Faculty Bibliography

PURPOSE/OBJECTIVE:There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features. METHODS:Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II-IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with > 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis. RESULTS:There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393). CONCLUSIONS:Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas.

OBJECTIVE:To develop a clinical consensus statement on the use of balloon dilation of the eustachian tube (BDET). METHODS:An expert panel of otolaryngologists was assembled with nominated representatives of general otolaryngology and relevant subspecialty societies. The target population was adults 18 years or older who are candidates for BDET because of obstructive eustachian tube dysfunction (OETD) in 1 or both ears for 3 months or longer that significantly affects quality of life or functional health status. A modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. RESULTS:After 3 iterative Delphi method surveys, 28 statements met the predefined criteria for consensus, while 28 statements did not. The clinical statements were grouped into 3 categories for the purposes of presentation and discussion: (1) patient criteria, (2) perioperative considerations, and (3) outcomes. CONCLUSION/CONCLUSIONS:This panel reached consensus on several statements that clarify diagnosis and perioperative management of OETD. Lack of consensus on other statements likely reflects knowledge gaps regarding the role of BDET in managing OETD. Expert panel consensus may provide helpful information for the otolaryngologist considering the use of BDET for the management of patients with OETD.

OBJECTIVE:To describe and assess intraoperative and postoperative outcomes in the insertion of osseointegrated auditory implants with a newly designed surgical instrumentation set through a punch type technique. STUDY DESIGN/METHODS:Retrospective case series. METHODS:Patients who underwent bone anchored auditory implant surgery using the Minimally Invasive Ponto Surgery (Oticon Medical, Somerset, NJ) surgical set through a punch technique at nine neurotology tertiary referral based practices were identified. Demographic data, skin thickness at implant site, implant used, duration of surgery, adverse intraoperative events, and postoperative outcomes were recorded. RESULTS:Seventy-five patients comprised the study cohort (32 males, 43 females). Most patients (57. 3%) were aged 51 to 75 years while 30.7% of the cohort comprised those aged 18 to 50 years and 12% were over 75 years. All but two patients received 4 mm fixtured implants and 68% received the Oticon Medical BioHelix implant. Two patients received 3 mm fixture implants and 32% received the Oticon Medical Wide Ponto implant. Mean surgical time was 12.2 minutes (6-45 min, standard deviation of 6.88 min). In three instances, surgery was converted to a linear incision to control brisk bleeding. Skin condition was Holgers 0 to 1 in 91.8%, while 5.5% had Holgers 2, and 2.7% had Holgers 3 at the first postoperative visit. At second postoperative visit, 94.3% had Holgers 0 to 1, 4.3% had Holgers 2, and 1.4% had Holgers 3. All instances of adverse skin reactions were treated with topical or systemic antibiotics and/or local debridement. There were no instances of implant loss. One patient had his implant traumatically displaced to a 45-degree angle necessitating implant replacement at a second site. CONCLUSION/CONCLUSIONS:Punch technique placement of osseointegrated auditory implants using the Minimally Invasive Ponto Surgery surgical set represents a safe technique that further simplifies a progressively minimally invasive surgery.

OBJECTIVES/UNASSIGNED:To examine the frequency in which angled endoscopes are necessary to visualize the true maxillary ostium (TMO) following uncinectomy and prior to maxillary antrostomy. Additionally, to identify preoperative computed tomography (CT) measures that predict need for an angled endoscope to visualize the TMO. STUDY DESIGN/UNASSIGNED:Retrospective study. SETTING/UNASSIGNED:Tertiary academic hospital. PATIENTS AND METHODS/UNASSIGNED:Patients who underwent endoscopic sinus surgery (ESS) between December of 2017 and August of 2018 were retrospectively identified. Cases were reviewed if they were primary ESS cases for chronic rhinosinusitis without polyposis and if they were at least 18 years of age. RESULTS/UNASSIGNED:Sixty-three maxillary antrostomies were reviewed (82.5% were from bilateral cases). Thirty-five cases (55.6%) required an angled endoscope in order to visualize the TMO. Of the preoperative CT measures examined, a smaller sphenoid keel-caudal septum-nasolacrimal duct (SK-CS-NL) angle was significantly associated with need for an angled endoscope intraoperatively to visualize the TMO (17.1° SD ± 3.2 vs 15.0° SD ± 2.9; P = .010). CONCLUSION/UNASSIGNED:Angled endoscopes are likely required in the majority of maxillary antrostomies to visualize the TMO. This is important to recognize in order to prevent iatrogenic recirculation. The SK-CS-NL angle may help to identify cases preoperatively which require an angled endoscope to identify the TMO during surgery.

Performance on cognitive tasks during learning is used to measure knowledge, yet it remains controversial since such testing is susceptible to contextual factors. To what extent does performance during learning depend on the testing context, rather than underlying knowledge? We trained mice, rats and ferrets on a range of tasks to examine how testing context impacts the acquisition of knowledge versus its expression. We interleaved reinforced trials with probe trials in which we omitted reinforcement. Across tasks, each animal species performed remarkably better in probe trials during learning and inter-animal variability was strikingly reduced. Reinforcement feedback is thus critical for learning-related behavioral improvements but, paradoxically masks the expression of underlying knowledge. We capture these results with a network model in which learning occurs during reinforced trials while context modulates only the read-out parameters. Probing learning by omitting reinforcement thus uncovers latent knowledge and identifies context- not "smartness"- as the major source of individual variability.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To describe recurrence patterns in patients with recurrent respiratory papillomatosis (RRP) following surgical intervention. STUDY DESIGN/METHODS:Single-center, retrospective, longitudinal case series. METHODS:Initial and follow-up laryngoscopic examinations of seven previously untreated adult-onset RRP patients were reviewed. Patients were followed longitudinally for periods ranging from 3 months to 7 years. Lesion locations were recorded using a twenty-one region laryngeal schematic, and maps were generated to illustrate the distribution of disease before and after cold-knife or potassium-titanyl-phosphate laser intervention. Univariate and multivariate analyses were employed to examine variables affecting recurrence patterns. RESULTS:Across all patients, a statistically significant correlation between initial distribution and primary recurrence was observed. Seventy-five percent of new lesions were adjacent to regions with preexisting disease; 83% of new glottic lesions were adjacent to preexisting glottic lesions, and 66% of supraglottic lesions were adjacent to preexisting supraglottic regions. No statistically significant differences in recurrence rate were observed across sites. CONCLUSIONS:In previously untreated patients with adult-onset recurrent respiratory papillomatosis, lesions tended to recur either in the same regions or regions adjacent to those affected at the time of initial surgery. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 2019.

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.

OBJECTIVE:The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa? MATERIALS AND METHODS/METHODS:A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified. RESULTS:Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies. CONCLUSIONS:Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa.

General dentists (GDs) have the opportunity to examine their patients for oral premalignancy/malignancy. We estimated the annualized per dentist number of oral lesions suspicious for premalignancy/malignancy discovered by United States (U.S.) general dentists and the annualized per dentist number of histologically-confirmed cancers subsequently diagnosed. Eligible participants were licensed, clinically-active U.S. GDs who were members of the U.S. National Dental Practice-Based Research Network. An a priori sample size of 900 was determined; 2000 GDs were invited to participate; 1,073 completed the study. Self-reported, cross-sectional data were obtained via an online questionnaire during 4/12/2017-8/31/2017 and analyzed. The reported numbers of suspicious oral lesions and histologically-confirmed oral cancer cases diagnosed over the previous six months were quantified. Potential outcome predictors were evaluated as covariates in multivariable analyses. Crude and adjusted statistics were produced by regressing each outcome on each independent variable while assuming a Poisson distribution, log link and utilizing robust standard errors. Eighty-seven percent of dentists reported discovering 1+ lesion suspicious for oral premalignancy/malignancy during the preceding six months. The mean number of suspicious lesions/dentist/year was 9.5; adjusted mean: 9.6. Fifteen percent of participants reported discovering 1+ lesion confirmed as cancer during the same period, 213 confirmed cancer cases/6 months or 426/year. Crude and adjusted mean numbers of histologically-confirmed oral cancers were both 0.4 cancers/dentist/year. Our findings suggest that many U.S. general dentists are actively identifying oral lesions suspicious for premalignancy/malignancy, thereby aiding in the discovery of oral malignancies and representing an important component in the frontline against cancer.

Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.