Global productivity and research trends of colorectal carcinoma: A scientometric analysis of studies published between 1980 and 2021

Although colorectal cancer (CRC) is a serious cause of death and has a significant impact on patients’ quality of life and incidence rate of CRC has increased among the younger populations, bibliometric research of CRC has not been conducted yet. To perform a comprehensive analysis of scientific publications on CRC using various statistical and bibliometric techniques. Publications on CRC published between 1980 and 2021 were downloaded from the Web of Science database and analyzed using statistical methods. The trending topics, collaborations among countries, and citation relationships were analyzed using bibliometric network visualization mapping. The number of articles to be probably published in the next 5 years was estimated using the exponential smoothing estimator. The Spearman’s correlation rank correlation coefficient was used to analyze the correlations among the variables. A total of 122,717 publications were found in the fields of oncology, gastroenterology, hepatology, and surgery. Of the published articles, 64,774 publications were research articles. The top five countries that contributed the most to the literature were the USA (16,604; 25.6%), China (10,567; 16.3%), Japan (7932; 12.2%), the UK (5009; 7.1%), and Italy (4287; 6.6%). The most prolific author, institution, and journal in the field of CRC were Zhang Y (n = 331), University of Texas System (n = 1646), and Diseases of the Colon and Rectum (n = 2090), respectively. The most influential journal based on the average number of citations received per article was CA-A Cancer Journal for Clinicians (citations per article; 286). There was a significant positive correlation between the number of articles produced by the countries on CRC and gross domestic product and human development index (r = 0.726, P < .001; r = 0.658, P < .001, respectively). Additionally, a significant moderate correlation of CRC was found with gross domestic product per capita (r = 0.711, P < .001). Keywords like overall survival, neoadjuvant chemoradiotherapy, locally advanced rectal cancer, robotic surgery, anastomotic leakage, chemoradiotherapy, metastatic colorectal cancer, KRAS, meta-analysis, colorectal surgery, and laparoscopic surgery were studied.


Introduction
Colorectal cancer (CRC) is a type of gastrointestinal malignancy originating from either the colon or rectum.Although the malignancy can be simply defined as colon or rectal cancers depending on their origin, they are often merged because of the several similar biological and clinical features. [1]denocarcinoma is the most common colorectal malignancy (up to 95% of cases), followed by carcinoid tumors, gastrointestinal stromal tumors, lymphomas, and sarcomas. [2]RC is a complex disease that arises from the accumulation of genetic alterations in the key regulatory genes and pathways, including the RAS-MAPK, Wnt and P13K pathways.KRAS, neuroblastoma RAS viral oncogene homolog, and BRAF genes. [3,4]Subsequently, it became clear that genetic mutations play a partial role in the colorectal carcinogenesis.Epigenetic variations in cancer-related genes and noncoding RNAs are believed to be strongly involved in cancer initiation and progression. [3,4]n a large number of patients, CRC may remain silent for a long time until it grows and spreads substantially, adversely impacting the prognosis.In symptomatic patients, particularly in patients with advanced stage of cancer, the disease may cause changes in the bowel motility (e.g., diarrhea or constipation), occult or evident colorectal bleeding, abdominal discomfort, cramping, unexplainable weight loss, weakness, and fatigue. [1]he leading risk factors for CRC include family history, physical inactivity, overweight and obesity, large intake of alcoholic beverages, precancerous conditions, tall stature, high consumption of red or processed meat, and modest intake of dairy products and foods containing whole grains or dietary fiber, avoiding which makes this disease potentially preventable. [1,5,6]More than 50% CRC cases and deaths are attributable to modifiable risk factors and a substantial proportion of the cases could be further prevented through screening and surveillance. [6]The incidence and mortality rates of CRC also substantially vary by geographical differences, race, and ethnicity.The sex disparity in CRC cases also varies with the age of the patients. [6]n 2020, approximately 19.3 million cancer cases were diagnosed and about 10 million cancer deaths were reported worldwide.Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0%), prostate (7.3%), and stomach (5.6%) cancers.Lung cancer remained the leading cause of death due to cancer with an estimated 1.8 million deaths (18%) followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancer cases.The incidence rates of CRC were found to be 29 and 20 cases per 100,000 men and women, respectively, in countries with high/very high human development index (HDI) versus 7.4 and 5.4 cases per 100,000 men and women, respectively, in countries with low/medium HDI. [7]In general, CRC ranks third in terms of incidence rate but is second in the terms of mortality.There is a significant variation in the incidence rates of colon cancer in different regions of the world.The highest incidence rates were observed in Europe, Australia/New Zealand, Northern America, Hungary, and Norway, while the lowest incidence rates were seen in Africa and South Central Asia [7] CRC is the second most common cause of cancer-related deaths in the United States. [5,6]According to the latest report of the American Cancer Association, there are about 147,950 new cases of CRC in the United States in 2020, including 104,610 and 43,340 cases of colon cancer and rectal cancer, respectively. [5,6]olorectal cancer can be considered as a marker of socioeconomic development, as the incidence rate of CRC tends to rise uniformly with increasing HDI in the developing countries. [7,8]he increasing incidence rate in the formerly low-risk and lower HDI countries probably reflects the effect of changes in lifestyle factors that are associated with increasing the colorectal cancer risk and suggests the importance of strengthening preventive measures and conducting appropriate screening programs especially in countries undergoing major social and economic transition. [1,7]The accelerated decline since the 2000s is chiefly attributed to the increased colonoscopy screening and removal of precursor lesions. [6,7,9]Despite consistent improvements in screening strategies and the development of effective treatment methods, 5-year survival rate for advance stages of cancer is still not promising. [4,10]Although the overall incidence and mortality rates of CRC are continuously declining, this progress is increasingly confined to the older age groups. [6]ibliometrics is the technique to analyze the scientific publications using various statistical methods. [11,12][13] Although CRC is a major cause of death with an increasing incidence rate in young age groups and has a significant impact on patients' quality of life, a bibliometric research has not been conducted for CRC.This study aimed to perform a holistic analysis of the scientific publications on CRC published between 1980 and 2021 using various statistical and bibliometric methods.

Statistical analysis
The number of publications in the coming years was estimated by observing the past publication trends using the exponential smoothing estimator with seasonal correction run in the Microsoft Office Excel program.Bibliometric network visualizations and citation analysis were performed using the VOSviewer (Version 1.6.16,Leiden University's Center for Science and Technology Studies) software package. [14]The website (https:// app.datawrapper.de)was used to draw the world map.Statistical analyses were performed using Statistical Package for the Social Sciences (Version: 22.0, SPSS Inc., Chicago, IL, License: Hitit University) software package.The data was checked for normality of distribution using the Kolmogorov-Smirnov test.The association between global scientific productivity on CRC and some economic and development indicators of countries was investigated by analyzing the correlation between the number of articles produced by countries and Gross Domestic Product (GDP), Gross Domestic Product per capita (GDP per capita), and HDI using the Spearman's rank correlation coefficient as the data was non-normally distributed (data were obtained from the World Bank. [15]) Statistical significance was set at a P < .05.

Overview of the included publications
The literature review in the WoS database yielded 176,364 publications in all research fields related to CRC published between 1980 and 2021.Of these, 122,717 publications in the fields of oncology, gastroenterology, hepatology, and surgery were included in the study.These publications were divided into articles (64,774; 52.7%), meeting abstracts (40,782; 33.2%), review articles (5904; 4.8%), proceedings papers (3784; 3%), and letters (3759; 3%).The remaining publication were grouped into other types of publications (editorial materials, corrections, news items, book chapters, notes, early access, retracted publications, retractions, corrections, additions, discussions, books, book reviews, reprints, data papers, expression of concern, publication with expression of concern, bibliographies, biographical items).Publications categorized as articles (n = 64,774) were included in the bibliometric analyses.It was found that 97% (n = 62,856) articles were published in English and the remaining articles were published in other languages, such German (n = 858), French (n = 562), Spanish (n = 225), Russian (n = 102), Italian (n = 50), Korean (n = 49), Polish (n = 46), Turkish (n = 12), Portuguese (n = 6), Chinese (n = 2), Danish (n = 2), Dutch (n = 2), and Slovenian (n = 2).Almost all of the articles were indexed in Science Citation Index Expanded (SCI-Expanded; n = 61,208; 94.4%) and Emerging Sources Citation (3149; 4.8%) indexes.The remaining few studies were indexed in Conference Proceedings Citation Index-Science, Social Sciences Citation Index, Book Citation Index-Science, and Conference Proceedings Citation Index-Social Science and Humanities.www.md-journal.com

Publication trends by year
The number of published articles in different years is shown in Figure 1.The results of the exponential smoothing estimation model that were used to estimate the number of articles likely to be published 2022 onward are shown in Figure 1.The estimation model analysis revealed that approximately 4527 articles (95% confidence interval [CI]: 4270-4783) are likely to be published in 2022 and 5398 (95% CI: 4862-5934) articles will likely be published in 2026 (Fig. 1).

Correlation analysis
There was a strongly significant positive correlation between the number of articles produced by countries on CRC and GDP and HDI (r = 0.726, P < .001;r = 0.658, P < .001,respectively); however, there was a moderately significant correlation of publication on CRC with GDP per capita (r = 0.711, P < .001).

Active institutions
The top 20

Active journals
A total of 64,774 articles on CRC had been published in 836 different journals.The top 56 journals publishing 300 or more articles, the total number of citations received by the journals, and the average number of citations received per article are presented in Table 1.

Citation analysis
Of the 64,774 articles on CRC, the top 25 articles with the highest number of total citations are presented in Table 2.The last column of Table 2 indicates the average number of citations received by the articles per year.

Trend topics
The 64,774 articles published on CRC used 47,496 keywords.Of these keywords, 97 had been used in at least 200 different articles, as shown in Table 3.The cluster network visualization map showing the results of the cluster analysis among these keywords is shown in Figure 4.The trend network visualization map showing trend topics is shown in Figure 5.The citation network visualization map showing the most cited topics is shown in Figure 6.

Discussion
The The projected estimations for the next 5 years points to a continued upward trend of the number of articles likely to be published on CRC.Analysis of the distribution of publications by countries found that 18 of the top 20 countries that contributed the most to the literature on CRC were the developed countries (the USA, Japan, the UK, Italy, Germany, France, South Korea, the Netherlands, Spain, Canada, Australia, Sweden, Taiwan, Table 1 The 56 most active journals that have published more than 300 articles on colorectal cancer.Denmark, Switzerland, Belgium, Norway, and Greece).Only two of the 20 most active countries in terms of publication on CRC (China, Turkey) were the developing countries.However, these countries have large economies.In the most active countries in term of CRC research, we observed the presence of strong-moderate correlations of the number of articles produced by countries on CRC with GDP, GDP per capita, and HDI, suggesting that publication productivity in the field of CRC is primarily influenced by the economy size and development status of the countries.The incidence and mortality rates of CRC are known to be associated with the level of development of the countries, especially with HDI. [7,9]Our study found that the academic productivity has a high level of correlation with HDI, suggesting that increased incidence rate of CRC in developed countries leads to increased academic productivity.The density map created while considering the score of total collaboration among countries showed that the countries with the most intensive collaboration were the USA, England (in the UK), Germany, Italy, France, Spain, the Netherlands, Australia, Sweden, Belgium, China, Canada, Japan, Denmark, most influential study was the article published by Fong et al [28] titled "Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases" published in the Annals of Surgery.The fifth most influential study was an article by Siegel et al [29] Based on the average number of citations received per year, the first and  second most influential studies were the articles published by Siegel et al and Siegel et al on colorectal cancer statistics. [6,29]he third most influential study was conducted by Arnold et al [30] entitled "Global patterns and trends in colorectal cancer incidence and mortality" published in the GUT journal.The fourth most influential study was an article by Andersen et al. [26] The fifth most influential study was Siegel et al [31] article entitled "Colorectal cancer statistics, 2014" published in the CA: A Cancer Journal for Clinicians.Based on the number of co-citations of all the analyzed articles, the most influential studies were those by Sauer et al, Kapiteijn et al, Bray et al, Hurwitz et al, Fearon et al. [16][17][18][19][20] We can recommend that clinicians and researchers interested in this topic should read these publications.
Our literature review on CRC found no comprehensive bibliometric study that was directly related to CRC.The strength of our comprehensive study is that it is the first bibliometric research on this subject.Wrafter et al [32] identified the top 100 articles on CRC with the highest number of citations.Darroudi et al conducted bibliometric research on CRC treatment, whereas Jin et al conducted bibliometric research on the management of liver metastasis in CRC. [33,34]The literature review in this study was confined to the WoS database, which can be a limitation of the study.However, the PubMed database does not allow citation and co-citation analysis.The Scopus database, on the other hand, also indexes low-impact journals.3]

Conclusion
This research on CRC has exhibited an upward trend in the number of articles in recent years, and this comprehensive bibliometric research provided an overview of 64,774 articles published between 1980 and 2021.We hypothesize that the number of articles on CRC will continue to grow in number.Analysis of the trend topics revealed that the following keywords were studied in recent years: proliferation, biomarker, migration, EMT, overall survival, autophagy, neoadjuvant chemoradiotherapy, locally advanced rectal cancer, biomarkers, robotic surgery, anastomotic leakage, chemoradiotherapy, metastatic colorectal cancer, KRAS, BRAF, invasion, methylation, meta-analysis, colorectal surgery, laparoscopic surgery, and neoadjuvant therapy.We believe that further research is needed to elucidate the causes of the increasing incidence rates of CRC in young and middle-aged adults.Although there are international collaborations occurring globally, CRC research should be further supported and increased, especially in the underdeveloped countries.This article can guide clinicians, scientists, and surgical assistants about the global outcomes of research on CRC.

Figure 1 .
Figure 1.Bar graph showing the distribution of articles published on colorectal cancer in different years and the estimated number of articles for upcoming 5 years.

Figure 2 .
Figure 2. Global productivity world map showing the distribution of articles published on colorectal cancer by different countries.The bar chart shows the top 20 countries with the highest number of articles.
institutions that produced the highest number of articles on CRC were the University of Texas System (n = 1646), Harvard University (n = 1642), University of California System (n = 1180), The University of Texas MD Anderson Cancer Center (n = 1168), Assistance Publique Hopitaux Paris (n = 1082), Institut National De La Sante Et De La Recherche Medicale (n = 1072), Unicancer (n = 1057), Mayo Clinic (n =

Figure 3 .
Figure 3. A. Network visualization map of cluster analysis showing international collaboration between countries for research on colorectal cancer.Different colors indicate different clusters.Bigger size of the circle indicates the higher number of articles published by the country.B. Density map showing the extent of international collaboration of countries for research on colorectal cancer.The strength of international collaboration score increases from blue to red (blue-green-yellow-red).

Figure 4 .
Figure 4. Network visualization map for cluster analysis based on keyword analysis identifying clustering of colorectal Cancer topics.Different colors indicate different clusters.Keywords in the same cluster are of the same color.The size of the circle indicates the number of uses of the keyword.

Figure 5 .
Figure 5. Network visualization map based on keyword analysis showing past and current trends in colorectal cancer research.In the indicator given in the lower right corner of the figure, the actuality of the topics increases from blue to red (blue-green-yellow-red).The size of the circle indicates the number of times the keyword has been used.

Figure 6 .
Figure 6.Network visualization map based on keyword analysis showing the most cited topics in colorectal cancer.In the indicator given in the lower right corner of the figure, the number of references received by the topic increases from blue to red (blue-green-yellow-red).The size of the circle indicates the number of times the keyword was used.

Table 2
The top 25 most cited articles on colorectal cancer by total number of citations.