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Yang Y, Wang T, Xiao M, Hou Z, Liu Y, Zhang K, Yang L, Sun S. Polysaccharides as submucosal injection materials (SIMs) in endoscopic resection: A comprehensive review. Carbohydr Polym 2025; 355:123360. [PMID: 40037734 DOI: 10.1016/j.carbpol.2025.123360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/31/2025] [Accepted: 02/05/2025] [Indexed: 03/03/2025]
Abstract
Submucosal injection materials (SIMs) play a vital role in the endoscopic treatment of benign and early malignant gastrointestinal lesions by effectively elevating lesions while significantly reducing the risks of thermal injury and bleeding. However, the traditional use of normal saline (NS) presents challenges due to its rapid absorption, which necessitates frequent reapplications and complicates procedural efficiency. Therefore, there is a pressing need for ideal SIMs that are cost-effective, readily available, and suitable for personalized therapy, while also demonstrating excellent biocompatibility and physicochemical stability. Recent advancements have highlighted the potential of polysaccharide-based natural polymers, such as sodium hyaluronate, cellulose, starch derivatives, chitosan, and sodium alginate, due to their superior biocompatibility and biodegradability. These polysaccharides have exhibited enhanced operational characteristics and therapeutic efficacy in animal and clinical studies. Nevertheless, ongoing research must address several challenges, including optimizing cost-effectiveness, improving mechanical strength and bioactivity, and mitigating intraoperative and postoperative complications. This review systematically examines the progress of polysaccharide-based natural polymers in SIMs, evaluates their current status and challenges in both research and clinical applications, and proposes future directions to enhance their utilization in gastrointestinal endoscopic therapy.
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Affiliation(s)
- Yaochen Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China; Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Tingting Wang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Miaomiao Xiao
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yang Liu
- Innovative Engineering Technology Research Center for Cell Therapy, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, China
| | - Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Liqun Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Siyu Sun
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China; Department of Gastroenterology, Endoscopic Center, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang 110004, China.
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Bhatt A, Bucobo JC, Abdi M, Akshintala VS, Chen D, Chen YI, Copland AP, Das KK, Desilets DJ, Girotra M, Han S, Kahn A, Krishnan K, Leung G, Lichtenstein DR, Mishra G, Muthusamy VR, Obando JV, Onyimba FU, Pawa S, Rustagi T, Sakaria SS, Saumoy M, Shahnavaz N, Trikudanathan G, Trindade AJ, Vinsard DG, Yang J, Law R. Submucosal injection fluid and tattoo agents. Gastrointest Endosc 2024; 100:797-806. [PMID: 39269377 DOI: 10.1016/j.gie.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND AND AIMS EMR and endoscopic submucosal dissection (ESD) are minimally invasive endoscopic techniques, developed for the removal of benign and early malignant lesions throughout the GI tract. Submucosal injection of a marking agent can help to identify lesions during surgery. Endoscopic resection frequently involves "lifting" of the lesions by injection of a substance within the submucosal space to create a cushion for safe resection. This review summarizes the current techniques and agents available for endoscopic marking and lifting of GI tract lesions. METHODS The MEDLINE database was searched through April 2023 for relevant articles related to the lifting and marking aspect of EMR by using key words such as "endoscopy" or "endoscopic" combined with "marking," "tattoo," and "lifting." The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS This technology review describes the techniques for endoscopic tattoo placement and submucosal lifting, along with currently available agents, safety, and costs. CONCLUSIONS Endoscopists performing EMR and ESD have several choices in submucosal injection materials for lifting and marking agents for tattoos. These may be commercially prepared agents or off-the-shelf materials with or without additives to facilitate visualization. A thorough understanding of the indications, techniques, properties of various agents, costs, and adverse events is necessary in choosing the appropriate materials and technique to optimize lesion resection in EMR and ESD.
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Affiliation(s)
- Amit Bhatt
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Juan Carlos Bucobo
- Gastroenterology Services, Northwell Health Gastroenterology Institute, Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, USA
| | - Maaza Abdi
- Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - Venkata S Akshintala
- Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
| | - Dennis Chen
- Digestive Diseases Center, University of Chicago, Chicago, Illinois, USA
| | - Yen-I Chen
- Division of Gastroenterology & Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Andrew P Copland
- Division of Gastroenterology and Hepatology, University of Virginia Health Systems, Charlottesville, Virginia, USA
| | - Koushik K Das
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - David J Desilets
- Division of Gastroenterology, Baystate Medical Center, Springfield, Massachusetts, USA
| | - Mohit Girotra
- Department of Gastroenterology, Swedish Medical Center, Issaquah, Washington, USA
| | - Samuel Han
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Allon Kahn
- Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Kumar Krishnan
- Division of Gastroenterology, Department of Internal Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Galen Leung
- Department of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - David R Lichtenstein
- Division of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Girish Mishra
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - V Raman Muthusamy
- Division of Digestive Diseases, UCLA Health System, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jorge V Obando
- Division of Gastroenterology, Duke University Health System, Raleigh, North Carolina, USA
| | - Frances U Onyimba
- Department of Gastroenterology, WellSpan Digestive Health, York, Pennsylvania, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Tarun Rustagi
- Department of Gastroenterology, Kern Medical Center, Bakersfield, California, USA
| | - Sonali S Sakaria
- Division of Digestive Diseases, Emory University, Atlanta, Georgia, USA
| | - Monica Saumoy
- Department of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nikrad Shahnavaz
- Division of Digestive Diseases, Emory University, Atlanta, Georgia, USA
| | - Guru Trikudanathan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - Arvind J Trindade
- Department of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, New Hyde Park, New York, USA
| | | | - Julie Yang
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Ryan Law
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Bulking agents in gastrointestinal endoscopy: present applications and future advances. Curr Opin Gastroenterol 2022; 38:472-480. [PMID: 35881970 DOI: 10.1097/mog.0000000000000858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW Bulking agents are inert materials injected into an organ to affect the physical properties of the organ for a therapeutic purpose. Various agents have been developed to aid in the treatment of diseases like gastroesophageal reflux disease (GERD), fecal incontinence, obesity, malignancy, hemostasis, and tissue dissection. Here, we review the state of the art in bulking agents in gastrointestinal endoscopy, past failures, current limitations, and where we see the field heading in the future. RECENT FINDINGS Though bulking agents have been trialed for various different gastrointestinal diseases, there are currently limited uses in gastrointestinal endoscopy. Though various agents have been trialed for GERD, numerous complications and adverse events have limited its current use. However, for the treatment of fecal incontinence endoscopic bulking agent therapy is a reasonable option. Though in early stages of exploration, bulking agent therapy for enteric protection from radiotherapy may be a promising tool to improve treatment of pancreatic cancer. Bulking agents for tissue dissection have substantially improved lifting agents and complex polyp removal. Bulking agent therapy has not really been explored for endoscopic bariatric therapy or hemostasis but may be a fruitful area for exploration in the future. SUMMARY Bulking agent therapy has been trialed for various gastrointestinal diseases with mixed success. There is currently a therapeutic roll in the endoscopic management of fecal incontinence and tissue dissection. A future role in the treatment of GERD, obesity, malignancy, and hemostasis seem feasible.
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Abe S, Hirai Y, Uozumi T, Makiguchi ME, Nonaka S, Suzuki H, Yoshinaga S, Oda I, Saito Y. Endoscopic resection of esophageal squamous cell carcinoma: Current indications and treatment outcomes. DEN OPEN 2022; 2:e45. [PMID: 35310709 PMCID: PMC8828247 DOI: 10.1002/deo2.45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 07/05/2021] [Indexed: 11/16/2022]
Abstract
Endoscopic resection (ER) is an alternate minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). We aimed to review the clinical indications and treatment outcomes of ER for SESCC. Endoscopic mucosal resection is relatively easy and efficient for SESCC ≤ 15 mm. In contrast, endoscopic submucosal dissection (ESD) is recommended to achieve en bloc resection for lesions >15 mm, in view of the accurate pathological evaluation. The Japan Gastroenterological Endoscopy Society guidelines recommend ER for non-circumferential cT1a-EP/LPM (epithelium/lamina propria mucosae), cT1a-MM/T1b-SM1 (muscularis mucosa/superficial submucosa ≤ 200μm) SESCC, and whole-circumferential T1a-EP/LPM SESCC ≤ 50 mm (upon implementing preventive measures for stenosis), considering the risk-benefit balance of ER. It defines pT1a-EP/LPM without lymphovascular invasion as a curative endoscopic resection. The guidelines recommend additional esophagectomy or chemoradiotherapy for pT1b SESCC or any SESCC, with lymphovascular invasion. However, there is no recommendation for or against the administration of additional treatments for pT1a-MM without lymphovascular invasion, owing to limited evidence. Researchers have reported on high en bloc and R0 resection rates of ESD, and a randomized controlled trial demonstrated that clip-line traction-assisted ESD could significantly reduce the ESD procedural time. Moreover, steroid treatment has been developed to prevent post-ESD esophageal strictures. There have been reports on favorable long-term outcomes of ESD. However, most of them are retrospective studies. Further robust data in prospective trials are warranted to achieve a definitive evidence of ESD, which will be beneficial to patients with SESCC.
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Affiliation(s)
- Seiichiro Abe
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | - Yuichiro Hirai
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | - Takeshi Uozumi
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | | | - Satoru Nonaka
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | | | | | - Ichiro Oda
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
- Department of Internal MedicineKawasaki Rinko General HospitalKanagawaJapan
| | - Yutaka Saito
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
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Rex DK, Lahr RE, Peterson MM, Vemulapalli KC. Impact of including epinephrine in the submucosal injectate for colorectal EMR on postprocedural pain: a randomized controlled trial. Gastrointest Endosc 2022; 95:535-539.e1. [PMID: 34896443 DOI: 10.1016/j.gie.2021.11.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/20/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS EMR is first-line therapy for colorectal laterally spreading lesions. Some colonoscopists include epinephrine in the submucosal injectate, which we observed increased postprocedure discomfort. Our aim was to determine whether inclusion of epinephrine in the submucosal injectate increases postprocedure pain after EMR. METHODS We performed a randomized, controlled, double-blind trial comparing epinephrine in submucosal injectate versus injectate alone for abdominal pain at 30 and 60 minutes after EMR. RESULTS Mean polyp diameter in both arms was >40 mm. There were no differences in procedure times or amounts of fluid injected. Mean pain was higher on a visual analog scale in the epinephrine group at 30 minutes (47 vs 14, P = .022) and at 60 minutes (44 vs 13, P = .035). Recovery room stay was longer in the epinephrine group (68 vs 53 minutes, P = .034). CONCLUSIONS Epinephrine in the submucosal injectate for EMR increases postprocedural pain, which could cause diagnostic confusion and prolong observation time in the recovery area. (Clinical trial registration number: NCT04065451.).
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Affiliation(s)
- Douglas K Rex
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Rachel E Lahr
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Merritt M Peterson
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Krishna C Vemulapalli
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Rashid MU, Alomari M, Afraz S, Erim T. EMR and ESD: Indications, techniques and results. Surg Oncol 2022; 43:101742. [DOI: 10.1016/j.suronc.2022.101742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/21/2022] [Accepted: 03/08/2022] [Indexed: 12/11/2022]
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Hirose R, Nakaya T, Naito Y, Yoshida T, Bandou R, Daidoji T, Inoue K, Dohi O, Yoshida N, Itoh Y. An innovative next-generation endoscopic submucosal injection material with a 2-step injection system (with video). Gastrointest Endosc 2021; 93:503-513.e5. [PMID: 32565186 DOI: 10.1016/j.gie.2020.06.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 06/05/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Next-generation submucosal injection materials (SIMs) with higher performance and flexibility than the current SIMs (eg, 0.4% sodium hyaluronate solution [HA]) are expected to improve the outcomes of endoscopic submucosal dissection (ESD) but are difficult to develop. We developed a next-generation SIM by devising a 2-solution-type SIM comprising 2.0% calcium chloride solution (Ca) and 0.4% sodium alginate solution (SA) and evaluated its performance. METHODS Viscoelasticity, submucosal elevation height, and injection pressure of HA, SA, and the next-generation SIM were measured. Outcomes of ESDs on pseudo-lesions in ex vivo porcine stomach/colon models were compared. RESULTS The dramatic increase in SA viscoelasticity with the addition of Ca facilitated the formation of highly viscous submucosal cushions that can be controlled by endoscopists. The submucosal elevation height of the next-generation SIM was significantly higher than that of HA or SA with the same injection pressure. The ESD procedure time using the next-generation SIM was significantly shorter than that using HA or SA (14.2 ± 6.1 vs 29.2 ± 9.1 minutes, P = .0004, or 14.2 ± 6.1 vs 29.1 ± 5.9 minutes, P <.0001). Furthermore, the total injection volume for the next-generation SIM was considerably lower than that for HA or SA (7.0 ± 0.9 vs 17.2 ± 3.4 mL, P <.0001, or 7.0 ± 0.9 vs 16.2 ± 2.9 mL, P <.0001). CONCLUSIONS We developed an ideal next-generation SIM that achieved high performance and high flexibility in ex vivo models. Our findings warrant further investigations in a patient population.
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Affiliation(s)
- Ryohei Hirose
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takaaki Nakaya
- Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuji Naito
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takuma Yoshida
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Risa Bandou
- Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomo Daidoji
- Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ken Inoue
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Osamu Dohi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Naohisa Yoshida
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Hirose R, Yoshida N, Naito Y, Yoshida T, Bandou R, Daidoji T, Inoue K, Dohi O, Konishi H, Nakaya T, Itoh Y. Development of Sodium Polyacrylate-Based High-Performance Submucosal Injection Material with Pseudoplastic Fluid Characteristics. ACS Biomater Sci Eng 2019; 5:6794-6800. [PMID: 33423472 DOI: 10.1021/acsbiomaterials.9b01373] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The development of high-performance submucosal injection materials (SIMs) has significantly contributed to the advancement of rapid and safe endoscopic submucosal dissection (ESD). A previous study authored by us described that pseudoplastic fluid was more suitable for high-performance SIMs than Newtonian fluid. Herein, a novel high-performance SIM is developed, which is primarily composed of sodium polyacrylate (SPA) and exhibits pseudoplastic fluid characteristics. As a representative of current high-performance SIMs with Newtonian fluid characteristics, 0.4% sodium hyaluronate (HA) was selected as the target for comparison. Further, viscoelasticity, submucosal elevation height (SEH), and injection pressure (IP) of HA and SPA were evaluated. The results obtained by ESD were compared using HA or SPA in an ex vivo model. According to the measured viscoelasticity, the concentration of SPA was adjusted to 0.07%; this was aimed at obtaining the IP of SPA, which is equal to that of 0.4% HA. Moreover, no significant difference was observed between the IP values (31.6 ± 1.7 vs 31.4 ± 3.1 psi). SEHs of 0.07% SPA were higher than those of 0.4% HA at all postinjection times (P < 0.001). The duration of the ESD procedure using 0.07% SPA was significantly shorter than that obtained using 0.4% HA (16.6 ± 3.7 vs 22.2 ± 2.9 min, P = 0.0276); further, the total volume of the injected 0.07% SPA was significantly less than that of 0.4% HA (9.0 ± 3.1 vs 15.7 ± 3.9 mL, P = 0.0165). Based on rheological analysis, a high-performance SIM (0.07% SPA) with pseudoplastic fluid characteristics was theoretically developed. It was observed that the SIM performance of 0.07% SPA was higher than that of 0.4% HA.
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Normal saline solution versus other viscous solutions for submucosal injection during endoscopic mucosal resection: a systematic review and meta-analysis. Gastrointest Endosc 2017; 85:693-699. [PMID: 27940101 DOI: 10.1016/j.gie.2016.12.003] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 12/01/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS EMR is being increasingly practiced for the removal of large colorectal polyps. A variety of solutions such as normal saline solution (NS) and other viscous and hypertonic solutions (VS) have been used as submucosal injections for EMR. A systematic review and meta-analysis is presented comparing the efficacy and adverse events of EMR performed using NS versus VS. METHODS Two independent reviewers conducted a search of all databases for human, randomized controlled trials that compared NS with VS for EMR of colorectal polyps. Data on complete en bloc resection, presence of residual lesions, and adverse events were extracted using a standardized protocol. Pooled odds ratio (OR) estimates along with 95% confidence intervals (CI) were calculated using fixed effect or random effects models. RESULTS Five prospective, randomized controlled trials (504 patients) met the inclusion criteria. The mean polyp sizes were 20.84 mm with NS and 21.44 mm with VS. On pooled analysis, a significant increase in en bloc resection (OR, 1.91; 95% CI, 1.11-3.29; P = .02; I2 = 0%) and decrease in residual lesions (OR, 0.54; 95% CI, 0.32-0.91; P = .02; I2 = 0%) were noted in VS compared with NS. There was no significant difference in the rate of overall adverse events between the 2 groups. CONCLUSIONS Use of VS during EMR leads to higher rates of en bloc resection and lower rates of residual lesions compared with NS, without any significant difference in adverse events. Endoscopists could consider using VS for EMR of large colorectal polyps and NS for smaller polyps because there is no significant difference in the outcomes with lesions <2 cm.
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Ning B, Abdelfatah MM, Othman MO. Endoscopic submucosal dissection and endoscopic mucosal resection for early stage esophageal cancer. Ann Cardiothorac Surg 2017; 6:88-98. [PMID: 28446997 PMCID: PMC5387148 DOI: 10.21037/acs.2017.03.15] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 02/16/2017] [Indexed: 12/20/2022]
Abstract
Mortality from esophageal cancer remains high despite advances in medical therapy. Although the incidence of squamous cell carcinoma of the esophagus remains unchanged, the incidence of the esophageal adenocarcinoma has increased over time. Gastroesophageal reflux disease (GERD and obesity are contributing factors to the development of Barrett's esophagus and subsequent development of adenocarcinoma. Early recognition of the disease can lead to resection of esophageal cancer prior to the development of lymphovascular invasion. Various modalities have been implemented to aid identification of precancerous lesions and early esophageal cancer. Chromoendoscopy, narrowband imaging and endoscopic ultrasound examination are typically used for evaluating early esophageal lesions. Recently, confocal laser endomicroscopy (CLE) and volumetric laser scanning were implemented with promising results. Endoscopic management of early esophageal cancer may be done using endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Both techniques allow resection of the mucosa (and possibly a portion of the submucosa) containing the early tumor without interruption of deeper layers. A submucosal injection creating a cushion coupled with snare resection or cap assisted mucosal suction followed by ligation and snare resection are the most common techniques of EMR. EMR can remove lesions less than 2 cm in size en bloc. Larger lesions may require resection in piecemeal fashion. This may limit assessment of the margins of the lesion and orienting the lesion's border. ESD offers en bloc dissection of the lesion regardless of its size. ESD is performed with specialized needle knives, which allow incision followed by careful dissection of the lesion within the submucosal layer. Tumor recurrence after ESD is rare but the technique is labor intensive and has an increased risk of perforation. Esophageal stenosis remains a concern after extensive EMR or ESD. Dilation with balloon or stent placement is usually sufficient to treat post-resection stenosis.
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Affiliation(s)
- Bo Ning
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Mohamed M. Abdelfatah
- Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA
| | - Mohamed O. Othman
- Division of Gastroenterology, Department of Internal Medicine, East Carolina University, Greenville, NC, USA
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Arantes V, Uedo N, Pedrosa MS, Tomita Y. Clinical relevance of aberrant polypoid nodule scar after endoscopic submucosal dissection. World J Gastrointest Endosc 2016; 8:628-634. [PMID: 27668074 PMCID: PMC5027034 DOI: 10.4253/wjge.v8.i17.628] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Revised: 04/26/2016] [Accepted: 07/13/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To describe a series of patients with aberrant polypoid nodule scar developed after gastric endoscopic submucosal dissection (ESD), and to discuss its pathogenesis and clinical management.
METHODS We reviewed retrospectively the endoscopic database of two academic institutions located in Brazil and Japan and searched for all patients that underwent ESD to manage gastric neoplasms from 2003 to 2015. The criteria for admission in the study were: (1) successful en bloc ESD procedure with R0 and curative resection confirmed histologically; (2) postoperative endoscopic examination with identification of a polypoid nodule scar (PNS) at ESD scar; (3) biopsies of the PNS with hyperplastic or regenerative tissue, reviewed by two independent experienced gastrointestinal pathologists, one from each Institution. Data were examined for patient demographics, Helicobacter pylori status, precise neoplastic lesion location in the stomach, tumor size, histopathological assessment of the ESD specimen, and postoperative information including medical management, endoscopic and histological findings, and clinical outcome.
RESULTS A total of 14 patients (10 men/4 women) fulfilled the inclusion criteria and were enrolled in this study. One center contributed with 8 cases out of 60 patients (13.3%) from 2008 to 2015. The second center contributed with 6 cases (1.7%) out of 343 patients from 2003 to 2015. Postoperative endoscopic follow-up revealed similar findings in all patients: A protruded polypoid appearing nodule situated in the center of the ESD scar surrounded by convergence of folds. Biopsies samples were taken from PNS, and histological assessment revealed in all cases regenerative and hyperplastic tissue, without recurrent tumor or dysplasia. Primary neoplastic lesions were located in the antrum in 13 patients and in the angle in one patient. PNS did not develop in any patient after ESD undertaken for tumors located in the corpus, fundus or cardia. All patients have been followed systematically on an annual basis and no malignant recurrence in the ESD scar has been identified (mean follow-up period: 45 mo).
CONCLUSION PNS may occur after ESD for antral lesions and endoscopically look concerning, especially for the patient or the family doctor. However, as long as curative R0 resection was successfully achieved and histology demonstrates only regenerative and hyperplastic tissue, PNS should be viewed as a benign alteration that does not require any type of intervention, other than endoscopic surveillance.
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Abstract
ESD is an established effective treatment modality for premalignant and early-stage malignant lesions of the stomach, esophagus, and colorectum. Compared with EMR, ESD is generally associated with higher rates of en bloc, R0, and curative resections and a lower rate of local recurrence. Oncologic outcomes with ESD compare favorably with competing surgical interventions, and ESD also serves as an excellent T-staging tool to identify noncurative resections that will require further treatment. ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures including EMR. As such,sufficient training is critical to ensure safe conduct and high-quality resections. A standardized training model for Western endoscopists has not been clearly established,but will be self-directed and include courses, animal model training, and optimally an observership at an expert center.Numerous dedicated ESD devices are now available in the United States from different manufacturers. Although the use of ESD in the United States is increasing, issues related to technical difficulty, limited training opportunities and mentors, risk of adverse events, long procedure duration,and suboptimal reimbursement may limit ESD adoption in the United States to a modest number of academic referral centers for the foreseeable future.
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ARANTES VITOR. DISECCIÓN ENDOSCÓPICA DE SUBMUCOSA EN EL TRATAMIENTO DEL CÁNCER PRECOZ DE ESÓFAGO. REVISTA MÉDICA CLÍNICA LAS CONDES 2015. [DOI: 10.1016/j.rmclc.2015.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Sold M, Kähler G. Improved Techniques for Endoscopic Mucosal Resection (EMR) in Colorectal Adenoma. VISZERALMEDIZIN 2015; 30:33-8. [PMID: 26286120 PMCID: PMC4513797 DOI: 10.1159/000358243] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. Method Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. Results Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. Conclusion Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge.
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Affiliation(s)
- Moritz Sold
- Zentrale Interdisziplinäre Endoskopie ZIE, Universitätsmedizin Mannheim, Germany
| | - Georg Kähler
- Zentrale Interdisziplinäre Endoskopie ZIE, Universitätsmedizin Mannheim, Germany
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Hwang JH, Konda V, Abu Dayyeh BK, Chauhan SS, Enestvedt BK, Fujii-Lau LL, Komanduri S, Maple JT, Murad FM, Pannala R, Thosani NC, Banerjee S. Endoscopic mucosal resection. Gastrointest Endosc 2015; 82:215-26. [PMID: 26077453 DOI: 10.1016/j.gie.2015.05.001] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 05/01/2015] [Indexed: 02/06/2023]
Abstract
EMR has become an established therapeutic option for premalignant and early-stage GI malignancies, particularly in the esophagus and colon. EMR can also aid in the diagnosis and therapy of subepithelial lesions localized to the muscularis mucosa or submucosa. Several dedicated EMR devices are available to facilitate these procedures. Adverse event rates, particularly bleeding and perforation, are higher after EMR relative to other basic endoscopic interventions but lower than adverse event rates for ESD. Endoscopists performing EMR should be knowledgeable and skilled in managing potential adverse events resulting from EMR.
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Burgess NG, Bahin FF, Bourke MJ. Colonic polypectomy (with videos). Gastrointest Endosc 2015; 81:813-35. [PMID: 25805461 DOI: 10.1016/j.gie.2014.12.027] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 12/04/2014] [Indexed: 02/08/2023]
Affiliation(s)
- Nicholas G Burgess
- Department of Gastroenterology and Hepatology, Westmead Hospital; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Farzan F Bahin
- Department of Gastroenterology and Hepatology, Westmead Hospital; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
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Arantes V, Albuquerque W, Freitas Dias CA, Demas Alvares Cabral MM, Yamamoto H. Standardized endoscopic submucosal tunnel dissection for management of early esophageal tumors (with video). Gastrointest Endosc 2013; 78:946-952. [PMID: 23810327 DOI: 10.1016/j.gie.2013.05.031] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2012] [Accepted: 05/27/2013] [Indexed: 12/12/2022]
Affiliation(s)
- Vitor Arantes
- Endoscopy Unit, Alfa Institute of Gastroenterology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
| | - Walton Albuquerque
- Endoscopy Unit, Alfa Institute of Gastroenterology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Carlos Alberto Freitas Dias
- Endoscopy Unit, Alfa Institute of Gastroenterology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Tochigi, Japan
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Abstract
The value of performing comprehensive screening colonoscopy with complete colon polypectomy is widely accepted. Colon cancer is a significant cause of worldwide mortality and prospective studies have proven that colonoscopic polypectomy reduces both the incidence and mortality related to this disease. Over the past few decades the array of instruments and techniques have greatly expanded to assist with the safe endoscopic removal of colon polyps. This article will review the published literature regarding efficacy and safety of standard polypectomy techniques such as snare polypectomy, electrocautery, and endoscopic mucosal resection along with newer techniques such as endoscopic submucosal dissection and combined laparoscopic techniques.
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Pontone S, Manfredelli S, Krizzuk D, Leonetti G. Is long-lasting mucosal elevation the only valid parameter when evaluating a lifting agent? Clin Exp Gastroenterol 2012; 5:101-2. [PMID: 22767996 PMCID: PMC3387827 DOI: 10.2147/ceg.s33106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Stefano Pontone
- Department of Surgical Sciences, "Sapienza" University of Rome, Rome, Italy
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Wen W, Shi C, Shi Y, Ji G, Wu P, Fan Z, Zhang F. A pilot animal and clinical study of autologous blood solution compared with normal saline for use as an endoscopic submucosal cushion. Exp Ther Med 2012. [PMID: 23181111 PMCID: PMC3503630 DOI: 10.3892/etm.2012.626] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Normal saline is the most popular agent used during endoscopic submucosal injection. However, endoscopists have never identified an optimal submucosal injection solution, which is not only safe and cost-effective but has a unique lifting ability with endoscopic submucosal cushion and causes less tissue damage. This study aimed to evaluate the effectiveness and microscopic characteristics of a blood solution, including whole blood and plasma solution, as a submucosal cushioning agent, compared with normal saline. Endoscopic submucosal dissection (ESD) procedures in pig stomachs were performed by injecting plasma solution (n=4) and normal saline (n=4). A total of 38 patients with gastrointestinal neoplasms underwent endoscopic musocal resection (EMR) procedures. Of 38 EMRs, 7 used whole blood injection, and 31 of 38 acting as the control group used normal saline. A tissue damage scoring system was developed based on injection-induced hydrops and tears for the evaluation of tissue damage. In animal experiments, the lifting time of the injection with normal saline in the pig colon was shorter than that of the group with plasma solution (18.25±5.44 min vs. 6.5±2.38 min, P=0.007). In animal experiments with ESD procedures in the stomach, the hydrops in the normal saline injection group were more extensive than those in the group with plasma (P=0.011). The degree of tearing in the group with normal saline was observed to be less than that in the group with plasma (P=0.008). In patients with EMR, using the histological scoring method, it was determined that the degree of hydrops in the group with normal saline injection was more extensive than that in the group with whole blood (P<0.001). The effective submucosal tearing in the group with normal saline was less than that in the group with blood (P<0.001). The blood solution, including whole blood and plasma solution, as a novel submucosal injection agent, may outperform normal saline with a unique lifting ability, less pronounced tissue damage and marked effective submucosal blunt dissection.
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Affiliation(s)
- Wei Wen
- Institute of Digestive Endoscopy and Medical Center for Digestive Diseases and
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Santos CEOD, Malaman D, Pereira-Lima JC. Endoscopic mucosal resection in colorectal lesion: a safe and effective procedure even in lesions larger than 2 cm and in carcinomas. ARQUIVOS DE GASTROENTEROLOGIA 2011; 48:242-7. [DOI: 10.1590/s0004-28032011000400005] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2011] [Accepted: 07/14/2011] [Indexed: 02/07/2023]
Abstract
CONTEXT: Endoscopic mucosal resection is a minimally invasive technique used in the treatment of colorectal neoplasms, including early carcinomas of different size and morphology. OBJECTIVES: To evaluate procedure safety, efficacy, outcomes, and recurrence rate in endoscopic mucosal resection of colorectal lesions. METHODS: A total of 172 lesions in 156 patients were analyzed between May 2003 and May 2009. All lesions showed pit pattern suggestive of neoplasia (Kudo types III-V) at high-magnification chromocolonoscopy with indigo carmine. The lesions were evaluated for macroscopic classification, size, location, and histopathology. Lesions 20 mm or smaller were resected en bloc and lesions larger than 20 mm were removed using the piecemeal technique. Complications and recurrence were analyzed. Patients were followed up for 18 months. RESULTS: There were 83 (48.2%) superficial lesions, 57 (33.1%) depressed lesions, 44 (25.6%) laterally spreading tumors, and 45 (26.2%) protruding lesions. Mean lesion size was 11.5 mm ± 9.6 mm (2 mm-60 mm). Patients' mean age was 61.6 ± 12.5 years (34-93 years). Regarding lesion site, 24 (14.0%) lesions were located in the rectum, 68 (39.5%) in the left colon, and 80 (46.5%) in the right colon (transverse, ascending, and cecum). There were 167 (97.1%) neoplasms: 142 (82.5%) adenomatous lesions, 24 (14.0%) intramucosal carcinomas, and 1 (0.6%) invasive carcinoma. En bloc resection was performed in 158 (91.9%) cases and piecemeal resection in 14 (8.1%). Bleeding occurred in 5 (2.9%) cases. Recurrence was observed in 4.1% (5/122) of cases and was associated with lesions larger than 20 mm (P<0.01), piecemeal resection (P<0.01), advanced neoplasm (P = 0.01), and carcinoma compared to adenoma (P = 0.04). CONCLUSIONS: Endoscopic mucosal resection of colorectal lesions is a safe and effective procedure, with low complication and local recurrence rates. Recurrence is associated with lesions larger than 20 mm and carcinomas.
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Endoscopic mucosal resection with the grasp-and-snare technique through a double-channel endoscope in humans. Gastrointest Endosc 2011; 73:349-52. [PMID: 21295646 DOI: 10.1016/j.gie.2010.10.030] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2009] [Accepted: 10/19/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND EMR is being used to manage premalignant lesions of the GI tract. Lifting of the lesion is required to perform EMR. Earlier biopsy or snare may cause scarring and preclude adequate lifting. OBJECTIVE We report our experience with a novel grasp-and-snare EMR technique that can be used when a good lifting is not achieved or the location of the lesion is challenging for standard EMR, such as in a fold. DESIGN Single-center case series. SETTING Tertiary referral academic gastroenterology unit. PATIENTS Patients referred for endoscopic treatment of flat gastrointestinal polyps. INTERVENTIONS Single-session EMR performed with a grasp-and-snare technique through a double-channel gastroscope or colonoscope. MAIN OUTCOME MEASUREMENTS Technical success, complication rates, and recurrence rates. RESULTS Seventeen patients with flat gastrointestinal polyps were referred: mean age 70 years, 11 (65%) male, polyp size 0.8 to 6 cm; 13 colonic, 2 duodenal, 1 gastric, and 1 esophageal EMR performed with grasp-and-snare technique in single sessions. Six polyps (35%) did not lift after injection of hydroxypropylmethylcellulose. Fourteen polyps (82%) were resected completely. Two complications occurred (12%): 1 bleeding treated medically and 1 perforation treated surgically. Residual disease at 1 year was 18%, but 8 patients (47%) had not yet had their 1-year follow-up. LIMITATIONS Single-center, uncontrolled, not randomized. Limited follow-up. CONCLUSIONS The grasp-and-snare technique can be used to perform EMR with good outcomes and low complication rates in areas where poor lifting and accessibility are problems.
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Abstract
PURPOSE OF REVIEW Colorectal cancer screening and prevention is a pivotal element in every gastroenterologist practice. Recent advances in imaging technology and treatment opened the field for endoscopic management of large flat colorectal polyps and early cancer. RECENT FINDINGS High-definition white light colonoscopy allowed for better characterization of colon polyps, particularly flat lesions. Chromoendoscopy facilitated the identification of colon polyps as well as better endoscopic polyp characterization, with strong correlation with final pathological diagnosis, opening the field of 'virtual' biopsy. One particular technology, confocal endomicroscopy can magnify an image approximately 1000 times resembling optical microscopy with very good correlation with histology. Endoscopic mucosal resection has gained great acceptance to manage flat colorectal polyps with the two major complications being bleeding and perforation, both now under 5% in experienced hands. Endoscopic submucosal resection was developed to increase en-bloc resection (less residual disease) of a flat colorectal lesion but one has to accept a higher perforation rate around 10%. SUMMARY Current technology allows for better polyp identification and characterization, which can be managed endoscopically.
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