLR was not ( P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child‐Pugh class A (n = 94), low‐NLR had higher OS vs high‐NLR (25.4 vs 12.2 months, P < 0.01). In Child‐Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low‐ vs high‐NLR: 6.7 vs 2.9 months, P = 0.2). Child‐Pugh class acted as an effect modifier on MVA for NLR ( P = 0.0124).

          Conclusions

          The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.

          Abstract

          The neutrophil‐to‐lymphocyte ratio (NLR) has the strongest impact as a prognostic marker in intrahepatic cholangiocarcinoma (ICC) versus the platelet‐to‐lymphocyte ratio and systemic immune‐inflammation index, and increased NLR is associated with decreased survival in ICC. The NLR has decreased prognostic utility in patients with advanced liver disease.

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          Most cited references36

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          Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

          T. Patel (2001)
          Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma. Between 1973 and 1997, the incidence and mortality rates from intrahepatic cholangiocarcinoma markedly increased, with an estimated annual percent change (EAPC) of 9.11% (95% CI, 7.46 to 10.78) and 9.44% (95%, CI 8.46 to 10.41), respectively. The age-adjusted mortality rate per 100,000 persons for whites increased from 0.14 for the period 1975-1979 to 0.65 for the period 1993-1997, and that for blacks increased from 0.15 to 0.58 over the same period. The increase in mortality was similar across all age groups above age 45. The relative 1- and 2-year survival rates following diagnosis from 1989 to 1996 were 24.5% and 12.8%, respectively. In conclusion, there has been a marked increase in the incidence and mortality from intrahepatic cholangiocarcinoma in the United States in recent years. This tumor continues to be associated with a poor prognosis.
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            Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

            Nader N Massarweh, Hashem El-Serag (2017)
            Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most frequently occurring types of primary liver cancer and together are among the most common incident cancers worldwide. There are a number of modifiable and nonmodifiable HCC and ICC risk factors that have been reported. A review of the existing literature the epidemiology and risk factors for HCC and ICC was performed. There are a number of major infectious, lifestyle, metabolic, and heritable risk factors for both HCC and ICC. Some of these risk factors are either potentially preventable (eg, alcohol and tobacco use) or are currently treatable (eg hepatitis infection). In most cases, the molecular pathway or mechanism by which these etiologic factors cause primary liver cancer has not been well delineated. However, in nearly all cases, it is believed that a given risk factor causes liver injury and inflammation which results in chronic liver disease. Given the rising prevalence of several common HCC and ICC risk factors in the western world, the best opportunities for improving the care of these patients are either through the prevention of modifiable risk factors that are associated with the development of chronic liver disease or the identification of at risk patients, ensuring they are appropriately screened for the development of primary liver cancer, and initiating treatment early.
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              Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?

              Yasser H. Shaib, Jessica A. Davila, Kathryn McGlynn … (2004)
              The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size <5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975-1979 to 26.3% in 1995-1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size <5 cm, and microscopic confirmation suggest a true increase of ICC.
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                Author and article information

                Contributors
                Hyun S. Kim:
                ORCID: https://orcid.org/0000-0002-3077-9989
                kevin.kim@yale.edu
                Journal
                Journal ID (nlm-ta): Cancer Med
                Journal ID (iso-abbrev): Cancer Med
                Journal ID (doi): 10.1002/(ISSN)2045-7634
                Journal ID (publisher-id): CAM4
                Title: Cancer Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2045-7634
                Publication date (Electronic): 20 August 2019
                Publication date Collection: October 2019
                Volume: 8
                Issue: 13 ( doiID: 10.1002/cam4.v8.13 )
                Pages: 5916-5929
                Affiliations
                [ 1 ] Section of Interventional Radiology, Department of Radiology and Biomedical Imaging Yale School of Medicine New Haven Connecticut
                [ 2 ] Department for Diagnostic and Interventional Radiology University Medical Center Goettingen Goettingen Germany
                [ 3 ] Department of Diagnostic and Interventional Radiology and Neuroradiology University Hospital Essen, University of Duisburg‐Essen Essen Germany
                [ 4 ] Section of Medical Oncology, Department of Internal Medicine Yale School of Medicine New Haven Connecticut
                [ 5 ] Yale Cancer Center, Yale School of Medicine New Haven Connecticut
                Author notes
                [*] [* ] Correspondence

                Hyun S. Kim, Yale School of Medicine, Yale Cancer Center, 330 Cedar Street, P.O. Box 208042, New Haven, CT 06510.

                Email: kevin.kim@ 123456yale.edu

                Author information
                https://orcid.org/0000-0002-3077-9989
                Article
                Publisher ID: CAM42373
                DOI: 10.1002/cam4.2373
                PMC ID: 6792510
                PubMed ID: 31429524
                SO-VID: 64c9774f-c6e3-4fbe-8333-35f5f7d1eb3e
                Copyright © © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 February 2019
                Date revision received : 08 June 2019
                Date accepted : 12 June 2019
                Page count
                Figures: 3, Tables: 3, Pages: 14, Words: 7063
                Funding
                Funded by: U.S. Department of Defense , open-funder-registry 10.13039/100000005;
                Award ID: CA160741
                Categories
                Subject: Original Research
                Subject: Clinical Cancer Research
                Subject: Original Research
                Custom metadata
                source-schema-version-number 2.0
                cover-date October 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.0 mode:remove_FC converted:10.10.2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: bile ducts,cholangiocarcinoma,intrahepatic,liver cirrhosis,lymphocytes,neutrophils,platelets
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: bile ducts, cholangiocarcinoma, intrahepatic, liver cirrhosis, lymphocytes, neutrophils, platelets

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