Risk factors for occurrence and progression of external auditory canal cholesteatoma.

OBJECTIVE: External auditory canal cholesteatoma (EACC) is characterized by retained squamous debris within the external canal and variable amounts of localized bone destruction. The etiology of primary EACC remains incompletely understood. This study was conducted to analyze the clinical features and backgrounds of patients with primary EACC and to clarify the risk factors for the occurrence and progression of EACC. METHODS: Sixty-nine ears of 62 patients diagnosed with primary EACC were included in this study (EACC group). Additionally, 74 ears of 60 patients with chronic otitis media (COM) with perforation who underwent tympanoplasty or myringoplasty were included as controls (COM group). We retrospectively investigated the clinical features, life history, and medical history of the patients in both groups. In addition, to investigate the risk factors for progression of EACC, we compared the clinical features and medical history of patients with stage IV (advanced) disease versus stage I + II (mild) disease. RESULTS: The inferior wall of the bony canal was the main structure affected in patients with primary EACC of all stages. The following factors were significantly more common in the EACC than COM group: older age, female sex, left-sided disease, osteoporosis, renal dysfunction, anemia, and treatment with bisphosphonates. Among these, the most significant factor associated with EACC was renal dysfunction (odds ratio, 11.4; 95 % confidence interval, 2.32-55.9). The significant factors observed in patients with stage IV disease were younger age, male sex, posterior wall involvement, and otorrhea. Surgical treatment was required for more than half of the patients with stage III and IV EACC. CONCLUSION: Patients with renal dysfunction are at risk of primary EACC. In particular, younger patients and relatively younger elderly patients with posterior wall involvement have a risk of progression to advanced-stage EACC. Canalplasty should be considered in patients with EACC who have these risk factors to prevent progression to advanced-stage disease.

Site of distant metastasis affects the prognosis with recurrent/metastatic head and neck squamous cell carcinoma patients treated with Nivolumab.

BACKGROUND: Nivolumab is approved for the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the influence of the site of distant metastasis on the efficacy of immune checkpoint inhibitor in R/M HNSCC remains unclear. We investigated the prognosis of R/M HNSCC patients treated with nivolumab, focusing on the site of distant metastasis. METHODS: We reviewed the data of R/M HNSCC patients treated with nivolumab between April 2017 and June 2020 at Saitama Prefectural Cancer Center. The differences in the prognosis were evaluated according to the site of distant metastasis. RESULTS: Of the 41 patients enrolled, 26 (63.4%) had lung metastasis, 7 (17.1%) had bone metastasis, and 4 (9.8%) had liver metastasis. Ten patients (24.4%) had single-organ distant metastasis (lung metastasis in all cases). Univariate analysis identified lung metastasis alone (single-organ distant metastasis) was associated with a significantly better prognosis [HR0.37 (95% CI) 0.14-0.97 p = 0.04], while liver metastasis was associated with a significantly worse prognosis [HR3.86 (95% CI) 1.26-11.8 p = 0.02]. Multivariate analysis identified lung metastasis alone and liver metastasis as independent prognostic factors. While 7 patients (70%) with lung metastasis alone could be continued on nivolumab treatment or received subsequent chemotherapy, only 1 patient (25%) with liver metastasis received subsequent chemotherapy. CONCLUSION: The site of distant metastasis affects the prognosis of R/M HNSCC patients treated with nivolumab. Lung metastasis alone appears to be associated with a better prognosis, in that it allows easier transition to subsequent chemotherapy, while liver metastasis associates with a worse prognosis.

Myringoplasty for Eosinophilic Otitis Media.

OBJECTIVE: Surgical intervention of eosinophilic otitis media (EOM) has been considered contraindicated because middle ear surgery is associated with a risk of deafness. Myringoplasty is believed to be less invasive. Therefore, we analyzed the surgical results of myringoplasty for perforated eardrums in patients with EOM treated by biological drugs (biologics). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Nine ears of seven patients with EOM with eardrum perforation associated with bronchial asthma were treated with add-on biologics; myringoplasty was then performed. The controls comprised 17 ears of 11 patients with EOM treated by myringoplasty without biologics. INTERVENTIONS: The EOM status of each patient of both groups was assessed using severity scores, hearing acuity, and temporal bone computed tomography scores. MAIN OUTCOME MEASURES: Preoperative and postoperative changes in severity scores and hearing acuity, postoperative closure of the perforation, and relapse of EOM. RESULTS: Severity scores significantly decreased after the use of biologics but did not change after myringoplasty. One patient developed postoperative relapse of middle ear effusion (MEE); in the control group, however, 10 ears developed recurrence of MEE. Significant improvement of the air conduction hearing level was obtained in the biologics group. No patients showed deterioration of the bone conduction hearing level. CONCLUSIONS: This is the first report to describe successful surgical interventions with add-on biologics for patients with EOM. In the era of biologics, surgical interventions such as myringoplasty will be indicated to improve hearing and to avoid recurrence of MEE in patients with EOM with perforated eardrums, with the use of biologics.

Clinical characteristics of atelectatic eardrums and adhesive otitis media in children.

OBJECTIVES: Atelectatic eardrum and adhesive otitis media in children are related to persistent otitis media with effusion (OME) and eustachian tube dysfunction in infancy. However, the pathogenesis of these diseases is not fully understood, and some cases even progress to pars tensa cholesteatoma. This study analyzed the clinical characteristics of children with atelectatic eardrum and adhesive otitis media to clarify associated causes of and risk factors for progression of these middle ear pathologies in children. PATIENTS AND METHODS: This retroactive study included 38 ears of 31 children with atelectatic eardrums (atelectasis group), and 19 ears of 17 children with adhesive otitis media (adhesive OM group). Thirty-two contralateral non-cholesteatoma ears of 32 children with congenital cholesteatoma were also examined as a control group. Participants were aged 15 or younger. Life history (obtained via questionnaire), associated diseases, hearing acuity, aeration and development of the temporal bone were investigated. RESULTS: All children in the atelectasis and adhesive OM groups had a history of recurrent acute otitis media (rAOM) and/or OME. The prevalence of perennial allergic rhinitis was 18 cases (58%) in the atelectasis group and 16 cases (94%) in the adhesive OM group. The prevalence of perennial allergic rhinitis was significantly higher in the adhesive OM group compared to the control group (P < 0.01). The development of mastoid air cells, categorized by MC classification, showed MC0 + MC1 (poor pneumatization) in 19 ears (50.0%) with atelectatic eardrums and 12 ears (63.2%) with adhesive OM. Poor pneumatized mastoid was more frequently observed in the ears of the atelectasis and adhesive OM groups compared to the control group (P < 0.01). No significant difference was found in regards to aeration of the middle ear between the two groups; however, aeration was significantly poorer in both groups compared to the control group (P < 0.01). Three characteristics were analyzed using multivariate logistic regression: perennial allergic rhinitis (odds ratio [OR] 4.319, P = 0.013), poor mastoid pneumatization (OR 8.457, P = 0.012), and pars flaccida retraction pocket (OR 20.897, P = 0.006). These characteristics were shown to be significant risk factors for atelectatic eardrums and adhesive OM. In addition, the predisposition to perennial allergic rhinitis was shown to be the most important factor in the progression from atelectatic eardrum to adhesive otitis media (OR 16.615, P = 0.012). CONCLUSION: Children with perennial allergic rhinitis, poor development of mastoid air cells, poor aeration of the temporal bone, and with pars flaccida retraction pocket were at an increased risk of developing an atelectatic eardrum and adhesive OM. In particular, perennial allergic rhinitis was shown to be a significant risk factor in the progression from atelectatic eardrum to adhesive otitis media. Allergic inflammation may affect not only the nasal passages but also the eustachian tube, resulting in persistent middle ear dysfunction. Therefore, children with rAOM/OME who have these risk factors should be carefully monitored and treat over time in effort to prevent progression of pathology.

[SUCCESSFUL TREATMENT FOR OTITIS MEDIA AND SINUSITIS ASSOCIATED WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS USING ANTI-IL-5 RECEPTOR MONOCLONAL ANTIBODY BENRALIZUMAB].

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-related vasculitis. Asthma and sinusitis occur first in the course of EGPA, followed by vasculitis symptoms such as fever, weight loss, and peripheral neuropathy. Otitis media with effusion and sensorineural hearing loss occur occasionally in EGPA patients. Here we report a case of a 39-years-old female patient with asthma that developed at age 37 and sinusitis. The patient was diagnosed with EGPA and treatment was started with oral corticosteroids. During the course of treatment, otitis media with effusion and sensorineural hearing loss developed. Benralizumab was administered for severe asthma. After treatment with benralizumab, the symptoms of asthma, otitis media with effusion and sinusitis dramatically improved. This is the first reported case in which benralizumab was used for treating otitis media and sinusitis associated with EGPA. The findings suggest that benralizumab may be effective for otitis media and sinusitis associated with EGPA.

Comparative study on adhesive otitis media and pars tensa cholesteatoma in children.

OBJECTIVE: Recurrent otitis media and persistent otitis media with effusion in early childhood may cause an atelectatic eardrum and adhesive otitis media, which sometimes progress to pars tensa cholesteatoma. When and how children with adhesive otitis media should be operated on remain controversial. Therefore, this study aimed to analyze the clinical characteristics of children with adhesive otitis media and pars tensa cholesteatoma, and to determine the risk factors of progression to cholesteatoma. METHODS: Seventeen ears of 15 children with adhesive otitis media (adhesive group) and 14 ears of 13 children with pars tensa cholesteatoma (tensa cholesteatoma group) who underwent tympanoplasty were included in this study. We analyzed the following clinical characteristics of children in both groups: medical and life history, associated diseases, sites of the adhesion, and development and aeration of mastoid air cells as shown by temporal bone computed tomography. RESULTS: Most of the children in both groups had a history of recurrent otitis media and/or persistent otitis media with effusion. They showed a male predominance and a frequent association of allergic rhinitis. The number of ears showing undeveloped mastoid air cells in the tensa cholesteatoma group was significantly larger than that in the adhesive otitis media group (P=0.0068). A lack of aeration of the middle ear, including the eustachian tube, was more frequently found in ears with pars tensa cholesteatoma than in ears with adhesive otitis media (P=0.0012). Using multivariate logistic regression, the presence of otorrhea (odds ratio [OR], 14.847; 95% confidence interval [CI], 0.834-264.184), total adhesion (OR, 28.550; 95% CI, 0.962-847.508), and undeveloped mastoid air cells (OR, 19.357; 95% CI, 1.022-366.589) were related to pars tensa cholesteatoma. CONCLUSION: Children with adhesive otitis media should be carefully followed up in the outpatient setting. Ears with poor mastoid development may develop pars tensa cholesteatoma. Additionally, ears with middle ear effusion, total adhesion, and the presence of otorrhea tend to be at risk of pars tensa cholesteatoma. Tympanoplasty or tympanostomy tube insertion should be considered for children with adhesive otitis media who have these risk factors to prevent progression to pars tensa cholesteatoma.

Cancer of the mandibular gingiva metastasizing to the small intestine.

Head and neck cancer metastasizing to the small intestine is very rare. Here we report a case of cancer of the mandibular gingiva metastasizing to the small intestine. The patient was an 82-year-old man who had squamous cell carcinoma of the mandibular gingiva staged as T2N2bM0. Two months after surgery, he presented with lower abdominal pain accompanied by signs of peritoneal irritation. Urgent abdominal surgery was performed, during which a crater-shaped perforation was noted on the wall of the ileum. Microscopic findings at this site confirmed a diagnosis of metastatic squamous cell carcinoma in the small intestine from the mandibular gingiva. To our knowledge, this is the first case report of oral cancer metastasizing to the small intestine. If gastrointestinal symptoms appear in a patient with advanced oral cancer, a differential diagnosis of metastasis to the gastrointestinal tract should be kept in mind.

High-Concentration Synthesis of Sub-10-nm Copper Nanoparticles for Application to Conductive Nanoinks.

A simple, high-concentration (up to 0.6 M Cu salt) synthesis of sub-10-nm copper nanoparticles (Cu NPs) was developed in ethylene glycol at room temperature under ambient air conditions using 1-amino-2-propanol (AmIP) as the stabilizer. Monodispersed AmIP-Cu NPs of 3.5 ± 1.0 nm were synthesized in a high yield of ∼90%. Thus, nearly 1 g of sub-10-nm Cu NP powder was obtained using a one-step synthesis for the first time. It is proposed that metallacyclic coordination stability of a five-membered ring type between the Cu and AmIP causes the high binding force of Am IP onto the Cu surface, resulting in the superior stability of the AmIP-Cu NPs in a solution. The purified powder of AmIP-Cu NPs can be redispersed in alcohol-based solvents up to high Cu contents of 45 wt % for the preparation of Cu nanoink. The resistivity of the conductive Cu film obtained from the Cu nanoink was 30 µΩ cm after thermal heating at 150 °C for 15 min under a nitrogen flow. The long-term resistance stability of the Cu film under an air atmosphere was also demonstrated.