Takatoshi Furukawa

Feasibility and Advantages of Transcanal Endoscopic Myringoplasty

Objective When performing transcanal myringoplasty under a microscope, the total circumference of the perforation can be difficult to confirm in patients where the external ear canal is narrow and/or protruded. In such patients, a retroauricular incision approach is usually used. However, we have developed a transcanal endoscopic myringoplasty procedure, and the microscopic and endoscopic views are compared herein for the first time. The feasibility and advantages of transcanal endoscopic myringoplasty were examined. Study Design A prospective case series. Setting Tertiary referral center. Patients Transcanal endoscopic myringoplasty was performed on 25 ears in 21 patients with chronic otitis media between September 2011 and December 2012. Intervention Microscopic and endoscopic views were compared for each patient. The 2 fields of views were both recorded and evaluated to determine the advantages and disadvantages of microscopes and endoscopes. Myringoplasty was performed using an endoscopic technique while comparing views as necessary. Results Endoscopic views revealed the entire tympanic membrane in a single field with clear visualization of the perforation edges even when the ear canal was curved. This clear visualization facilitated reliable refreshing of the perforation edges and grafting. The anterior edge of the perforation was not visible under microscopy in 5 of 25 ears. Under an endoscopic wide view, the tympanic cavity was observable through the perforation, and the orifice of the tube, ossicular chain, and tympanic isthmus were visible especially with large perforations. Transcanal endoscopic myringoplasty was successfully performed with a simple underlay technique or with an intracanal incision in cases of marginal perforation. Conclusion Comparison of microscopic and endoscopic views revealed superior visualization and operability of the endoscopic approach as opposed to transcanal simple underlay myringoplasty. Transcanal endoscopic myringoplasty does not require surgical exposure such as a retroauricular skin incision to get an anterior view. Our results demonstrated that transcanal endoscopic myringoplasty can be performed, regardless of the perforation size and the narrowness and/or protrusion of external ear canal.

Clinical and pathological characteristics of IgG4-related sclerosing sialadenitis†

A new concept of IgG4‐related sclerosing sialadenitis characterized by high serum IgG4 levels and tissue infiltration of IgG4‐expressing plasmacytes has recently been proposed. To determine appropriate serum levels of IgG4 for monitoring disease activity, a total of 36 serum samples and eight tissue samples from patients with IgG4‐related sclerosing sialadenitis were studied.

Roles of IL-17, Th1, and Tc1 Cells in Patients With IgG4-Related Sclerosing Sialadenitis

Immunoglobulin G4 (IgG4)‐related sclerosing sialadenitis is a recently recognized disease entity characterized by high serum IgG4 concentration and IgG4‐producing plasma cell expansion in affected organs, which show fibrotic or sclerotic changes. However, little is known about the roles of CD4+ and CD8+ T cells or interleukin (IL)‐17 in this disease. The purpose of this study was to evaluate the characteristics of CD4+ and CD8+ T cells and IL‐17 in patients with IgG4‐related sclerosing sialadenitis.

Extension of indications for transcanal endoscopic ear surgery using an ultrasonic bone curette for cholesteatomas.

Background One-handed endoscopic procedures have, up until now, limited the indications for transcanal endoscopic ear surgery (TEES) in cholesteatoma surgery. However, the development of electrically powered instruments has opened the door to such one-handed endoscopic procedures in restricted surgical spaces. Objective We examined the feasibility of using one such powered instrument, the ultrasonic bone curette (UBC) in TEES for cholesteatoma surgery. The UBC offers several advantages, including nonrotational motion and the combination of both suction and irrigation in a single handpiece. Study Design A prospective case series. Setting Tertiary referral center. Patients TEES was performed on 43 cases of primary cholesteatoma between September 2011 and December 2012, including 14 cases extending to the antrum. Intervention Zero-, 30-, or 70-degree angled rigid endoscopes with an outer diameter of 2.7 mm (Karl Storz) were used together with a high-definition video system. A Sonopet UBC (Stryker) was used to cut bony tissue. The nonrotational motion of the UBC prevents injury to the tympanomeatal flap and other soft tissue, which may result with standard drills. Transcanal endoscopic retrograde mastoidectomy on demand was performed to access the pathologies in the attic and antrum. Results A minimum attico-antrotomy was performed using the UBC, removing only the bony tissue necessary to visualize the pathology. The cholesteatoma was completely removed from the antral mucosa under clear endoscopic visualization in 13 of 14 cases. After removal of the cholesteatoma, the canal wall was reconstructed using cartilage taken from the tragus. This procedure resulted in greater mastoid preservation. Conclusion The transcanal endoscopic approach to the antrum using the UBC proved to be less invasive and more functional. The UBC contains both a suction and irrigation system in a single handpiece, and this UBC is an appropriate cutting tool that extends the indications for TEES.

Transcanal endoscopic ear surgery for pediatric population with a narrow external auditory canal

OBJECTIVES To retrospectively determine the size of the external auditory canal (EAC) in a pediatric population and to describe our experience with transcanal endoscopic ear surgery (TEES) in this pediatric population which had been successfully treated for middle ear disease using TEES. METHODS We analyzed 31 patients ranging in age from 2 to 13 years old (median: 7.6 years) with middle ear disease who underwent TEES between November 2011 and August 2014. Sixteen of these patients had surgery for cholesteatomas; 11 for chronic otitis media; and 4 for malformation of the middle ear. A preoperative CT scan was performed to evaluate the middle ear disease. Transcanal endoscopic tympanoplasty was performed using a rigid endoscope with a 2.7mm outer diameter. Transcanal endoscopic atticoantrotomy was also performed, as necessary, on some patients to access pathologies in the antrum. The values of anterior-posterior diameters and superior-inferior diameters of the bony parts of EAC were measured retrospectively based on the preoperative CT scan data. RESULTS TEES was successfully performed in all 31 pediatric patients without resorting to a retroauricular incision. Twenty-seven patients were evaluated for postoperative hearing levels which were found to fall within an acceptable range and for postoperative air-bone gap (ABG) by pure tone audiometry with a resulting mean of 8.6dB. The smallest anterior-posterior diameters of the external ear canal ranged from 3.2 to 7.1mm (5.0±1.0mm) and the smallest superior-inferior diameters ranged from 3.4 to 10.3mm (5.9±1.3mm). CONCLUSION TEES can be used to safely and effectively treat middle ear disease even in the pediatric population in its narrow EAC.

Roles of TGF-beta and periostin in fibrosclerosis in patients with IgG4-related diseases.

Abstract Conclusion: These results suggest that transforming growth factor (TGF)-beta and periostin could be useful as novel biomarkers and therapeutic targets in IgG4-related disease. Objectives:IgG4-related disease is an uncommon fibrosclerosing and inflammatory mass-forming disease that can be systemic or can affect single organs. To clarify the roles of TGF-beta, periostin, and interleukin (IL)-13 in the pathogenesis of IgG4-related disease, we studied a total of 36 serum and 11 tissue samples from patients with IgG4-related disease. Methods: This was a retrospective clinical study. The patient group consisted of six females and seven males (average age 60 years, range 38–74 years). Serum IgG4 levels, the tissue density of IgG4-positive plasmacytes, and the expression of TGF-beta and periostin in the affected tissues were examined immunohistochemically. Results: Serum IgG4 levels were elevated in all patients (mean 776.6, range 185–2820 mg/dl), and IgG4-positive plasmacytes were observed in the affected salivary glands. Seven patients with prominent infiltration of the involved glands with IgG4-positive plasmacytes had fatal systemic complications, including pancreatitis, after swelling of the salivary glands. Overexpression of TGF-beta and periostin was observed in affected tissues obtained from these patients.

Role of the CM2 Protein in the Influenza C Virus Replication Cycle

ABSTRACT CM2 is the second membrane protein of influenza C virus. Although its biochemical characteristics, coding strategy, and properties as an ion channel have been extensively studied, the role(s) of CM2 in the virus replication cycle remains to be clarified. In order to elucidate this role, in the present study we generated CM2-deficient influenza C virus-like particles (VLPs) and examined the VLP-producing 293T cells, VLPs, and VLP-infected HMV-II cells. Quantification of viral RNA (vRNA) in the VLPs by real-time PCR revealed that the CM2-deficient VLPs contain approximately one-third of the vRNA found in wild-type VLPs although no significant differences were detected in the expression levels of viral components in VLP-producing cells or in the number and morphology of the generated VLPs. This finding suggests that CM2 is involved in the genome packaging process into VLPs. Furthermore, HMV-II cells infected with CM2-deficient VLPs exhibited significantly reduced reporter gene expression. Although CM2-deficient VLPs could be internalized into HMV-II cells as efficiently as wild-type VLPs, a smaller amount of vRNA was detected in the nuclear fraction of CM2-deficient VLP-infected cells than in that of wild-type VLP-infected cells, suggesting that the uncoating process of the CM2-deficient VLPs in the infected cells did not proceed in an appropriate manner. Taken together, the data obtained in the present study indicate that CM2 has a potential role in the genome packaging and uncoating processes of the virus replication cycle.

Influenza C Virus NS1 Protein Upregulates the Splicing of Viral mRNAs

ABSTRACT Pre-mRNAs of the influenza A virus M and NS genes are poorly spliced in virus-infected cells. By contrast, in influenza C virus-infected cells, the predominant transcript from the M gene is spliced mRNA. The present study was performed to investigate the mechanism by which influenza C virus M gene-specific mRNA (M mRNA) is readily spliced. The ratio of M1 encoded by a spliced M mRNA to CM2 encoded by an unspliced M mRNA in influenza C virus-infected cells was about 10 times larger than that in M gene-transfected cells, suggesting that a viral protein(s) other than M gene translational products facilitates viral mRNA splicing. RNase protection assays showed that the splicing of M mRNA in infected cells was much higher than that in M gene-transfected cells. The unspliced and spliced mRNAs of the influenza C virus NS gene encode two nonstructural (NS) proteins, NS1(C/NS1) and NS2(C/NS2), respectively. The introduction of premature translational termination into the NS gene, which blocked the synthesis of the C/NS1 and C/NS2 proteins, drastically reduced the splicing of NS mRNA, raising the possibility that C/NS1 or C/NS2 enhances viral mRNA splicing. The splicing of influenza C virus M mRNA was increased by coexpression of C/NS1, whereas it was reduced by coexpression of the influenza A virus NS1 protein (A/NS1). The splicing of influenza A virus M mRNA was also increased by coexpression of C/NS1, though it was inhibited by that of A/NS1. These results suggest that influenza C virus NS1, but not A/NS1, can upregulate viral mRNA splicing.

Palmitoylation of CM2 is dispensable to influenza C virus replication

CM2 is the second membrane protein of influenza C virus. The significance of the posttranslational modifications of CM2 remains to be clarified in the context of viral replication, although the positions of the modified amino acids on CM2 have been determined. In the present study, using reverse genetics we generated rCM2-C65A, a recombinant influenza C virus lacking CM2 palmitoylation site, in which cysteine at residue 65 of CM2 was mutated to alanine, and examined viral growth and viral protein synthesis in the recombinant-infected cells. The rCM2-C65A virus grew as efficiently as did the parental virus in cultured HMV-II cells as well as in embryonated chicken eggs. The synthesis and biochemical features of HEF, NP, M1 and mutant CM2 in the rCM2-C65A-infected HMV-II cells were similar to those in the parental virus-infected cells. Furthermore, membrane flotation analysis of the infected cells revealed that equal amount of viral proteins was recovered in the plasma membrane fractions of the rCM2-C65A-infected cells to that in the parental virus-infected cells. These findings indicate that defect in palmitoylation of CM2 does not affect transport and maturation of HEF, NP and M1 as well as CM2 in virus-infected cells, and palmitoylation of CM2 is dispensable to influenza C virus replication.

Safety of ultrasonic bone curette in ear surgery by measuring skull bone vibrations.

Hypothesis Mastoidectomy using an ultrasonic bone curette (UBC) is as safe for the inner ear as a mastoidectomy using a high-speed drill. Background Transcanal endoscopic ear surgery (TEES) is a minimally invasive, secure, and functional technique, which has been performed using high-speed drills. We have started to use a UBC instead of the high-speed drill because a UBC allows for simultaneous bone cutting, irrigation, and aspiration. These features of the UBC make it an excellent candidate for use in one-handed TEES, but the safety of the UBC still needs to be confirmed. We thus measured skull vibrations caused by the UBC to estimate the effects of UBC on the inner ear. Methods Eight patients with cholesteatoma underwent mastoidectomy using a Sonopet UST-2001 UBC (Stryker, MI, USA) and 2 high-speed drills (drills A and B). Skull vibrations were measured using polyvinylidene difluoride film taped to the forehead as a piezoelectric vibration sensor. The recorded data were transformed to the power spectrum in the frequency domain by fast Fourier transform. The mean and peak values of vibrations were analyzed in four frequency bands: 200 to 500 Hz, 500 to 2,000 Hz, 2,000 to 8,000 Hz, and 8,000 Hz to 20 kHz. Results Both the mean values and the peak values of skull vibrations caused by the UBC were significantly smaller than those values obtained for drill B between 500 and 8,000 Hz, (p < 0.05). No significant differences were found among the 3 instruments below 500 Hz or above 8,000 Hz. Conclusion Skull vibration levels generated by the UBC were found to be comparable or even lower than those levels associated with conventional high-speed drills. These findings indicated that the UBC can be safely applied to TEES without the risk of harmful effects on the inner ear.