Specimen-Based Resection Margins and Local Control during Transoral Robotic Surgery for Oropharyngeal HPV-Mediated Squamous Cell Carcinoma.

OBJECTIVES: The aim of the study was to investigate the association of surgical margin conditions, including positive specimen margins revised to negative relative to local recurrence, disease-free survival, and overall survival (OS) within a cohort of HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC) who underwent en bloc resection via transoral robotic surgery (TORS). MATERIALS AND METHODS: Retrospective cohort of patients with untreated HPV-mediated OPSCC cT1 or T2 undergoing TORS resection between October 2014 and March 2020. The methodologic description of our interdisciplinary institutional approach, number of cut-through margins (CTMs) during intraoperative consultation, percentage of final positive margin cases, and disease-free survival and OS stratified by margin status and margin tumor-free distance is identified. RESULTS: 135 patients with primary cT1/T2 HPV-mediated OPSCC met inclusion criteria. Twenty-eight of 135 (20.7%) specimens revealed CTM and were revised during the same operative setting. Three of 135 (2.2%) surgical cases had positive final margin status. Local control rate was 97%. On univariate analysis, margin distance did not impact OS. CTM and final positive margins had lower OS than initially negative margins (p = 0.044). Pathologic N-stage significantly impacted OS (p < 0.001). CONCLUSIONS: High local control rate and low final positive margin status confound the study of specimen margin-based techniques in HPV-mediated OPSCC resected en bloc with TORS. Pathologic N-stage may impact OS more than margin status. Larger numbers are needed to confirm differences.

Supplementing Intraoperative Mastoidectomy Teaching With Video-Based Coaching.

OBJECTIVES: Video-based coaching might complement general surgery education, but little is known of its applicability for otologic microsurgical teaching. Our purpose was thus to evaluate the content and resident-perceived benefit of video-based coaching for mastoidectomy education. METHODS: In this mixed-methods pilot design, mastoidectomies were recorded from operative microscopes and reviewed during 30-minute video-based coaching sessions at 2 tertiary care centers. Eight residents and 3 attendings participated. Ten-point Likert-type questionnaires on the extent to which attendings taught 12 topics through 8 techniques were completed by residents after surgical and coaching sessions. Coaching sessions and structured interviews with residents were audio-recorded, transcribed and iteratively coded. RESULTS: Seven audio-recordings were available for coaching sessions, during which a mean of 2.22 ± 0.5 topics per minute were discussed. Of the 12 teaching topics, technique was discussed most frequently (32%, 0.71 ± 0.2 topics/min), followed by anatomy (16%, 0.31 ± 0.16 topics/min). Of all 8 ratings between coaching and operative sessions, residents indicated a greater extent of discussion of anatomy (median difference, [95% confidence interval (CI)] of 3 [1-4]), progress (2.25 [95% CI, 0.5-4]), technique (3.5 [95% CI, 1.5-5.5]), pitfalls (2.5 [95% CI, 1-3.5]), and summarizing (3 [95% CI, 1-5]). In structured interviews, residents reported improved self-confidence and global perspective. CONCLUSIONS: Video-based coaching is educationally dense and characterized by perceived richer teaching and promotion of a deeper surgical understanding. It requires no additional resources, can be completed in a short period of time and can be implemented programmatically for any otolaryngologic subspecialty utilizing video-recording capable equipment.

Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined. OBJECTIVE: To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA. METHODS: PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated. RESULTS: Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance ( P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies. CONCLUSION: ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.

TORS elective lingual tonsillectomy has less acute morbidity than therapeutic base of tongue TORS.

OBJECTIVE: To determine the impact of diagnostic TORS lingual tonsillectomy (DTLT) on objective swallowing measures for carcinoma of unknown primary (CUP). METHODS: Between 10/2016-1/2020, 27 patients with p16+ squamous cell carcinoma (SCC) level 2a nodal disease underwent DTLT and ipsilateral neck dissection for CUP. No patient had a history of cutaneous SCC. Patients participated in Modified Barium Swallow (MBS) three weeks post-TORS, which were then compared to those from a contemporaneous cohort of 40 patients with clinically-identified p16+ base of tongue (BOT) primary tumors. DIGEST scores were retrospectively calculated. Univariate and multivariate analysis performed, stratified by BOT glossectomy (n = 40) versus lingual tonsillectomy for CUP (n = 27). Radiation to the resected primary or potential primary sources was omitted if margins were ≥3 mm or if no primary identified. RESULTS: Twenty-seven consecutive patients with clinical stage cT0N1 HPV-associated OPSCC had a BOT primary pathologically identified in 18/27 (67%). Univariate analysis of functional swallow assessment on MBSImP correlated with improved post-TORS DIGEST scores for CUP. On multivariate analysis (MVA) DIGEST safety scores were improved for CUP than cT1 BOT glossectomy [Odds Ratio (OR) 0.28, p = 0.038]. MVA on matched pT1 CUP (n = 27) vs. pT1 BOT (n = 19), OR of moderate/severe dysphagia for CUP was 0.54 [0.12-2.38, p = 0.417] for DIGEST safety scores and 0.27 [0.06-1.18, p = 0.082] for DIGEST efficiency scores. Moderate/severe dysphagia as determined by DIGEST overall scores for CUP compared to cT1 and pT1 yielded an OR of 0.39 (p = 0.081) and 0.42 (p = 0.195), respectively. Twenty-six total patients received adjuvant RT, and 18 (11 with ≥3 mm margins, 9 with negative specimens) were spared intentional RT to the oropharynx. Median follow-up was 22.6 months with 100% PFS. CONCLUSIONS: Patients undergoing DTLT for CUP demonstrated acute swallow defecits in the post-operative setting. A comparison of long-term functional results between DTLT and elective irradiation of the primary site should be studied. LEVEL OF EVIDENCE: Level III.

Characterizing postoperative physiologic swallow function following transoral robotic surgery for early stage tonsil, base of tongue, and unknown primary human papillomavirus-associated squamous cell carcinoma.

BACKGROUND: Data objectively evaluating acute post-transoral robotic surgery (TORS) swallow function are limited. Our goal was to characterize and identify clinical variables that may impact swallow function components 3 weeks post-TORS. METHODS: Retrospective cohort study. Pre/postoperative use of the Modified Barium Swallow Impairment Profile (MBSImP) and Penetration-Aspiration Scale (PAS) was completed on 125 of 139 TORS patients (2016-2019) with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scores were retrospectively calculated. Uni/multivariate analysis was performed. RESULTS: Dysfunctional pre-TORS DIGEST scores were predictive of post-TORS dysphagia (p = 0.015). Pre-TORS MBSImP deficits in pharyngeal stripping wave, swallow initiation, and clearing pharyngeal residue correlated with airway invasion post-TORS based on PAS scores (p = 0.012, 0.027, 0.048, respectively). Multivariate analysis of DIGEST safety scores declined with older age (p = 0.044). Odds ratios (ORs) for objective swallow function components after TORS were better for unknown primary and tonsil primaries compared to base of tongue (BOT) (OR 0.35-0.91). CONCLUSIONS: Preoperative impairments in specific MBSImP components, older patients, and BOT primaries may predict more extensive recovery in swallow function after TORS.

Implementation and evaluation of eight virtual surgical electives for medical students during the COVID-19 pandemic.

BACKGROUND: Eight novel virtual surgery electives (VSEs) were developed and implemented in April-May 2020 for medical students forced to continue their education remotely due to COVID-19. METHODS: Each VSE was 1-2 weeks long, contained specialty-specific course objectives, and included a variety of teaching modalities. Students completed a post-course survey to assess changes in their interest and understanding of the specialty. Quantitative methods were employed to analyze the results. RESULTS: Eighty-three students participated in the electives and 67 (80.7%) completed the post-course survey. Forty-six (68.7%) respondents reported "increased" or "greatly increased" interest in the course specialty completed. Survey respondents' post-course understanding of each specialty increased by a statistically significant amount (p-value = <0.0001). CONCLUSION: This initial effort demonstrated that VSEs can be an effective tool for increasing medical students' interest in and understanding of surgical specialties. They should be studied further with more rigorous methods in a larger population.

Implementation and Evaluation of a Virtual Elective in Otolaryngology in the Time of COVID-19.

OBJECTIVE: To develop and evaluate a virtual otolaryngology medical student elective created during the COVID-19 crisis with the intention of teaching the basic tenets of otolaryngology and increasing exposure to the specialty. STUDY DESIGN: Cross-sectional survey. SETTING: Emory University School of Medicine. METHODS: A 1-week virtual otolaryngology curriculum was offered to third- and fourth-year medical students that centered on the American Academy of Otolaryngology-Head and Neck Surgery Foundation's handbook Primary Care in Otolaryngology (fourth edition). The course covered a variety of topics and was conducted remotely via online video conferencing software. We applied multiple teaching modalities and surveyed students regarding the effectiveness of the course. Mixed methods analysis was employed to analyze the course data. RESULTS: Twelve students participated; 67% reported their baseline precourse understanding of otolaryngology in the "poor-fair" range. After the course, 92% of students reported increased understanding, with 42% and 58% reporting "good" and "very good" understanding, respectively. Following completion of the course, posttest scores on summative assessments were significantly higher than pretest scores (P < .001). Ninety-two percent of students reported either "increased" or "greatly increased" interest in otolaryngology postcourse. Qualitative survey results revealed students' appreciation of course organization, formative assessments, and case-based learning. CONCLUSIONS: An otolaryngology elective administered through a virtual format can be effective at providing an educational experience and garnering interest in the field. Positive exposure to otolaryngology can increase medical students' interest in pursuing the specialty and expand their general knowledge of consultation, diagnosis, and management in otolaryngology.

Multisystem Inflammatory Syndrome in Children in February 2020 and Implications of Genomic Sequencing for SARS-CoV-2.

Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized disease process that can complicate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present what we believe to be the earliest case of MIS-C, occurring in February 2020. Our patient's SARS-CoV-2 infection was caused by an emerging lineage with the D614G variant in the spike protein. This lineage would subsequently become the predominant cause of SARS-CoV-2 outbreaks in Europe and the United States where MIS-C was first described.

Uncertainty: An Uncomfortable Companion to Decision-making for Infants.

Although parents are typically the most appropriate decision-makers for their children, there are limits to this authority. Medical providers may be ethically obligated to seek state intervention against a parental decision if the parent places a child at significant and imminent risk of serious harm. When parents make medical decisions for their children, they assess both the projected benefits and risks of their choices for their family. These assessments are impacted by uncertainty, which is a common feature of neonatal intensive care. The relative presence or absence of uncertainty may impact perceptions of parental decisions and a medical provider's decision to seek state intervention to overrule parents. In this article, we propose a model integrating prognostic uncertainty into pediatric decision-making that may aid providers in such assessments. We will demonstrate how to apply this model to 3 neonatal cases and propose that the presence of greater uncertainty ought to permit parents greater latitude to incorporate family values into their decision-making even if these decisions are contradictory to the recommendations of the medical team.

Development of 89Zr-Ontuxizumab for in vivo TEM-1/endosialin PET applications.

PURPOSE: The complexity of sarcoma has led to the need for patient selection via in vivo biomarkers. Tumor endothelial marker-1 (TEM-1) is a cell surface marker expressed by the tumor microenvironment. Currently MORAb-004 (Ontuxizumab), an anti-TEM-1 humanized monoclonal antibody, is in sarcoma clinical trials. Development of positron emission tomography (PET) for in vivo TEM-1 expression may allow for stratification of patients, potentially enhancing clinical outcomes seen with Ontuxizumab. RESULTS: Characterization of cell lines revealed clear differences in TEM-1 expression. One high expressing (RD-ES) and one low expressing (LUPI) cell line were xenografted, and mice were injected with 89Zr-Ontuxizumab. PET imaging post-injection revealed that TEM-1 was highly expressed and readily detectable in vivo only in RD-ES. In vivo biodistribution studies confirmed high radiopharmaceutical uptake in tumor relative to normal organs. EXPERIMENTAL DESIGN: Sarcoma cell lines were characterized for TEM-1 expression. Ontuxizumab was labeled with 89Zr and evaluated for immunoreactivity preservation. 89Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed. CONCLUSION: 89Zr-Ontuxizumab can be used in vivo to determine high versus low TEM-1 expression. Reliable PET imaging of TEM-1 in sarcoma patients may allow for identification of patients that will attain the greatest benefit from anti-TEM-1 therapy.