Abstract
Objective
Citation analysis represents one of the best available methods to identify the most influential articles. This study aimed to identify and characterize the top 100 highly cited articles (T100) that focus on hepatocellular carcinoma and to reveal the trends in accomplishments within this field.
Methods
A search of the Thomson Reuters Web of Science citation indexing database was conducted using terms related to hepatocellular carcinoma. The T100 were selected and analyzed further based on the number of citations, authorship, year of publication, journal, country of origin, institution, and article type.
Results
Hepatology published the highest number of papers (n = 15), and the United States produced the highest number of contributions (n = 31). Barcelona University was the institution with the highest number of articles in the T100 (n = 9). The T100 articles included 35 observational studies, 13 randomized control studies, 25 basic research articles, 18 reviews, seven clinical guidelines, and two meta-analyses.
Conclusions
This is the first bibliometric study to identify the most influential papers in hepatocellular carcinoma research. This report presents major advances and changes in research regarding hepatocellular carcinoma and can serve as a guide for writing a citable article.
Keywords
Introduction
Hepatocellular carcinoma (HCC) is one of the most common cancers and is a leading cause of cancer death worldwide. 1 Numerous articles have been published regarding HCC in various fields, such as clinical pathology, clinical oncology, clinical radiology, and basic research. Through such efforts, great progress has been made in understanding and treating HCC. However, it is difficult to identify the most influential or important articles among the considerable number of publications.
Establishing a citation rank list can identify which published works have had the greatest intellectual influence. 2 For example, researchers with medical and surgical specialties have utilized citation rank analysis to identify the most influential articles in their fields, such as orthopedic surgery, 3 plastic surgery, 4 general surgery, 5 and oncology. 6 Notably, there is a need to determine the most influential research themes in the diagnosis and management of HCC. Additionally, there is a need to assemble a registry of the most cited papers. Although a comprehensive analysis of overall research trends in the past 10 years has been performed for HCC, 7 a wide-ranging bibliometric analysis of HCC research has not been performed in terms of the most influential papers in the field. Therefore, this study aimed to identify and characterize the top 100 highly cited articles (T100) that have focused on HCC and to highlight trends in accomplishments within this field.
Materials and methods
A search of the Thomson Reuters Web of Science citation indexing database was conducted for the period from 1 January 1983 to 11 October 2017 (the beginning of the search window was limited by the terms of our access to the database). The following search terms were used: “hepatocellular carcinoma,” “hepatoma”, “liver cancer,” and “liver cell carcinoma.” The search was conducted on a single day, 11 October 2017, to minimize adjustments to the number of citations during the search. The search strategy was limited to full manuscripts published in English, and the results were sorted by the number of citations, in accordance with the method initially developed by Paladugu and colleagues. 5 The final Web of Science database interrogation was performed jointly by two independent reviewers (HJW and KH) to ensure its relevance to HCC. The selected T100 articles were then evaluated further based on the following parameters: number of citations, authorship, year of publication, journal, country of origin, institution, and article type. Because a potential bias in this type of study is that older manuscripts may have a higher number of citations because of the extended period since publication, a “citation rate” was determined by dividing the number of citations by the number of years since publication.
Statistical analysis of the data—comprising one-way analysis of variance of the citation numbers of clinical research, review, and basic research articles—was performed using IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY, USA). Differences with P < 0.05 were considered to be statistically significant.
Results
The Web of Science database search returned 71,639 full manuscript publications. Table 1 lists the 100 most frequently cited articles from the initial list. The number of citations ranged from 500 for Okuda et al. 8 (“Hepatocellular carcinoma: Recent progress”) to 4,730 for Llovet et al. 9 (“Sorafenib in advanced hepatocellular carcinoma”). The mean number of citations for all articles was 1,002.67 ± 718.57. The citation rate was highest for the review article, “Management of hepatocellular carcinoma: An update,” by Bruix et al (543.17). 10
The top 100 cited papers on HCC.
Thirteen authors had more than two first or last authorships in the T100 (Table 2). J. Llovet had the highest number of first authorships (n = 10; 17,452 citations), and J. Bruix had the highest number of last authorships (n = 9; 16,358 citations).
First and last authors with multiple articles in the top 100.
The selected T100 were published between 1983 and 2012, with half of the articles published from 2001 to 2010 (n = 54; see Figure 1). The year that yielded the highest number of T100 articles was 1999 (n = 10; 10,706 citations), followed by 2006 (n = 9; 8,013 citations). The oldest article featured in the T100 was published in 1983 by Yamada et al. (“Hepatic artery embolization in 120 patients with unresectable hepatoma”). The most recent article, published in 2012 by El-Serag et al., 11 described an investigation of the epidemiology of viral hepatitis and HCC.
Numbers of publications stratified by 5-year intervals from 1983 to 2015.
The T100 were published in 31 journals (Table 3). Although Hepatology had a lower 5-year impact factor than the New England Journal of Medicine (NEJM) (11.930 vs. 64.201), Hepatology published the most papers in the T100 (n = 15; 14,586 citations). NEJM generated the highest number of citations (n = 11; 17,105 citations).
Journals with four or more articles in the top 100.
The highest number of contributions was produced by groups in the United States (n = 31), followed by Japan (n = 17) and Spain (n = 16) (Figure 2). The University of Barcelona was the institution with the highest number of articles in the T100 (n = 9; 14,012 citations; Table 4).
Distribution of the top 100 articles by country of origin from 1983 to 2015.
Institutions with three or more articles in the top 100.
The T100 articles included 35 observational studies, 25 basic research articles, 18 reviews, 13 randomized control studies, seven clinical guidelines, and two meta-analyses. Figure 3 shows the topical distribution of the T100 by 5-year periods from 1983 to 2015 (the first period is truncated to 1983-1985 because of the search constraints). After 2000, the proportion of observational studies declined, whereas the proportion of basic research studies increased.
Publication trends for specific article types stratified by 5-year intervals from 1983 to 2015.
We subdivided the T100 by article types: clinical research (n = 48), review article (n = 27), and basic research (n = 25). Although clinical research articles comprised approximately half of the T100, the mean number of citations was significantly higher for review articles than for other article types (P = 0.010; Figure 4).
Bar graph showing the number of citations (mean ± standard deviation) for the top 100 articles from 1983 to 2015, stratified by article type (clinical research, review article, basic research). Black bar, mean; whiskers, standard deviation; box, 95% confidence interval.
Discussion
Bibliometric analysis identifies the most influential articles in the field during the past several decades, highlights contributions that have led to significant advances, and reveals current trends in the field. This type of analysis reveals key advancements and provides a useful perspective on historical developments in the field. 12 The top 100 highly cited articles worldwide have been published in various fields, such as cardiology, 13 neurosurgery, 14 endocrinology, 15 radiology, 16 and ophthalmology. 17 However, to the best of our knowledge, this study is the first bibliometric analysis of the most influential citations regarding HCC.
The number of citations of an article depends partly on when the article was published, as citations accumulate over time. However, with the exception of the 2011 to 2015 period, the number of articles included in the T100 tended to increase for newer articles; thus, more than half of the articles in our study were published between 2001 and 2010. These findings are consistent with those of other recent bibliometric analyses.12,13,17 The results demonstrate that new articles with novel discoveries and advanced technologies continue to be published, and that newer articles receive more citations than previous articles.
The leading article by Llovet et al. 9 described a multicenter, randomized control study on sorafenib for treatment of advanced HCC, which may be the most important advancement in medical management of HCC. Some bibliometric studies have reported that journals with high impact factors, such as NEJM or Nature, were the leading journals within their respective fields.18–20 However, we found that Hepatology and Gastroenterology were the most productive journals, despite their relatively low impact factors; indeed, they published 15 and 10 articles in the T100, respectively. This result highlights a growing trend in which highly influential articles are published in specialized journals, and are not limited to the most well-known general medical journals.
Although the United States was the most productive country in terms of research regarding HCC, most of the top productive institutions were evenly distributed among other countries, such as Japan, Spain, and Italy. Of note, countries within East Asia produced more than one-quarter of the T100 articles, in contrast to the trend reported in other bibliometric analyses. These countries had a particularly high prevalence of viral hepatitis and subsequent occurrence of HCC. 21 The high prevalence of HCC led to elevated production of influential studies, similar to the relationship with regional disease rates shown in a bibliometric analysis of influential studies regarding gastric cancer. 22 According to a recent bibliometric analysis, 7 China contributed the most publications regarding overall HCC research in recent decades, although it was the fifth country in terms of T100 articles in the present study. Because of the high prevalence of HCC in China, extensive research funding has been used to study diagnosis and treatment of HCC, such that China has shown considerable progress in HCC research.
Since the year 2000, the proportion of clinical research studies (e.g., observational studies and randomized control trials) has gradually decreased, relative to overall HCC-related publications, whereas the proportions of basic research studies, clinical guidelines, and meta-analyses have increased (Figure 3). This phenomenon suggests that the accumulation of knowledge and experience related to HCC have led to additional publications comprising comprehensive analyses, rather than intermittent clinical trials. In addition, the remarkable developments in molecular biology and genetics with regard to HCC have facilitated publication of basic research studies in high impact journals: Nature, Nature Medicine, Cancer Cell, and Science. Nevertheless, clinical studies comprise one-half of publications in the T100, indicating that clinical research continues to attract the interest of researchers in the field. 23
In bibliometric analysis for other gastrointestinal cancers, there has been increasing publication of articles regarding basic cancer research, such as cancer genetics, chemotherapy regimens, and monoclonal antibody. However, one-half of the top 100 HCC studies comprised clinical studies, such that there was a relative lack of basic research studies on HCC, compared with studies of other gastrointestinal malignancies. Therefore, further developments involving chemotherapeutic agents and basic cancer research are needed to improve the survival rate of HCC.
There are various treatment modalities for HCC: liver transplantation, hepatectomy, radiofrequency ablation, transarterial chemoembolization, and chemotherapy. The top 10 of the T100 primarily included studies involving treatment modalities of HCC (n = 6). Although the surgical method for resolution of HCC is regarded as the preferred approach, 24 articles describing non-surgical treatments were more frequently represented in the top 10, as well as the overall T100. This may be due to the increasing need for treatment of unresectable and recurrent HCC. This trend is consistent with that described in bibliometric analyses regarding other gastrointestinal cancers.12,22,25 Among the top 10 articles, two described randomized control trials of the effects of sorafenib on HCC; one of these two was the most highly cited, and was published in NEJM.
The main limitation of this manuscript is the potential for several types of bias, which may have affected the results. Disproportionate or inappropriate citations may result from institutional bias, language bias, self-citation, powerful person bias, in-house bias, or the deliberate omission of citations for a variety of reasons, including competition. 26 Moreover, older articles may receive more citations due to the relative length of time since their publication. To correct this bias, the citation rate was analyzed, in which the number of citations was divided by the number of years since publication. Despite these attempts, the lead time for publication of citing articles may have resulted in under-representation of more recent articles in our study. 22 Another limitation is the inclusion of only the first and senior authors and the institutions of the first author. Thus, several authors in the T100 may have contributed to multiple manuscripts, although in a lesser role than that of first or senior author.
Conclusion
To our knowledge, this is the first bibliometric study to identify the most influential papers in HCC research. This report presents major advances and changes in research regarding HCC and can serve as a guide for writing a citable article.
Declaration of conflicting interest
The authors declare that there is no conflict of interest.
Footnotes
Funding
This research was supported by Hallym University Research Fund 2018 (HURF-2018-17).