COSM13: Otolaryngologists Share Research, Insights at Annual Meetings

ORLANDO—The Combined Otolaryngology Spring Meetings, held here April 10–14, featured the annual meetings of several otolaryngology organizations, covering topics ranging across ear, nose and throat care. Here are a few highlights from the programs of some of these organizations.

Progress Treating Neurofibromatosis Type 2

American Neurotology Society

Several trials are ongoing and showing some promise in the treatment of neurofibromatosis type 2 (NF2), said Bradley Welling, MD, PhD, chair of otolaryngology-head and neck surgery at Ohio State University’s College of Medicine in Columbus, during his William F. House Lecture at the Annual Spring Meeting of the American Neurotology Society.

Lapatinib, an erbB2/EGF-inhibitor, is being studied in a phase 0 trial, with enrollment nearing a close. Patients will be treated 10 days pre-operatively, and then the tumor will be removed, with the drug concentration and molecular target assessed. That trial is being led by Johns Hopkins, along with Ohio State and other centers.

An earlier phase 2 study found a 15 percent reduction in tumor volume in four of 17 patients and a 10-decibel improvement in hearing in four of 13 (Neuro Oncol. 2012;14:1163-1170).

In the first study of the VEGF-inhibitor bevacizumab in NF2, 13 of 23 showed a hearing response, some with “quite remarkable” improvement, Dr. Welling said (Otol Neurotol. 2012;33:1046-1052). Two Phase 2 trials, which will assess hearing response and radiographic change, are getting underway, he said.

At Ohio State, a phase 1 study of the HDAC-inhibitor AR42 will assess safety. While the study was originally meant to include only liquid tumors, solid tumors, including NF2 patients, have been added. Eighteen patients, five with NF2-related tumors, have been enrolled in the dose-escalation study.

In all, eight drugs are now in trials for NF2, and are critically needed considering that the disorder has a 20-year survival rate of just 38 percent and causes deafness, facial paralysis and stroke. For now, treatment has to take into account the seriousness of the tumors found, along with the patient’s willingness to accept the risk of clinical trials.

Beyond that, the research has some other challenges, Dr. Welling said. He emphasized that the drugs will have to be well-tolerated because they may need to be taken for a lifetime. “How do we define success?” he said. “Certainly, I think if we stop tumor growth, for most of us, we consider that successful. We don’t necessarily have to see the tumor regress. Do we decide based on the effect of the growth on the target? And how sustainable is the treatment?”

Evidence in Rhinology Care

American Rhinologic Society

Panelists at the American Rhinologic Society Meeting talked about evidence in the literature, both published and not yet published, that has helped them, and how they incorporate it into their practice.

Michael Stewart, MD, MPH, chairman of the department of otolaryngology-head and neck surgery at Weill Cornell Medical College in New York and editor in chief of The Laryngoscope, emphasized that there is “good evidence out there, which unfortunately takes a long time to get disseminated.”

John Krouse, MD, PhD, chair of otolaryngology-head and neck surgery at Temple University in Philadelphia, said he recalled a 2005 study that showed that the topical intranasal antihistamine azelastine performed better than oral antihistamines, which he said was a “paradigm shift” for him and led him to greatly reduce his use of oral antihistamines.

David Poetker, MD, MA, of the Medical College of Wisconsin in Milwaukee, acknowledged that he often looks to the literature “to justify what I’ve been doing” rather than to seek out best practices, which he cautioned against. Literature can also be helpful to communicate to patients the “rationale” of treatment in order to encourage better compliance.

Dr. Stewart cautioned that it can be easy to “fall into the trap” of relying on one well-done study and not taking into account all of the other evidence.

Bionic Approaches to Facial Reanimation

American Academy of Facial Plastic and Reconstructive Surgery

At the Spring Meeting of the American Academy of Facial Plastic and Reconstructive Surgery, Alice Frigerio, MD, PhD, of the Carolyn and Peter Lynch Center for Laser and Reconstructive Surgery at Harvard Medical School in Boston, discussed her group’s efforts to refine the use of infrared light beams as a technology for eye-blink detection this biosignal serves as a trigger for facial pacing. The focus, at this point, is to elicit biomimetic eye blinks on the paralyzed side of a face using a close-looped device that can record

movement of the healthy side of the face and pace-assisted movements on the contralateral side, in case of unilateral facial nerve injury. Using infrared light beams, her group tested a prototype of goggles and obtained perfect results, defined as no false positives or false negatives, in 25 percent of the trials. Eighty-seven percent had true positives, while 11 percent had false positives, half of which were due to the software mistaking a twitch for a blink.

In another presentation, Daniel McDonnall, PhD, director of research at Salt Lake City-based Ripple, a medical device manufacturer, said his firm has found—in a small, six-person study—that a pain-free “evoked blink” using facial electrical stimulation is feasible in facial paralysis patients. The technique involves multi-channel stimulation across the eyelid and is not feasible for long-term denervation patients, Dr. McDonnall said.

One of the biggest challenges was assessing pain level, he said, and researchers settled on a scale of 1 to 5, with 1 being barely perceptible and 5 being “very mildly irritating.”

“It’s really not something that’s clinically relevant if we can’t do this in a comfortable region,” he said. Plus, he said, the electrodes posed an engineering challenge because they need to be thin and flexible enough during their 10-year lifetime to allow flex tens of millions of times as patients blink.

Hearing Loss and Dementia

American Otological Society

In a population-based study featured at the Annual Spring Meeting of the American Otological Society, researchers led by Richard Gurgel, MD, assistant professor of otolaryngology-head and neck surgery at the University of Utah in Salt Lake City, found that hearing loss was an independent predictor of dementia and of faster decline in cognition.

The study, which began in 1995 and centered on Cache County in northern Utah, was remarkable in that 90 percent of the potential subjects were actually enrolled. That group was assessed for dementia using screening and an expert panel. Researchers found 4,463 subjects who were older than 65 and did not have dementia, thereby meeting the study’s criteria. Of these, 836 had hearing loss. Of those with hearing loss, 16.3 percent developed dementia, compared with just 12.1 percent of those without hearing loss (p<.001). It took an average of 10.3 years for those with hearing loss to develop dementia, compared with 11.9 for those who had no hearing loss (p <.001)

After controlling for factors including gender, age, education level and genetic risk, researchers found hearing loss to be an independent predictor of dementia. They also found, after controlling for other factors, that hearing loss was associated with faster decline on the Modified Mini Mental State Examination, at a rate of 0.26 points worse per year than those without hearing loss.

Dr. Gurgel acknowledged that the assessment of hearing loss was done qualitatively, not quantitatively. He also cautioned that it was an epidemiological study that reveals associations and not necessarily causes.

However, the findings at least raise, again, the question of why this link exists, Dr. Gurgel said. “Hearing loss, on one hand, could be just a correlation: those who have hearing loss, we know, often become more socially isolated (and) social isolation, in and of itself, is a risk factor,” he said. “Another thought is that there is a real neurobiological association between hearing loss and dementia, that when one person loses neurological function in one sensory domain, that may be a harbinger for a neurological decline in another domain.”

Lateral Sinus ThrombosisAmerican Neurotology Society

In one case that drew attention at a session during the 48th Annual Spring Meeting of the American Neurotological Society, panelists discussed a 56-year-old diabetic man with a neck mass and otorrhea, complaining of neck stiffness and fever. The patient was found to be running a fever, with low blood pressure and a high heart rate, an elevated white count and edema. Greenish pus was running out of his ear and he had post-auricular swelling down into the neck. He was eventually found to have lateral sinus thrombosis (LST).

Panelists discussing the case said they would generally proceed conservatively with anti-coagulation, unless imaging showed a dire situation, noting that the standard is moving toward this approach. In this case, drainage was actually performed, along with anti-coagulation and IV antibiotics.

Fred Telischi, MD, chairman of otolaryngology at the University of Miami, who presented the case, said LST can be difficult to diagnose but that headaches, often accompanied by malaise, spiking fevers, chills and post-auricular edema, are common. “Headaches are a critical complaint, though non-specific,” Dr. Telischi said. “We should take it seriously if a patient presents like this, has headaches and some of these other symptoms.” Swelling of the optic nerve is also an important symptom to watch for, he said.

He said the goal in managing LST is to clear the infection but not necessarily to re-establish blood flow, with a needle aspiration done if necessary. If patients develop brain edema and intracranial hypertension, he said, consult with neurosurgery and take steps to reduce the pressure. Anti-coagulation, generally with IV heparin followed by subcutaneous heparin, is particularly appropriate when ICH and a decline in mental status are problems, Dr. Telischi.

In the case of a risk of septic emboli, more urgent steps should be taken, he said. “This is probably the one indication to ligate the internal jugular vein,” Dr. Telischi said.