Endolymphatic Sac Tumors Associated With von Hippel-Lindau: A Case Report Highlighting Opportunity for Novel Orphan Drug Therapy.

OBJECTIVE: To discuss the potential benefit of belzutifan therapy in a patient with von Hippel-Lindau (VHL) disease-associated endolymphatic sac tumor (ELST). PATIENTS: Case report. INTERVENTIONS: Clinical details of a patient with residual ELST after hearing preservation surgery who initiated belzutifan therapy postoperatively for concurrent renal cell carcinoma, as well as literature review of belzutifan and ELST. MAIN OUTCOME MEASURES: The patient remained without radiologic evidence of growth of her residual tumor at 17 months post-initiation of belzutifan. It is unknown whether this represents therapeutic drug effect, nonviability of residual tumor, or slow tumor growth not captured radiographically within the duration of follow-up. CONCLUSIONS: Belzutifan could have direct therapeutic benefit in patients with VHL-associated ELST.

Efficacy of endolymphatic duct blockage in treating Ménière's disease. / å† æ·‹å·´ç®¡å¤¹é—­æœ¯æ²»ç–—æ¢ å°¼åŸƒç— çš„æ•ˆæžœ.

OBJECTIVES: Ménière's disease (MD) is an idiopathic inner ear disorder characterized by recurrent episodes of episodic rotational vertigo, fluctuating hearing loss, tinnitus, and a feeling of ear stuffiness. Endolymphatic sac (ES)-related surgery is used primarily in patients with MD who have failed to respond to pharmacologic therapy. Endolymphatic duct blockage (EDB) is a new procedure for the treatment of MD, and related clinical studies are still scarce. This study aims to investigate the dynamic changes in endolymphatic hydrops (EH) and the long-term surgical outcomes in MD patients undergoing EDB, and to evaluate the impact of different types of ES on the surgical efficacy. METHODS: A retrospective analysis was conducted on 33 patients with refractory MD who underwent EDB. Based on the morphology of their endolymphatic sacs, patients were divided into a normal-type group (n=14) and an atrophic-type group (n=19). The frequency of vertigo symptoms, hearing, vestibular function, and the dynamic changes of gadolinium-enhanced MRI of the inner ear were compared were compared before and after surgery between the 2 groups. RESULTS: Compared with the atrophic-type group, the patients in the normal-type group had a higher rate of complete vertigo control, better cochlear and vestibular function, and a lower endolymph to vestibule volume ratio (all P<0.05). In addition, 7 patients in the normal-type group were found to have reversal of EH, while no reversal of EH was detected in the atrophic-type group after surgery. CONCLUSIONS: The response to EDB treatment varies between normal and atrophic MD patients, suggesting that the 2 pathological types of endolymphatic sacs may have different underlying mechanisms of disease.

Retrolabyrinthine Bone Thickness as a Radiologic Marker for the Hypoplastic Endotype in Menière Disease.

BACKGROUND AND PURPOSE: Menière disease (MD) manifests in 2 major endotypes: one with a hypoplastic, underdeveloped endolymphatic sac (MD-hp) and the other with a normally developed sac that degenerates over time (MD-dg). Determining the specific endotype in patients is important for predicting disease progression, tailoring patient counseling, and optimizing treatment strategies. Endotype diagnosis involves measuring an angular trajectory of the vestibular aqueduct (ATVA), with an ATVA ≥140° indicative of MD-hp and an ATVA ≤120° of MD-dg. However, assessing the ATVA can be challenging. This study aimed to explore the link between ATVA and the thickness of the retrolabyrinthine bone as an alternative diagnostic measure that could provide differentiation between MD endotypes using CT and MR imaging. MATERIALS AND METHODS: Retrospective review of CT temporal bone imaging from 32 adult patients with definite MD (60 ears) and 33 age-matched controls without MD or other inner ear symptoms (61 ears) was performed. The ATVA and retrolabyrinthine bone thickness were measured using uniform methodology on standardized axial CT images. Comparative analyses were performed to determine the correlation between ATVA and retrolabyrinthine bone thickness. Additionally, from a separate cohort of 11 patients (22 ears), CT and MR examinations of the temporal bone were retrospectively reviewed for retrolabyrinthine bone thickness measurements, to verify the correlation across the 2 modalities. RESULTS: The average retrolabyrinthine bone thickness was statistically significantly different between MD endotypes, being a mean of 0.8 (SD, 0.3) mm in patients with MD-hp (ATVA ≥140°) and 2.0 (SD, 0.9) mm in patients with MD-dg (ATVA ≤120°), with a consistent pattern of thin retrolabyrinthine bone in MD-hp and variable thickness in MD-dg. Receiver operating characteristic curve analysis within the MD cohort revealed that a retrolabyrinthine bone thickness ≥1.2 mm effectively rules out MD-hp. Excellent interrater reliability was noted for the retrolabyrinthine measurement, and there was near-perfect correlation between CT and MR measurements. CONCLUSIONS: Retrolabyrinthine bone thickness proved to be a useful and straightforward alternative marker for distinguishing MD endotypes, being particularly useful for excluding MD-hp. Including information on retrolabyrinthine bone thickness should be considered a routine part of reporting in the context of MD imaging.

Endolymphatic sac tumor misdiagnosed as metastatic renal cell carcinoma: Pitfalls in morphology and immunohistochemistry.

Endolymphatic sac tumor (ELST) is a rare disease that originates from the endolymphatic sac system of the inner ear. Being a low-grade malignant tumor, ELST has a mild morphology and is characterized by a slow but aggressive growth. Most clinicians and pathologists are unfamiliar with this disease. ELST can be misdiagnosed as metastatic renal cancer because of the similarity in morphology and expression of nephrogenic markers such as PAX8. The presented case of a 27-year-old man revealed that observing the characteristic location and confirming the absence of renal neoplasm to rule out the possibility of metastasis are critical for obtaining an accurate final diagnosis.

A New Methodology for Evaluation of Large Vestibular Aqueduct in CT and MRI Images.

HYPOTHESIS: Development of a new method for large vestibular aqueduct (LVA)/large endolymphatic sac anomaly (LESA) assessment using magnetic resonance imaging (MRI) and computed tomography (CT)/cone beam CT (CBCT) images. The secondary objective was to compare both modalities. BACKGROUND: The gold standard for LVA diagnosis is the analysis of CT images using Valvassori and Clemis or Cincinnati criteria. The previous studies showed inconclusive results regarding the correlation between audiological and radiological data. METHODS: Retrospective analysis of radiological images from 173 patients (315 ears), who were diagnosed with LVA/LESA based on CT/CBCT and/or MRI images of the temporal bone. The images obtained using both techniques were used to measure the following dimensions of vestibular aqueduct (VA)/endolymphatic duct (ED)/intraosseous endolymphatic sac (ES): width of the opening, length, and width at external aperture. In MRI images, the maximal contact diameters of the extraosseous or intraosseous ES and dura mater were measured as well. RESULTS: LVA has been reported to be bilateral in 82% (142 patients) and unilateral in 18% (31 patients) of cases. Comparison of MRI and CT/CBCT measurements showed a moderate correlation (0.64) in external aperture, a moderate correlation (0.57) in the width of the VA opening, and a weak correlation (0.34) in length measurements (p < 0.05). CONCLUSION: We developed a new method to identify the heterogeneous pathology of LVA/LESA using reconstruction along the VA/ED/intraosseous ES axis, three measurements on two planes, and focus on the maximal contact diameter between the extraosseous or intraosseous ES and dura mater.

Functional outcomes and caloric response changes after endolymphatic sac decompression.

OBJECTIVE: To evaluate caloric response changes after endolymphatic sac decompression (ESD), together with hearing outcomes and the functional benefit of the operation. METHODS: A retrospective chart review of subjects who underwent endolymphatic sac decompression at a tertiary referral centre was performed. Data on audiological results, caloric testing, and functional level scale of the patients were analysed. RESULTS: Twenty-eight patients who met our criteria were eligible for enrolment in the study. The average follow-up after surgery was 25 months (range, 13-41). Postoperative pure-tone threshold averages and reduced vestibular response values (RVR) were not significantly altered by ESD; whereas, functional level scores improved significantly. CONCLUSION: Endolymphatic sac decompression is a surgical procedure that preserves hearing and vestibular function, and improves the daily functional level of patients with Ménière's disease. ESD can be preferred both in bilateral and unilateral disease because it does not alter vestibular function and preserves hearing.

Occlusion of the Lateral Semicircular Canal, Endolymphatic Sac Surgery, and Cochlear Implantation: A Low Destructive Treatment for Unilateral Ménière's Disease and Deafness.

INTRODUCTION: Surgical treatment of Ménière's disease (MD) and deafness aims to treat vertigo and hearing disabilities. Current treatment options like labyrinthectomy and cochlear implantation (CI) have shown acceptable results but are destructive. Less destructive procedures, like the occlusion of the lateral semicircular canal and endolymphatic sac surgery, have been shown to be successful in vertigo control. The combination of both procedures with CI has not been investigated; therefore the objective of this study was to investigate the outcome of this combination in patients with single-sided MD and moderately severe to complete sensorineural hearing loss. METHODS: In this retrospective study, 10 patients with single-sided MD and moderately severe to complete sensorineural hearing loss were included. In all of them, a single-staged surgery, which consisted of CI, endolymphatic sac surgery, and occlusion of the lateral semicircular canal, was performed. The surgery was performed after a failed conservative therapy trial. The clinical outcome was evaluated by the Dizziness Handicap Inventory (DHI) and audiological tests. These were assessed preoperatively, 3 and 6 months after surgery. An MRI with a hydrops sequence was performed to support the clinical diagnosis. RESULTS: After the combined surgery, the mean DHI testing improved significantly from 71 to 30. Mean audiological monosyllabic speech testing outcome with the cochlea implant was 65% at 65 dB. The residual hearing of 2 patients could be preserved after the surgical procedure. CONCLUSION: The combination of occlusion of the lateral semicircular canal, endolymphatic sac surgery, and CI is an efficient low traumatic treatment for patients with a single-sided MD and moderately severe to complete sensorineural hearing loss.

A Rare Case of Angiofibroma Presenting as an Endolymphatic Sac Tumor.

A 30-year-old man presented with minute-long episodes of vertigo and severe autophony. CVEMP showed a decreased threshold when testing the left side, potentially indicating SSCD. A subsequent MRI demonstrated a multi-lobulated, cystic mass in the temporal bone and the radiological diagnosis at that time was ELST. Tumor excision was performed, and microscopic examination of the excised material revealed fibrovascular tissue without signs of papillary or cystic projections. The conclusion of the histological assessment rendered a diagnosis of angiofibroma. We were unable to find a previous report of ENA originating around the endolymphatic sac. Laryngoscope, 134:1897-1900, 2024.

Development and validation of prediction model to estimate vertigo risk after endolymphatic sac decompression in Meniere's disease: a retrospective cohort study.

PURPOSE: To study the efficacy predictors of endolymphatic sac decompression (ESD) in Meniere's disease (MD), and to establish and verify the prediction model of vertigo after ESD in patients with MD. METHODS: The retrospective cohort data of 56 patients with unilateral MD who underwent ESD surgery were recorded. A stepwise regression method was used to select optimal modeling variables, and we established a logistic regression model with the outcome of vertigo after ESD. The bootstrap method was used for internal validation. RESULTS: Potential predictors included sex, age, follow-up duration, disease course, attack duration, frequency of attack, pure-tone threshold average (PTA) of the patient's speech frequency, audiogram type, glycerin test results, MD subtype, and 10-year atherosclerotic cardiovascular disease risk classification. Using the stepwise regression method, we found that the optimal modeling variables were the audiogram type and PTA of the patient's speech frequency. The prediction model based on these two variables exhibited good discrimination [area under the receiver operating characteristic curve: 0.72 (95% confidence interval: 0.57-0.86)] and acceptable calibration (Brier score 0.21). CONCLUSION: The present model based on the audiogram type and PTA of the patient's speech frequency was found to be useful in guidance of ESD efficacy prediction and surgery selection.

Significance of endolymphatic sac surgery with and/or without simultaneous cochlea implant surgery in respect of vertigo control and speech perception in patients with Menière's disease.

PURPOSE: The focus on treating patients with Menière's Disease (MD) lies on the reduction of vertigo attacks and the preservation of sensory function. Endolympathic hydrops is considered as an epiphenomenon in MD, which can potentially be altered by endolymphatic sac surgery (ESS). Purpose of the study was to investigate the influences on vertigo control through manipulation of the perilymphatic system with or without ESS. METHODS: Retrospective data analysis of 86 consecutive patients with MD according to current diagnostic criteria after endolymphatic sac surgery alone (ESSalone; n = 45), cochlear implantation (CI) alone (CIalone; n = 12), and ESS with CI (ESS + CI; n = 29), treated at a tertiary referral center. MAIN OUTCOME MEASURES: vertigo control, speech perception pre- and postoperatively. RESULTS: Gender, side, and preoperative treatment were similar in all groups. Age was younger in the ESSalone-group with 56.2 ± 13.0 years (CIalone = 64.2 ± 11.4 years; ESS + CI = 63.1 ± 9.7 years). Definitive MD was present in all the CIalone, in 79.3% of the ESS + CI and in 59.6% of the ESSalone-patients. Likewise, vertigo control rate was 100% in the CIalone, 89.7% in the ESS + CI and 66.0% in the ESSalone-group. CONCLUSIONS: Vertigo control was improved in all three groups, however, superior in groups treated with CI, potentially contributed by the manipulation of both the endo- and perilymphatic systems. A more systematic characterization of the patients with larger case numbers and documentation of follow up data would be needed to evaluate a clinical effect more properly.

Endolymphatic Duct and Sac Decompression: A New Life for an Old Technique.

BACKGROUND: Ménière's disease is an inner ear disorder causing recurrent vertigo, hearing loss, and tinnitus. Diagnosis is based on the variability of the symptoms over time and absence of radiological abnormalities. Medical therapy is effective only in a small percentage of patients. Surgical strategies remain controversial. In this article, we revisit a surgical technique neglected over the years: endolymphatic sac surgery. METHODS: Fifty-four patients affected by Ménière's disease underwent endolymphatic duct and sac decompression. According to the American Academy of Otolaryngology-Head and Neck Surgery criteria, vertigo control was evaluated with follow-up at 6 months, 1 year, and 2 years from the intervention. Hearing results were evaluated before the surgery and at 2 years of follow-up using the pure tone average. The results were compared with similar techniques of endolymphatic sac surgery described in the literature. RESULTS: According to the American Academy of Otolaryngology-Head and Neck Surgery criteria classification, 2 years after surgery, 87% patients achieved complete control of vertigo (class A). The hearing remained stable in 93.5% of patients. The results appear compatible with other publications data regarding endolymphatic sac surgeries. CONCLUSION: The duct and endolymphatic sac decompression allows the control of vertigo and preserves hearing from the pathological effects of Ménière's disease. The revised technique allows the functional restoration of endolymphatic homeostasis.

Potential biomarkers in peripheral blood mononuclear cells of patients with sporadic Ménière's disease based on proteomics.

BACKGROUND: Ménière's disease (MD) mainly refers to the endolymphatic hydrops in membranous labyrinth of the inner ear. Application of the mass spectrometry-based proteomics techniques has not been applied in the field of MD. OBJECTIVES: To search for potential differential proteins to identify the disease biomarkers and reveal disease bioinformatics-related mechanisms through applying protein technology to analyze the expression changes of peripheral blood mononuclear cells (PBMCs) in sporadic MD patients. MATERIAL AND METHODS: 15 MD patients and 15 healthy individuals were enrolled. PBMCs from them were extracted, and their protein expression was identified and compared by LC-MS/MS and spectra analysis. RESULTS: There was significant difference in protein expression between MD patients and the control group. GO and KEGG analysis showed that endocytosis was involved in MD patients. Western blot results of CHMP1A and MMP9 protein showed that the expression of CHMP1A was higher in the MD group than that in the control group, while MMP9 was down-regulated. Immunohistochemistry confirmed that CHMP1A and MMP9 were expressed in the endolymphatic sacs of MD patients and in the inner ear of adult mice. CONCLUSIONS AND SIGNIFICANCE: Endocytosis may be involved in the pathogenesis of sporadic MD, furthermore CHMP1A, VPS4A, FCN3 and MMP9 could be considered as potential biomarkers.

背景：梅尼埃病（MD）主要是指内耳耳膜迷路中的内淋巴积液。 基于质谱的蛋白质组学技术尚未在MD治疗上得到应用。目的：通过应用蛋白质技术分析散发性MD患者外周血单核细胞（PBMcs）的表达变化, 寻找潜在的分异性蛋白来识别该病生物标志物, 揭示该病生物信息学相关机制。材料和方法：纳入 15 名 MD 患者和 15 名健康人。 提取PBMcs, 通过lc-Ms/Ms和光谱分析鉴定并比较其蛋白表达。结果：MD患者与对照组的蛋白表达存在显著差异。 GO和KeGG分析表明, MD患者具有内吞作用。 chMP1a和MMP9蛋白的蛋白质印迹结果显示, MD组chMP1a的表达高于对照组, 而MMP9表达下降。 免疫组织化学证实, chMP1a和MMP9在MD患者的内淋巴囊和成年小鼠的内耳中有表达。结论及意义：内吞作用可能参与散发性MD的发病机制, chMP1a、VPs4a、FcN3和MMP9可作为潜在的生物标志物。.

Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.

OBJECTIVE: To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. BACKGROUND: Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. METHODS: We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. RESULTS: In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. CONCLUSION: The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.

Surgical Management of Endolymphatic Sac Tumor: A Systematic Review and Meta-Analysis.

The aim of our study was to report rates of facial nerve palsy and residual tumor following surgical intervention and subsequent tumor recurrence in patients with endolymphatic sac tumors. A systematic literature review of preoperative assessment and surgical management is also included. Studies including patient/s affected by sporadic or von Hippel-Lindau disease related endolymphatic sac tumors, reporting levels of facial nerve function, residual and recurrence pathology following a surgical procedure, were considered. Data were combined for proportional meta-analysis, and the selected studies' methodological quality was also evaluated. Overall 34 papers, including 202 subjects (209 cases of endolymphatic sac tumors) were analyzed. Pooled proportion rate (95% CI) of overall facial nerve palsy was 39.7% (28.2-51.9) and residual tumor was 16.5% (10.3-23.7) after surgical procedure. Pooled proportion rate (95% CI) of tumor recurrence was 14.0% (9.7-19.3) during a mean follow-up period of 49.7 months (8-136). Our results showed that preoperative facial nerve function is impaired in almost 30% of patients with endolymphatic sac tumors. Surgical management of endolymphatic sac tumor may cause a worsening of facial nerve function in a low percentage of treated subjects. Residual and/or recurrence of endolymphatic sac tumors are not rare events, and follow-up strategies should be designed accordingly.

Surgical Treatment of an Endolymphatic Sac Tumor.

Endolymphatic sac tumors (ELST) are low-grade papillary adenocarcinoma originating from the endolymphatic sac. Usually slow-growing, with local aggressiveness and a low risk of distant metastases, ELST can be sporadic but also frequently associated with von Hippel Lindau disease. The current treatment of ELST is primarily surgical resection. A 55-year-old woman accessed our otologic tertiary level referral center for a sudden worsening of hearing loss in her left ear and vertigo. A magnetic resonance (MRI) and computer tomography scan study subsequently showed a mass in the petrous bone; hence, the presence of an ELST was hypothesized. After embolization of the mass, the patient underwent surgical removal of the lesion. The resection of the mass was done through a translabirinthine approach, with an uneventful procedure. No residual disease remained after surgery. After 24 months of radiologic follow up with MRI, there are no signs of recurrence disease. This paper reports the management of this sporadic ELST, as well as the follow up results, providing clinicians this protocol for the handling of such a challenging otologic skull base surgery and rare disease.

Radiological feature heterogeneity supports etiological diversity among patient groups in Meniere's disease.

We aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere's disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm3, MD-hp; 5.25 [3.45] cm3, MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31-0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse-developmental and degenerative-disease etiologies manifesting with distinct radiological temporal bone abnormalities.

[Endolymphatic sac tumor with intralabyrinthine hemorrhage: a case report].

A 27-year-old female patient suffering endolymphatic sac tumor with intralabyrinthine hemorrhage was reported. The patient had hearing loss in the left ear with continuous tinnitus, and MRI showed the soft tissue shadow of endolymphatic sac. Considering that the tumor involved semicircular canal and vestibule,endolymphatic cyst tumor resection was performed by labyrinth route. After surgery, there was no cerebrospinal fluid leakage and facial nerve function was normal. More importantly, enhanced MRI of temporal bone showed no tumor recurrence 1 year after surgery.