EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Double stenting with silicone and metallic stents for malignant airway stenosis.

For severe malignant airway stenosis, there are several types of commercially available airway stents, and each has its own advantages and disadvantages. We herein describe the safety and efficacy of combination stenting with silicone and metallic stents for patients with extended malignant airway stenosis. Seven patients with malignant airway stenosis were treated via combination stenting with a silicone stent and a metallic stent for extended airway stenosis from the central to peripheral airways. Five patients were diagnosed with advanced esophageal cancer, two of whom had tracheoesophageal fistulas. One patient had adenoid cystic carcinoma, and another had mediastinal tumor. There were no specific complications related to the double stenting. Combination stenting with silicone and metallic stents proved to be a safe option for patients with severe, extended, and complicated malignant airway stenosis.

Novel powdered anti-adhesion material: preventing postoperative intra-abdominal adhesions in a rat model.

BACKGROUND: Although laparoscopic surgery has decreased postoperative adhesions, complications induced by adhesions are still of great concern. The aim of this study was to investigate the anti-adhesive effects of a novel powdered anti-adhesion material that can be applied during laparoscopic surgery in comparison with other anti-adhesion materials. METHODS: Our novel powdered anti-adhesion material is composed of aldehyde dextran and ε-poly(L-lysine). In 40 male rats, a 2.5×2.0-cm abdominal wall resection and cecum abrasion were performed. The rats were randomized into four groups based on the anti-adhesion treatments: normal saline; Seprafilm(®); Interceed(®); and novel powdered anti-adhesion material. The animals were euthanized on days 7 and 28 to evaluate the adhesion severity, area of adhesion formation, gross appearance, and pathological changes. RESULTS: The adhesion severities on both days 7 and 28 were significantly lower for all anti-adhesion material groups compared with the normal saline group (p<0.05). Pathologically, all groups showed inflammatory cell infiltration on day 7 and complete regeneration of the peritoneum on day 28. CONCLUSIONS: Our novel powdered anti-adhesion material was found to be effective for reducing postoperative intra-abdominal adhesions and showed equivalent efficacy to commercial anti-adhesion materials.

Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects.

Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions. Peripheral bronchi from pigs, decellularized using a detergent enzymatic method, were engrafted onto tracheal defects of Brown Norway (BN) rats. BN rats were implanted with native pig bronchi (Xenograft group), decellularized pig bronchi (Decellularized Xenograft), or Decellularized Xenograft and ADMSCs (Decellularized Xenograft+ADMSC group). In the latter group, ADMSCs were injected intravenously immediately post implantation. Harvested graft implants were assessed histologically and immunohistochemically. We found that acute rejections were milder in the Decellularized Xenograft and Decellularized Xenograft+ADMSC groups than in the Xenograft group. Mild inflammatory cell infiltration and reduced collagen deposition were observed in the Decellularized Xenograft+ADMSC group. Additionally, ADMSC administration decreased CD8+ lymphocyte counts but increased CD163+ cell counts. In the Decellularized Xenograft+ADMSC group, serum levels of vascular endothelial growth factor and IL-10 were elevated and tissue deposition of IgM and IgG was low. The significant immunosuppressive effects of ADMSCs illustrate their potential use as immunosuppressive agents for xenogeneic biomaterial-based implants.

Does fibrin glue prevent biliary and pancreatic fistula after surgical resection?

BACKGROUND/AIMS: Efficacy of fibrin glue to prevent biliary or pancreas fistula at the resected edge of the liver or pancreas is controversial. We examined surgical results of fibrin glue use in patients who underwent hepatectomy or pancreatectomy to assess the efficacy of its use. METHODOLOGY: Subjects were divided into two groups; the fibrin glue group in hepatectomy (n=228) and in pancreatectomy (n=113), and the non-fibrin glue group in hepatectomy (n=94) and in pancreatectomy (n=24). In case of hepatectomy, the fibrin glue was sprayed on the cut-surface or anastomotic site of hepatico-jejunostomy. In case of pancreatectomy, the fibrin glue was sprayed on the anastomotic site of pancreato-jejunostomy or closed pancreatic stump. RESULTS: In the hepatectomy group, uncontrolled ascites were more frequent in the fibrin glue group (p<0.05). The use of fibrin glue for both groups has been less frequent in recent years. Prevalence of biliary fistula was not significantly different between groups. Hospital stay in the fibrin glue group was significantly longer than that in the non-fibrin glue group, and was not significantly different between hepatectomy or pancreatectomy groups. There was no significant difference of any complications including pancreatic fistula between groups. Prevalence of pancreatic fistula was not significantly different between the fibrin glue group and the non-fibrin glue group. CONCLUSIONS: Use of fibrin glue did not prevent biliary or pancreatic fistula in patients who underwent hepatectomy and pancreatectomy with or without enteric anastomosis.

Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study.

INTRODUCTION: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000030489).

Development of a new tissue-engineered sheet for reconstruction of the stomach.

We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60-80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract.

Evaluation of laparoscopic forceps jaw contact pressure and distribution using pressure sensitive film.

In this study, the authors used the Fujifilm Prescale Pressure Measuring System to measure the contact pressure and distribution at the jaws of laparoscopic grasping forceps. This data was then correlated with measured pressures at the forceps handles to understand the relationship between the surgeon's actuating pressure and that on the organ being manipulated. The purpose of this study is to create a database of tactile information to provide guidelines in defining minimally invasive surgery (MIS). This is expected to be important as today's society continues to progress in the use of automation, IoT, AI and MIS. In order to achieve the above, the authors developed an experimental device consisting of an actuator, a load cell and an MCU to stably actuate and control the handle side of grasping forceps. Target organs were simulated using triangular prisms of various silicone rubber materials. The experimental method involved actuating the handle side with preset pressure values for fixed time periods and using sensitive film to measure the pressure at the forceps tip. The film data was then scanned, processed and analyzed.

Adsorption characteristics of oligopeptides composed of acidic and basic amino acids on titanium surface.

The adsorption characteristics of octapeptides, containing different numbers of aspartic acid, lysine, and alanine residues (i.e., D(4)K(0)A(4), D(4)K(1)A(3), D(4)K(3)A(1), D(4)K(4)A(0), and D(0)K(4)A(4)) on the surface of titanium (Ti) particles were investigated in the pH range of 3.0-8.8 at 30 degrees C. The adsorption isotherms for octapeptides having four plural aspartic acid residues with or without lysine residues showed two distinct adsorption modes, i.e., irreversible and reversible modes, at pHs 3.0-6.5; at pH 7.0 or higher, the adsorption mode was reversible. Increasing the number of lysine residues at a fixed number of aspartic acid residues (i.e., 4) decreased the amount of peptides adsorbed in both modes. D(4)K(4)A(0) adsorbed irreversibly at pHs 3.0-6.5, due to the fact that negatively charged carboxyl groups directly interact with a positively charged Ti surface, whereas positively charged amino groups of lysine residues are directed in an opposite direction toward the solution side, as predicted by molecular mechanics/dynamics calculations.

Sequential Washing with Electrolyzed Alkaline and Acidic Water Effectively Removes Pathogens from Metal Surfaces.

Removal of pathogenic organisms from reprocessed surgical instruments is essential to prevent iatrogenic infections. Some bacteria can make persistent biofilms on medical devices. Contamination of non-disposable equipment with prions also represents a serious risk to surgical patients. Efficient disinfection of prions from endoscopes and other instruments such as high-resolution cameras remains problematic because these instruments do not tolerate aggressive chemical or heat treatments. Herein, we develop a new washing system that uses both the alkaline and acidic water produced by electrolysis. Electrolyzed acidic water, containing HCl and HOCl as active substances, has been reported to be an effective disinfectant. A 0.15% NaCl solution was electrolyzed and used immediately to wash bio-contaminated stainless steel model systems with alkaline water (pH 11.9) with sonication, and then with acidic water (pH 2.7) without sonication. Two bacterial species (Staphylococcus aureus and Pseudomonas aeruginosa) and a fungus (Candida albicans) were effectively removed or inactivated by the washing process. In addition, this process effectively removed or inactivated prions from the stainless steel surfaces. This washing system will be potentially useful for the disinfection of clinical devices such as neuroendoscopes because electrolyzed water is gentle to both patients and equipment and is environmentally sound.

Effects of carboxyl groups on the adsorption behavior of low-molecular-weight substances on a stainless steel surface.

The adsorption isotherms of various carboxylic acids and several amines on a stainless steel surface were taken as a function of pH and the ionic strength of the solution at 30 degrees C. In particular, the effect of the number of carboxyl groups on the adsorption behavior was investigated. Monocarboxylic acids such as benzoic acid and n-butyric acid were reversibly adsorbed on the stainless steel particles and showed a Langmuir-type adsorption isotherm, i.e., Q=KqmC/(1+KC), where Q and C are, respectively, the amount of adsorbate adsorbed and the equilibrium concentration in the bulk solution, qm, the maximum adsorbed amount, and K is the adsorption equilibrium constant. Carboxylic acids having plural carboxyl groups had much higher affinity to the surface and were adsorbed in both reversible and irreversible modes. The adsorption isotherms for the carboxylic acids having plural carboxyl groups could be expressed by a modified Langmuir-type adsorption isotherm, i.e., Q=q(irrev)+Kq(rev)C/(1+KC), where q(irrev) and q(rev) are, respectively, the maximum amounts adsorbed irreversibly and reversibly. The K and q(irrev) values increased with an increase in the number of carboxyl groups except for isophthalic acid and terephthalic acid. On the basis of the pH dependencies of K, qm, q(irrev), and q(rev) as well as the surface properties of the stainless steel, both reversible and irreversible adsorptions were considered to occur through the electrostatic interaction between negatively charged carboxyl groups and the positively charged sites on the surface. The dependency of the q(irrev) value on ionic strength was discussed on the basis of the differences in their adsorbed state with the interaction forces to the surface and repulsive forces among the adsorbed molecules. The adsorption of amine components was quite weak. The RA-IR and molecular dynamics calculation were done to investigate the adsorption states of phthalic acid, trimellitic acid, and mellitic acid.

Adsorption behavior of methylene blue and its congeners on a stainless steel surface.

Methylene blue and its congeners as model dyes were adsorbed onto stainless steel particles at different ionic strengths, pH values, and ethanol contents, and the adsorption mechanism was investigated. A Fourier transform infrared spectroscopy (FTIR) analysis of the dyes adsorbed on the stainless steel plate was carried out to determine the orientations of the adsorbed dyes on stainless steel surface. The adsorption isotherms for all the dyes tested were approximated by a Langmuir equation (Q=Kq(m)C/(1+KC)) in most cases except under strongly basic conditions. From the ionic strength and ethanol content dependencies of the K value in the Langmuir equations, both the electrostatic and hydrophobic interactions were indicated to contribute to the adsorption of the dyes at neutral pH. By comparing the K and q(m) values for the methylene blue congeners and with the aid of the FTIR analyses, it was found that the kind of substituent groups at most positions of the polyheterocycles of methylene blue strongly affects the adsorption behavior, particularly the area occupied by an adsorbed dye molecule, the affinity for the stainless steel surface, and the orientation of the adsorbed dye molecule on the stainless steel surface.

Usefulness of vessel-sealing devices combined with crush clamping method for hepatectomy: a retrospective cohort study.

BACKGROUND: Blood loss during resection of the hepatic parenchyma in hepatectomy can be minimized using vessel-sealing (VS) devices. Some sealing devices were retrospectively compared to evaluate the efficacy of each device for controlling blood loss, transection time and postoperative complications in hepatectomy as a cohort study. METHODS: Between 2005 and September 2012, hepatectomy was underwent in 150 patients using one of three types of LigaSure™ (Dolphin Tip Laparoscopic Instrument, Precise or Small Jaw) or the Harmonic Focus or Ace ultrasonic dissecting sealer. Results were compared to crush-clamping alone as the control method by the historical study (n = 81). RESULTS: Irrespective of the vessel-sealing device used for underlying chronic hepatitis, blood loss, blood transfusion rate, operating time and transection time were significantly reduced in the VS group compared with controls (p < 0.05). Rates of postoperative bile leakage and intra-abdominal abscess formation were significantly lower in the VS group than in controls (p < 0.05). Comparing devices, LigaSure Small Jaw and Harmonic Focus showed lower blood loss, shorter transection time and reduced rates of post-hepatectomy complications, in turn resulting in shorter hospital stays (p < 0.05). Tendencies toward uncontrolled ascites and bile leakage were only concern with the use of Harmonic Focus. Satisfactory surgical results were achieved using the sealing device for laparoscopic hepatectomy. CONCLUSIONS: The use of energy sealing devices improves surgical results and avoids hepatectomy-related complications. Adequate use of vessel sealers is necessary for safe and rapid completion of hepatic resection.

Anterior chest wall reconstruction with titanium plate sandwiched between two polypropylene sheets.

Extensive sternal resection carries the risk of difficult reconstruction and surgical complications. A 79-year-old woman underwent sternal resection and reconstruction for sternal chondrosarcoma. However, 18 months after the first operation, she developed six metastatic tumors on the anterior chest wall. She underwent subtotal sternectomy and rib resection, leaving a defect measuring 17 × 14 cm. Reconstruction of the anterior chest wall using a titanium plate sandwiched between two polypropylene mesh sheets is described. This method is potentially applicable to extensive anterior chest resection, and its advantages compared with conventional prostheses are rigidity, flexibility, and usability.

Long-term results of chest wall reconstruction with DualMesh.

The aim of this study was to evaluate the clinical outcomes of chest wall reconstruction using a new, expanded polytetrafluoroethylene prosthesis, 'DualMesh'. Between December 2005 and March 2010, chest wall reconstruction using 2-mm DualMesh was performed in 11 patients. The indication for resection was primary lung cancer in six patients, malignant mesothelioma in one patient, recurrent lung cancer in one patient, recurrent invasive thymoma in one patient, postirradiated osteomyelitis in one patient, and chondro-hamartoma in one patient. The mean observation period was 23 months, and four cases were observed for more than three years. There were no operative deaths and no wound infections. There were two postoperative complications: prolonged air leakage occurred in a patient with pulmonary emphysema who underwent right lower lobectomy, and slight paradoxical respiration occurred in the patient who underwent resection of the entire sternal body for osteomyelitis. Follow-up chest computed tomography was performed routinely. No dehiscence occurred in any cases. Chest wall reconstruction using DualMesh demonstrated acceptable durability and biocompatibility, even after long-term follow-up. DualMesh has the potential to become an ideal prosthesis for the bony chest wall as an alternative to conventional polytetrafluoroethylene or polypropylene grafts.

Creation of a uniform pleural defect model for the study of lung sealants.

OBJECTIVE: Animal models are indispensable for the development of new therapeutic methods for the closure of alveolar air leakage. However, it is difficult to create a uniform pleural defect model. The purpose of this study was to establish an appropriate animal model for assessing the efficacy and histotoxicity of synthetic sealants for lung surgery. METHODS: Nine beagle dogs were used to evaluate the pleural defect model in comparison with conventional resection procedures. A donut-shaped silicon ring with an inner diameter of 15 mm was placed on the pleura, and 0.1 mL of cyanoacrylate was dropped into the ring. A pleural defect was created by sliding a microtome blade just beneath the polymerized cyanoacrylate. Hemostasis was performed by pressure with a sponge. RESULTS: Morphologically, round areas of the pleura were uniformly resected with our procedure. The resected tissue consisted of pleura and thin underlying lung parenchyma. Among the results from 3 surgeons, there were no significant differences in the mean time required for hemostasis (P = .69), the mean thickness of the resected tissue (P = .13), and the mean amount of air leakage from the resected area (P = .19). No penetration of cyanoacrylate into the lung parenchyma was evidenced by immunofluorescence microscopy. Histologically, when the pleura was resected without using cyanoacrylate, a thick fibrocellular layer extended to the lung parenchyma. Furthermore, severe fibrosis was observed when electrocautery was used for hemostasis. However, when the pleura was resected using cyanoacrylate, the normal alveolar structure was preserved. CONCLUSIONS: Our uniform pleural defect model using cyanoacrylate may be feasible for the evaluation of synthetic sealants for alveolar air leakage.

Development of new biodegradable hydrogel glue for preventing alveolar air leakage.

OBJECTIVE: Air leakage is a frequent complication during lung surgery. A new hydrogel glue was created by mixing aldehyded dextran and epsilon-poly(l-lysine), and its feasibility as a surgical sealant was evaluated in comparison with that of conventional fibrin glue. METHODS: Bursting pressure after application of each glue to 30 x 30-mm pleuroparenchymal defects was evaluated in two groups of 14 beagle dogs. Biodegradability and histotoxicity of the glues were evaluated in another 6 dogs with 15-mm circular pleuroparenchymal defects. Adhesions, infections, and histologic changes were observed on scheduled days for 6 months. RESULTS: The mean bursting pressure after application was 38.4 +/- 4.6 cm H2O for the new glue and 32.1 +/- 4.5 cm H2O for fibrin glue (P = .02), the former providing more effective sealing of pulmonary air leakage than the latter. Macroscopically, no adhesions or infections were observed in areas of glue application. About 90% of the new glue degraded within 3 months, but complete disappearance was not observed by 6 months. On the other hand, the fibrin glue was replaced by white pleural tissue at 4 weeks. Histologically, the new glue was covered by one layer of mesothelial cells at 2 weeks and completely covered by thick fibrous tissue at 4 weeks. Inflammatory reaction was minimal around the residual glue after 3 months. Although the new glue degraded more slowly than did the fibrin glue, the biocompatibility of the new glue was sufficient for clinical use. CONCLUSION: Our new hydrogel glue demonstrates a strong sealing effect, with good biocompatibility, and has potential usefulness as an adhesive in lung surgery.