Ji JN, Yin ZB. Visualizing the landscape of appendiceal tumor research after 2010: A bibliometric study. World J Gastrointest Surg 2024; 16(6): 1894-1909 [PMID: 38983319 DOI: 10.4240/wjgs.v16.i6.1894]
Corresponding Author of This Article
Zhi-Bin Yin, MD, Director, Department of General Surgery, The Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, No. 2 Station North Road, Luoshe Town, Huishan District, Wuxi 214187, Jiangsu Province, China. wxshsqrmyyyzb@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Scientometrics
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
Jia-Nan Ji, Zhi-Bin Yin, Department of General Surgery, The Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi 214187, Jiangsu Province, China
Author contributions: Ji JN analyzed the data, created figures, and wrote the manuscript; Yin ZB reviewed and revised the manuscript; and all authors read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Bin Yin, MD, Director, Department of General Surgery, The Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, No. 2 Station North Road, Luoshe Town, Huishan District, Wuxi 214187, Jiangsu Province, China. wxshsqrmyyyzb@163.com
Received: February 26, 2024 Revised: May 3, 2024 Accepted: May 17, 2024 Published online: June 27, 2024 Processing time: 124 Days and 23.8 Hours
Abstract
BACKGROUND
Despite the rarity of appendiceal tumors, research in this field has intensified, resulting in a growing number of studies and published papers. Surprisingly, no comprehensive bibliometric analysis has specifically addressed appendiceal tumors.
AIM
To offer a thorough analysis of the current landscape and future trends in appendiceal tumor research.
METHODS
In our bibliometric analysis studies, we explored the Web of Science Core Collection database. The bibliographic details of the chosen publications were automatically converted and analyzed using the bibliometric package in the R environment. Additionally, we employed VoSviewer to create cooperation network maps for countries, institutions, and authors, as well as clustering maps for keywords. Furthermore, CiteSpace, another software tool, was utilized to build dual-map overlays of journals and analyze references with citation bursts.
RESULTS
Our study included 780 English-language articles published after 2010. The number of related publications and citations has increased in the past decade. The United States leads in this area, but there is a need to improve cooperation and communication among countries and institutions. Co-occurrence analysis also revealed close collaboration among different authors. Annals of Surgical Oncology was the most influential journal in this field. Analysis of references with high co-citations and references with citation bursts, consistent with analysis of keywords and hotspots, indicated that current research primarily centers on the classification and management of appendiceal mucinous neoplasms and consequent pseudomyxoma peritonei. Despite the abundance of clinical studies, a greater number of in-depth basic research studies should be conducted.
CONCLUSION
Current research on appendiceal tumors focuses on classification and management of appendiceal mucinous neoplasms and pseudomyxoma peritonei. Enhanced collaboration and basic research are vital for further advancement.
Core Tip: In this bibliometric study, we reviewed both the top 10 most co-cited references and 10 references with citation bursts, which helped us better understand the foundation of research in this area and the revolution of research hotspots and frontiers in the perspective of the timeline. The findings showed that scholars had more interest in the classification and management of appendiceal tumors. We believe that maintaining consistency in their classification is advantageous for more precise management. Therefore, we have visualized the classification and summarized the management of appendiceal tumors based on different classifications.
Citation: Ji JN, Yin ZB. Visualizing the landscape of appendiceal tumor research after 2010: A bibliometric study. World J Gastrointest Surg 2024; 16(6): 1894-1909
Appendiceal tumors are not common, with only 0.12 cases per million people. They are often discovered incidentally during an appendectomy for acute appendicitis[1]. The classification of this tumor has been historically varied and confusing. For instance, Connor et al[2] categorized appendiceal tumors as benign, carcinoid, and primary malignant, while Van de Moortele et al[3] divided them into the following four subtypes: Colonic-type adenocarcinoma; mucinous neoplasm; goblet cell carcinoma; and neuroendocrine neoplasm. Despite being uncommon, research into this tumor continues to deepen, with an increasing number of studies and published papers from various perspectives. Therefore, establishing a knowledge framework about appendiceal tumors and identifying the research hotspots and trends is necessary to guide future studies.
Bibliometric analysis is a reliable and commonly used method for tracking trends in a specific field over time. This approach employs literature metrics to assess contributions and forecast future developments using tools such as CiteSpace[4], VoSviewer[5], and R package “bibliometrix”[6]. Bibliometric analysis has found extensive application in various fields of medical research, such as in ophthalmology[7], rheumatology[8], oncology[9], and dermatology[10]. However, no bibliometric analysis has yet focused on appendiceal tumors. To provide a comprehensive analysis of the current state of research in this area, we conducted an in-depth investigation using data from the Web of Science Core Collection (WoSCC). Our findings illuminate the development and contributions in appendiceal tumor research as well as potential future focal points in this field.
MATERIALS AND METHODS
Literature search and screening
We searched the WoSCC database to conduct bibliometric analysis studies. All searches were completed on September 25, 2023. The filtering strategy was set to ((((TI = (tumor)) OR TI = (neoplasm)) OR TI = (carcinoma)) OR TI = (cancer)) AND (((TI = (appendiceal)) OR TI = (appendix))). The inclusion criteria were as follows: (1) Language: English; and (2) Publication years: 2010-2023. A total of 1472 publications were included and assessed via the exclusion criteria of letters, editorial materials, corrections, books, data sets, proceedings papers, retractions, and retracted publications. Finally, 780 publications were retrieved. Full records and cited references of all the publications that met the inclusion and exclusion criteria were exported and downloaded as plain text files.
Data analyses and visualization
All the available information of these screened publications was downloaded from WoSCC. The bibliographic details of the selected publications were automatically converted and analyzed using the bibliometric package (v3.0.0) in the R environment (v4.3.2). The bibliometric package was used to extract and analyze the following information: Title; author; institution; country or region; total number of citations; year of publication; journal; keyword; and impact factor (IF). The IF was represented by the H-index, a high citation index proposed by Hirsch[11] in 2005 as a quantitative evaluation method of academic achievements. VoSviewer (v1.6.19) was utilized to generate the cooperation network map of countries, institution, authors, and keyword clustering[12]. CiteSpace (v6.2.4), a software developed by Synnestvedt et al[4] for bibliometric analysis and visualization, was applied to map the dual-map overlay of journals and to analyze references with citation bursts. Additionally, Microsoft Office Excel 2019 was used to conduct quantitative analysis of publication.
RESULTS
Analysis of publication and citations
A total of 780 related publications from January 2010 to September 2023 were finally retrieved (Figure 1), including 670 “articles” and 110 “reviews”. Figure 2 presents the annual number of publications. It was evident that literature was limited and grew slowly from 2010 to 2016, while the number of publications increased significantly between 2016 and 2020. After 2020, this number became stable and hovered at around 100 per year.
Figure 1 Publications screening flowchart.
A total of 1472 publications were included according to the filtering strategy and inclusion criteria. Then, 692 publications were excluded according to exclusion criteria of letters, editorial materials, corrections, books, data sets, proceedings papers, retractions, and retracted publications. In total, 780 publications were retrieved. WoSCC: Web of Science Core Collection.
Figure 2 Annual output of appendiceal tumor research.
Each point represents the number of papers published in the respective year.
The total citations from these 780 publications was 10133, and average citations per document was 12.99. The number of citations for 780 manuscripts is 338 (43.33%) for 1-9 citations, 245 (31.41%) for 10-99 citations, and 10 (1.28%) for more than 100 citations (Figure 3). A total of 187 (23.97%) manuscripts never received citations in other publications, with 88 of them being published in 2023. In 2000, The Pancreas published the article with the most citations, 352 in total[13]. As a consensus guideline, this paper elaborated the diagnosis and treatment of neuroendocrine tumors (NETs), including those occurring in the appendix. In addition, we filtered out the publications with the most citations and listed them in Table 1.
Figure 3 Number of publications by different total citations.
The bars of different length correspond to the number of papers in different total citation ranges.
Table 1 Top 10 publications with the most citations in appendiceal tumor research.
Title
Publication year
Total citations
The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum
2010
352
ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas
2012
298
Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma: the 3d English Edition
2019
276
ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas)
2016
160
The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei
2017
138
ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas
2012
132
Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms
2013
118
Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade
2014
108
The rise in appendiceal cancer incidence: 2000-2009
2015
102
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1000 patients with perforated appendiceal epithelial tumours
2016
100
Analysis of countries and institutions
Overall, all these manuscripts came from 67 countries or regions and 1212 institutions. First, we visualized the geographic distribution of countries or regions contributing to this field of research and built a collaborative network based on the number of publications and connections in each country or region (Figure 4). Countries or regions in this visual network contributed at least two relative publications. In this study, nine clusters were created, each colored differently. Larger nodes indicated a higher frequency, while thicker lines indicated a higher degree of collaboration. Notably, there was a lot of active cooperation between different countries. For example, China had active cooperation with Japan and Germany, and Belgium, Denmark, Turkey, and Israel had close cooperation with each other.
Figure 4 Geographical distribution and visualization of countries/regions.
A: Intensity of the blue color represents publication count and thickness of the line represents cooperation intensity; B: Node size represents publication count, and link size indicates cooperation intensity.
We subsequently analyzed the countries or regions and institutions of these manuscripts to identify the high-impact studies. From all 60 countries, the United States contributed both the most publications (n = 427, 36.46%) and the highest number of citations (n = 6975, 49.91%). The top 10 high-yield countries were distributed in Europe (n = 5), North America (n = 2), and Asia (n = 2). Table 2 showed the specific number of articles, total citations, and average article citations of these countries. The United Kingdom published the fourth most articles, but the average number of citations was the second highest. Germany, despite ranked 10th in terms of articles, it ranked 1st in terms of average citations. Therefore, these two countries conduct high-quality research. The top 10 high-yield research institutions are listed in Table 3. Nine of them are located in the United States, proving the country’s prominent position in this field. We then screened 58 institutions with at least five publications and created a visualized network according to the collaborative relationships among them. Figure 5 shows institutions as dots, with dot size indicating article count and connections showing cooperation. Six clusters were formed based on cooperation closeness. Figure 5 illustrates that the University of Texas MD Anderson Cancer Center served as a hub for collaboration, and the connections between institutions in America were exceptionally strong. In Asia, some institutions such as Osaka University, National Cancer Center (Korea), and Juntendo University also shared links with each other. However, it is evident that cross-continental cooperation remains relatively rare but should be strengthened in the future.
Figure 5 Collaboration network of institutions.
Node size represents publication count, and link size indicates cooperation intensity. The time of contributions is presented by the brightness of the color.
Table 2 Top 10 countries on research of appendiceal tumors.
Country
Articles
Total citations
Average article citations
United States
427
6975
16.3
China
98
460
4.7
Japan
84
556
6.6
United Kingdom
70
1497
21.4
Australia
48
455
9.5
Turkey
46
325
7.1
Italy
42
546
13
Canada
31
448
14.5
France
23
271
11.8
Germany
27
705
26.1
Table 3 Top 10 institutions for research of appendiceal tumors.
Institution
Articles
Citations
University of Texas MD Anderson Cancer Center
24
925
University of Pittsburgh
23
667
University of California, San Diego
19
342
Ohio State University
18
184
Mercy Medical Center
17
347
University of New South Wales
16
118
Mayo Clinic
13
181
Vanderbilt University
13
158
Emory University
12
191
Memorial Sloan Kettering Cancer Center
12
614
Journals and co-cited journals
In total, 226 journals published the 780 manuscripts. We identified the top 10 high-impact journals according to the H-index (Table 4). It was notable that Annals of Surgical Oncology, as the most influential journal, also published the most papers. We then selected 39 journals with at least five relevant publications and created a journal network map (Figure 6A). Annals of Surgical Oncology had active citation relationships with Frontiers in Oncology, American Journal of Surgery, and Journal of Surgical Oncology.
Figure 6 Network of journals and co-cited journals.
A: Network of journals; B: Network of co-cited journals. Node size represents frequency of journal, and link size indicates cooperation intensity.
Table 4 Top 10 journals for research of appendiceal tumors.
Journal
H-index
Articles
IF
Q
Annals of Surgical Oncology
22
67
3.7
2
European Journal of Surgical Oncology
13
28
3.8
2
Journal of Surgical Oncology
9
24
2.5
3
American Journal of Surgical Pathology
8
9
5.6
1
Archives of Pathology & Laboratory Medicine
8
11
4.6
2
Diseases of the Colon & Rectum
7
9
3.9
2
Neuroendocrinology
7
7
4.1
2
Histopathology
6
7
6.4
2
Journal of Pediatric Surgery
6
6
2.4
3
Journal of the American College of Surgeons
6
6
5.2
2
We also filtered journals with the minimum co-citation equal to 150 and mapped the co-citation network (Figure 6B). Diseases of the Colon & Rectum had positive co-citation relationships with American Journal of Surgery, Annals of Surgical Oncology, and Journal of Gastrointestinal Surgery. Using a dual-map overlay, citation relationships between journals and their co-cited journals were visualized, with citing journals on the left and cited journals on the right (Figure 7). The green path shown in Figure 7 represents the main citation path, indicating that research published in Health/Nursing/Medicine journals was mainly cited by literature in Medicine/Medical/Clinical journals.
Figure 7 Dual-map overlay of journals.
Clusters of citing journals on the left and clusters of cited journals on the right. The lines show relationships between the citing and cited journals. The thickest green curve represents the main citation path.
Authors and co-cited authors
In total, 4090 authors dedicated themselves to researching appendiceal tumors. In Table 5, we listed the top 10 high-impact authors according to H-index and the number of papers they have published. We also created a collaborative network based on authors who have published five or more papers (Figure 8A). Edward A Levine, Haroon A Choudry, Perry Shen, and David L Bartlett have the largest nodes due to their extensive publications on the topic. Additionally, we have noted significant collaboration among these authors, such as the close partnership between Edward A Levine and Perry Shen, as well as the active cooperation between Haroon A. Choudry and Reetesh K Pa and David L Bartlett.
Figure 8 Collaboration network of authors and co-cited authors.
A: Collaboration network of authors; B: Collaboration network of co-cited authors. Node size represents frequency of author, and link size indicates cooperation intensity.
Table 5 Top 10 most influential authors according to the H-index.
Author
H-index
Articles
Edward A Levine
12
22
David L Bartlett
10
15
Haroon A Choudry
10
15
Vadim Gushchin
10
21
Reetesh K Pai
10
11
Armando Sardi
10
21
Perry Shen
10
19
C Nieroda
9
16
Konstantinos I Votanopoulos
9
18
Brendan John Moran
8
10
Among the 6603 co-cited authors, 39 authors were co-cited more than 50 times. We visualized a co-citation network of these 39 authors. A large node in Figure 8B revealed that Paul H Sugarbaker is the most co-cited author (n = 493), followed by Norman J Carr (n = 481) and Joseph Misdraji (n = 281). Lines in Figure 8B showed that there were also active collaborations among different co-cited authors, such as R M Smeenk, Pierre Jacquet, and Daniel Elias.
Analysis of references
There were 8609 co-cited references on research of appendiceal tumor after 2010. 10 most co-cited references listed in Table 6 were co-cited at least 75 times, with the highest being cited 188 times. Citation bursts refer to references frequently cited by scholars in a specific field over time. In our study, CiteSpace identified 10 references with strong citation bursts (Figure 9). Citation bursts for references were observed from 2010 to 2023. “A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process” by Carr et al[28] received the strongest citation burst (strength = 28.59) which occurred between 2017 and 2021. “Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy” from Chua et al[34], hold the second place in citation burst (strength = 16.35) between 2013 and 2017.
Figure 9 Top 10 references with citation burst.
The red bar represents the duration of strong citation burstiness. The burst strength represents the scientific value of the article.
Table 6 Top 10 co-cited references in appendiceal tumor research.
Co-cited reference
Citations
carr nj, 2016, am j surg pathol, v40, p14, doi 10.1097/pas.0000000000000535
188
mccusker me, 2002, cancer, v94, p3307, doi 10.1002/cncr.10589
163
connor sj, 1998, dis colon rectum, v41, p75, doi 10.1007/bf02236899
137
chua tc, 2012, j clin oncol, v30, p2449, doi 10.1200/jco.2011.39.7166
131
misdraji j, 2003, am j surg pathol, v27, p1089, doi 10.1097/00000478-200308000-00006
pai rk, 2009, am j surg pathol, v33, p1425, doi 10.1097/pas.0b013e3181af6067
97
ronnett bm, 1995, am j surg pathol, v19, p1390, doi 10.1097/00000478-199512000-00006
97
sugarbaker ph, 2006, lancet oncol, v7, p69, doi 10.1016/s1470-2045 (05)70539-8
77
carr nj, 2017, histopathology, v71, p847, doi 10.1111/his.13324
76
Hotspots and frontiers
We identified 20 keywords with the highest co-occurring frequency, accurately capturing the research hotspots in appendiceal tumor research (Table 7). Pseudomyxoma peritonei (PMP) and cytoreductive surgery (CRS) were the most frequently mentioned keywords, indicating the main areas of research interest. Keywords with 50 or more occurrences were filtered and subjected to cluster analysis using VoSviewer (Figure 10A). The thickness of lines connecting nodes indicates the strength of the relationship between keywords. Three distinct clusters were identified, each representing a unique research direction. The green cluster encompassed keywords such as PMP, CRS, hyperthermic intraperitoneal chemotherapy (HIPEC), clinicopathological analysis, etc. The keywords in the red cluster included diagnosis, prognosis, management, right hemicolectomy, etc. The keyword in the blue cluster only included classification.
Figure 10 Keyword cluster analysis and trend topic analysis.
A: Keyword cluster analysis. Frame size represents frequency of keyword, and each color represents a cluster; B: Trend topic analysis. Node size represents trend frequency, and line length represents the duration.
Table 7 Top 20 high-frequency keywords in appendiceal tumor research.
Rank
Keyword
Counts
1
Pseudomyxoma peritonei
289
2
Appendix
192
3
Cytoreductive surgery
150
4
Neoplasms
149
5
Management
138
6
Hyperthermic intraperitoneal chemotherapy
135
7
Tumor
118
8
Origin
117
9
Classification
106
10
Survival
97
11
Clinicopathological analysis
96
12
Diagnosis
90
13
Carcinomatosis
84
14
Cancer
79
15
Adenocarcinoma
74
16
Carcinoid-tumors
65
17
Prognosis
64
18
Appendectomy
61
19
Mucocele
53
20
Systemic chemotherapy
52
The analysis of keyword trends (Figure 10B) indicated that the development of appendiceal research can be roughly divided into three stages. In stage 1 (2014-2018), scholars focused on the origin and clinicopathological analysis of appendiceal tumors. In stage 2 (2018-2020), the focus shifted to the management of appendiceal tumors. In stage 3 (after 2020), scholars turned their attention to the risks and outcomes associated with appendiceal tumors, which revealed the current research hotspots.
DISCUSSION
Our study analyzed 780 publications about appendiceal tumors published after 2010. Quantitative analysis of publications revealed that research on appendiceal tumors has gained increased attention since 2016 and has remained intense, with approximately 100 annual publications in recent years. Upon analyzing the citations, we discovered that most of these publications have been cited more than 10 times, demonstrating significant academic value. Moreover, the majority of the top 10 most cited articles are guidelines, indicating that our understanding of appendiceal tumors is still unclear and constantly evolving.
Combining the analysis of country and institution, we can easily conclude that the United States was the most productive country in this area, as it contributed the most publications and nine of the top ten high-yield institutions are located in the United States. China, despite being ranked second in the number of articles, had an average article citation of only 4.7. In contrast, Germany, ranked 10th in the number of articles, had the highest average number of citations. This comparison highlights the disparity in research quality between the two countries.
Cooperation and communication between countries and institutions can alleviate such imbalances. In fact, cooperative relationships already exist between some countries and institutions, such as the close cooperation among European countries like the United Kingdom, Turkey, Denmark, and Germany. Similarly, there was tight communication among institutions in the United States, such as the University of Texas MD Anderson Cancer Center, Mayo Clinic, and the University of Pittsburgh. However, the breadth and intensity of cooperation is not yet ideal. For instance, there was only limited cooperation between institutions in Europe and Asia, potentially impeding the advancement of this research field over the long term. Consequently, we strongly recommend that institutions across various countries establish broad connections and cooperation to enhance the progress of research on appendiceal tumors.
Most appendiceal tumor research has been published in the Annals of Surgical Oncology (IF = 3.7, Q2), making it the most popular journal in this field. Among them, Histopathology had the highest IF (IF = 6.4, Q2), followed by the American Journal of Surgery (IF = 5.6, Q1). Co-cited journals mostly included high-impact Q1 journals, such as Annals of Surgery (IF = 9.0, Q1), British Journal of Surgery (IF = 9.6, Q1), and Journal of Clinical Oncology (IF = 45.3, Q1). Clearly, these are high-quality international journals that support appendiceal tumor research. Additionally, current appendiceal tumor research was primarily published in clinically related journals focused on Medicine, Medical, and Health, indicating a lack of basic research in the biology and molecular fields.
From our perspective, Edward A Levine appeared to be the most influential figure in this field due to his H-index and overall academic output. His research primarily focuses on the treatment of appendiceal neoplasms with peritoneal dissemination. In 2008, he reported that oxaliplatin could be utilized in intraperitoneal hyperthermic chemoperfusion for treating peritoneal surface dissemination from colorectal and appendiceal cancers[14]. In 2022, he assessed the therapeutic effects of HIPEC with an incomplete cytoreduction[15]. In his basic research, he was the first to employ gene expression profiling for appendiceal cancer and demonstrated genomic signatures confirming their unique biology[16].
Reetesh K Pa, in close collaboration with Haroon A Choudry, published several articles on the diagnosis, grading, staging, and histological features of different types of appendiceal cancer, particularly appendiceal mucinous neoplasms[17-19]. In fact, the majority of the articles by these 10 authors were focused on peritoneal dissemination/metastases and PMP, which has been convincingly linked to appendiceal mucinous neoplasms, indicating the hotspots and frontiers in appendiceal tumor research.
Paul H Sugarbaker and Norman J Carr, the most co-cited authors, have different research focuses. Paul H Sugarbaker primarily focuses on peritoneal malignant lesions, such as peritoneal metastases, PMP, and peritoneal mesothelioma[20-23]. Norman J Carr continually updates the classification, diagnosis, and treatment of various types of appendiceal cancer, including mucinous appendiceal neoplasms, appendiceal adenocarcinomas, and neuroendocrine neoplasms of the appendix[24-27]. The work of these two authors established the current consensus that PMP, the primary focus of research on appendiceal tumors, is a complex disease with distinct biological behavior that typically originates from appendiceal mucinous neoplasms[28].
Co-cited references are those that are cited by multiple publications and can be seen as the foundation of research in a particular field. In addition, citation burst references have been heavily cited in a certain time span, reflecting emerging research topics[29]. In this bibliometric study, we reviewed both the top 10 most co-cited references and 10 references with citation bursts, which helped us better understand the foundation of research in this area and the revolution of research hotpots and frontiers.
Early in 1990s, Ronnett et al[30] comprehensively described the pathologic features and prognosis of PMP, which was poorly understood at that time. They separated PMP into two diagnostic categories: Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis (PMCA). They identified the relationship with appendiceal mucinous adenoma and appendiceal mucinous adenocarcinoma, respectively. In 1998, Connor et al[2] conducted a retrospective clinicopathologic analysis of appendiceal tumors and classified appendiceal tumors into benign (adenoma), carcinoid/adenocarcinoid, and primary malignant (adenocarcinoma). It is interesting that there was very little overlap between these two early studies. This situation changed after entering the 21st century.
The concept of “mucinous” was becoming popular and controversial. McCusker et al[31] classified appendiceal tumors into “colonic type” adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, goblet cell carcinoid, and “malignant carcinoid” in their population-based study in 2002. One year later, appendiceal mucinous neoplasms, one type of appendiceal tumor, was studied by Misdraji et al[32] and was divided into low-grade appendiceal mucinous neoplasm (LAMN), mucinous adenocarcinomas. In 2008, the connection between PMP and appendiceal tumors was formally strengthened through the bridge of appendiceal mucinous neoplasm. Smeenk et al[33] concluded that one-third of primary epithelial lesions of the appendix lesions are mucinous epithelial neoplasms and may progress into PMP.
Since then, research has focused on PMP and associated appendiceal mucinous neoplasm. Sugarbaker[21] regarded CRS combined with HIPEC as a new standard of care for appendiceal mucinous neoplasms and PMP. The outcome data of this strategy was analyzed by Chua et al[34] in 2012. They proved that CRS and HIPEC was acceptable for PMP originating from appendiceal mucinous neoplasm. Furthermore, Fournier et al[35] concluded that LAMN have a lower risk for recurrence and clinical surveillance, and expectant management is a viable choice after radical resection.
Despite the evolution of the knowledge of appendiceal tumors and PMP, the classification of PMP and its primary appendiceal neoplasia is still contentious, especially for nomenclature and terminology. Carr et al[24] in 2017 and Carr et al[28] in 2016 published two consecutive papers attempting to standardize the histopathological classification and diagnosis of appendiceal tumor and PMP. These two papers were both high co-cited references and references with citation bursts, indicating the importance in this research area. In fact, these studies focused on PMP more, while the American Society of Colon and Rectal Surgeons provided clinical practice guidelines stating the classification of appendiceal neoplasms more clearly[36].
The frequent use of popular keywords and the changing trends in topics align with the development of co-cited references and references with citation bursts. Analysis of keywords and topic trends showed a growing scholarly interest in the categorization of appendiceal tumors as well as the risks and outcomes of various treatments like CRS and HIPEC. We believe that maintaining consistency in their classification is advantageous for more precise management. As a result, we have visualized the classification and summarized the management of appendiceal tumors based on different classifications through a literature review of the aforementioned references (Figure 11).
Figure 11 Classification of appendiceal neoplasm.
Visualization of classification of appendiceal neoplasm according to influential references. PMP: Pseudomyxoma peritonei; DPAM: Disseminated peritoneal adenomucinosis; PMCA: Peritoneal mucinous carcinomatosis; PMCA-S: Peritoneal mucinous carcinomatosis with signet ring cells; NET: Neuroendocrine tumor; LAMN: Low-grade appendiceal mucinous neoplasm; HAMN: High-grade appendiceal mucinous neoplasm.
Epithelial appendiceal neoplasms
We hypothesize that the progression from adenoma to LAMN to high-grade appendiceal mucinous neoplasm (HAMN), and ultimately to adenocarcinoma, is a process of increasing invasiveness and cytological atypia. Adenoma is a cytologically bland mucinous neoplasm clearly confined to the appendix without extra-appendiceal mucin or neoplasia[37]. LAMNs are characterized by well-differentiated adenomas that can proliferate outside the appendix in a malignant fashion, and HAMNs share some histological features with LAMNs but exhibit more aggressive cytologic atypia[22]. Adenoma and LAMN without perforation or peritoneal involvement have shown very low recurrence rates after appendectomy[35]. Appendectomy alone is usually enough to treat HAMN, but care should be taken to rule out the presence of associated invasive adenocarcinoma[36]. Adenocarcinoma exhibits infiltrative invasion and poses a high risk, as the rate of metastatic disease to regional lymph nodes ranges from 20% to 67%[38]. Right hemicolectomy is recommended for nonmetastatic adenocarcinoma and goblet cell carcinoid of the appendix, which is considered a variant of adenocarcinoma with some features similar to traditional NETs[39,40].
Nonepithelial appendiceal neoplasms
Nonepithelial appendiceal neoplasms include NETs. Somatostatin receptor scintigraphy can be used to identify the foci of NETs[41]. Somatostatin receptor scintigraphy is also more sensitive for detection of well-differentiated NETs (e.g., those expressing somatostatin receptors), whereas 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography detects more poorly differentiated NETs[42]. Lesions < 1 cm in diameter and without unfavorable features are adequately treated with appendectomy[43]. Tumors > 2 cm are best treated with formal right hemicolectomy[44]. The largest clinical study found no nodal disease in primary tumors < 2 cm, and some experts suggest appendectomy alone for all lesions under this size[45].
Peritoneal metastases and PMP
Appendiceal neoplasms with peritoneal metastases are not equal to PMP. PMP refers to the buildup of mucus within the peritoneum due to mucinous neoplasia, often originating from appendiceal tumors. The term PMP is used when appendiceal tumors perforate and spread throughout the peritoneal cavity, leading to the production of significant mucin. Depending on the cellularity within the mucin, PMP is categorized as acellular mucin, low-grade mucinous carcinoma peritonei, or disseminated peritoneal adenomucinosis, high-grade mucinous carcinoma peritonei or PMCA, and high-grade mucinous carcinoma peritonei with signet ring cells or PMCA with signet ring cells[28]. Despite the nuanced differences between these concepts, CRS is recommended for appendiceal tumors with signs of peritoneal spread[46]. Patients treated with combined HIPEC may improve their long-term survival, reduce tumor recurrence, prolong time to disease progression, and reduce the frequency of repeated surgical interventions[34,47,48].
Advantages and shortcomings
In our study, we systematically analyzed publication trends, research evolution, and future research foci on appendiceal tumors using different bibliometric tools. Scholars interested in related research can benefit from this study since bibliometric analysis provides a more complete insight than traditional reviews. However, there are still some shortcomings to consider. First, the study only analyzed publications retrieved from the WoSCC database after 2010, which limits its ability to fully understand the historical development of this field. Second, only English articles were included, potentially underestimating the impact of non-English papers. Publications after October 2023 were not included either. If all these articles were also included, the results would be slightly different.
CONCLUSION
Despite the low incidence, research on appendiceal tumors is highly valued by scholars worldwide, and the number of related publications continues to increase. The United States was the leading country in this field, but cooperation and communication among various countries and institutions need to be strengthened. In recent years, research has mainly focused on appendiceal mucinous neoplasms and their close association with PMP. Scholars have shown more interest in the classification and management of appendiceal tumors, publishing numerous clinical-related articles. It is important to also focus on basic research of appendiceal tumors, such as in biology and molecular fields.
ACKNOWLEDGEMENTS
We would like to thank Dr. Si-Yu Gu for her assistance and guidance in this research.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade A
Novelty: Grade A
Creativity or Innovation: Grade A
Scientific Significance: Grade A
P-Reviewer: Soreq L, United Kingdom S-Editor: Wang JJ L-Editor: A P-Editor: Che XX
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