Department of Otolaryngology, Head and Neck Surgery

BACKGROUND: Patient-reported outcome measures have been associated with survival in oncology patients. Altered intake and malnutrition are common symptoms for patients treated for head and neck cancer and esophageal cancer (HNC/EC). The purpose of this study was to examine the relationship between patient-reported satisfaction with medical care and nutrition status. METHODS: This prospective cohort study collected data from 11 international cancer care sites. RESULTS: One hundred and sixtythree adult patients (n = 115 HNC; n = 48 EC) completed a patient satisfaction questionnaire (the Canadian Health Care Evaluation Project Lite) and were included. HNC/EC patient global satisfaction with medical care was 88.3/100 ± 15.3 at baseline and remained high at 86.6/100 ± 16.8 by 6 months (100 max satisfaction score). Poor nutrition status, as defined by the Patient-Generated Subjective Global Assessment Short Form, was associated with lower patient satisfaction with overall medical care, relationship with doctors, illness management, communication, and decision-making 6 months into treatment (P < 0.01). There was no difference in global satisfaction between patients who did and did not report swallowing difficulty (P = 0.99) and patients with and without feeding tube placement (P = 0.36). Patients who were seen by a dietitian for at least one nutrition assessment had global satisfaction with care that was 16.7 percentage points higher than those with no nutrition assessment (89.3 ± 13.8 vs 72.6 ± 23.6; P = 0.005) CONCLUSION: In HNC/EC patient-centered oncology care, decreasing malnutrition risk and providing access to dietitian-led nutrition assessments should be prioritized and supported to improve patient satisfaction and standard of care. Feeding tube placement did not decrease patient satisfaction with medical care.

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

BACKGROUND: Oral potentially malignant disorders (OPMDs) occur in up to 4%-5% of the population, of which oral leukoplakia (OL) is the most common subtype. Predicting high-risk OL remains a challenge. Early diagnosis and effective treatment are thought to be of paramount importance to improve outcomes. METHODS: We searched PubMed and Clinicaltrials.gov data for updates in the clinical management of OL from 2015 to current. RESULTS: Recent publication of large cohorts of patients with OL aids in counseling patients regarding risk of malignant transformation. Management for OL includes surveillance, excision, and laser surgery, as well as local and systemic approaches to chemoprevention. Several new entities show promise regarding candidate biomarkers, chemoprevention agents, and diagnostic adjuncts, though all require further validation. CONCLUSION: This update serves to further inform clinical management of OL and provide impetus for future investigations. TRIAL REGISTRATION: NCT00099021, NCT00951379, NCT05727761, NCT05727761.

Mucoepidermoid Carcinoma (MEC) is a common salivary malignant neoplasm. Approximately 60 % of MECs harbor translocations between CRTC1 or CRTC3 and MAML2, which are thought to drive disease pathogenesis. However, the precise structural mechanism driving this rearrangement remains uncharacterized. Here, we performed multi-omic and long read genomic sequencing, discovering a chain of alterations that created the CRTC1::MAML2 fusion, but also an unexpected MAML2 to MYBL1 rearrangement, suggesting that MYBL1 may play a larger role in salivary gland cancers than previously recognized. Furthermore, we discovered and validated recurrent TERT rearrangements and amplifications in MEC models. 5/5 MEC cell lines and 36/39 (92 %) primary MEC tumors harbored a TERT rearrangement or copy number amplification. Custom sequencing of the TERT locus confirmed translocation breakpoints in 13/33 (39 %) MECs, while exome sequencing confirmed frequent TERT amplifications. Critically, TERT knockdown in NCI-H292, a cell line with TERT promoter rearrangement, reduced clonogenic cell survival, supporting a critical role of this gene in MEC tumorigenesis. Overall, our data suggest that complex chromothripsis rearrangement mechanisms drive the formation of structural variation in CRTC1::MAML2 fusion positive and negative tumors and reveal highly recurrent structural variation driving TERT rearrangement in MEC.

The repair of an infant with cleft lip includes treatment of the nasal deformity using surgical repositioning of the nasal cartilages. In some cases, the nose is molded before surgery, termed nasoalveolar molding, and in others, postoperatively with nostril stents for a variable amount of time. This best practice evaluation fails to make a definitive evidence-based conclusion, yet the benefits of stenting seem to outweigh the risks.

PURPOSE OF REVIEW: Patients with cleft lip -palate (CLP) experience morbidity and social stigma, particularly in low-income and middle-income countries (LMICs) such as those of sub-Saharan Africa (SSA). Delays in treatment secondary either to lack of awareness, skills, equipment and consumables; poor health infrastructure, limited resources or a combination of them, has led to SSA having the highest rates of death and second highest rates of disability-adjusted life years in patients with CLP globally. Here we review current perspectives on the state of comprehensive cleft lip and palate repair in Africa. RECENT FINDINGS: To bridge gaps in government health services, nongovernmental organizations (NGOs) have emerged to provide care through short-term surgical interventions (STSIs). These groups can effect change through direct provision of care, whereas others strengthen internal system. However, sustainability is lacking as there continue to be barriers to achieving comprehensive and longitudinal cleft care in SSA, including a lack of awareness of CLP as a treatable condition, prohibitive costs, poor follow-up, and insufficient surgical infrastructure. With dedicated local champions, a comprehensive approach, and reliable partners, establishing sustainable CLP services is possible in countries with limited resources. SUMMARY: The replacement of CLP missions with locally initiated, internationally supported capacity building initiatives, integrated into local healthcare systems will prove sustainable in the long-term.

OBJECTIVE: The shape of esophageal dilators has not changed in over 350 years. Clinical and animal research suggests that the upper esophageal sphincter (UES) is not round but approximates a kidney shape and that cylindrical dilators may be suboptimal. The Infinity UES Dilation System has been developed specifically for the anatomic configuration of the UES. This study evaluates the safety of the UES-specific Infinity Dilation System. METHODS: All patients undergoing dilation of the UES between January 1, 2022 and September 1, 2023 were included. Demographics, procedure indication, dilator type, minor adverse events, and major complications were abstracted. Minor adverse events, complications, and maximum dilation dimension (mm) were compared between groups. RESULTS: A total of 477 patients were included. Eight hundred and seventy-three total UES dilations were performed. The primary indications for UES dilation were cricopharyngeus muscle dysfunction (43%) and stenosis from radiation toxicity (40%). Twenty-three percent (202/873) of dilations were performed with an Infinity balloon, 31% (270/873) were performed using two conventional balloons placed side by side, and 46% (401/873) were performed with one singleton conventional balloon. The average maximum dilation dimension was 33 (±4.7) mm for Infinity balloons, 32 (±3.8) mm for two side-by-side balloons, and 18 (±3.4) mm for singleton balloons. There were three major complications with conventional balloons and none with Infinity balloons. There were no significant differences in minor adverse events between groups. CONCLUSIONS: A UES-specific esophageal dilator provides a greater maximum dilation dimension and appears to be at least as safe as dilation with a single cylindrical balloon designed to dilate the esophagus. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

BACKGROUND: Orbital roof fractures are often the result of high-velocity collisions and are seen in 1-9% of patients with craniofacial trauma. Although the majority of orbital roof fractures are displaced superiorly, a subset results in inferior displacement of fracture fragments, posing a risk for muscle/nerve entrapment and possible blindness. Many of these patients have severe traumatic brain injury (TBI) and, in addition to orbital fractures, also have elevated intracranial pressure (ICP). Management of depressed orbital roof fractures in the setting of severe TBI with elevated ICP represents a management dilemma. CASE DESCRIPTION: Two cases of severe TBI with associated downward displacement of orbital roof fractures were reviewed. Both cases exhibited elevated ICP correlated with the degree of orbital roof fracture depression. Surgical intervention involving elevation and repair of the fractures was undertaken when there was a significant risk of injury to the extraocular muscles and/or the optic nerve due to the extent of the fracture depression. CONCLUSION: Depressed orbital roof fractures may migrate in response to changes in ICP. Serial computed tomography scans and eye examinations may aid with determining the need for and timing of surgical intervention.

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions: Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.