Neck scar perception after neck dissection in HPV-associated oropharyngeal squamous cell carcinoma.

IMPORTANCE: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population. OBJECTIVE: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified. Data analysis was performed in January 2022. MAIN OUTCOMES AND MEASURES: Dermatology Life Quality Index was modified (mDLQI) to assess patients' perceptions of their scars. The primary outcome was the mean mDLQI survey score with higher scores corresponding to worse perceptions. Three questions adapted from the Self-Consciousness Scale (SCS) were also included to assess awareness of appearance. All questions were scaled on a 0-3 Likert Scale. Tweedie generalized linear model was used to understand the relationship between mDLQI score and patient- and procedure-specific factors (including the three SCS survey questions). An additional exploratory logistic regression was performed to understand the risk factors for clinically significant mDLQI score change. RESULTS: A total of 67 patients (response rate 57 %) completed the survey with a mean mDLQI survey score of 0.84 (max 30). Although there was a statistically significant negative association between private insurance and mDLQI survey score (95 % Confidence Interval [CI]: -2.72 - -0.38), and a positive association between the SCS score and mDLQI survey score (95 % CI: 0.23-0.81) (p < 0.05), these variables were not found to be risk factors for a clinically significant difference in mDLQI on multivariable analysis. CONCLUSION: The majority of patients felt their neck scars did not interfere with their daily lives. Patient perceptions of neck scars were consistent despite differing patient characteristics and treatment regimens.

Submental Island Flap After Prior Contralateral Neck Dissection: A Case Series and Technical Considerations.

OBJECTIVES: The submental island flap is a dependable workhorse in head and neck reconstruction. However, the viability of this flap has not been established for oral cavity reconstruction when a contralateral neck dissection has already been performed in an earlier surgical setting. The aim of this study is to highlight technical considerations and outcomes of this approach with a small case series. METHODS: Three cases of oral cavity reconstruction with a submental island flap elevated in the context of a prior contralateral neck dissection are presented. RESULTS: In all cases, a doppler was used to identify the maintenance of the submental perforator in the neck opposite the previous neck dissection. In 2 cases, level IA was included within the dissection field of the previous neck dissection. Additionally, the old neck scar was included within the skin paddle of the submental island flap in 2 cases. In all cases, excellent healing of the flap was observed without partial or complete loss. CONCLUSIONS: The submental island flap appears to be a reliable reconstruction when a previous contralateral neck dissection has been performed, even when level IA was included in the prior dissection.

Immediate postoperative non-invasive positive pressure ventilation following midface microvascular free flap reconstruction.

BACKGROUND: There is a rare need for postoperative non-invasive positive pressure ventilation (NIPPV) following microvascular reconstruction of the head and neck. In midface reconstruction, the free flap vascular pedicle is especially vulnerable to the compressive forces of positive pressure delivery. CASE: A 60 year old female with Amyotrophic Lateral Sclerosis (ALS) presented with squamous cell carcinoma of the anterior maxilla, for which she underwent infrastructure maxillectomy and fibula free flap reconstruction. To avoid tracheotomy, the patient was extubated postoperatively and transitioned to NIPPV immediately utilizing a full-face positive pressure mask with a soft and flexible sealing layer. The patient was successfully transitioned to NIPPV immediately after extubation. The free flap exhibited no signs of vascular compromise postoperatively, and healed very well. CONCLUSION: Postoperative non-invasive positive pressure ventilation can be successfully applied following complex microvascular midface reconstruction to avoid tracheotomy in select patients without vascular compromise of the free flap.

An equity-based narrative review of barriers to timely postoperative radiation therapy for patients with head and neck squamous cell carcinoma.

OBJECTIVES: The majority of patients with head and neck squamous cell carcinoma (HNSCC) do not commence postoperative radiation treatment (PORT) within the recommended 6 weeks. We explore how delayed PORT affects survival outcomes, what factors are associated with delayed PORT initiation, and what interventions exist to reduce delays in PORT initiation. METHODS: We conducted a PubMed search to identify articles discussing timely PORT for HNSCC. We performed a narrative review to assess survival outcomes of delayed PORT as well as social determinants of health (SDOH) and clinical factors associated with delayed PORT, using the PROGRESS-Plus health equity framework to guide our analysis. We reviewed interventions designed to reduce delays in PORT. RESULTS: Delayed PORT is associated with reduced overall survival. Delays in PORT disproportionately burden patients of racial/ethnic minority backgrounds, Medicaid or no insurance, low socioeconomic status, limited access to care, more comorbidities, presentation at advanced stages, and those who experience postoperative complications. Delays in PORT initiation tend to occur during transitions in head and neck cancer care. Delays in PORT may be reduced by interventions that identify patients who are most likely to experience delayed PORT, support patients according to their specific needs and barriers to care, and streamline care and referral processes. CONCLUSIONS: Both SDOH and clinical factors are associated with delays in timely PORT. Structural change is needed to reduce health disparities and promote equitable access to care for all. When planning care, providers must consider not only biological factors but also SDOH to maximize care outcomes.

Transoral Excision of Parapharyngeal Space Tumors.

Transoral excision of parapharyngeal space (PPS) tumors has increased in popularity along with the increased use of robotic and endoscopic surgical technology. Here, the authors highlight the indications, techniques, outcomes, and complications of transoral approaches to PPS tumors, with a special emphasis on salivary tumors of the PPS and the transoral robotic surgery approach.

Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction.

INTRODUCTION: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. METHODS: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. RESULTS: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6-88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 ("I cannot swallow certain solid foods") or better. Ninety-six percent (23/24) reported speech of 70 ("difficulty saying some words, but I can be understood over the phone") or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 ("I can eat soft solids but cannot chew some foods"). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. CONCLUSION: STSG reconstructions for pathologic T1-T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS: ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Beyond Depth of Invasion: Adverse Pathologic Tumor Features in Early Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: In small (≤2 cm) oral tongue squamous cell carcinoma (OTSCC), we sought to clarify the contribution of pathologic features including perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion-5 (WPOI-5) to clinical outcomes relative to tumor depth of invasion (DOI) of > or ≤ 4 mm. METHODS: Cases of ≤2 cm OTSCC treated surgically between 2000 and 2017 at an academic cancer center were reviewed, with retrospective pathologic slide review of DOI, LVI, PNI, and WPOI-5. Primary outcome measures included occult nodal positivity, 2-year locoregional recurrence (LRR), disease-specific survival (DSS), and overall survival (OS). RESULTS: One hundred tumors were included in analyses; 50 had DOI ≤ 4 mm, while 50 had DOI > 4 mm. When DOI was ≤4 mm, the presence of PNI, LVI, or WPOI-5 was not associated with higher rates of occult cervical metastasis, LRR, or OS. When DOI was >4 mm, there was no difference in rates of occult cervical metastasis or LRR with each feature. On multivariate analysis, only the presence of two or more adverse features was associated with higher LRR (OR 5.7, P = .01) and worse DSS (HR 6.5, P = .02). CONCLUSION: The rate of occult cervical metastases in small (≤2 cm) OTSCC when DOI is ≤4 mm is very low even when PNI, LVI, or WPOI-5 is present, and 2-year LRR is no different. When DOI is >4 mm, the strongest predictor of recurrence and survival on multivariate analysis is the presence of two or more features in the tumor. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1715-1720, 2020.

Predictors of Mortality in HPV-Associated Oropharynx Carcinoma Treated With Surgery Alone.

OBJECTIVE: Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). METHODS: We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method. RESULTS: Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non-ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three-year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five-year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non-ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1-T2, with negative margins, pN0-N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3-year OS rates were 93% and 95%, respectively, and the 5-year OS rates were 91% and 95%, respectively. CONCLUSION: In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1-T2, pN0-N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E423-E435, 2020.

Surgeon-Performed Ultrasound for Chronic Obstructive Sialadenitis Helps Predict Sialendoscopic Findings and Outcomes.

Objective To determine the accuracy of surgeon-performed ultrasound (SP-US) features for predicting intraoperative sialendoscopic findings and to correlate ultrasound features with short-term symptomatic outcomes following sialendoscopy-assisted salivary duct surgery (SASDS). Study Design Case series with chart review. Setting The practices of 2 academic sialendoscopy surgeons. Subjects and Methods Between February 2014 and September 2015, 82 patients with 105 symptomatic glands underwent SASDS, of whom 56 patients (75 glands) met inclusion criteria. SP-US and sialendoscopic findings were reviewed for patients with chronic obstructive sialadenitis who underwent SASDS and who had been prospectively evaluated with the University of California-San Francisco Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire (scored 0-100) administered preoperatively and 3 months postoperatively. Results The positive predictive value (PPV) and negative predictive value (NPV) of SP-US for identifying sialoliths intraoperatively were 94% (33/35) and 91% (39/43), respectively. Of glands with sialoliths on SP-US, 97% (34/35) had complete symptom resolution (COSS ≤10) after SASDS. The PPV and NPV of salivary duct dilation on SP-US for finding a corresponding stenosis on sialendoscopy were 93% (14/15) and 50% (14/28), respectively. Nonsialolith SP-US features with the highest PPV for complete or partial symptom resolution (COSS ≤25) following SASDS included distal duct dilation of all glands (86%; 6/7) and dilation of both distal and proximal parotid ducts (75%; 6/8). Conclusion SP-US has high accuracy for ruling in and ruling out sialoliths, as well as for ruling in but not for necessarily ruling out stenosis presence and location. Ultrasound is helpful in estimating degree of short-term symptom response following SASDS.

EPHRIN-B1 Mosaicism Drives Cell Segregation in Craniofrontonasal Syndrome hiPSC-Derived Neuroepithelial Cells.

Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function. Although the mechanistic basis for cellular interference in CFNS has been hypothesized to involve Eph/ephrin-mediated cell segregation, no direct evidence for this has been demonstrated. Here, by generating hiPSCs from CFNS patients, we demonstrate that mosaicism for EPHRIN-B1 expression induced by random X inactivation in heterozygous females results in robust cell segregation in human neuroepithelial cells, thus supplying experimental evidence that Eph/ephrin-mediated cell segregation is relevant to pathogenesis in human CFNS patients.

Unidirectional Eph/ephrin signaling creates a cortical actomyosin differential to drive cell segregation.

Cell segregation is the process by which cells self-organize to establish developmental boundaries, an essential step in tissue formation. Cell segregation is a common outcome of Eph/ephrin signaling, but the mechanisms remain unclear. In craniofrontonasal syndrome, X-linked mosaicism for ephrin-B1 expression has been hypothesized to lead to aberrant Eph/ephrin-mediated cell segregation. Here, we use mouse genetics to exploit mosaicism to study cell segregation in the mammalian embryo and integrate live-cell imaging to examine the underlying cellular and molecular mechanisms. Our data demonstrate that dramatic ephrin-B1-mediated cell segregation occurs in the early neuroepithelium. In contrast to the paradigm that repulsive bidirectional signaling drives cell segregation, unidirectional EphB kinase signaling leads to cell sorting by the Rho kinase-dependent generation of a cortical actin differential between ephrin-B1- and EphB-expressing cells. These results define mechanisms of Eph/ephrin-mediated cell segregation, implicating unidirectional regulation of cortical actomyosin contractility as a key effector of this fundamental process.