Faculty Bibliography

Educational Objective: At the conclusion of this presentation, the participants should be able to define "collision tumor", describe a novel collision tumor of the parotid, and discuss the complexity in managing similar unexpected operative findings.
Objective(s): 1) To present a novel collision tumor of the parotid gland: concurrent squamous cell carcinoma and small cell lymphoma; and 2) to analyze the operative approach to collision tumors.
Study Design: Case report. Abridged Case History: A 75 year old male with left ear lobule melanoma was concurrently found to have a right parotid mass. Pre-operative CT showed a right parotid mass and all FNA attempts were non-diagnostic. The patient was taken to the operating room for excision of the left ear melanoma, as well as for right superficial parotidectomy and right modified neck dissection. The operation was complicated by frozen pathology suggestive of a novel collision tumor.
Result(s): The final histopathology revealed components of both squamous cell carcinoma and small cell lymphoma in both the parotid tumor and ipsilateral cervical lymph nodes. The combination of a parotid collision tumor containing squamous cell carcinoma and small cell lymphoma has never been described and poses a diagnostic and therapeutic challenge. This particular tumor combination is especially complex as the therapeutic approach to each tumor is distinct: squamous cell carcinoma is most often approached surgically, whereas lymphoma is primarily treated with chemotherapy. Ultimately, each tumor must be treated independently and consideration should be given to treating the more lethal component, though the timing and method of such treatment is still a path yet uncharted.
Conclusion(s): Given the rarity of collision tumors, it is difficult to establish a standardized treatment plan, however, perhaps through future reporting of similar cases better therapeutic recommendations can be made

A portable real-time speech processor that implements an acoustic simulation model of a cochlear implant (CI) has been developed on the Apple iPhone / iPod Touch to permit testing and experimentation under extended exposure in real-world environments. This simulator allows for both a variable number of noise band channels and electrode insertion depth. Utilizing this portable CI simulator, we tested perceptual learning in normal hearing listeners by measuring word and sentence comprehension behaviorally before and after 2 weeks of exposure. To evaluate changes in neural activation related to adaptation to transformed speech, fMRI was also conducted. Differences in brain activation after training occurred in the inferior frontal gyrus and areas related to language processing. A 15-20% improvement in word and sentence comprehension of cochlear implant simulated speech was also observed. These results demonstrate the effectiveness of a portable CI simulator as a research tool and provide new information about the physiological changes that accompany perceptual learning of degraded auditory input.

Objective: To assess the frequency of electrode deactivation over time in post meningitic cochlear implant (CI) recipients Study Design: Retrospective chart review Methods: A retrospective chart review of all post meningitic cochlear implant recipients at New York University from 1984 2008 was conducted Patients with more than 2 years of follow up programming and speech perception data were included. Percent of active electrodes was calculated relative to maximum number of programmable electrodes Frequency and pattern of electrode deactivation over time was analyzed and compared to published data on non meningitic CI patients Results: A total of 14 patients with 17 implanted ears were included. Length of follow up ranged from 2 25 years (average 7.3). A total of 9 (53%) ears experienced a reduction in active electrodes. Of these, 3 patients had deactivation of 1 electrode, 4 patients lost 2 electrodes, and the remaining 2 patients had had 5 and 6 electrodes deactivated, respectively. All patients except one had a minimum of 11 active electrodes at all times. Rate of deactivation over time was variable with loss of electrodes occurring up to 4 years post operatively. Three of the 9 ears with electrode deactivation received Nucleus 24 double array devices Loss of electrodes was not correlated with a decline in speech perception, age at implantation or duration of deafness. There was one device failure. Conclusions: Deactivation of CI electrodes over time is common in post meningitic CI recipients (53%) and exceeds rates from non meningitic patients (1%.). Although electrode deactivation is multi factorial, anatomic considerations, such as ongoing compromise of the electrode neural interface by labyrinthitis ossificans, may contribute to deactivation in both the short and long term

Introduction: Diplopia following cerebellopontine angle (CPA) surgery is usually attributed to neuropathy of III, IV or VI cranial nerves. Diplopia in the absence of cranial neuropathy following CPA surgery is rare. We present a series of patients who developed vertical diplopia from skew deviation following resection of tumors in the CPA or labyrinthectomy. Primarily associated with brainstem lesions, this vertical misalignment of the visual axis is postulated to result from unilateral disruption of supranuclear input from the otolithic organs.
Method(s): Retrospective review of patients with complaints of diplopia following CPA surgery. Patients underwent neuroophthalmologic consultation and examination, including opticokinetic testing, confrontational visual field assessment, color plate, pupillary reflex, slit lamp examination and Head Tilt Test.
Result(s): Four patients with residual hearing preoperatively developed skew deviation immediately following surgical intervention, including translabyrinthine(n=1) and retrosigmoid (n=2) approaches to the CPA and labyrinthectomy (n=1). Neuroophthalmologic exam demonstrated intact extraocular movements, and 2-14 mm prism diopter hypertropia on both primary gaze and Head Tilt Testing. In all cases, skew deviation resolved spontaneously with normalization of the neuroophthalmologic examination within 10 weeks.
Conclusion(s): Patients undergoing CPA surgery or labyrinthectomy can develop postoperative diplopia due to skew deviation as a consequence of acute vestibular deafferentation. Patients with significant hearing preoperatively, a probable marker for residual vestibular function, may be specially at risk for developing skew deviation. As vestibular ablation occurs routinely with each of these procedures, skew deviation likely occurs more frequently than is currently diagnosed. Complaints of diplopia should prompt neuro-ophthalmologic consultation to reliably diagnose skew deviation and exclude cranial neuropathy. Patients can be reassured as spontaneous resolution typically occurs within 10 weeks

BACKGROUND: Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. METHODS: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. RESULTS: HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). CONCLUSION: Our study confirms a positive correlation of HPV infection with oral tongue cancer.

As science continues to unravel the genetic basis of disease, an understanding of genetics has become increasingly critical to the practicing clinician. Otorhinolaryngology, a comprehensive specialty in which the physician is responsible for delivering both medical and surgical care within their scope of practice, requires the practitioner to have a fund of knowledge in genetics to effectively communicate and counsel patients. This introductory chapter highlights what is known about the complexity of the human genome and various applications of genetics throughout the field of otorhinolaryngology to be discussed in subsequent chapters. These entities include the genetics of hearing impairment, skull base tumors, molecular genetics in head and neck cancer and systemic diseases with otolaryngologic features

RATIONALE: Natalizumab is a monoclonal antibody (mAb) indicated for treatment of multiple sclerosis. Natalizumab has special attributes which must be addressed when planning rapid desensitization for immediate hypersensitivity reactions (HSR.) Immediate HSRs during rapid desensitization are common, with consequent need to hold the infusion, treat the HSR, and possibly maintain a slower infusion rate. Complete infusion could require more than 8 hours, however, per FDA approved instructions, each bag of natalizumab solution must be infused within 8 hours of preparation or be discarded. Natalizumab is only supplied as 300 mg singledose vials. One published 3-bag, 12-step rapid desensitization protocol wastes approximately 10% of the drug, by discarding most solution in the first 2 bags. Accordingly, one must open another vial of natalizumab, costing approximately $3,000, or the patient will only receive approximately 90% of the typical intended dose. METHODS: Report of two patients with history of immediate HSR to natalizumab, and adaptation of a 3-bag, 12-step, rapid desensitization protocol as follows: Bag #1-0.6 mg in 50ml; Bag #2-6 mg in 50ml; Bag #3 and Bag #4-each 146.7 mg in 122.25ml. Bag #4 was not prepared until Bag #2 was mostly infused. Bags #2, #3 and #4 were infused completely. RESULTS: 99.8% of the intended dose was infused, without immediate HSR. CONCLUSIONS: With adaptation of a published protocol, rapid desensitization to natalizumab 300 mg is possible, utilizing only one single-dose vial, and with minimal chance of exceeding the FDA-approved eight hour infusion window from the time of preparation of each bag

RATIONALE: Rituximab is a monoclonal antibody shown to be effective in treating pediatric chronic idiopathic thrombocytopenic purpura (ITP). Hypersensitivity reactions (HSR), both immediate HSR and systemic delayed HSR have been reported to rituximab, but not in the same patient. METHODS: We report a pediatric patient with immediate HSR to rituximab who underwent successful rapid drug desensitization and later developed serum sickness. RESULTS: On Day 0, this 4 YO male with chronic refractory ITP, developed urticaria and bronchospasm during initial rituximab infusion and the infusion was terminated. On Day 4, rituximab was infused without immediate HSR, utilizing a published 3-bag, 12-step, rapid desensitization protocol, with a maximum infusion rate of 40 ml/hour. On Day 11, rituximab was infused again without immediate HSR, utilizing the same protocol and infusion rates. On Day 14, he developed serum sickness. CONCLUSIONS: This 3-bag, 12-step rapid desensitization protocol, previously shown effective in adult subjects, was successful in a 4 YO. The patient later developed serum sickness, which rapid desensitization would not be expected to prevent. There are published reports of patients developing both immediate and delayed HSRs to a drug, however the delayed HSRs in those cases were cutaneous due to topical drug exposure, whereas in the present case, the delayed HSR was systemic from intravenous administration. We believe this is the first report of a pediatric patient receiving rituximab by rapid desensitization and first report of a pediatric patient developing both immediate HSR and systemic delayed HSR to the same drug, in this case, rituximab