Faculty Bibliography

INTRODUCTION:/UNASSIGNED:Congenital unilateral lower lip palsy is an infrequently encountered condition that manifests as lower lip asymmetry during smiling, laughing, and crying. Treatment options are not well characterized. METHODS:/UNASSIGNED:The authors present the case of a 51-year-old woman who was referred for surgical intervention for facial paralysis. Physical examination demonstrated a symmetric face at rest that became asymmetric when smiling. The asymmetry, evident by inappropriate inferior displacement of the lower lip, was secondary to unilateral contraction and presence of the depressor labii inferioris. The depressor anguli oris was symmetric bilaterally. Her presentation was consistent with congenital unilateral lower lip palsy. RESULTS:/UNASSIGNED:Lidocaine was injected into the depressor labii inferioris on the side of the face that demonstrated unilateral presence and contraction. This resulted in symmetry of the smile and lower lip without untoward effect. Onabotulinum toxin A was thereafter injected into the depressor labii inferioris. In-office treatment with botulinum toxin injection resulted in a 4-month improvement in smile symmetry. CONCLUSION:/UNASSIGNED:Chemodenervation is a safe and minimally invasive method to improve smile symmetry and lower lip position in cases of congenital unilateral lower lip palsy.

Objectives (1) To determine the short-term effectiveness of oral steroids in women with benign vocal fold lesions and (2) to determine the effectiveness of adjuvant oral steroids in women undergoing voice therapy for benign vocal fold lesions. Study Design Randomized, double-blind, placebo-controlled clinical trial. Setting Tertiary voice care center. Subjects and Methods Thirty-six patients undergoing voice therapy for the treatment of phonotraumatic vocal fold lesions randomly received either a 4-day course of oral steroids or a placebo prior to initiating voice therapy. Voice Handicap Index-10 (VHI-10) scores, video and audioperceptual analyses, acoustic and aerodynamic analyses at baseline, and patient perception of improvement after a short course of steroids or a placebo and at the conclusion of voice therapy were collected. Results Thirty patients completed the study, of whom 27 (only female) were analyzed. The primary outcome measure, VHI-10, did not improve after the 4-day course of steroids or placebo. Secondary measures similarly showed no improvement with steroids relative to placebo. Voice therapy demonstrated a positive effect on both VHI-10 and patient-perceived improvement of voice in all subjects. Conclusion A short course of oral steroids did not benefit women with phonotraumatic vocal fold lesions. In addition, steroids had little beneficial effect when used adjunctively with voice therapy in this patient cohort.

Objective To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design Cross-sectional study. Setting A tertiary care academic children's hospital in the Bronx, New York. Subjects and Methods In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants' haplotype. Results Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations. Conclusions The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

Background/UNASSIGNED:Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods/UNASSIGNED:Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results/UNASSIGNED:Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%). Conclusions/UNASSIGNED:Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

OBJECTIVECerebral venous sinus thrombosis (CVST) is a known complication of surgeries near the major dural venous sinuses. While the majority of CVSTs are asymptomatic, severe sinus thromboses can have devastating consequences. The objective of this study was to prospectively evaluate the true incidence and risk factors associated with postoperative CVST and comment on management strategies.METHODSA prospective study of 74 patients who underwent a retrosigmoid, translabyrinthine, or suboccipital approach for posterior fossa tumors, or a supratentorial craniotomy for parasagittal/falcine tumors, was performed. All patients underwent pre- and postoperative imaging to evaluate sinus patency. Demographic, clinical, and operative data were collected. Statistical analysis was performed to identify incidence and risk factors.RESULTSTwenty-four (32.4%) of 74 patients had postoperative MR venograms confirming CVST, and all were asymptomatic. No risk factors, including age (p = 0.352), BMI (p = 0.454), sex (p = 0.955), surgical approach (p = 0.909), length of surgery (p = 0.785), fluid balance (p = 0.943), mannitol use (p = 0.136), tumor type (p = 0.46, p = 0.321), or extent of resection (p = 0.253), were statistically correlated with thrombosis. All patients were treated conservatively, with only 1 patient receiving intravenous fluids. There were no instances of venous infarctions, hemorrhages, or neurological deficits. The rate of CSF leakage was significantly higher in the thrombosis group than in the nonthrombosis group (p = 0.01).CONCLUSIONSThis prospective study shows that the radiographic incidence of postoperative CVST is higher than that previously reported in retrospective studies. In the absence of symptoms, these thromboses can be treated conservatively. While no risk factors were identified, there may be an association between postoperative CVST and CSF leak.

BACKGROUND:Cetuximab combined with radiation therapy (RT) is an evidence-based treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, locoregional failure remains the primary cause of cancer-related death in this disease. Intratumoral injection of epidermal growth factor receptor (EGFR)-antisense plasmid DNA (EGFR-AS) is safe and has been associated with promising lesional responses in patients who have recurrent/metastatic HNSCC. For the current study, the authors investigated the antitumor effects of cetuximab and EGFR-AS in preclinical HNSCC models and reported their phase 1 experience adding intratumoral EGFR-AS to cetuximab RT. METHODS:Antitumor mechanisms were investigated in cell line and xenograft models. Phase 1 trial eligibility required stage IVA through IVC HNSCC and a measurable lesion accessible for repeat injections. Patients received standard cetuximab was for 9 weeks. EGFR-AS was injected weekly until they achieved a lesional complete response. RT was delivered by conventional fractionation for 7 weeks, starting at week 3. Research biopsies were obtained at baseline and week 2. RESULTS:When added to cetuximab, EGFR-AS decreased cell viability and xenograft growth compared with EGFR-sense control, partially mediated by reduced EGFR expression. Six patients were enrolled in the phase 1 cohort. No grade 2 or greater EGFR-AS-related adverse events occurred. The best lesional response was a complete response (4 patients), and 1 patient each had a partial response and disease progression. EGFR expression decreased in 4 patients who had available paired specimens. CONCLUSIONS:In preclinical models, dual EGFR inhibition with cetuximab and EGFR-AS enhanced antitumor effects. In a phase 1 cohort, intratumoral EGFR-AS injections, cetuximab, and RT were well tolerated. A phase 2 trial is needed to conduct an extended evaluation of safety and to establish efficacy.

PURPOSE:To assess the safety of medical-ward bedside percutaneous dilatational tracheostomy (GWB-PDT). MATERIALS AND METHODS:A retrospective study of all patients who underwent elective GWB-PDT between 2009 and 2015. A joint otolaryngology-ICU team performed all GWB-PDTs. The patients were followed until decannulation, discharge or death. Complications were divided into early (within 24 h) and late, and into minor and major. RESULTS:Two hundred and fifty six patients were included in the study. The mean age was 77.7 ± 11.8 Medical history included cardiac comorbidities (42.6%) and cerebrovascular accidents (34.4%). Overall, 48 patients (18.9%) had 60 complications, of which 70% (42/60) were minor (13 early; 29 late complications). Fifteen patients (5.9%) had major complications. Eight patients had early major complications (loss of airway - two patients [0.8%], pneumothorax - two patients [0.8%], resuscitation - one patient [0.4%], and a single patient (0.4%) died within 24 h following PDT). Two additional patients (0.8%) underwent conversion to an open tracheostomy. Seven patients had late complications (airway complications in six patients [2.3%] and major bleeding in a single patient [0.4%]). Of the seven patients with late major complications, three had two major complications. Half of the complications occurred by POD 3. CONCLUSION:GWB-PDT is a feasible and safe solution for tracheostomies in general-ward ventilated patients.

Afirma GSC utilizes RNA sequencing and machine-learning algorithms to classify cytologically indeterminate thyroid nodules into benign (B) and suspicious (S) categories. Detection of genomic variants and fusions was recently expanded beyond BRAF V600E and RET/PTC1&3 by the Xpression Atlas (XA), which identifies 761 nucleotide variants and 130 fusion gene pairs in 511 genes. Here we used XA to analyze the mutational spectrum of 190 Bethesda III/IV nodules with gold standard histologic diagnoses.190 nodules previously collected in a prospective multicenter blinded trial design were analyzed with the XA.Among the 145 histologically benign nodules, 35 (24%) contained a variant or fusion (XA+). In the 99 benign nodules with GSC-B results there were 15 (15%) with XA variants and none with a fusion. These variants were 7 TSHR, 3 SPOP, 2 EIF1AX, 1 PTEN, 1 TSHR + EZH1, and 1 GNAS. In the 46 benign nodules with GSC-S results, 18 (39%) harbored a variant and 2 (4%) a fusion. There were 9 NRAS, 6 HRAS, 2 TSHR, and 1 SPOP. Two had a PAX8/PPRARG fusion. Among the 45 histologically malignant nodules (41 GSC-S; 91% sensitivity), 22 were XA+ (49% sensitivity). In the 41 malignant nodules with GSC-S results, there were 19 variants (46%) and 2 fusions (5%). The variants were 9 NRAS, 3 HRAS, 3 BRAF V600E, 1 SPOP, 1 KRAS + EIF1AX, 1 EIF1AX, and 1 BRAF K601E. Fusions were BRAF/MKRN1 and 1 ETV6/NTRK3. In the 4 GSC-B false negative nodules (2 PTC, 1 fvPTC, 1HCC), only theHCCcontained a variant (TSHR). In 190 thyroid nodules with definitive histology, malignant nodules were twice as likely to be XA+ than benign nodules (49% vs 24%, p = 0.003 [v2]). Although GSC-S nodules were nearly 3 times more likely than GSC-B nodules to be XA+ (47% vs 16%, p < 0.0001), the PPV for malignancy did not differ among all GSC-S, GSC-S XA+, and GSC-S XA-nodules (47%, 51%, and 43%, respectively; p = 0.77). When XA+, GSC S nodules expressed mainly RAS variants, and GSC B nodules predominantly TSHR variants. Conversely, the NPV for XA was 83%. These findings support GSC as better than XA to rule-out cancer while the addition of XA to GSC-S nodules may provide additional insights into pathway activation and potential cancer treatment targets