Endoscopic Sealing With a Polyglycolic Acid Sheet for Restoration of Vocal Fold Mucosa in Dogs.

OBJECTIVES/HYPOTHESIS: Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet. STUDY DESIGN: Animal experiment. METHODS: Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed. RESULTS: The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups. CONCLUSIONS: The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E436-E443, 2020.

Stable Tracheal Regeneration Using Organotypically Cultured Tissue Composed of Autologous Chondrocytes and Epithelial Cells in Beagles.

OBJECTIVES: In tracheal regeneration, the slow process of epithelialization is often a barrier to the stability and safety of the transplanted trachea. The aim of this study was to examine a new tracheal regeneration technique using organotypically cultured tissue composed of autologous cells. METHODS: Nine beagles were prepared. Chondrocytes from auricular cartilage and epithelial cells from buccal mucosa were isolated and cultured. Tissue-engineered cartilages were fabricated with chondrocytes at a density of 1 × 107 cells/mL (high-density group) and 1 × 106 cells/mL (low-density group). A fabricated epithelial cell sheet was laid on a poly(lactic-co-glycolic acid) block in atelocollagen gel containing the chondrocytes, and the organotypically cultured tissues were transplanted into a partially resected trachea. The control group had only the block transplanted. RESULTS: The tissue-engineered cartilages in the high-density group contained many viable chondrocytes and many cartilage matrices. The low-density group had abundant collagen fibers and no chondrocytes. Tracheal endoscopy revealed no deformation or atrophy at the transplant site in the high-density group. Histologically, partially hyaline cartilages covered with epithelium and lamina propria were found in the high-density group but not in the low-density and control groups. CONCLUSIONS: Stable tracheal regeneration was achieved using organotypically cultured tissue fabricated with autologous high-density chondrocytes and epithelial cells.

Vibratory function and healing outcomes after small intestinal submucosa biomaterial implantation for chronic vocal fold scar.

OBJECTIVES/HYPOTHESIS: Vocal fold scar is a major cause of dysphonia, and optimal treatments do not currently exist. Small intestinal submucosa (SIS) is a biomaterial developed for the treatment of a variety of pathologies. The purpose of this study was to investigate the effects of SIS implantation on tissue remodeling in scarred vocal folds using routine staining, immunohistochemistry, and high-speed videoendoscopy (HSV). STUDY DESIGN: Prospective, blinded group analysis. METHODS: Thirteen New Zealand White rabbits underwent a vocal fold scarring procedure followed by microflap elevation with or without SIS implantation. Seven months later, they underwent a phonation procedure with HSV and laryngeal harvest. Alcian blue and elastica van Gieson staining and immunohistochemistry for collagen types I and III were used to evaluate histological healing outcomes. Dynamic functional remodeling of the scarred vocal fold in the presence of SIS implants was evaluated using HSV imaging to capture restoration of vibratory amplitude, amplitude ratio, and left-right phase symmetry. RESULTS: Density of collagen I was significantly decreased in SIS versus microflap-treated vocal folds. No differences were found between groups for hyaluronic acid, elastin, or collagen type III. Organization of elastin in the subepithelial region appeared to affect amplitude of vibration and the shape of the vocal fold edge. CONCLUSIONS: SIS implantation into chronic scar reduced the density of collagen I deposits. There was no evidence of a negative impact or complication from SIS implantation. Regardless of treatment type, organization of elastin in the subepithelial region may be important to vibratory outcomes. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:901-908, 2018.

Pegylated interferon-α2a inhibits proliferation of human liver cancer cells in vitro and in vivo.

PURPOSE: We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells. METHODS: The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined. RESULTS: PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 µg/kg, 0.06 µg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control. CONCLUSIONS: Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.

First demonstration of laser engagement of 1-Hz-injected flying pellets and neutron generation.

Pellet injection and repetitive laser illumination are key technologies for realizing inertial fusion energy. Numerous studies have been conducted on target suppliers, injectors, and tracking systems for flying pellet engagement. Here we for the first time demonstrate the pellet injection, counter laser beams' engagement and neutron generation. Deuterated polystyrene (CD) bead pellets, after free-falling for a distance of 18 cm at 1 Hz, are successfully engaged by two counter laser beams from a diode-pumped, ultra-intense laser HAMA. The laser energy, pulse duration, wavelength, and the intensity are 0.63 J per beam, 104 fs, and 811 nm, 4.7 × 10(18) W/cm(2), respectively. The irradiated pellets produce D(d,n)(3)He-reacted neutrons with a maximum yield of 9.5 × 10(4)/4π sr/shot. Moreover, the laser is found out to bore a straight channel with 10 µm-diameter through the 1-mm-diameter beads. The results indicate potentially useful technologies and findings for the next step in realizing inertial fusion energy.

Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead.

BACKGROUND: As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. METHODS AND RESULTS: The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6+/-2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. CONCLUSIONS: Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures.

Long-term outcome of the endoscopic correction of vesico-ureteric reflux: a comparison of injected substances.

OBJECTIVE: To summarize the long-term outcome of endoscopic surgery to correct vesico-ureteric reflux (VUR) using different injected substances, i.e. autologous blood, hyaluronan/dextranomer copolymer (HDC), PTFE and glutaraldehyde cross-linked bovine dermal (GAX) collagen. PATIENTS AND METHODS: Treatment results on 270 ureters of 185 patients followed for >5 years (mean 8.5) were summarized according to the injected substances. The substances were injected into the 6 o'clock position of the ureteric orifice endoscopically. "Success" was defined as the absence of VUR for >5 years after a single injection. RESULTS: The treatment was successful in two of 24 patients (8%) with autologous blood, 17 of 32 (53%) with HDC, 108 of 171 (63%) with PTFE and 24 of 43 (56%) with GAX collagen. The success rate was lower in patients with higher grades of VUR. CONCLUSIONS: Autologous blood is unsuitable for clinical application because of its poor durability. We will no longer use PTFE because its safety is not well established. The overall success rates of endoscopic surgery with GAX collagen and HDC were insufficient compared with surgical reimplantation, but it is advantageous that this procedure is less invasive and can be repeated. The cure rate could be improved by excluding high-grade VUR from the indications for endoscopic surgery.