Multiple symmetric lipomatosis (Madelung's disease) with symptoms and signs of hypertension, lipodystrophy, and dyspnea: A case report and literature review.

Madelung's disease generally refers to a benign symmetrical lipomatosis of the neck, but its presentation can vary. It is treated surgically and different approaches can be implemented. In cases of a threatened airway, a tracheostomy can be performed.

Epidemiological Characteristics and Survival Analysis of Patients With Nasopharyngeal Cancer in Western Greece.

Purpose The purpose of this study is to assess the overall survival (OS) of patients with nasopharyngeal cancer and the factors affecting the survival rates. Methods A retrospective cohort study was performed, including 77 patients with nasopharyngeal cancer diagnosed and treated in the Otorhinolaryngology Clinic of the University Hospital of Patras during 1990-2017. The prognostic impact of age, gender, occupation, smoking/alcohol, and TNM staging were evaluated using Kaplan-Meier analysis. Results During the last 28 years, nasopharyngeal cancer (NPC) was higher in men (80.5% of patients) than women (19.5%) (mean age 56-years). Most patients were smokers (64.9%, mean 70 pack-years) and 35 (45.5%) of them were alcohol users. Postoperative staging indicated 39% stage-III, 26% stage-IV, and 26% stage-I. Histologically, 70.1% of the volumes were WHO-III, 20.8% WHO-II, and 5.2% WHO-I. Also, 98.7% of patients received radiotherapy, 85.7% chemotherapy, and 20.8% surgery. More than half were farmers (26%), self-employed (16.9%), and workers (14.3). During the follow-up (mean 66 months), 38 (49.5%) patients died, 88.9% from disease-related causes. The 5-year survival was 58.8%, 74.5% for non-smokers, and 49.1% for smokers, and 10-year survival was 43.6%, 63.4%, and 31.6%, respectively (p=0.016). Moreover, significant statistical differences were observed in age (p=0.054), time period of diagnosis and treatment (p=0.002), cause of death (p=0.033), and metastatic disease (p=0.023). Conclusions Age, stage in disease detection, tumor characteristics, treatment, and tobacco abuse are important factors that affect the OS of patients with NPC during the three last decades.

Impact of different therapeutic regimens on survival of patients with nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) demonstrates specific histo-genetic features that affect its biological behaviour. Our aim was to investigate the correlation between different therapeutic approaches and survival of patients with NPC in southwestern Greece based on specific clinicopathological features. METHODS: Seventy-two NPC patients (n=72) were treated between 1990 and 2014 at the University Hospital of Patras. Patient demographics, tumor histology, use of tobacco and alcohol, exposure to mutagenic agents, chosen treatment and survival were recorded. All patients were treated with radiotherapy (RT), chemotherapy, surgery or their combinations. RESULTS: In the patients who used immobilization mask during RT, the 5-year survival rate and overall survival was higher than the rest of patients (57% and 6 years vs. 13.6% and 3.36 years, p=0.0001, respectively)*. RT with mask combined with chemotherapy increased survival rates compared to RT without chemotherapy conventional regimen (p=0.0001). Additionally, patients who received chemotherapy demonstrated a 5-year survival of 51.6% compared to those without chemotherapy (11% p=0.0014). (*The 5-year survival rate group of patients refers to the percentage of people who will be alive 5 years after diagnosis. It does not include those who die from other diseases. Sometimes, this includes all people with a specific cancer type. Researchers call this an overall rate. In contrast, overall survival provides information for the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the overall survival is one way to see how well a new treatment works.) Conclusions: In the majority of examined NPC cases treated with the use of immobilization RT mask along with chemotherapy, a significantly better prognosis compared to conventional RT-chemotherapy treatment was observed. Thus, chemotherapy offers an advantage to patient survival as an adjuvant treatment regimen in conjunction with RT.

High PINCH1 Expression in Human Laryngeal Carcinoma Associates with Poor Prognosis.

Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Protein expressions of cofilin, N-WASP, α-parvin, ß-parvin, and PINCH1 were examined by immunohistochemistry in 72 human laryngeal squamous cell carcinomas. Correlations with clinicopathological data and survival were evaluated. All proteins examined were overexpressed in human laryngeal carcinomas compared to adjacent nonneoplastic epithelium. High expression of PINCH1 was associated significantly with high grade, lymph node-positive, and advanced stage disease. Moreover, high PINCH1 expression significantly associated with poor overall and disease-free survival and high cytoplasmic PINCH1 expression was shown by multivariate analysis to independently predict poor overall survival. In conclusion, we provide novel evidence that focal adhesion signaling to actin cytoskeleton is implicated in human laryngeal carcinogenesis and PINCH1 has prognostic significance in the disease.

HPV infection in oropharyngeal squamous cell carcinomas: correlation with tumor size.

PURPOSE: Human papillomavirus (HPV) is implicated in carcinogenesis of a variety of epithelia, including oropharyngeal and laryngeal. High risk (HR) HPV persistent infection in head and neck squamous cell carcinomas (HNSCC) is a significant event, but its influence regarding the prognosis and survival in these patients remains under consideration. Our aim was to analyze a series of oropharyngeal (OP) SCCs at the HPV DNA level, correlating them to the survival status of the corresponding patients. METHODS: Using HPV DNA polymerase chain reaction (PCR) microarray technology, 28 formalin-fixed, paraffinembedded primary OPSCCs were cored and analyzed. RESULTS: Positive DNA amplicons for HPV infection were detected in 3 SCC cases (sub types: HPV 31/35/70). Interestingly, HPV persistent infection was associated with larger tumors (p=0.029) which also affected survival status (p=0.007) in the corresponding patients. Overall survival was also significantly dependent on the stage of the malignancies (p=0.022). Furthermore, tumor size was significantly and negatively correlated with age (p=0.015), meaning that younger patients will probably develop larger tumors. CONCLUSIONS: HPV-depended OPSCCs - although not so common as the laryngeal ones, but still not so rare in the rural population in Greece - are characterized by a combination of specific features. Our results showed that survival was adversely effected by the stage of the disease and tumor size and indirectly by the presence of HPV - especially in young adults - while the combined surgery/radiotherapy/ chemotherapy therapy seems to prolong survival. Additionally, HPV co-existence seems to be associated with larger tumors and poor survival.

Deregulation of PTEN Expression in Laryngeal Squamous Cell Carcinoma Based on Tissue Microarray Digital Analysis.

BACKGROUND/AIM: Phosphatase and tensin homolog (PTEN) (gene locus: 10q23.3) -a tumor suppressor gene- is deleted, mutated or epigenetically hyper-methylated in a variety of malignancies. PTEN acts as a negative regulator in PI3K/AKT/mTOR signaling transduction pathway. Our aim was to investigate PTEN protein expression patterns in laryngeal squamous cell carcinomas (LSCC). MATERIALS AND METHODS: Using tissue microarray technology, fifty (n=50) primary LSCCs were cored and re-embedded into one recipient block. Immunohistochemistry and digital image analysis were implemented for evaluating protein expression levels. RESULTS: Abnormal protein expression (low to negative staining intensity values) was observed in 28/50 (56%) tissue cores. Overall PTEN expression was associated with the anatomical region of the malignancies (p=0.039), whereas a borderline correlation with the differentiation grade was also assessed (p=0.05). CONCLUSION: Aberrant expression of PTEN tumor-suppressor gene in LSCCs seems to affect their biological behavior. Well-differentiated tumors express moderate to high protein levels, an evidence of normal gene function, whereas loss of its expression correlates with a progressive tumor dedifferentiation. Additionally, loss of its expression is detected more frequently in specific anatomical regions of the larynx (glottis, predominantly, and partially supraglottis).

mTOR deregulation in oral cavity squamous cell carcinoma.

Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF). mTOR protein acts as a serine-threonine kinase that belongs to the PI3K-related kinase family. It mediates protein and lipid synthesis, mitochondrial metabolism, biogenesis, proliferation and also negatively regulates autophagy. Two distinct multiprotein complexes have been mainly identified and cloned: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR is deregulated predominantly due to mutations, deletions, loss of heterozygosity (LOH) or abnormal phosphorylation of the upstream molecules inside the current pathway. Pure mTOR mutations are very rare. Development of specific inhibitors at the basis of targeted therapeutic strategies such as rapamycin (rapalogs) is an evolution in handling patients with mTOR abnormal overactivity. In the current special article we explored the role of the gene deregulation leading to abnormal protein expression in oral cavity squamous cell carcinoma (SCC).

Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis.

PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. METHODS: Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. CONCLUSIONS: Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents.

A link between RelB expression and tumor progression in laryngeal cancer.

Laryngeal cancer is a frequent malignancy originating from the squamous vocal epithelium in a multi-stage fashion in response to environmental carcinogens. Although most cases can be cured by surgery and/or radiotherapy, advanced and relapsing disease is common, and biomarkers of such dismal cases are urgently needed. The cancer genome of laryngeal cancers was recently shown to feature a signature of aberrant nuclear factor (NF)-κB activation, but this finding has not been clinically exploited. We analyzed primary tumor samples of 96 well-documented and longitudinally followed patients covering the whole spectrum of laryngeal neoplasia, including 21 patients with benign laryngeal diseases, 15 patients with dysplasia, 43 patients with early-stage carcinoma, and 17 patients with locally advanced carcinoma, for immunoreactivity of RelA, RelB, P50, and P52/P100, the main NF-κB subunits that activate transcription. Results were cross-examined with indices of tumor progression and survival. Interestingly, RelB expression increased with tumor stage, grade, and local extent. Moreover, patients displaying high RelB immunoreactivity exhibited statistically significantly poorer survival compared with patients featuring low levels of RelB expression (P = 0.018 by log-rank test). Using Cox regression analyses and tumor stage, local extent, grade and RelA/RelB immunoreactivity, we develop a new score that can independently predict survival of patients with laryngeal cancer. Hence we provide a simple and affordable NF-κB-based test to predict prognosis in laryngeal cancer.

Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review.

Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature.

Chronic rhinocerebral mucormycosis: a rare case report and review of the literature.

Rhinocerebral mucormycosis is an invasive infection caused by filamentous fungi of the Mucoraceae family. The rhinocerebral form of the disease represents the most common form and has two distinct clinical entities. The common presentation consists of a rapidly progressive infection with high mortality rate, while the other presentation is that of a chronic infection with lower mortality. In the present paper we report a rare case of chronic rhinocerebral mucormycosis. An 85-year-old male with a 6-month history of purulent and odorous nasal discharge, and sporadic episodes of epistaxis and anosmia, presented to the outpatient department of our clinic. Initial cultures were positive only for Pseudomonas aeruginosa. The patient was unresponsive to ciprofloxacin treatment, developing necrotic areas of the nasal septum suspicious for rhinocerebral mucormycosis. Admission to the ENT clinic followed, with histopathologic evaluation of the vomer bone confirming the diagnosis. The patient was treated with amphotericin B and was discharged 3 weeks later on oral posaconazole therapy. Chronic rhinocerebral mucormycosis may present with atypical symptoms or coinfection with another agent. A high degree of clinical suspicion is required for correct diagnosis and prompt initiation of appropriate treatment.

MMP-2 expression in 102 patients with glottic laryngeal cancer.

In order to evaluate the potential of matrix metalloproteinase 2 (MMP-2) as a prognostic factor for glottic laryngeal cancer. One hundred and two surgical specimens from patients with glottic laryngeal cancer who underwent laryngectomy for their disease in the University Hospital of Patras, Greece from 1998 to 2005 were reviewed retrospectively regarding MMP-2 expression via immunohistochemistry. Immunostaining was performed using a streptavidin-biotin peroxidase complex technique (LSAB). Results revealed that 54 of 102 patients (52.9%) had positive cytoplasmic staining for MMP-2. Kaplan-Meier analysis demonstrated statistically significant difference (p = 0.037) for the 5-year overall survival rate between the groups with positive and negative MMP-2 expression, and marginal statistical significance for the disease free survival rate (p = 0.048). The capsule rupture of metastatic lymph nodes and MMP-2 expression in primary tumor site also seems to be related (p = 0.047). Statistical significance could not be established between MMP-2 expression and the clinicopathological features of the disease (T stage, N stage, clinical stage, differentiation). In conclusion, MMP-2 expression was related with worse overall and disease-free survival and could be considered as a potential marker of poor prognosis.

Pharyngocutaneous fistula complicating laryngectomy: can metronidazole help?

AIM: To evaluate the use of metronidazole as a prophylactic agent against pharyngocutaneous fistula (PCF) formation. PATIENTS AND METHODS: Seventy patients who underwent total laryngectomy between 2000 and 2008 in our department were divided into two groups. The first group (M+ group) was placed on a 10-day metronidazole regimen (2 days prior to surgery and 7 days following). The second group (M- group) received only regular preoperative chemoprophylaxis. RESULTS: In total, 17 (24.3%) incidents of PCF were reported, 3 of which were in the M+ group, with the remainder in the M- group. A statistically significant reduction in the PCF rate was noted in favor of metronidazole in the overall population (p = 0.005), as well as in the patient group that had received radiotherapy prior to surgery (p = 0.03). CONCLUSION: Metronidazole administered for a total of 10 days pre- and postoperatively seems to lower the incidence rate of PCF formation.

Laryngeal cancer and passive smoking: the neglected factor?

In the present paper we investigate the relationship of environmental tobacco smoke (ETS) exposure to laryngeal cancer. 209 patients who were diagnosed with laryngeal cancer from 2000 to 2009 at the University Hospital of Patras, Western Greece, were reviewed with regard to patient age, disease stage at presentation, tumor differentiation, tobacco product use, alcohol consumption, occupation, and ETS exposure in the working environment. Pearson Chi-square method was used to determine the effect of ETS exposure on cancer stage, TNM classification and tumor differentiation in the dichotomized population (exposed vs. not exposed) and in groups of low, medium and high ETS exposure. ETS exposure in the working environment was found to significantly affect overall disease stage and T stage (p < 0.01) both in the dichotomic analysis and the group analysis. Minor significance was also noted for N stage (p = 0.047) in the exposure group analysis. Our data suggest that occupational ETS exposure presents a contributing risk factor for laryngeal cancer that requires further research to determine its significance.

Survival after laryngectomy: a review of 133 patients with laryngeal carcinoma.

Survival trends in survival for laryngeal cancer in Europe are varied. Five-year survival varied around 60-64% but numbers below 50% have been commonly reported. The aim of this study was to assess the factors influencing survival in patients with laryngeal cancer in our region. A total of 128 male and 5 female patients with larynx cancer (91 glottic and 42 supraglottic) were treated at Patras University Hospital between March 1992 and August 2004. Except 3, all were smokers and 56 (41%) heavy alcohol users. Postsurgical staging showed that most had been classified at stages III (38%) and IV (49%). By histology, 31 tumors were classified as poorly differentiated, 78 as moderately differentiated and 23 as well differentiated. All patients underwent laryngectomy with extension of the procedure where appropriate. Also, a total of 45 patients received adjuvant therapy (either chemotherapy or radiotherapy). Farmers, construction workers, professional drivers and mechanics and coffee shop and bar employees account for more than 70% of patients. Results showed that 64 (48.1%) patients died during the follow-up, 58 (43.6%) of them died from cause related to their disease. With a median follow-up of 25 months, the 5-year disease-free survival (DFS) was 53% and the 5-year overall survival (OS) was 45%. Significant prognostic factors for OS included patient age, advanced staging, heavy alcohol use and poor tumor differentiation while for DFS affected mainly by poor tumor differentiation. We conclude that the disease stage at presentation, tumor grade and alcohol consumption prove to be important predictors for the OS as well as the DFS in our series.

Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression.

OBJECTIVES/HYPOTHESIS: Invasive squamous cell carcinomas (SCC) of the larynx, like most solid tumors, are surrounded by a reactive stroma, in which cancer associated fibroblasts (CAFs) are the predominant cell type. This mesenchymal reaction may affect cancer progression multiply. The proinflammatory enzyme cyclooxygenase-2 (COX-2) has been correlated with head and neck cancer. This study aims to explore the impact of epithelial and stromal COX-2 expression on SCC behavior. STUDY DESIGN: Retrospective case review study performed in a tertiary health center institution. METHODS: Double immunohistochemistry of COX-2 and the CAF marker alpha-smooth muscle actin (alpha-SMA) was utilized in 97 laryngeal cancer patients. Follow-up data were collected in 52 cases. RESULTS: Low COX-2 immunostaining in cancer cells was associated with advanced grade (P = .044) and shorter recurrence-free period (P = .035). CAF expression was positively correlated with the grade of the infiltrating tumor (P = .030). CONCLUSIONS: In laryngeal SCCs, COX-2 may exert its deleterious effect by alterations in the tumor microenvironment. CAF-derived, COX-2-mediated paracrine influences on malignant cells possibly facilitate cancer progression. Overlooking the stromal remodeling could account for unsuccessful treatments of epithelial neoplasms.

Tuberculosis of the parotid gland.

Tuberculosis (Tbc) presented as an isolated parotid mass is rare. Preoperative diagnosis is difficult and the symptomatology is nonspecific. In the majority of the cases an initial diagnosis of a parotid tumor, often a pleomorphic adenoma, is made. We present a 35-year old woman with a six months duration right parotid lump. The mass was firm and nontender without ipsilateral cervical lymphadenopathy, suggesting a parotid neoplasm. The computerized tomography scan showed an intraparotideal tumor resembling a pleomorphic adenoma and thus the patient underwent to a superficial parotidectomy. Fine needle aspiration biopsy was performed but it was not diagnostic. Histological examination revealed an intraparotideal lymph node with changes of granulomatous lymphadenopathy type, like those demonstrated in the tuberculosis and sarcoidosis. Ziehl-Nielsen staining was negative, while the tuberculin skin test (PPD, 5 IU) was positive. The patient's treatment regimen consisted of a 2-month initial phase of isoniazid, rifampin, pyrazinamide and ethambutol followed by a 7 month continuation phase of isoniazid and rifampin. Postoperatively, there was only a mild paresis of the facial nerve resolved a week after. Parotid Tbc is very rare but should be considered as a differential diagnosis of parotid lumps. Fine needle aspiration biopsy (FNAB) is of outmost importance for diagnosis, since the treatment of this entity is primarily conservative. However, surgery could be both therapeutic and diagnostic, especially when other diagnostic examinations fail.

Glottic versus supraglottic tumors: differential molecular profile.

Glottis and supraglottis, although anatomically interconnected, are embryologically distinct. Moreover, squamous cell carcinomas arising from these subsites, differ in terms of epidemiology, risk factors, clinical behaviour and prognosis. This study aims to explore any possible differences between their molecular profiles. We investigated in the two tumor types, the expression of epidermal growth factor receptor (EGFR), nuclear factor-kappaB (NF-kappaB) and retinoid X receptor alpha (RXRalpha), principal signal transducers associated with cancer, as well as cyclooxygenase-2 (COX-2), an enzyme induced in malignant neoplasms. The clinical material includes tumor specimens from 61 patients with laryngeal cancer of glottic or supraglottic origin. Subsite groups were matched for gender, age and histological grade. Paraffin-section immunohistochemistry was performed, to detect the aforementioned molecules. Staining patterns were membranic and cytoplasmic for EGFR, purely cytoplasmic for COX-2, nuclear for RXRalpha and cytoplasmic, as well as nuclear, for NF-kappaB. Intense EGFR and RXRalpha expression was significantly associated with glottic tumor descent (P = 0.011 and 0.001, respectively). No significant relationship was established between neoplasm location and expressions of NF-kappaB, COX-2. Our results show that tumors emerging from the two laryngeal regions, are different with regard to their molecular constitution. Upregulation of EGFR and RXRalpha in carcinomas of the glottis, might be important in the design of subsite-specific chemotherapeutic approaches.

Neurotoxicity of BFM-95 on the medial olivocochlear bundle assessed by means of contralateral suppression of 2f1-f2 distortion product otoacoustic emissions.

OBJECTIVE: Berlin-Frankfurt-Munster 95 (BFM-95) is a common chemotherapeutic protocol against acute lymphoblastic leukemia (ALL). This prospective study investigates whether this protocol has an adverse effect on the medial olivocochlear bundle (MOCB) and/or outer hair cells' (OHCs) function. The distortion product otoacoustic emissions (DPOAEs) and their suppression by means of contralateral application of white noise were used for assessing the function of OHCs and the MOCB, respectively. STUDY DESIGN: Prospective study. SETTING: Oncology and otorhinolaryngology departments in a pediatric hospital. PATIENTS: Thirty-six children treated with ALL-BFM-95. INTERVENTIONS: Before chemotherapy, a baseline audiologic evaluation with tympanogram, standard and extended high frequency, pure-tone audiometry, and DPOAEs in the absence and presence of white noise was performed in all children. This population was divided in three groups. In a first group (n = 12), the evaluation was repeated after four sessions of vincristine administration; in the second group (n = 12), after 8 sessions; and in the third group (n = 12), several months after completion of the protocol. MAIN OUTCOME MEASURE: DPOAEs suppression by contralateral application of white noise. RESULTS: In the first and the third groups, we observed no changes in DPOAE amplitudes. Nevertheless, in the second group, the DPOAEs demonstrated significant decrease at 1416, 1685, 2002, and 2380 Hz. At baseline examination, all groups presented significant suppression at all frequencies. After eight vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 of 12 frequencies. Efferent-mediated DPOAE suppression reappeared in the third group at all frequencies (significant at 5 of 12 frequencies). CONCLUSION: ALL-BFM-95 seems to exert an early and reversible toxic effect on the MOCB, whereas its effects on OHCs are minimal and reversible. These minimal cochleotoxic and neurotoxic properties of ALL-BFM-95 might prove useful for research studies on the role of efferent innervation in hearing.