Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 51-61
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.51
Current state and clinical outcome in Turkish patients with hepatocellular carcinoma
Omer Ekinci, Bulent Baran, Asli Cifcibasi Ormeci, Ozlem Mutluay Soyer, Suut Gokturk, Sami Evirgen, Arzu Poyanli, Mine Gulluoglu, Filiz Akyuz, Cetin Karaca, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu
Omer Ekinci, Asli Cifcibasi Ormeci, Ozlem Mutluay Soyer, Suut Gokturk, Sami Evirgen, Filiz Akyuz, Cetin Karaca, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu, Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
Omer Ekinci, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
Bulent Baran, Department of Gastroenterology, Koç University Hospital, Istanbul 34010, Turkey
Arzu Poyanli, Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
Mine Gulluoglu, Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
Author contributions: Ekinci O and Baran B contributed to primary investigator, acquisition, analysis and interpretation of data, statistical analysis; Ormeci AC, Soyer OM, Gokturk S and Evirgen S contributed to acquisition of data, patient recruitment; Poyanli A contributed to evaluation of radiological data; Gulluoglu M contributed to evaluation and analysis of liver specimens; Akyuz F, Karaca C, Demir K, Besisik F and Kaymakoglu S contributed to critical revision of the manuscript for important intellectual content; Kaymakoglu S contributed to mentor, primary investigator, study concept and design, study supervision; Ekinci O and Baran B contributed equally to the study.
Institutional review board statement: This study was reviewed and approved by the ethics committee of Istanbul Faculty of Medicine, Istanbul University. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. Document no: 2010/786-24, approval date: Nov 25, 2010.
Informed consent statement: This study is a retrospective cohort study, therefore informed consent to be included in the study is not required according to the regulations of Republic of Turkey. All the treatments were established and indicated treatment modalities, and no experimental tool or medication were used in the study. Nevertheless, all patients were needed to give written permission, before undergoing specific treatments including TACE, TARE, liver transplantation, and surgical resection. In addition, according to the regulations of Istanbul University, at admission all patients give informed consent for their medical information can be used for research purposes anonymously.
Conflict-of-interest statement: All authors declare that there are no financial or other relationships that might lead to a conflict of interest.
Data sharing statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sabahattin Kaymakoglu, MD, Professor, Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Cape, Istanbul 34390, Turkey.
Telephone: +90-212-4142000 Fax: +90-212-6319743
Received: August 20, 2017
Peer-review started: August 23, 2017
First decision: December 4, 2017
Revised: December 7, 2017
Accepted: December 29, 2017
Article in press: December 29, 2017
Published online: January 27, 2018
Research background

HCC is a leading cause of cancer-related death with curative treatment options limited to orthotopic liver transplantation, surgical resection and local ablation. Several prognostic scoring systems were developed to predict the prognosis for patients with HCC, and to individualize treatment by matching best therapeutic option with the patient who is most likely to benefit. Nevertheless, no classification is completely satisfactory because of many other risk factors which also influence patient survival.

Research motivation

Primary treatment modality, which must be among the most important determinants of patient outcome, has not been evaluated as a prognostic indicator in relation to other determinants of survival until now. Therefore, the authors investigated the association between established prognostic factors of HCC and treatment to show how chosen treatment modality affects the prognosis.

Research objectives

Primary objective of the study was to define potential factors that have influence on prognosis, specifically to determine survival benefit associated with primary treatment modality of HCC in a real-life setting. Secondary objective of the study was to find out the relationship between pre-diagnosis screening characteristics, clinical stage of the disease at diagnosis and overall survival.

Research methods

In the present study, the authors investigated clinical, etiological, and prognostic features in a large, single-center cohort of patients with HCC who were diagnosed, treated and followed-up in the last decade. The diagnosis was established by histopathological and/or radiological criteria that was based on the recommendations reported by the EASL panel of experts in 2001. The authors reviewed demographic, clinical and staging characteristics, laboratory data, etiology of primary liver disease, imaging characteristics and treatments of HCC patients. Number and size of nodules, total tumor diameter (TTD), type of tumor, presence of major vascular involvement and extrahepatic metastasis were determined according to baseline imaging records. Univariate and multivariate Cox regression analyses were performed to find out factors associated with overall survival of patients with HCC.

Research results

A total of 545 patients with HCC who were diagnosed and followed-up between January 2001 and August 2011 were included in the study. Predictor variables of vascular invasion and extrahepatic metastasis were investigated by univariate and multivariate logistic regression analyses. The authors showed that HBV infection, multinodular and diffuse-infiltrative HCC, TTD, and AFP level were associated with vascular invasion at initial diagnosis of HCC. At multivariate analysis, independent predictor variables of vascular invasion were found to be AFP > 200 ng/mL, TTD > 5 cm and HBV. The only predictor variable for the presence of extrahepatic metastasis at initial diagnosis was TTD. Stage of liver disease, tumor type, HBV infection, number of nodules, presence of vascular invasion and AFP level did not predict extrahepatic metastasis. The best survival outcome was achieved in patients with HCC who underwent surgical treatments as OLT and hepatic resection. Treatment modalities including TACE, Yttrium-90 radioembolization, RFA were also found to be associated with improved overall survival. Ethanol/acetic acid ablation was not associated with any survival benefit. Systemic treatment with sorafenib was associated with a survival advantage at a borderline significance compared with no treatment, which can be explained by low number of patients receiving systemic therapy. Patients who had regular follow-up and screening with AFP-ultrasonography were diagnosed at an earlier BCLC stage and had a significantly better survival.

Research conclusions

It has been known that liver functional reserve, tumor extension and alfa-fetoprotein level are among the most important determinants of patient survival. The authors showed that in addition to patient and tumor related factors, initial choice of treatment is a strong and independent predictor of survival. Survival benefit of non-curative treatments including transarterial chemoembolization and Yttrium-90 radioembolization has been an area of uncertainty. Transarterial chemoembolization and Yttrium-90 radioembolization provided a significant and comparable survival benefit in patients with hepatocellular carcinoma in the real-life setting.

Research perspectives

Primary modality of treatment for hepatocellular carcinoma is a major determinant of patient survival that should be incorporated while estimating prognosis in the future trials evaluating benefits of investigational new drugs.