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This chapter will expand on Chap. 2 which focused on powered transcanal endoscopic ear surgery (TEES) by looking at the surgical setup and safety concerns related primarily to powered TEES as well as what was referred to in Chap. 2 as “non-powered TEES.” To reiterate “non-powered TEES” is not a general term used in the literature and is used here to refer to what is typically simply called TEES. Successful TEES, in general, and powered TEES, specifically, requires careful preparation including procuring the proper equipment together with properly positioning and preparing that equipment, the surgical staff, and the patient. The safety issues which also need to be addressed for powered TEES include proper use of the powered instruments within the middle ear, heat generation of light sources, and the potential impact of skull vibrations generated by these powered instruments.

This book Innovations in Endoscopic Ear Surgery is designed with two objectives in mind: (1) to introduce new and exciting innovations, as our title implies in endoscopic ear surgery, and specifically transcanal endoscopic ear surgery (TEES), to those who are already experienced TEES surgeons and (2) to spark interest in those ear surgeons who are either unfamiliar with TEES or familiar with TEES but unsure of its value and/or safety.

While the endoscope plays the starring role in transcanal endoscopic ear surgery (TEES), TEES has a supporting cast of equipment that have helped guarantee its success, particularly the 3-charged-coupled device (CCD) camera and more recently the complementary metal-oxide semiconductor (CMOS) cameras connected to video monitors. These cameras and monitors, which were originally high definition (HD) and more recently ultra HD or 4K, combine to produce clear images that allow surgeons to confidently perform transcanal surgery with an endoscope within the delicate anatomical structures of the middle ear.

The surgical field within the middle ear is small, has been, up until recently, largely hidden from view, difficult to visualize, and filled with tiny, delicate anatomical structures. Thus, surgeons operating in the middle ear had to, by necessity, gather critical information only after they expose the surgical field as they perform microscopic ear surgery (MES). This situation made middle ear surgery particularly challenging. However, technological advances achieved from the turn of the twentieth century up to the present day in the fields of computer software and diagnostic imaging have helped to provide ear surgeons with better qualitative and quantitative data than was previously obtainable. Developments in both computer and imaging technology made complete computer simulation of middle ear surgical procedures possible for MES using programs such as Voxel-Man [1] and the OSU virtual temporal bone system [2] for education and training purposes.

Ear surgery in many ways lagged behind other surgical fields because of the delicate anatomical structures within the ear which leave surgeons with little room for error. Thus, while surgical instruments have long been available, their use in the ear would most often do more damage than good. This state of affairs remained the status quo well into the first half of the 20th century. However, the introduction of powered surgical instruments, specifically the electric drill used in conventional microscopic ear surgery (MES) and the ultrasonic aspirator, the Sonopet® Omni, in transcanal endoscopic ear surgery (TEES) marked major turning points. Yet, these breakthroughs have also raised concerns about whether the use of these powered surgical instruments within the confines of the ear generated so much noise and vibrations that patients could suffer sensorineural hearing loss as a result of the surgery itself. This paper reviews the intersection between the noise and vibrations generated during surgery; the history of surgical instruments, particularly powered surgical instruments, used in ear surgeries and the two main types of surgical procedures to determine whether these powered surgical instruments may pose a threat to postoperative hearing.

The main application of endoscopic surgery relies on the middle ear cholesteatoma surgical treatment, although for a definitive validation and acceptance by scientific community, long-term results are needed about recurrent and residual rates of the pathology. The aim of the present paper was to analyze the single institution experience with the long-term results of surgical treatment of attic cholesteatoma.

Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA-bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-β1 (TGF-β1), B cell-activating factor of the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.

Objective To assess the efficacy of a color-mapped diffusion-weighted image combined with a computed tomography scan (CMDWI-CT) in preoperatively evaluating the anatomical location of cholesteatomas and determining whether a patient is indicated for transcanal endoscopic ear surgery (TEES) to reduce intraoperative switching to microscopic ear surgery (MES). Study design Prospective case study. Setting A single university hospital. Patients Fifty-five patients scheduled for middle ear cholesteatoma surgery. Intervention The CMDWI-CT is produced in a multistep process. A color-mapped fusion image (CMFI) is created by performing MR cisternography on a 1-mm thin-slice nonecho planar diffusion-weighted imaging (non-EPI DWI) and then by performing color mapping on the resulting image to enhance cholesteatoma visualization. False positives are reduced by taking a T1-weighted image (T1WI), whereas false negatives are further reduced by preoperative endoscopic examination. As cholesteatomas are difficult to locate on a CMFI in the temporal bone region, we stripped out the MR cisternography data from the CMFI and then fused the CMFI to the initial computer tomography (CT) scan to create a CMDWI-CT. This CMDWI-CT better clarifies the cholesteatoma position within temporal bone. Main outcome measure(s) CMDWI-CT preoperative findings were compared with intraoperative findings. The positive predictive value and negative predictive value were also evaluated depending on the cholesteatoma location. Results CMDWI-CT facilitated accurate detection of the cholesteatoma anatomical location in the temporal bone region which was reflected in positive predictive and negative predictive values of over 90% for all areas of the middle ear. Conclusion CMDWI-CT is a reliable diagnostic modality for evaluating the anatomical location of cholesteatomas that seem as high-signal regions on a CMFI and for determining whether TEES is indicated for treatment in such patients.

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 2.7 mm 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 8.6 dB. The smallest anterior–posterior diameters of the external ear canal ranged from 3.2 to 7.1 mm (5.0 ± 1.0 mm) and the smallest superior–inferior diameters ranged from 3.4 to 10.3 mm (5.9 ± 1.3 mm). Conclusion TEES can be used to safely and effectively treat middle ear disease even in the pediatric population in its narrow EAC.

OBJECTIVE To compare levels and causes of postoperative pain after cholesteatoma removal by transcanal endoscopic ear surgery (TEES) versus microscopic ear surgery (MES). STUDY DESIGN Prospective case series. SETTING Tertiary referral center. PATIENTS One-hundred-and-sixty-one patients who had undergone middle ear surgery between February 2013 and April 2016. INTERVENTIONS Comparison of postoperative pain between TEES and MES groups and among TEES and MES subgroups divided by range of bone removal. MAIN OUTCOME MEASURES Two parameters were used to assess postoperative pain: a pain numeric rating scale (NRS) and number of times a non-steroidal anti-inflammatory drug (NSAID) was taken from postoperative days (PODs) 1 to 7. We also examined the primary factor behind postoperative pain looking at: 1) the surgical incision; 2) bone removal; and 3) number of involved middle ear regions. RESULTS One-hundred-and-six patients underwent TEES and 55 underwent MES. The mean pain NRS for the 7-day postoperative period was significantly lower for the TEES group (1.1) than the MES group (2.8) (p

Immunoglobulin A nephropathy (IgAN) is characterized by a qualitative abnormality of IgA in the circulation and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils. Follicular dendritic cell-secreted protein (FDC-SP), a small novel secretory protein that may regulate the induction of B-cell responses, has been suggested to control IgA production. Given this background, this study investigated the expression of FDC-SP and its correlation with IgA production in the tonsils of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to compare the expression of FDC-SP in the tonsils of IgAN patients with tonsillitis and of non-IgAN patients with chronic tonsillitis. The location of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. We found that FDC-SP expression significantly decreased and was correlated negatively with enhanced IgA production in the tonsils of IgAN patients. FDC-SP secreted by follicular dendritic cells may act on germinal center B cells and participate in the modulation of IgA generation in the tonsils. Our study demonstrated that FDC-SP may be involved in IgA production in the tonsils of IgAN patients, making this protein an attractive candidate immunomodulator, and highlighting a promising strategy for therapeutic intervention in IgAN.

This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection.Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection.Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis.The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

Objective: Sinonasal inverted papilloma has been traditionally managed with external surgical approaches. Advances in imaging guidance systems, surgical instrumentation, and intraoperative multi-visualization have led to a gradual shift from external approaches to endoscopic surgery. However, for anatomical and technical reasons, endoscopic surgery of sinonasal inverted papilloma extending to the frontal sinuses is still challenging. Here, we present our experience in endoscopic surgical management of sinonasal inverted papilloma extending to one or both frontal sinuses. Methods: We present 10 cases of sinonasal inverted papilloma extending to the frontal sinuses and successfully removed by endoscopic median drainage (Draf III procedure) under endoscopic guidance without any additional external approach. Results: The whole cavity of the frontal sinuses was easily inspected at the end of the surgical procedure. No early or late complications were observed. No recurrence was identified after an average follow-up period of 39.5 months. Conclusion: Use of an endoscopic median drainage approach to manage sinonasal inverted papilloma extending to one or both frontal sinuses is feasible and seems effective.

Objectives: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan. Methods: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis. Results: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis. Conclusion: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.

Objective Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. Study design Retrospective case review. Setting Tertiary referral center. Patients A total of 675 patients with Bell's palsy who had grade V and grade VI on the House-Brackmann (HB) scale were treated in our department between 1995 and 2014. These patients could be divided into a normal-dose group and high-dose group. Methods We separately assessed treatment outcomes for HB grade V patients and HB grade VI patients. Logistic regression analysis was also performed to investigate factors that can impact treatment outcomes, i.e., sex, age, days to start of treatment, PSL dosage, and antiviral drug administration. Results Recovery rates were significantly better in the high-dose steroid + Hespander + Mannitol group in comparison with the normal-dose steroid group for HB grade V (100% versus 77.7%) and HB grade VI (92.5% versus 68.2%). Additional effects of antiviral agents were only shown in the normal-dose group. Significant factors for treatment outcomes were PSL 200 mg/d administration and early initiation of treatment. Insignificant factors were sex, age, and the antiviral agent. Conclusion We showed the high-dose steroid + Hespander + Mannitol administration produced significantly better outcomes than normal-dose steroid administration in the treatment of patients with Bell's palsy.

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.A prospective case series.Tertiary referral center.Transcanal endoscopic myringoplasty was performed on 25 ears in 21 patients with chronic otitis media between September 2011 and December 2012.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.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.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.

Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of ranula extending to the parapharyngeal space.The aim of this study was to evaluate the outcome and complications of the OK-432 treatment of patients with ranula extending to the parapharyngeal space.This was a case series with planned data collection at Yamagata University and Fukase clinic. We tried this therapy in six patients with ranula extending to the parapharyngeal space, between January 2001 and February 2012. We injected OK-432 solution into the lesion with an 18 or 27 gauge needle depending on the patient's condition (location and size of ranula and complications). This treatment was performed on an outpatient basis without hospitalization.Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the injection sites did not occur in any patients. As side effects, local pain at the injection site and fever (37-39°C) were observed in 40% of the patients who had this therapy, but such problems resolved within a few days.

Office-based transtympanic endoscopy through the perforation made by laser-assisted myringotomy (LAM) has been introduced for diagnosis of ossicular interruption, stapes fixation, tympanosclerosis, congenital cholesteatoma, and perilymphatic fistula. Endoscopy of the middle ear reveals minor anomalies around the incudostapedial joint and the superstructure of the stapes. This procedure can be also applied to diagnose stapes fixation and perilymphatic fistula not diagnosed presurgically, and requires exploratory tympanotomy to make a definite diagnosis. Transtympanic endoscopy using LAM is a direct and reliable preoperative diagnostic method for abnormalities of the middle ear, offers better surgical indications and patient consultation, and is a potential alternative to exploratory tympanotomy.

The 3-year progression-free survival rate of non-invasive salivary duct carcinoma (SDC) or adenocarcinoma not otherwise specified (NOS) was significantly better than that of invasive SDC or adenocarcinoma NOS in Carcinoma ex pleomorphic adenoma (CXPA). The presence of invasion is an important prognostic factor for SDC and adenocarcinoma NOS in CXPA.CXPA is a rare parotid gland malignant tumor for which therapy is not yet standardized. The purpose of this study was to review the characteristics of CXPA patients and to analyze their outcomes in the Northern Japan Head and Neck Cancer Society.The medical records of 33 patients who had been provided initial treatment in 12 institutes of northern Japan from 2002-2011 were reviewed as a multi-institutional retrospective study.The 3-year overall and progression-free survival rate of all patients was 79.9% and 76.8%, respectively. Both the 3-year overall and progression-free survival rates were 87.5% for patients with non-invasive SDC or adenocarcinoma NOS. The 3-year overall and progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS were 60.4% and 30.5%, respectively. The progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS was significantly poor (p 0.05).

Objectives/Hypothesis: 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. Study Design: A retrospective clinical study at the Yamagata University School of Medicine. Methods: The patient group consisted of six males and four females with an average age of 57.9 years (range, 38 to 73years). Subsets of T helper (Th)1, Th2, T cytotoxic type (Tc)1, and Tc2 cells from patients with IgG4-related sclerosing sialadenitis were examined by using intracellular cytokine flow cytometry. Expression of IL-17 in the patients' lesions was also investigated immunohistochemically. Results: Six patients with IgG4-related sclerosing sialadenitis with high ratios of IgG4/IgG and prominent infiltration of IgG4-positive plasmacytes in the involved salivary glands had systemic complications, including pancreatitis, retroperitoneal fibrosis, and/or inflammatory pseudotumor of the lung after the initial swelling of the salivary glands. Populations of Th1 and Tc1 cells were significantly greater in IgG4-related sclerosing sialadenitis than in the controls (P < .05), but Th2 and Tc2 cell populations were not significantly increased. Expression of IL-17 was observed in the lesions of affected patients. Conclusions: Increases in Th1 and Tc1 cell populations and IL-17 expression might be involved in the mechanism of pathogenesis of IgG4-related sclerosing sialadenitis. Laryngoscope, 2012

IgA nephropathy (IgAN), the common primary glomerulonephritis, is a tonsillar focal infection characterized by the qualitative abnormality of IgA in circulation and IgA deposition in the renal mesangium. Mesangial deposition of IgA, which is composed predominantly of poorly galactosylated polymeric IgA1 (pIgA1), seems to be the initiating event in the pathogenesis of IgAN. The origin of poorly galactosylated IgA, however, remains unclear. Recent studies suggest that the mesangial polymeric IgA1 deposition could be derived from mucosally primed plasma cells. B cells may undergo IgA class switching to acquire the expression of IgA via T-cell-dependent or T-cell-independent pathways in mucosa-associated lymphoid tissue and then differentiate to IgA plasma cells or home in on systemic sites. Dendritic cells, including plasmacytoid dendritic cells and another type of antigen-retaining cell, follicular dendritic cells, have an irreplaceable role in IgA class-switch mechanisms by producing IgA-inducing signals. Furthermore, an increased number of pIgA1-secreting plasma cells in the bone marrow and tonsil, as well as increased IgA class switching, have been found in IgAN, providing a link between the mucosal immunity and IgAN. The favorable effect of tonsillectomy on patients with IgAN showed that tonsillar focal infection may be closely related to pIgA1 deposition in glomerular mesangium of patients with IgAN and at least a part of pIgA1 may originate from affected tonsils. Therefore, the indication for tonsillectomy should be considered in patients with IgA nephropathy, especially at a mild or early stage, to prevent future renal deterioration. In this paper, we focus on IgA class switching and the role of tonsils with focal infection in IgAN.

IgG4関連疾患は，全身の諸臓器にCD4ないしCD8陽性Tリンパ球とIgG4陽性形質細胞が浸潤する全身性疾患であり，IgG4陽性細胞の浸潤は，唾液腺，甲状腺，膵臓，胆管，後腹膜などに認められることが多い。近年，自己免疫性膵炎，硬化性胆管炎，後腹膜線維症など，これまで独立して診断されてきた疾患が，新しい疾患概念であるIgG4関連疾患の一つの表現型である可能性が示唆されている。耳鼻咽喉科領域においては，ミクリッツ病やキュットナー腫瘍などの硬化性唾液腺炎やRiedel甲状腺炎などがIgG4関連疾患であるといわれている。IgG4関連疾患では，自己免疫性膵炎や硬化性胆管炎で発症する例も少なくないが，耳下腺，顎下腺，涙腺の腫脹が自覚症状として認識しやすいため，耳鼻咽喉科や眼科を最初に受診する例が多く存在する。また無痛性であるため，医療機関を受診していない例も相当数存在すると予想される。しかしながら，IgG4関連疾患は単独の病変にとどまらず，経過中に全身諸臓器に病変を生じることが知られており，注意が必要である。当科で経験した症例においても，その約半数に自己免疫性膵炎をはじめとした他臓器合併症を認め，他科との連携治療を行っている。IgG4関連疾患は，たとえ初診時の症状や所見が軽微なものであったとしても，詳細な全身検索と長期間の経過観察，また他科との密接な連携を要する疾患である。

Background : Pendrin and periostin are newly identified mediators of the inflammatory process. The expression of these proteins in human sinonasal tissue and their roles in allergic rhinitis and chronic rhinosinusitis remain to be elucidated. This study investigated the expression of pendrin and periostin in sinonasal tissue of patients with allergic rhinitis, chronic rhinosinusitis, and aspirin-induced asthma. Prospective control study conducted at Yamagata University, Japan. Methods : Surgical samples were investigated by means of real-time reverse transcription-polymerase chain reaction to evaluate the expression of pendrin and periostin mRNA. The presence and location of pendrin and periostin were determined by immunohistochemistry and Western blotting. Results : Pendrin and periostin production was significantly higher in patients with nasal disorders than in controls. Further significant increases in periostin expression were noted in patients with chronic rhinosinusitis with nasal polyps and in those with aspirin-induced asthma. Immunohistochemistry revealed positive staining for pendrin in epithelial cells and submucosal glands and for periostin in the basement membrane in all three disorders, and additionally for periostin in nasal polyp tissue in chronic rhinosinusitis and aspirin-induced asthma. Conclusions : Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin- induced asthma.

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

Objective: Intratympanic (IT) steroid therapy has been proposed as an alternative treatment option for patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, the number and frequency of IT treatments and drug delivery methods remain to be determined. The purpose of this study was to evaluate the efficacy of daily short-term IT dexamethasone (DEX) treatment alone in ISSNHL patients using laser-assisted myringotomy (LAM) for the drug delivery route as an initial and/or salvage treatment. Study Design: Retrospective study. Setting: University hospital. Patients: Seventy-six ISSNHL patients receiving IT DEX. Patients with low-tone hearing loss, unilateral or bilateral fluctuating hearing loss or contralateral hearing loss were excluded. Intervention: DEX (4 mg/ml) was injected through a perforation made by LAM. IT DEX administration was performed on 8 sequential days. Main Outcome Measures: Pre- and postprocedure hearing levels. The average hearing level was determined by 5 frequencies (250, 500, 1000, 2000 and 4000 Hz). Results: Nineteen out of 76 patients fit the criteria for initial treatment in the study (group I), while 24 patients, who had failed systemic therapy, received salvage treatment (group S). The mean age of the patients in groups I and S was 56.2 years with a range from 31 to 73 years of age and 46.0 years with a range from 11 to 76 years of age, respectively. The mean number of days from onset of symptoms to IT therapy in groups I and S was 4.8 days with a range of 1–23 days and 15.3 days with a range of 6–28 days, respectively. In group I, 18 of the 19 patients (95%) showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 40 dB. Twelve patients (63%) recovered completely and 16 patients (84%) demonstrated successful results with an improvement of more than 30 dB. In group S, 14 of the 24 patients (58%) showed improvement of more than 10 dB with a mean improvement of 16 dB. Two (8%) of the 7 patients (29%) with successful results recovered completely. Conclusions: Daily short-term IT DEX administration using LAM for ISSNHL patients without concurrent therapy showed a high response rate and high cure rate and proved to be an alternative therapeutic option to high-dose systemic steroids as a first- and/or second-line treatment.

Mutations in the connexin26 gene (GJB2) are the most common genetic cause of congenital bilateral non-syndromic sensorineural hearing loss. Transgenic mice were established carrying human Cx26 with the R75W mutation that was identified in a deaf family with autosomal dominant negative inheritance [Kudo T et al. (2003) Hum Mol Genet 12:995-1004]. A dominant-negative Gjb2 R75W transgenic mouse model shows incomplete development of the cochlear supporting cells, resulting in profound deafness from birth [Inoshita A et al. (2008) Neuroscience 156:1039-1047]. The Cx26 defect in the Gjb2 R75W transgenic mouse is restricted to the supporting cells; it is unclear why the auditory response is severely disturbed in spite of the presence of outer hair cells (OHCs). The present study was designed to evaluate developmental changes in the in vivo and in vitro function of the OHC, and the fine structure of the OHC and adjacent supporting cells in the R75W transgenic mouse. No detectable distortion product otoacoustic emissions were observed at any frequencies in R75W transgenic mice throughout development. A characteristic phenotype observed in these mice was the absence of the tunnel of Corti, Nuel's space, and spaces surrounding the OHC; the OHC were compressed and squeezed by the surrounding supporting cells. On the other hand, the OHC developed normally. Structural features of the lateral wall, such as the membrane-bound subsurface cisterna beneath the plasma membrane, were intact. Prestin, the voltage-dependent motor protein, was observed by immunohistochemistry in the OHC basolateral membranes of both transgenic and non-transgenic mice. No significant differences in electromotility of isolated OHCs during development was observed between transgenic and control mice. The present study indicates that normal development of the supporting cells is indispensable for proper cellular function of the OHC.

Office treatment for chronic tympanic membrane (TM) perforations has limitations, and alternative methods to myringoplasty are sometimes needed. Serum lacks antigenicity and contains a large variety of growth factors known to modulate proliferation of various tissues to promote wound healing effects. Our purpose was to evaluate the feasibility of autologous serum eardrops therapy with a chitin membrane for closing TM perforations.In the outpatient clinic, the perforation margin was cauterized with silver nitrate, and the perforation was covered with a chitin membrane. Patients were instructed to apply autologous serum eardrops daily. Patients were examined every 2 weeks, and the procedure was repeated.We treated 19 sequential patients with chronic TM perforation in 1 ear between October 2005 and September 2007. Closure of the TM was achieved in 11 (58%) of 19 ears, and reduction of the perforation size was observed in 2 ears (11%). Closure rates for small, medium, and large perforations were 57 (8 of 14), 0 (0 of 1), and 75% (3 of 4), respectively. Closure rates for perforations attributable to intratympanic dexamethasone treatment, after myringoplasty and chronic otitis media were 67 (2 of 3), 67 (2 of 3), and 54% (7 of 13), respectively. Time for closure took from 15 to 175 days, with an average of 68 days (5.9 clinic visits). During autologous serum eardrop therapy with a chitin membrane, no remarkable side effects in the treated ears were observed. Measurement of the concentration of the epidermal growth factor, transforming growth factor beta1, fibronectin, and interleukin 6 in the serum showed no decrease in 14 days, suggesting activity remained stable in that period.Autologous serum eardrops therapy with a chitin membrane, which requires no surgical intervention, was found to be a promising office-based technique for the closure of chronic TM perforations because of its ease, safeness, and feasibility. However, additional studies are needed to independently analyze the specific benefits of the serum drops and the chitin membrane.

今回我々は, 多人数の町民を対象とした岩木健康増進プロジェクトの一環として, 20歳以上の弘前市の旧岩木町民のうち956名に対して, 聴覚検診とアンケート調査を行い, 年代別聴力像と種々の検査項目との関連について検討した。年代別平均聴力閾値は年代順に上昇しており, 特に高音域でその上昇幅が増大していた。また, 男女別聴力像では, 1,000Hzにおいては男女間に有意差を認めなかったが, 4,000Hzにおいては50歳代以降の男性が女性に比べて有意に閾値が上昇していた。男性の騒音暴露の機会が多いことが誘因と考えられ, 農業従事者が多いという調査地域の特性がその一因ではないかと考えた。さらに, 耳鳴, 耳閉感, 難聴については, それぞれ32.2%, 15.9%, 36.9%の人が自覚していた。難聴を自覚する人は70歳代以降で多くみられたが, 耳鳴を訴える人は80歳代で減少した。