Association of Epstein-Barr virus with nasopharyngeal carcinoma and current status of development of cancer-derived cell lines

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, currently only one EBV+ human NPC cell line (C-666) in long-term culture has been reported. Hence, most of the NPC cell lines may not be representative of the disease itself. In order to better understand and treat NPC, there is an urgent need to develop more EBV+ human NPC cell lines. In this review, we discuss the authenticity of existing NPC cell lines and the impact of our understanding of NPC biology on the treatment of the disease and the relationship of EBV to NPC in the context of cell lines

Ototoxicity from Combined Cisplatin and Radiation Treatment: An In Vitro Study

Objective. Combined cisplatin (CDDP) and radiotherapy is increasingly being used to treat advanced head and neck cancers. As both CDDP and radiation can cause hearing loss, it is important to have a better understanding of the cellular and molecular ototoxic mechanisms involved in combined therapy. Procedure. The effects of CDDP, radiation, and combined CDDP-radiation on the OC-k3 cochlear cell line were studied using MTS assay, flow cytometry, Western blotting, and microarray analysis. Results. Compared to using CDDP or radiation alone, its combined use resulted in enhanced apoptotic cell death and apoptotic-related gene expression, including that of FAS. Phosphorylation of p53 at Ser15 (a marker for p53 pathway activation in response to DNA damage) was observed after treatment with either CDDP or radiation. However, posttreatment activation of p53 occurred earlier in radiation than in CDDP which corresponded to the timings of MDM2 and TP53INP1 expression. Conclusion. Enhanced apoptotic-related gene expressions leading to increased apoptotic cell deaths could explain the synergistic ototoxicity seen clinically in combined CDDP-radiation therapy. CDDP and radiation led to differential temporal activation of p53 which suggests that their activation is the result of different upstream processes. These have implications in future antiapoptotic treatments for ototoxicity

Cochlear Implant Outcomes: A Comparison between Irradiated and Non-irradiated Ears

ObjectivesRadiotherapy for head and neck tumors is known to potentially induce sensorineural hearing loss, which is possibly due to damage to the cochlear and/or auditory pathways. Since the success of cochlear implantation depends on a functional auditory nerve, this paper aims to study the hearing outcomes of cochlear implantation in irradiated ears.MethodsA retrospective study of cochlear implant recipients from our institution who had previously received radiotherapy for head and neck cancers was performed. A control group with cochlear implants who did not receive radiotherapy was recruited. A review of case records, speech discrimination scores (SDS), and a validated subjective questionnaire in the form of the Abbreviated Profile of Hearing Aid Benefit (APHAB) was administered to the study group who fulfilled the inclusion criteria. Global and category scores in both groups were averaged and statistically compared via non-inferiority (NI) testing.ResultsWith the control group (n=8) as the reference, the -ΔNI was defined, and a one-tailed lower 95% confidence interval was used for the irradiated group (n=8). The APHAB degree of improvement (%) results were as follows: global, 28.9% (19.32%, -ΔNI=16.3%); ease of communication, 67.0% (58.36%, -ΔNI=37.5%); background noise, 53.2% (44.14%, -ΔNI=26.8%); reverberation, 41.7% (28.85%, -ΔNI=32.7%); and aversiveness, -46.2% (-67.80%, -ΔNI=-56.9%). The SDS was 66.9% (56.02%, -ΔNI=51.0%). From the results, lower 95% confidence interval limits of global APHAB, SDS, ease of communication, and background noise scores of the irradiated group were within the defined -ΔNI boundary and hence are not inferior to the control. The categories of reverberation and aversiveness could not be proven, however.ConclusionThis study demonstrated marked improvements in hearing measured both objectively and subjectively. The overall hearing outcomes after cochlear implantation for post-irradiated patients were not worse than patients who have had no prior irradiation to ear structures

Effect of radiation on the sensori-neural auditory system and the clinical implications

Ph.DDOCTOR OF PHILOSOPH

Skull Base Osteomyelitis from Otitis Media Presenting as the Collet-Sicard Syndrome

Skull base osteomyelitis can involve the jugular foramen and its associated cranial nerves resulting in specific clinical syndromes. The Collet-Sicard syndrome describes the clinical manifestations of palsies involving cranial nerves IX, X, XI, and XII. We present a rare atypical case of skull base osteomyelitis originating from infection of the middle ear and causing the Collet-Sicard syndrome. Caused by Pseudomonas aeruginosa and Klebsiella pneumoniae, this occurred in an elderly diabetic man subsequent to retention of a cotton swab in an ear with chronic suppurative otitis media. This case report illustrates the possibility of retained cotton swabs contributing to the development of otitis media, skull base osteomyelitis, and ultimately the Collet-Sicard syndrome in the ears of immune-compromised patients with chronically perforated eardrums

Concomitant Obstructive Sleep Apnoea in Patients with Meniere’s Disease: A Case Report and Literature Review

Meniere’s disease (MD) is a condition characterised by fluctuating and progressive hearing loss, aural fullness, tinnitus, and intermittent attacks of vertigo. The disabling vertigo symptoms can be controlled in most patients by lifestyle changes and medications such as diuretics. Should standard medical therapy fail, the patient may require surgery in order to control the disease, but such surgical procedures can be functionally destructive. Obstructive sleep apnoea syndrome (OSAS) is common, especially in people who are grossly overweight. Up to 15% of patients with MD may have concomitant OSA. Unless the OSA is well controlled, such patients may continue to experience MD symptoms despite receiving adequate standard medical therapy for MD. Moreover, MD patients may experience insomnia as a result of vertigo and/or tinnitus where sedatives are indicated. The use of sedatives with muscle relaxant properties may inadvertently further aggravate OSA resulting in a vicious cycle of symptoms. Symptoms suggestive of concomitant OSA must be proactively sought as these patients do not necessarily exhibit the obvious phenotypic features of OSA. This is especially so in Asians where OSAS is commonly observed in people who are not overly obese. We report a case of a female patient who presented with recalcitrant MD disease and was later found to have concomitant OSA. The relevant literature will be reviewed, and learning points will be discussed from the perspective of the otologist/neurotologist. The clinician must always be mindful of the existence of concomitant “silent” OSAS as this impacts the management of patients with MD

Accidental Explantation of a Cochlear Implant in a Child Who Developed Cholesteatoma as a Late Complication of Cochlear Implantation

Introduction. Although rare, cholesteatoma can develop as a late complication of cochlear implantation. The electrode array may then be exposed in the external auditory canal surrounded by cholesteatoma debris. Case Report. The cochlear implant of a child was inadvertently explanted by a clinician during a routine aural toilet procedure. The child had previously reported recurrent ear infections, pain, and unexplained implant function degradation. Reimplantation was carried out 2 days later with good postoperative hearing results. Part of the electrode array was observed to be embedded in cholesteatoma. Postreimplantation recovery was complicated by a breakdown of the blind-sac. Discussion. Clinical indicators that could alert the clinician to the possibility of this late complication include recurrent infections, presence of keratotic debris in the external auditory canal, unexplained implant function degradation, and nonauditory stimulation. Although this patient managed to achieve excellent postreimplantation hearing outcomes, a delay in reimplantation surgery following explantation could possibly compromise successful reinsertion of the electrode array. External ear canal overclosure without mastoid cavity obliteration has merit in facilitating CT scan surveillance, but it may increase the risk of the blind-sac breaking down. This case also illustrated how the electrode array could have facilitated propagation of the cholesteatoma from the middle ear to the mastoid. Conclusion. If aural toilet is required in the implanted ear of a cochlear implant recipient, any complaint of hearing change, pain, or discharge should alert the clinician of the possibility of cholesteatoma developing. It warrants prompt evaluation by an experienced otologist in order to prevent accidental explantation. Keywords. Cochlear implant, cochlear implant complications, chronic suppurative otitis media, cholesteatoma, reimplantation, blind-sac, external auditory canal overclosure, mastoid cavity obliteration

The Value of the Hearing Education Arcade in Educating Caregivers of Hearing-Impaired Patients

Introduction: Although technological advancements have improved the treatment outcomes of hearing-impaired patients, challenges still exist as caregivers are not able to fully appreciate patients' difficulties in communication. An effective education programme is deemed important, including an experiential learning component where people in contact with the patient could experience the sounds actually heard by the patient. This led to the setting up of the Hearing Education Arcade (HEAR), an interactive gallery which contains information about various aspects of hearing loss. This pilot study aims to assess the usefulness of HEAR as an educational tool for caregivers of hearing-impaired patients. Methods: Two separate surveys were carried out. The first survey sought to find out if HEAR had been informative and educational. The second, a focus-group survey on caregivers of hearing impaired children and adults, gauged knowledge levels before and after experiencing HEAR. Results: Most respondents found HEAR to be very informative (86.4%) and highly educational (75.8%). The respondents in both focus groups recorded improvement in knowledge scores after going through HEAR. Conclusion: This study supports the belief that HEAR is a useful tool in the education of caregivers of hearing-impaired patients about hearing, its disorders, the treatment and the needs of the hearing-impaired. When the family and caregivers are properly educated on matters of hearing loss, it can have a positive effect on management outcomes