Association of Matrix Metalloproteinase-2 mRNA Expression with Subtypes of Pediatric Cholesteatoma.

OBJECTIVE: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed MMP2 mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples. METHODS: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization. RESULTS: There were no significant differences in MMP2 mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type (p < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida (p < 0.001). MMP2 mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium. CONCLUSION: Our study reveals that MMP2 mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of MMP2 mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.

Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy.

Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.

Availability of audiological evaluation for the differential diagnosis of clinical otosclerosis.

OBJECTIVE: The availability of an audiological evaluation for the differential diagnosis of clinical otosclerosis (OS) was examined. METHODS: Included were 98 patients (107 ears) with OS and 19 patients (20 ears) with incudostapedial disconnection (ISD) diagnosed by surgery between 2009 and 2017 at Aichi University Hospital. Results of preoperative pure-tone audiometry and impedance audiometry were analyzed. The most reliable index for distinguishing the two diseases was evaluated, and the cut-off value, sensitivity, and specificity were calculated. RESULTS: In the univariate analysis, age, static compliance, reversed ipsilateral acoustic reflex (reversed IAR) at 0.5 kHz and 2 kHz, negative contralateral acoustic reflex (negative CAR), difference between the air-bone gap at 0.25 and 2 kHz (0.25-2 kHzABG) and that at 0.25 and 4 kHz (0.25-4 kHzABG) showed statistical significance between the two diseases, whereas the Carhart notch did not. Multivariate logistic regression analysis by the variable selection method showed that reversed IAR (0.5 kHz), negative CAR, and 0.25-4 kHzABG were statistically significantly better factors for the differential diagnosis of the two diseases. The receiver operating characteristic curve for diagnosing OS using the difference between air-bone gap at 0.25 kHz and 4 kHz showed moderate accuracy. If the cut-off value of 0.25-4 kHzABG was 10 dB, then the sensitivity and specificity were 81.1% and 55.0%, respectively. In other words, if the cut-off value of 0.25-4 kHzABG was less than 10 dB, then the possibility of diagnosing ISD becomes higher, and if greater than 10 dB, then the possibility of diagnosing OS becomes higher. CONCLUSION: The differences in the air-bone gap at low and high frequency in pure-tone audiometry, static compliance, and acoustic reflex in impedance audiometry are useful for distinguishing OS from ISD. However, combinations of several examinations including computed tomography imaging are needed for the differential diagnosis of other ear diseases and specific preoperative planning.

A novel larynx-preserving pharyngectomy technique using a thyroid gland flap after chemoradiotherapy.

This case report describes larynx-preserving pharyngectomy after chemoradiotherapy using a thyroid gland flap. A thyroid gland flap has good blood supply and reconstruction can be done in the same surgical field. The thyroid gland flap has potential as a novel appropriate flap for use in head and neck surgery.