Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms.

OBJECTIVE: To evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin C/dexamethasone (VT-M/D), compared with normal tympanic membrane and acute TMPs. METHODS: Fifty male Sprague-Dawley rats were divided into three experimental groups: a normal control group (n = 5), an acute TMP group (n = 5) (i.e. 3 days post-myringotomy) and a VT-M/D group (n = 40). The TMs were regularly assessed by otoscopy. The normal control animals were sacrificed on day 0 and the acute TMP group was sacrificed 3 days post-myringotomy for histological and immunohistochemical evaluations. The VT-M/D group was sacrificed at various time points - 14 and 17 days, 3, 4, 6, 8 and 10 weeks. RESULTS: On longitudinal histological examination, compared with normal TM and acute TMP, the perforation edges at the later time points illustrated thickened stratified squamous epithelium rimming around the edges, significant increase in keratin and collagen deposition, increased macrophage infiltration as well as reduced cellular proliferation. Three phases of TMP healing process were identified - the acute healing phase (3-17 days), the transition phase (3-4 weeks) and the chronic phase (6-10 weeks). CONCLUSION: Based on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3-4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks.

Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone.

OBJECTIVE: Chronic tympanic membrane perforation (TMP) in a clinical setting may attract surgical intervention. With the advent of modern biomaterials, new options are available for myringoplasty but safety and efficacy need evaluation in a chronic TMP animal model. The aim of this study was to evaluate the efficacy of ventilation tube (VT) insertion in conjunction with topical application of mitomycin C/dexamethasone (M/D) for the creation of chronic TMP in rats. METHODS: Thirty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were divided into three experimental groups: spontaneous healing (myringotomy control), VT insertion for 2 weeks and VT insertion for 2 weeks in conjunction with topical application of M/D (VT-M/D). All TMs were regularly assessed by otoscopy for 10 weeks and then animals were sacrificed for histological evaluation. RESULTS: In the VT-M/D group, seven out of ten (70%) perforations were patent at 10 weeks (mean patency, 57.9 days; P<0.01). The VT group had two out of ten (20%) perforations patent at 10 weeks (mean patency, 26.5 days; P<0.01), while all TMPs from the myringotomy control group were closed by day 9 (mean patency, 7.2 days). Histologically, the TMPs patent at week 10 had a stratified squamous epithelialized rim, keratinocyte layer thickening around the perforation edge as well as increased collagen deposition and macrophage infiltration. CONCLUSION: Chronic TMP in a rat model was successfully created by VT insertion and the efficacy was increased in combination with topical application of M/D.

Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy.

OBJECTIVES: Surgical intervention such as myringoplasty or tympanoplasty is an option in the current clinical management of chronic tympanic membrane perforation (TMP). Animal models of chronic TMP are needed for pre-clinical testing of new materials and to improve existing techniques. We evaluated several reported animal model techniques from the literature for the creation of chronic TMPs. The aim of this study was to evaluate production of chronic TMPs in a rat model using topical mitomycin C/dexamethasone, paper insertion into middle ear cavity (MEC) or re-myringotomy. METHODS: Forty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were randomly divided into 3 experimental groups: application of topical mitomycin C/dexamethasone, paper insertion into middle ear cavity, or re-myringotomy. Control perforations were allowed to close spontaneously. TMs were assessed regularly with otoscopy for 8 weeks. At the end of 8 weeks, animals were sacrificed for histology. RESULTS: The closure of TMPs was significantly delayed by mitomycin C/dexamethasone (mean patency, 18.9 days; P≤0.01) compared with the control (mean patency, 7 days), but was not significantly delayed in the paper insertion group (mean patency, 9.4 days; P=0.74). Repeated myringotomy of closed perforations (mean number of myringotomies, 8.9 per ear) stimulated acceleration of closure rather than delay. Histologically, the mitomycin C/dexamethasone group had almost normal TM morphology, while the paper insertion group revealed inflammatory and granulomatous responses. The re-myringotomy group had a thickened TM fibrous layer with collagen deposition. CONCLUSIONS: Mitomycin C/dexamethasone delayed TMP closure in rats but the effect was not sufficiently long-lasting to be defined as a chronic TMP. Neither paper insertion into middle ear cavity nor re-myringotomy created chronic TMP in rats.

Rates of revision and device failure in cochlear implant surgery: a 30-year experience.

OBJECTIVES/HYPOTHESIS: To characterize revision cochlear implant surgery and quantify rates of revision and device failure. STUDY DESIGN: Retrospective review of 235 cases of revision cochlear implant surgery performed at the Sydney Cochlear Implant Center over a period of 30 years, between January 1982 and June 2011. METHODS: Patient demographics and characteristics of revision surgery were retrospectively extracted from a centralized database. Analyses of overall and cumulative rates were performed. RESULTS: During the study period, 2,827 primary cochlear implantations were performed in 2,311 patients, with 201 primary implants in 191 patients of this cohort (109 children and 82 adults) undergoing 235 revision surgeries. The most common indication for revision surgery was device failure (57.8%), followed by migration/extrusion (23.4%), infection/wound complication (17.0%), and poor outcome/secondary pathology (6.4%). The majority of revision surgeries were reimplantations. Overall revision and device failure rates were 8.3% and 4.8%, respectively. The cumulative revision rate for primary implants at all ages increased linearly by 1% per year. The cumulative revision rate was significantly higher in children, and decreased with more recently performed implantations and with newer generations of implants. CONCLUSIONS: The cumulative revision rate for primary implants suggests an ongoing linear relationship between the time of postprimary implantation and the need for revision surgery. We have formed an evidence base that characterizes the nature and frequency of revision surgery in a high-volume setting, allowing clinicians to effectively counsel prospective patients and clinics to understand the burden of revision surgery and device failure.

Relapse of Non-Hodgkin's Lymphoma Involving the Trachea: Acute Subglottic Obstruction.

Relapsing lymphoma involving the trachea causing tracheal obstruction is exceedingly uncommon. Despite its rarity, it should be considered in the differential diagnosis when a patient with known lymphoma presents with signs of airway obstruction such as stridor. We report an unusual case of relapsing non-Hodgkin's lymphoma with tracheal involvement in a 57-year-old female and review the relevant literature. It is highly unusual for relapsing lymphoma to involve the trachea causing tracheal obstruction. Despite its rarity, it can present with life-threatening airway obstruction which may be rapidly progressive requiring immediate surgical intervention such as tracheostomy.

Animal models of chronic tympanic membrane perforation: in response to plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice.

Tympanic membrane perforations (TMP) are relatively common but are typically not treated in their acute stage, as most will heal spontaneously in 7-10 days. Those cases which fail to heal within 3 months are called chronic TMP which attract surgical intervention (e.g. myringoplasty), typically with a temporalis fascia autograft. New materials for the repair of chronic TMP are being developed to address deficiencies in the performance of autografts by undergoing evaluation in animal models prior to clinical study. However, there is currently a lack of ideal chronic TMP animal models available, hindering the development of new treatments. Various techniques and animal species have been investigated for the creation of chronic TMP with varied success. In the present commentary, we bring to the attention of readers the recent report by Shen et al. in Journal of Translational Medicine. The study reported the creation of a chronic TMP animal model in plasminogen gene deficient mice. However, the short observation time (9, 19 days), lack of success rate and the scarcity of solid evidence (e.g. otoscopic & histologic images) to confirm the chronicity of TMP warrant a more thorough discussion.

Animal models of chronic tympanic membrane perforation: a 'time-out' to review evidence and standardize design.

OBJECTIVE: To review the literature on techniques for creation of chronic tympanic membrane perforations (TMP) in animal models. Establishing such models in a laboratory setting will have value if they replicate many of the properties of the human clinical condition and can thus be used for investigation of novel grafting materials or other interventions. METHODS: A literature search of the PubMed database (1950-August 2014) was performed. The search included all English-language literature published attempts on chronic or delayed TMP in animal models. Studies of non English-language or acute TMP were excluded. RESULTS: Thirty-seven studies were identified. Various methods to create TMP in animals have been used including infolding technique, thermal injury, re-myringotomy, and topical agents including chemicals and growth factor receptor inhibitors. The most common type of animal utilized was chinchilla, followed by rat and guinea pig. Twenty three of the 37 studies reported success in achieving chronic TMP animal model while 14 studies solely delayed the healing of TMP. Numerous experimental limitations were identified including TMP patency duration of <8 weeks, lack of documentation of total number of animals attempted and absence of proof for chronicity with otoscopic and histologic evidence. CONCLUSION: The existing literature demonstrates the need for an ideal chronic TMP animal model to allow the development of new treatments and evaluate the risk of their clinical application. Various identified techniques seem promising, however, a need was identified for standardization of experimental design and evidence to address multiple limitations.

The vestibular schwannoma surgery learning curve mapped by the cumulative summation test for learning curve.

OBJECTIVE: To demonstrate and quantify the learning curve for microsurgical excision of vestibular schwannoma in a newly formed neurootologic team by using the cumulative summation test for learning curve (LC-CUSUM). To secondarily identify the factors influencing postoperative facial nerve outcome. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Between 1999 and 2011, 153 consecutive cases of vestibular schwannoma excision. INTERVENTION: One-hundred and fifty-three patients underwent excision of vestibular schwannoma. MAIN OUTCOME MEASURES: Facial nerve outcomes were assessed using the House-Brackmann (HB) facial nerve grading system. Postoperative facial nerve outcomes at 12 months were analyzed using the LC-CUSUM method with HB Grades I to III being defined as successful outcomes. The factors that influence postoperative facial nerve outcome were analyzed. RESULTS: The constructed learning curve shows a gradual improvement in facial nerve outcomes. The learning curve crossed the derived LC-CUSUM barrier at the 56th procedure, indicating that sufficient evidence had accumulated to demonstrate that the surgeon had achieved optimal outcomes at this point. Tumor size (p = 0.008) and surgical approach (p = 0.005) were 2 additional significant factors influencing postoperative facial nerve outcome. CONCLUSION: The learning curve is evident in this series of microsurgical excisions of vestibular schwannoma. A newly formed team needs to perform at least 56 cases to gain sufficient experience to accomplish optimal results. Position along the learning curve, tumor size, and familiarity with a preferred surgical approach are the factors, which dominated facial nerve outcome. We recommend the use of LC-CUSUM test for learning curve analysis.

Predictors of outcome in patients with metastatic cutaneous head and neck squamous cell carcinoma involving cervical lymph nodes: Improved survival with the addition of adjuvant radiotherapy.

BACKGROUND: The purpose of this study was to compare the outcome of surgery against surgery plus radiotherapy in patients with metastatic cutaneous head and neck squamous cell carcinoma (HNSCC) to cervical nodes. METHODS: We conducted a 28-year retrospective analysis of 122 patients whom were treated for metastatic cutaneous HNSCC involving the cervical nodes (levels I-V). RESULTS: After surgery alone, 11 patients (55%) developed recurrence compared with 23 patients (23%) after surgery plus radiotherapy. On multivariate analysis, the following variables were significantly associated with disease-free survival (DFS): immunosuppression (p = .002), treatment modality (p < .001), extracapsular spread (p = .009), and pathological nodal stage (p = .04). Patients undergoing surgery plus radiotherapy had a significantly better 5-year DFS (74% vs 34%; p = .001) and 5-year overall survival (OS; 66% vs 27%; p = .003) compared with surgery alone. CONCLUSION: In patients with metastatic cutaneous HNSCC involving cervical nodes, survival was significantly improved with the addition of radiotherapy.