Top classic citations in pancreatic cancer research

Background The number of times that articles are cited by is widely used to evaluate the impact of an article or an individual author has on its scientific community. This bibliometric analysis aimed to explore the top classic citations in pancreatic cancer (PC) research. Methods A computerized literature search was conducted using the database, the Science Citation Index Expanded. The top 100 highly cited articles were included and further analyzed. Results The most cited article had 3,032 citations, with a mean of 626 citations per paper. These highly cited articles were published in 37 journals, led by Cancer Research (15 articles). Of the 100 articles, 40 were observational studies, 36 dealt with basic science, and 14 were randomized controlled trials. These articles came from 11 countries, with the USA contributing 79 articles. Fifty-one institutions produced these 100 citation classics, led by Johns Hopkins University (20 articles). Twenty-seven persons authored two or more of the top-cited articles, led by Kern SE (6) and Yeo CJ (5). Conclusions This analysis of the top highly cited articles allows for the recognition of major advances in PC research and gives a historic perspective on the progress of this specialty of PC research.


Background
Currently, pancreatic cancer (PC) remains a fatal disease with poor prognosis [1]. In recent decades, significant growth has been seen in the field of pancreatic cancer research. Though these advancements in PC research are widely known by the clinicians, the most important papers are not commonly known and identified. Recently, many specialities and diseases have identified and analyzed their "citation classics" (the articles most highly cited or the articles cited more than 100 times) in their fields [2][3][4][5][6]. Besides, there were also a few journals which published their own citation classics [7,8]. The purpose of our present study was to identify the top classic citations in PC research.

Methods
A computerized literature search was conducted using the database, the Science Citation Index Expanded founded by the Institute for Scientific Information (1966( -Sep 25, 2015 [9]. The relevant articles were identified by searching using a highly sensitive search strategy, and all phases of the search strategy are shown in Table 1. There was no journal restriction. The top 100 highly cited articles were included for further analysis. The titles and abstracts of the articles would be reviewed to estimate whether they are related to PC research. We analyzed the articles and calculated the data according to the following predefined items: number of citations, publication year, country of origin, institution, journal, publication type (e.g., basic science, observational study), and authorship (only calculating the corresponding, first, and second author).

Results
The literature search involved 27,413 publications using the Science Citation Index Expanded founded by the Institute for Scientific Information (ISI) (1966-present). The top 100 highly cited articles were showed in Table 2 according to the number of citation. The most frequently cited article received 3032 citations, and the least frequently cited article received 330 citations. Twelve articles received more than 1000 citations. The mean number of citations per paper was 626. We also evaluated the 10year citations of the paper published before 2006. The most frequently cited article received 1354 citations, and the least frequently cited article received 5 citations. The proportions of 10-year after publication of 1970-1979, 1980-1989, 1990-1999, and 2000-2005 were 20.5, 41.2, 49.8, and 68.0%, respectively ( Table 3).
The top 100 classic citations were published from 1970 to 2013. The decade of 1990-1999 produced the most classic citations with 42 ones, followed by 37 ones from 2000 to 2009 (Fig. 1). The most classic papers published were 7 ones in 1993, 1997, 2004, and 2007.
The top-cited articles were published in 37 highimpact journals (Table 4), led by Cancer Research (15 articles), followed by Journal of Clinical Oncology (9), Annals of Surgery (9), and New England Journal of Medicine (8).
The 100 top-cited articles came from 11 countries, with the USA producing 79 articles, followed by UK with 6 ones, and Germany with 4 ones (Table 5). Altogether, 51 institutions produced these 100 topcited papers. Among them, 12 institutions produced 2 or more of the top-cited papers (Table 6), led by Johns Hopkins University (20 articles), followed by the University of Texas (7 articles), and Harvard University (7 articles).
In the 100 top-cited articles, 3 ones were authored by a single author and 5 ones by 2 authors. Twenty-seven persons authored two or more of the top citations. Table 6 presents a list of these "most frequent authors," which is led by Kern SE who authored 6 classic papers and Yeo CJ who authored 5 classic papers.

Discussion
Bibliometric analysis of most frequently cited articles and the journals in which they appear serves several purposes. It identifies and emphasizes the impact of the work of our colleagues and predecessors, recognizes key advances in pancreatic cancer research, and adds useful perspective on historical developments in this specialty. The use of citation analysis to examine the pancreatic cancer research literature also reveals quantitative information about authors, topics, and journals that is helpful in identifying classic works and high-impact journals. As far as we know, this is the first bibliometric analysis on the top citations in the field of pancreatic cancer research.
Although it is very difficult to provide a detailed analysis of all the 100 top citations, some interesting observations could be made about the top 10. These 10 classic citations revealed major advances in PC research and a number of hot topics in the past five decades. The leading article by Burris HA 3rd reported the first largesize RCT on gemcitabine in advanced PC which may be the most important advance in the field of medical treatment of PC research in the past decades. At position 2, Moore MJ firstly described a large-size clinical RCT of erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced PC. At position 3 and 5, core signaling pathways revealed by global genomic analyses and mutant c-K-ras genes were reported. At position 4 and 9, identification of pancreatic cancer stem cells and the effect on tumor growth and metastatic activity of distinct populations of pancreatic cancer stem cells were described. At position 6, Guillemin R founded that growth hormone-releasing factor from a human pancreatic tumor could cause acromegaly. At position 7, Conroy T conducted a RCT of FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. At position 8, Warshaw AL reviewed the advances of pancreatic cancer. At position 10, Neoptolemos JP compared chemoradiotherapy and chemotherapy after resection of pancreatic cancer in a RCT.
Most of the classic articles are still regularly cited now. Time has much effect on an article's citation, because of that an article's citations depend on its publication time, as citations accumulate over time. Hence, the group of the highly cited articles could be dominated by the earliest papers. However, the decade 1990-1999 and 2000-2009 produced the most classic citations with 42 and 37 ones, respectively, which indicated that much more advances were achieved in these two decades than the others, such as gemcitabine. Besides, in the most recent years, many new journals were developed, and therefore, the number of published articles has grown rapidly and more references are cited.
There were 15, 9, and 9 classic articles published in Cancer Research, Journal of Clinical Oncology, and Table 1 All phases of the search strategy to identify potential articles title=(pancreatic or pancreas) AND title=(adenocarcinoma or adenocarcinomas or carcinoma or carcinomas or cancer or cancers or neoplasm or neoplasms or tumor or tumors or malignancy or malignancies)     Annals of Surgery, respectively, which showed that these three journals were the leading ones in the speciality of PC research. New England Journal of Medicine, Journal of the American Medical Association, and Lancet were the most famous general medical journals, and 16 articles were published in these three journals. The fact that papers on PC research are regularly published on these journals documents that PC is an important topic and health issue to humans. The finding that most top-cited articles originated from the USA is anticipatory and is consistent with the origins of the citation classics in other fields [2][3][4][5]. Furthermore, 11 of the 12 top productive institutions lie in USA. These findings confirm the USA's overwhelming impact on PC research because of its large population and abundant financial supports to the scientific community.
The list of the most frequent authors on PC research just gave a sample of some of the best recognized  Fig. 1 The numbers of classic citations in the past decades scientists in PC research. It was not surprising that not all famous scientists in PC research were mentioned, which was consistent with the previous studies on top citation classics [2][3][4][5]. The editors may consider inviting these researchers to submit subsequent manuscripts or reviews. In many cross-discipline studies of highlycited articles, reviews usually predominate [10]. In this study, there were 7 reviews in the top 100 cited articles. Some of the articles reported are not original research articles, except the reviews. They are highly cited because they are "opinion" articles, that for several reasons became classic in the field of pancreatology. For example, the article from Crile keeps being cited since it is an example of the so-called nihilistic approach to pancreatic cancer. Although they are not original research articles, they are also very important to the advance of pancreatic cancer, and thus, they are constantly cited.
In this literature analysis, by searching for "pancreatic cancer research", the top articles were mainly on oncology and basic cancer research. This paper maybe Table 4 Journals in which the top 100 cited articles were published just provides a good view of the medical part of the research world and does not fully reflect the great contribution to this field from surgeons. Some important surgical advances were achieved before several decades, when not many medical journals were published and the number of citations could not fully reflect the influence.

Conclusions
The top-cited articles identify topics, authors, and institutions that contributed to major advances in the speciality of PC research. This analysis allows for the recognition of major advances in PC research and gives a historic perspective on the progress of PC research.
Abbreviations PC: Pancreatic cancer; RCT: Randomized controlled trials