Awards for the best Triological theses this year went to three researchers, including two co-Mosher Award winners and a Fowler award winner. The awards were given here at the 115th Annual Meeting of the Triological Society on April 20, held as part of the Combined Otolaryngology Spring Meetings.
Nira Goldstein, MD, MPH, associate professor of otolaryngology at SUNY Downstate Medical Center in Brooklyn, N.Y., received a Mosher Award for her work in developing a clinical assessment test that seems to reliably evaluate children for sleep-disordered breathing.
Judith Lieu, MD, MSPH, assistant professor of otolaryngology-head and neck surgery at Washington University School of Medicine in St. Louis, tracked the educational performance and cognitive abilities of children with unilateral hearing loss (UHL), work that also earned her a Mosher Award.
Quyen Nguyen MD, PhD, an associate professor in the division of otolarynology-head and neck surgery at the University of California, San Diego, won the Fowler Award for developing probes that illuminate tumor tissues and nerves, which helps with resections.
Pediatric Sleep-Disordered Breathing
In her study, Dr. Goldstein set out to establish a reliable way to evaluate children for sleep-disordered breathing in the clinic rather than requiring expensive overnight polysomnography (PSG), a method not always easily available even if the expense is justified.
“Greater than 90 percent of children in the United States are treated for sleepdisordered breathing based on clinical assessment alone,” Dr. Goldstein said. “Prior studies have shown the accuracy of clinical assessment in predicting a positive sleep study is rather poor. It ranges from 30 to 81 percent [in children].”
Researchers offered enrollment to 104 families with children between the ages of 2 and 12 years old; 100 enrolled, with 94 of them actually getting overnight studies. In the PSG, 66 children tested positive and 60 had surgery as a result, and 28 of those had post-operative studies. Before the PSG, the parents of the children completed the OSA-18 and PedsQL 4.0 (two quality-of-life assessments) and the Child Behavior Checklist (a standardized measure of child behavior). Researchers reduced the 30 initial assessment items to 15, which became the basis for the CAS-15 test, after an item reduction and principal components analysis.
The area under the curve for the CAS-15 in predicting a positive polysomnography test was 77 percent. Researchers determined that the optimal score was greater than or equal to 32, which resulted in a sensitivity of 77.3 percent and a specificity of 60.7 percent. All 41 children with a CAS-15 of 32 or greater and who underwent a PSG had a post-operative CAS-15 score of less than 32, indicating improvement. The highest post-operative score was 30.
“Using a cutoff score of greater than or equal to 32, CAS-15 exhibited very good sensitivity and specificity in our referred sample,” Dr. Goldstein said. “Therefore, it may be used for the evaluation of most children. We can save PSG for the evaluation of complicated patients, children with discrepancies between their histories and physical examination, and children who remain symptomatic after [tonsillectomy and adenoidectomy].”
Children with Unilateral Hearing Loss
In her study, Dr. Lieu set out to determine whether speech-language and educational performance or behavioral problems improved or worsened over time in a group of school-age children with unilateral hearing loss. The aim was to drill down further beyond what is already known about the problems among children with UHL.
“The effects of unilateral hearing loss … in children has been documented since the early 80s, where people have found educational and behavioral problems in multiple studies,” Dr. Lieu said.
Studies have found that between 22 and 59 percent of kids with UHL have such problems, and that 24 to 35 percent fail a grade in school, compared with 3 percent of children without hearing loss (Arch Otolaryngol Head Neck Surg. 2004;130:524-530). Studies have also found that children with UHL have poorer oral speech skills and have a greater risk of needing an individualized education program (IEP) and speech therapy than children without hearing loss (Pediatrics. 2010;125:e1348-1355).
Dr. Lieu’s study followed children ages 6 to 8 at the time of recruitment for more than three years, with researchers looking at standardized test scores on cognition, language and achievement, as well as the Child Behavior Check List, hearing on audiograms and school records on IEPs and speech therapy.
There were improvements across almost all categories. There were statistically significant improvements in full IQ, verbal IQ, oral expression and oral composite scores. Even though the group as a whole showed improvements over the three years, more than 20 percent of the group still scored at the third percentile or lower in competency scales for activities, social skills and school performance. And 24 percent had an academic area of weakness or executive function problems as reported by teachers, while roughly 50 percent continued to participate in IEPs over three years.
The study found that starting IQ scores and participation in an IEP may play a role in the improvement. As an example, Dr. Lieu showed a graph of oral composite scores over time for those with baseline IQs of higher than 90 and for those with IQs of 90 or lower. Those with higher IQ scores showed an upward slope, while those with a lower IQ actually showed a drop-off in score. In another example, those with an IEP showed greater improvements in verbal IQ than those without one. In fact, the IEP group started off with lower scores but had essentially caught up to the other group.
Dr. Lieu said that while the standardized scores acted as an implicit control group, the lack of a true control group was a limitation in the study’s ability to assess the students’ progress. Whether the changes were a regression to the mean, a true catch-up, or an improvement that occurred just by virtue of taking the standardized tests, is unknown, she said.
“We feel that further studies in older children and adolescents are needed in order to answer some of these questions,” she said. “Are there interventions that can improve the cognitive and language skills in children with UHL, such as the IEPs, and does UHL affect matriculation to higher education and occupational choices?”
Tumor Tissue Margin Clarity
Dr. Nguyen discussed a probe she and her team developed that can turn tumor tissue a bright fluorescent color.
In resection, it’s all about getting clear margins. “It’s not always clear,” Dr. Nguyen said. “We try our best but often we have to send the frozen specimen to the pathology lab and wait for the pathologist to tell us whether or not the margins are clear…. Wouldn’t it be better if we could see the difference with our own eyes, see the difference between what’s cancerous and what’s normal?”
The probe molecule includes two parts: one that acts as the “sticky” portion (a positively charged peptide) and one that is a kind of nonstick backing like that on a book of stamps. The two parts can be taken apart by enzymes made by tumors, Dr. Nguyen said. A fluorescent dye is attached to the sticky portion. Since only the tumor cells will cause the molecules to become sticky, they bind only to tumor tissue.
“The tumor now has the molecular scissors which can then cut these two pieces apart,” Dr. Nguyen said. “The nonstick backing floats away and the tumor labels itself.”
By using the probe in animal models, the team found there was a 90 percent improvement over standard surgery in the amount of residual tumor that remained, Dr. Nguyen said. When the team used the probe to detect metastatic lymph nodes in a study involving22 nodes in 10 animals, they found no false positives or false negatives.
She and her team have also produced a probe that can similarly light up nerves. “The ability to preserve the nerves is equally important as it is to remove the tumor,” she said. “With the injectable probe, now the tumor’s boundaries are really clear.”