Accuracy of High-Resolution Computed Tomography Compared to High-Definition Ear Endoscopy to Assess Cholesteatoma Extension.

OBJECTIVE: To correlate radiographic evidence of cholesteatoma in the retrotympanum with intraoperative endoscopic findings in cholesteatoma patients and to evaluate the clinical relevance of radiographic evidence of cholesteatoma in the retrotympanum. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. METHODS: Seventy-six consecutive cases undergoing surgical cholesteatoma removal with preoperative high-resolution computed tomography (HRCT) were enrolled in this study. A retrospective analysis of the medical records was conducted. The extension of cholesteatoma regarding different middle ear subspaces, into the antrum and mastoid were reviewed radiologically in preoperative HRCT and endoscopically from surgical videos. Additionally, facial nerve canal dehiscence, infiltration of the middle cranial fossa, and inner ear involvement were documented. RESULTS: Comparison of radiological and endoscopic cholesteatoma extension revealed statistically highly significant overestimation of radiological cholesteatoma extension for all retrotympanic regions (sinus tympani 61.8% vs 19.7%, facial recess 69.7% vs 43.4%, subtympanic sinus 59.2% vs 7.9%, and posterior sinus 72.4% vs 4.0%) and statistically significant overestimation for mesotympanum (82.9% vs 56.6%), hypotympanum (39.5% vs 9.2%), and protympanum (23.7% vs 6.6%). No statistically significant differences were found for epitympanum (98.7% vs 90.8%), antrum (64.5% vs 52.6%), and mastoid (26.3% vs 32.9%). Statistically significant radiological overestimation of facial nerve canal dehiscence (54.0% vs 25.0%) and invasion of tegmen tympani (39.5% vs 19.7%) is reported. CONCLUSION: Radiologic cholesteatoma extension in different middle ear subspaces is overestimated compared to the intraoperative extension. The preoperative relevance of radiological retrotympanic extension might be limited in the choice of approach and transcanal endoscopic approach is always recommended first.

Differentiated Papillary NUT Carcinoma: An Unexpected, Deceptively Bland Presentation of a Sinonasal Carcinoma.

BACKGROUND: In recent years, the list of tumor entities in the sinonasal tract has significantly expanded, requiring advanced diagnostic testing. We report the case of a 32-year-old patient with an unusual NUT carcinoma originating in the maxillary sinus, which showed extensive well-differentiated, papillary squamous morphology, similar to the spectrum of the recently described DEK::AFF2 fusion-associated carcinoma. METHODS: We performed immunohistochemical and molecular studies including EBV- and HPV-testing, as well as DNA/RNA next generation sequencing. RESULTS: The tumor showed predominantly exophytic papillary growth with mature squamous differentiation. An additional component harbored atypical, less differentiated basaloid tumor cells with infiltration of the adjacent stroma. Conspicuous inflammation was evident. There was no evidence of HPV DNA or EBV RNA. Next-generation sequencing revealed a NUT::NSD3 gene fusion corresponding to ("speckled-type") immunopositivity of NUT in the tumor cells. CONCLUSIONS: We describe a NUT::NSD3 gene fusion-associated NUT carcinoma of the sinonasal tract with a deceptively well-differentiated papillary growth pattern, thus expanding the morphological spectrum of this typically poorly differentiated neoplasm.

Variability of the retrotympanum and its association with mastoid pneumatization in cholesteatoma patients.

PURPOSE: This study aimed to investigate the variability of the retrotympanum in patients undergoing surgical treatment for cholesteatoma. METHODS: We included 59 ears of patients undergoing middle ear surgery for cholesteatoma who had preoperative computed tomography scans. A retrospective analysis of the medical records was conducted. The sinus tympani (ST), subtympanic sinus (STS) and facial recess (FR) were classified into types A-C based on the relationship of their extension to the facial nerve. The mastoid and petrous apex were assessed and categorized as normal pneumatized or sclerotic. RESULTS: Type A extension was the most frequently found in all sinuses (ST 64%, FR 77%, STS 69%), Type B extension was found more often in ST (34%) and STS (24%) than in FR (15%). A very deep extension was found only rarely (ST 2%, FR 8%, STS 7%). A sclerotic mastoid was found in 67% of cases. Those cases showed a statistically significant difference regarding retrotympanum pneumatization when compared with normal mastoid. CONCLUSION: The most frequent variant of retrotympanic pneumatization in relation to the facial nerve was type A in all subsites in cholesteatoma patients. The variability among patients with cholesteatoma is different to previously published results in healthy subjects. Moreover, the pneumatization of the retrotympanum is associated with mastoid pneumatization.

Signal Alteration of the Inner Ear on High-Resolution Three-Dimensional Constructive Interference in Steady State Sequence in Patients with Ménière's Disease and Labyrinthitis.

INTRODUCTION: The aim of this study is to evaluate signal alteration in the inner ear using three-dimensional (3D)-constructive interference in steady state (CISS) sequence in patients with Ménière's disease and labyrinthitis and its correlation with clinical and audiological parameters. METHODS: The medical records of the department of otorhinolaryngology were searched for patients with Ménière's disease or labyrinthitis who underwent MRI with 3D-CISS sequence. Blinded analysis of these patients and of MRI from control subjects without middle or inner ear symptoms was performed to detect any signal asymmetry of the inner ear structures. The results were correlated with clinical symptoms and results of audiological and vestibular tests. RESULTS: Fifty-eight patients with definite Ménière's disease and 5 patients with labyrinthitis as well as 41 control exams were included. A separate analysis was performed for patients with probable Ménière's disease (n = 68). A total of 172 3D-CISS sequences were analyzed by 2 blinded independent neuroradiologists. A CISS-hypointense signal of the inner ear structures was found in 3 patients with definite Ménière's disease (5.2%), in 4 patients with probable Ménière's disease (5.9%), and 2 patients with labyrinthitis (40%). No CISS hypointensity was found in the control group. Although no significant difference in symptoms or audiological test results was found between patients with and without this signal change, the side of hypointensity was frequently correlated with the symptomatic side and with hearing impairment. DISCUSSION/CONCLUSION: CISS hypointensity of the inner ear structures was evident in patients with clinical conditions other than vestibular schwannoma - more frequently in labyrinthitis than in Ménière's disease. This signal alteration was frequently encountered on the same symptomatic side as that of the pathological audiology tests, but it is not a predictor for hearing or vestibular impairment.

Surgical implications of 3D vs 2D endoscopic ear surgery: a case-control study.

PURPOSE: To compare 3D to 2D technology in endoscopic ear surgery (EES); to report surgeons' feedback on the use of 3D in EES; to describe the operative setting for 3D EES. METHODS: A case-control study on EES was performed at a tertiary university center. All consecutive cases of 3D EES (case group) were matched to a control group operated with the standard 2D technique. Data on surgical approach, type of surgery, operative time, outcomes, and complications were compared between the two groups. After each surgery, the operating surgeons were asked to give a feedback on the use of 3D endoscopy, filling in a questionnaire based on 5-point Likert scales. RESULTS: None of the 3D procedures was switched to 2D. Nor intraoperative or long-term complications were recorded. The operative time was similar in both groups. Postoperative hearing function did not show any statistically significant difference between 3 and 2D patients. Ninety-six percent of participants agreed or strongly agreed on better views of anatomy and pathology with the 3D technique. Discomfort induced by 3D vision was rarely reported. CONCLUSION: Surgical and functional results from EES respectively performed with 3D and 2D systems are overall similar, suggesting that both techniques are safe and effective. According to the surgeons' feedback, 3D provides better depth perception and improved view of anatomy and pathology. Several surgeons are willing to use the 3D system for future EES. To guarantee the best 3D EES experience, the setting in the operating room plays a crucial role.

Cancer therapy modulates VEGF signaling and viability in adult rat cardiac microvascular endothelial cells and cardiomyocytes.

This work was motivated by the incomplete characterization of the role of vascular endothelial growth factor-A (VEGF-A) in the stressed heart in consideration of upcoming cancer treatment options challenging the natural VEGF balance in the myocardium. We tested, if the cytotoxic cancer therapy doxorubicin (Doxo) or the anti-angiogenic therapy sunitinib alters viability and VEGF signaling in primary cardiac microvascular endothelial cells (CMEC) and adult rat ventricular myocytes (ARVM). ARVM were isolated and cultured in serum-free medium. CMEC were isolated from the left ventricle and used in the second passage. Viability was measured by LDH-release and by MTT-assay, cellular respiration by high-resolution oxymetry. VEGF-A release was measured using a rat specific VEGF-A ELISA-kit. CMEC were characterized by marker proteins including CD31, von Willebrand factor, smooth muscle actin and desmin. Both Doxo and sunitinib led to a dose-dependent reduction of cell viability. Sunitinib treatment caused a significant reduction of complex I and II-dependent respiration in cardiomyocytes and the loss of mitochondrial membrane potential in CMEC. Endothelial cells up-regulated VEGF-A release after peroxide or Doxo treatment. Doxo induced HIF-1α stabilization and upregulation at clinically relevant concentrations of the cancer therapy. VEGF-A release was abrogated by the inhibition of the Erk1/2 or the MAPKp38 pathway. ARVM did not answer to Doxo-induced stress conditions by the release of VEGF-A as observed in CMEC. VEGF receptor 2 amounts were reduced by Doxo and by sunitinib in a dose-dependent manner in both CMEC and ARVM. In conclusion, these data suggest that cancer therapy with anthracyclines modulates VEGF-A release and its cellular receptors in CMEC and ARVM, and therefore alters paracrine signaling in the myocardium.