Designing a Prolonged Method of Therapeutic Delivery to Support Rehabilitation From Ototoxic Damage in a Schwann Cell Model.

HYPOTHESIS: The ototoxicity of gentamicin and cisplatin can be evaluated with a Schwann cell model to screen for otoprotective agents that can be encapsulated into poly (lactic-co-glycolic acid) (PLGA) microparticles for drug delivery to the inner ear. BACKGROUND: Aminoglycosides and cisplatin are widely prescribed but known to cause ototoxicity. There is strong evidence that compromise to Schwann cells ensheathing inner ear afferent neurons results in inner ear dysfunction mimicking drug-induced ototoxicity. There is a need for a model for ototoxic demyelination to screen medications for protective potential and to subsequently target and tune the delivery of any promising agents. METHODS: RT4-D6P2T rat schwannoma cells were used as a Schwann cell model to assess gentamicin and cisplatin toxicity and to screen for protective agents. Cell viability was evaluated with the MTT cell proliferation assay. N -acetylcysteine (NAC) was encapsulated into a PLGA microparticle, and its elution profile was determined. RESULTS: The estimated 50% lethal concentration dose for gentamicin was 805.6 µM, which was 46-fold higher than that for cisplatin (17.5 µM). In several trials, cells dosed with NAC and cisplatin demonstrated a 22.6% ( p < 0.001) increase in cell viability when compared with cisplatin alone. However, this protective effect was not consistent across all trials. NAC was encapsulated into a PLGA microparticle and elution plateaued at 5 days. CONCLUSION: When dosed at their respective therapeutic ranges, cisplatin is more likely than gentamicin to induce damage to the Schwann cell model. Although NAC demonstrates an uncertain role in protecting against cisplatin-induced Schwann cell cytotoxicity, this study establishes a method to screen for other otoprotective medications to encapsulate into a tunable microparticle for localized drug delivery.

Impact of defensins-containing body cream on skin composition.

BACKGROUND AND AIMS: Defensins are peptides capable of reactivating latent LGR6 stem cells in the basal layer. When applied topically, these peptides can reduce signs of skin aging and increase dermal thickness. This study investigates the effects of a topical defensin formulation on extremity skin composition. METHODS: An open label, single arm clinical trial was conducted on participants with dry, photoaged, or dull skin. A defensin-containing hand and body cream was applied twice daily for 6 weeks to the hands, forearms, elbows, and knees. Photographs and objective measurements of skin hydration, viscoelasticity (VE), retraction time (RT), thickness, density/transepidermal water loss (TEWL), as well as self-evaluation of skin quality and characteristics were obtained pre- and post- intervention. RESULTS: After the study period, RT decreased by 56% across all body sites (p < 0.001) and VE improved at the elbow (125%, p = 0.009) and knee (110%, p < 0.001). Skin density also increased in all 4 body sites (40%, p < 0.001), while skin thickness increased at the elbow (29%, p = 0.03) and knee (17%, p = 0.04). Skin hydration increased at the elbow, knee, and forearm by 99%, 28%, and 16%, respectively (p < 0.05), while TEWL improved at the elbow only (-39%, p = 0.02). Patients' self-evaluations showed improvements in overall skin quality and in the domains of dryness, ashiness, wrinkling, pigmentation, redness, roughness, and discomfort (p < 0.05). CONCLUSIONS: Following 6-week use of a defensin-containing cream, subjects reported significant improvement across many subjective skin domains. Similarly, objective measurements demonstrated significant improvement in skin architecture at select sites.

Head & neck melanoma: A 22-year experience of recurrence following sentinel lymph node biopsy.

OBJECTIVE: To examine the clinicopathologic factors that contribute to regional and distant recurrence in intermediate to high risk head and neck melanoma patients after sentinel lymph node biopsy (SLNB). METHODS: This study is a retrospective review from an academic tertiary care center. Patients treated with SLNB for head and neck melanoma from 1997 to 2019 were reviewed and characterized by sentinel lymph node (SLN) status. Clinical variables were examined for the impact on regional and distant recurrence in SLNB-negative patients using univariable and multivariable Cox regression analysis. RESULTS: One hundred and fifty four patients were included. Of note, 127 (82.5 %) were men, and the average age was 61.3 years. Median follow-up was 68.6 weeks. Pathologic review of SLNs found 3.9% positive for metastatic melanoma; 96.1% were negative. Regional recurrence was significantly associated with tumor stage and age on multivariate analysis. A total of 4.5% of patients recurred in a previously labeled negative basin. Scalp subsite accounted for 30.5% of primary tumors and was more likely to yield a positive SLN on univariate analysis (P = .023). Tumor stage and age were significantly associated with distant metastasis on multivariable analysis (P = .026, P < .001 respectively). CONCLUSION: We report a number of prognostic trends in head and neck melanoma. SLN positivity was found more often in patients with a primary tumor of the scalp. Regional recurrence was significantly associated with age and tumor stage, whereas distant recurrence was significantly associated with tumor staging and scalp subsite. Scalp subsite was associated with an increased risk for nodal metastasis and distant recurrence. LEVEL OF EVIDENCE: 3.

Cancer of the Larynx and Hypopharynx.

The Radiation Therapy Oncology Group 91-11 trial and US Veterans Affairs trial revolutionized the way locally advanced laryngeal cancers are treated. Adjuvant therapies exist aimed toward laryngeal preservation using docetaxel, cisplatin, and fluorouracil. Cetuximab is a cornerstone of treatment due to the large role of epidermal growth factor receptor in laryngeal and hypopharyngeal carcinomas. In addition, the immune system is vital in the prevention of recurrence, and various immunomodulators against programmed cell death receptor 1 are being investigated. Multidisciplinary management of the patient with laryngeal and hypopharyngeal is key, as many vital functions are affected by this devastating disease.

Crayon in the Orbit and Sinuses in a Pediatric Patient.

Penetrating transorbital injury with skull base involvement is a rare occurrence from a crayon. We report a case of a 2-year-old male who sustained a penetrating crayon injury through the right orbit and lamina papyracea into the posterior ethmoid sinus complicated by cerebrospinal fluid leak. There have been no other reported cases of this type of injury by a crayon.

Cutaneous Cancer Biology.

There has been a drastic increase in the incidence of nonmelanoma (NMSC), including squamous, basal cell, and melanoma skin cancers worldwide. Most cases of skin cancer can be treated effectively with surgery; fewer than 10% of cases are advanced and may require additional therapies. A better understanding of the biology of skin cancer will help contribute to better prognostic information and identification of possible new therapeutic targets. Herein, the authors review the biology and pathogenesis of both NMSC and melanoma, focusing on critical cell signaling pathways mediating the disease and current therapeutic strategies targeted to underlying genetic pathways.

Age-Related Trends of Patients Undergoing Thyroidectomy: Analysis of US Inpatient Data from 2005 to 2013.

OBJECTIVES: As the country ages, thyroidectomies can be expected to be performed more frequently among the elderly. In this study, we stratified patients by age to explore demographics and complications of patients undergoing thyroidectomy. STUDY DESIGN: Retrospective study with a national database. SETTING: Nationwide Inpatient Sample. SUBJECTS AND METHODS: A total of 414,079 thyroidectomy cases from 2005 to 2013 were identified. Complications, outcomes, demographics, length of stay, and hospital charges were evaluated among patients and stratified by age into 4 cohorts: younger (<65 years), advanced age (65-74 years), elderly (75-84 years), and superelderly (≥85 years). RESULTS: Of 414,079 thyroidectomy cases identified, patients aged <65 years accounted for 75.6% of cases, while those aged 65-74, 75-84, and ≥85 years accounted for 16.3%, 7.2%, and 0.9%, respectively ( P < .001). There was a significant difference in length of stay, total hospital charges, and mortality throughout the different age groups ( P < .001), all trending upward with advancing age. In the aging population, incidence of recurrent laryngeal nerve injury, transfusion of erythrocytes, and acute cardiac complications increased with increasing age ( P < .001), while hypoparathyroidism decreased with age ≥65 but ≤85 years ( P < .001). Patients aged ≥75 years had increased odds of mortality as compared with their younger counterparts ( P < .001). CONCLUSION: This study utilized a national database to describe and elucidate trends in older populations undergoing thyroidectomy. Thyroid-related complications, including blood transfusion and recurrent laryngeal nerve injury, increased with increasing patient age. This information will help to guide pre- and postoperative care for aging patients undergoing thyroidectomy.

Supraglottic Squamous Cell Carcinoma: A Population-Based Study of 22,675 Cases.

OBJECTIVES/HYPOTHESIS: The authors used the Surveillance, Epidemiology, and End Results (SEER) database to analyze epidemiological features of patients presenting with supraglottic squamous cell carcinoma (SCCa) and to evaluate treatment trends and outcomes. METHODS: The SEER database was queried for patients with supraglottic SCCa from 1973 to 2013. Information on demographics; tumor size; histologic grade; American Joint Committee on Cancer (AJCC) stage; SEER local, regional, distant stage; and treatment modality were analyzed. RESULTS: There were 22,675 cases of primary supraglottic SCCa identified. The mean age at diagnosis was 62.3 years, with males accounting for 70.3% of all cases. A high percentage of patients presented with stage IV disease (44.9%). The most common treatment modality was radiotherapy (46.6%), followed by combination of surgery and radiotherapy (29.2%) and surgery alone (15.0%). Overall 5-year disease-specific survival (DSS) for all cases was 54.0%. When stratified by treatment modality, 5-year DSS was best for patients receiving surgery alone (64.2%). However, for patients with AJCC stage IV disease, survival was significantly better with combined surgery and radiotherapy (52.5%). CONCLUSION: In general, supraglottic SCCa is treated most commonly with radiotherapy, followed by surgery and radiotherapy. Patients managed surgically had better 5-year DSS when compared to patients treated by other modalities. However, when stratified by stage, patients with AJCC stage IV disease had significantly better survival with combined surgery and radiotherapy. Of patients receiving surgery, supraglottic laryngectomy was found to have a significantly better 5-year DSS when compared to both total laryngectomy and laryngectomy, not otherwise specified. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1822-1827, 2019.

Utility of early postoperative imaging after combined endoscopic and open ventral skull base surgery.

PURPOSE: Immediate postoperative imaging is frequently obtained after combined skull base surgery (SBS) with endoscopic endonasal and open transcranial approaches. The importance of early postoperative imaging for detecting complications in these patients is still debatable. In this study, we investigated the clinical utility of early postoperative imaging after combined SBS for determination of postoperative complications. METHODS: A retrospective chart analysis of 21 cases of combined SBS between 2009 and 2015 was performed. Data on postoperative computed tomography (CT) and magnetic resonance imaging (MRI), and the hospital course were collected. We separated interpretations of postoperative imaging into two groups: (1) when using the radiologist's interpretation alone, and (2) when using the surgeon's knowledge of the case in conjunction with imaging. RESULTS: Forty-two postoperative scans were obtained (21 CT, 21 MRI) within 48 hours of surgery. There was a significant statistical difference between imaging interpretation by surgeons and radiologists for CT interpretation only. For CT interpretation the true positive (TP), false positive (FP), true negative (TN), and false negative (FN) rates for radiologists (TP, 0/21; FP, 6/21; TN, 11/21; FN, 4/21) slightly deviated from surgeons' interpretation (TP, 1/21 [p = 0.9999]; FP, 0/21 [p = 0.0207]; TN, 17/21 [p = 0.1000]; FN, 3/21 [p = 1.000]). Rates for MRI interpretation by both groups were nearly identical, with no significant difference found. Overall, four patients experienced seven postoperative complications, which led to a complication rate of 19.0% (4/21). The patients exhibited clinical symptoms in all instances of postoperative complications that required further intervention. CONCLUSION: The benefit of early postoperative imaging to detect complications after combined SBS was limited. In this cohort of patients, positive imaging findings' effects on patient management were dictated by the presence of supporting clinical symptoms.

Laryngeal Verrucous Carcinoma.

Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are a topic of ongoing conversation, and no definitive treatment protocol based on T stage and presentation exists. This review examines characteristics, treatment modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE, and Web of Science. Methods Databases were searched through October 29, 2015, for literature detailing individual patient cases of LVC. Variables analyzed included patient demographics, tumor characteristics, tumor size, treatment, and outcomes. Results Thirty-seven articles with 369 cases were included. LVC was found more commonly in males (13.8:1), at an average age of 58.7 years, and located in the glottis (74.0%). Most patients had local disease at presentation (94.9%). The most common presenting symptom was hoarseness (92.3%). The most common primary treatment was surgery alone (72.3%), with local excision as the most common technique (56.8%). In patients with data available on both surgical modality and T stage, most patients who presented as T1 and were managed surgically underwent local excision (79.2%). Surgical treatment alone led to high rates of disease-free survival at follow-up (86.8%). A large number of patients presenting with T1 disease were disease free at follow-up (88.6%). Overall survival was 80.3%. Conclusion LVC is most often managed surgically. The extent of surgical resection may be guided by T stage, with smaller tumors resected via local excision and larger tumors via partial or total laryngectomy. Regardless of T stage or therapy, LVC has a good posttreatment prognosis.

Sphenoid sinus malignancies: a population-based comprehensive analysis.

BACKGROUND: Sinonasal malignancies are rare, representing less than 1% of all cancers, with the sphenoid sinus accounting for 1% to 2% of these cases. Sphenoid sinus malignancies exhibit very poor outcomes. There is a paucity of literature describing their histopathological features, incidence trends, treatment, and survival. We seek to elucidate these factors using a national population-based resource. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify malignant sphenoid sinus tumors. The results were analyzed for demographics, incidence, and clinicopathologic trends. Survival was calculated using Kaplan-Meier analysis. RESULTS: The search identified 472 cases. The mean and median age at diagnosis was 60.0 years. Males represented 54.9% of cases. By race/ethnicity, 82.4% were white and 8.5% were black. The four most common histopathologies were squamous cell neoplasms (29.4%), adenocarcinomas (14.4%), non-Hodgkin's mature B-cell lymphomas (13.1%), and unspecified epithelial neoplasms (11.0%). The overall incidence from 2000 to 2012 was 0.030 per 100,000. Kaplan-Meier analysis demonstrated an overall 5-year disease-specific survival (DSS) of 48.1%. Of the most common histopathological subtypes, 5-year DSS was best for mature B-cell NHL (64.0%) and worst for unspecified epithelial neoplasms (25.6%). CONCLUSION: Sphenoid sinus malignancies are rare, with high prevalence in white males. The most common histopathology is squamous cell neoplasms. They exhibit significant locoregional extension. Of the common sphenoid sinus malignant subtypes, 5-year DSS is best for mature B-cell NHL and worst for unspecified epithelial neoplasms.

Frontal Sinus Malignancies: A Population-Based Analysis of Incidence and Survival.

OBJECTIVE: Primary neoplasms originating in the frontal sinus are rare. As such, existing literature describing frontal sinus malignancies (a subset of frontal sinus neoplasms) is limited. Prognostic implications of these malignancies are difficult to determine. This study seeks to analyze trends in epidemiology, clinicopathology, incidence, and survival for these rare malignancies. STUDY DESIGN: Retrospective database analysis. METHODS: The SEER 18 database (Surveillance, Epidemiology, and End Results; 1973-2012) was searched for frontal sinus malignancies from 1973 to 2012 and analyzed for demographic and clinicopathologic trends. The Kaplan-Meier model was utilized for survival analysis. RESULTS: A total of 171 cases of frontal sinus malignancies were identified. Incidence was 0.011 per 100,000 individuals. The mean age at diagnosis was 61.1 years, with males constituting the majority of cases (61.4%). 80.1% of patients were white, 9.4% Asian, and 8.2% black. The average tumor size was 3.8 cm. The most common histology encountered was squamous cell carcinoma (39.8%). Overall 5-year disease-specific survival was 44.2%. Five-year disease-specific survival was highest for mature B-cell non-Hodgkin's lymphomas (72.3%) and lowest for adenocarcinomas (15.4%). CONCLUSIONS: Malignant tumors of the frontal sinus are rare and are more common in males. Squamous cell carcinoma is the most common entity encountered. Of the 4 most common histologies, survival is best for mature B-cell non-Hodgkin's lymphomas and worst for adenocarcinomas.

Characteristics of patients treated for orbital cellulitis: An analysis of inpatient data.

OBJECTIVES/HYPOTHESIS: Orbital cellulitis represents a spectrum of diseases, some of which may progress to potentially serious complications. The authors used the Nationwide Inpatient Sample (NIS) database to analyze the epidemiologic features of pediatric and adult patients admitted for the treatment of orbital cellulitis and to examine associations with surgical management. METHODS: The NIS was queried for patients admitted for treatment of orbital cellulitis from 2002 to 2010. Patient demographics, length of stay, hospital charges, and concomitant diagnoses were analyzed. RESULTS: There were 14,149 cases of orbital cellulitis identified with 1,717 (12.1%) having undergone surgical management. Surgical patients were older (29.6 ± 23.4) and more commonly male (62.0%) (P = 0.004 and < 0.001, respectively). Patients who had surgical intervention had longer length of stay and higher hospital charges than nonsurgical patients (P < 0.001). Our study showed that the proportion of pediatric patients age 10 to 19 years (22.1%) undergoing surgery was four times that of patients < 5 years of age (5.1%) (P < 0.001). Patients with concomitant diagnoses of acute and chronic sinusitis, acute osteomyelitis, exophthalmos, diplopia, and conjunctival edema had significantly increased odds ratio of surgical intervention. Frontal sinusitis was the site most commonly associated with surgical intervention among sinusitis patients. CONCLUSION: This study describes the characteristics of pediatric and adult patients admitted for orbital cellulitis from a national perspective. Patients 10 to 19 years of age were most likely to undergo surgical management. Acute and chronic sinusitis, acute osteomyelitis, exophthalmos, diplopia, and conjunctival edema were concomitant diagnoses associated with significantly increased odds ratio of surgical intervention. LEVEL OF EVIDENCE: 2C. Laryngoscope, 126:554-559, 2016.

Laryngeal adenosquamous carcinoma: A population-based perspective.

OBJECTIVES/HYPOTHESIS: Adenosquamous carcinoma (ASC) is a rare entity, with fewer than 100 cases having been reported in the upper aerodigestive tract. Thus, no large samples characterizing its clinical behavior are available in the literature. Investigation of ASC has been further limited by difficulty in establishing histopathologic diagnosis. Our objective was to use a national population-based resource to evaluate patient demographics, clinical behavior, incidence, and survival for laryngeal adenosquamous carcinoma (LASC). STUDY DESIGN: Retrospective population-based analysis. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to search for patients diagnosed with LASC between 1973 and 2012. Patient demographics, tumor characteristics, incidence, and survival trends were analyzed. RESULTS: Of the 68 identified LASC patients, 79.4% were male and 20.6% were female. The mean age at diagnosis was 66.0 ± 10.8 years. Whites represented 80.9% of patients, but no racial predominance was noted. LASC most commonly affected the glottis (47.1%), followed closely by the supraglottis (42.6%). Most cases were poorly differentiated (59.2%) and presented with stage IV disease (40.7%). Metastasis (M1) was noted in 10.7% of cases. The overall incidence was 0.003/100,000. The 5-year disease-specific survival rate was 36.6%, with a median observed survival of 33.6 months. CONCLUSIONS: This study notes that LASC has low overall incidence. It has a predilection for males, but does not demonstrate racial predominance. LASC tends to present with stage IV disease, with distant metastasis noted in approximately one in 10 cases. Overall prognosis is poor, with a median survival under 3 years. LEVEL OF EVIDENCE: 4.