Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. METHODS: Our institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. RESULTS: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p < 0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p = 0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p = 0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p = 0.46). KPS < 90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p = 0.03). CONCLUSION: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

Is Dental Specialty Referral Associated With Earlier Presentation of Oral Cavity Squamous Cell Carcinoma?

BACKGROUND: Oral cavity squamous cell carcinoma (OSCC) may mimic other more common odontogenic processes such as infection, trauma, and benign pathology. Delays in diagnosis and treatment are known to result in poorer survival outcomes. PURPOSE: The study purpose was to measure the association between referral type and OSCC stage at time of presentation. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study composed of newly diagnosed OSCC patients treated with surgical resection from 2014 to 2023 at Roswell Park Comprehensive Cancer Center. Patients who presented with self-referrals or had surgical treatment outside of Roswell Park Comprehensive Cancer Center were excluded. PREDICTOR VARIABLE: The primary predictor was referral source (dental vs medical specialty). MAIN OUTCOME VARIABLE: The primary outcome was pathological T stage (pT stage). The secondary outcome was overall survival (OS). COVARIATES: Covariates included demographic data and cancer-related variables (symptomatology, subsite, and risk factors). ANALYSES: A multivariate logistical regression model for pT stage was constructed using all significant covariates as well as preoperative patient and tumor characteristics. For OS, Kaplan-Meier survival curves were constructed and compared with the log-rank test. A P < .05 was considered statistically significant. RESULTS: A total of 215 subjects were included in the study sample. The majority were referred by a dental provider (n = 132, 62.3%). Dental referrals presented with significantly earlier T stage disease (RRpT3/T4 0.65, P < .01) and had lower rates of cervical nodal positivity (RRpN1-N3 0.62, P = .01). Dental referral independently increased the odds of early pT stage presentation (odds ratio 5.10, P < .01) after controlling for age, sex, oral pain symptoms, social history (smoking and drinking), head neck cancer history, and tumor subsite. Dental referrals had significantly improved OS (P = .03) and were also associated with lower rates of oral pain symptoms (RRoral pain 0.80, P = .02), lymphovascular invasion (RRLVI 0.50; P = .04), and perineural invasion (RRPNI 0.63, P = .04). CONCLUSIONS AND RELEVANCE: Among subjects with similar risk factors, those referred from dental providers were found to have earlier stage disease. Unfortunately, over half of dental referrals still presented with pain symptoms and more than a third presented with locally advanced disease. Dental providers appear to be positioned to detect earlier OSCC; however, there is room for improvement.

Comparing the Outcomes of Osteocutaneous Radial Forearm and Fibula Free Flaps in the Reconstruction of Mandibular Osteoradionecrosis.

BACKGROUND: This study compares the outcomes of osteocutaneous radial forearm free flap (OC-RFFF) and fibula free flap (FFF) reconstruction of mandibular osteoradionecrosis (ORN). METHODS: Retrospective review of patients undergoing OC-RFFF/FFF reconstruction for mandible ORN between 2005 and 2020 at a tertiary center. Patient characteristics, postoperative complications, and functional outcomes were evaluated using chi-squared and logistic regression analysis. RESULTS: Fifty-six patients were included (OC-RFFF: 38; FFF: 18). Significantly more OC-RFFF patients had lateral mandible defects (94% vs. 61%, p = 0.0014). There were significantly more patients with exposed intraoral bone in the OC-RFFF group (23% vs. 0% p = 0.02), but no significant differences in hardware complications or flap failure. Donor site partial skin graft loss was more common in the FFF group (22% vs. 2.6%, p = 0.016), but no other significant differences in donor site morbidity were seen. Bivariable analysis showed no impact of flap type, tobacco/alcohol use, diabetes, or hypothyroidism on postoperative complications. Sixty percent of OC-RFFF, and 67% of FFF, patients resumed an oral diet after surgery. Oral diet was not impacted by flap type (OR = 0.769, 95% CI = 0.201-2.706, p = 0.688). CONCLUSION: The OC-RFFF is an acceptable option in the reconstruction of ORN involving the lateral mandible, though there is increased risk of bone exposure. These findings can help guide surgeon selection of microvascular free flap donor sites and appropriate patient counseling.

Association of pre-treatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

BACKGROUND: Given the role of systematic inflammation in cancer progression, lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of LMR with survival outcomes in North American patients with head and neck cancer. METHODS: A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation from June 2007 to April 2021 at the Roswell Park Comprehensive Cancer Center. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS). Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze OS and CSS. Pre-radiation LMR was then stratified into high and low based on its median value. Propensity scored matching was used to reduce the selection bias. RESULTS: A total of 476 patients met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0,90, 95% confidence interval [CI] 0.82-0.99, p = 0.03) and CSS (aHR 0.83, 95% CI 0.72-0.95, p = 0.009). The median value of LMR was 3.8. After propensity score matching, a total of 186 pairs were matched. Lower LMR than 3.8 remained to be associated with worse OS (HR 1.59, 95% CI 1.12-2.26, p = 0.009) and CSS (HR 1.68, 95% CI 1.08-2.63, p = 0.02). CONCLUSION: Low LMR, both as a continuous variable and dichotomized variable, was associated with worse OS and CSS. Further studies would be warranted to evaluate the role of such prognostic marker to tailor interventions.

Pathogenesis and progression of anosmia and dysgeusia during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of COVID-19 which was detected in late 2019 in Wuhan, China. As of September 2022, there have been over 612 million confirmed cases of COVID-19 with over 6.5 million associated deaths. In many cases, anosmia and dysgeusia have been identified as primary symptoms of COVID-19 infection in patients. While the loss of smell (anosmia) and loss of taste (dysgeusia) due to COVID-19 infection is transient in most patients, many report that these symptoms persist following recovery. Understanding the pathogenesis of these symptoms is paramount to early treatment of the infection. We conducted a literature review of Google Scholar and PubMed to find and analyze studies discussing anosmia and dysgeusia in the context of COVID-19 to understand the progression and management of these symptoms. The mechanism for dysgeusia is largely unknown; however, pathogenesis of anosmia includes inflammation and cytokine release resulting from the infection that alters neuronal signaling, thus inducing the loss of smell that patients experience. Anosmia may be managed and potentially resolved sooner with a combination therapy of olfactory training and budesonide irrigation of the nasal cavity. It is important to note that the variants of SARS-CoV-2 are genetically distinguished from the original virion due to a mutation in their spike proteins, giving them a different symptom profile regarding anosmia and dysgeusia. This variability in symptomatology is an area of study that needs to be further explored.

Immediate Free Fibula Flap After Maxillectomy With Simultaneous Full-arch Dental Implant-Supported Prosthetic Rehabilitation of the Midface and Mandible: The "Super Reconstruction Concept".

Immediate reconstruction and dental rehabilitation for ablative defects of the head and neck in one surgery is now a commonly used technique among reconstructive surgeons. Often patients are edentulous or partially edentulous in the jaw opposing that with pathology. In this case, only rehabilitating the dental arch affected by pathology would not render the patient with a functional occlusion. We introduce the "super reconstruction" concept which includes not only rehabilitating the dental arch affected by pathology but also the opposing arch, giving the patient a fully functional occlusion at the time of ablative surgery. This concept is described through a case of a patient with a T4aN0M0 squamous cell carcinoma of the maxilla who underwent total maxillectomy, immediate fibula flap reconstruction of the maxilla with, and full arch dental implant placement into the maxilla and opposing mandible with prosthetic rehabilitation.

A pain in the neck: Salmonella spp. as an unusual cause of a thyroid abscess. A case report and review of the literature.

BACKGROUND: Thyroid gland infections are rare. Their incidence is estimated to be less than 1% in immunocompromised hosts. Most common pathogens isolated are Gram positive aerobic cocci. Infections with Gram negative facultative aerobes such as Salmonella are rare. CASE PRESENTATION: A 55-year-old female with type II diabetes mellitus and a history of a colloid right thyroid lobe nodule presented with neck pain and fever. She was found to have a thyroid abscess 2 weeks following a non-specific diarrheal illness. A needle aspiration for symptomatic and diagnostic purposes was performed. Cultures grew Salmonella enterica serotype Heidelberg. She was treated with a 12-week course of oral antibiotics and serial aspiration. CONCLUSION: A thyroid abscess is a rare occurrence; however, a high index of suspicion is required to make the diagnosis. The management is directed at minimizing morbidity. The mainstay treatment is medical, but surgery is sometimes necessary to achieve adequate source control, particularly when complications arise.

Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4.

BACKGROUND: Respiratory syncytial virus (RSV) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. Mast cells are important effector cells in allergy, with sentinel cell roles in host defense. However, the role of mast cells in response to RSV infection is unknown. OBJECTIVE: Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease. METHODS: Human cord blood-derived mast cells and the HMC-1 mast cell line were exposed to RSV or UV-inactivated RSV. Viral gene and protein expression were evaluated by using PCR and flow cytometry. The expression of interferon-stimulated genes and selected mediators were evaluated by using quantitative PCR and ELISA. RESULTS: Human mast cells expressed multiple RSV genes after exposure to RSV, and a small percentage of mast cells supported RSV antigen protein expression. RSV induced mast cells to upregulate production of chemokines, including CCL4, CCL5, and CXCL10, as well as type I interferons, and interferon-stimulated gene expression. However, production of the granulocyte chemoattractants CXCL8 and CCL11 was not induced. Antibody blockade of the type I interferon receptor on human cord blood-derived mast cells reduced the RSV-mediated induction of CXCL10 and CCL4 but not CCL5. Leukotriene C4 production by mast cells was not enhanced by exposure to RSV. CONCLUSION: Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease.

Open and Endoscopic Endonasal Optic Nerve Decompression for Craniofacial Fibrous Dysplasia in an Adolescent: 2-Dimensional Operative Video.

Craniofacial fibrous dysplasia (CFFD) is a benign, bony disease that may affect the skull base.1,2 Most cases are asymptomatic and observed; however, advanced disease can present with cranial neuropathy or craniofacial deformity requiring intervention.3-5 A 16-year-old adolescent girl with known CFFD involving the sphenoid and frontal bones with severe bilateral optic canal narrowing developed progressive right eye visual decline and frontal cosmetic deformity. Visual acuity worsened oculus dextrus (OD) to 20/30 with a new superior nasal scotoma and 20% loss in the retinal nerve fiber layer and remained oculus sinister (OS) 20/20. The patient was recommended a staged subfrontal craniotomy for right optic decompression and simultaneous correction cosmetic deformity followed by endonasal right optic decompression. On postoperative day one, visual acuity OD improved to 20/20; however, she developed OS visual decline to 20/800. Curiously, there were no episodes of intraoperative hypotension or additional iatrogenic compression. Use of methylprednisolone led to improvement OS 20/400. Given persistent visual decline, urgent second stage endonasal bilateral optic nerve decompression, rather than unilateral, was performed. Postoperatively, vision improved to OS 20/200. At one month, her vision improved to OD 20/15 and OS returned to 20/20 with a paracentral scotoma and 29% decline in left retinal nerve fiber layer with further improvement anticipated. This video describes a multidisciplinary, multistaged approach in treatment of optic nerve compression due to CFFD in addition to the management of unanticipated contralateral visual decline. The patient consented to the procedure and publication of her image. No Institutional Review Board/ethics committee approval was necessary for this case report.

Predicting outcomes in head and neck surgery with modified frailty index and surgical apgar scores.

OBJECTIVE: To compare the efficacy of the Modified Frailty Index and Modified Surgical Apgar scores in predicting postoperative outcomes in head and neck cancer patients. METHODS: We retrospectively reviewed patients who underwent major head and neck surgery between 2012 and 2015. Modified Surgical Apgar, and Frailty Index, scores were calculated on 723 patients. The primary outcome was 30-day complication and/or mortality. RESULTS: The mean Modified Frailty Index was 0.11 ± 0.12, and mean Modified Surgical Apgar score was 6.15 ± 1.67. Both scores were significantly associated with 30-day complication (P<0.05). The Modified Surgical Apgar score was superior to the Modified Frailty Index in predicting complications (Area Under the Curve (AUC) = 0.76; 95 % Confidence Interval (CI), 0.722-0.793; and AUC=0.59; 95 % CI, 0.548-0.633, respectively). Concurrent use of both scoring systems (AUC=0.77) was not superior to individual use. An increase in the mFI from 0.27 to 0.36 was associated with an increase in the risk of complication postoperatively (Odds Ratio (OR) = 3.67; 95 % CI, 1.30-10.34, P=.014). A reduction in the mSAS from 7 to 6 increased the risk of complication following surgery (OR=2.64; 95 % CI, 1.45-4.80; P=.002). CONCLUSION: Both scores are useful in risk stratifying head and neck cancer patients. The Modified Surgical Apgar score was superior at predicting complications; concurrent use of both scores added minimal benefit.

Muscle transposition and free muscle transfer in facial nerve reanimation.

PURPOSE OF REVIEW: This review highlights recent advances in facial reanimation surgery particularly related to muscle transposition and free functional muscle transfer (FFMT). RECENT FINDINGS: FFMT and muscle transposition are mainstays in the treatment of chronic facial paralysis. Recent literature evaluates single versus dual innervated FFMT, reanimation of the periocular region and lower lip depressors, and indications for such methods over gold standard FFMT techniques. New donor sites for muscle transposition and FFMT are also described. SUMMARY: Gracilis FFMT (GFMT) continues to be the gold standard in dynamic facial reanimation for patients with chronic facial paralysis. Muscle transposition should be considered in older patients, those medically unfit for long operative procedures, and individuals who prefer more immediate results. With respect to FFMT, described nerve coaptation patterns, surgical stages, and donor muscle choice vary. Standardization of data reporting and outcome measures is needed in future studies.

Association of Body Mass Index With Outcomes Among Patients With Head and Neck Cancer Treated With Chemoradiotherapy.

Importance: Combined modality therapy, such as chemoradiotherapy, often results in significant morbidity among patients with head and neck cancer. Although the role of body mass index (BMI) varies based on cancer subtypes, its association with treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer remains unclear. Objective: To evaluate the role of BMI in treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer undergoing chemoradiotherapy. Design, Setting, and Participants: This retrospective, observational, single-institution cohort study conducted at a comprehensive cancer center included 445 patients with nonmetastatic head and neck cancer who underwent chemoradiotherapy from January 1, 2005, to January 31, 2021. Exposure: Normal vs overweight or obese BMI. Main Outcomes and Measures: Metabolic response after chemoradiotherapy, locoregional failure (LRF), distant failure (DF), overall survival (OS), and progression-free survival (PFS), with Bonferroni correction used to adjust for multiple comparisons and P < .025 being considered statistically significant. Results: A total of 445 patients (373 men [83.8%]; median age, 61 years [IQR, 55-66 years]; 107 [24.0%] with normal BMI, 179 [40.2%] with overweight BMI, and 159 [35.7%] with obese BMI) were included for analysis. Median follow-up was 48.1 months (IQR, 24.7-74.9 months). On Cox proportional hazards regression multivariable analysis, only overweight BMI was associated with improved OS (5-year OS, 71.5% vs 58.4%; adjusted hazard ratio [AHR], 0.59 [95% CI, 0.39-0.91]; P = .02) and PFS (5-year PFS, 68.3% vs 50.8%; AHR, 0.51 [95% CI, 0.34-0.75]; P < .001). On logistic multivariable analysis, overweight BMI (91.6% vs 73.8%; adjusted odds ratio [AOR], 0.86 [95% CI, 0.80-0.93]; P < .001) and obese BMI (90.6% vs 73.8%; AOR, 0.89 [95% CI, 0.81-0.96]; P = .005) were associated with complete metabolic response on follow-up positron emission tomography-computed tomography after treatments. On Fine-Gray multivariable analysis, overweight BMI was associated with reduction in LRF (5-year LRF, 7.0% vs 25.9%; AHR, 0.30 [95% CI, 0.12-0.71]; P = .01), but not DF (5-year DF, 17.4% vs 21.5%; AHR, 0.92 [95% CI, 0.47-1.77]; P = .79). Obese BMI was not associated with LRF (5-year LRF, 10.4% vs 25.9%; AHR, 0.63 [95% CI, 0.29-1.37]; P = .24) or DF (5-year DF, 15.0% vs 21.5%; AHR, 0.70 [95% CI, 0.35-1.38]; P = .30). Conclusion: In this cohort study of patients with head and neck cancer, when compared with normal BMI, overweight BMI was an independent factor favorably associated with complete response after treatments, OS, PFS, and LRF. Further investigations are warranted to improve understanding on the role of BMI among patients with head and neck cancer.

Dengue virus infection of mast cells triggers endothelial cell activation.

Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection.

Defining the optimal threshold and prognostic utility of pre-treatment hemoglobin level as a biomarker for survival outcomes in head and neck cancer patients receiving chemoradiation.

OBJECTIVES: We sought to define the optimal threshold for anemia in North American head and neck cancer patients and evaluate its role as a prognostic biomarker. MATERIALS AND METHODS: A single-institution database was queried for patients with head and neck cancer who underwent chemoradiation from January 2005 to April 2021. An optimal threshold of hemoglobin (Hgb) level was defined based on maximum log-rank test statistic. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate treatment outcomes. RESULTS: A total of 496 patients were identified. Threshold for Hgb was determined to be 11.4 for both overall survival (OS) and progression-free survival (PFS). Low Hgb was associated with worse OS (adjusted hazards ratio [aHR] 2.41, 95 % confidence interval [CI] 1.53-3.80, p < 0.001) and PFS (aHR 2.01, 95 % CI 1.30-3.11, p = 0.002). Similar findings were observed among 39 matched pairs for OS (5-year OS 22.3 % vs 49.0 %; HR 2.22, 95 % CI 1.23-4.03, p = 0.008) and PFS (5-year PFS 24.3 % vs 39.1 %; HR 1.78, 95 % CI 1.02-3.12, p = 0.04). Among those with HPV-negative tumors, low Hgb was associated with worse OS (aHR 13.90, 95 % CI 4.66-41.44, p < 0.001) and PFS (aHR 5.24, 95 % CI 2.09-13.18, p < 0.001). However, among those with HPV-positive tumors, low Hgb was not associated with both OS (aHR 1.75, 95 % CI 0.60-5.09, p = 0.31) and PFS (aHR 1.13, 95 % CI 0.41-3.14, p = 0.82). CONCLUSION AND RELEVANCE: Low Hgb below 11.4 was an independent adverse prognostic factor for worse survival. It was also prognostic among patients with HPV-negative tumors, but not for HPV-positive tumors.

Association of Pack-Years of Cigarette Smoking With Survival and Tumor Progression Among Patients Treated With Chemoradiation for Head and Neck Cancer.

Importance: After 10 pack-years of smoking was initially established as a threshold for risk stratification, subsequent clinical trials incorporated it to identify candidates for treatment deintensification. However, several recent studies were unable to validate this threshold externally, and the threshold for smoking exposure remains unclear. Objective: To estimate the threshold of pack-years of smoking associated with survival and tumor recurrence among patients with head and neck cancer. Design, Setting, and Participants: This single-institution, cohort study included patients with nonmetastatic head and neck cancer receiving chemoradiation from January 2005 to April 2021. Data were analyzed from January to April 2022. Exposures: Heavy vs light smoking using 22 pack-years as a threshold based on maximizing log-rank test statistic. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF). Results: A total of 518 patients (427 male [82.4%]; median [IQR] age, 61 [55-66] years) were included. Median (IQR) follow-up was 44.1 (22.3-72.8) months. A nonlinear Cox regression model using restricted cubic splines showed continuous worsening of OS and PFS outcomes as pack-years of smoking increased. The threshold of pack-years to estimate OS and PFS was 22. Cox multivariable analysis (MVA) showed that more than 22 pack-years was associated with worse OS (adjusted hazard ratio [aHR] 1.57; 95% CI, 1.11-2.22; P = .01) and PFS (aHR, 1.38; 95% CI, 1.00-1.89; P = .048). On Fine-Gray MVA, heavy smokers were associated with DF (aHR, 1.71; 95% CI, 1.02-2.88; P = .04), but not LRF (aHR, 1.07; 95% CI, 0.61-1.87; P = .82). When 10 pack-years of smoking were used as a threshold, there was no association for OS (aHR, 1.23; 95% CI, 0.83-1.81; P = .30), PFS (aHR, 1.11; 95% CI, 0.78-1.57; P = .56), LRF (aHR, 1.19; 95% CI, 0.64-2.21; P = .58), and DF (aHR, 1.45; 95% CI, 0.82-2.56; P = .20). Current smoking was associated with worse OS and PFS only among human papillomavirus (HPV)-positive tumors (OS: aHR, 2.81; 95% CI, 1.26-6.29; P = .01; PFS: aHR, 2.51; 95% CI, 1.22-5.14; P = .01). Conclusions and Relevance: In this cohort study of patients treated with definitive chemoradiation, 22 pack-years of smoking was associated with survival and distant metastasis outcomes. Current smoking status was associated with adverse outcomes only among patients with HPV-associated head and neck cancer.

Injection laryngoplasty during transoral laser microsurgery for early glottic cancer: a randomized controlled trial.

BACKGROUND: Transoral laser microsurgery is widely used for treating T1/T2 glottic cancers. Hyaluronic acid (HA) is commonly used in vocal cord augmentation. We investigated the impact of intra-operative injection laryngoplasty on voice outcomes in early glottic cancer. METHODS: Twenty patients were randomized to the treatment group receiving HA injection to the vocal cord contralateral to the lesion; or the control group, receiving no injection. Patients had a Voice Handicap Index-10 (VHI-10) questionnaire and a Maximum Phonation Time (MPT) measurement preoperatively and at 3, 12 and 24 months post-operatively. Mean change in VHI-10 and MPT, compared to baseline and between time points, were compared. Survival estimates were calculated. RESULTS: Mean VHI-10 scores improved over time amongst all patients. There were no changes in mean VHI-10 from pre-operative values to 3, 12 or 24 months post-operatively. There were no significant differences when comparing various timepoints between groups. There were no significant changes in MPT amongst the groups, or the time-points compared. Two-year overall survival was 91.7%; disease free survival was 80.9%; no difference in recurrence free survival was seen between the groups. CONCLUSION: Subjective voice scores improved over time in both groups; there were no improvements in VHI-10 or MPT scores in the injection group, over control, at any time points. We saw no significant impact for intra-operative HA injection laryngoplasty on subjective or objective voice outcomes following surgery for early glottic cancers.

Ovarian Cancer Metastasis to the Larynx: A Case Report and Review of the Literature.

Laryngeal secondary malignancies are rare, and most spread locoregionally from hypopharyngeal or thyroid primaries. Metastasis of ovarian carcinoma to the larynx is extremely rare. A 65-year-old woman with a history of high grade serous ovarian carcinoma was undergoing carboplatin chemotherapy for recurrence. She presented with progressive dysphagia and hoarseness; a computer tomography (CT) scan demonstrated bilateral necrotic lymphadenopathy and hypopharyngeal fullness. A hypopharyngeal mass was confirmed on examination, and operative biopsy identified it as high-grade serous ovarian. To our knowledge, this report describes the second immunohistochemically proven metastatic ovarian cancer detected in the larynx in the world literature.

The accuracy of standard audiometric hearing level thresholds in pediatric patients.

OBJECTIVES: Standard audiograms provide decibels Hearing Level (dB HL) thresholds, which are referenced to normative values specified in decibels Sound Pressure Level in an acoustic coupler. Due to variability in external ear acoustics, the actual sound levels reaching the eardrum can vary across individuals. The real-ear to coupler difference (RECD) is a frequency-specific measurement of the difference between sound levels measured at the eardrum and in a coupler. Here, we compare the standard audiogram dB HL levels to RECD corrected hearing thresholds (dB RECHL) in children. METHODS: Children who underwent standard audiometric and RECD testing were included. The dB RECHL was established and the differences between dB HL and dB RECHL (threshold error) was calculated. A threshold error >5 dB was considered significant. RESULTS: A total of 166 children were included (mean age 12 years). Overall, 14% had normal hearing, 52% had conductive hearing loss and 27% had sensorineural hearing loss. Hearing threshold levels were overestimated by the standard audiogram compared to dB RECHL, at all frequencies (250-6000 Hz). In the lower frequencies and at 6000 Hz, 33-59% of patients were overestimated, with a threshold error up to 25 dB. In the mid frequencies, 33% were overestimated with a similar threshold error. CONCLUSION: Standard audiogram thresholds overestimated hearing levels in children which may have clinical implications. This problem can be addressed by correcting thresholds with RECD. More studies are needed to assess the effect of correcting thresholds on hearing outcomes in children.

Multiple Venous Malformations as a Cause of Pulsatile Tinnitus.

INTRODUCTION: Pulsatile tinnitus is a relatively common presentation in otolaryngology clinics, most cases of which have a treatable cause. This presentation warrants a thorough workup to identify treatable, and rule out life-threatening, etiologies. We present a case of a patient with pulsatile tinnitus arising from multiple dilated venous channels in the head and neck. Case Presentation. We present the case of a 65-year-old Caucasian female with a two-year history of progressive, bilateral pulsatile tinnitus, which had become debilitating. Computed-tomographic angiography (CTA) studies ruled out an intracranial vascular cause for her symptoms. However, computed tomography (CT) scanning and magnetic resonance imaging (MRI) revealed multiple dilated bilateral, low-flow, venous channels throughout the head and neck. The proximity of such dilated venous channels to the temporal bone provides a route for sound to be transmitted to the inner ear. CONCLUSION: Arterial, venous, and systemic etiologies can cause pulsatile tinnitus. Arteriovenous malformations (AVMs) of the head and neck represent less than 1% of cases. In our patient, dilated low-flow venous malformations are the likely source of her symptoms, which is the first reported case in the literature.