Faculty Bibliography

OBJECTIVE:Currently no established criteria exist to guide use of ex utero intrapartum treatment (EXIT) for fetal neck mass management. This study aims to correlate prenatal radiographic findings with incidence of ex utero intrapartum treatment and necessity of airway intervention at delivery. METHODS:We reviewed our EXIT experience between 2012 and 17. Furthermore, we performed a literature review of articles reporting incidences of fetal neck masses considered for EXIT. Articles that were included (1) discussed prenatal radiographic findings such as size, features, and evidence of compression and (2) reported extractable data on delivery outcomes and airway status. RESULTS:Ten cases at our institution were reviewed. Another 137 cases across 81 studies met inclusion criteria. These studies showed aerodigestive tract compression to be significantly associated with neck masses undergoing EXIT. Additionally, there was significantly higher incidence of airway intervention in cases where polyhydramnios, anatomic compression, and solid masses were seen on prenatal diagnostic imaging, while mass location and size did not correlate with airway intervention. CONCLUSION/CONCLUSIONS:With this data, we propose that any neck mass with anatomic compression on fetal imaging in the 3rd trimester should be considered for EXIT. When radiographic findings do not show compression but do display polyhydramnios or a solid neck mass (regardless of polyhydramnios), an airway surgeon should be available for perinatal airway assistance.

We describe the use of minimally invasive trigeminal ablation, an endoscopic ablative technique to treat trigeminal neuralgia in patients who are traditionally poor surgical candidates. We present 4 patients who presented with refractory unilateral trigeminal neuralgia. Three of the patients had previously failed stereotactic radiosurgery and three of them have multiple sclerosis. Due either to lack of neurovascular compression, minimally invasive trigeminal ablation was offered. Intraoperatively, an incision is made along the buccal mucosa or mid-brow and the tissue is endoscopically dissected in a plane towards the symptomatic nerve. Once isolated, the epineurium is partially ablated with thermocautery and the tissue surrounding the nerve is decompressed. All patients reported resolution of their pain post-operatively and were pain free at last follow up. Two patients had mild hypesthesia over the ablated nerve territory. Minimally invasive trigeminal ablation is a safe and effective technique for symptomatic control of trigeminal neuralgia. The efficacy, low risk, and relative ease of the procedure makes it ideal for use in patients who are refractory to medical management and have no neurovascular compression, are unable to tolerate traditional surgery or have failed other therapies.

Objective/UNASSIGNED:were assayed to optimize siRNA-mediated alteration of gene expression. Methods/UNASSIGNED:-siRNA complex. Results/UNASSIGNED:-complexed Smad3 siRNA at 1 day postinjection. Qualitative suppression of Smad3 expression persisted to 3 days following injury, but did not achieve statistical significance. Conclusions/UNASSIGNED:yielded effective, yet temporally limited knockdown of Smad3 in vivo. Peptoids may provide a versatile platform for the discovery of siRNA delivery vehicles optimized for clinical application. Level of Evidence/UNASSIGNED:NA.

IDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms.

Recurrent Respiratory Papillomatosis (RRP) is a rare disease of the aerodigestive tract caused by the Human Papilloma Virus (HPV) that manifests as profoundly altered phonatory and upper respiratory anatomy. Current therapies are primarily symptomatic; enhanced insight regarding disease-specific biology of RRP is critical to improved therapeutics for this challenging population. Multiplex PCR was performed on oral rinses collected from twenty-three patients with adult-onset RRP every three months for one year. Twenty-two (95.6%) subjects had an initial HPV positive oral rinse. Of those subjects, 77.2% had an additional positive oral rinse over 12 months. A subset of rinses were then compared to tissue samples in the same patient employing HPViewer to determine HPV subtype concordance. Multiple HPV copies (60-787 per human cell) were detected in RRP tissue in each patient, but a single dominant HPV was found in individual samples. These data confirm persistent oral HPV infection in the majority of patients with RRP. In addition, three novel HPV6 isolates were found and identical HPV strains, at very low levels, were identified in oral rinses in two patients suggesting potential HPV subtype concordance. Finally, somatic heteroplasmic mtDNA mutations were observed in RRP tissue with 1.8 mutations per sample and two nonsynonymous variants. These data provide foundational insight into both the underlying pathophysiology of RRP, but also potential targets for intervention in this challenging patient cohort.

BACKGROUND:Is posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC). METHODS:In an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality. RESULTS:Across all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31). CONCLUSIONS:Posttreatment functional status is a strong prognostic marker of survival in patients with HNC.

BACKGROUND: There is no effective therapy for patients (pts) with IDH-mutant gliomas that progress after RT and chemotherapy. At time of progression, these tumors have often transformed to glioblastoma (GBM) and have increased numbers of somatic mutations, i.e. have a ?hypermutator phenotype?. We hypothesized that there is synergistic efficacy of Avelumab (anti-PD-L1) combined with HFRT in pts with secondarily trans- formed IDH-mutant GBMs. Safety-lead-in results will be presented.
METHOD(S): This is a phase II, open-label, single-arm, multicenter study of Avelumab with HFRT in adults with transformed IDH-mutant GBM who previously received RT and TMZ and/or PCV. All pts received Avelumab 10 mg/kg IV followed at Day 8 by HFRT (25 Gy in 5 daily 5-Gy fractions) and then Avelumab 10 mg/kg IV every 2 weeks. A 3 + 3 design was used for a 6-patient safety-lead-in cohort. Adverse events were recorded according to CTCAE.
RESULT(S): Six pts (F=4, M=2) with a median age= 45.5 yrs (range 31.5-54.4 yrs) were enrolled in the safety-lead-in cohort. No DLT was observed. Grade >= 3 AEs included increased cerebral edema (3 pts), hyponatremia (1 pt) and worsening hemiparesis (3 pts). Grade <= 2 AEs included nausea, hypothyroidism, lymphopenia, thrombocytopenia, transaminase elevation, and fever/chills. Median follow-up time was 8.9 mo. Best treatment response was SD in 1 patient. At time of last follow-up all pts have discontinued treatment for PD. Median PFS was 4.2 mo (range 1.4-5.7). Median OS was 10.1 (range 6.8-21+) mo. 4 pts (67%) died, 2 pts remain alive in follow-up at 6.9 and 21.6 months after treatment initiation. The study was closed after the safety lead-in completed enrollment due to slow accrual.
CONCLUSION(S): Avelumab combined with HFRT was tolerable without dose-limiting toxicity in this safety-lead-in cohort of adult patients with transformed IDH-mutant GBM. Further studies are necessary to determine efficacy of this treatment regimen

OBJECTIVES/OBJECTIVE:The Quick Spectral Modulation Detection (QSMD) test provides a quick and clinically implementable spectral resolution estimate for cochlear implant (CI) users. However, the original QSMD software (QSMD(MySound)) has technical and usability limitations that prevent widespread distribution and implementation. In this article, we introduce a new software package EasyQSMD, which is freely available software with the goal of both simplifying and standardizing spectral resolution measurements. DESIGN/METHODS:QSMD was measured for 20 CI users using both software packages. RESULTS:No differences between the two software packages were detected, and based on the 95% confidence interval of the difference between tests, the difference between the tests is expected to be <2% points. The average test duration was under 4 minutes. CONCLUSIONS:EasyQSMD is considered functionally equivalent to QSMD(MySound) providing a clinically feasible and quick estimate of spectral resolution for CI users.

BACKGROUND:The aim of the study is to analyse the factors related to permanent surgical complications in children and adolescents with papillary thyroid carcinoma treated by total thyroidectomy with central and bilateral neck dissections. METHODS:Children and adolescents aged ≤18-year-old at presentation with papillary thyroid carcinoma during the years 1988-2010 underwent thyroid and lymph-node surgeries (with a median follow-up of 19.6 years) were analysed for post-surgical complications. RESULTS:Permanent surgical morbidity occurred in 14% (n = 70) of patients who underwent total thyroidectomy as well as bilateral central and lateral neck dissections (n = 509). Factors associated with permanent complications included pN1 with extra-nodal extension, > 4 metastatic lymph nodes in the central neck compartment, presence of distant metastases and younger age of patients at surgery. Patients who received extensive surgery had better relapse-free survival rates (p < 0.001). CONCLUSION/CONCLUSIONS:Total thyroidectomy and bilateral central as well as lateral neck dissections for children and adolescents with papillary thyroid carcinoma was associated with substantial postoperative complications. Nevertheless, it is associated with better prognosis for young patients with thyroid cancer. Prophylactic compartment-oriented lymph node dissections to these patients could be the management protocol in experienced hands.