Fluid Cushion Research Articles

Temperature-sensitive injectable chitosan-based hydrogel for endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) is an effective treatment for polyps and early gastrointestinal cancers, but requires a high level of operator skill. Injecting submucosal materials (SIM) helps create a fluid cushion between the mucosal and muscular layers, making the procedure easier and reducing associated risks. However, SIMs commonly used in current clinical practice tend to spread quickly and fail to provide long-lasting submucosal fluid cushions (SFC). Thus, there is a critical need for a material that is easy to inject while also maintaining a durable barrier. We prepared succinylated hydroxybutyl chitosan (HBC-SA) by adding succinic anhydride (SA) to hydroxybutyl chitosan (HBC). The hydrogel had excellent temperature-sensitive properties and was able to be injected via an endoscopic injection needle even after gel formation. In vitro and in vivo studies showed that it has satisfactory biocompatibility. Functional experiments showed that the submucosal lifting properties of this hydrogel were significantly better than that of normal saline (NS) and sodium hyaluronate (SH), two commonly used clinical materials. In addition, the hydrogel possessed excellent hemostatic properties. Based on these results, HBC-SA is a promising candidate for submucosal injection during ESD.

Efficacy and safety of a submucosal injection solution of sodium alginate for endoscopic resection in a porcine model

Endoscopic resection techniques require the use of submucosal injection. Normal saline and sodium hyaluronate solutions are mainly used for this purpose, but an ideal solution has not yet been developed. The aim of this study was to assess a new solution, MC-003—a novel submucosal injection solution developed with sodium alginate as the main ingredient. Normal saline, a commercial sodium hyaluronate solution (Endo-Ease), and MC-003 were examined. A total of 18 gastric submucosal cushions were created in the stomachs of six pigs. The height of mucosal elevation was measured sequentially using endoscopic sonography. After euthanizing the animals either 2 h or 5 days after the procedure, pathologic examination was performed for each injection site. Although not statistically significant over the entire study period, MC-003 showed a superior result to normal saline and an equivalent result to Endo-Ease in the submucosal cushion height and its rate of decrease. There were no adverse outcomes after injection of the three solutions and there was no pathologically identified detrimental change in the resected specimens. MC-003 creates a sufficient submucosal fluid cushion without apparent tissue damage. It can be considered as an effective submucosal injection material.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Hybrid argon plasma coagulation (HybridAPC) versus sharp excision for the treatment of endometriosis: a prospective randomized clinical trial

PurposeEndometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC.MethodsIn this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate.ResultsThe eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p < .05). No intra- and postoperative complications were registered.ConclusionThis clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis.

Potential clinical complications of Orise™ gel use, a new submucosal lifting agent: experience from a tertiary care center and review of the literature.

BackgroundEndoscopic mucosal resection (EMR) involves forming a fluid cushion in the submucosal area with a lifting agent, followed by superficial resection. Orise™ gel is one of the commonly used lifting agents for EMR. We present a case series and literature review that analyzes the characteristic histopathological findings and clinical implications observed where Orise™ gel was used before EMR.MethodsColon resection specimens and prior EMR specimens where Orise™ gel was used were reviewed for patients undergoing EMR between January 2018 and December 2020. The literature review included relevant studies from the Medline and Cochrane databases from January 2018 to December 2020.ResultsA total of 12 colon polyp EMRs using Orise gel were performed during the study period. Seven patients (58.34%) underwent surgical resection. Histological examination revealed that, after the EMR procedure, the Orise™ gel material changed its morphological characteristics over time from a basophilic (bluish) non-inflamed pattern to an eosinophilic (pink) type pattern, eliciting a foreign body reaction. The endoscopic appearance and examination of the excised specimens weeks after injection gave the impression of a mass in some cases. The material was also present transmurally and in some cases in the peri-intestinal adipose tissue.Conclusions It was observed that Orise™ gel use elicits a foreign body-type granulomatous reaction. This potential side effect may lead to overdiagnosis of a mass/lesion and unnecessary surgical interventions. This case series and review of the literature aims to increase awareness of the changes caused by Orise™ gel in the gastrointestinal tract.

Investigation of Thermoplastic Polyurethane Finger Cushion with Magnetorheological Fluid for Soft-Rigid Gripper

This paper presents a study of penetrating a pin into a magnetorheological fluid (MR) cushion focused on the force measurement. The research is supported by detailed finite element analysis (FEA) of the magnetic field distributions in several magnetic field exciters applied to control rheological properties of the MR inside the cushion. The cushion is a part of the finger pad of the jaw soft-rigid gripper and was made of thermoplastic polyurethane (TPU) using 3D printing technology. For the pin-penetrating setup, the use of a holding electromagnet and a magnetic holder were considered and verified by simulation as well as experiment. In further simulation studies, two design solutions using permanent magnets as the source of the magnetic field in the cushion volume to control MR fluid viscosity were considered. The primary aim of the study was to analyze the potential of using an MR fluid in a cushion pad and to investigate the potential for changing its viscosity using different magnetic field sources. The analysis included magnetic field simulations and tests of pin penetration in the cushion as an imitation of object grasping. Thus, an innovative application of 3D printing and TPU to work with MR fluid is proposed.

Injectable Thermosensitive Chitosan Solution with β-Glycerophosphate as an Optimal Submucosal Fluid Cushion for Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is a surgical procedure to remove early neoplastic lesions in the gastrointestinal tract with the critical issue of perforation. A submucosal fluid cushion, such as normal saline, is used as a cushioning agent to prevent perforation; however, its cushioning maintenance is insufficient for surgery. In this study, we introduce an injectable thermosensitive chitosan solution (CS) with β-glycerophosphate (β-GP) as a submucosal injection agent for ESD. The CS/β-GP system with optimal β-GP concentration showed drastic viscosity change near body temperature while other commercial products did not. Additionally, the injectability of the solution was similar to or greater than other commercial products. The solution with low β-GP concentration showed low cytotoxicity similar to other products. An in vivo preclinical study illustrated maintenance of the high cushioning of the thermosensitive solutions. These results indicate that a CS/β-GP system with optimal β-GP concentration might be used as a submucosal injection agent in ESD, and further studies are needed to validate the effectiveness of the solutions in vivo.

Application of Hemocoagulase Bothrops Atrox in the submucosal injection for endoscopic submucosal dissection: a preliminary trial.

ObjectiveThis study aimed to evaluate the efficacy and safety of using Hemocoagulase Bothrops Atrox in the submucosal injection solution for endoscopic submucosal dissection (ESD).MethodsA total of 120 patients with superficial neoplastic lesions of the esophagus, stomach, and colon receiving ESD were randomly divided into two groups: The epinephrine group used epinephrine-containing submucosal fluid cushion for ESD, while the hemocoagulase group used Hemocoagulase Bothrops Atrox-containing submucosal fluid cushion for ESD. The preoperative, intraoperative, and postoperative clinical parameters and postoperative adverse events of the two groups were recorded, and comparative analysis within and between groups was performed.ResultsThere was no significant difference in the demographic and clinical characteristics between the hemocoagulase and epinephrine group (all P > 0.05). ESD surgery was completed in all patients. The hemocoagulase group had significantly shorter surgery time (P = 0.003) and less number of intraoperative bleeding (P = 0.010) than the epinephrine group. However, there was no significant difference in the incidences of postoperative delayed hemorrhage, and adverse events between the two groups (all P > 0.05). Multivariate linear regression demonstrated that the epinephrine group had significantly more number of intraoperative bleeding (B: 0.98, 95% confidence interval: 0.04–1.93) as compared with the hemocoagulase group.ConclusionCompared with epinephrine, using Hemocoagulase Bothrops Atrox in the submucosal injection for ESD surgery can significantly reduce the number of intraoperative bleeding, shorten the operation time, and did not elevate the incidence of adverse events.

Injectable Thermogel Generated by the "Block Blend" Strategy as a Biomaterial for Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection is an established method for the removal of early cancers and large lesions from the gastrointestinal tract but is faced with the risk of perforation. To decrease this risk, a submucosal fluid cushion (SFC) is needed clinically by submucosal injection of saline and so on to lift and separate the lesion from the muscular layer. Some materials have been tried as the SFC so far with disadvantages. Here, we proposed a thermogel generated by the "block blend" strategy as an SFC. This system was composed of two amphiphilic block copolymers in water, so it was called a "block blend". We synthesized two non-thermogellable copolymers poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) and blended them in water to achieve a sol-gel transition upon heating in both pure water and physiological saline. We explored the internal structure of the resultant thermogel with transmission electron microscopy, three-dimensional light scattering, 13C NMR, fluorescence resonance energy transfer, and rheological measurements, which indicated a percolated micelle network. The biosafety of the synthesized copolymer was preliminarily confirmed in vitro. The main necessary functions as an SFC, namely, injectability of a sol and the maintained mucosal elevation as a gel after injection, were verified ex vivo. This study has revealed the internal structure of the block blend thermogel and illustrated its potential application as a biomaterial. This work might be stimulating for investigations and applications of intelligent materials with both injectability and thermogellability of tunable phase-transition temperatures.

Fluid cushion protects against thermal damage during argon plasma coagulation.

BackgroundThermal damage to the muscle layer during mucosal application of argon plasma coagulation (APC) may be avoided by creating a fluid cushion within the submucosal layer, but the minimum injection volume needed or the ideal injection fluid are yet to be established. We conducted a systematic ex vivo study with this aim.MethodsAll experiments were performed in an ex vivo porcine gastrointestinal tract model. Five different fluids (saline, Glyceol, Gelafundin, Voluven, and Eleview) of different volumes were injected into the submucosa of different parts of the gastrointestinal tract. APC was applied to the mucosa at different power settings. Immediately after APC treatment, the temperature was measured through a thermocouple placed inside the fluid cushion, just on top of the muscle layer. The minimum volume of fluid needed to protect the muscle layer from thermal damage was determined.ResultsThere was no difference in the temperature measured among the different injection fluids at the surface of the muscle, in all the locations, at equal injection volumes and power settings. The minimum amounts of fluid needed to protect the muscle layer were 2 and 3 mL for power settings of 30-90 W and 90-120 W, respectively.ConclusionsNormal saline and 4 commercially available submucosal injection fluids possess similar thermal protective effects. To reduce the likelihood of thermal damage to deeper layers when APC is applied, a minimum injection volume of 3 mL is recommended if less than 90 W power will be utilized over 3 sec.

A Comparative Study on Aqueous Chitosan Solution and Various Submucosal Injection Fluids Using a Three-Dimensional Sensor.

Background/AimsChitosan, a natural polymer widely used in the biomaterials field, has been proposed as a potential submucosal injection solution. The purpose of this study was to compare the performance and efficacy of aqueous chitosan solution and commercialized submucosal injection fluids using a three-dimensional sensor and to evaluate the efficacy of the measured parameters.MethodsNormal saline (0.9% NaCl), as a control, Eleview® (Poloxamer 188), Blue EyeTM (0.4% hyaluronic acid), and aqueous chitosan solution (2.0%) were injected into the submucosa of porcine stomachs ex vivo. The mucosal elevation height, elevated surface area, and angle of the tangent of the submucosal fluid cushion were measured using a three-dimensional sensor. The rates of change for each variable were calculated, and the correlation between parameters was analyzed. Tissue specimens were stained with hematoxylin and eosin.ResultsAll variables exhibited the highest values under chitosan injection. The mucosal elevation height rate of change differed significantly between normal saline and chitosan solution (p=0.024). The elevated surface area rates of change for normal saline and Eleview® were significantly different from those for TS-905 and chitosan solution (p=0.006 and p=0.009, respectively). Further, height, area, and angle showed a positive correlation (p<0.001). A histological examination revealed an even distribution of aqueous chitosan within the submucosa without tissue damage.ConclusionsAqueous chitosan was superior to normal saline and Eleview® and was noninferior to TS-905. A three-dimensional sensor and the measured parameters were effective and useful for evaluating the performance of submucosal fluids.

A145 A SUBMUCOSAL FLUID CUSHION PREVENTS MUSCLE LAYER DAMAGE DURING ARGON PLASMA COAGULATION

Abstract Background Thermal damage to the muscle layer of the gastrointestinal wall can occur during mucosal application of argon plasma coagulation (APC). This injury may be mitigated by creating a fluid cushion within the submucosal layer that physically separates the mucosa from the muscle layer and suppresses unwanted tissue temperature elevation. This in turn protects the muscle layer from thermal damage. The coagulative threshold of muscle proteins is known to be about 60°C, but there are no published systematic assessments of the minimum injection volume needed nor the ideal injectate to prevent thermal damage to the muscle layer during mucosal APC ablation. Aims Our aims were, firstly, to measure the final temperature inside the fluid cushion after mucosal ablation with APC and then to determine any differences in the final temperature between various injectable solutions. Secondly, we sought to determine the minimum volume of injectate required to protect the muscle layer from thermal damage. Methods All experiments were performed in an ex-vivo porcine gastrointestinal tract model. Five different fluids (normal saline, Glyceol, Gelafundin, Voluven and Eleview) of different volumes (range 0 - 5mL) were injected into the submucosa of the esophagus, stomach (fundus) and rectum to create a fluid cushion. APC was applied to the mucosa for a fixed duration (3s) at different power settings (ranging from 30 - 120W). Immediately after APC treatment, the final temperature was measured by placing a contact thermometer inside the fluid cushion, just on top of the muscle layer. Results There was no significant difference in the temperature measured at the surface of the muscle layer between elevation with normal saline, Glyceol, Gelafundin, Voluven and Eleview at all 3 tissue locations at equal injection volumes and power settings. The experiments showed that the temperature rose for each injectate with heightened power settings but also decreased with increasing volume of injected fluid. The minimum amount of fluid needed to protect the muscle layer from thermal damage was 2mL for the esophagus, stomach and rectum in the case of a power setting between 30 to 90W and 3mL in the case of 90 to 120W. Conclusions Normal saline and four commercially available submucosal injectates possess similar thermoregulatory effects as an insulator of the muscle layer during APC treatment. As opposed to the choice of injectate or anatomic location treated, the volume of fluid injected is the main determinant of the final temperature at the level of the muscularis propria. To reduce the likelihood of thermal damage to deeper layers of the GI tract when APC is applied, a minimum injection volume of 2mL is recommended if &amp;lt;90W of power is utilized. Funding Agencies None

Emergence and Developmental Roles of the Cerebrospinal Fluid System.

We summarize recent work illuminating how cerebrospinal fluid (CSF) regulates brain function. More than a protective fluid cushion and sink for waste, the CSF is an integral CNS component with dynamic and diverse roles emerging in parallel with the developing CNS. This review examines the current understanding about early CSF and its maturation and roles during CNS development and discusses open questions in the field. We focus on developmental changes in the ventricular system and CSF sources (including neural progenitors and choroid plexus). We also discuss concepts related to the development of fluid dynamics including flow, perivascular transport, drainage, and barriers.

The Interstitial System of the Brain in Health and Disease.

The brain interstitial fluid (ISF) and the cerebrospinal fluid (CSF) cushion and support the brain cells. The ISF occupies the brain interstitial system (ISS), whereas the CSF fills the brain ventricles and the subarachnoid space. The brain ISS is an asymmetrical, tortuous, and exceptionally confined space between neural cells and the brain microvasculature. Recently, with a newly developed in vivo measuring technique, a series of discoveries have been made in the brain ISS and the drainage of ISF. The goal of this review is to confer recent advances in our understanding of the brain ISS, including its structure, function, and the various processes mediating or disrupting ISF drainage in physiological and pathological conditions. The brain ISF in the deep brain regions has recently been demonstrated to drain in a compartmentalized ISS instead of a highly connected system, together with the drainage of ISF into the cerebrospinal fluid (CSF) at the surface of the cerebral cortex and the transportation from CSF into cervical lymph nodes. Besides, accumulation of tau in the brain ISS in conditions such as Alzheimer’s disease and its link to the sleep-wake cycle and sleep deprivation, clearance of ISF in a deep sleep via increased CSF flow, novel approaches to remove beta-amyloid from the brain ISS, and obstruction to the ISF drainage in neurological conditions are deliberated. Moreover, the role of ISS in the passage of extracellular vesicles (EVs) released from neural cells and the rapid targeting of therapeutic EVs into neural cells in the entire brain following an intranasal administration, and the promise and limitations of ISS based drug delivery approaches are discussed

Gastric mucosal devitalization (GMD): translation to a novel endoscopic metabolic therapy.

Background and study aims The metabolic effects of bariatric surgery may partially result from removal of the gastric mucosa, an often underappreciated endocrine organ. Using argon plasma coagulation (APC), we may be able to selectively devitalize (ablate) the mucosa. The aim of this study was to identify the optimal tissue color that would correspond to selective gastric mucosal devitalization (GMD) using ex-vivo human stomach specimens. Patients and methods Stomach specimens were obtained at sleeve gastrectomy. Prior to APC application, a submucosal fluid cushion was created. APC was then applied over a 2 × 2-cm area to the fundus and body, aiming for the three indicator colors (white, golden, brown). Pathological analysis was then performed independently and in a blinded fashion by two pathologists to determine the depth of mucosal and submucosal percent thermal injury and mucosal percent cell death. Results Six patients were enrolled. There was a significant correlation between tissue color and mucosal percent thermal injury. The highest percent mucosal thermal injury was seen with brown (99.6 %, 95 % CI: 98.7, 100), followed by golden (92.5 %, 95 % CI: 85.5, 99.5), and then white (75.2 %, 95 % CI: 58.3, 92.1, P < 0.01). Submucosal thermal injury was seen in 88.9 % of the slides. Greater than minimal submucosal injury (> 10 % depth) was found significantly more with brown tissue color (91.6 %) than golden (75 %) or white (33.3 %, P < 0.05). However, 91.7 % of the entire sample set < 50 % injury. Conclusion GMD is achievable using APC without thermal injury to muscularis propria. A golden color results in sufficient mucosal injury with only superficial injury to the submucosa.

Recent Advances in Injectable Hydrogels for Biomedical Applications

Injectable hydrogels, a class of hydrogel, have received a lot of attention in biomedical applications due to its versatility. It is reported that injectable hydrogel can be applied in various biomedical procedures for example as submucosal fluid cushion, periodontal implant, and cartilage and bone tissue engineering. In addition to its easy delivery (implantation), this class of hydrogel can be tailored to match specific applications. The customization of this hydrogel can be easily executed by changing polymeric backbone of hydrogel, choosing different types of crosslinking or by adding nanoparticles to form hybrid hydrogel systems. Physical properties, compatibility and biodegradability of the resulted materials are important factors for designing injectable hydrogels. In this Recent Research Progress, we highlight the state-of-the-art injectable hydrogels and note the general requirements of an ideal injectable hydrogel for biomedical applications.

EndoClot®SIS Polysaccharide Injection as a Submucosal Fluid Cushion for Endoscopic Mucosal Therapies: Results of Ex Vivo and In Vivo Studies.

There are many studies on submucosal injection materials, but their clinical use is restricted for various reasons. The objective of this study was to compare the feasibility and safety of injected EndoClot®SIS polysaccharide as a submucosal injection material (SFC) in ESD in the pig stomach to that of injected sigMAVisc™ or Eleview™. Four pig stomachs were used for the ex vivo study. Eighteen pigs were used for the in vivo study. In the ex vivo study, four injections were made in the gastric submucosa to induce submucosal uplift and extend its duration. Tissue change was observed. The in vivo study was performed in 2 steps. First, 3 injections were made in the esophageal mucosa to induce submucosal uplift and extend its duration. Histological change was observed. Second, ESD was performed in the stomach by injecting EndoClot®SIS polysaccharide, sigMAVisc™, or Eleview™ (each, n = 6) as an SFC. The effects of these agents on wound healing were examined. We evaluated the efficacy and safety of endoscopic surgery after EndoClot®SIS polysaccharide injection. EndoClot®SIS polysaccharide produced a longer-lasting elevation with clearer margins than was achieved by sigMAVisc™, Eleview™, or 0.9% NaCl and thereby enabled precise ESD without complications, such as bleeding and perforation. No obvious histopathological damage was observed at the injection site on endoscopy and histology. Submucosally injected EndoClot®SIS polysaccharide increased the effective separation of the mucosa and submucosa and reduced surgical complications. Hence, EndoClot®SIS polysaccharide injection is a safe and effective submucosal injection material.

Injectable Hybrid Hydrogels, with Cell-Responsive Degradation, for Tumor Resection.

Biocompatible soft materials have recently found applications in interventional endoscopy to facilitate resection of mucosal tumors. When neoplastic lesions are in organs that can be easily damaged by perforation, such as stomach, intestine, and esophagus, the formation of a submucosal fluid cushion (SFC) is needed to lift the tumor from the underlying muscle during the resection of neoplasias. Such procedure is called endoscopic submucosal dissection (ESD). We describe an injectable, biodegradable, hybrid hydrogel able to form a SFC and to facilitate ESD. The hydrogel, based on polyamidoamines, contains breakable silica nanocapsules covalently bound to its network and able to release biomolecules. To promote degradation, the hydrogel is composed of cleavable disulfide moieties that are reduced by the cells through secretion of glutathione. The same stimulus triggers the breaking of the silica nanocapsules; therefore, the entire hybrid material can be completely degraded and its decomposition depends entirely on the presence of cells. Interestingly, the hydrogel precursor solution showed rapid gelation when injected in vivo and afforded a long-lasting high mucosal elevation, keeping the cushion volume constant during the dissection. This novel material can provide a solution to ESD limitations and promote healing of tissues after surgery.

Role of Hybrid Argon-Plasma Coagulation (Hybrid APC) in the Management of Barrettʼs Esophagus: A Case Series Report

Barrett's esophagus (BE) is defined as metaplasia of the esophageal epithelium resulting in the replacement of normal squamous epithelium by columnar epithelium. It is associated with gastroesophageal reflux disease. Patients with BE are at increased risk of developing esophageal adenocarcinoma and require close monitoring. Management of BE has changed remarkably with the introduction of endoscopic thermal ablative therapies that include radiofrequency ablation (RFA) and argon-plasma coagulation (APC).Both therapies are associated with risk of stricture formation and APC increases the risk of buried metaplastic glands under the neosquamous epithelium. To overcome these disadvantages, a novel hybrid ablation method that combines APC and submucosal saline injection called Hybrid APC has been recently developed that has shown to decrease the rate of these complications by creating a submucosal fluid cushion prior to ablation. We present two cases where employment of Hybrid APC resulted in the eradication of BE following endoscopic mucosal resection (EMR) and refractory to multiple RFA therapies. A 67 year old male diagnosed with BE, long segment with high grade dysplasia (HGD) and intramucosal adenocarcinoma status post EMR two years back was closely monitored with surveillance EGD and subsequently underwent RFA four times with satisfactory response but with disease persistence. Patient was deemed to be high risk candidate for surgery. Hybrid APC was employed resulting in significant macroscopic and histologic remission following therapy. Patient continues to be followed up closely with no disease recurrence. A 62 year old male diagnosed with BE, long segment with HGD and intramucosal adenocarcinoma status post EMR four years back was closely monitored with surveillance EGD and subsequently underwent EMR three times, and RFA eight times with disease persistence. Patient was deemed to be a high risk candidate for surgery. Hybrid APC was performed resulting in significant macroscopic and histologic remission following therapy. Patient continues to be followed up closely with no disease recurrence. Hybrid APC is a new novel treatment modality shown to be effective and safe in the management of BE. Manner et.al showed macroscopically complete remission (CR) in 46 of the 48 patients and histologically CR out of 46 patients from BE. Further multicenter prospective trials are required to study this promising new technique compared to other treatment techniques.

Development of Mucoadhesive Chitosan Derivatives for Use as Submucosal Injections.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been used for surgical treatment of early gastric cancer. These endoscopic techniques require proper submucosal injections beneath the tumor to provide a sufficiently high submucosal fluid cushion (SFC) to facilitate clean dissection and resection of the tumor. Until now, the submucosal injection materials developed for endoscopic techniques such as EMR and ESD of tumors have been composed of macromolecules, proteins, or polysaccharides. We have been investigating the use of chitosan, a product that is obtained by the alkaline deacetylation of chitin, the second-most abundant natural polysaccharide. Specifically, we have been studying a photocrosslinked chitosan hydrogel (PCH) and solubilized chitosan derivatives for use as novel submucosal injections for endoscopic techniques. Notably, chitosan derivatives with lactose moieties linked to the amino groups of its glucosamine units can specifically interact with acidic mucopolysaccharides and mucins in submucosa without the need for the incorporation of harmful photoreactive groups nor potentially mutagenic ultraviolet irradiation.