Utility of abdominal imaging to assess for liver metastasis in patients with head and neck cancer and abnormal liver function tests.

PURPOSE: To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed. RESULTS: Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%). CONCLUSIONS: While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC.

Voice Outcomes Following Serial Office-Based Steroid Injections and Voice Therapy for Vocal Fold Scar.

OBJECTIVE: Previous studies indicate that certain voice outcomes can improve following a single office-based steroid injection with voice therapy for vocal fold scar. We evaluated voice outcomes after a series of three timed office-based steroid injections with voice therapy. STUDY DESIGN: Retrospective case series with chart review. SETTING: Academic medical center. METHODS: We evaluated pre-and postprocedural patient-reported, perceptual, acoustic, aerodynamic, and videostroboscopic parameters. We evaluated 23 patients who underwent three office-based dexamethasone injections into the superficial lamina propria one month apart. All patients pursued voice therapy. RESULTS: Voice Handicap Index (n = 19; P= .030) decreased after injection series. Total GRBAS score (grade, roughness, breathiness, asthenia, strain) decreased (n = 23; P = 0.001). Dysphonia severity index score improved (n = 20; P = 0.041). Phonation threshold pressure did not decrease significantly (n = 22; P = 0.536). Videostroboscopic parameters of vocal fold edge (P = 0.023), right mucosal wave (P = 0.023) improved or normalized after injection series. Glottic closure (P = 0.134) did not improve. CONCLUSIONS: Series of three office-based steroid injections combined with voice therapy for vocal fold scar does not appear to provide further benefit than one injection. Despite lack of improvements of PTP and other parameters, injection series is likewise unlikely to worsen dysphonia. A partially negative study provides value in investigation of less invasive treatment alternatives for a disorder that is challenging to treat. Future studies exploring effects of voice therapy alone without other intervention and consideration of sham injection versus steroid injection are warranted.

Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle-aged women of White race and non-Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls. STUDY DESIGN: Molecular analysis of clinical biospecimens. METHODS: We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age-, sex-, and race/ethnicity-matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label-free quantitative mass spectrometry techniques, and acquired genome-wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment. RESULTS: Proteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome-based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (BTD). Follow-up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data. CONCLUSION: iSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies. LEVEL OF EVIDENCE: Not applicable Laryngoscope, 131:E540-E546, 2021.

Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma.

OBJECTIVES: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro. METHODS: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs. RESULTS: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 µM. The two drugs similarly inhibited clonogenic cell survival. At 1 µM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation. CONCLUSION: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1470-1478, 2020.

Use of the Teres Major Muscle in Chimeric Subscapular System Free Flaps for Head and Neck Reconstruction.

IMPORTANCE: We present what we believe to be the first case series in which the teres major muscle is used as a free flap in head and neck reconstruction. OBJECTIVES: To describe our experience with the teres major muscle in free flap reconstruction of head and neck defects and to identify advantages of this approach. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed at 2 tertiary care centers between February 1, 2007, and June 30, 2012. Data analysis was conducted from July 31, 2014, through December 1, 2014. INTERVENTION: Teres major muscle free flap for use in head and neck reconstruction. MAIN OUTCOMES AND MEASURES: Indications for use, complications, and outcomes including donor site morbidity. RESULTS: The teres major free flap was used in 11 patients as a component of chimeric subscapular system free flaps for a variety of complex head and neck defects. The teres major muscle was used to fill soft-tissue defects of the neck, face, and nasal cavity; it provided substantial soft-tissue volume but was less bulky than the latissimus dorsi muscle. The teres major muscle was also used to provide protection for vascular anastomoses and/or great vessels and to enhance soft-tissue coverage of the mandibular reconstruction plate. In addition, the muscle was selected as a substrate for skin grafting where inadequate neck skin remained. Flap survival occurred in 10 of 11 flaps (91%). Two flaps (18%) demonstrated venous congestion that was managed successfully. Two patients (18%) developed minor recipient-site complications (submental fistula and infection with recurrent wound dehiscence and plate exposure). All donor sites healed well, with chronic, mild shoulder pain noted in 2 patients (18%) and no postoperative seromas observed in any patient. CONCLUSIONS AND RELEVANCE: Addition of the teres major muscle to a subscapular system free flap is an option for reconstruction of a variety of complex head and neck defects, particularly when a moderate amount of soft tissue is required. In select cases, the teres major muscle may have advantages over the latissimus dorsi muscle.

Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a Mouse Model.

OBJECTIVE: To demonstrate the feasibility of detecting and quantifying extracellular signal-related kinase (ERK) phosphorylation status using nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head and neck squamous carcinoma cell lines in vitro and in a murine xenograft model. SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates, tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including nonphosphorylated, monophosphorylated, and diphosphorylated species, could be reliably detected, distinguished, and quantified in a single assay using a single antibody. In vitro treatment of Cal27 cells with the epidermal growth factor receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib-treated cells could be further reduced by the addition of the insulin-like growth factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies demonstrated altered ERK profiles after 2 days of gefitinib treatment compared with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the activation state of signaling molecules such as ERK in nanoscale in vitro and in vivo samples across a wide dynamic range. As such, it has potential to provide molecular diagnostic information before, during, and after treatment using a minimally invasive technique. Further study is warranted to determine its utility in assessing signaling proteins as biomolecular outcome predictors in clinical trials.