Artificial Neural Network-Assisted Classification of Hearing Prognosis of Sudden Sensorineural Hearing Loss With Vertigo.

This study aimed to determine the impact on hearing prognosis of the coherent frequency with high magnitude-squared wavelet coherence (MSWC) in video head impulse test (vHIT) among patients with sudden sensorineural hearing loss with vertigo (SSNHLV) undergoing high-dose steroid treatment. This study was a retrospective cohort study. SSNHLV patients treated at our referral center from December 2016 to December 2020 were examined. The cohort comprised 64 patients with SSNHLV undergoing high-dose steroid treatment. MSWC was measured by calculating the wavelet coherence analysis (WCA) at various frequencies from a vHIT. The hearing prognosis were analyzed using a multivariable Cox regression model and convolution neural network (CNN) of WCA. There were 64 patients with a male-to-female ratio of 1:1.67. The greater highest coherent frequency of the posterior semicircular canal (SCC) was associated with the complete recovery (CR) of hearing. After adjustment for other factors, the result remained robust (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.86-2.35). In the feature extraction with Resnet-50 and proceeding SVM in the horizontal image cropping style, the classification accuracy [STD] for (CR vs. partial + no recovery [PR + NR]), (over-sampling of CR vs. PR + NR), (extensive data extraction of CR vs. PR + NR), and (interpolation of time series of CR vs. PR + NR) were 83.6% [7.4], 92.1% [6.8], 88.9% [7.5], and 91.6% [6.4], respectively. The high coherent frequency of the posterior SCC was a significantly independent factor that was associated with good hearing prognosis in the patients who have SSNHLV. WCA may be provided with comprehensive ability in vestibulo-ocular reflex (VOR) evaluation. CNN could be utilized to classify WCA, predict treatment outcomes, and facilitate vHIT interpretation. Feature extraction in CNN with proceeding SVM and horizontal cropping style of wavelet coherence plot performed better accuracy and offered more stable model for hearing outcomes in patients with SSNHLV than pure CNN classification. Clinical and Translational Impact Statement-High coherent frequency in vHIT results in good hearing outcomes in SSNHLV and facilitates AI classification.

Novel airway-cartilage combined model for medialization laryngoplasty and laryngotracheal reconstruction surgery planning.

BACKGROUND: The clinical outcomes of surgical treatments for vocal cord paralysis and tracheal stenosis, such as medialization laryngoplasty and laryngotracheal reconstruction, vary owing to the complex anatomy and physiology of the human upper airway. However, advances in three-dimensional (3D) simulation and printing ushered its use on an office-based workstation to aid in several surgical areas. METHODS: The preoperation neck computed tomography image was loaded into the InVesalius 3.0 software for manual segmentation of airway and nearby important anatomic landmarks including hyoid bone, thyroid cartilage, and cricoid cartilage. The 3D model of the desired anatomy structure was manufactured and used for presurgical planning and rehearsal of the surgery. RESULTS: We review cases of four patients: two cases of unilateral vocal palsy undergoing medialization laryngoplasty and two cases of tracheal stenosis patients who used the air-cartilage combined model. CONCLUSION: Preoperation planning of the medialization thyroplasty could be more precise by prevision of the paralyzed vocal cord plane. Tracheal surgery could benefit from a preoperative design of segmented length. The novel airway-cartilage combined model offers new insight into vocal cord and trachea surgery.

Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit.

The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival (p = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.

Comparison of a home sleep test with in-laboratory polysomnography in the diagnosis of obstructive sleep apnea syndrome.

BACKGROUND: In-laboratory, polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea syndrome (OSAS). However, the long waiting list and sleeping at a hospital make patients hesitate to undergo the examination, thereby delaying diagnosis. During coronavirus disease 2019 (COVID-19) pandemic, sleep labs are almost closed, and the delay is worsening. The home sleep test (HST) enables subjects to be tested at home, a familiar and comfortable environment, without a long waiting list. This study assessed the accuracy of a type III HST in diagnosing OSAS in the Taiwanese population and identified factors affecting the diagnostic accuracy. METHODS: This retrospective study included 67 patients with clinically suspected OSAS. All patients were allocated to receive both PSG and the HST. The apnea-hypopnea index (AHI) measured through PSG was used as the standard. The sensitivity, specificity, and accuracy of the HST in diagnosing and evaluating the severity of OSAS were analyzed. RESULTS: Among the 67 patients, no significant difference was noted in the average AHI values obtained using PSG and the HST ( p = 0.103). The AHI obtained from HST was significantly correlated with that obtained from PSG, with the correlation coefficient being 0.779 ( p < 0.001). The sensitivity, specificity, and accuracy of the HST in diagnosing OSAS were 94.9%, 62.5%, and 91.0%, respectively, and 80.0%, 74.1%, and 77.6% in diagnosing moderate to severe OSAS. Furthermore, the difference in AHIs measured using the two tests were positively correlated with the severity of sleep apnea. CONCLUSION: The HST used in preliminary screening of patients with suspected OSAS achieved an accuracy of >90%. For patients with moderate to severe OSAS, the accuracy was below 80%. Therefore, for patients who receive an OSAS diagnosis through the HST, arrangement of PSG is recommended for determining the severity of the OSAS and giving proper treatment.

Ulcerative Warthin Tumor: A Case Report and Review of the Literature.

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer.

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.

Simultaneous Reduction of Volume and Dose in Clinical Target Volume for Nasopharyngeal Cancer Patients.

PURPOSE: To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods. RESULTS: From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P < .001) and salvage survival (79.3% vs 20.7%; P < .01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007). CONCLUSIONS: Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.

Screening for Hearing Impairment in Older Adults by Smartphone-Based Audiometry, Self-Perception, HHIE Screening Questionnaire, and Free-Field Voice Test: Comparative Evaluation of the Screening Accuracy With Standard Pure-Tone Audiometry.

BACKGROUND: Hearing impairment is the most frequent sensory deficit in humans, affecting more than 360 million people worldwide. In fact, hearing impairment is not merely a health problem, but it also has a great impact on the educational performance, economic income, and quality of life. Hearing impairment is therefore an important social concern. OBJECTIVE: We aimed to evaluate and compare the accuracy of self-perception, Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) questionnaire, free-field voice test, and smartphone-based audiometry as tests for screening moderate hearing impairment in older adults in China. METHODS: In this study, 41 patients were recruited through a single otology practice. All patients were older than 65 years. Patients with otorrhea and cognitive impairment were excluded. Moderate hearing impairment was defined as mean hearing thresholds at 500, 1000, 2000, and 4000 Hz >40 dB hearing loss (pure-tone average > 40 dB hearing loss). All patients completed 5 hearing tests, namely, the self-perception test, HHIE-S questionnaire test, free-field voice test, smartphone-based audiometry test, and standard pure-tone audiometry by the same audiologist. We compared the results of these tests to the standard audiogram in the better-hearing ear. RESULTS: The sensitivity and the specificity of the self-perception test were 0.58 (95% CI 0.29-0.84) and 0.34 (95% CI 0.19-0.54), respectively. The sensitivity and the specificity of the HHIE-S questionnaire test were 0.67 (95% CI 0.35-0.89) and 0.31 (95% CI 0.316-0.51), respectively. The sensitivity and the specificity of the free-field voice test were 0.83 (95% CI 0.51-0.97) and 0.41 (95% CI 0.24-0.61), respectively. The sensitivity and the specificity of the smartphone-based audiometry test were 0.92 (95% CI 0.60-0.99) and 0.76 (95% CI 0.56-0.89), respectively. Smartphone-based audiometry correctly diagnosed the presence of hearing loss with high sensitivity and high specificity. CONCLUSIONS: Smartphone-based audiometry may be a dependable screening test to rule out moderate hearing impairment in the older population.

Correlation of 18F-FDG uptake and thyroid cancer stem cells.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) has the potential to detect various types of cancers, including thyroid cancer (TC), at a potentially curable stage. Increased uptake of 18F-FDG was observed in anaplastic and poorly differentiated thyroid cancer cells, and PET-positive tumors are more likely to be resistant to 131I treatment. As cancer stem cells (CSCs) possess a dedifferentiated phenotype and are resistant to many anticancer therapies, we hypothesized that the expression of CSC-related markers is correlated with the ability of tumor cells in TC to uptake FDG. METHODS: The present study cohort included 12 patients with TC, who underwent 18F-FDG PET/CT imaging before surgery. Quantitative polymerase chain reaction (QPCR) and immunohistochemical (IHC) staining were performed to analyze the expression patterns of gene markers related to embryonic stem (ES) cells and CSCs in TC. RESULTS: The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue. There was a positive and statistically significant correlation between FDG uptake (SUVmax) of tumor and relative mRNA levels of CD133, CD44, Oct4, and Nanog. The IHC results demonstrated that CD133 and Nanog were expressed in TC tissue but not in normal thyroid tissue, however, CD44 expression was observed in both TC and normal thyroid tissue. Comparisons of the clinicopathological parameters between TC tissues with low and high SUVmax demonstrated significant differences in protein level of CD133 but not in that of Nanog. CONCLUSIONS: The pre-therapeutic tumor SUVmax obtained from 18F-FDG PET/CT may be a potential predictor for evaluating the proportion of CSC population in individual patients with TC.

Sarcopenia results in poor survival rates in oral cavity cancer patients.

OBJECTIVE: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. DESIGN: This study was a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. PARTICIPANTS: The cohort comprised 276 patients with OSCC undergoing primary surgery. MAIN OUTCOME MEASURES: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5-year overall survival (OS) and disease-specific survival (DSS) were analysed using a multivariable Cox regression model. RESULTS: There were 276 patients with a male-to-female ratio of 12:1. A low SMM (<47.5 cm2 /m2 ) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14-2.67) and disease-specific survival (HR 1.67, 95% CI 1.04-2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22-2.97; HR = 1.91, 95% CI 1.27-3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14-3.22; HR = 2.12, 95% CI 1.23-3.64) with low SMM. CONCLUSIONS: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management.

Platelet-lymphocyte and neutrophil-lymphocyte ratios: Predictive factors of response and toxicity for docetaxel-combined induction chemotherapy in advanced head and neck cancers.

BACKGROUND: Although the effect of induction chemotherapy (IC) is still controversial in cancers of the oral cavity, the oropharynx, and the sinonasal tract, it is still used in some inoperable cases and for organ preservation in laryngeal or hypopharyngeal cancers. Taxane has played a greater role and produces a better overall response but a higher rate of acute toxicity. We investigated the response and risk of IC with docetaxel-combined regimens in advanced head and neck cancers. METHODS: We retrospectively reviewed the medical history of patients with advanced head and neck cancer between 2011 and 2017. We enrolled 40 patients who completed the initial tumor survey, ICs with docetaxel-combined regimens, and definite therapeutic strategies including concurrent chemoradiation or surgery. The demographic data, laboratory results, overall response, and acute toxicity were analyzed. RESULTS: There were 14 patients (35.0%) with partial response at least. There were 24 (60.0%) with at least one acute toxicity beyond grade III. Univariate analysis and multivariate linear regression analysis showed that a platelet-lymphocyte ratio (PLR) <8.5 correlates with a better overall response (p < 0.05), and a neutrophil-lymphocyte ratio (NLR) ≥3.5 correlates with a higher possibility of severe acute toxicity within one month after ICs (p < 0.05), especially hematologic side effects. CONCLUSION: A pretreatment PLR <8.5 could predict better overall response, and a pretreatment NLR ≥3.5 could predict more severe acute toxicity after docetaxel-combined ICs. Through a simple hematological examination, we could try to identify a better response of tumor regression and anticipate potentially harmful side effects after ICs.

Ptosis and macroglossia in a woman with systemic light-chain amyloidosis.

BACKGROUND: Amyloidosis is a rare and variable disease, characterized by extracellular deposits of amyloid protein in different tissues and organs. Patients may present with a range of symptoms, depending on the extent of involvement. Rapid, accurate diagnosis is still challenging in clinical practice. CASE REPORT: A 72-y-old woman presented with a 1-y history of droopy upper left eyelid, resulting in decreased visual acuity, and progressive tongue swelling, resulting in dysarthria, dysphagia, and sleep apnea. Physical examination revealed puffy eyes, moderate swelling up to 1 cm of the upper left eyelid, swollen submental region, and protrusion of the tongue, causing an inability to close the mouth. An abnormal serum free light chain ratio implied the presence of monoclonal gammopathies, and Congo red staining revealed amyloid deposits in specimens from both the tongue and left eyelid. Therefore, a diagnosis of systemic light-chain (AL) amyloidosis was confirmed. The patient then received oral melphalan therapy and surgical intervention for macroglossia. Clinical symptoms including dysarthria, dysphagia, and sleep apnea were under control at 6-month follow-up. CONCLUSIONS: We report an uncommon case presenting initially with both ptosis and macroglossia, for which a final diagnosis of systemic AL amyloidosis was made. Detailed history and laboratory investigation must be implemented on suspicion of amyloidosis, because early recognition of amyloid-associated diseases and appropriate treatment can improve clinical outcomes.

Obliquely-arranged double skin paddles: A novel design to reconstruct extensive head and neck defects with a single fibula or peroneal flap.

OBJECTIVE: To reconstruct extensive head and neck defects usually necessitates double free flaps, which require a time-and-manpower-consuming surgical procedure. We present using a single fibula or peroneal flap with the novel design of obliquely-arranged double skin paddles to reconstruct an extensive head and neck defect. METHODS: From 1998 to 2016, eight patients with the age of 52.25 (35-71) years old had extensive head and neck defects after oral cancer ablation. All of the defects were through and through with the size of 16.25 (12-24) cm × 8.8 (4.5-11) cm. Six of the defects were due to buccal cancer. One was due to tongue cancer, and another one was due to gingiva cancer. All the defects were reconstructed with obliquely-arranged double-paddle free fibula or peroneal flaps. The long axis of the skin paddles was arranged at certain angle (30-45 degrees) to the long axis of lower leg, and the two separate skin paddles were used as the form of island flaps by isolating the cutaneous perforators to create a true chimeric flap. RESULTS: The skin paddle sizes were 14 cm × 3 cm-24 cm × 11 cm and 9.5 cm × 4.5 cm-13 cm × 8 cm. The average length of harvested fibula was 19 (10-30) cm. All of the eight flaps survived without obvious donor site morbidity. One patient had partial skin necrosis over recipient site, requiring surgical debridements and closure. One patient had superficial necrosis over the edge of outer skin paddle, which healed spontaneously. After the follow-up periods of 1 month to 3 year and 8 months, two patients died of sepsis. Six of them could resume soft diet and had no saliva drooling. The remaining two remained nasogastric diet and had saliva drooling. CONCLUSION: With the design of obliquely-arranged double paddles, we may maximize the harvested skin area of lateral lower leg to reconstruct an extensive head and neck defect with a single free flap.

Log margin-to-thickness ratio improves disease-specific survival prediction in oral cancer: A single cancer centre database.

OBJECTIVE: We examined whether dynamic margin criteria margin-to-thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). DESIGN: This is a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. PARTICIPANTS: A cohort of 302 patients with OSCC who had undergone surgical management. MAIN OUTCOMES MEASURES: Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi-square, Akaike information criterion (AIC) and Harrell's C tests. RESULTS: After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi-square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR <33% was associated with less favourable 5-year disease-specific survival (DSS) (P = 0.006) in the entire oral cancer study cohort. Other significant factors included perineural invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001) and differentiation category (P = 0.022). CONCLUSIONS: Log MTR < 33% may be a predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed both resection margin and tumour thickness alone in terms of discriminative analysis. Our study could help in presurgical planning for high-risk patients and in aiding the decision-making process for adjuvant treatment.

Hyperglycemia crisis in head and neck cancer patients with platinum-based chemotherapy.

BACKGROUND: The development of a hyperglycemic crisis in platinum-based chemotherapy-treated head and neck cancer patients, such as hyperosmolar hyperglycemic state (HHS), has been reported. Hyperglycemic crises are associated with a high risk of comorbidity and may delay cancer treatment if not promptly managed. METHODS: This is a retrospective study using cancer registry data from a tertiary medical center. Head and neck cancer patients who had been treated with platinum-based chemotherapy from January 2014 to December 2015 were enrolled for review. Exclusion criteria included patients with a known history of type 2 diabetes mellitus (DM). Characteristics of patients who developed type 2 DM after initiation of chemotherapy were compared with non-DM patients, following which the clinical course of the patients developing a hyperglycemic crisis were reviewed. RESULTS: A total of 185 patients were enrolled, of which seven patients (3.8%) had developed type 2 DM after initiation of platinum-based chemotherapy. No statistically significant differences in age, body mass index, sex, cancer subsite, cancer stage, or chemotherapy regimen were found when comparing new-onset type 2 DM patients with the rest of the patients. Three patients developed diabetic ketoacidosis, HHS, or impending HHS after initiating chemotherapy treatment. The incidence of hyperglycemic crises was 3 out of 185 (1.6%) in this patient group. CONCLUSION: Hyperglycemic crisis after cisplatin may be underestimated and may lead to a life-threatening condition. We suggest regular weekly follow-ups of serum glucose level after platinum-based chemotherapy for early detection of hyperglycemia and prevention of a life-threatening crisis.

Exposure to nicotine-derived nitrosamine ketone and arecoline synergistically facilitates tumor aggressiveness via overexpression of epidermal growth factor receptor and its downstream signaling in head and neck squamous cell carcinoma.

Long-term nicotine-derived nitrosamine ketone (NNK) and arecoline exposure promotes carcinogenesis and head and neck squamous cell carcinoma (HNSCC) progression, although most associated data on the two were analyzed individually. The molecular mechanisms underlying tumor progression associated with the synergistic effects of NNK and arecoline remain unclear. We treated SCC-25 and FaDu cells with NNK and arecoline (separately or in combination) for 3 months. Comparative analysis was performed to investigate the mechanism underlying the acquisition of properties related to tumor promotion, including stemness, anti-apoptosis, and resistance to HNSCC therapeutics. Long-term exposure to NNK and arecoline resulted in an increase in cancer stem cell properties, anti-apoptosis, and the resistance to cisplatin in HNSCC. We detected abundant epidermal growth factor receptor (EGFR) expression in HNSCC cells after combined treatment with NNK and arecoline. EGFR was pivotal in inducing tumor promotion and anti-apoptosis in cancer cells by inducing pAKT and NFκB. Combined treatment with NNK and arecoline synergistically facilitated tumor aggressiveness via EGFR-AKT signaling. Targeting EGFR-AKT signaling may be a feasible strategy for treating HNSCC.

Factors contributing to surgical site infection in patients with oral cancer undergoing microvascular free flap reconstruction.

PURPOSE: Surgical site infections (SSIs) are associated with considerable medical expenditure. While head and neck free flap reconstruction has gradually become routine management following an ablative oncologic resection, reports on factors contributing to the SSIs are lacking. METHODS: We retrospectively analyzed 173 new patients with oral cancer without any antecedent treatment at a tertiary medical center from 2010 to 2015. We determined incidence rates of SSIs within 30 days postoperatively and identified independent risk factors using multivariate logistic regression analysis. RESULTS: Of 173 patients, 67 (38.7%) had SSIs. Multivariate analysis demonstrated operative time [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.036-1.389], mandibulectomy (OR = 2.759; 95% CI = 1.245-6.111), and oro-neck communication (OR = 5.358; 95% CI = 2.150-13.355) as independent predictors for SSIs. CONCLUSIONS: For patients with oral cancer undergoing free tissue reconstruction, mandibulectomy, oro-neck communication, and prolonged operative time were associated with increased incidence of SSIs.

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS.

The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA. Moreover, restoring cGAS expression results in an anti-tumour immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harbouring high levels of miR-25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumour progression, and reveal a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumour microenvironment, thus unveiling potential new therapeutic strategies.

Vascular anatomy is a determining factor of successful submental flap raising: a retrospective study of 70 clinical cases.

The vascular anatomy of submental flaps (SFs) represents a determining factor in successful SF raising. However, little attention has been focused on the venous return of SFs. Thus, the present study aimed to investigate SF venous return. This study enrolled patients who underwent SF reconstructive surgery in a tertiary referral center between November 2009 and October 2016. The drainage pathway of the SF venous return was routinely identified during the course of our operations to prevent damage during head and neck surgery. The venous return data of 70 patients were reviewed. The size of the flaps ranged from 15 to 84 cm2, and total flap loss was not observed in the case series. All of the submental arteries originated from the facial artery; however, the submental veins of 70 patients returned to either the internal jugular vein (IJV, 72.9%) or the external jugular vein (EJV, 27.1%). Our data suggest that drainage of the submental vein into the EJV, which has been previously overlooked, should receive greater attention during SF surgeries. The results support mandatory preservation of the EJV and IJV and indicate that vascular anatomy is a determining factor for successful SF raising.