Submucosal Injection Solution Research Articles

Tu1513 Prospective Analysis of Associated Pain After ESD Using Submucosal Injection Solution With Lidocaine

The factors of pain after endoscopic submucosal dissection (ESD) are not well known. In previous a report, 41% of the patients suffered from pain over 1hr after ESD. To be better quality after ESD, management of pain is essential for patients. The effect of lidocaine mixture for degree of pain by visual analogue scale after ESD was evaluated.

PTU-012 A novel submucosal injection solution: data on safety and efficacy from a large prospective EMR series

Introduction Submucosal injection is an integral part of EMR. The ideal solution will produce a long lasting high elevation, and an avascular field with delineation of tissue planes. This requires a combination of various drugs and solutions. However, no such mix is commercially available. This has resulted in a wide range of mix being used in this country, with no data on the safety, efficacy and long-term results of these solutions. We have developed an ideal mix of gelofusine (colloid) to provide a long lasting lift with adrenaline to reduce the vascularity of the field and indigo carmine to adequately delineate tissue planes. We aim to illustrate the feasibility, safety and efficacy and long-term effects of our novel submucosal lifting solution. Methods The lifting solution was: 500 mls gelofusine, 2 mls 1:1000 adrenaline and 5 mls indigocarmine 0.4%. We reviewed all EMRs since 2005. Records were assessed to collect data on efficacy of the solution, immediate and late mucosal and systemic effects. Data were collected on type and size of lesions, procedure time and volume of solution used. Results A total of 546 lesions were removed. 411 polypectomies and 135 upper GI EMRs. Volume used was between 5-250 mls, dependent on lesion size and procedure time (range 20 min–180 min). Distribution of upper GI lesions: 99 oesophageal EMRs, 20 gastric EMRs and 16 duodenal EMRs. Endoscopic follow-up data were available on 107 cases, with a mean interval of 3 months (range: 2–6 months). There was no evidence of immediate or late complications, including tissue injury, necrosis or stenosis related to the solution. For the lower GI lesions: 411 polyps removed. There were 143 polyps >2 cm in size. Left sided lesions=121 (median 45 mm range 20–150), right sided lesions=22 (median 31 mm, range 20–50). Procedure time 20 min–180 min. There were follow-up data on 117 colonic EMRs, with a mean interval of 4 months (range 0.5–60 months). There was no evidence of any late complications, including tissue injury necrosis or stenosis at the previous polypectomy sites. The endoscopist found the solution extremely effective and provided good lift after one injection in all of the cases examined. There was a short lived 5–20% rise in pulse rate. There were no immediate cardiac complications preventing completion of the procedures. No anaphylaxis or allergic reaction. There was no local or systemic sepsis related to the solution. No obvious renal or hepatic effects reported. Conclusion Largest reported series on submucosal injection solution in the world; Have clearly demonstrated the feasibility and efficacy of this novel injection mix; Shows immediate and long-term safety of this solution; Shows some systemic effects like tachycardia so caution is advised in cardiac patients.

S1421: The Safety and Efficacy of a Novel Sub-Mucosal Injection Solution: Results From a Large Prospective EMR Series

S1421: The Safety and Efficacy of a Novel Sub-Mucosal Injection Solution: Results From a Large Prospective EMR Series

347l: Modification of Submucosal (SM) Injection Solution Significantly Improves Technical Outcomes in Colonic Endoscopic Mucosal Resection (EMR): A Randomized, Double-Blind Controlled Trial of Succinylated Gelatin (SG) Versus Normal Saline for EMR of Laterally Spreading Tumours (LSTs) and Large Sessile Lesions of the Colon

SG (Gelofusine®, B.Braun, Switzerland) is a clear, inexpensive, safe, colloidal plasma volume expanding solution that is commonly used for hypovolaemia. When compared to normal saline (NS) for SM injection in a porcine model, SG provided superior vertical elevation of the lesion resulting in a 42% increase in EMR specimen size. The present study is the first to investigate SG for human colonic EMR.

ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE COLORECTUM: PRESENT STATUS AND FUTURE PROSPECTS

Endoscopic submucosal dissection (ESD) can successfully resect early stage gastrointestinal tumors, but colorectal ESDs are not widely performed, even by Japanese endoscopists, because of several negative factors. Besides being considerably more difficult in terms of technical demands, colorectal ESDs involve a longer procedure time and have a higher complication rate compared to gastric ESDs. In addition, most colorectal lesions are adenomas or intramucosal cancers that despite their large size that can be curatively treated by endoscopic mucosal resection including piecemeal resection. There is, however, no doubt about ESD having a major therapeutic advantage in being able to achieve a higher en-bloc resection rate resulting in enhanced curability and more accurate histopathological assessment. Continued improvement in the technical skills of endoscopists, further refinement of such devices as electrical surgical knives and a special colonoscope as well as the development of more effective submucosal injection solutions and new traction systems are expected to facilitate easier, faster and safer colorectal ESD procedures in the relatively near future.

Comparing Safety and Effectiveness of Glycerol and Sodium Hyaluronate Submucosal Injection Solutions for Colorectal Endoscopic Mucosal Resection - A Pilot Study

Background: Various submucosal (sm) injection solutions have been developed for colorectal endoscopic mucosal resection (EMR) to facilitate en-bloc resections and reduce the risk of perforations and bleeding. We previously reported on the superiority of a 10% glycerol solution compared to normal saline for colorectal EMR. Recently, 0.4% sodium hyaluronate (SH) has been approved for clinical use in Japan. Higher en-bloc resection and lower perforation rates for endoscopic submucosal dissection (ESD) using SH have been reported although one disadvantage is its high cost.

Progress Towards the Ideal Submucosal Injection Solution for Endoscopic Mucosal Resection (EMR) - A Randomized Blinded Trial of Succinylated Gelatin (SG) Versus Normal Saline (NS) for Colonic EMR in a Porcine Model

Progress Towards the Ideal Submucosal Injection Solution for Endoscopic Mucosal Resection (EMR) - A Randomized Blinded Trial of Succinylated Gelatin (SG) Versus Normal Saline (NS) for Colonic EMR in a Porcine Model

Efficacy of a reverse-phase polymer as a submucosal injection solution for EMR: a comparative study (with video)

Reverse-phase polymers undergo a temperature-dependent liquid-to-gel transition that may provide a more durable cushion for EMR and could yield improvements in safety and efficacy. Our purpose was to assess the efficacy of poloxamer solution PS137-25 as a submucosal injection. Comparative study among 3 different solutions for EMR using ex vivo and in vivo porcine models. A total of 120 gastric submucosal cushions were performed in fresh ex vivo porcine stomachs with saline solution 0.9% (n = 40), hydroxypropyl methylcellulose (HPMC) (n = 40), and PS137-25 (n = 40). Five in vivo porcine colon EMRs were then performed. Height and duration of submucosal cushions were measured in the ex vivo model, and the usefulness of reverse-phase polymers was assessed by in vivo en bloc resection. Ex vivo: The height of mucosal elevation was greater with PS137-25 (10.3 +/- 2.2 mm) than with saline solution (8.3 +/- 2.6 mm) or HPMC (9.05 +/- 2.3 mm, not significant). All submucosal elevations with PS137-25 lasted longer (more than 20 minutes) than with saline solution (20.9 +/- 11 minutes, P < .01) or HPMC (89 +/- 32 minutes, P < .01). After 120 minutes, the elevations obtained with PS137-25 showed no differences in size, shape, or consistency from initial measurements. In vivo: All 5 EMRs were successfully performed after 1 injection of PS137-25. No repeat injections were needed. During resection, a large gel cushion was noted. Mucosal elevation with PS137-25 is more durable than with other substances, with no changes in size or consistency observed over 120 minutes. Additionally, reverse-phase polymers performed well in in vivo colon EMRs. These results suggest that reverse-phase polymers may provide increased safety and efficacy for EMR procedures.

Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: A prospective multi-center open-label trial

BackgroundSodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion". Recently, we proved the usefulness and safety of 0.4% SH solution in endoscopic resection for gastric mucosal tumors. To evaluate the usefulness of 0.4% SH as a submucosal injection solution for colorectal endoscopic resection, we conducted an open-label clinical trial on six referral hospitals in Japan.MethodsA prospective multi-center open-label study was designed. A total of 41 patients with 5–20 mm neoplastic lesions localized in the colorectal mucosa at six referral hospitals in Japan in a single year period from December 2002 to November 2003 were enrolled and underwent endoscopic resection with SH. The usefulness of 0.4% SH was assessed by the en bloc complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. Safety was evaluated by analyzing adverse events during the study period.ResultsThe usefulness rate was high (82.5%; 33/40). The following secondary outcome measures were noted: 1) steepness of mucosal lesion-lifting, 75.0% (30/40); 2) intraoperative complications, 10.0% (4/40); 3) time required for mucosal resection, 6.7 min; 4) volume of submucosal injection, 6.8 mL and 5) ease of mucosal resection, 87.5% (35/40). Two adverse events of bleeding potentially related to 0.4% SH were reported.ConclusionUsing 0.4% SH solution enabled sufficient lifting of a colorectal intramucosal lesion during endoscopic resection, reducing the need for additional injections and the risk of perforation. Therefore, 0.4% SH may contribute to the reduction of complications and serve as a promising submucosal injection solution due to its potentially superior safety in comparison to normal saline solution.

Different solutions used for submucosal injection influenced early healing of gastric endoscopic mucosal resection in a preclinical study in experimental pigs

BackgroundWe hypothesised that different solutions for submucosal injection may influence early healing of endoscopic mucosal resection (EMR). The aim of this study was to evaluate histological and immunological changes after EMR in experimental pigs.Materials and methodsTwo parallel EMRs on the anterior and posterior wall of the gastric body were performed by means of the cap technique in 21 female pigs. A glycerol-based solution (anterior EMR) and hydroxypropyl methylcellulose solution (posterior EMR) were applied for submucosal injection. The animals were sacrificed 7 days later, and tissue sections of all EMRs were stained using combined trichrome. Computer image analysis was used for objective evaluation of elastic and collagen fibres content. Two-colour indirect immunophenotyping of blood and gastric samples were performed using mouse anti-pig monoclonal antibodies.ResultsThe values of collagen fibre content 7 days after EMR were significantly higher in lesions after the use of solution A in comparison with solution B (2.10 ± 0.25% versus 1.57 ± 0.25%, p = 0.009). Concordant results were found in elastic fibres (3.23 ± 0.49% versus 2.93 ± 0.61%, p = 0.018). No systemic changes in major leukocyte subpopulations were found. In gastric tissue, lymphocyte subsets exhibited only minor changes. CD4+ T-lymphocytes were increased in the healing tissue after EMR using solution A (17.08 ± 9.24% versus 9.76 ± 7.97%, p = 0.011). Significant increase of SWC3+ leukocytes was observed after EMR using solution B (47.70 ± 25.41% versus 18.70 ± 12.16%, p = 0.001).ConclusionsThe use of glycerol-based solution for submucosal injection was associated with more pronounced histological signs of early healing of EMRs compared with hydroxypropyl methylcellulose.

Submucosal injection solution for gastrointestinal tract endoscopic mucosal resection and endoscopic submucosal dissection

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have provided new alternatives for minimally invasive treatment of gastrointestinal adenomas and early-stage cancers that involve a minimum risk of lymph-node metastasis. The use of submucosal injections is essential to the success of these endoscopic resection techniques. The "ideal" submucosal injection solution should provide a sufficiently high submucosal fluid cushion for safe and effective EMRs and ESDs while also preserving lesion tissue for accurate histopathological assessment. In the past, normal saline (NS) solution was commonly used for this purpose, but it is difficult to achieve the proper submucosal elevation and maintain the desired height with NS. Therefore, other safe and effective facilitative submucosal injection solutions have been developed that also take into account relevant cost-benefit considerations. This review examines recent advances in the development of effective submucosal injection solutions for use during endoscopic resections.

W1112 Efficacy of a Reverse Phase Polymer As a Submucosal Injection Solution for EMR: A Comparative Study

W1112 Efficacy of a Reverse Phase Polymer As a Submucosal Injection Solution for EMR: A Comparative Study

New solution for submucosal injection in gastric cancer

Submucosal injection of sodium hyaluronate solution during endoscopic resection of gastric neoplasms, has been shown to sufficiently lift the intramucosal lesion for simplified resection and reduce the number of injections needed (Gastrointest Endosc, published online Dec 20, 2007; DOI:10.1016/j.gie.2007.07.039).

Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid “cushion” in endoscopic resection for gastric neoplasms: a prospective multicenter trial

Sodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion." Our purpose was to assess the usefulness and safety of 0.4% SH solution in endoscopic resection. A prospective multicenter randomized controlled trial. Six referral hospitals in Japan. One hundred forty patients with 5- to 20-mm gastric intramucosal neoplastic lesions. Patients were randomized into 0.4% SH and control groups. Endoscopic resection was performed with 0.4% SH or normal saline solution for submucosal injection. The usefulness of 0.4% SH solution was assessed by en bloc complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. (1) steepness of mucosal lesion lifting, (2) complications, (3) time required for mucosal resection, (4) volume of submucosal injection solution, and (5) ease of mucosal resection. Safety was assessed by analyzing adverse events during the study period. The usefulness rate was significantly higher for the 0.4% SH group (88.4%, 61/69) than for the control group (58.6%, 41/70). As secondary outcome measures, significant intergroup differences (P < .001) were noted for (1) steepness of mucosal lesion lifting, (2) volume of submucosal injection solution, and (3) ease of mucosal resection. No serious adverse events were encountered in either group. Lack of blinding. Safety was not a powered outcome measure. Using 0.4% SH as a submucosal injection solution in endoscopic resection enabled the formation and maintenance of sufficient mucosal lesion lifting for gastric intramucosal lesions, reducing the need for additional injections and simplifying mucosal resection. Use of 0.4% SH thus simplifies the complicated procedures involved in endoscopic resection.

Effectiveness of Sodium Alginate as a Submucosal Injection Material for Endoscopic Mucosal Resection in Animal

Although various solutions are being tested for submucosal injection during endoscopic resection, ideal solution has not been established yet. We performed an animal study to evaluate the possibility of sodium alginate as an ideal submucosal injection solution for endoscopic mucosal resection (EMR). To compare the lesion-lifting properties of different solutions, injection was done to the submucosal layer of porcine stomach. Then the height of mucosal elevation was measured. In addition, EMR was performed after submucosal injection of sodium alginate solution in six dogs. Two were euthanized after 30 minutes of endoscopic observation while the others were euthanized after 1-4 weeks. Retrieved stomachs were examined microscopically. Sodium alginate and sodium hyaluronate solutions maintained longer elevation of the submucosal layer than other solutions. There was no significant difference in the height between two solutions. A clear separation of the mucosal layer from the proper muscle layer was achieved by injecting sodium alginate solution. Histological examination of EMR-induced artificial ulcers revealed no apparent tissue damage and showed normal healing process. Sodium alginate solution creates a sufficient submucosal fluid cushion without apparent tissue damage. It can be considered as an effective submucosal injection material.

Clinical efficacy of EMR with submucosal injection of a fibrinogen mixture: a prospective randomized trial

Submucosal injection is essential to performing EMR easily, and various solutions have been proposed to create a long-lasting submucosal fluid cushion. To assess the efficacy of a fibrinogen mixture (FM) as a submucosal injection solution. A prospective, randomized, controlled trial. At a tertiary care, academic medical center. A total of 72 patients with early gastric neoplasm were randomly assigned to receive EMR with submucosal injection of normal saline solution (NS) or an FM. We performed EMR only with a conventional method. En bloc resection rate, complete resection rate, complications, and other procedure-related outcomes. No significant differences were observed between the 2 groups (the FM group vs the NS group) in the rates of en bloc resection (80.6% vs 88.9%), complete resection rate (86.1% vs 80.6%), and recurrence rate (3% vs 6.1%). Mean procedure time was significantly shorter in the FM group vs the NS group (11.39 +/- 3.07 minutes vs 13.93 +/- 3.26 minutes; P < .05). Mean submucosal injection volume of the FM group was significantly less than that of the NS group (9.81 +/- 2.26 mL vs 14.32 +/- 2.35 mL; P < .05). Also, additional submucosal injection to maintain elevation of the lesion was less frequently required in the FM group than in the NS group (5.6% vs 33.3%; P < .05). The main limitations were the method of EMR (only included the conventional method) and the size of lesions (<30 mm), because a long-lasting submucosal fluid cushion was more important in the dissection method and larger tumors. The FM is a reliable submucosal injection solution for conventional EMR.

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR RECURRENT GASTRIC TUMORS

Endoscopic resection has been accepted as the standard treatment for intramucosal gastric tumors of differentiated type. However, the indication was limited to small tumors to achieve en bloc resection and prevent local recurrence in cases of conventional endoscopic mucosal resection (EMR) such as the strip biopsy and the cap technique. To avoid multi‐fragmental resection, we have developed endoscopic submucosal dissection (ESD) as a new endoscopic resection technique. ESD is a remarkable technique, because we make it possible to remove the lesions en bloc regardless of size, shape, coexisting ulcer, and location. However, it is difficult or impossible to resect recurrent tumors en bloc in conventional EMR owing to hard fibrosis, and some patients need laparotomy. Using ESD, we can dissect the submucosal layer as we directly look at the submucosa, and remove the lesion safely and reliably even in cases of hard fibrosis. The key to treatment of recurrent tumors in ESD are as follows: (i) using enough submucosal injection solution (we use a mixture of Glyceol and 1% 1900 kDa hyaluronic acid preparation); (ii) incising the mucosa without fibrosis; (iii) understanding characteristics of various cutting devices, and changing other devices in difficult situations. In these ways we can remove the majority of the recurrent tumors en bloc. Hence, we consider that ESD is a very effective treatment which achieves excellent en bloc and complete resection rates and enables patients with intramucosal gastric tumors to a recurrent‐free survival even in recurrent tumors.

Comparison of the characteristics of submucosal injection solutions used in endoscopic mucosal resection

Objective. Submucosal injection is used to prevent complications, such as perforation, during endoscopic mucosal resection (EMR). Since injection of normal saline produces mucosal elevation of short duration, repeated injection is needed for extensive resection. To overcome this limitation, various submucosal injection solutions have been developed but there are few data comparing their efficacy. This study was therefore conducted to compare the physical and chemical properties and the duration of mucosal elevation of various submucosal injection solutions. bA fresh transverse colon specimen acquired from a mongrel was used. Experiments were repeated four times. To compare the efficacy of mucosal elevation, 1 ml of each solution was injected into the submucosa: 0.9% NaCl, 20% mannitol, 0.1% sodium hyaluronate, 0.3% hydroxypropyl methylcellulose (HPMC), and 2% fibrinogen. Physical and chemical properties such as viscosity and osmolarity were compared. b The heights of initial mucosal elevations were 6.52±0.26 mm, 6.87±0.05 mm, 6.92±0.09 mm, 6.90±0.08 mm, and 6.90±0.08 mm for normal saline, mannitol, sodium hyaluronate, HPMC, and fibrinogen, respectively. Whereas injection of normal saline took about 20 min and mannitol about 30 min for the initial elevation to be reduced to more than half the initial height, it took more than 60 min for all the other agents. A correlation was found between the duration of mucosal elevation and viscosity but not with osmolarity. Conclusions. The mucosal elevation lasted longer with sodium hyaluronate, HPMC, and fibrinogen than with mannitol or normal saline, and this seems to be due to the viscosity rather than the osmolarity of each solution.

Tissue damage of different submucosal injection solutions for EMR

When choosing submucosal injection solutions for EMR, tissue damage should be considered, as well as the lesion-lifting ability. The objective of the study was to find out the potential tissue damage of submucosal injection solutions. The submucosal injection solutions examined were the following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5% fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and 0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable concentration without tissue damage. A total of 2 mL of each solution per stomach were injected by endoscopy into the submucosal layer at the separate sites of 4 living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic observations, and the others were euthanized after additional endoscopic observations a week after injection. There was no apparent tissue damage in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic solutions, except Glyceol and 10% DW, have more or less potency of tissue damage. In 3.75% NaCl and DW with concentrations of >or=20%, considerable tissue damage was observed, which might affect resected EMR specimens and ulcer healing. Use of hypertonic solutions except Glyceol is not recommended with respect to tissue damage. A combination of HA and Glyceol is the most favorable submucosal injection solution, considering tissue damage and lesion-lifting ability.

Effectiveness of glycerol as a submucosal injection for EMR

EMR traditionally is performed by using normal saline solution (NS) as the submucosal fluid cushion. It is thought, however, that NS does not maintain the proper mucosal elevation for EMR of large, flat lesions. We investigated the efficacy of glycerol as the submucosal injection solution. A total of 110 colorectal laterally spreading tumors (LST) were treated by EMR with glycerol. For comparison, 113 LSTs treated by using NS were studied. The en bloc resection, complete resection, and associated complications rates were evaluated retrospectively. The en bloc resection rate in the glycerol group was 63.6% (70/110) compared with 48.9% (55/113) in the NS group (p < 0.05). The complete resection rate in the glycerol group was 45.5% (50/110) compared with 24.6% (28/113) in the NS group (p < 0.01). The associated complications rate was similar in both groups. It technically was easier and as safe to perform EMR of colorectal LSTs when using glycerol as the submucosal injection solution.