Effect of preoperative programmed death-1 or programmed death ligand-1 immune check point inhibition on complications after surgery for primary head and neck cancer.

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.

IL-8 correlates with nonresponse to neoadjuvant nivolumab in HPV positive HNSCC via a potential extracellular vesicle miR-146a mediated mechanism.

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPVpos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPVpos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPVpos tumors displaying higher levels than HPVneg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPVpos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPVpos HNSCC patients.

A novel simulation module for segmental mandibulectomy and mandible reconstruction using 3D models.

INTRODUCTION: Mandibular resection and reconstruction are common but complex procedures in head and neck surgery. Resection with adequate margins is critical to the success of the procedure but technical training is restricted to real case experience. Here we describe our experience in the development and evaluation of a mandibular resection and reconstruction simulation module. METHODS: 3D printed (3DP) models of a mandible with a pathologic lesion were developed from imaging data from a patient with an ameloblastoma. During an educational conference, otolaryngology trainees participated in a simulation in which they reviewed a CT scan of the pathologic mandible and then planned their osteotomies before and after handling a 3DP model demonstrating the lesion. The adequacy of the osteotomy margins was assessed and components of the simulation were rated by participants with pre- and post-training surveys. RESULTS: 52 participants met criteria. After reviewing the CT scan, 34 participants (65.3 %) proposed osteotomies clear of the lesion. This proportion improved to 48 (92.3 %, p = 0.001) after handling the 3D model. Among those with initially adequate margins (n = 33), 45.5 % decreased their margins closer to the ideal, 27.2 % made no revision, 21.2 % widened their margins. 92 % of participants found the simulation beneficial for surgical planning and technical training. After the exercise, the majority of participants had increased confidence in conceptualizing the boundaries of the lesion (69.2 %) and their abilities to ablate (76.5 %). CONCLUSIONS: The structured mandibulectomy simulation using 3DP models was useful in the development of trainee experience in segmental mandible resection. LAY SUMMARY: This study presents the first mandibulectomy simulation module for trainees with the use of 3DP models. The use of a 3DP model was also shown to improve the quality of surgical training.

Functional Swallow-Related Outcomes Following Transoral Robotic Surgery for Base of Tongue Carcinoma.

In an era where the incidence of oropharyngeal cancer is growing steadily, there have been few studies exploring functional outcomes for individuals whose definitive cancer management approach includes transoral robotic surgical (TORS) resection. This study was designed to examine swallow-related outcomes in individuals newly diagnosed with base of tongue cancer whose treatment plan included surgical resection via TORS. The aims of this study were to determine whether TORS resection for early stage BOT SCCA affected: (a) lingual strength, (b) swallow safety and efficiency, (c) oral intake, and (d) swallowing-related quality of life. Nine individuals meeting the inclusion criteria were recruited to participate from March 2017 to April 2018. Each participant was evaluated at four distinct time points: (a) preoperatively, (b) 1 week postoperatively, (c) 1 month postoperatively, and (d) 3 months postoperatively. The following data were collected at each time point: (a) maximum isometric lingual pressure, (b) Penetration-Aspiration Scale score, (c) Yale Pharyngeal Residue Severity Rating Scale scores, (d) Functional Oral Intake Scale score, and (e) EAT-10 score. Data analysis revealed that a significant decline in maximum isometric lingual pressure, EAT-10 scores, and Functional Oral Intake Scale scores occurred between preoperative baseline measurements and 1 week post surgery. All participants in the study demonstrated a return to levels at or near their baseline level of function for maximum isometric lingual pressure, EAT-10 score, and Functional Oral Intake Scale score by 1 or 3 months post surgery. There were no significant changes in swallow safety or efficiency observed at any time point during the study.

Risk factors for gastrostomy tube dependence in transoral robotic surgery patients.

OBJECTIVES: To determine the rate of gastrostomy tube dependence after transoral robotic surgery (TORS), and to determine which patient or surgical factors increase the likelihood of gastrostomy tube dependence. METHODS: Retrospective chart review of all patients who underwent TORS for oropharyngeal squamous cell carcinoma (OPSCC) at a single institution from January 2011 through July 2016. Patients who underwent TORS for recurrent OPSCC were excluded. Primary outcome was gastrostomy tube (g-tube) dependence. Univariable and multivariable logistic regression were performed to identify risk factors for g-tube dependence at 3-months and 1-year. RESULTS: A total of 231 patients underwent TORS during the study period. At 3-month follow-up, 58/226 patients (25.7%) required g-tube. At 1-year and 2-year follow-up, 8/203 (3.9%) and 5/176 (2.8%), remained dependent on g-tube, respectively. Advanced T stage (T3) (OR = 6.07; 95% CI, 1.28-28.9) and discharge from the hospital with enteral access (OR = 7.50; 95% CI, 1.37-41.1) were independently associated with increased risk of postoperative gastrostomy tube dependence at 1 year on multivariable analysis. CONCLUSIONS: Long-term gastrostomy tube dependence following TORS is rare, particularly in patients that receive surgery alone. Patients with advanced T stage tumors have poorer functional outcomes. Early functional outcomes, as early as discharge from the hospital, are a strong predictor for long-term functional outcomes.

Patient experiences of sialendoscopy with monitored anesthesia care versus general anesthesia.

OBJECTIVE: To compare the experiences of patients who received sialendoscopy under general anesthesia (GA) with those who received monitored anesthesia care (MAC). METHODS: Patients who underwent sialendoscopy for sialadenitis or sialolithiasis from July 1, 2020, to July 31, 2021, were offered inclusion to this prospective observational study. A survey was sent to consenting patients on post-operative day 1 to record aspects of their pre-, intra-, and post-operative experience. The primary outcome was overall satisfaction. Secondary outcomes included pain tolerability and preference for similar anesthetic modality in the future. RESULTS: Seventy-five patients completed the post-operative survey (86% response rate), of which 39 patients received GA and 36 received MAC. Patient overall satisfaction was similar between groups (GA: "Poor/Average/Good" = 23%, "Excellent" = 77%; MAC: "Poor/Average/Good" = 25%, "Excellent" = 75%, p = 1.00). Tolerability of immediate post-operative pain was likewise similar between the GA (82%) and MAC (97%) groups (p = 0.058). Patients who received MAC reported intra-operative pain as "none/tolerable" 72% of the time and "uncomfortable" 28% of the time. Patients who received GA would prefer the same anesthetic in the future more often than in the MAC group (85% versus 61%, respectively, OR 3.50, 95% CI 1.17-10.50, p = 0.035). CONCLUSION: In regard to patient satisfaction, both MAC and GA are acceptable anesthetic choices in sialendoscopy for appropriate cases. Patients report similar overall satisfaction and post-operative pain tolerance under either anesthetic modality. Patients who undergo GA report higher rates of preference for similar anesthetic modality in the future. Further study is needed to determine the most appropriate criteria for anesthesia modality selection.

Recurrence of premalignant oral cavity and oropharynx lesions after pulsed diode laser treatment.

PURPOSE: Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser. MATERIALS AND METHODS: Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment. RESULTS: Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain. CONCLUSIONS: Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

BACKGROUND: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. METHODS: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. RESULTS: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). CONCLUSIONS: With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Upper airway stimulation: Fewer complications, ED presentations, readmissions, and increased surgical success.

OBJECTIVES: Evaluate the rate of complications, readmissions, emergency department presentations, and surgical success rates amongst three standard surgical treatment options for obstructive sleep apnea: upper airway stimulation, transoral robotic surgery, and expansion sphincter pharyngoplasty. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary care center. METHODS: Patients were included who were aged ≥18 years old and underwent upper airway stimulation, transoral robotic surgery, or expansion sphincter pharyngoplasty between January 2011 and May 2020. RESULTS: 345 patients were identified: 58% (n = 201) underwent upper airway stimulation, 10% (n = 35) underwent transoral robotic surgery, and 32% (n = 109) patients underwent expansion sphincter pharyngoplasty. There were 22 emergency department presentations and 19 readmissions, most of which were experienced by patients receiving transoral robotic surgery (six emergencies, seven readmissions) and expansion sphincter pharyngoplasty (12 emergencies, 11 readmissions). Patients with upper airway stimulation had four emergencies and one readmission. Only 2% of the upper airway stimulation cohort had a complication, whereas this was 20% and 12% for the transoral robotic surgery and expansion sphincter pharyngoplasty cohorts, respectively. Patients experienced the highest surgical success rate with upper airway stimulation (69%), whereas patients who received transoral robotic surgery and expansion sphincter pharyngoplasty had success rates of 50% and 51%, respectively. CONCLUSION: Treating obstructive sleep apnea with upper airway stimulation led to lower rates of complications, emergency department presentations, and readmissions in this series. In those for whom upper airway stimulation is appropriate, it may be more effective in successfully treating obstructive sleep apnea than transoral robotic surgery and expansion sphincter pharyngoplasty.

Improved efficiency of sialendoscopy procedures at an ambulatory surgery center.

OBJECTIVES: To compare time spent on day of surgery and post-surgical outcomes for sialendoscopy procedures at an ambulatory surgery center versus in a hospital operating room. METHODS: Retrospective chart review for patients who underwent sialendoscopy for sialadenitis or sialolithiasis from March 2017 to May 2020 were included. Surgery location (ambulatory surgery center or hospital operating room) was compared. Primary outcomes included total time in hospital, operative time, total time in operating room. and recovery time. Secondary outcomes included rate of symptoms resolutions, requiring further medical management, and requiring further surgical intervention. RESULTS: A total of 321 procedures were included. Sialendoscopy in an ambulatory surgery center compared to main operating room decreased median hospital time (166 min reduction, p < 0.001), operative time (18 min reduction, p < 0.001), total time in operating room (34 min reduction, p < 0.001), and recovery time (64 min reduction, p < 0.001). Sialendoscopy in an ambulatory surgery center had similar rates of post-operative resolution of symptoms and further medical or surgical intervention compared to procedures in a hospital operating room. CONCLUSION: Sialendoscopy can be safely performed in an ambulatory surgery center for sialadenitis or appropriate sialolithiasis cases while decreasing hospital time, operative time, total time in operating room time, and recovery time.

Comparison of general anesthesia and monitored anesthesia care for sialendoscopy procedures.

OBJECTIVES: The literature remains scarce in terms of comparing different anesthesia modalities in sialendoscopy. Due to the lack of a standard of care or guidelines to anesthetic care, it is generally accepted that surgeons perform these surgeries under the anesthetic modality in which they are most comfortable. In this study, we evaluate time spent on the day of surgery and post-surgical outcomes for patients receiving sialendoscopy under monitored anesthesia care versus general anesthesia. MATERIALS AND METHODS: We retrospectively assessed patients who underwent sialendoscopy using a solely endoscopic approach for sialadenitis or sialolithiasis from March 2017 to December 2019. Anesthesia modality (monitored anesthesia care versus general anesthesia) was compared. Main outcomes included total time in hospital, operative time, total time in operating room, anesthesia time, and recovery time. Secondary outcomes included rate of resolution of symptoms, requiring further medical management, requiring further surgical intervention, and complications. RESULTS: A total of 172 procedures were included. Sialendoscopy under monitored anesthesia care center compared to general anesthesia decreased median hospital time (141 min reduction), anesthesia time (46 min reduction), operative time (24 min reduction), time in operating room (43 min reduction), and recovery time (56 min reduction). Utilizing monitored anesthesia care demonstrated similar rates of post-operative resolution of symptoms, complications, and further medical or surgical intervention compared to the general anesthesia cohort. CONCLUSION: Sialendoscopy can be safely performed under monitored anesthesia care for appropriate sialadenitis or sialolithiasis cases while decreasing hospital time, operative time, time in operating room, anesthesia time, and recovery time while maintaining similar post-operative outcomes. Monitored anesthesia care should be considered for solely endoscopic cases as guided by surgeon and patient comfort.

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

BACKGROUND: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown. METHODS: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers. RESULTS: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69). CONCLUSIONS: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.

SMARCB1 (Integrase Interactor 1)-Deficient Sinonasal Carcinoma of the Maxillary Sinus: A Newly Described Sinonasal Neoplasm.

SMARCB1 (integrase interactor 1) is a tumor suppressor gene encoded on chromosome 22q11.2 that encodes a core subunit of SWI/SNF chromatin remodeling complexes and plays a critical role in regulating gene expression and chromatin structure. We describe a case of SMARCB1 (integrase interactor 1)-deficient sinonasal carcinoma of the left maxillary sinus in a 63-year-old woman with an initial presentation of numbness of the maxillary teeth and facial swelling.

INI1/SMARCB1-Deficient Carcinoma (Rhabdoid Tumor) of the Lacrimal Gland.

Integrase interactor 1 (INI1) is a tumor suppressor gene that is ubiquitously expressed in all nucleated cells. The loss of INI1 protein activity was first demonstrated in aggressive pediatric tumors, including atypical teratoid/rhabdoid (AT/RT) tumor of the central nervous system and malignant rhabdoid tumor of the kidney. Subsequently, INI1 deficiency was discovered in other pediatric and some adult neoplasms. The spectrum of INI1-negative tumors includes a wide variety of neoplasms that occur over a wide age range, are variably aggressive, and have a variable rhabdoid component on histopathologic evaluation. In this report, the authors describe a 27-year-old gravid woman with INI1-deficient carcinoma of the lacrimal gland, previously not described in this location.

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer.

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer.

Orbital Involvement by NUT Midline Carcinoma.

A 32-year-old female presented with a sino-orbital lesion that proved to be a NUT midline carcinoma. This is only the third case of orbital involvement by this aggressive lesion. The clinical, radiographic, and histopathologic features of NUT midline carcinoma are discussed, as well as its management options.

Modified Frailty Index Associates With Transoral Robotic Surgery Complications and Survival: A National Database Study.

OBJECTIVE: The modified frailty index (mFI-5) is a National Surgical Quality Improvement Program-derived 5-factor index that has been proven to reflect frailty and predict morbidity and mortality. We hypothesize that mFI-5 is a valid predictive measure in the transoral robotic surgery (TORS) population. METHODS: Retrospective study utilizing the TriNetX US-collaborative health records network querying for TORS patients. Cohorts were stratified by mFI-5 score which uses five ICD-10 codes: nonindependent functional status, hypertension, obstructive respiratory disease, heart failure, and diabetes mellitus. Cohorts were matched by age using propensity score matching. Outcome measures included survival, infection, pneumonia, tracheostomy dependence, and percutaneous endoscopic gastrostomy dependence. Reported odds ratios were normalized to mFI-5 = 0. RESULTS: A total of 9,081 patients were included in the final analysis. Greater mFI-5 scores predicted decreased survival and increased incidence of postoperative infection and pneumonia. Odds of 5-year mortality were 1.93 (p = 0.0003) for mFI-5 = 2 and 1.90 (p = 0.0002) for mFI-5 = 3. Odds of 2-year mortality were 1.25 (p = 0.0125) for mFI-5 = 1, 1.58 (p = 0.0002) for mFI-5 = 2, and 1.87 (p = 0.003) for mFI-5 = 3. Odds of postoperative infection were 1.51 (p = 0.02) for mFI-5 = 2 and 1.78 (p = 0.05) for mFI-5 = 3. Two-year odds of developing pneumonia were 1.69 (p = 0.0001) for mFI-5 = 2 and 2.84 (p < 0.0001) for mFI-5 = 3. Two-month odds of pneumonia were 1.50 (p = 0.0259) for mFI-5 = 2 and 2.55 (p = 0.0037) for mFI-5 = 3. mFI-5 = 4 or 5 had too few patients to analyze. Using polynomial regression to model age versus incident 5-year post-TORS death (R2 = 0.99), mFI-5 scores better predicted survival than age alone. CONCLUSION: This study demonstrates that mFI-5 predicts mortality, pneumonia, and postoperative infection independently of age. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Outcomes of Head and Neck Free Tissue Transfer in Renal Failure Patients.

OBJECTIVE: To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications. METHODS: Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined. RESULTS: Seventy-three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001). CONCLUSIONS: Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre-operatively in this patient population with consideration for regional flaps in the appropriate patient. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:688-694, 2024.

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy.

Microvascular reconstruction of midface osteoradionecrosis.

BACKGROUND: Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. METHODS: Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54). RESULTS: The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02). CONCLUSION: In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.