Outcomes and prognostic factors in parotid gland malignancies: A 10-year single center experience.

Objectives:To describe a 10-year single center experience with parotid gland malignancies and to determine factors affecting outcomes. Study Design:Retrospective review. Methods:The institutional cancer registry was used to identify patients treated surgically for malignancies of the parotid gland between January 2005 and December 2014. Clinical and pathologic data were collected retrospectively from patient charts and analyzed for their association with overall survival (OS) and disease-free survival (DFS). Results:Two hundred patients were identified. Mean age at surgery was 57.8 years, and mean follow-up time was 52 months. One hundred two patients underwent total parotidectomy, while 77 underwent superficial parotidectomy, and 21 underwent deep lobe resection. Seventy patients (35%) required facial nerve (FN) sacrifice. Acinic cell carcinoma was the most common histologic type (22%), followed by mucoepidermoid carcinoma (21.5%) and adenoid cystic carcinoma (12.5%). Twenty-nine patients (14.5%) experienced recurrences, with mean time to recurrence of 23.6 months (range: 1-82 months). Five- and 10-year OS were 81% and 73%, respectively. Five- and 10-year DFS were 80% and 73%, respectively. In univariate analyses, age > 60, histologic type, positive margins, high grade, T-stage, node positivity, perineural invasion, and FN involvement were predictors of OS and DFS. In the multivariate analysis, histology, positive margins, node positivity, and FN involvement were independent predictors of OS and DFS. Conclusions:Our single-center experience of 200 patients suggests that histology, positive margins, node positivity, and FN involvement are independently associated with outcomes in parotid malignancies. Level of Evidence:4

CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4(+) and CD8(+) T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4(+) and CD8(+) T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4(+) T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4(+) and CD8(+) T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8(+) T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4(+) T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4(+) and CD8(+) T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches

Medical students\u27 knowledge of HPV, HPV vaccine, and HPV-associated head and neck cancer

On the basis of their training, medical students are considered the best case scenario among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (β = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (β = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (β = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (β = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC

Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We validate this selective expression in three published cohorts of patients with ACC. Our data provide a potential explanation for the biphasic nature of low- and intermediate-grade ACC and may help direct new therapeutic strategies against these tumors

Prevention of Postexenteration Complications by Obliteration of the Orbital Cavity

Objective: In patients for whom aggressive disease processes have necessitated the surgical removal of the orbital contents, many reconstructive options are available to address the exenteration cavity. While cavity lining, such as with a skin graft, has been commonly employed, areas of bone injury or loss may still provide a pathway for bacteria to access the cranial vault. We suggest that complete obliteration of the cavity provides a protective barrier, which minimizes this risk. Design: A retrospective review of four patients with significant intracranial infectious complications following orbital exenteration. All patients were managed at a tertiary care academic medical center. Results: Three of the four patients developed large brain abscesses, and one was symptomatic with computed tomography (CT) evidence of epidural enhancement in areas of bony dehiscence in the orbital cavity. Overall, three of the patients had free-tissue transfer to obliterate the orbit, and two of these had no further infectious problems. In one patient, the flap pulled away from the superior orbit leading to infectious complications, which were successfully managed by obliterating the remaining area of the orbit with a temporoparietal fascia flap. Conclusions: In light of the overall prognosis of patients requiring orbital exenteration, we believe that tissue obliteration of the cavity as an initial management strategy provides advantages that outweigh the increased surgical time and loss of socket visualization

Novel voice prosthesis after total laryngectomy with laryngoplasty reconstruction

BackgroundAlthough many patients achieve serviceable speech after total laryngectomy (TL), others are limited by un‐naturally low pitch. We describe a cadaveric study to provide proof of concept for a novel voice prosthesis after TL with free tissue laryngoplasty.MethodsDevices were implanted into fresh frozen cadavers after TL and free tissue laryngoplasty. Phonation pressures were measured using a custom Blom‐Singer Manometer (InHealth Technologies, Carpinteria, CA) and acoustic files were analyzed using Praat, a speech analysis software.ResultsTwo fresh frozen cadavers were implanted with the voice prosthesis. Both prostheses demonstrated appropriate stenting of the laryngoplasty. Successful sound production was achieved after airflow generation at the proximal trachea. An average phonation pressure of 3.5 cmH2O (SD 1.7 cmH2O) was necessary to generate a sound intensity of 80.6 dB (SD 0.2 dB) at an average fundamental frequency of 299.5 Hz (SD 112.6 Hz).ConclusionsThe novel voice prosthesis described herein offers a feasible voice generation mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167126/1/hed26592_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167126/2/hed26592.pd

A Contemporary Review of Molecular Therapeutic Targets for Adenoid Cystic Carcinoma

ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB–NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies

Molecular Biomarkers of Malignant Transformation in Head and Neck Dysplasia

Head and neck squamous cell carcinoma (HNSCC) and its treatments are associated with substantial morbidity, often resulting in cosmetic deformity and loss of physiologic functions including speech and swallowing. Despite advancements in treatment, 5-year survival rates for mucosal malignancies remain below 70%. Effective prevention of HNSCC demands an understanding of the molecular pathways of carcinogenesis. Specifically, defining features of pre-cancerous dysplastic lesions that indicate a better or worse prognosis is necessary to help identify patients who are likely to develop a carcinoma and allow a more aggressive approach to management. There remains a need for identification of biomarkers that can provide both early prognostic and predictive value in clinical decision-making by serving as both therapeutic targets as well as predictors of therapy response. Here, we comprehensively review the most frequently altered molecular biomarkers of malignant transformation in head and neck dysplasia. These markers are involved in a wide range of cellular processes in head and neck carcinogenesis, including extracellular matrix degradation, cell motility and invasion, cell–cell adhesion, solute transport, immortalization, metabolism, the cell cycle and apoptosis, transcription, and cell signaling

Correlates of human papillomavirus (HPV) vaccination initiation and completion among 18–26 year olds in the United States

Purpose: To examine correlates of HPV vaccination uptake in a nationally representative sample of 18–26-year-old adults. Methods: Young adults aged 18–26 years were identified from the 2014 and 2015 National Health Interview Survey (n = 7588). Survey-weighted multivariable logistic regression models estimated sociodemographic factors associated with HPV vaccine initiation (≥1 dose) and completion (≥3 doses). Results: Approximately 27% of study participants had initiated the HPV vaccine and 16% had completed the HPV vaccine. Participants were less likely to initiate the vaccine if they were men [(adjusted odds ratio) 0.19; (95% confidence interval) 0.16–0.23], had a high school diploma (0.40; 0.31–0.52) or less (0.46; 0.32–0.64) vs. college graduates, and were born outside the United States (0.52; 0.40–0.69). But, participants were more likely to initiate the HPV vaccine if they visited the doctor's office 1–5 times (2.09; 1.56–2.81), or ≥ 6 times (1.86; 1.48–2.34) within the last 12 months vs. no visits. Odds of completing HPV vaccine uptake followed the same pattern as initiation. And after stratifying the study population by gender and foreign-born status, these variables remained statistically significant. Conclusions: In our nationally representative study, only one out of six 18–26 year olds completed the required vaccine doses. Men, individuals with high school or less education, and those born outside the United States were less likely to initiate and complete the HPV vaccination. Our findings suggest that it may be useful to develop targeted interventions to promote HPV vaccination among those in the catch-up age range