Abstract
Background and aims
Treatment of acute gastric variceal bleeding (AGVB) in patients with large spontaneous portosystemic shunts (SPSS) remains challenging due to the severe, refractory nature of bleeding and the limitations of guideline-recommended therapies, which are associated with difficulty in achieving hemostasis, procedure-related complications, and resource-limited settings. This study aimed to explore the feasibility of balloon-occluded retrograde transvenous obliteration (BRTO)-assisted endoscopic cyanoacrylate injection (ECI) as a potential therapy for AGVB with large SPSS.
Methods
This retrospective single-center case series included adult patients (aged 18 or older) who underwent BRTO-assisted ECI for the treatment of AGVB with large SPSS (≥1.2 cm) from March 2022 to December 2024, with a 1-year follow-up.
Results
A total of 12 patients were enrolled (mean age 57.8 years; 83.3% male). Among them, 8 were classified as GOV2 and 4 as IGV1, with a median SPSS diameter of 1.6 cm (IQR: 1.2–2.6). All cases of GVs (gastric varices) were attributed to liver cirrhosis, most commonly secondary to hepatitis B virus (58.3%). The majority of patients had Child-Pugh class B (50.0%) or C (41.7%). The clinical success rate was 91.6% (11/12), and no symptomatic embolism or organ dysfunction was observed. There was no early rebleeding (0/12), while the late rebleeding rate was 33.3% (4/12) due to GVs recurrence without regular secondary prophylaxis of bleeding. Although no procedure-related deaths occurred, the 1-year mortality from all causes was 41.7%, primarily from progression of primary liver diseases and co-morbidities.
Conclusion
BRTO-assisted ECI appears to be a potential therapy for treating AGVB with large SPSS, with high clinical success and no observed ectopic embolization. Larger prospective multicenter studies are needed to confirm these findings and evaluate long-term outcomes.
Keywords: acute gastric variceal bleeding, potential therapy, balloon-occluded retrograde transvenous obliteration assisted endoscopic cyanoacrylate injection, large spontaneous portosystemic shunt, retrospective study
Introduction
Gastric varices (GVs), though less common than esophageal varices (EVs) in patients with portal hypertension, are clinically more difficult to control owing to severe bleeding and high rebleeding rates, reaching up to 80%–90% in some reports (1–3). According to the Sarin classification, GVs are categorized into gastroesophageal varices type 1 (GOV1, extending along the lesser curvature), GOV2 (extending toward the fundus), isolated gastric varices type 1 (IGV1, located in the fundus), and IGV2 (elsewhere in the stomach). While GOV1 is most prevalent, GV hemorrhage commonly occurs from GOV2 and IGV1. Endoscopic cyanoacrylate injection (ECI) has long been the standard treatment for acute gastric variceal bleeding (AGVB) (4–8), but ectopic embolization remains a major safety concern, especially in subpopulation with spontaneous portosystemic shunts (SPSS) (9, 10).
Notably, IGV1 and GOV2 are prone to developing SPSS, in particular gastrorenal shunts (GRS) or splenorenal shunts (SRS). The presence of SPSS is associated with more severe GVs bleeding, greater difficulty in achieving hemostasis, and increased risks of ectopic embolization and rebleeding. Endoscopic ultrasonography (EUS)-guided coil embolization and cyanoacrylate injection demonstrates strong performance in lowering embolization and rebleeding rates by enabling targeted delivery and reducing the injected volume (11, 12). Current recommendations suggest coil deployment when the shunt diameter exceeds 0.5 cm, with coil size determined by the diameters of the varices and shunt (13). However, suitable coils may be unavailable in patients with large SPSS due to size mismatch, given that the maximum available coil diameter is 2.0 cm, whereas the diameter of an SPSS can exceed 2.0 cm (14, 15). Furthermore, the available coil size varies across centers. For instance, the maximum coil diameter available at our center is 1.2 cm, which limits EUS-guided therapy for patients with SPSS exceeding this diameter. Moreover, EUS-guided therapy may be faced with risks of operational failure and ectopic embolism, for which current international guidelines do not adequately address this key point (4–6). In addition, EUS-guided therapy is also impractical in resource-limited settings, considering its steep learning curve and the demand for substantial operator expertise (16).
Balloon-occluded retrograde transvenous obliteration (BRTO) and transjugular intrahepatic portosystemic shunt (TIPS) are considered alternative strategies for AGVB with large SPSS (17–19). However, BRTO has long been viewed as a less favorable option due to risks associated with large sclerosant volumes and increased portal pressure, potentially leading to renal dysfunction, progression of esophageal varices, or refractory ascites (20, 21). As for TIPS in this subpopulation, it may not work as anticipated, since it may induce or exacerbate hepatic encephalopathy (HE) and progressive liver failure (22, 23). Moreover, TIPS is limited in patients with portal vein thrombosis (24, 25). There are no clear recommendations in current international guidelines for the treatment of this subpopulation (4–6). More recently, previous studies have reported BRTO-assisted ECI showed potential in AGVB with SPSS (26–29), but evidence remains scarce regarding its efficacy and safety in this subpopulation with large SPSS.
To address this gap, we conducted a retrospective study to explore the potential feasibility of BRTO-assisted ECI for the treatment of AGVB with large SPSS.
Materials and methods
Study cohort
This was a retrospective single-center case series study, and adult patients (aged 18 or older) who underwent BRTO-assisted ECI for treating AGVB with large SPSS from March 2022 to December 2024 at Peking Union Medical College Hospital (PUMCH) were retrospectively identified through electronic medical records.
Between March 2022 and December 2024, patients presenting AGVB (GOV2 or IGV1) and large SPSS were considered for the combined therapy, which was judged based on initial endoscopic signs of active or recent bleeding (red spot, adherent clot, etc.) and pre-procedural portal vein assessment with enhanced computed tomography (CT). It was noted that CT-detected SPSS diameters exceeding 1.2 cm were enrolled for the combined therapy in this study, considering the fact that the maximum diameter of the coil in our center was 1.2 cm (Nester Coils; Cook Medical, Bloomington, Indiana, USA). Although EUS-guided coil embolization and cyanoacrylate injection is technically mature and widely applied in AGVB with SPSS at our center, it was not performed for this subpopulation because the diameter of the SPSS exceeded the maximum available coil diameter at our center, which may result in inadequate anchoring and systemic migration or ectopic embolization. Other pre-procedural assessments included clinical evaluation and laboratory tests (complete blood counts, comprehensive metabolic panel, INR, ammonia, etc.). Exclusion criteria included: (1) age <18 years; (2) SPSS diameter <1.2 cm; (3) multiorgan failure with contraindications to endoscopic intervention; (4) pregnant or lactating women; (5) a history of upper gastrointestinal tract surgery; (6) refusal to undergo the procedure. A study flow chart detailing the screening and enrollment process is presented in Figure 1. Informed consent was obtained from the patient or his/her surrogate.
Figure 1.
Screening chart of eligible patients. AGVB, acute gastric variceal bleeding; SPSS, spontaneous portosystemic shunts; BRTO, balloon-occluded retrograde transvenous obliteration; ECI, endoscopic cyanoacrylate injection.
The study was approved by the institutional ethics committee of PUMCH (No. K3377) and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Data collection and study design
Upon admission, all enrolled patients were planned to undergo BRTO-assisted ECI, which was performed in the interventional radiology suite under general anesthesia and in the supine position. An upper GI endoscope (H260J, Olympus) was initially introduced into the stomach to confirm AGVB and criminal GV, and a transfemoral approach was used to position an angiographic balloon-occluding catheter into the SPSS for further angiography and balloon occlusion. Criminal GV was then treated with the “sandwich” method, comprising consecutive endoscopic injections of lauromacrogol-cyanoacrylate-lauromacrogol into GV. The amount of cyanoacrylate was decided by endoscopists according to the size of the targeted GV. The balloon-occluding catheter was deflated and withdrawn 2 min after ECI. Endoscopic band-ligation was performed simultaneously if the patient also had a high-risk EV (Figure 2).
Figure 2.
Schematic representation of BRTO-assisted ECI in treating GV with large GRS or SRS. (A) Relationship of the GRS relative to the GVs and systemic circulation (left renal vein); (B) Angiographic catheter balloon occlusion of the GRS via the transfemoral route; (C) Endoscopic injection of cyanoacrylate into the GVs following balloon occlusion of the GRS. (D) Relationship of the SRS relative to the gastric varices and systemic circulation (left renal vein); (E) Angiographic catheter balloon occlusion of the SRS via the transfemoral route; (F) Endoscopic injection of cyanoacrylate into the gastric varices during balloon occlusion of the SRS. GV, gastric varix; GRS, gastrorenal shunts; IVC, inferior vena cava; SRS, splenorenal shunts.
The primary outcome was clinical success, defined as the achievement of complete hemostasis from GVs with no recurrence of bleeding within the first 5 days after BRTO-assisted ECI (5). The secondary outcomes included overall rebleeding, early rebleeding (cases where rebleeding occurred between the 6th and 42nd day since BRTO-assisted ECI), late rebleeding (cases where rebleeding occurred after 6 weeks since BRTO-assisted ECI) (6), reinterventions needed, reappearance of GVs, treatment-related complications (newly developed or aggravated EVs, ectopic embolism, etc.), 6-week and 1-year mortality from all causes. Rebleeding was defined as recurrent melena or hematemesis occurring more than 5 days after treatment, resulting in any 1 of the following: (1) hospital admission, (2) blood transfusion, (3) 3-g/dL drop in hemoglobin, or (4) death within 6 weeks (18).
Long-term follow-up, extending up to 12 months from enrollment or until the date of death or liver transplantation, was scheduled to assess rebleeding, reintervention, complications, and survival.
Statistical analysis
Clinical data, including patient age, sex, clinical history, diagnosis and co-morbidities, laboratory results, endoscopic findings, technical details of the combined therapy, adverse events, and outcomes were collected. Categorical variables were presented as counts (percent), and continuous variables as mean ± standard deviation (SD). Non-normally distributed variables were summarized as median [interquartile range (IQR)]. Statistical analysis was performed utilizing the SPSS software version 26 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp, USA).
Results
Baseline characteristics
From March 2022 to December 2024, 336 patients with AGVB were assessed for eligibility at Peking Union Medical College Hospital. A total of 324 patients were excluded (Figure 1) because of an SPSS diameter <1.2 cm (n = 311), multiorgan failure with contraindications to endoscopic intervention (n = 8), prior upper gastrointestinal surgery (n = 2), and refusal to undergo the procedure (n = 3). Three patients who refused the procedure achieved short-term clinical improvement after conservative treatment and declined further invasive intervention. Finally, A total of 12 patients with AGVB and large SPSS were enrolled in this study (Table 1). The cohort consisted of 10 males and 2 females, with a mean age of 57.8 ± 11.7 years. All cases of GVs were attributed to liver cirrhosis, and the most common cause was hepatitis B-related cirrhosis (58.3%, 7/12), followed by alcoholic cirrhosis (16.7%, 2/12); other causes included cirrhosis secondary to hepatitis C (8.3%, 1/12), autoimmune hepatitis (AIH) (8.3%, 1/12), and Langerhans cell histiocytosis (LCH) (8.3%, 1/12). Among the seven patients with HBV-related cirrhosis, four had comorbid hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). The majority of patients were classified as Child-Pugh class B (50%, 6/12) or C (41.7%, 5/12), with a mean Child-Pugh score of 8.8 ± 2.1. Ascites was present in 75% of patients, while 25% had HE. 8 patients were classified as GOV2 and 4 patients as IGV1. The mean GV diameter was 3.17 ± 0.84 cm. The majority of SPSS were GRS (83.3%, 10/12), while the remaining 16.7% (2/12) were SRS, with an overall median diameter of 1.6 cm (IQR: 1.2–2.6).
Table 1.
Summary of patients’ clinical characteristics.
| Characteristics | Value |
|---|---|
| Patients, n | 12 |
| Sex (M/F) | 10/2 |
| Age, y, mean (SD) | 57.8 (11.7) |
| Etiology of cirrhosis, n (%) | |
| HBV | 7 (58.3%) |
| HCV | 1 (8.3%) |
| Alcohol | 2 (16.7%) |
| AIH | 1 (8.3%) |
| LCH | 1 (8.3%) |
| Hb, g/L, mean (SD) | 60.1 (20.8) |
| PLT, ×106, mean (SD) | 63.9 (22.8) |
| ALB, g/L, mean (SD) | 29.4 (5.4) |
| Tbil, μmol/L, mean (SD) | 29.1 (21.8) |
| PT, s, median (IQR) | 17.3 (14.9–18.6) |
| Ascites, n (%) | |
| None | 3 (25%) |
| Mild | 8 (66.7%) |
| Moderate | 1 (8.3%) |
| HE, n (%) | 3 (25%) |
| Comorbid HCC, n (%) | 4 (33.3%) |
| Comorbid PVTT, n (%) | 4 (33.3%) |
| Child-Pugh class, n (%) | |
| A | 1 (8.3%) |
| B | 6 (50%) |
| C | 5 (41.7%) |
| Child-pugh score, mean (SD) | 8.8 (2.1) |
| Type of GVs, n (%) | |
| IGV1 | 4 (33.3%) |
| GOV2 | 8 (66.7%) |
| Type of SPSS, n (%) | |
| GRS | 10 (83.3%) |
| SRS | 2 (16.7%) |
| Diameter of GV, cm, mean (SD) | 3.17 (0.84) |
| Diameter of SPSS (cm), median (IQR) | 1.6 (1.2–2.6) |
SD, standard deviations; IQR, interquartile range; HBV, hepatitis B virus; HCV, hepatitis C virus; AIH, autoimmune hepatitis; LCH, Langerhans cell histiocytosis; HB, hemoglobin; PLT, platelet; ALB, albumin; TBil, total bilirubin; PT, prothrombin time; HE, hepatic encephalopathy; HCC, hepatocellular carcinoma; PVTT, portal vein tumor thrombus; GVs, gastric varices; IGV, isolated gastric varices type 1; GOV2, gastroesophageal varices type 2; GRS, gastrorenal shunts; SRS, splenorenal shunts; SPSS, spontaneous portosystemic shunts.
Outcomes
Primary and secondary outcomes are summarized in Table 2. The clinical success was achieved in 91.6% (11/12), and 3 patients completed endoscopic esophageal variceal ligation simultaneously (Figure 3). During postoperative surveillance, no symptomatic ectopic embolism, infection, renal dysfunction, or liver function deterioration was observed. No newly developed or aggravated ascites or HE was documented. One patient (8.3%, 1/12) was found to have aggravated EV on follow-up endoscopy at 1-month post-procedure. During the follow-up period, the overall rebleeding rate was 33.3% (4/12), with no early rebleeding (0%, 0/12) and a late rebleeding rate of 33.3% (4/12), occurring on days 52, 115, 207, and 303 post-procedure, respectively. It was noted that none of the four patients who experienced rebleeding had received primary disease therapy or secondary prophylaxis for variceal hemorrhage due to personal reasons (e.g., decreased treatment compliance or poor economic status). Endoscopic examination confirmed that all late rebleeding episodes were attributable to GVs recurrence. Two of these patients were successfully managed with repeated BRTO-assisted ECI, while the other two declined further invasive treatment after their condition stabilized with conservative therapy. Accordingly, the rates of GVs recurrence and reintervention were 33.3% (4/12) and 16.7% (2/12), respectively. No mortality was observed within the first six weeks. Although no procedure-related deaths occurred, the 1-year mortality from all causes was 41.7% (5/12), due to hepatocellular carcinoma progression and multiorgan failure in four patients and COVID-19 infection in one patient.
Table 2.
Treatment and follow-up outcomes.
| Outcomes | Value |
|---|---|
| Clinical success, n (%) | 11 (91.6%) |
| Total Rebleeding, n (%) | 4 (33.3%) |
| Early rebleeding, n (%) | 0 (0%) |
| Late rebleeding, n (%) | 4 (33.3%) |
| Reintervention, n (%) | 2 (16.7%) |
| 6-week mortality from all causes | 0 (0%) |
| 1-year mortality from all causes | 5 (41.7%) |
| Recurrence of GVs, n (%) | 4 (33.3%) |
| Procedure-related complications, n (%) | 1 (8.3%) |
| Infection | 0 (0%) |
| Renal dysfunction | 0 (0%) |
| Liver function deterioration | 0 (0%) |
| Symptomatic ectopic embolism | 0 (0%) |
| Newly developed or aggravated EVs | 1 (8.3%) |
| Newly developed or aggravated ascites | 0 (0%) |
| Newly developed or aggravated HE | 0 (0%) |
GVs, gastric varices; EVs, esophageal varices; HE, hepatic encephalopathy.
Figure 3.
A case of BRTO-assisted ECI for AGVB with large SPSS in a 40-year-old man. (A) Large GRS (white arrow) with a diameter of 2.1 cm; (B) Large GV (GOV2) with a diameter of 3 cm; (C) Successful balloon occlusion of the GRS; (D) Real-time x-ray fluoroscopic monitoring of ECI following BRTO; (E) Endoscopic view showing successful completion of BRTO-assisted ECI; (F) Complete GV obliteration on endoscopic view follow-up at 8 months. BRTO, balloon-occluded retrograde transvenous obliteration; ECI, endoscopic cyanoacrylate injection; AGVB, acute gastric variceal bleeding; SPSS, spontaneous portosystemic shunts; GRS, gastrorenal shunts; GV, gastric varices; GOV2, gastroesophageal varices type 2.
Discussion
Currently, EUS-guided coil embolization and cyanoacrylate injection is recommended for the management of AGVB with SPSS, especially when the shunt exceeds 0.5 cm (5, 13). However, its implementation remains challenging for patients with large SPSS lacking matched coil sizes, or centers with limited EUS expertise, while BRTO increases portal pressure post-procedure, leading to complications such as aggravated EVs or refractory ascites (30). Up to now, existing clinical guidelines provide no clear therapeutic recommendation (4–6), calling for research to address this issue. To address this issue, we conducted a retrospective single-center case series study including 12 patients with AGVB and large SPSS who were considered unsuitable for EUS-guided therapy. In this case series, BRTO-assisted ECI achieved clinical success in 91.6% of patients with AGVB and large SPSS, and no symptomatic ectopic embolization was observed during follow-up. These findings suggest that this combined approach is technically feasible and provides rapid initial hemostasis in this subpopulation without severe complications. In addition, considering that rebleeding and mortality mainly result from primary disease progression and comorbidities, subsequent comprehensive management is also crucial following the control of AGVB (31).
Compared to previous studies, this study presents several noteworthy advantages (26–29). Firstly, it is the first study directly focusing on the application of BRTO-assisted ECI for AGVB subpopulation with large SPSS, which is of relatively high-risk systemic embolization following conventional ECI and challenging for EUS-guided therapy. Compared with EUS-guided therapy for GVs with conventional-sized SPSS (32), our study showed BRTO-assisted ECI had similar clinical success and safety in this subpopulation with large SPSS. The study provides practical clinical evidence supporting the feasibility of this combined approach in patients challenging for EUS-guided intervention or in EUS-limited settings, and may help inform clinical decision-making for this challenging subgroup, for whom current guidelines offer limited guidance. Secondly, several technical refinements were also introduced. A modified sandwich injection method (lauromacrogol–cyanoacrylate–lauromacrogol) was employed utilizing a three-way stopcock technique, reducing cyanoacrylate consumption and hospitalization costs (33). In addition, compared with previous studies (29, 34), this combined procedure resulted in a shorter balloon occlusion time and no ectopic embolism, enhancing patient comfort during the treatment. Thirdly, this study preliminarily explored the safety of the combined technique in cirrhosis patients with Child-Pugh class C or HE, who were commonly excluded in previous trials (29).
Mechanistically, BRTO-assisted ECI combines two complementary actions: venous outflow control and targeted embolization. Retrograde balloon occlusion temporarily halts shunt outflow, inducing flow stagnation that facilitates cyanoacrylate polymerization. Crucially, this direct mechanical blockade of the SPSS may help prevent embolic material from entering the systemic circulation, thereby circumventing the challenge of coil size mismatch entirely. The subsequent endoscopic “sandwich” injection sequence ensures rapid and controlled delivery of lauromacrogol and cyanoacrylate, preventing premature solidification and catheter blockage. Together, these effects enhance variceal obliteration while minimizing systemic embolization, particularly in high-flow shunt conditions. Furthermore, this combined procedure enables immediate postoperative removal of the balloon catheter, thus avoiding the complications associated with prolonged balloon retention in conventional BRTO and the resultant aggravated portal hypertension.
Certainly, several limitations should be acknowledged. Firstly, this was a single-center retrospective case series with a limited sample size, as it was designed to target a specific and rare AGVB subpopulation with large SPSS exceeding 1.2 cm, which was associated with more severe AGVB and poorer prognosis. Given the lack of clear guideline recommendations for this high-risk subgroup, our study provides descriptive data to inform clinical decision-making, although the absence of a comparator group limits the ability to draw definitive conclusions. Secondly, changes in portal pressure and collateral circulation were not systematically measured due to the retrospective design. In addition, data on procedural costs and hospitalization duration were not reliably available, because most patients were treated in an emergency setting and subsequently transferred to affiliated hospitals within the medical consortium, precluding comprehensive data collection. Thirdly, the duration of follow-up was relatively short. Finally, there is currently no standardized definition for large SPSS. In this study, we operationally defined it as a shunt diameter exceeding 1.2 cm, a cutoff determined by the maximum coil size available at our center, to guide subsequent treatment decisions. In clinical practice, this definition should be adapted based on the specific resources and devices of local centers. Future multicenter prospective studies with larger patient cohorts and longer follow-up are warranted to confirm the safety, efficacy, and long-term outcomes of this combined approach.
In conclusion, this single-center case series suggests that BRTO-assisted ECI is technically feasible and achieved initial hemostasis for the treatment of most intractable AGVB with large SPSS, with no ectopic embolization observed. These findings preliminarily demonstrate its potential for treating this challenging subpopulation. Further multicenter, prospective, large-scale studies are needed to confirm these findings and evaluate the long-term outcomes.
Acknowledgments
The authors would like to thank Dr Yabing Wang and Dr Tao Wang for their invaluable advice in the preparation of this manuscript.
Funding Statement
The author(s) declared that financial support was received for this work and/or its publication. This work was supported by Beijing Municipal Health Commission Research Ward Excellence Clinical Research Program (No. BRWEP2024W034010107), National High-Level Hospital Clinical Research Funding (2025-PUMCH-H-009), State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases Funding (No. SKL-HIDCA-2024-GB3), National High-Level Hospital Clinical Research Funding (No. 2022-PUMCH-C-063), National Natural Science Foundation of China (No. 22232006), National Key Research and Development Program of China (No. 2023YFA0915304), Beijing Natural Science Foundation (No. L232120).
Footnotes
Edited by: Gabriel Sandblom, Karolinska Institutet (KI), Sweden
Reviewed by: Urmimala Chaudhuri, Wright State University Boonshoft School of Medicine, United States
Berk Baş, Adnan Menderes University, Türkiye
Abbreviations AGVB, acute gastric variceal bleeding; BRTO, balloon-occluded retrograde transvenous obliteration; ECI, endoscopic cyanoacrylate injection; SPSS, spontaneous portosystemic shunts; GVs, gastric varices; EVs, esophageal varices; GOV1, gastroesophageal varices type 1; GOV2, gastroesophageal varices type 2; IGV1, isolated gastric varices type 1; IGV2, isolated gastric varices type 2; EUS, endoscopic ultrasonography; GRS, gastrorenal shunts; SRS, splenorenal shunts; TIPS, transjugular intrahepatic portosystemic shunt; HE, hepatic encephalopathy; CT, computed tomography; AIH, autoimmune hepatitis; LCH, Langerhans cell histiocytosis; HCC, hepatocellular carcinoma; PVTT, portal vein tumor thrombus.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by institutional ethics committee of Peking Union Medical College Hospital, approval number K3377. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because the study was retrospective, and data collected was de-identified.
Author contributions
KH: Writing – review & editing, Writing – original draft. LY: Writing – original draft. KP: Writing – original draft. KW: Writing – original draft. HX: Writing – review & editing. WC: Writing – review & editing. DY: Writing – review & editing. QX: Writing – review & editing. SL: Writing – review & editing. RL: Writing – review & editing. HW: Writing – review & editing. WS: Writing – review & editing. ZW: Writing – review & editing. QW: Writing – review & editing.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
- 1.Nett A, Binmoeller KF. Endoscopic management of portal hypertension-related bleeding. Gastrointest Endosc Clin N Am. (2019) 29:321–37. 10.1016/j.giec.2018.12.006 [DOI] [PubMed] [Google Scholar]
- 2.Ma L, Tseng Y, Luo T, Wang J, Lian J, Tan Q, et al. Risk stratification for secondary prophylaxis of gastric varices due to portal hypertension. Dig Liver Dis. (2019) 51:1678–84. 10.1016/j.dld.2019.05.020 [DOI] [PubMed] [Google Scholar]
- 3.Martins FP, De Macedo EP, De Paulo GA, Nakao FS, Ardengh JC, Ferrari AP. Endoscopic follow-up of cyanoacrylate obliteration of gastric varices. Arq Gastroenterol. (2009) 46:81–4. 10.1590/s0004-28032009000100020 [DOI] [PubMed] [Google Scholar]
- 4.Kaplan DE, Ripoll C, Thiele M, Fortune BE, Simonetto DA, Garcia-Tsao G, et al. AASLD practice guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology (Baltimore, Md.). (2024) 79:1180–211. 10.1097/HEP.0000000000000647 [DOI] [PubMed] [Google Scholar]
- 5.de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Abraldes JG, et al. Baveno VII—renewing consensus in portal hypertension. J Hepatol. (2022) 76:959–74. 10.1016/j.jhep.2021.12.022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Gralnek IM, Camus Duboc M, Garcia-Pagan JC, Fuccio L, Karstensen JG, Hucl T, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: european society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy. (2022) 54:1094–120. 10.1055/a-1939-4887 [DOI] [PubMed] [Google Scholar]
- 7.Stanley AJ, Laine L. Management of acute upper gastrointestinal bleeding. BMJ (Clin Res Ed.). (2019) 364:l536. 10.1136/bmj.l536 [DOI] [PubMed] [Google Scholar]
- 8.Lee EW, Shahrouki P, Alanis L, Ding P, ST K. Management options for gastric variceal hemorrhage. JAMA Surg. (2019) 154:540–8. 10.1001/jamasurg.2019.0407 [DOI] [PubMed] [Google Scholar]
- 9.Cheng LF, Wang ZQ, Li CZ, Lin W, Yeo AET, Jin B. Low incidence of complications from endoscopic gastric variceal obturation with butyl cyanoacrylate. Clin Gastroenterol Hepatol. (2010) 8:760–6. 10.1016/j.cgh.2010.05.019 [DOI] [PubMed] [Google Scholar]
- 10.Frassei JS, Franco CS, Brambilla VR, Loureiro BMC, Kiebert CS, Fonseca EKUN, et al. Cyanoacrylate pulmonary embolism after endoscopic sclerotherapy of gastric varices. Einstein (Sao Paulo, Brazil). (2021) 19:eAI5778. 10.31744/einstein_journal/2021AI5778 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Jhajharia A, Yadav S, Singh S, Ashdhir P, Nijhawan S. Endoscopic ultrasonography-guided coil embolization and cyanoacrylate injection versus cyanoacrylate injection alone for gastric varices: a randomized comparative study. Endoscopy. (2024) 57:107–15. 10.1055/a-2408-6905 [DOI] [PubMed] [Google Scholar]
- 12.Bhat YM, Weilert F, Fredrick RT, Kane SD, Shah JN, Hamerski CM, et al. EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years (with video). Gastrointest Endosc. (2016) 83:1164–72. 10.1016/j.gie.2015.09.040 [DOI] [PubMed] [Google Scholar]
- 13.Zhu H, Jiang F, Zhu J, Du Y, Jin Z, Li Z. Assessment of morbidity and mortality associated with endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions: a systematic review and meta-analysis. Dig Endosc. (2017) 29:667–75. 10.1111/den.12851 [DOI] [PubMed] [Google Scholar]
- 14.Simón-Talero M, Roccarina D, Martínez J, Lampichler K, Baiges A, Low G, et al. Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis. Gastroenterology. (2018) 154:1694–705.e4. 10.1053/j.gastro.2018.01.028 [DOI] [PubMed] [Google Scholar]
- 15.Garcia-Sumalla A, Maisterra S, Amador-Navarrete A, Castellote J, Gornals JB. Nonadhesive massive coiling endoscopic ultrasound-guided embolization in a single session for treatment of gastric varices: learning points of a technical variant. Endoscopy. (2022) 54:E228–9. 10.1055/a-1492-2182 [DOI] [PubMed] [Google Scholar]
- 16.Venkatachalapathy S, Nayar MK. Therapeutic endoscopic ultrasound. Frontline Gastroenterol. (2017) 8:119–23. 10.1136/flgastro-2016-100774 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Henry Z, Patel K, Patton H, Saad W. AGA Clinical practice update on management of bleeding gastric varices: expert review. Clin Gastroenterol Hepatol. (2021) 19:1098–1107.e1. 10.1016/j.cgh.2021.01.027 [DOI] [PubMed] [Google Scholar]
- 18.Biswas S, Vaishnav M, Gamanagatti S, Swaroop S, Arora U, Aggarwal A, et al. Endoscopic glue injection vs glue plus BRTO or TIPSS for preventing gastric variceal bleeding: a randomized controlled trial. Clin Gastroenterol Hepatol. (2025) 23:954–64.e10. 10.1016/j.cgh.2024.06.023 [DOI] [PubMed] [Google Scholar]
- 19.Ninoi T, Nishida N, Kaminou T, Sakai Y, Kitayama T, Hamuro M, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices with gastrorenal shunt: long-term follow-up in 78 patients. Am J Roentgenol. (2005) 184:1340–6. 10.2214/ajr.184.4.01841340 [DOI] [PubMed] [Google Scholar]
- 20.Shinkai K, Sakamori R, Yamada R, Tahata Y, Nozaki Y, Matsumoto K, et al. Prognostic impact of worsening of esophageal varices after balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol. (2022) 37:1148–55. 10.1111/jgh.15853 [DOI] [PubMed] [Google Scholar]
- 21.Jang SY, Kim GH, Park SY, Cho CM, Tak WY, Kim JH, et al. Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study. Clin Mol Hepatol. (2012) 18:368–74. 10.3350/cmh.2012.18.4.368 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Borentain P, Soussan J, Resseguier N, Botta-Fridlund D, Dufour J-C, Gérolami R, et al. The presence of spontaneous portosystemic shunts increases the risk of complications after transjugular intrahepatic portosystemic shunt (TIPS) placement. Diagn Interv Imaging. (2016) 97:643–50. 10.1016/j.diii.2016.02.004 [DOI] [PubMed] [Google Scholar]
- 23.Friis KH, Thomsen KL, Laleman W, Montagnese S, Vilstrup H, Lauridsen MM. Post-Transjugular intrahepatic portosystemic shunt (TIPS) hepatic encephalopathy-A review of the past decade’s literature focusing on incidence, risk factors, and prophylaxis. J Clin Med. (2023) 13:14. 10.3390/jcm13010014 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Lv Y, Pan Y, Xie H, Yang C, Fan D, Han G. Timing of TIPS for the management of portal vein thrombosis in liver cirrhosis. J Transl Intern Med. (2023) 11:316–9. 10.2478/jtim-2023-0095 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Du S, Luo X, Yang L, Wang X. Clinical significance of portal vein thrombosis in patients with decompensated cirrhosis: a still matter of debate. J Transl Intern Med. (2025) 13:100–3. 10.1515/jtim-2025-0011 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Bazerbachi F, Dobashi A, Kumar S, Misra S, Buttar NS, Wong Kee Song LM. Efficacy and safety of combined endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous occlusion (BRTOcc) of gastrorenal shunts in patients with bleeding gastric fundal varices. Gastroenterol Rep (Oxf). (2020) 9:212–8. 10.1093/gastro/goaa082 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Chu J, Lu Z, Chi C, Zhang W, Bi Q, Ma X, et al. Balloon-occluded retrograde transvenous obliteration and simultaneous endoscopic cyanoacrylate injection for treating gastric varices draining through gastrorenal shunts. Arab J Gastroenterol. (2023) 24:218–22. 10.1016/j.ajg.2023.07.004 [DOI] [PubMed] [Google Scholar]
- 28.Ma L-L, Luo T-C, Tseng Y-, Huang X-Q, Luo J-J, Zhang W, et al. Balloon-occluded retrograde transvenous obliteration of portovenous shunts during endoscopic therapy for the treatment of gastric varices. Surg Laparosc Endosc Percutan Tech. (2018) 28:e113. 10.1097/SLE.0000000000000572 [DOI] [PubMed] [Google Scholar]
- 29.Wu Q, Jiang H, Linghu E, Zhang L, Wang W, Zhang J, et al. BRTO assisted endoscopic histoacryl injection in treating gastric varices with gastrorenal shunt. Minim Invasive Ther Allied Technol. (2016) 25:337–44. 10.1080/13645706.2016.1192552 [DOI] [PubMed] [Google Scholar]
- 30.Lipnik AJ, Pandhi MB, Khabbaz RC, Gaba RC. Endovascular treatment for variceal hemorrhage: TIPS, BRTO, and combined approaches. Semin Intervent Radiol. (2018) 35:169–84. 10.1055/s-0038-1660795 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Hudu SA, Shinkafi SH, Jimoh AO. A critical review of diagnostic and prognostic markers of chronic hepatitis B infection. Med Rev (2021). (2024) 4:225–34. 10.1515/mr-2024-0022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Huang Z, Zhang W, Lv F, Ma L, Xiao Y, Gao S, et al. Efficacy and safety of EUS-guided coil embolization combined with endoscopic cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration for gastric varices with high-risk ectopic embolism: a multicenter and retrospective cohort study. Endosc Ultrasound. (2023) 12:74. 10.4103/EUS-D-21-00260 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Zeng X-Q, Ma L-L, Tseng Y-J, Chen J, Cui C-X, Luo T-C, et al. Endoscopic cyanoacrylate injection with or without lauromacrogol for gastric varices: a randomized pilot study. J Gastroenterol Hepatol. (2017) 32:631–8. 10.1111/jgh.13496 [DOI] [PubMed] [Google Scholar]
- 34.Sato W, Kamada K, Goto T, Ohshima S, Miura K, Shibuya T, et al. Efficacy of combined balloon-occluded retrograde transvenous obliteration and simultaneous endoscopic injection sclerotherapy. Intern Med (Tokyo, Japan). (2015) 54:261–5. 10.2169/internalmedicine.54.3465 [DOI] [PubMed] [Google Scholar]
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.