The intrabulbar or extrabulbar growth pattern and its surgical outcomes of jugular foramen paragangliomas.

OBJECTIVE: This study is to define a subclassification system of jugular foramen paragangliomas (JFPs) and to demonstrate corresponding microsurgical outcomes of JFPs. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: We conducted a retrospective review of the clinical data of 44 patients with JFPs who underwent surgical management. Extrabulbar(Be) tumor and intrabulbar(Bi) tumor are defined based on the growth patterns, receiver operating characteristic (ROC) curves of the imaging profile were generated and was confirmed based on intraoperative findings. Area Under Curve (AUC), accuracy, sensitivity, and specificity for diagnostic imaging were revealed. We also compared the correlation between the two growth patterns with Fisch's classification, blood loss, lower cranial nerves (LCNs) deficit. RESULTS: There are 27 (69%) cases of Bi tumor and 17 (39%) cases of Be tumor. Significant radiomics features between the two growth patterns were demonstrated, ROC curves achieved excellent AUCs for MRI sequences (T1W1 MRI, MR contrast-enhanced sequence, MR complex sequences and MR complex + DSA by 0.833, 0.833, 0.875, 0.944) and had statistically significant in diagnosis of two growth patterns (P<0.05). There was no statistical correlation between growth patterns of JFPs and intra-operative blood loss. Preoperative LCNs deficits and Fisch's classification of tumors were correlated with the growth patterns of JFPs (P < 0.05). CONCLUSION: We proposetd two growth patterns of JFPs in term of the inferior petrous sinus involvement. Identification of Bi or Be growth patterns preoperatively is helpful to design optimal surgical strategies and minimize postoperative complications.

An Improved Staging System of Adenoid Cystic Carcinoma in the External Auditory Canal.

OBJECTIVE: The purpose of this study was to define an improved staging system for adenoid cystic carcinoma (ACC) in the external auditory canal (EAC) based on biological behaviors, image findings, and the prognosis of patients with ACC in the EAC. STUDY DESIGN: A retrospective study. SETTING: A single center data. METHODS: We performed a single-institution retrospective review of 154 patients with ACC in the EAC between January 2004 and September 2021. Risk factors associated with disease-free survival (DFS) and cancer-specific survival (CSS) of ACC in the EAC were identified using univariate and multivariate cox regression analysis. Then an improved staging system was proposed and compared with the Pittsburgh-modified tumor, node, and metastasis (TNM) staging system for statistical differences in DFS and CSS. RESULTS: An improved staging system of ACC in the EAC was defined, in which stage T4 were subclassified into T4a and T4b and were statistically different from the Pittsburgh-modified TNM staging system in DFS and CSS. We also found that the dura mater, facial nerve, sigmoid sinus, deep lobe of parotid gland, and parapharyngeal space involvement were significantly associated with poor prognosis of ACC in the EAC. CONCLUSION: The improved staging system is more accurate in predicting survival prognosis than Pittsburgh-modified TNM staging system for patients with ACC in the EAC, and may provide more efficient guidance of treatment strategy. SUMMARY: The improved staging system of ACC in the EAC is more accurately to predict survival prognosis, and provide guidance of treatment plan than Pittsburgh-modified TNM staging system.

Nomogram for predicting early hypophosphatemia in term infants.

BACKGROUND: Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. METHODS: We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. RESULTS: According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668-0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSIONS: The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.

The Role of Parotid Gland Invasion in Adenoid Cystic Carcinoma of the External Auditory Canal.

OBJECTIVE: This study aimed to investigate the significance of parotid gland invasion in predicting distant metastasis of adenoid cystic carcinoma in the external auditory canal. STUDY DESIGN: Single-institution retrospective cohort study. METHODS: A retrospective review of patients with adenoid cystic carcinoma of the external auditory canal who underwent surgery was performed. Information on patient demographics, parotid gland invasion, tumor stage, perineural invasion, lymphovascular invasion, and follow-up data were collected and analyzed. RESULTS: One hundred twenty-nine patients were identified for review. Parotid gland invasion was noted in 45 patients (34.9%). Parotid gland invasion was significantly associated with tumor stage, perineural invasion, distant metastasis, and postoperative adjuvant therapy. Distant metastasis was noted in 30 patients (23.3%). Multivariate Cox proportional hazards analysis identified parotid gland invasion as an independent risk factor for predicting distant metastasis. The 5-year distant metastasis-free survival rate was 83.6% for patients without parotid gland invasion and 61.8% for patients with parotid gland invasion (p = 0.010). CONCLUSIONS: The parotid gland invasion rate is relatively high in adenoid cystic carcinoma of the external auditory canal and is significantly related to tumor stage. Parotid gland invasion is associated with worse distant metastasis-free survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:419-425, 2024.

[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.

Whole-brain monosynaptic outputs and presynaptic inputs of GABAergic neurons in the vestibular nuclei complex of mice.

GABAergic neurons in the vestibular nuclei (VN) participate in multiple vital vestibular sensory processing allowing for the maintenance and rehabilitation of vestibular functions. However, although the important role of GABA in the central vestibular system has been widely reported, the underlying neural circuits between VN GABAergic neurons and other brain functional regions remain elusive, which limits the further study of the underlying mechanism. Hence, it is necessary to elucidate neural connectivity based on outputs and inputs of GABAergic neurons in the VN. This study employed a modified rabies virus retrograde tracing vector and cre-dependent adeno-associated viruses (AAVs) anterograde tracing vector, combined with a transgenic VGAT-IRES-Cre mice, to map the inputs and outputs of VN GABAergic neurons in the whole brain. We found that 51 discrete brain regions received projections from VN GABAergic neurons in the whole brain, and there were 77 upstream nuclei innervating GABAergic neurons in the VN. These nuclei were mainly located in four brain regions, including the medulla, pons, midbrain, and cerebellum. Among them, VN GABAergic neurons established neural circuits with some functional nuclei in the whole brain, especially regulating balance maintenance, emotion control, pain processing, sleep and circadian rhythm regulation, and fluid homeostasis. Therefore, this study deepens a comprehensive understanding of the whole-brain neural connectivity of VN, providing the neuroanatomical information for further research on the neural mechanism of the co-morbidities with vestibular dysfunction.

Gut Microbiome and Metabolome Changes in Mice With Acute Vestibular Deficit.

Vestibular deficit is a very common disorder in clinical practice and is characterized by vertigo, spontaneous nystagmus, and autonomic nervous symptoms, including nausea, vomiting, and sweating. In addition, the comorbidity of vestibular deficit and anxiety has long been an integral component of the medical literature. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of vestibular and cerebellar networks. Emerging evidence has shown that the microbiota-gut-brain axis plays a key role in the regulation of affective disorders. Thus, we hypothesized that the gut microbiota may be involved in the comorbidity of vestibular deficit and anxiety. To verify this, we constructed a unilateral labyrinthectomy mouse model to simulate vestibular deficit. Then, 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to analyze the microbiome and metabolome of the cecal samples collected from mice in the unilateral labyrinthectomy, sham surgery, and control groups. Notably, unilateral labyrinthectomy shaped the composition of the mouse gut microbiome, resulting in increased abundance of Lachnospiraceae NK4A136 group, Odoribacter and Roseburia and decreased abundance of Prevotella and Parasutterella at the genus level. Tax4Fun functional prediction indicated a decrease in tryptophan metabolism in mice in the unilateral labyrinthectomy group. Moreover, functional correlation of changes in gut microbes and metabolites between different groups showed that the oleamide level was negatively correlated with Odoribacter abundance (r = -0.89, p = 0.0002). The butyric acid level was positively correlated with Parasutterella abundance (r = 0.85, p = 0.0010). The propanoate level was negatively correlated with Prevotella abundance (r = -0.81, p = 0.0020). The 20-HETE level was positively correlated with Parasutterella abundance (r = 0.84, p = 0.0013). The altered microbes and metabolites were closely related to the pathogenesis of affective disorders. Our results not only offer novel insights into the vestibular deficit comorbid with anxiety but also build an important basis for future research on this etiology.

Prognostic value of pre-operative peripheral inflammation markers in patients with squamous cell carcinoma of the external auditory canal / Valor prognóstico dos marcadores de inflamação periférica pré-operatórios em pacientes com carcinoma espinocelular do meato acústico externo

Abstract Introduction: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. Objective: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. Methods: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. Results: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p< 0.0001, p< 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. Conclusions: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease.

Resumo Introdução: O carcinoma espinocelular do meato acústico externo é uma doença rara. Estudos anteriores sugeriram preditores de recorrência do tumor. Entretanto, a maioria dos fatores prognósticos se originou do aspecto clínico-patológico. Objetivo: Analisar a correlação entre marcadores inflamatórios periféricos pré-operatórios e os desfechos de sobrevida e identificar biomarcadores prognósticos para pacientes com carcinoma espinocelular do meato acústico externo. Método: Analisamos retrospectivamente pacientes com diagnóstico de carcinoma espinocelular do meato acústico externo submetidos à cirurgia em nosso instituto. Os marcadores inflamatórios circulantes pré-operatórios, como as contagens de neutrófilos, linfócitos, plaquetas e monócitos, foram medidos e as suas relações calculadas, inclusive as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos. O valor prognóstico dos parâmetros hematológicos medidos em relação aos desfechos de sobrevida também foi avaliado. Resultados: Foram incluídos 83 pacientes, entre os quais 26 apresentaram recorrência tumoral e 57 não apresentaram. A contagem de neutrófilos e a relação neutrófilo/linfócito estavam intimamente associadas ao estágio do tumor. Nos pacientes com recorrência, a contagem de neutrófilos, a relação neutrófilos/linfócitos e a relação plaquetas/linfócitos eram elevadas (p < 0,0001, p > 0,0001 e p = 0,001), enquanto a contagem de linfócitos e a relação linfócitos/monócitos estavam diminuídas (p = 0,012 ep = 0,016, respectivamente). A análise da curva, Receiver Operating Characteristic, indicou que a relação neutrófilos/linfócitos pré-operatória era um potencial marcador prognóstico para a recorrência de carcinoma espinocelular do meato acústico externo (Área sob a curva = 0,816) e o ponto de corte foi de 2,325. Conclusão: A contagem pré-operatória de neutrófilos e linfócitos, as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos estão significativamente correlacionadas com a recorrência do tumor em pacientes com carcinoma espinocelular do meato acústico externo. Além disso, a relação neutrófilos/linfócitos pode ser um fator prognóstico desfavorável dessa doença.

Prognostic value of pre-operative peripheral inflammation markers in patients with squamous cell carcinoma of the external auditory canal.

INTRODUCTION: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. OBJECTIVE: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. METHODS: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. RESULTS: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p < 0.0001, p < 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. CONCLUSIONS: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease.

Grading system and surgical approaches for endolymphatic sac tumors.

PURPOSE: Endolymphatic sac tumors (ELSTs) are rare, low-grade adenocarcinomas arising from the endolymphatic sac. This study aims to present a novel grading system for ELSTs to determine the optimal management strategy. METHODS: We performed a retrospective analysis of 16 patients with 17 ELSTs. The tumor location and involved adjacent neurovascular structures on CT and MRI were selected to establish the grading system. RESULTS: Based on the novel grading system, grade III a tumors were most common (7/17), followed by grade I (4/17), grade II (3/17), and grade III b (3/17) tumors. Eight advanced ELSTs (grade III a and III b) received an infra-temporal fossa approach, while the other 6 early stage ELSTs (grade I and II) underwent either a retrolabyrinthine approach with posterior petrosectomy or a translabyrinthine approach combined with subtotal temporal bone resection. Hearing preservation was achieved in 2 grade I patients. Postoperative facial nerve function was HB II in 1 grade III a patient who underwent anterior facial nerve transposition and was HB III in 4 advanced patients who received facial nerve grafts with the great auricular nerve or facial-hypoglossal nerve anastomosis. The mean follow-up time was 35.1 months. Two grade III patients and 1 grade II patient had tumor recurrence during follow-up, among whom 1 grade III b patient had two cases of recurrence. CONCLUSION: A correct initial diagnosis was established in all patients after meticulous imaging studies. Surgical resection is still the first choice to manage patients with ELSTs. The novel grading system enables surgeons to select tailored surgical approaches. Long-term follow-up is necessary following surgical intervention.

Endolymphatic Hydrops in Patients With Intralabyrinthine Schwannomas.

Purpose: The presence of endolymphatic hydrops (EH) in patients with intralabyrinthine schwannomas (ILSs) is poorly understood. This study aims to determine whether there is a correlation between endolymphatic hydrops and clinical presentations of ILS. Methods: Data from nine patients with ILSs were retrospectively reviewed between 2007 and 2020. Temporal bone MRI with intratympanic or intravenous injection of gadolinium was applied to detect ILSs and EH. Results: 3D real inversion recovery (IR) sequence MRI of the temporal bone confirmed ipsilateral EH in four patients (4/6). All four patients with EH on MRI presented with vertigo similar to Meniere's disease. Among these patients with EH, one patient with EH in the cochlea showed moderate sensorineural hearing loss, while three patients with EH in both the vestibule and cochlea showed profound hearing loss. MRI demonstrated a transmacular tumor (TMA) in one patient, intravestibular (IV) in four patients, and vestibulocochlear (VC) in four patients. Two IV cases showed moderated hearing loss, while the TMA and VC cases showed profound hearing loss. Transotic resection of the tumor was applied in five patients; translabyrinthine resection was applied in one patient; two patients were under observation; and one patient was given intratympanic injection of gentamicin (ITG). During follow-up, all of the treated patients reported relief of vertigo, and postoperative MRI was performed in two patients, which showed no tumor recurrence. The two patients under observation showed no deterioration of hearing loss or vertigo. One patient was lost to follow-up. Conclusion: EH concurrent with ILSs has been underestimated previously. With the extensive application of temporal bone MRI paradigms, such as 3D-real IR sequence MRI, more cases of potential EH in patients with ILS will be identified. The severity of hearing loss may be associated with the location of the tumor and the degree of EH.

Correlation between the pathology and clinical presentations in patients with adenoid cystic carcinoma of the external auditory canal.

BACKGROUND: The purpose of this study was to analyze the correlation between the pathology and clinical presentations in patients with adenoid cystic carcinoma (ACC) of the external auditory canal. METHODS: Twenty-nine patients with ACC of the external auditory canal who underwent surgery were retrospectively reviewed. RESULTS: Fifty percent of patients with solid pattern disease had recurrences, followed by those with cribriform (33%) and tubular (0%) pattern. Perineural invasion was common (55%), and occurred most frequently in the solid subtype (67%). The rate of otalgia was less in patients with perineural invasion (31% vs 46%). Most tumors (59%) involved the parotid gland, but it was not seen on preoperative MRI (35%). CONCLUSION: The solid subtype presents the worst prognosis, and is prone to perineural invasion. Despite frequently occurring in ACC of the external auditory canal, perineural invasion may not be associated with otalgia. In ACC of the external auditory canal, high rates of occult parotid involvement support adjunctive superficial parotidectomy.

Expression profiling of long noncoding RNA identifies lnc-MMP3-1 as a prognostic biomarker in external auditory canal squamous cell carcinoma.

Our previous studies suggested external auditory canal squamous cell carcinoma (EACSCC) is a rare malignancy with heterogeneous outcomes. This study aimed to identify lncRNA profile of EACSCC and determine the clinical application. Differential expression genes (DEGs) were investigated in EACSCC by whole transcriptome lncRNA arrays (GPL23178). RT-PCR was used to quantify the microarray data. Bioinformatics analyses were performed to evaluate DEGs regulations in gene ontology and cellular pathways. Fluorescence in situ hybridization (FISH) was utilized to validate lncRNA expression. The overall survival was determined by Kaplan-Meier and log-rank analyses. Our microarrays data had been submitted to Gene Expression Omnibus (GSE98912). We identified 5621 DEGs (3185 mRNAs, 2436 lncRNAs) in EACSCC. Lnc-MMP3-1 was the top one upregulated lncRNA in EACSCC with fold change of 237.2 (P < 0.001). RT-PCR results showed similar expression levels as microarrays data. Bioinformatics analyses indicated development of EACSCC was involved in aberrant alternations of multiple biological processes and cellular pathways. FSIH assays also found lnc-MMP3-1 was significantly differentially overexpressed in EACSCC (P < 0.001). Tumor lnc-MMP3-1 levels were closely associated with differentiation degree (P = 0.016), tumor invasion (P = 0.015) and TNM stage (P = 0.015). Moreover, lnc-MMP3-1 expression was a significant prognostic factor in EACSCC (χ2  = 4.276, P = 0.039). The study is the first screening and analysis of lncRNAs profile in EACSCC and provides new insights into pathogenesis of this rare disease. Our findings offered convincing evidences that lnc-MMP3-1 is a novel survival predictor of EACSCC patients.