IMPORTANCE Ficlatuzumab can be used to treat head and neck squamous cell carcinoma (HNSCC) by inhibiting c-Met receptor-mediated cell proliferation, migration, and invasion. OBJECTIVE To understand the effect of ficlatuzumab on HNSCC proliferation, migration, and invasion. DESIGN, SETTING, AND PARTICIPANTS The effects of ficlatuzumab on HNSCC proliferation, invasion, and migration were tested. Mitigation of c-Met and downstream signaling was assessed by immunoblotting. The tumor microenvironment has emerged as an important factor in HNSCC tumor progression. The most abundant stromal cells in HNSCC tumor microenvironment are tumor-associated fibroblasts (TAFs). We previously reported that TAFs facilitate HNSCC growth and metastasis. Furthermore, activation of the c-Met tyrosine kinase receptor by TAF-secreted hepatocyte growth factor (HGF) facilitates tumor invasion. Ficlatuzumab is a humanized monoclonal antibody that sequesters HGF, preventing it from binding to and activating c-Met. We hypothesized that targeting the c-Met pathway with ficlatuzumab will mitigate TAF-mediated HNSCC proliferation, migration, and invasion. Representative HNSCC cell lines HN5, UM-SCC-1, and OSC-19 were used in these studies. EXPOSURES FOR OBSERVATIONAL STUDIES The HNSCC cell lines were treated with ficlatuzumab, 0 to 100 µg/mL, for 24 to 72 hours. MAIN OUTCOMES AND MEASURES Ficlatuzumab inhibited HNSCC progression through c-Met and mitogen-activated protein kinase (MAPK) signaling pathway. RESULTS Ficlatuzumab significantly reduced TAF-facilitated HNSCC cell proliferation (HN5, P< .001; UM-SCC-1, P< .001), migration (HN5, P = .002; UM-SCC-1, P = .01; and OSC-19, P = .04), and invasion (HN5, P = .047; UM-SCC-1, P = .03; and OSC-19, P = .04) through a 3-dimensional peptide-based hydrogel (PGmatrix). In addition, ficlatuzumab also inhibited the phosphorylation of c-Met at Tyr1234/1235 and p44/42 MAPK in HNSCC cells exposed to recombinant HGF. CONCLUSIONS AND RELEVANCE We demonstrate that neutralizing TAF-derived HGF with ficlatuzumab effectively mitigates c-Met signaling and decreases HNSCC proliferation, migration, and invasion. Thus, ficlatuzumab effectively mitigates stromal influences on HNSCC progression.
Objective To compare pain control (opioid consumption and postsurgical pain scores) in head and neck (H&N) free flap reconstruction patients who undergo traditional means of postoperative analgesia including use of opioids versus a novel protocol that includes ketamine and gabapentin. Methods Single‐institution retrospective cohort study. Results Eighty‐six patients who underwent H&N free flap reconstruction from 2015 to 2018 were included. Forty‐three patients were in the control cohort treated with opioids only, and 43 patients were in the treatment group. There was a statistically significant decrease in opioid consumption in each of the first 5 postoperative days ranging from 80% to 83% in the treatment group. The daily pain scores were significantly lower in the treatment group in the first 2 postoperative days. At the 1‐month postoperative visit, there was no significant difference in pain scores between the groups; however, by the 2‐month visit, the treatment group reported significantly lower pain scores than the control group (P = 0.001). No adverse outcomes of ketamine or gabapentin were experienced. Conclusion Ketamine and gabapentin are safe and effective analgesics in H&N free flap surgery that significantly decrease opioid use in the acute postoperative setting and may improve pain control. Level of Evidence 3a Laryngoscope, 130:1686–1691, 2020
Objectives: Early on during the COVID-19 pandemic, the US Centers for Medicare & Medicaid Services (CMS) and other government as well as medical institutions recommended that surgeons postpone nonessential surgeries. The aim of our study is to examine the impact of the COVID-19 pandemic on otolaryngology surgical training by evaluating changes in surgical volumes through various time points relative to the height of the pandemic. Methods: We performed a retrospective review of all surgical cases performed by the Otolaryngology-Head and Neck Surgery department at a tertiary care academic center from 3 time periods: July 1st, 2018, to June 30th, 2019; July 1st, 2019, to June 30th, 2020; and July 1st, 2020, to June 30th, 2021. Results: From the 2018-19 period to the 2020-21 period, the total number of overall cases decreased by 9.9%, from 2386 to 2148 cases. During this same time duration, the number of key indicator cases decreased by 13.4%, from 1715 to 1486 cases. Relative to other cases, ethmoidectomy, rhinoplasty, and stapes/OCR cases decreased the most during the 2019-20 period by 41.9%, 41.8%, and 29.5%, respectively. From the 2018-19 period to the 2020-21 period, thyroid/parathyroid cases decreased the most by 35.4%. Only ethmoidectomy and oral cavity cases showed increases during this period at 9.7% and 24.4%, respectively. Conclusions: Although case volumes have stayed relatively constant, key indicator case volumes at the present tertiary care academic center have not yet fully recovered from the COVID-19 pandemic. Efforts must be made to determine how this has impacted residency surgical education.
Online genealogical databases provide a unique resource of public information that is acceptable to institutional review boards for patient follow-up in clinical reviews. Utilization of Ancestry.com data led to significant improvement in follow-up duration and increased the number of patients with sufficient data that could be included in our retrospective study.
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