Intraductal papillary mucinous neoplasms (IPMN) are pancreatic tumors that arise from the pancreatic ductal system [1]. Histological analyses of these tumors reveal mucin secreting columnar epithelium with a variable degree of dysplastic epithelium [2]. Current evidence suggests that these cystic tumors have the potential to undergo malignant transformation as part of the dysplasia-carcinoma sequence, with 30–50% tumors undergoing such transformation [2][3]For this reason, research has been focussed on expanding our knowledge regarding the molecular aspects, clinical presentation and management of these pancreatic cystic tumors. Advances in our knowledge of IPMN will influence and subsequently transform clinical practice enabling the creation of suitable treatment strategies and surveillance protocols.

A citation rank list enables identification of published research that bears most intellectual influence [4]. Once a publication is referenced by another peer-reviewed article, a citation is received. It is likely that original research with the most influence over the scientific community would be cited several times. The process of citation analysis consists of ranking articles based on the number of citations it has received. This technique can also be utilized to rank journals based on their impact on the scientific community [4].

To date several medical specialities have conducted a citation rank analysis in order to highlight the most influential papers within their own field. This includes general surgery, plastic surgery and trauma and orthopaedic surgery [4][5][6]. Currently, no study has assessed for the most influential IPMN manuscripts. An examination of this data would allow an understanding of how our knowledge regarding IPMN has changed and how this has impacted on clinical management. The aim of this study was to identify the studies of greatest clinical influence that has enhanced our knowledge regarding IPMN.

The Thomson Reuters Web of Science citation indexing database was searched. The following search terminology was utilized, the term "Intraductal papillary mucinous neoplasm" or "IPMN" and "panc*" was used. The Web of Science database search was completed by two independent researchers in order to ensure that appropriate studies were included. A method described by Paladugu et al. was applied in order to review the data. The returned search from the Thomson Reuters Web of Science database was filtered to contain full manuscripts of English language only, which were subsequently sorted by number of citations [7]. Exclusion criteria consisted of non-English articles and articles that did not focus on IPMN related research. The 100 most cited manuscripts were noted. Data was extracted from each manuscript for title, author list, topic, country of origin and year of publication. The individual, and five year impact factor of each included journal was noted.

The Thomson Reuters Web of Science database search produced 2,833 full-length, English language papers. Table 1 highlights the 100 most cited IPMN articles [8][9][10][11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] [82] [83] [84] [85] [86] [87] [88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [12] [100] [101] [102] [103] [104] [105] [106] . The total number of citations ranged from 1006 by Tanaka et al. (International consensus on the management of intraductal papillary mucinous neoplasm of the pancreas) [8] to 93 by Bernard et al. (Intraductal papillary mucinous tumors of the pancreas: predictive criteria of malignancy according to the pathological examination of 53 cases) [106] . The most recent published manuscript was produced by Kallen et al. in 2016 (Intraductal oncocytic papillary neoplasm of the pancreas) [51] . The oldest manuscript within the 100 most cited manuscripts was published in 1994 by Sessa et al. (Intraductal papillary-mucinous tumors represent a distinct group of pancreatic neoplasms: an investigation of tumor cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients) [17] .

The 100 most influential IPMN articles were published across 36 journals. The total number of articles per journal ranged from 1 to 13 (Table 2). The Annals of Surgery published the most articles and subsequently had most citations (n = 13 and 2889 citations). The journal with the highest impact factor (18.187) and highest five year impact factor (15.417) was Gastroenterology. The United States of America was the country with most articles in the top 100 (n = 46), followed by Japan (n = 27) (Figure 1). The Johns Hopkins Medical Institute had the most articles in the top 100 (n = 11) and highest number of citations (n = 2383) (Table 3). Within the 100 most cited IPMN articles, 1 author had 5 and 2 authors had 3 first author publications.

One possible limitation of this study is that historical manuscripts may accumulate a higher number of citations despite lacking the impact of newer publications. In order to overcome the potential bias, the citation rate (number of citations divided by number of years since publication) was calculated for each article (Table 4). The citation rate for the top 10 articles ranged from 147 for Tanaka et al. (International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas) [9] to 25 for Rodriguez et al. (Branch-Duct Intraductal Papillary Mucinous Neoplasms: Observations in 145 Patients Who Underwent Resection) [24] . USA had the most articles in the top 10 citation rate, closely followed by Japan.

Within the 100 most cited IPMN papers, management was the most frequently discussed topic (29 articles) (Table 5). Of which 14 articles were related to surgery and 9 articles focused on IPMN diagnosis. The second most common discussed topic was histology (18 of the top 100 papers). Seventeen articles reviewed IPMN prognosis. Fourteen papers reviewed the pathology of IPMN. Articles published prior to 2000, frequently published on the following topics: histology, etiology/pathophysiology and pathology of IPMN. However, this did differ when compared to papers published after 2006, where the most frequently published topics was management and prognosis of IPMN.

Improvements in the histological classification of IPMN, accurate diagnostic radiological imaging algorithms and a further understanding of the impact of genetics on the pathophysiology of the disease represent 71% of the articles in this bibliometric analysis. This has resulted in the development of evidence based management protocols and improved risk stratification of patients with IPMN. This process improves the identification of patients for resection who will likely receive the greatest benefit.

Publications with the highest levels of influence over the scientific community are theoretically much more likely to be cited. The subsequent citations form the foundation of the impact factor. The impact factor can be used as a proxy measure to identify journals with higher quality research and most influential manuscripts. The impact factor highlights the average citations of the article published within the journal during a predefined time period. The journals with the highest impact factor within this study are Gastroenterology, Gut and Hepatology (Impact Factor of 18.19, 14.92 and 11.711 respectively). The median impact factor of this study was 4.54 with 39% of the manuscripts published in journals with an impact factor less than 3.00. One proposed explanation for this is the impact of novelty of the findings of these articles. Novelty may be associated to science in general or only IPMN. Previously published findings established in other disease processes may then be reproduced and re-established in IPMN. It is unlikely that these original articles would be published in high impact factor journals. In the setting of this study these articles are considered likely to be influential.

Within this bibliometric analysis of the 100 most cited IPMN manuscripts, a variety of topics were covered. Histology of IPMN was the principle focus of 18 of the 100 most cited articles. Historically, diverse descriptive terminology was used to describe IPMN, thus causing diagnostic confusion. Recent advances in the histological analysis of IPMN have allowed the identification and subclassification of IPMN into 4 unique histopathological subtypes. These subtypes include oncocytic, gastric, pancreaticobiliary and intestinal types [104] . The sub-classification is dependent on the immunophenotypes and cryoarchitectural features of the tumor. As a consequence of this sub-classification, we have a greater understanding of the malignant transformation potential of these tumors. This newly acquired knowledge influences our current treatment strategies and surveillance protocols for IPMN. Another important factor to consider is that these advances in histology permits correct identification of differential diagnoses of IPMN enabling the identification of benign tumors with a more favorable prognosis.

The definitive treatment for IPMN is surgery. However, surgery as a main topic of focus was only present in 17 of the 100 most cited papers and therefore is underrepresented in this study. Of the 17 papers that focussed on surgery, over half discussed novel surgical techniques for IPMN management, ranging from the role of laparoscopic surgery to techniques that preserve pancreatic parenchyma. Despite advances in surgical technique, pancreatic surgery remains to be associated with postoperative morbidity and mortality. A global change in the approach to pancreatic cystic tumor management has been noted. Historically, early aggressive surgery had been advocated. However as our understanding of the pathophysiology and the natural history of the disease have improved, surgery is reserved for patients´ with cystic tumors associated with high risk stigmata (dilated pancreatic duct, cyst >3cm, presence of high grade dysplasia) [107] . Surveillance protocols have been created by consensus of expert opinion that permit organized follow-up and monitoring of patients with IPMN who fail to meet the criteria for resection. This allows close observation for the development of concerning cystic features providing a good example of how advances in our understanding of the disease pathophysiology impacts and influences current management strategies.

There are study limitations within this manuscript. The main limitation is the potential for several types of bias, which in theory may affect the validity of the study results. English language bias, self-citation, powerful person bias and institutional bias may result in disproportionate citation. It is worth highlighting that older manuscripts are likely to collect more citations. An attempt has been made to overcome this potential bias through calculating the citation rate index. The most influential manuscripts may take several years to accumulate citations as a consequence of the publication lead-time for the citing manuscripts. Thus newly published articles with sufficient citations to be included in the top 100 contain useful and relevant information that have added importance to the pre-existing literature regarding IPMN. Only the first and senior authors, and subsequently the institution of the first author was included in the analysis of this study. This represents another study limitation. It is likely that first authors would have collaborated and co-authored other manuscripts in the top 100 resulting in a under representation in the current study design.

This bibliometric analysis has highlighted the most cited IPMN manuscripts, which describe the pathophysiology of the disease and the current management strategies. Advances in our knowledge regarding the histology and prognosis of IPMN have influenced current practices. A paradigm shift has been observed from early aggressive surgery to the identification of patients with high risk cystic tumor features to establishing screening surveillance protocols to monitor the disease. The content of the 100 most cited manuscripts regarding IPMN demonstrated the diversity and the breadth of the newly acquired knowledge regarding IPMN over the last 23 years. This has resulted in improved treatment outcomes for patients with IPMN. The vast majority of these articles were published within journals with a recorded impact factor of less than 10, suggestive of an assumed lack of novelty to the general scientific community. This study not only identifies the most influential manuscripts in IPMN, it also creates a reference for both clinicians and scientific researchers who undertake research in the field of IPMN to what makes a citable paper. This study proposes that newer publications associated with higher citation rates, will significantly influence clinical practice and impact on the top 100 over the next 5 to 10 years.

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