Perifacial Lymph Node Metastasis After Treatment of Oropharyngeal Primary Malignancy: A Case Report.

With the rate of oropharyngeal cancer on the rise, appropriate surgical management is an increasingly important consideration. Much debate currently exists regarding the necessary extent of neck dissections when performing curative surgery for primary oropharyngeal malignancies. Here, we present the case of a 64-year-old patient with p16+ T1N1M0 squamous cell carcinoma (SCC) of the right tonsil. Approximately four years following transoral robotic surgery oropharyngectomy and ipsilateral level II-IV right selective neck dissection, metastatic SCC was discovered on fine-needle aspiration biopsy of a right perifacial lymph node (level Ib). The patient then underwent a revision right neck dissection at levels Ia and Ib. Adjuvant immunotherapy was recommended following revision neck dissection. Postoperative imaging and flexible laryngoscopy three months after surgery were not concerning for cervical lymphadenopathy or oropharyngeal lesions. Although rare, physicians must maintain a healthy level of suspicion for recurrence to level Ib in oropharyngeal primary malignancies.

Positive margins matter regardless of subsequent resection findings.

OBJECTIVES: In the resection of oral cavity squamous cell carcinoma (OCSCC), an intraoperative positive surgical margin (SM) communicated to the head and neck surgeon necessitates further resection of the area of identified involvement to achieve a final negative SM. The prognostic implication of initial positive SM when the final SM is negative is understudied. MATERIALS AND METHODS: We retrospectively reviewed 249 patients with non-metastatic (stage I-IVB) OCSCC who underwent a resection from 2010 to 2019 to assess the prognostic impact of an initial positive SM. Chi-squared analysis was used to evaluate the association between an initial positive SM and clinicopathologic parameters. A Kaplan-Meier analysis was performed to estimate patient outcomes with Cox regression analysis used to determine absolute hazards. RESULTS: At a median follow-up of 28.4 months, the 2-year freedom from local recurrence (FFLR), disease-free survival (DFS), and overall survival (OS) rates were 82.1%, 63.5%, and 78.5%, respectively. Fifty patients (20.1%) had an initial positive SM which was revised to a negative SM on frozen and permanent sections by resecting further tissue while 12 patients (4.8%) had a final positive SM. An initial positive SM was independently associated with a worse FFLR (HR: 2.696, p = 0.004), DFS (HR: 1.57, p = 0.044), and OS (HR: 1.72, p = 0.029). CONCLUSION: An initial positive SM is independently associated with worse disease control and patient survival. A positive SM may be a surrogate for diffusely infiltrative disease as further malignancy identified on the re-resection specimen was associated with worse outcomes.

Dual blockade of EGFR and CDK4/6 delays head and neck squamous cell carcinoma progression by inducing metabolic rewiring.

Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreERtam;LSL-KrasG12D/+;Trp53R172H/+) studies showed a significant reduction in the tumor growth and delayed tumor progression after combination treatment. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation.

Postoperative thyroid hormone supplementation rates following thyroid lobectomy.

BACKGROUND: Thyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well differentiated thyroid cancer. We aimed to determine factors associated with thyroid stimulating hormone over goal (TH) following lobectomy. METHODS: We performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. TH was defined as need for thyroid hormone in accordance with guidelines. Univariate and multivariate logistic regression analysis was performed. RESULTS: One hundred patients were included and 47% developed. TH: 73% of those with cancer, 38% with benign pathology (p = 0.002). Patients with TH were more likely to have thyroiditis 26% versus 3.8% (p = 0.002); higher preoperative TSH: mean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003). CONCLUSIONS: After thyroid lobectomy, TH is associated with preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal.

Differential mutation spectrum and immune landscape in African Americans versus Whites: A possible determinant to health disparity in head and neck cancer.

African Americans (AA) with Head and Neck Squamous Cell Carcinoma (HNSCC) have a worse disease prognosis than White patients despite adjusting for socio-economic factors, suggesting the potential biological contribution. Therefore, we investigated the genomic and immunological components that drive the differential tumor biology among race. We utilized the cancer genome atlas and cancer digital archive of HNSCC patients (1992-2013) for our study. We found that AA patients with HNSCC had a higher frequency of mutation compared to Whites in the key driver genes-P53, FAT1, CASP8 and HRAS. AA tumors also exhibited lower intratumoral infiltration of effector immune cells (CD8+, γδT, resting memory CD4+ and activated memory CD4+ T cells) with shorter survival than Whites. Unsupervised hierarchical clustering of differentially expressed genes demonstrated distinct gene clusters between AA and White patients with unique signaling pathway enrichments. Connectivity map analysis identified drugs (Neratinib and Selumetinib) that target aberrant PI3K/RAS/MEK signaling and may reduce racial disparity in therapy response.

Postoperative thyroid hormone supplementation rates following thyroid lobectomy.

BACKGROUND: Thyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well-differentiated thyroid cancer. We aimed to determine factors associated with need for thyroid hormone supplementation following thyroid lobectomy. METHODS: We performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. Thyroid hormone supplementation was assessed postoperatively based on guidelines for thyroid stimulating hormone (TSH) level goal for benign (0.5-4.5mIU/L) or malignant (<2mIU/L) final pathology. Univariate and multivariate logistic regression analysis was performed. RESULTS: One hundred patients were included and overall 47% required thyroid hormone supplementation after thyroid lobectomy: 73% of those with cancer, 38% with benign pathology (p = 0.002). Patients requiring thyroid hormone supplementation were more likely to have thyroiditis 26% versus 3.8% of those who remained euthyroid (p = 0.002); have a higher preoperative TSH: mean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and have a smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003). CONCLUSIONS: After thyroid lobectomy, the need for thyroid hormone supplementation is associated with higher preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy on final pathology. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal. For patients with benign pathology after thyroid lobectomy the majority will not require thyroid hormone supplementation to achieve TSH goal.

PET/CT Evaluation of Head and Neck Cancer of Unknown Primary.

The diagnosis of carcinoma of unknown primary in the head and neck is made when there is a metastasis but no primary lesion is identified after physical exam and diagnostic CT or MR imaging. PET/CT is the first step in searching for a primary lesion, followed by more invasive techniques such as endoscopy and surgery. Knowledge of the different tumor histologic types, preferential locations of nodal spread, imaging pitfalls, and other special considerations such as cystic metastases can be helpful in the ultimate identification of primary tumors, which leads to improved overall patient survival.

Deep Parotid Lobe Abscess Presenting with Dysphagia and Trismus.

An abscess of the deep parotid lobe is an uncommon complication of acute parotitis. Characterized by warm erythematous facial skin and ipsilateral cheek swelling, parotid abscesses have often been associated with decreased saliva production and immunodeficiency. We offer a case of a large deep parotid lobe abscess presenting similarly to a peritonsillar mass, causing significant odynophagia and difficulty swallowing. Computed tomography scan revealed an infected deep parotid lobe sialocele which was surgically drained transorally and treated expectantly with antibiotics.

Immunometabolic Alterations by HPV Infection: New Dimensions to Head and Neck Cancer Disparity.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC.

Emerging therapeutic potential of graviola and its constituents in cancers.

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.

The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration.

Quantitative analysis of misplaced pedicle screws in the thoracic spine: how much pullout strength is lost?: presented at the 2009 Joint Spine Section Meeting.

OBJECT: The object of this study was to investigate the effects of iatrogenic pedicle perforations from screw misplacement on the mean pullout strength of thoracic pedicle screws. METHODS: Forty human thoracic vertebrae (T6-11) from human cadavers were studied. Before pedicle screws were inserted, the specimens were separated into 4 groups according to the type of screw used: 1) standard pedicle screw (no cortical perforation); 2) screw with medial cortical perforation; 3) screw with lateral cortical perforation; and 4) "airball" screw (a screw that completely missed the vertebral body). Consistency among the groups for bone mineral density, pedicle diameter, and screw insertion depth was evaluated. Finally, each screw was pulled out at a constant displacement rate of 10 mm/minute while ultimate strength was recorded. RESULTS: Compared with well-placed pedicle screws, medially misplaced screws had 8% greater mean pullout strength (p = 0.482) and laterally misplaced screws had 21% less mean pullout strength (p = 0.059). The difference in mean pullout strength between screws with medial and lateral cortical perforations was significant (p = 0.013). Airball screws had only 66% of the mean pullout strength of well-placed screws (p = 0.009) and had 16% lower mean pullout strength than laterally misplaced screws (p = 0.395). CONCLUSIONS: This in vitro study showed a significant difference in mean pullout strength between medial and lateral misplaced pedicle screws. Moreover, airball screws were associated with a significant loss of pullout strength.

Surgical management of moyamoya disease: a review.

Moyamoya disease (MMD) is a progressive, occlusive disease of the distal internal carotid arteries associated with secondary stenosis of the circle of Willis. Symptoms include ischemic infarcts in children and hemorrhages in adults. Bypass of the stenotic vessel(s) is the primary surgical treatment modality for MMD. Superficial temporal artery-to-middle cerebral artery bypass is the most common direct bypass method. Indirect techniques rely on the approximation of vascularized tissue to the cerebral cortex to promote neoangiogenesis. This tissue may be in the form of muscle, pericranium, dura, or even omentum. This review highlights the surgical options available for the treatment of MMD.