Objective: In vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) ...imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema. Methods : A partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T 2 -weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds. Results : For both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 μm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis. Conclusion : This paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging. Significance: The ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.
Objectives/Hypothesis
The presence of regional metastases in head and neck squamous cell carcinoma (HNSCC) patients is a common and adverse event associated with poor prognosis. Understanding the ...molecular mechanisms that mediate HNSCC metastasis may enable identification of novel therapeutic targets. E‐cadherin plays a key role in epithelial intercellular adhesion; its downregulation is a hallmark of the epithelial‐to‐mesenchymal transition (EMT) (an essential process during tumor progression); and it is associated with invasion, metastasis, and decreased survival. Inflammatory cytokines have been implicated in the progression of HNSCC. Herein, the mechanisms by which the inflammatory mediator, Interleukin‐1β (IL‐1β), might contribute to EMT in HNSCC is investigated.
The pathways involved in E‐cadherin regulation in HNSCC had not previously been defined. It is hypothesized that 1) inflammatory mediators upregulate cyclooxygenase‐2/prostaglandin E2 (COX‐2/PGE2), which then in turn regulate E‐cadherin expression in HNSCC; and 2) PGE2 downregulates E‐cadherin via transcriptional repressors of E‐cadherin (such as Snail) in HNSCC. The outcome of the proposed research will allow us to define how resistance to epidermal growth factor receptor (EGFR)‐selective tyrosine kinase inhibitors is mediated and whether the benefits of combination therapy are due to the capacity of COX‐2 inhibitors to increase E‐cadherin expression and thus create a more sensitive target for EGFR TK inhibition.
Study Design
Basic science, molecular biology, animal model, immunohistochemistry.
Methods
We evaluated the effect of IL‐1β on the molecular events of EMT in surgical specimens and HNSCC cell lines. We examined the correlation with tumor histologic features, and a severely compromised immunodeficient (SCID) xenograft model was used to assess the effects in vivo.
Results
COX‐2‐dependent pathways contribute to the modulation of E‐cadherin expression in HNSCC. An inverse relationship between COX‐2 and E‐cadherin was demonstrated in situ by double immunohistochemical staining of human HNSCC tissue sections. Treatment of HNSCC cells with IL‐1β caused the downregulation of E‐cadherin expression and upregulation of COX‐2 expression. This effect was blocked in the presence of COX‐2 small hairpin RNA (shRNA). IL‐1β ‐treated HNSCC cell lines demonstrated a significant decrease in E‐cadherin messenger RNA (mRNA) and an increase in the mRNA expression of the transcriptional repressor Snail. IL‐1β exposure led to enhanced Snail binding at the chromatin level. ShRNA‐mediated knockdown of Snail interrupted the capacity of IL‐1β to downregulate E‐cadherin. Snail overexpression in normal oral keratinocytes and HNSCC cells is sufficient to drive EMT and confers resistance to erlotinib. In a SCID xenograft model, HNSCC Snail overexpressing cells demonstrated significantly increased primary and metastatic tumor burdens.
Conclusions
The inflammatory mediator IL‐1β modulates Snail and thereby regulates COX‐2‐dependent E‐cadherin expression in HNSCC. This is the first report indicating the role of Snail in the inflammation‐induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E‐cadherin in HNSCC has important implications for targeted chemoprevention and therapy.
Level of Evidence
N/A Laryngoscope, 125:S1–S11, 2015
Objective
Esthesioneuroblastoma is an uncommon malignancy of the sinonasal tract arising from the olfactory epithelium. Surgical management of the primary site, often via an endoscopic approach, with ...or without adjuvant radiation, is often curative. There is growing but ultimately limited data regarding management of the neck and the risk of nodal metastases. In this study, we examine the incidence and patterns of esthesioneuroblastoma‐related cervical nodal metastases using the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
The SEER registry was queried for all patients with esthesioneuroblastomas diagnosed between 1973 and 2012. Patient data was then analyzed with respect to age, sex, race, modified Kadish stage, grade, survival functions, and nodal disease including specific nodal basins.
Results
Three hundred and eighty‐one cases of esthesioneuroblastoma with information on nodal metastases were identified. The overall cervical nodal metastasis rate was 8.7%. Level II metastases were most common (6.6%). A total of 4.5% of cases presented with multiple positive nodal basins. Male sex (P = 0.009) and higher tumor grade (P = 0.009) correlated with the presence of level II metastases. There was no association of primary tumor site to the presence of nodal metastases (P > 0.05). The presence of nodal disease significantly predicted poorer overall (P = 0.001) and disease‐specific survival (P = 0.017).
Conclusion
The incidence of nodal metastases in esthesioneuroblastoma at diagnosis is rare, and elective management of the neck remains controversial. Primary tumor site does not appear to predict metastases at specific nodal basins. Higher tumor grade may be a harbinger of eventual nodal metastases.
Level of Evidence
NA Laryngoscope, 129:1025–1029, 2019
Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation ...is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics.
The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has ...been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans.
Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components.
Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average.
Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.
Objectives/Hypothesis
The objective of this study was to examine the difference between a narrow (between 1 and 2 cm) and a wide (>2 cm) margin in the surgical resection of head and neck cutaneous ...melanoma.
Study Design
Population‐based cohort analysis.
Methods
The Surveillance, Epidemiology, and End Results database was employed to identify patients who had cutaneous melanoma of the head and neck from 2004 to 2014. Outcome measures were overall survival (OS) and disease‐specific survival (DSS).
Results
Among the total of 3,583 cases of cutaneous melanoma of the head and neck with known resection margins, 2,641 individuals had narrow resection margins, and 942 patients had wide margins. Most of the tumors presented in the skin of the scalp and neck, followed by the face, external ear, and other areas. The 5‐year and 10‐year Kaplan‐Meier OS probabilities for narrow and wide margins were 65% and 66%, respectively, compared with 49% and 48%, respectively. The DSS probabilities exhibited similar trends between the two groups at these time points. In the Cox regression model, the patients who received narrow margins had similar OS (95% confidence interval CI: 0.918‐1.217) and DSS (95% CI: 0.856‐1.352) compared with the wide resection margin group, even when controlled for age, sex, T stage, and histology.
Conclusions
The survival of patients with cutaneous melanoma of the head and neck depends on age, depth of tumor invasion, and histology. Within the head and neck, a wider resection margin of >2 cm does not confer any additional survival benefit compared with a narrower margin. Future studies should examine whether wider surgical margins would confer survival benefit in local or recurrent melanoma.
Level of Evidence
4
Laryngoscope, 129:1386–1394, 2019
Objectives/Hypothesis
Determine the rate, diagnoses, and risk factors associated with 30‐day nonelective readmissions for patients undergoing surgery for oropharyngeal cancer.
Study Design
...Retrospective cohort study.
Methods
We analyzed the Nationwide Readmissions Database for patients who underwent oropharyngeal cancer surgery between 2010 and 2014. Rates and causes of 30‐day readmissions were determined. Multivariate logistic regression was used to identify risk factors for readmission.
Results
Among 16,902 identified cases, the 30‐day, nonelective readmission rate was 10.2%, with an average cost per readmission of $14,170. The most common readmission diagnoses were postoperative bleeding (14.1%) and wound complications (12.6%) (surgical site infection 8.6%, dehiscence 2.3%, and fistula 1.7%). On multivariate regression, significant risk factors for readmission were major ablative surgery (which included total glossectomy, pharyngectomy, and mandibulectomy) (odds ratio OR: 1.29, 95% confidence interval CI: 1.06‐1.60), advanced Charlson/Deyo comorbidity (OR: 2.00, 95% CI: 1.43‐2.79), history of radiation (OR: 1.58, 95% CI: 1.15‐2.17), Medicare (OR: 1.34, 95% CI: 1.06‐1.69) or Medicaid (OR: 1.82, 95% CI: 1.32‐2.50) payer status, index admission from the emergency department (OR: 1.19, 95% CI: 1.02‐1.40), and length of stay ≥6 days (OR: 1.57, 95% CI: 1.19‐2.08).
Conclusions
In this large database analysis, we found that approximately one in 10 patients undergoing surgery for oropharyngeal cancer is readmitted within 30 days. Procedural complexity, insurance status, and advanced comorbidity are independent risk factors, whereas postoperative bleeding and wound complications are the most common reasons for readmission.
Level of Evidence
4. Laryngoscope, 129:910–918, 2019
Purpose of Review
The complex and varied drainage patterns in the head and neck present a challenge in the regional control of cutaneous neoplasms. Lymph node involvement significantly diminishes ...survival, often warranting more aggressive treatment. Here, we review the risk factors associated with lymphatic metastasis, in the context of the evolving role of sentinel lymph node biopsy.
Recent Findings
In cutaneous head and neck melanomas, tumor thickness, age, size, mitosis, ulceration, and specific histology have been associated with lymph node metastasis (LNM). In head and neck cutaneous squamous cell carcinomas, tumor thickness, size, perineural invasion, and immunosuppression are all risk factors for nodal metastasis. The risk factors for lymph node involvement in
Merkel cell carcinoma
are not yet fully defined, but emerging evidence indicates that tumor thickness and size may be associated with regional metastasis.
Summary
The specific factors that predict a greater risk of LNM for cutaneous head and neck cancers generally include depth of invasion, tumor size, mitotic rate, ulceration, immunosuppression, and other histopathological factors.
Objectives/Hypothesis
To report the clinical presentation, treatment, and management outcomes of patients with Epstein‐Barr virus‐positive mucocutaneous ulcer (EBVMCU) of the head and neck, which is ...a newly characterized pathologic entity with aggressive morphology but follows an indolent, self‐limiting clinical course.
Study Design
Case report and literature review.
Methods
A case of EBVMCU of the base of tongue is reported and a retrospective review of all cases of EBVMCU of the head and neck at a single academic institution was conducted between January 1, 1986 and April 1, 2015. The MEDLINE database was additionally queried from January 1, 1950 to April 1, 2015 for all reports of EBVMCU of the head and neck, and all pertinent clinical data were extracted.
Results
The clinical presentation, treatment, and response of a patient with EBVMCU of the base of tongue are presented. Interim follow‐up of the patient has revealed a complete remission with discontinuation of immunosuppression and rituximab therapy. A review of the literature supports conservative management and reduction of immunosuppression. Overall, 96.6% of patients with follow‐up greater than 2 months achieved complete remission with conservative management. The current study is the largest series to report on the clinical presentation and treatment outcomes of EBVMCU of the head and neck.
Conclusions
EBVMCU tends to follow an indolent and self‐limiting clinical course, responding to reduction of immunosuppression and conservative treatment. It is imperative for clinicians to consider EBVMCU in the differential diagnosis of mucocutaneous ulcers of the head and neck to avoid excessive treatment.
Level of Evidence
Laryngoscope, 126:2500–2504, 2016
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