Cutaneous hyperpigmentation following bleomycin sclerotherapy for vascular malformations.

Systemic bleomycin therapy is associated with pulmonary fibrosis and cutaneous side effects. While it is believed that there is little to no systemic distribution of bleomycin when utilized to treat vascular malformations (VMs), we present a case series in which cutaneous, adhesive-related hyperpigmentation suggests that there is systemic egress of bleomycin following direct puncture sclerotherapy (DPS). This risk of hyperpigmentation after intralesional bleomycin should be discussed with patients, and steps to minimize the chances of it occurring should be implemented.

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study.

Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy ( p = 0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis ( p < 0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Postoperative and 1-Year Functional Outcomes After Free Flap Surgery Among Patients 80 Years or Older.

OBJECTIVE: To evaluate the postoperative and 1-year functional outcomes after free flap surgery among patients ≥80 years old. STUDY DESIGN: Retrospective chart review. SETTING: Single tertiary care center. METHODS: We conducted a retrospective review of 596 patients who underwent head and neck ablation and reconstruction with free tissue over a 7-year period. Patients ≥80 years of age were included. RESULTS: Fifty patients were ≥80 years old, with an average age of 83.7 years. Ninety-day mortality was 12.0%, and those who died were of older age (87.5 vs 83.1 years, P = .036). Prior radiation therapy (odds ratio, 6.8 [95% CI, 1.1-42.7]) and a Charlson Comorbidity Index ≥3 (odds ratio, 10.0 [95% CI, 1.5-67.0]) were associated with an increased risk of 90-day mortality. Overall 21 (42.0%) patients experienced a 30-day complication; 7 (14.0%) were readmitted within 30 days; and 5 (10.0%) underwent additional flap-related operations. Flap failure occurred in 2 (4.0%) patients. Before surgery, 45 (90%) patients were living independently or within assisted living; among these, 19.5% declined to dependent functional status at 90-day follow-up. At 90 days, 2 (8.3%) of 24 patients remained tracheostomy dependent, and 20 (66.7%) of 30 patients required feeding tube supplementation. Among 42 patients, 36 (85.7%) had unrestricted or modified oral diets at 90 days. Charlson Comorbidity Index ≥2 was associated with an increased risk of 1-year mortality (odds ratio, 5.1 [95% CI, 1.4-18.6]). CONCLUSION: The potential for functional decline and risk of 90-day mortality should be discussed with patients aged ≥80 years.

Infantile Hemangioma Treated with Propranolol Readmission Trends, Complications of Therapy, and Cost: A PHIS Database Study.

Objective: To examine admission trends, complications, and costs for inpatient infantile hemangioma (IH) associated with propranolol therapy utilizing the Pediatric Health Information System (PHIS) database. Study Design. A retrospective cohort study was completed using the PHIS database. The PHIS database was queried from 2008 to 2020 for children without cardiac disease and between the ages of three weeks and one year who were admitted with a diagnosis of IH and administered propranolol. Admissions were trended annually and by geographic region. Primary outcomes were length of stay (LOS), readmission, mortality, propranolol-related complications, and costs. Bivariate and multivariable analyses were employed to identify predictors of the primary outcomes. Results: A total of 2290 unique patient encounters were identified. Admissions steadily decreased after 2011, with variations by geographic region. There was no mortality and only 60 (2.6%) propranolol-related complications. African-American race (odds ratio (OR) 1.20 [95% CI: 1.02-1.41]), respiratory comorbidities (OR 2.04 [95% CI: 1.42-2.93]), neurologic conditions (OR 1.34 [95% CI: 1.09-1.59]), admission to an intensive care unit (OR 1.31 [95% CI: 1.09-1.59]), bronchospasm (OR 1.37 [95% CI: 1.22-1.55]), and hyperkalemia (OR 1.86 [95% CI: 1.08-3.20]) were associated with increased LOS. Neurologic conditions (OR 2.87 [95% CI: 1.76-4.67]) and respiratory comorbidities (OR 2.48 [CI: 1.43-4.30]) were associated with readmission. Average cost per admission was $5,158 ($3,259 to $8,560 range). Conclusion: There is an overall national decline in rate of admissions for IH propranolol therapy. Inpatient admission may be beneficial for patients with neurologic or respiratory conditions.

Systematic review of neuroendocrine carcinomas of the oropharynx.

Data describing features and management of oropharyngeal neuroendocrine carcinomas (NEC) remain sparse. A systematic review was performed. Patients were stratified by treatment modality and examined for disease progression and survival outcomes. Ninety-four patients from 50 publications were included. Average age at diagnosis was 59.7 years (range 14-83). 73.4% were male. Most studies did not document HPV status. Forty patients (85.1%) were p16 positive, and 34 (85.0%) were HPV-ISH positive. Overall survival was 75.4% at 1 year, and 40.0% at 2 years. Of patients with locoregional disease, 33.8% developed distant metastasis. 12.5% of patients developed locoregional recurrence. Patients who developed distant metastases had worse overall survival (p = 0.0004). No significant difference was found between treatment modalities. Human papilloma virus may be associated with oropharyngeal NEC. Current treatments provide locoregional control, but distant metastases are common and confer low overall survival.

An assessment of racial differences in epidemiological, clinical and psychosocial factors among head and neck cancer patients at the time of surgery.

OBJECTIVE: Racial disparities have been well characterized and African American (AA) patients have 30% lower 5-year survival rates than European Americans (EAs) for head and neck squamous carcinoma (HNSCC). This poorer survival can be attributed to a myriad of different factors. The purpose of this study was to characterize AA-EA similarities and differences in sociodemographic, lifestyle, clinical, and psychosocial characteristics in HNSCC patients near the time of surgery. METHODS: Setting: Single tertiary care center. Participants: Thirty-nine newly diagnosed, untreated HNSCC patients (n = 24 EAs,n = 15 AAs) who were to undergo surgery were recruited. Study Design: Cross-sectional study Sociodemographic, lifestyle factors, and disease factors (cancer site, AJCC clinical and pathologic stage, and HPV status)were assessed. Risk factors, leisure time, quality of life and social support were also assessed using validated questionnaires. Exposures: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs and significantly increased time to treatment. RESULTS: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs. AAs also had significantly increased time to treatment (P = 0.05). The majority of AA patients (62%) had later stage pathologic disease. AA were less likely to complete high school or college (P = 0.01) than their EA counterparts. Additionally, AAs were more likely to report having a gap in health insurance during the past decade (37% vs. 15%). CONCLUSIONS: This preliminary study demonstrates a similar profile of demographics, clinical and psychosocial characteristics preoperatively for AAs and EAs. Key differences were AAs tending to have later pathologic stage disease, educational status, delays in treatment initiation, and gaps in health insurance.

Impact of Delay in Treatment Initiation on Overall Survival in Laryngeal Cancers.

OBJECTIVE: Delayed treatment significantly affects survival in head and neck cancer, but defining delays for specific subsites remains controversial. The purpose of this study is to elicit the time point for delay in treatment initiation in all laryngeal cancers using a large cohort of patients within the National Cancer Database (NCDB). STUDY DESIGN: A retrospective cohort study. SETTING: NCDB. SUBJECTS AND METHODS: Patients with laryngeal cancer within the NCDB from 2006 to 2014 were identified. A recursive partition analysis (RPA) was performed to identify the time point at which delay contributed to increased hazard. Patients were stratified into 3 groups: no delay, at risk, and overtly delayed. Kaplan-Meier method was used to compare overall survival of these cohorts. Multivariate logistic regression analysis was used to identify predictors of delay. A multivariate Cox regression model was used to identify the final covariates that significantly affect overall survival. RESULTS: RPA identified the threshold for delay becomes significant at 46 days and exceeds baseline hazard at 73 days. Delay beyond 73 days is associated with a 16.1-month decrease in median survival ( P < .001). To ensure this was not due to any confounding variables, a subsequent Cox multivariate regression confirmed a significantly increased adjusted hazard ratio (HR) for patients who were at risk or delayed (adjusted HR [confidence interval], 1.09 [1.04-1.15] and 1.26 [1.18-1.35], respectively). CONCLUSION: Treatment of laryngeal cancer requires a multidisciplinary approach, and coordinating this care can take time. Our study highlights that delay beyond 46 to 73 days significantly affects survival and identifies patients experiencing these delays.

The outcomes of hypoglossal nerve stimulation in the management of OSA: A systematic review and meta-analysis.

OBJECTIVES: Obstructive sleep apnea (OSA) is a prevalent disease with significant health impacts. While first line therapy is CPAP, long-term compliance is low and device misuse is common, highlighting the need for alternative therapies. Upper airway surgery is one alternative, but substantial side effects hamper efficacy. A new alternative is an implantable hypoglossal nerve stimulator (HNS). These devices utilize neuromodulation to dilate/reinforce the airway and reduce side effects associated with traditional surgery. Several recent trials investigated the efficacy of these devices. The purpose of this study was to perform meta-analysis of available HNS studies investigating treatment of OSA to analyze objective and subjective outcomes and side effects. METHODS: A comprehensive literature search of PubMed and Scopus was performed. Two independent reviewers examined clinical trials investigating HNS in treatment of sleep apnea in adults. Studies with objective and subjective endpoints in sleep were included for analysis. Adverse events from trials were also recorded. RESULTS: Across 16 studies, 381 patients were analyzed. At 6 months (p = 0.008), mean SAQLI improved by 3.1 (95%CI, 2.6-3.7). At 12 months (p < 0.0001), mean AHI was reduced by 21.1 (95%CI, 16.9-25.3), mean ODI was reduced by 15.0 (95%CI, 12.7-17.4), mean ESS was reduced by 5.0 (95%CI, 4.2-5.8), mean FOSQ improved by 3.1 (95%CI, 2.6-3.4). Pain (6.2%:0.7-16.6), tongue abrasion (11.0%:1.2-28.7), and internal (3.0%:0.3-8.4)/external device (5.8%:0.3-17.4) malfunction were common adverse events. CONCLUSIONS: HNS is a safe and effective treatment for CPAP refractory OSA. Further study comparing HNS to other therapies is required.

Gland-preserving surgery for salivary stones and the utility of sialendoscopes.

BACKGROUND: Sialoendoscopy is the standard treatment for sialolithiasis; however, some patients may be unlikely to benefit from an endoscopic approach. This study assesses predictors of failure in the endoscopic management of sialoliths. METHODS: Patients treated for sialolithiasis from 2012 to 2017 at two centers were stratified into 3 groups: successful interventional sialendoscopy, incisional sialolithotomy, and gland excision. Patient, disease, and surgical factors were compared. RESULTS: Interventional sialendoscopy was attempted in 156 of 206 cases and successful for 42 (27%). Endoscopically retrieved calculi were smaller (4.96 mm) compared to incisional sialolithotomy (7.90 mm). Nonendoscopic approaches were required more often in submandibular cases 87% (P ≤ .005). Palpable stones were present in 74% of incisional sialolithotomies (P < .001). Submandibular location (OR 3.50, 1.53-7.98), palpability (OR 2.74, 1.21-6.18), CT localization (OR 3.05, 1.32-7.10, P = .010), and increased diameter (OR 1.25, 1.09-1.44) were predictive of incisional management. CONCLUSION: Stone size/location, CT-localization, and palpability were predictive of calculi that require an incisional approach. If these factors are recognized, the surgeon can consider proceeding directly to incisional sialolithotomy. LEVEL OF EVIDENCE: III.

Prognostic Impact of High-Risk Pathologic Features in HPV-Related Oropharyngeal Squamous Cell Carcinoma and Tobacco Use.

OBJECTIVES: To assess the impact of pathologic features and chronic tobacco use on human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Case series with chart review. SETTING: Single tertiary care referral center. SUBJECT AND METHODS: A total of 301 patients were treated for OPSCC from 2008 to 2016. Clinical and pathologic T and N stage, American Joint Committee on Cancer (AJCC) stage (seventh and eighth edition staging manuals), cigarette pack years, alcohol use, and presence of extranodal extension (ENE), perineural invasion (PNI), or lymphovascular invasion (LVI) were assessed. Patients were stratified into HPV negative, HPV-positive heavy smokers (≥20 pack years), and HPV-positive nonsmokers. Five-year survival by Kaplan-Meier method was assessed. RESULTS: Of the HPV-positive patients, 97 were nonsmokers and 73 were heavy smokers. HPV-positive heavy smokers had significantly decreased survival compared to their nonsmoking counterparts ( P = .02). The presence of ENE was associated with a significantly decreased 5-year survival ( P = .02) in heavy smokers relative to nonsmokers in HPV-positive patients. Furthermore, for the AJCC eighth edition, clinically stage 1 HPV-positive heavy smokers had significantly decreased survival relative to nonsmokers ( P = .01). CONCLUSIONS: This series highlights the potential need for more aggressive therapy for HPV-positive patients with extensive tobacco use under the new staging system.

Association of Treatment Delays With Survival for Patients With Head and Neck Cancer: A Systematic Review.

Importance: Delays in the delivery of care for head and neck cancer (HNC) are a key driver of poor oncologic outcomes and thus represent an important therapeutic target. Objective: To synthesize information about the association between delays in the delivery of care for HNC and oncologic outcomes. Evidence Review: A systematic review of the English-language literature in PubMed/MEDLINE and Scopus published between January 1, 2007, and February 28, 2018, was performed to identify articles addressing the association between treatment delays and oncologic outcomes for patients with HNC. Articles that were included (1) addressed cancer of the oral cavity, oropharynx, hypopharynx, or larynx; (2) discussed patients treated in 2004 or later; (3) analyzed time of diagnosis to treatment initiation (DTI), time from surgery to the initiation of postoperative radiotherapy, and/or treatment package time (TPT; the time from surgery through the completion of postoperative radiotherapy); (4) included a clear definition of treatment delay; and (5) analyzed the association between the treatment time interval and an oncologic outcome measure. Quality assessment was performed using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. Findings: A total of 18 studies met inclusion criteria and formed the basis of the systematic review. Nine studies used the National Cancer Database and 6 studies were single-institution retrospective reviews. Of the 13 studies assessing DTI, 9 found an association between longer DTI and poorer overall survival; proposed DTI delay thresholds ranged from more than 20 days to 120 days or more. Four of the 5 studies assessing time from surgery to the initiation of postoperative radiotherapy (and all 4 studies assessing guideline-adherent time to postoperative radiotherapy) found an association between a timely progression from surgery to the initiation of postoperative radiotherapy and improved overall or recurrence-free survival. Of the 5 studies examining TPT, 4 found that prolonged TPT correlated with poorer overall survival; proposed thresholds for prolonged TPT ranged from 77 days or more to more than 100 days. Conclusions and Relevance: Timely care regarding initiation of treatment, postoperative radiotherapy, and TPT is associated with survival for patients with HNC, although significant heterogeneity exists for defining delayed DTI and TPT. Further research is required to standardize optimal time goals, identify barriers to timely care for each interval, and design interventions to minimize delays.

Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.

PURPOSE: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for patients with advanced HNSCC, and the clinical safety, antitumor, and molecular activity of rapamycin administration on HNSCC. PATIENTS AND METHODS: Patients with untreated stage II-IVA HNSCC received rapamycin for 21 days (day 1, 15 mg; days 2-12, 5 mg) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre- and posttreatment biopsies and blood were obtained for toxicity, immune monitoring, and IHC assessment of mTOR signaling, as well as exome sequencing. RESULTS: Sixteen patients (eight oral cavity, eight oropharyngeal) completed rapamycin and definitive treatment. Half of patients were p16 positive. One patient had a pathologic complete response and four (25%) patients met RECIST criteria for response (1 CR, 3 PR, 12 SD). Treatment was well tolerated with no grade 4 or unexpected toxicities. No significant immune suppression was observed. Downstream mTOR signaling was downregulated in tumor tissues as measured by phosphorylation of S6 (P < 0.0001), AKT (P < 0.0001), and 4EBP (P = 0.0361), with a significant compensatory increase in phosphorylated ERK in most patients (P < 0.001). Ki67 was reduced in tumor biopsies in all patients (P = 0.013). CONCLUSIONS: Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC.

Cryotherapy for the Treatment of Chronic Rhinitis: A Qualitative Systematic Review.

BACKGROUND: Chronic rhinitis impacts 60 million Americans and is associated with significant costs for patients. Although medical treatments are first line, some patients require surgical intervention such as vidian or posterial nasal neurectomy. Previous reviews have investigated the role of surgical management in chronic rhinitis, but none have investigated a longstanding treatment with recent interest: cryotherapy. OBJECTIVE: To identify the safety, efficacy, and durability of treatment response of cryotherapy in treating chronic rhinitis. METHODS: A systematic literature review was performed to identify studies that investigated the utility of cryotherapy in chronic rhinitis. Only studies with the primary objective of assessing the efficacy of cryotherapy on chronic rhinitis were included. Patients were classified as allergic rhinitis, nonallergic rhinitis (vasomotor rhinitis), or mixed rhinitis using the original author's criteria. Data were extracted regarding reported complications, treatment efficacy, and length of follow-up. RESULTS: A total of 110 abstracts were identified, of which 15 were included in this review. Epistaxis and nasal obstruction were commonly reported complications. No serious adverse events were reported. For obstructive symptoms, "reduced" symptoms were reported in 63.4% to 100% of patients. In regard to rhinorrhea, reports of reduced symptoms were experienced from 77% to 100% of patients. Seven studies used only patient-reported improvements without stratifying results based on symptom type; general improvements ranged from 67% to 100%. Nine studies noted symptom improvement in nonallergic cohorts ranging from 67% to 97.5% of patients. Four studies noted improvement in allergic cohorts ranging from 63.4% to 80% of patients. Two studies noted improvement in patients with mixed pictures ranging from 92.5% to 100%. CONCLUSIONS: Although cryotherapy appears safe and efficacious, heterogeneous past investigations with low-quality evidence make strong, evidence-based recommendations difficult to make. Further study with validated metrics and controlled populations is certainly warranted and should be encouraged.

The Sinus and Nasal Quality of Life Survey (SN-5) in the Management of Pediatric Chronic Rhinosinusitis: A systematic review and meta-analysis.

OBJECTIVES: Pediatric chronic rhinosinusitis (CRS) is a prevalent condition with quality of life (QoL) impacts that are seldom reported in the literature. We aimed to conduct a systematic review and meta-analysis on studies using the Sinus and Nasal Quality of Life Survey (SN-5), the only validated symptom questionnaire in pediatric CRS. METHODS: A literature search was conducted to identify studies that used the SN-5 to measure QoL before and after medical or surgical interventions for pediatric CRS. Comparison of means and standard deviations was performed between pre- and post-intervention SN-5 scores. RESULTS: A total of 10 studies, consisting of 13 separate treatment arms of either medical therapy, adenoidectomy, balloon catheter sinuplasty (BCS), or functional endoscopic sinus surgery (FESS) were identified. The vast majority (92.3%) of the treatment arms demonstrated minimal clinically important differences between baseline and post-intervention SN-5 scores. Rates of treatment success and minimal clinically important difference among all treatment arms ranged from 43.2% to 94.0%. Comparison of means showed an improvement in SN-5 score of 1.97 [95% CI, 1.18 to 2.76; p < 0.00001] for BCS, 1.83 [95% CI, 1.47 to 2.19; p < 0.00001] for FESS, and 1.15 [95% CI, 0.36 to 2.66; p = 0.13) for medical treatment. CONCLUSION: There is a paucity of literature on QoL outcomes in pediatric CRS. More studies using the SN-5, particularly those controlling for baseline patient characteristics, are necessary to fully elucidate the impact of various interventions on QoL in pediatric CRS.

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study

Abstract Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy (p =0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p <0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

The liquid biopsy in lung cancer.

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.