Advances in gastrointestinal vascular bleeding disorders: Successful sirolimus treatment in colonic angioectasia

Abstract

BACKGROUND

Gastrointestinal (GI) vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment responses. Despite advancements in diagnostic and therapeutic techniques, optimal management strategies remain elusive, necessitating further research.

AIM

To assess research trends and clinical advancements in GI vascular bleeding disorders, highlighting key themes and therapeutic progress.

METHODS

A bibliometric analysis was conducted using the Web of Science Core Collection database, reviewing publications from 2000 to 2024 to identify trends, high-frequency keywords, and key contributions from leading research institutions. In addition, a case study highlighted the effective application of sirolimus in managing colonic angioectasia in a patient with recurrent GI bleeding who had not responded to previous treatments.

RESULTS

The analysis reviewed 470 scholarly articles from 203 countries, involving 2817 authors across 1502 institutions. The United States led in publication contributions, with strong collaborations with countries like China, England, and Germany. A significant trend was observed in the shift from traditional endoscopic interventions to pharmacological therapies, particularly highlighting the successful use of sirolimus in treating colonic angioectasia. High-frequency keywords such as “angiodysplasia”, “colon”, and “management” were identified, indicating key research themes. The study also noted a growing interest in drug therapies, as evidenced by the increasing prominence of keywords like “thalidomide” since 2018.

CONCLUSION

This study links bibliometric analysis and clinical insights, highlighting the shift to pharmacological management in GI vascular bleeding disorders to improve patient outcomes.

Key Words: Gastrointestinal bleeding; Vascular anomalies; Angioectasia; Pharmacological; Sirolimus

Core Tip: This study uncovers a pivotal shift from traditional endoscopic methods to pharmacological strategies in managing gastrointestinal vascular bleeding disorders. Notably, it highlights the novel use of sirolimus in effectively treating colonic angioectasia, offering fresh insights and potential improvements in patient outcomes.

INTRODUCTION

Gastrointestinal (GI) bleeding is a prevalent and potentially life-threatening condition that affects the entire digestive tract, from the esophagus to the rectum. Its clinical presentations vary, ranging from acute massive bleeding, resulting in severe anemia and shock, to chronic occult bleeding, leading to iron-deficiency anemia[1,2] The etiology of GI bleeding encompasses various causes, such as peptic ulcers, malignancies, inflammatory bowel disease, and vascular anomalies[3-5]. Vascular anomalies such as vascular ectasia, angiodysplasia, telangiectasia, and arteriovenous malformations are particularly noteworthy, especially in elderly patients and those with chronic conditions. The high recurrence and persistence of these anomalies significantly impair quality of life and prognosis. Evidence shows that up to 20% of patients experience re-bleeding within 30 days of discharge, leading to substantial medical costs[6]. Additionally, a systematic review indicates that 42.7% of patients experience re-bleeding even after endoscopic treatment, complicating further therapeutic interventions[7].

The diagnosis and treatment of bleeding associated with vascular anomalies present significant challenges due to complex pathophysiological mechanisms and often subtle clinical presentations. Current management strategies are diverse, including endoscopic treatments, pharmacotherapy, interventional radiology, and surgical procedures[8]. While these approaches have improved patient outcomes, treatment failures and complications remain common. For instance, endoscopic techniques such as electrocoagulation and sclerotherapy, demonstrate limited efficacy in certain lesion locations[9]. Pharmacological treatments, including hormonal therapy, somatostatin analogs, thalidomide, and vascular endothelial growth factor (VEGF) neutralizing antibodies, show promise in controlling bleeding and enhancing quality of life, but their efficacy and safety require further validation[10-12]. Interventional and surgical methods carry high risks and costs, underscoring the urgent need for new therapeutic targets[13].

Despite advancements in diagnostic and therapeutic techniques for GI bleeding, substantial gaps remain in our understanding of the molecular biology of vascular anomalies and the identification of novel therapeutic targets. Current studies are often limited to individual cases or small-scale clinical observations. Bibliometric analysis, a systematic research method, can reveal trends and hotspots, identify influential studies, and suggest potential treatment directions[14]. Such analyses are crucial for a comprehensive understanding and improved management of GI vascular bleeding disorders. Angioectasia accounts for 10% of all GI bleeding cases, contributing to approximately 4%-7% of non-variceal upper GI bleeding, 30%-40% of obscure small bowel bleeding, and 3%-40% of colonic bleeding[15]. It is the most common cause of occult GI bleeding in patients over 60 years old. These lesions are not linked to hereditary, dermatological, or systemic diseases and can affect any part of the GI tract[16]. Nonetheless, there is still considerable debate regarding their pathogenesis, optimal diagnostic methods, and effective therapeutic strategies.

This study integrates bibliometric analysis with clinical observations to systematically assess research progress on GI vascular bleeding disorders. It aims to identify research hotspots, emerging trends, and delineate the overall research landscape, including publication patterns, high-frequency keywords, significant research institutions, and highly cited literature. Furthermore, the study includes clinical observations of specific cases of colonic angioectasia to highlight the successful application of sirolimus. By combining these approaches, the study seeks to uncover recent research trends and provide robust clinical evidence on the efficacy of sirolimus. This comprehensive analysis is intended to offer valuable scientific insights for future research and clinical practice, ultimately aiding clinicians in optimizing diagnostic and therapeutic strategies to enhance patient management and outcomes.

MATERIALS AND METHODS

Data sources

To obtain data from the Web of Science Core Collection database, rigorous research methodologies were employed, utilizing a diverse array of data sources. The search query was defined as follows: [TI = (“gastrointestinal bleeding” OR “upper gastrointestinal bleeding” OR “lower gastrointestinal bleeding” OR “obscure gastrointestinal bleeding” OR “small intestinal bleeding” OR “small bowel bleeding” OR “large intestinal bleeding” OR “large bowel bleeding” OR “esophagus bleeding” OR “stomach bleeding” OR “duodenum bleeding” OR “jejunum bleeding” OR “ileum bleeding” OR “colon bleeding” OR “rectum bleeding”) AND TI = (“angiodysplasia” OR “vascular ectasia” OR “angioectasia” OR “telangiectasia” OR “arteriovenous malformation”) OR AK = (“gastrointestinal bleeding” OR “upper gastrointestinal bleeding” OR “lower gastrointestinal bleeding” OR “obscure gastrointestinal bleeding” OR “small intestinal bleeding” OR “small bowel bleeding” OR “large intestinal bleeding” OR “large bowel bleeding” OR “esophagus bleeding” OR “stomach bleeding” OR “duodenum bleeding” OR “jejunum bleeding” OR “ileum bleeding” OR “colon bleeding” OR “rectum bleeding”) AND AK = (“angiodysplasia” OR “vascular ectasia” OR “angioectasia” OR “telangiectasia” OR “arteriovenous malformation”) OR AB = (“gastrointestinal bleeding” OR “upper gastrointestinal bleeding” OR “lower gastrointestinal bleeding” OR “obscure gastrointestinal bleeding” OR “small intestinal bleeding” OR “small bowel bleeding” OR “large intestinal bleeding” OR “large bowel bleeding” OR “esophagus bleeding” OR “stomach bleeding” OR “duodenum bleeding” OR “jejunum bleeding” OR “ileum bleeding” OR “colon bleeding” OR “rectum bleeding”) AND AB = (“angiodysplasia” OR “vascular ectasia” OR “angioectasia” OR “telangiectasia” OR “arteriovenous malformation”)]. To ensure specificity, we selected English-language articles and review papers published from January 1, 2000 to June 30, 2024. Searches and data collection were completed in a single day to minimize biases from database updates. Only studies directly relevant to our research theme were included, excluding unrelated publications. Initially, 596 articles were identified. A pre-processing phase, using predefined exclusion criteria, removed duplicates and off-topic entries, resulting in 470 validated articles. These manuscripts’ details-titles, authors, affiliations, abstracts, journals, publication dates, and references-were archived in TXT format as “full paper records and references”. The data were then compiled into an Excel database for further analysis.

Bibliometric analysis

Bibliometric analysis is applied to study GI vascular bleeding disorders, using tools like CiteSpace and VOS Viewer for effective data visualization and analysis[17]. CiteSpace aids in co-clustering and graphical representation of temporal data, allowing the identification of key trends and developments. VOS Viewer is utilized to visualize data involving keywords, authors, and institutions through various perspectives. By combining these tools, we systematically organize and analyze the literature to uncover research patterns and progressions within the field.

Study population

We presented a case involving a patient with colonic angioectasia who had previously experienced limited success with blood transfusions and endoscopic treatment. Subsequently, the patient received oral sirolimus (Yixinke; North China Pharmaceutical Group Corporation, Hebei Province, China) therapy at the Air Force Medical Center in Beijing, China. Written informed consent was obtained from the patient prior to treatment. Laboratory tests, fecal occult blood tests and capsule endoscopy assessments, were conducted. This study was carried out in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of the Air Force Medical Center (No. 2021-97-PJ01).

RESULTS

Number of papers published

Within the scope of this inquiry, a total of 470 scholarly articles were meticulously reviewed, encompassing contributions from 203 countries and representing the collaborative efforts of 2817 authors affiliated with 1502 institutions. Figure 1 illustrates the temporal distribution of publications related to GI vascular bleeding disorders research. It is evident that the volume of publications in this field has shown a steady increase since 2000, reaching its zenith in 2019. Over the past decade, there has consistently been more than 20 papers published annually, likely driven by advancements in endoscopic technology, which have heightened interest and focus on this area of study.

Figure 1 Annual publications and citations on gastrointestinal vascular bleeding disorders from 2000 to 2024.

Countries and institutions

To identify the nations that have significantly impacted GI vascular bleeding disorders research over the past two decades, we conducted an exhaustive analysis of publication output from 203 countries. Figure 2A displays the distribution of scholarly articles by country and the collaborative networks. The lines represent inter-country collaborations, with thicker and darker lines indicating more frequent interactions. The United States emerges as the leading country in terms of publications, maintaining strong collaborations with numerous countries, including China, England, and Germany. Other key contributors in this field include China, Japan, England, Germany, Italy, and Spain, all of which also demonstrate substantial inter-country collaborations. Table 1 presents the leading 20 countries and institutions, strategically dispersed across continents such as Europe, Asia, North America, South America, and Oceania. Europe (n = 10) and Asia (n = 6) exhibit notable dominance. Among these regions, the United States (n = 141, 30% of the total) stands out as the foremost contributor, followed by Japan (n = 50, 11%) and China (n = 49, 10%).

Figure 2 Collaborative mapping of contributions to publications on gastrointestinal vascular bleeding disorders. A: Countries; B: Institutions.

Table 1 Top 20 countries and institutions contributing to research in gastrointestinal vascular bleeding disorders.

Rank	Country	Counts	Percent (%)	Institutions	Counts	Percent (%)
1	United States	141	30	Harvard University	20	4
2	Japan	50	11	Mayo Clinic	20	4
3	China	49	10	Massachusetts General Hospital	15	3
4	Italy	41	9	Harvard Medical School	14	3
5	England	36	8	University of Toronto	12	3
6	Spain	26	6	Cleveland Clinic Foundation	11	2
7	Germany	25	5	University of California System	11	2
8	South Korea	21	4	University of London	10	2
9	Canada	20	4	Johns Hopkins University	9	2
10	France	18	4	Saint Michaels Hospital Toronto	9	2
11	Netherlands	14	3	University College London	9	2
12	Turkey	10	2	Us Department of Veterans Affairs	9	2
13	Australia	9	2	Veterans Health Administration Vha	9	2
14	Ireland	8	2	Ciber Centro De Investigacion Biomedica En Red	8	2
15	Israel	8	2	Assistance Publique Hopitaux Paris Aphp	7	1
16	Greece	6	1	Consejo Superior De Investigaciones Cientificas Csic	7	1
17	Argentina	5	1	Csic Centro De Investigaciones Biologicas Cib	7	1
18	India	5	1	University of Utah	7	1
19	Poland	5	1	Utah System of Higher Education	7	1
20	Saudi Arabia	5	1	Washington University Wustl	7	1

Institutions such as the Mayo Clinic, University of Utah, and University of Toronto are pivotal, having published a significant number of research articles and maintaining extensive collaborative networks (Figure 2B). Table 1 elucidates the top global institutions, with Harvard University leading (n = 20, 4%), followed by Mayo Clinic (n = 20, 4%), and Massachusetts General Hospital (n = 15, 3%). Notably, among the top 20 institutions, those based in the United States dominate, comprising twelve of the entries. Spain follows with three institutions, while Canada and England each contribute two. This distribution underscores the concentrated yet diverse nature of research excellence in this domain.

Author and journal analysis

The citation frequency of a research paper is a vital indicator for assessing its academic impact. In the realm of GI vascular bleeding disorders, 2817 authors have contributed to the body of literature. Among the prolific contributors, the top 10 ranked authors have each published four or more articles in this field. Notably, three authors have achieved over 80 citations: Shovlin CL tops the list with 113 citations, followed by Lewis BS with 92 citations, and Junquera F with 80 citations (Table 2). Using this dataset, we constructed a collaborative network diagram featuring authors who have published three or more papers (Figure 3A). This diagram highlights the strong collaborative relationships among key authors such as Al-Samkari H, Iyer VN, Kasthuri RS, Pagella F, Albinana V, and Pruthi RK, all of whom demonstrate significant interconnectedness.

Figure 3 Collaborative mapping of contributions to publications on gastrointestinal vascular bleeding disorders. A: Authors; B: Journals.

Table 2 Principal investigators and co-cited scholars.

Rank	Authors	Document	Co-cited authors	Citations
1	Al-samkari H	9	Shovlin CI	113
2	Blackshear JL	6	Lewis BS	92
3	Faughnan ME	6	Junquera F	80
4	lyer VN	6	Foutch PG	69
5	Mcnamara D	6	Pennazio M	62
6	Gossage JR	5	Boley SJ	62
7	Holleran G	5	Gostout CJ	59
8	Pagella F	5	Warkentin TE	54
9	Rodriguez-lopez J	5	Yamamoto H	54
10	Bernabeu C	4	Al-Samkari H	51

Since 2012, there has been a steady increase in articles related to GI vascular bleeding disorders, reflecting a burgeoning interest within the scholarly community. These articles have been published across 225 journals. Utilizing VOS Viewer, we constructed a journal network diagram based on a minimum publication threshold of three articles (Figure 3B). Notably, journals such as Digestive Disease and Sciences, European Journal of Gastroenterology and Hepatology, and Endoscopy are distinguished by their active citation relationships. Table 3 lists the top 10 journals by publication count. The European Journal of Gastroenterology and Hepatology leads with 19 articles, accumulating 203 citations and an average of 11 citations per article. Though Endoscopy ranks fourth with 13 articles, it boasts the highest citation rate per article at 96, along with the highest impact factor of 11.5. According to Table 4, a significant observation is that all the top 10 journals demonstrate citation counts surpassing 150. Gastrointestinal Endoscopy claims the highest number of citations with 982 co-citations, followed closely by the American Journal of Gastroenterology (749 co-citations) and Gastroenterology (654 co-citations). The New England Journal of Medicine stands out with an impressive impact factor of 96.2, underscoring its influence and prominence in the field.

Table 3 Leading academic journals by publication volume on gastrointestinal vascular bleeding disorders studies.

Rank	Journal	H-index	IF (2023)	JCR	Publications	Citations	Average citation/publication
1	European Journal of Gastroenterology and Hepatology	95	2.3	Q3	19	203	11
2	Digestive Diseases and Sciences	113	2.5	Q2	18	617	34
3	World Journal of Gastroenterology	129	4.3	Q1	15	378	25
4	Endoscopy	129	11.5	Q1	13	1243	96
5	Journal of Clinical Gastroenterology	102	2.8	Q2	13	291	22
6	Digestive and Liver Disease	84	4	Q1	8	181	23
7	Scandinavian Journal of Gastroenterology	105	1.6	Q3	8	117	15
8	Internal Medicine	64	1	Q3	7	61	9
9	Blood Coagulation and Fibrinolysis	67	1.2	Q4	6	79	13
10	Journal of Gastrointestinal and Liver Diseases	42	2.1	Q3	6	116	19

IF: Impact factor; JCR: Journal citation reports.

Table 4 Leading journals co-cited in studies on gastrointestinal vascular bleeding disorders over the past two decades.

Rank	Co-cited journal	H-index	IF (2023)	JCR	Co-citations
1	Gastrointestinal Endoscopy	188	7.7	Q1	982
2	American Journal of Gastroenterology	234	8	Q1	749
3	Gastroenterology	368	25.7	Q1	654
4	Endoscopy	129	11.5	Q1	587
5	New England Journal of Medicine	933	96.2	Q1	385
6	Gut	262	23	Q1	316
7	Digestive Diseases and Sciences	113	2.5	Q2	256
8	Journal of Clinical Gastroenterology	102	2.8	Q2	254
9	Journal of Heart and Lung Transplantation	122	6.4	Q1	193
10	blood	426	21	Q1	189

IF: Impact factor; JCR: Journal citation reports.

Co-cited references and reference bursts

Using VOS Viewer, we identified cited references that surpassed a minimum threshold of 10 citations to create a co-citation network visualization (Figure 4A). Enlarged circles in the visualization indicate a higher citation count, and thus, greater relevance of the referenced scholarly works. Noteworthy references such as “Jabbari M, 1984, Gastroenterology”, “Warkentin TE, 2003, Transfus Med Rev”, and “Bowers M, 2000, Brit J Haematol” exhibit significant co-citation associations. Table 5 presents the top 10 most cited references in this field of study. All these references have achieved a minimum of 30 citations, with one publication surpassing the landmark of 45 citations. This underscores the profound impact and significance of these works in advancing the understanding of GI vascular bleeding disorders, marking pivotal contributions to the ongoing discourse in the subject.

Figure 4 Co-cited references analysis of global research on gastrointestinal vascular bleeding disorders. A: Co-citation network visualization of cited references; B: Top 25 references with the strongest citation bursts.

Table 5 Most referenced works on gastrointestinal vascular bleeding disorders.

Rank	Co-cited reference	Citations
1	Shovlin CL (2000). J Am J Med Genet	45
2	Jabbari M (1984). Gastroenterology	41
3	Foutch PG (1993). Am J Gastroenterol	40
4	Vincentelli A (2003). New Engl J Med	40
5	Boley SJ (1977). Gastroenterology	35
6	Pennazio M (2004). Gastroenterology	34
7	Ell C (2002). Endoscopy	33
8	Gostout CJ (1992). J Clin Gastroenterol	33
9	Heyde EC (1958). New Engl J Med	31
10	Spahr L (1999). Gut	30

Cited references within citation bursts denote papers frequently cited by scholars in a given field over a defined period. Using CiteSpace, we identified 25 reference papers demonstrating significant citation bursts (Figure 4B). Detailed in Table 6, the reference with the most pronounced citation burst (8.54) is “Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: Results of a pilot study” by Lewis and Swain (2002), with the burst lasting from 2003 to 2007. Another notable reference, “Intravenous Bevacizumab for Refractory Hereditary Hemorrhagic Telangiectasia-Related Epistaxis and Gastrointestinal Bleeding” by Iyer VN, exhibited the most recent significant burst (6.47), with the burst period from 2020 to 2024.

Table 6 Proliferation of scholarly references for the top 10 articles on gastrointestinal vascular bleeding disorders.

Rank	Frequency	Centrality	Title	Journal	Author	Year
1	17	0.08	Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: Results of a pilot study	Gastrointest Endosc	Lewis BS	2002
2	16	0.08	The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding	Endoscopy	Ell C	2002
3	15	0.11	Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: Report of 100 consecutive cases	Gastroenterology	Pennazio M	2004
4	14	0	Intravenous Bevacizumab for Refractory Hereditary Hemorrhagic Telangiectasia-Related Epistaxis and Gastrointestinal Bleeding	Mayo Clin Proc	Iyer VN	2018
5	14	0.09	Review article: Gastrointestinal angiodysplasia - pathogenesis, diagnosis and management	Aliment Pharm Ther	Sami SS	2014
6	12	0.05	A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease	Gastroenterology	Costamagna G	2002
7	11	0.28	A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding	Am J Gastroenterol	Carey EJ	2007
8	10	0.15	Thalidomide for treatment of gastrointestinal angiodysplasia in patients with left ventricular assist devices: Case series and treatment protocol	J Heart Lung Transpl	Draper K	2015
9	10	0.14	ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding	Am J Gastroenterol	Gerson LB	2015
10	10	0.02	Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia	Orphanet J Rare Dis	Buscarini E	2019

Hotspots and frontiers

Keywords encapsulate the essence of scholarly publications, guiding the academic community through the breadth of existing literature. Utilizing VOS Viewer, we generated a visually compelling depiction of keyword clusters (Figure 5A). Keywords such as “angiodysplasia”, “colon”, and “management” exhibit high significance. Figure 5B delineates the top 20 key phrases extensively referenced in the field of GI vascular bleeding disorders over the past two decades. The most prominent key phrase eruption was “push enteroscopy” (7.08), followed by “hereditary hemorrhagic telangiectasia” (6.4). Notably, the phrase “thalidomide” began gaining traction in 2018, indicating a growing interest in the pharmacological management of GI vascular bleeding among researchers.

Figure 5 Keywords analysis and research hotspots of gastrointestinal vascular bleeding disorders research. A: Keyword co-occurrence network analysis; B: Keywords with the strongest citation bursts.

Successful sirolimus treatment in colonic angioectasia

A 66-year-old male patient was admitted due to intermittent melena persisting for one year. Each episode lasted 3-5 days, occurring once daily at intervals of 1-2 months. The patient reported associated symptoms of fatigue and dizziness, which significantly impacted his quality of life. His medical history included hypertension but no other chronic illnesses or coagulation abnormalities. He had no family history of GI bleeding or vascular disorders. Capsule endoscopy revealed diffuse colonic angioectasia (Figure 6A), which was confirmed by histopathology (Figure 6B). Laboratory tests showed a hemoglobin level of 93 g/L, with low serum iron and ferritin levels (ferritin: 15 ng/mL; normal range: 30-400 ng/mL), indicating chronic blood loss anemia. Despite receiving high-dose erythropoiesis-stimulating agents, iron supplements, blood transfusions, and endoscopic therapy, his hemoglobin level remained persistently low, and he continued to experience recurrent melena. With the patient’s informed consent, we initiated oral sirolimus capsules (Yixinke; North China Pharmaceutical Group Corp, Hebei Province, China). The initial dose was 0.8 mg/m² once daily, with adjustments made to maintain a therapeutic trough level of 5-10 ng/mL[18]. The patient was closely monitored during the first week of treatment for potential adverse effects. This regimen rapidly controlled GI bleeding. During a six-month follow-up, the patient experienced no further bleeding episodes, weekly fecal occult blood tests remained negative, and his hemoglobin level significantly increased to 110 g/L, eliminating the need for further transfusions. Serum iron and ferritin levels also returned to normal ranges, reflecting improved iron stores. Notably, the vascular lesion had significantly reduced (Figure 6C). No serious adverse events were observed during the follow-up period.

Figure 6 Endoscopic and histopathological findings of colonic angioectasia. A: Endoscopic image of diffuse colonic vascular lesions before sirolimus treatment; B: Histopathological image of the colonic angioectasia; C: Endoscopic image of colonic vascular lesions after sirolimus treatment, showing significant reduction.

DISCUSSION

Major findings

This study comprehensively examined the key trends, collaborative networks, and academic impacts in GI vascular bleeding disorders through a bibliometric analysis of research from 2000 to 2024. The results revealed a significant increase in scholarly articles, reflecting growing global interest and research efforts. Major contributors include institutions and authors from Europe, America, and Asia, highlighting extensive international collaboration. A notable clinical observation is the successful use of sirolimus for colonic angioectasia, demonstrating its potential efficacy in controlling GI bleeding. This marks a shift from traditional endoscopic techniques to pharmacological management as a viable treatment option. These findings provide valuable insights into advancing research and treatment strategies for GI vascular bleeding disorders.

Publication volume, countries, and institutions

Our analysis showed a steady increase in scholarly articles on GI vascular bleeding disorders since 2012, driven by advances in diagnostic technologies, such as improved endoscopic techniques and capsule endoscopy, as well as growing interest in pharmacological management options[19,20]. The United States stands out as the largest contributor, accounting for 30% of the literature, with active participation from European and Asian institutions as well. Prominent organizations like Mayo Clinic and Harvard University highlight the United States’s leading role in this field, while institutions such as the University of Toronto in Canada demonstrate strong research potential and foster international collaboration, introducing new perspectives and methodologies.

Authors and journals

At the author level, Shovlin CL, Lewis BS, and Junquera F are the most cited, with 113, 92, and 80 citations respectively. Shovlin CL is renowned for her extensive work on vascular disorders, particularly hereditary hemorrhagic telangiectasia. Her research has significantly contributed to understanding the genetic and clinical aspects of vascular anomalies, leading to improved diagnostic and therapeutic strategies[21]. Lewis BS has made significant contributions to gastroenterology, particularly in advancing endoscopic techniques for diagnosing and managing GI bleeding[22,23]. Junquera F is known for his research on therapeutic outcomes of interventions for GI vascular anomalies, including endoscopic and pharmacological treatments[24,25]. Collaboration networks reveal strong co-authorships among researchers like Al-Samkari H, Iyer VN, and Kasthuri RS, who focus on innovative diagnostic and therapeutic approaches, particularly in pharmacological management. Concerning journals, the European Journal of Gastroenterology and Hepatology leads with 19 articles, indicating its prominence in this filed. However, Endoscopy boasts the highest citations per article (96) and an impact factor of 11.5, highlighting its influence and academic impact. The New England Journal of Medicine stands out with an impressive impact factor of 96.2, emphasizing its authoritative position in medical research. While not exclusive to gastroenterology, its inclusion of impactful GI bleeding studies highlights the broader medical significance of this research, often driving shifts in clinical practice and research priorities.

Co-cited references

The co-citation network constructed using VOS Viewer highlights key references in GI vascular bleeding disorder research, such as “Jabbari M, 1984, Gastroenterology” and “Warkentin TE, 2003, Transfus Med Rev” which underscore their foundational role in the field[26,27]. The 2002 study by Lewis and Swain[28] on capsule endoscopy demonstrated the highest citation burst from 2003 to 2007, marking significant advancements in diagnostic techniques. More recently, the study by Iyer et al[29], has the most recent citation burst from 2020 to 2024, indicating a shift towards pharmacological therapies. By targeting VEGF A, bevacizumab offers a novel approach to manage severe bleeding, suggesting a pivot from traditional endoscopic techniques to drug therapies. While this shift holds promise for improving patient outcomes and quality of life, careful monitoring for side effects such as hypertension and proteinuria remains essential. Despite these advancements, challenges remain in fully understanding the molecular biology of vascular anomalies and identifying effective therapeutic targets. Current research focuses on pathways such as VEGF, Notch, and transforming growth factor-β, which are critical in angiogenesis and vascular anomalies[30-32]. However, small patient cohorts and limited multicenter validation often restrict the generalizability of findings. The complexity of pathway interactions and compensatory mechanisms further complicates therapy development, as targeting a single pathway may be insufficient. Additionally, genetic variability and epigenetic modifications can lead to diverse therapeutic responses. Future research should explore multi-pathway regulation and personalized therapeutic strategies. Integrating genomic and proteomic technologies could uncover novel therapeutic targets and biomarkers, advancing personalized medicine. Large-scale, multicenter clinical trials will be essential to validate these therapies and ensure their applicability across diverse populations.

Keyword analysis

Keyword analysis reveals key research trends and future directions in GI vascular bleeding disorders. Terms like “angiodysplasia”, “colon”, and “management” spotlight current research themes, while earlier focus on “push enteroscopy” and “hereditary hemorrhagic telangiectasia” emphasized endoscopic techniques[33]. Since 2018, the emergence of “thalidomide” as a keyword points to a shift towards drug therapies[34-36]. This is corroborated by co-citation analysis, with studies such as Iyer et al’s work on bevacizumab gaining attention, demonstrating growing interest in drug-based treatments to improve patient outcomes[29]. My recent study on sirolimus for colonic angioectasia aligns with this evolving focus. Sirolimus inhibits the mammalian target of rapamycin (mTOR) signaling pathway, suppressing tumor angiogenesis and limiting tumor growth and metastasis[37,38]. Commonly used as an immunosuppressant in organ transplantation, its ability to limit vascular endothelial cell activation and inflammatory cell infiltration supports its application in colonic angioectasia[39]. In this case, sirolimus effectively controlled GI bleeding and improved hemoglobin levels without serious adverse events during follow-up, despite potential side effects like mouth ulcers, diarrhea, and elevated triglycerides. Compared to other drugs, sirolimus demonstrates a favorable safety and efficacy profile. For example, bevacizumab, which targets VEGF, is effective in hereditary hemorrhagic telangiectasia but is limited by side effects like hypertension and proteinuria. Thalidomide reduces GI bleeding by inhibiting VEGF and tumor necrosis factor-α but is constrained by significant adverse effects such as peripheral neuropathy and teratogenicity. Octreotide, a somatostatin analog, reduces bleeding by decreasing splanchnic blood flow, but its long-term efficacy is inconsistent, and tolerance may develop. In contrast, sirolimus, as an mTOR inhibitor, uniquely regulate angiogenesis and inflammation, providing sustained bleeding control with relatively mild side effects, making it a safer and more promising option. Sirolimus also differs significantly in its mechanism of action. While bevacizumab and thalidomide primarily target the VEGF pathway, sirolimus inhibits mTOR, potentially acting through broader mechanisms such as suppressing cell proliferation and inflammation. This distinction supports its potential application in complex vascular diseases. However, current research on sirolimus remains limited, particularly lacking multi-center studies and long-term follow-up. Further research is needed to validate its efficacy and safety and establish its role in treating GI vascular bleeding. This underscores the importance of continued investment in drug development and clinical trials to advance treatment strategies for GI vascular bleeding disorders.

CONCLUSION

This study delivers an insightful analysis of GI vascular bleeding disorders, highlighting key research trends and clinical advancements. Through bibliometric analysis, it identifies essential themes like angiodysplasia and colon management and notes a shift from endoscopic to pharmacological therapies such as thalidomide and bevacizumab. The successful use of sirolimus in treating colonic angioectasia demonstrates the potential of drug therapies to manage GI bleeding and improve patient outcomes. This transition towards pharmacological management underscores the need for further research with larger cohorts and multi-center studies to evaluate new therapies. Overall, the study emphasizes the importance of continued investment in drug development and clinical trials to advance patient care.