American Head and Neck Society position statement on the use of PD-1 inhibitors for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: A position statement put forth by the American Head and Neck Society (AHNS) was constructed to provide evidence-based treatment recommendations for PD-1 inhibitor use in advanced cutaneous squamous cell carcinoma (cSCC). Secondarily, we sought to identify knowledge gaps warranting further investigation. METHODS: A literature search utilizing key terms: cutaneous squamous cell carcinoma, cutaneous cancer, checkpoint inhibitors, systemic therapy, Program Cell Death, PD-1 (PubMed, Cochrane, and Google Scholar) was carried out to generate evidence-based statements. The statements were distributed among the AHNS membership. Delphi methodology was applied to identify statements achieving 70% or greater consensus among the leadership team. RESULTS: Twenty-six position statements achieved consensus. Knowledge gaps for future research included: impact of immunosuppression on cSCC staging and associated treatment; role of PD-1 inhibitors in immunosuppressed patients. CONCLUSION: This comprehensive position statement put forth by the AHNS represents majority consensus by practicing head and neck surgeons throughout the country.

Ethical Considerations for Elderly Patients with Cutaneous Malignancy.

Discussions of ethics in surgery generally focus on the principles of beneficence, nonmalfeasance, autonomy, and justice. Caring for elderly patients with advanced cutaneous malignancies often requires the added consideration of narrative ethics to account for the expanded circle of care, complex medical conditions, and different goals of treatment often seen in this population. By focusing on the patient's illness narrative and relying on the collective experiences of the patient and surgeon, compassionate and appropriate care can be provided for these often-devastating disease processes.

Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)-related HNSCC to those of older patients. METHODS: A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114). RESULTS: When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, P < .01) and females (40.7% vs 24.6% of older patients, P = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, P = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, P = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients (P = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, P < .01). CONCLUSIONS: Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.

Cutaneous Head and Neck Malignancies in the Elderly.

Cutaneous malignancy of the head and neck affects a large proportion of elderly patients. The severity ranges from small, easily treatable lesions to large, invasive, potentially metastatic tumors. Surgical treatment is the primary treatment of most skin cancers; however, geriatric patients are more likely to have multiple comorbidities that increase the risk of surgery. Multiple treatment modalities exist, including surgical, radiation, and medical therapy. Recommendations and treatment options for basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and melanoma are outlined and reviewed.

Survival outcomes in elderly patients with untreated upper aerodigestive tract cancer.

BACKGROUND: This study is an evaluation of survival in patients with upper aerodigestive tract (UADT) cancer who did not receive guideline-directed therapy. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was examined to identify patients with invasive cancer of the UADT. Patients were classified as "untreated" if they received neither surgery nor radiotherapy. Kaplan-Meier observed survival estimates were computed and stage-specific actuarial estimates of relative survival were computed. RESULTS: Of 3589 untreated patients, 13.7% were black, compared to 9.5% white, and 9.2% all other races (p <.0001). Patients with stage IV disease were more likely to be untreated than those with stage I disease (11.9% vs 3.8%; p <.0001). Median survival was 39 months for treated patients and 4 months for untreated patients. CONCLUSION: The median survival for untreated patients was 4 months. Stage, race, and primary site were independently associated with untreated status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 215-218, 2017.

Antiangiogenic antibody improves melanoma detection by fluorescently labeled therapeutic antibodies.

OBJECTIVE: Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody-based imaging. STUDY DESIGN: Preclinical. METHODS: Panitumumab and control IgG were covalently linked to a near-infrared fluorescent probe (IRDye800CW). Immunodeficient mice with ear xenografts of melanoma cell lines (A375 and SKMEL5) were systemically injected (200 µg, tail vein) with either IgG-IRDye800CW, panitumumab-IRDye800CW, or a combination (bevacizumab [5mg/kg], administered 72 hours prepanitumumab-IRDye800CW) (n = 5). Primary tumors were imaged with open-field (LUNA, Novadaq, Toronto, Ontario, Canada) and closed-field (Pearl, LI-COR Biosciences, Lincoln, NB) imaging devices. Postresection, the concentration of labeled antibody within the tumor (µg/g) was calculated using normalized standards. RESULTS: The mean fluorescence within the melanoma tumors was greater for the combination group compared to panitumumab alone for both cell lines (P < 0.001). The tumor-to-background ratio (TBR) for the A375 tumors was greater for the combination (3.4-7.1) compared to the panitumumab alone (3.2-5.0) (P = 0.04). The TBR for SKMEL5 tumors was greater for the combination (2.4-6.0) compared to the panitumumab alone (2.2-3.9) (P = 0.02). Within A375 tumors, the concentration was lower for panitumumab (0.51 µg/g) compared to combination group (0.68 µg/g) (P = 0.036). Within SKMEL5 tumors, the concentration was lower for panitumumab (0.0.17 µg/g) compared to combination group (0.35 µg/g) (P = 0.048). Residual tumor (1.0-0.2 mg) could be differentiated from background in both panitumumab and combination groups. For both cell lines, panitumumab and combination groups had greater mean fluorescence of the tumor compared to control IgG. CONCLUSION: The addition of antiangiogenic therapy improves uptake of fluorescently labeled monoclonal antibodies within melanoma tumors. Clinical translation could improve detection of melanoma intraoperatively, reducing positive margins and sparing normal tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E387-E395, 2016.

The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages.

Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects.

Revision of the functionally devastated nasal airway.

Functional rhinoplasty can be especially challenging in a patient who has had previous surgery, trauma, anatomic abnormalities, or systemic disease affecting the nasal mucosa. A thorough analysis of the type and location of the obstruction is critical, and only after identifying the precise anatomic cause of the problem can surgical planning begin. Scarring, altered anatomy, and disrupted tissue planes all complicate this process. Structural support and nasal mucosa often require augmentation with autogenous grafts from the ear, rib, or other portions of the nasal cavity. Attention to nasal support mechanisms, the internal and external nasal valves, and internal lining during primary surgery may help to avoid future complications. Through careful analysis and planning, proper function may be restored to a functionally devastated nasal airway.

Revision aural atresia surgery: indications and outcomes.

OBJECTIVE: To determine the most common indications for revision congenital aural atresia (CAA) surgery and the postoperative healing and hearing outcomes of revision surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care academic otologic practice. PATIENTS: Patients undergoing revision surgery for CAA. INTERVENTION: Revision surgery for CAA. MAIN OUTCOME MEASURES: Indications for revision atresiaplasty, time to revision surgery, postoperative external auditory canal (EAC) patency, incidence of chronic drainage and/or infection, and postoperative speech reception thresholds (SRTs), and air-bone gaps. RESULTS: Indications for 75 ears (69 patients) undergoing 107 revision operations for CAA included 58% for EAC stenosis, 19% for chronic drainage and/or infection, and 20% for conductive hearing loss (CHL) alone. Fifty ears (67%) required a single revision. Twenty-five ears (33%) required more than 1 revision. With follow-up longer than 3 months (mean, 41 mo), 69% of ears revised for EAC stenosis achieved a patent canal (29% required >1 revision); 75% of ears revised for chronic drainage and/or infection (mean follow-up, 53 mo) realized a dry canal (22% required >1 revision). For all revision surgeries with adequate follow-up (n = 80), the mean postoperative short-term SRT of 24 dB HL was a significant improvement from the mean preoperative SRT of 39 dB HL (p < 0.01, paired t test). CONCLUSION: EAC stenosis is the most common indication for revision atresiaplasty. Despite the challenges of revision surgery, improvement in canal patency, epithelialization, and hearing utcomes can be achieved.

Construct validity of a simulator for myringotomy with ventilation tube insertion.

OBJECTIVES: To establish construct validity of an anatomic model as a simulator for myringotomy with ventilation tube insertion and to assess its subjective appeal. STUDY DESIGN: Cross-sectional, repeated-measures comparative evaluation of simulator. SETTING: University academic otolaryngology residency program. SUBJECTS AND METHODS: Using an anatomic model of the human auricle, ear canal, eardrum, and middle ear space, 18 otolaryngologists of various levels of training performed 10 timed procedures: myringotomy with ventilation tube insertion. Errors were recorded, and participants reported the quality of their experience. RESULTS: Both time-to-completion and errors per trial discriminated novices from non-novice participants; novices (02:23, 95% confidence interval [CI], 01:42-03:04) were 3.6 times slower than non-novices (00:39, 95% CI, 00:35-00:43) and 6.5 times more error prone (novices 2.16 errors/trial, 95% CI, 1.68-2.64; non-novices 0.33 errors/trial, 95% CI, 0.21-0.45). Errors were strongly correlated with prior surgical experience. All participants required more time to complete the first trial, and their performance stabilized thereafter. Overall, the simulation was perceived as a valuable experience. CONCLUSION: Our model is a valid platform for simulating myringotomy with ventilation tube insertion. The model discriminates novices from non-novices, has a learning curve, and is perceived to be a valuable and realistic teaching tool by users.

Complications with forehead flaps in nasal reconstruction.

OBJECTIVES/HYPOTHESIS: To determine what characteristics and comorbidities are associated with a higher rate of complications in patients undergoing nasal reconstruction with a forehead flap. STUDY DESIGN: Retrospective chart review. METHODS: Chart review was completed on all patients undergoing nasal reconstruction with forehead flap from 1995 to 2008. Three pre-existing comorbidities were tracked: diabetes, smoking, and vascular disease. Major complications (flap necrosis, nasal obstruction, alar notching) and minor adverse outcomes (partial nasal obstruction, epidermolysis, and alar asymmetry) were recorded. RESULTS: Two hundred five patients with a median age of 66 years had forehead flap reconstruction between October 1995 and July 2008. Sixty-two patients (30.2%) had full-thickness defects. Forty-eight patients (23.4%) were smokers, 17 (8.3%) were diabetics, and 90 (43.9%) fell into our category of vascular disease. Thirty-three (16.1%) developed a major complication at some point in their postoperative course, with 11 (5.4%) having some degree of flap necrosis, 10 (4.9%) nasal obstruction, and 20 (9.8%) alar notching. Full-thickness defects were significantly associated with higher incidences of any major complication, and had higher odds of flap necrosis and alar notching. Smokers had higher odds of developing flap necrosis. Neither the presence of diabetes, increased age, nor vascular disease was significantly associated with higher rates of major complications. CONCLUSIONS: Smokers with full-thickness defects are shown to be at greater odds for developing a postoperative complication. Laryngoscope, 2009.