Sato H, Kawabata H, Fujiya M. Gel immersion in endoscopy: Exploring potential applications. World J Gastroenterol 2025; 31(4): 101288 [DOI: 10.3748/wjg.v31.i4.101288]
Corresponding Author of This Article
Hiroki Sato, MD, PhD, Academic Fellow, Postdoctoral Fellow, Research Associate, Department of Internal Medicine, Asahikawa Medical University, 1-1, Midorigaoka Higashi 2 Jyo 1 Chome, Asahikawa 078-8510, Hokkaido, Japan. hirokisato@asahikawa-med.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
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/
Co-corresponding authors: Hiroki Sato and Mikihiro Fujiya.
Author contributions: Sato H and Kawabata H authored the introduction section and the section on the effect of gel through the adaptation of other gels; Sato H and Kawabata H also conducted a literature search for the section on the methods of utilizing gel immersion in digestive endoscopy; Sato H and Fujiya M reviewed literature related to the esophagus, stomach, duodenum and small intestine, and colon and rectum sections and the methods of utilizing gel immersion in digestive endoscopy section; Sato H and Fujiya M drafted these sections and created the associated tables (Tables 1, 2, 3, and 4); Sato H and Kawabata H reviewed literature related to the hepatobiliary and pancreas section, authored the relevant sections, and created the accompanying tables (Table 5); the future perspectives on gel immersion endoscopy and conclusion sections were written by Sato H, Kawabata H, and Fujiya M, based on collected literature; Sato H created Figure 1; Kawabata H created Figures 2 and 3; Sato H and Fujiya M performed a final review of all sections, coordinating necessary revisions with the respective co-authors of each section; This review article spans both the gastrointestinal and hepatobiliary-pancreatic fields. It was supervised by experts in each respective area: Fujiya M for the gastrointestinal field and Sato H for the hepatobiliary and pancreas field. This collaboration was essential to create a comprehensive, cross-organ review article.
Supported by the Japan Society for the Promotion of Science KAKENHI, No. 21KK0283 (to Sato H).
Conflict-of-interest statement: Mikihiro Fujiya: Others, OLYNPUS Co., Ltd., Boston Scientific Corporation, FUJIFILM Corporation, Otsuka Pharmaceutical Co., Ltd. There are no conflicts of interest associated with the authors who contributed to this manuscript.
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: Hiroki Sato, MD, PhD, Academic Fellow, Postdoctoral Fellow, Research Associate, Department of Internal Medicine, Asahikawa Medical University, 1-1, Midorigaoka Higashi 2 Jyo 1 Chome, Asahikawa 078-8510, Hokkaido, Japan. hirokisato@asahikawa-med.ac.jp
Received: September 10, 2024 Revised: November 19, 2024 Accepted: December 6, 2024 Published online: January 28, 2025 Processing time: 111 Days and 4.8 Hours
Abstract
The challenge of effectively eliminating air during gastrointestinal endoscopy using ultrasound techniques is apparent. This difficulty arises from the intricacies of removing concealed air within the folds of the gastrointestinal tract, resulting in artifacts and compromised visualization. In addition, the overlap of folds with lesions can obscure their depth and size, presenting challenges for an accurate assessment. Conversely, in intricately folded regions of the gastrointestinal tract, such as the stomach, intestine, and colon, insufficient delivery of air or CO2 into the cavity impedes luminal expansion, hindering the accurate visualization of lesions concealed within the folds. Although this underscores the requirement for substantial airflow, excessive airflow can hinder visualization of bleeding lesions and other abnormalities. Considering these challenges, an ideal endoscopic device would facilitate the observation of lesions without the requirement for air or CO2 delivery whereas, ensuring optimal expansion of the gastrointestinal tract. Recently, transparent gels with specific viscosities have been employed more frequently to address this issue. This review aims to elucidate how these gels address these challenges and provide a solution for enhanced endoscopic visualization.
Core Tip: This review examines the challenges associated with gastrointestinal endoscopy, particularly the difficulty of eliminating air during ultrasound techniques, which results in artifacts and reduced visualization quality. Insufficient or excessive airflow can impede accurate assessment of lesions within the gastrointestinal folds. This review highlights the use of transparent viscous gels to facilitate improved endoscopic visualization without requiring air or CO2 delivery, thereby enhancing lesion observation accuracy in complex regions of the gastrointestinal tract.
Citation: Sato H, Kawabata H, Fujiya M. Gel immersion in endoscopy: Exploring potential applications. World J Gastroenterol 2025; 31(4): 101288
The digestive tract contains a certain amount of gas or air, and appropriate insufflation during endoscopic insertion allows clear visualization and safe endoscopic procedures[1]. In 1952, Carter[2] reported cases of rectal perforation that occurred during rectal polypectomy[2]. Air embolism during endoscopy has also been reported, although rarely[3,4].
Recently, the effects of carbon dioxide (CO2) in endoscopic procedures have been investigated[5-8], and the use of CO2 has resulted in a reduction in pain and bowel gas retention. Excessive insufflation results in over-distension of the digestive tract, complicating the insertion of long tubes and hindering lesion access during procedures such as endoscopic submucosal dissection (ESD)[9]. The key technique of endoscopic ultrasound (EUS) relies on suctioning air through the digestive tract for optimal lesion ultrasonographic visualization[10]. As ultrasound waves cannot penetrate air, careful insufflation or appropriate deflation of the digestive tract, particularly the stomach and duodenum, is essential when inserting an endoscope.
Gastrointestinal hemostasis is another key indication for endoscopic procedures[11,12]. Although water is used to detect bleeding points, it quickly mixes with blood[13,14], making it difficult to maintain a clear field of view[15].
An endoscopic technique using gel was developed to address this issue. Initially, the gel was prepared using an oral rehydration solution[15]. This gel helps maintain a clear field of view by preventing interference from blood and food residue[16,17]. However, the electrical conductivity of monopolar hemostatic forceps decreased when used with the gel, imposing limitations on its utilization.
Considering these risks, transparent gels designed for gastrointestinal endoscopy have recently been developed[18,19]. This gel was initially tested ex vivo and found to have excellent stability. It can easily be injected through a forceps channel, which enhances its clinical applicability. Recent studies have reported the clinical usefulness of these gels, highlighting solutions for endoscopic observation and treatment.
This manuscript elucidates the usefulness of endoscopic gels across digestive organs and clinical conditions, and summarizes their potential applications in endoscopic procedures (Figure 1).
Figure 1 Gel use in gastrointestinal endoscopy is widely applied in all gastrointestinal tracts.
It is particularly characterized by its application in tumor resection and hemostasis in the stomach, intestine, and colon; esophageal varices treatment in the esophagus; and endoscopic ultrasound procedures in the hepatobiliary and pancreatic regions. ESD: Endoscopic submucosal dissection; EMR: Endoscopic mucosal resection; EUS: Endoscopic ultrasound; EVL: Endoscopic variceal ligation; EIS: Endoscopic injection sclerotherapy; ERCP: Endoscopic retrograde cholangiopancreatography. The authors have obtained the permission for figure using from the Adobe Stockphoto (Supplementary material).
THE EFFECT OF GEL THROUGH THE ADAPTATION OF OTHER GELS
Over the past few decades, efforts have been made to maintain direct visualization or ultrasound imaging using a liquid with a certain level of viscosity (jelly or gel).
Regarding the use of jelly/gel during this period, gel was predominantly used in miniature probe EUS examinations. In 2005, Soon et al[20] evaluated esophageal and duodenal lesions using a 12 MHz miniature probe with 2.5% carboxymethylcellulose jelly. They proposed a five-point scale for evaluating the imaging quality, focusing on air artifacts and visualization levels. The results indicated improved imaging quality and depiction ability of submucosal lesions in esophageal and duodenal cancers. However, no substantial difference in the penetration depth was observed. Ahn et al[21] evaluated images of esophageal subepithelial tumors using a miniature EUS probe (12 or 20 MHz) and rated EUS images on Soon’s five-point scale in 2017. A total of 138 cases were analyzed, including 98 in the water-filled control group and 40 in the lubricating jelly group. The imaging quality was reported to be superior when lubricating jelly was used. In 2005, Yamasaki et al[22] reported a technique involving the injection of jelly during ESD to facilitate its completion in an animal model.
The composition of endoscopic gels varies. Among them, TDM-623 (Purastat, 3-D Matrix Ltd., Tokyo, Japan) demonstrated excellent hemostatic effects. TDM-623 consists of 14-amino acid peptides that self-assemble into nanofibers. Particularly effective in non-spurting bleeding, Kubo et al[23] reported the efficacy of TDM-623 in providing outstanding hemostatic efficacy in upper gastrointestinal tract oozing. Additionally, it has proven useful in maintaining a clear field of view during hemostasis[24-26]. Ishida et al[25] reported the hemostatic effects of TDM-623 in Endoscopic Sphincterotomy-related hemorrhage during endoscopic retrograde cholangiopancreatography (ERCP). However, these studies have primarily focused on the hemostatic properties of gels. Owing to its low viscosity, water quickly flows out and mixes with food residue or blood, making it difficult to consistently maintain a clear field of view. Therefore, Yano et al[18] proposed "Gel Immersion Endoscopy (GIE)", a method using transparent gel to ensure visibility. Yamamoto et al[26] used OS-1 jelly (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) to identify colonic diverticular bleeding. OS-1 jelly is a gelatinized form of the oral rehydration solution OS-1. According to their findings, colonic diverticular bleeding was identified in 66.7% of patients, and successful hemostasis was achieved in 85.7% of cases. According to Miura et al[16], this gel is useful in ESD. However, the high electrolyte content of OS-1 jelly poses a drawback during hemostasis with a monopolar electrode as it weakens the effect. This disadvantage requires either complete aspiration of the gel or the use of a bipolar device.
A new gel, OPF-203 (VISCOCLEAR, Otsuka Pharmaceutical Factory, Tokyo, Japan), was developed. Yano et al[18] conducted ex vivo and in vivo experiments on this gel. The results demonstrated that at an electric conductivity of 224 microsecond/cm, OPF-203 exhibited effective electrocoagulation. Hiraki et al[19] injected OPF-203 into a waterjet channel to evaluate its viscosity. Results revealed reduced viscosity when injected through the water jet channel, compared with the endoscope forceps channel. Although the viscosity reduction varied by device, the guiding principle recommended injection through the forceps channel moving forward.
THE METHODS OF UTILIZING GEL IMMERSION IN DIGESTIVE ENDOSCOPY
In this manuscript, we report the utility of GIE for each organ. A literature search was conducted using PubMed and Google Scholar database with the keywords “gel and endoscopy” and “gel immersion endoscopy”. The inclusion criteria were as follows: (1) Case reports, case series, and case-control studies; (2) Studies involving endoscopic observation or procedures in the entire gastrointestinal tract, biliary system, pancreas, or liver; and (3) Studies that used gels (regardless of gel name or indication) for endoscopic observation or procedures. The exclusion criteria were as follows: (1) Cohort studies; (2) Non-human studies; (3) Basic research on the properties or characteristics of endoscopes or gels; (4) Studies that did not describe outcomes for the cases or patient groups under investigation; (5) Non-English articles; and (6) Other studies were deemed ethically inappropriate or unsuitable for literature review.
Esophagus
Reports on endoscopy using gels in the esophagus became available relatively early. This early availability is attributed to the tubular structure of the esophagus, which makes it relatively easy to retain the gel. Since the introduction of OPF-203, the number of endoscopic procedures performed using this gel has increased (Table 1).
Table 1 Reports on gel immersion endoscopy for esophageal lesions.
In 2021, Nakano et al[27] reported that during esophageal ESD, patients experiencing discomfort and irritability from CO2 insufflation could safely complete the procedure using a gel. This case report suggests that the use of gel for ESD may reduce discomfort. Furthermore, they reported 13 cases of esophageal ESD with gel, highlighting the safety and utility of GIE[28]. They specifically emphasized its effectiveness for lesions on the gravitational side of the middle and lower esophagus. During the same period, the use of GIE for pocket creation method has been reported to be beneficial[29,30]. Iwatsubo et al[31] proposed a technique for esophageal ESD in which an ERCP cannulation catheter was applied to the tip of the endoscope, and gel was injected through the tube.
Another application of gel in the esophagus is the identification and treatment of esophageal varices. In 2021, Kato et al[32] used lubricating jelly by employing a 14-Fr catheter through a two-channel endoscope and inserted the jelly through the forceps channel. Subsequently, EUS observations were conducted using a miniature probe (20 MHz ultrasound probe). Data were retrospectively collected using the water-filling method as a control. The results showed superior imaging quality with jelly, and perforating veins were depicted more clearly than with water alone. In treating esophageal varices, Sekiguchi et al[33] reported the first cases of gel immersion used in endoscopic variceal ligation (EVL) in 2022. They found that gel immersion facilitated the identification of the bleeding points. During the same period, Hasebe et al[34] reported the usefulness of gel immersion in identifying bleeding points in EVL. Their report referred to the bleeding points identified with gel immersion as "submarine volcanic eruptions". They reported that the use of water or air to flush out the gel from the channel enabled EVL to be performed at an appropriate suction pressure.
Sugawara et al[35] demonstrated the usefulness of gel immersion in Endoscopic Injection Sclerotherapy. They suggested that using a gel helps maintain low luminal pressure in the esophagus, which aids in identifying the blood vessels to be punctured.
Stomach
The first instance of GIE of the stomach was documented in 2018 by Miura et al[16]. They performed ESD using the pocket creation method and OS-1 jelly. During this procedure, water was injected into the pocket created during ESD and mixed easily with blood, complicating the efforts to maintain a clear field of view. Therefore, they used the OS-1 jelly to address this issue. However, as previously mentioned, this gel poses challenges owing to its low electrical conductivity. Therefore, the gel was aspirated using forceps after the bleeding point was identified (Table 2).
Table 2 Reports on gel immersion endoscopy for gastric lesions.
Cyanoacrylate injection; difficult to secure the endoscopic visual field due to the massive bleeding
Forceps channel irrigator (manual injection)
Continuous gel injection gradually improved the visual field. A total of 4 mL of cyanoacrylate was injected into the varices over five tries
A total of 500 mL of this gel was used
Miura et al[36] reported performing endoscopic mucosal resection (EMR) using gel immersion for a gastric tumor. In this case, underwater EMR was challenging because the lesion was difficult as water flowed out from the pyloric ring into the duodenum. As a result, they achieved stable observations through gel immersion. Kimura et al[37] also used gel immersion to perform EMR for gastric tumors located in the greater curvature. Michigami et al[38] reported the usefulness of gel immersion EMR for gastric metastasis of renal cell carcinoma.
Khurelbaatar et al[39] performed ESD for early gastric cancer using gel immersion. They injected gel into the ESD pocket and reported successful coagulation without complications. Muramatsu et al[40] further demonstrated the usefulness of ESD by employing a tunneling method with gel immersion to confirm its safety and efficacy.
Suto et al[41] highlighted the usefulness of gel immersion for EMR in preventing tumor prolapse into the duodenal side when located in the pyloric ring.
Orita et a[42] also reported the usefulness of gel immersion for bleeding gastric varices. In this case, where the bleeding point from the varices was unclear, gel immersion helped to identify the bleeding point, enabling successful cyanoacrylate injection.
Duodenum and small intestine (except ampulla of the Vater)
The usefulness of GIE in the small intestine was first reported by Yano et al[15] in an observational study. They primarily used balloon endoscopy and documented the effectiveness of the OS-1 jelly, particularly in cases of jejunal bleeding and bleeding from anastomotic ulcers of the ileum. Miyamoto et al[43] first reported the effectiveness of OPF-203, which was used for duodenal bulb ulcer bleeding, where the bleeding point was obscured by massive bleeding. The bleeding point was identified using gel, and hemostasis was subsequently achieved using hemostatic forceps. Hayashi et al[44] and Jinushi et al[45] reported similar cases in which successful hemostasis was achieved through clip ligation for bleeding duodenal diverticula, facilitated by improved visibility during observation (Table 3).
Table 3 Reports on gel immersion endoscopy for duodenal and small intestine lesions.
Duodenal ulcer in anterior surface of the duodenal bulb
Saline solution was quickly mixed with blood, making it difficult to identify the bleeding site
Secondary water delivery tube
Successful identification of the bleeding point was achieved, and hemostasis was accomplished with hemostatic forceps
There was only one forceps channel, making it impossible to insert both the gel and the hemostatic forceps simultaneously. Therefore, secondary water injection tube was used
Comparing gel-based EMR (GIER; n = 10) and Underwater EMR (UEMR; n = 14) in R0 resection rate, en-bloc resection rate, median procedure time, median amount of filling water/gel and adverse events
Forceps channel with auxiliary injection cap
Median procedure was shorter in GIEMR group. Median amount of filling water/gel was lesser in GIEMR group. There are no difference in adverse events rates
The small number of data points may lead to statistical instability; some patient data (such as chief complaints) might be missing
Unexpected massive bleeding occurred during submucosal dissection, obscuring the lesion and bleeding point
Forceps channel
Organ collapse was maintained with lower intraluminal pressure, ensuring stable endoscope maneuverability and a good approach to the lesion, allowing safe submucosal dissection
Due to the thin duodenal wall, there is a risk of perforation during ESD
Forceps channel with auxiliary injection cap
As ESD progressed, the buoyancy effect became more pronounced, ensuring working space to make dissection easier. Additionally, it was easy to identify bleeding points was also simplified
Flushing the lumen with water resulted in the immediate mixing of water and blood, making it impossible to identify the bleeding point
Forceps channel with auxiliary injection cap
Inflating the tip balloon of the double-balloon endoscope helped retain the gel in place, allowing for the identification and successful hemostasis of the intestinal hemangioma
Injecting water into the duodenum and small intestine resulted in quickly flowing out, leaving little water
Forceps channel
The gel remained near the jejunum tumor, clearly separating the jejunal wall from the tumor and enabling its identification
-
Several subsequent case reports have detailed procedures, such as ESD and EMR, for duodenal lesions. In 2021-2022, several case reports have been published on EMR using OPF-203[46], Tashima et al[47] and Yachida et al[48] reported cases in which they converted from underwater EMR to gel immersion EMR for superficial non-ampullary duodenal epithelial tumors (SNADETs). Gel immersion helped them avoid obstacles such as bile reflux, peristaltic movement, and air bubbles, allowing for safer EMR. The usefulness of GIE has been demonstrated for EMR of ampullary tumors[49].
Subsequently, Miyakawa et al[50] performed a retrospective analysis of 40 consecutive SNADET patients treated with either underwater or gel immersion EMR. They reported that the R0 resection rate was considerably higher with a shorter procedure time in gel immersion EMR. The effectiveness of gel immersion EMR was further confirmed through retrospective evaluation by Amino et al[51] in 2021. They performed EMR using a gel in six consecutive cases of SNADET. Among these cases, three lesions were distal to the papilla, three were proximal, and one was located in the bulbus within the proximal region. All the patients underwent en-bloc resection. Yamashina et al[52] later compared underwater and gel immersion EMR for SNADETs. Although there was no difference in en-bloc resection rates, they reported that the procedure time was substantially shorter with gel immersion EMR. Gels have since been used for EMR of tumors near the papilla[53] and for hyperplasia of Brunner's glands in the bulbus[54]. The gel has also been used for cold snare polypectomy of supra-ampullary duodenal adenomas[55].
Tashima et al[56] performed the first ESD using OPF-203 for duodenal epithelial tumors in 2022. They reported that not only did the gel facilitated easier identification of bleeding points, but also the buoyancy effect of gel immersion was useful in securing space for submucosal dissection.
Various reports have documented the use of GIE with balloon-assisted enteroscopy for endoscopic intervention of small intestinal lesions beyond the duodenum. Kawaguchi et al[57] reported a case of EMR for small intestinal polyps in a patient with Peutz-Jeghers syndrome. Initially, insufflation with CO2; however, the stalk was not visible. Subsequently, they used gel immersion, which allowed for visualization of the stalk and enabled successful EMR. Matsubara et al[58] successfully performed on a 15 mm polyp with erosion in the ileum using gel immersion under double-balloon enteroscopy. Horitani et al[59] reported the effectiveness of GIE using double-balloon enteroscopy for hemostasis in small intestinal bleeding.
Several reports have documented the use of gel immersion for EUS of esophageal lesions. Tomita et al[60] reported endoscopic ultrasonography for transgastric observation of a jejunal tumor using OPF-203n. They noted that ultrasound stably observed jejunal tumors through the gastric wall using this approach.
Colon and rectum
The application of gel immersion in the colon and rectum is primarily categorized into two areas: Treatment of hemorrhagic lesions, such as diverticular bleeding, and treatment of neoplastic lesions, such as ESD and EMR (Table 4).
Table 4 Reports on gel immersion endoscopy for colon and rectum.
Detecting of bleeding diverticulum could not be identified due to the large volume of clotted blood and severe active bleeding
Injected through long-hood
Gel retained within the long hood facilitated the detection of colonic diverticulum and enabled to identify the bleeding point, leading to successful hemostasis
Comparison between 6 cases of under-gel EMR with partial submucosal injection (PI) and 8 cases of under-gel precutting EMR among 348 patients with colorectal polyps
Forceps channel with auxiliary injection cap
En-bloc resection rate was 100% with under-gel EMR with PI, and 50% with under-gel precutting EMR
While it is a small, single-center retrospective case series, long-term outcomes were not assessed, and the quality of comparisons is low due to reliance on historical control data
To improve endoscopic visual field and submucosal approach due to the buoyancy of the lesion
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Easily approach to the submucosal layer and smooth creation of the tunnel owing to the buoyancy of the gel. Bleeding in the tunnel was clearly visible in the gel
The poor endoscopic view caused by contaminated bowel fluid
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Gel provided a clear endoscopic view and helped assess intestinal ischemia. The weight and pressure of the gel opened the twisted colon and facilitated volvulus passage in the left lateral decubitus position
Poor endoscopic view due to severity of the stricture
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Securing the visual field with gel and tapered tip of transparent hood
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Initial reports on OPF-203 use in the colon focused on hemorrhagic lesions. In 2021, Yano et al[61] reported the use of GIE with OS-1 jelly to treat lower gastrointestinal bleeding. They identified the source of the bleeding at the lower lip of the ileocecal valve and achieved hemostasis using clips.
Teshima et al[62], Suto et al[63], and Abiko et al[64] reported cases where OPF-203 was used for colonic diverticular bleeding. They successfully identified the bleeding point and achieved hemostasis by using hemostatic forceps and clips. Similarly, Kobayashi et al[65] reported two cases of hemostasis using endoscopic band ligation for colonic diverticula and hemorrhoids[65].
In reports on EMR and ESD, Takada et al[66] performed EMR using gel immersion for sessile serrated lesions in the cecum. The authors noted that the cecum, which accumulates fluid in the small intestine, often obstructs the field of view. They found that the viscosity of the gel helped secure the field of view. Kuwabara et al[67] and Jinushi et al[45] also performed EMR using OPF-203 for protruding lesions in the ascending and sigmoid colon. In a case report by Kuwabara et al[67], the specifications of OPF-203 allowed for a safe EMR. The efficacy of OPF-203 was later confirmed in
Ileocecal valve lesions often pose challenges for complete resection and are associated with high recurrence rates[68,69]. Although underwater EMR is a useful alternative, ensuring visibility remains a challenge, particularly at the proximal lip of the ileocecal valve. Yoshimoto et al[70] reported a case of EMR performed under-gel immersion, termed "under-gel EMR", in 2022 to overcome this issue. In this case, a double clip and rubber band were concurrently used to secure traction. Yamamoto et al[71] reported a retrospective case series in 2023, utilizing under-gel EMR and the partial injection method. Gel was used in all 14 cases, with 6 cases employing the partial injection method and the remaining cases utilizing gel followed by precutting before EMR. Although the study aimed to compare partial injection with precutting, the authors concluded that gel was beneficial, particularly in cases where blood or feces could easily mix into the endoscopic field of view when using only water. The utility of GIE for EMR has also been confirmed for laterally spreading tumors in the rectosigmoid[72], and piecemeal EMR for flat-elevated tumors[73].
Maruyama et al[74] and Tashima et al[75] reported cases in which ESD was performed using GIE. These case reports demonstrated that gel immersion enabled clear observation of bleeding points that were not identifiable with water irrigation alone during the procedure. Subsequently, Nakano et al[76] reported the usefulness of gel immersion in the tunneling method for ESD in 2023.
Reports of hemostasis in the colon and rectum have also included gels for stricture dilation. In some cases, GIE has been utilized for hemostasis of bleeding following endoscopic incision using an ESD knife for anastomotic stricture after low anterior resection[77]. This report highlights the utility of gels in identifying bleeding points in situations where the working space for identification is limited because of the presence of strictures.
Gel immersion is also useful for relieving sigmoid colon volvuli. Yamamoto et al[78] used OPF-203 to treat sigmoid volvuli in children. They observed that gel viscosity gradually expanded to the colon in the left decubitus position, allowing observation of the proximal side of the twisted colon lumen and achieving successful endoscopic detorsion with gel immersion.
The efficacy of gel immersion in EUS for rectal lesions has been documented previously. In 2023, Osera et al[79] reported the use of GIE for rectal EUS. They employed gel immersion for EUS observation in patients with rectal anastomotic obstruction after surgery. The proximal rectum was punctured using EUS and balloon dilation was performed. Gel use enabled a clearer visualization of the proximal rectum during EUS.
Stent insertion is another challenge for maintaining a clear view of the colon. Stent insertion in malignant strictures has recently gained attention. Nomura et al[80] successfully performed stent insertion for malignant colorectal obstructions with poor visualization, utilizing a tapered-tip transparent hood and OPF-203 to enhance the visualization.
Hepatobiliary and pancreas
GIE has mainly been employed to identify papillae in the hepatobiliary and pancreatic regions (Figure 2). In 2022, Toyonaga et al[81] utilized OPF-203 to treat periampullary tumors. GIE confirmed the absence of the muscularis propria using EUS. Although water is commonly used in such situations[82], gel allows for a more detailed observation of the papilla. Furthermore, the authors used gel immersion during EUS in 12 consecutive patients with ampullary tumors. As a result, duodenal lumen distension was satisfactory, allowing observation without the EUS probe contacting the mucosa (defined as “excellent”) in 75% of patients. In this study, the diagnostic accuracies for bile duct spread, pancreatic intraductal spread, invasion of the muscularis propria of the duodenum, and pancreatic invasion were 83%, 100%, 83%, and 92%, respectively[83]. The authors further examined the usefulness of gels on EUS by conducting a retrospective evaluation of ampullary depictions using gels in 59 cases. The final ampullary distention rate was 100% in the “excellent” duodenal inflation group and 98% in the overall group. The identification rate of intrapapillary pancreatobiliary ducts, defined as "ducts running through the papilla continuously from the pancreatobiliary duct in the pancreas", was 91%, demonstrating favorable outcomes[84]. Following this report, a comparative study with the water injection method, which has been traditionally used in EUS, was conducted by Sato et al[85]. Although it was a relatively small case series of 10 cases, they captured EUS images of the ampulla in each case, totaling 10 images per patient, and defined cases where "penetration of the pancreatic and biliary ducts into the duodenal muscularis propria" was achieved as "excellent". They used a water injection method, followed by GIE. The number of images judged as excellent per case in the GIE group was 3.8 ± 1.99, notably better than those in the water injection method group (Table 5).
Figure 2 Utility of gel in endoscopic ultrasound for hepatobiliary and pancreatic visualization.
A: Clear depiction of the main pancreatic duct near the papilla (yellow arrow); B: The confluence of the main pancreatic duct and bile duct (blue arrow); C: Pancreatic and bile ducts relation to the duodenal muscle layer (magenta arrowhead); D: The pancreatic duct and the ampulla of Vater (white arrowhead) are depicted.
Table 5 Reports on Gel immersion endoscopy for hepatobiliary and pancreas.
Evaluation whether the ampullary had duodenal muscularis propria or intraductal involvement. Securing visual field during papillectomy
Forceps channel with auxiliary injection cap
Successfully delineate the ampullary tumor without invasion of the duodenal muscularis propria or intraductal involvement. En-bloc endoscopic papillectomy was achieved
Evaluating the delineation and diagnosis of 12 consecutive patients study who were used gel immersion under the EUS observation
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Delineation of the ampullary tumors were achieved in all patients. The diagnostic accuracies of biliary spread, pancreatic intraductal spread, invasion into duodenal muscularis propria, and pancreatic invasion were 83%, 100%, 83%, and 92%
Hepatobiliary observational EUS (evaluation of ampulla)
Fifty-nine consecutive patients who received EUS with gel
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Duodenal distention was excellent, good, and poor in 58%, 34% and 7% of cases. The delineation rates of the papilla in the axial and longitudinal views were 98% and 66%
Retrospective, single-institution study; Radial and convex linear-arrayed echoendoscopes were used; Diagnostic ability of EUS with for periampullary lesions remains unknown
Hepatobiliary observational EUS (evaluation of ampulla)
Retrospective case series study: EUS images of the Vater were taken for 10 patients, with 10 images captured after injecting water into the duodenal lumen, followed by another 10 images after applying gel in the same manner.
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The number of excellent observations (as defined by Toyonaga et al[81]) was 0.4 ± 0.80 with water immersion, while it was 3.8 ± 1.99 with gel immersion, showing a significant advantage of gel immersion in the visualization of the papilla
Confirmation bias exists; Case series retrospective study
Succeeded EUS-guided transduodenal drainage without double mucosal puncture
-
Balloon-assisted ERCP has a relatively low technical success rate because of its application to reconstructed intestinal tracts (Figure 3). Excessive gas insufflation poses a risk of hepatic portal venous gas and air embolism owing to the lack of an Oddi sphincter[86,87]. Theoretically, GIE can mitigate these risks by expanding the lumen without causing gas insufflation. Yokoyama et al[88] reported successful balloon-assisted ERCP with intrahepatic bile duct stones following liver transplantation, achieving success without pneumobilia, and named this technique the minimal water exchange method. GIE has also been reported to be useful for identifying anastomotic strictures. In 2023, Okuno et al[89] performed balloon-assisted ERCP using gel for pancreaticojejunal anastomosis and found that identification was easily achieved. Additionally, to identify the afferent limb in Roux-en-Y reconstruction, injecting a gel mixed with a contrast agent from the intestinal bifurcation allows easier visualization of the afferent limb under fluoroscopy[90].
Figure 3 Utility of balloon-enteroscopy for hepatobiliary and pancreatic visualization.
A: The pancreaticojejunostomy opening is unclear without gel; B: Gel use enables identification of the pancreaticojejunostomy (yellow arrow); C: Catheter insertion through the identified pancreaticojejunostomy is achieved; D: The same site is dilated with a balloon catheter.
Although the safety of GIE for interventional EUS has not yet been fully verified, Ogura et al[91]. reported a case involving the insertion of a lumen-apposing metal stent for walled-off necrosis (WON). By injecting approximately 200 mL of gel into the WON under EUS observation during the initial puncture, it was possible to achieve sufficient distance for the insertion of the lumen-apposing metal stent. Additionally, gel has been used to sufficiently expand the duodenum to avoid double puncture, which involves piercing the duodenal mucosa and muscularis during transduodenal drainage[92].
Future perspectives on GIE
As discussed previously, the majority of studies on GIE have been case reports or case-control studies. However, several prospective clinical trials have emerged in recent years, highlighting increasing interest in this field.
One such instance is a randomized controlled trial (NCT04977401) that investigated the extent to which ORISETM gel enhances the speed of ESD. Similarly, a prospective cohort study (NCT04886609) assessed the feasibility of ORISE gels in ESD and EMR procedures. Trials using TDM-623 have also been conducted, including an observational study (NCT05886127), to examine its efficacy in preventing post-sphincterotomy bleeding during ERCP. Another randomized controlled trial (NCT05031325) investigated the extent to which TDM-623 reduces the incidence of delayed bleeding following ESD.
Further studies are being conducted in Japan, including a study on the safety and efficacy of gel immersion for 15-19 mm non-pedunculated colorectal neoplasms (jRCT1042240052) and a randomized controlled trial comparing underwater EMR with gel immersion EMR (jRCTs062220033). These trials are expected to contribute to quantitative evaluation of the effectiveness of gel immersion techniques in endoscopic procedures.
CONCLUSION
The usefulness of GIE is attributed not only to the higher viscosity of the gel compared to water but also to its numerous advantages. These include lesion identification during bleeding, enhanced safety during ESD and EMR, and ability to maintain lumen expansion with minimal adverse events. Additionally, the benefits of "visualization" extend beyond the optical sense and can be applied to EUS, enabling broad applications for hepatobiliary and pancreatic lesions. GIE is a versatile tool that can be applied universally, making it invaluable to numerous endoscopists.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Japan
Peer-review report’s classification
Scientific Quality: Grade A, Grade B
Novelty: Grade A, Grade A
Creativity or Innovation: Grade A, Grade B
Scientific Significance: Grade B, Grade B
P-Reviewer: Dimopoulou K; Martino A S-Editor: Li L L-Editor: A P-Editor: Zheng XM
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