Ultrasound Imaging of the Facial Muscles and Relevance with Botulinum Toxin Injections: A Pictorial Essay and Narrative Review.

High-resolution ultrasound is preferred as the first-line imaging modality for evaluation of superficial soft tissues, such as the facial muscles. In contrast to magnetic resonance imaging and computed tomography, which require specifically designated planes (axial, coronal and sagittal) for imaging, the ultrasound transducer can be navigated based on the alignment of facial muscles. Botulinum toxin injections are widely used in facial cosmetic procedures in recent times. Ultrasonography is recognized as a useful tool for pre-procedure localization of target muscles. In this pictorial review, we discuss the detailed sonoanatomy of facial muscles and their clinical relevance, particularly with regard to botulinum toxin injections. Furthermore, we have summarized the findings of clinical studies that report ultrasonographic imaging of facial muscles.

Prognosis of medication-related osteonecrosis of the jaws in metastatic prostate cancer patients.

OBJECTIVES: The aim of this study was to find out the prognosis of medication-related osteonecrosis of the jaws (MRONJ) in prostate cancer patients who received two different types of antiresorptive agents for bone metastasis. MATERIALS AND METHODS: We retrospectively surveyed a cohort of 95 metastatic prostate cancer patients with 122 MRONJ lesions treated in a single medical center. Treatment outcomes and prognostic factors were investigated. The cumulative complete response rate was calculated with the Kaplan-Meier method, and significance was examined with the log-rank and Breslow tests. Cox regression was used for the univariate and multivariate analyses of prognostic factors. RESULTS: The cumulative complete response rate of all patients at 12 months was 37.8%, and that of patients treated with zoledronic acid and denosumab was 22.9% and 70.5%, respectively. Denosumab, pretreatment C-terminal telopeptide of collagen I (CTX) level > 150 pg/ml, and anemia were identified as independent prognostic factors in a multivariate analysis with adjusted hazard ratios of 3.18 (95% confidence interval [CI], 1.24-8.11), 3.24 (95% CI, 1.39-7.53), and 0.42 (95% CI, 0.19-0.93), respectively. CONCLUSION: A higher pretreatment level of CTX, using denosumab as the antiresorptive agent and without anemia, indicates a better treatment outcome of MRONJ in prostate cancer patients.

Effects of Interleukin-6 on STAT3-regulated signaling in oral cancer and as a prognosticator of patient survival.

OBJECTIVES: Human oral squamous cell carcinoma (OSCC) produces an inflammatory microenvironment enriched with cytokines including interleukin-6 (IL-6); however, the underlying molecular mechanisms of OSCC progression are unclear. We aimed to delineate the STAT3-mediated signaling pathways involved in tumor cell survival and growth. MATERIALS AND METHODS: Immunohistochemistry was used to semi-quantitate IL-6 and STAT3 in 111 OSCC tissues. IL-6-induced STAT3 signaling pathways and effects on tumor cell survival and progression were investigated in vitro and in xenograft mouse models. Effects of blocking IL-6-induced activation of STAT3 in an OSCC cell line were determined in vitro. RESULTS: A higher level of IL-6 or STAT3 in situ was associated with an unfavorable prognosis in OSCC patients with regard to both disease-free and overall survival rates. Overexpressed or exogenous IL-6 could induce SAS cell proliferationin vitroand significantly enhanced tumor growthin vivo. In addition, knockdown or inhibition of STAT3 expression in SAS cells significantly reduced tumor growth and abolished the responsiveness to IL-6 stimulation. Siltuximab or Tocilizumab could also significantly suppress IL-6-induced STAT3 phosphorylation and STAT3 nuclear translocation, resulting in a significant decrease of downstream anti-apoptotic proteins Bcl-2, Bcl-xL, and survivin. CONCLUSION: The IL-6 level in the tumor microenvironment could serve as a stage-independent predictor of OSCC progression and survival. Further, IL-6 may play a role in this disease through STAT3-dependent upregulation of anti-apoptotic genes and subsequent proliferation of tumor cells.

Prognosis of medication-related osteonecrosis of the jaws in cancer patients using antiresorptive agent zoledronic acid.

BACKGROUND/PURPOSE: Anti-resorptive agents are commonly used in cancer patients with bone metastasis or multiple myeloma (MM). An adverse event termed medication-related osteonecrosis of the jaws (MRONJ) was discovered in patients using these agents but relatively little attention has been paid to its prognosis. Our aims were to find out the treatment outcomes and prognostic indicators of MRONJ in cancer patients who received zoledronic acid as antiresorptive therapy. METHODS: We retrospectively surveyed a cohort of 133 cancer patients who received zoledronic acid. A total of 150 MRONJ lesions were included for investigation. Cumulative complete response rate after treatment was calculated with the Kaplan-Meier method, and significance was examined with the log-rank tests. Cox regression was used for univariate and multivariate analyses of prognostic factors. RESULTS: The cumulative complete response rate of all patients at 24 months was 53.2%, and those of patients with MM, breast cancer and prostate cancer were 27.8%, 60.7% and 68.0%, respectively. Having MM was identified as an independent prognostic factor in a multivariate analysis with adjusted hazard ratios of 0.28 (95% confidence interval, 0.09-0.83). CONCLUSION: For cancer patients with ONJ related to zoledronic acid, patients with MM endure a worse treatment outcome.

Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1.

OBJECTIVES: Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion. MATERIALS AND METHODS: Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors. RESULTS: Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1ß and CXCR2 are also highly expressed in OSCC and IL-1ß mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1ß exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs. CONCLUSION: The induction of IL-1ß following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment.