Comparison of sodium alginate-based and sodium hyaluronate-based submucosal injection materials based on rheological analysis.

As a viscous high-performance submucosal injection material (SIM) used in endoscopic submucosal dissection (ESD), sodium alginate-based SIM (SA-SIM) was recently introduced as high-performance SIM equivalent to sodium hyaluronate-based SIM (HA-SIM) in Japan. However, a comprehensive, detailed comparison of SA and HA is yet to be performed. In this study, we precisely measured the viscoelastic properties, submucosal elevation height (SEH), and injection pressure (IP). Furthermore, we compared the outcomes of ESD using an ex vivo ESD model. There was no significant difference in SEHs between HA-SIM and SA-SIM at all post-injection times, and the IP of the SA-SIM injection was significantly higher than that of the HA-SIM injection in all conditions (P < 0.0001). The viscosity at high shear rates of SA-SIM was higher than that of HA-SIM; this result was consistent with SEH/IP measurement results. No significant difference was observed in ESD procedure time and total volume of injected SIM between HA-SIM and SA-SIM (18.1 ± 6.7 and 17.8 ± 6.0 min, P = 0.8987; 13.3 ± 5.3 and 11.6 ± 5.9 ml, P = 0.4658, respectively). Although SA-SIM was slightly more difficult to inject than HA-SIM, there was no significant difference in performance between the materials. Thus, this basic study demonstrated that SA-SIM can be used for endoscopic treatment as well as HA-SIM, and supported previous clinical research data.

The feasibility of a fully synthetic and self-assembled peptide solution as submucosal injection material: a preliminary animal study.

BACKGROUND AND AIM: An injection solution is required to create a submucosal cushion (SMC) for safe endoscopic resection procedures. The aim of this preliminary animal study was to clarify the safety and efficacy of a novel fully synthetic and self-assembled peptide (FSSP) solution as a submucosal injection material (SMIM). METHOD: To compare the submucosal-lifting properties, 0.3% FSSP, Eleview®, sodium hyaluronate acid solution (SHA) and normal saline (NS) were randomly injected using an injection needle into the submucosa of exposed stomach and colon in five living dogs in a blind fashion. The mean height, and volume of SMCs were measured using a digital caliper immediately and 10, 20, 30, and 40 min after injecting each solution. All resected specimens were examined histopathologically. RESULTS: In both the colon and stomach, ANOVA for repeated measures showed the significant interaction between time and solution for the time-dependent change in the height. In the colon, FSSP created significantly higher SMC than NS 20 min after injection (p = .0015) and Eleview® and NS 40 min after injection (p = .0009 and p = .0002). Furthermore, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. In the stomach, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. There were no significant differences between the histopathological finding and the injecting solutions used. CONCLUSION: FSSP seems to be useful as a SMIM for endoscopic resection especially in the colon. Further studies are needed prior to clinical use of FSSP.

Adhesive Submucosal Injection Material Based on the Nonanal Group-Modified Poly(vinyl alcohol)/α-Cyclodextrin Inclusion Complex for Endoscopic Submucosal Dissection.

Complete resection of early-stage cancer and subsequent wound care of the resection site are both important factors for successful endoscopic submucosal dissection (ESD). Although many submucosal injection materials (SIMs) have been developed to lift up lesions and completely remove cancers, a lack of materials with multiple functions, such as stable submucosal cushion formation, emergency perforation closure, and blood coagulation and wound sealing abilities, still exists. In this study, an adhesive submucosal injection material based on nonanal group-modified poly(vinyl alcohol) (C9-PVA) and α-cyclodextrin (α-CD) was developed to solve clinical problems associated with ESD. Focusing on the inclusion ability of α-CD for alkyl groups, a water-soluble α-CD/C9-PVA inclusion complex (IC) was prepared using water-insoluble C9-PVA in aqueous solutions. The IC of 2.5 mol % nonanal group-modified PVA (2.5C9-PVA), with 53 mM α-CD, showed good gel-sol reversibility and high injectability. Additionally, the α-CD/2.5C9-PVA IC performed well at submucosal cushion formation, with the increased height reaching 5.90 ± 0.38 mm. The complex also adhered well to the submucosa, successfully sealing wounds for over 7 days even in an aqueous environment. Furthermore, following incubation in physiological saline (1.80 ± 0.37 kPa), the burst strength of the α-CD/2.5C9-PVA IC was 1.5-fold higher compared with that of the commercial fibrin sealant, illustrating the possibility of emergency perforation closure. Finally, the complex promoted blood coagulation when mixed with fresh porcine whole blood. These results indicate that the multifunctional α-CD/2.5C9-PVA IC could be an ideal material for ESD.

Development of Sodium Polyacrylate-Based High-Performance Submucosal Injection Material with Pseudoplastic Fluid Characteristics.

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.

Identification of the critical viscoelastic factor in the performance of submucosal injection materials.

High-performance submucosal injection materials (SIMs) contribute to the success of endoscopic therapy for early-stage gastrointestinal neoplasms. This study aimed to identify the most important factor (viscoelastic parameter) that determines SIM performance and the ease of injection. To determine the ideal viscoelastic parameters of SIMs, submucosal elevation heights (SEHs) and the ease of submucosal injection [characterized by injection pressures (IPs)] were evaluated using a newly developed ex vivo model, in which a constant tension was applied to the studied specimen. The strongest positive correlation was observed between the loss modulus determined at an oscillation frequency of 0.1 rad/s and SEH (correlation coefficient > 0.9) and between the loss modulus at 10 rad/s and IP (correlation coefficient > 0.9). SIMs with high loss moduli (0.1 rad/s) also contributed to maintenance of the submucosal elevation. Moreover, the SEHs of pseudoplastic fluid SIMs (whose loss moduli increased slightly with increasing angular frequency) were greater than those of Newtonian fluid SIMs (whose loss modulus increased drastically with increasing angular frequency). In this study, the ideal viscoelastic SIM parameters were clarified. The loss modulus (0.1 rad/s) was the most important viscoelastic factor affecting SIM performance. Additionally, the development of pseudoplastic fluid SIMs may lead to the creation of next-generation SIMs, with a performance superior to that of sodium hyaluronate, which is currently used widely in endoscopic treatments.

Development of a new ex vivo model for evaluation of endoscopic submucosal injection materials performance.

BACKGROUND AND AIMS: Development of high-performance submucosal injection materials (SIMs) contribute to the advancement of endoscopic therapy for early-stage gastrointestinal neoplasms. This study aimed to develop a new ex vivo model that mimics the human gastrointestinal tract to evaluate the performance (the height and duration of the submucosal elevation) of various SIMs in detail. METHODS: A new ex vivo model that applies a constant tension to the tested specimen (the porcine gastric specimen) was developed. SIMs were injected into the submucosa at the center or edge of the tested specimen, and submucosal elevation heights (SEHs) were measured over time. RESULTS: The average value and standard deviation of SEH determined using the conventional model (the tested specimen was fixed with pins) were higher than those obtained using the new model, which showed that the new model could precisely measure the SEH of a given SIM. In addition, the performance (SEH) of SIMs decreased with increasing tension applied to the specimen, suggesting that the performance of SIMs deteriorates with the over-expansion of the gastrointestinal tract. The submucosal elevation formed at the specimen edge disappeared faster than that formed at the specimen's center. CONCLUSIONS: The proposed new ex vivo model allows accurate SEH measurement under uniform conditions and detailed comparison of the performances of various types of SIMs and can contribute to the development of high-performance materials.

Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer.

BACKGROUND AND AIM: We have focused on sodium alginate (SA) solution as a potential submucosal injection material for endoscopic submucosal dissection (ESD). A previous SA solution had high viscosity and problems such as difficult handling. After its properties were adjusted, SA solution was examined in vitro and its clinical safety was evaluated. METHODS: With 0.4% sodium hyaluronate (SH) solution as a control, catheter injectability and mucosa-elevating capacity of 0.3-0.8% SA solutions were evaluated. Next, 0.6% SA solution was used for ESD in 10 patients with early gastric cancer in a prospective clinical study. RESULTS: Compared with 0.4% SH solution, 0.6% SA solution exhibited no significant difference in catheter injectability but significant superiority in mucosa-elevating capacity. In the clinical study, no adverse events were observed in any patient. CONCLUSION: The safety of 0.6% SA solution as a submucosal injection material was confirmed and it is suggested that its efficacy should be investigated in a larger number of cases.