Epigallocatechin-3-gallate inhibits migration of human nasopharyngeal carcinoma cells by repressing MMP-2 expression.

Metastasis of the cancer cells to the regional lymph nodes parts of the body remains an important cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Epigallocatechin-3-gallate (EGCG), the most important ingredient in the green tea, has been reported to possess antioxidant and anticancer activities. However, the effects of EGCG on NPC cell metastasis are still unclear. In the present study, we examined the in vitro antimetastatic properties of EGCG on human NPC cells, NPC-39, HONE-1 and NPC-BM. The results revealed that EGCG considerably inhibited the migration abilities of three NPC cells. The matrix metalloproteinases-2 (MMP-2) activity and expression were also significantly inhibited by EGCG treatment. Furthermore, EGCG suppressed the phosphorylation of the Src signaling pathway. Moreover, blocking the Src pathway also inhibits MMP-2 expression and migration in the NPC cells. In conclusion, this study revealed that EGCG could inhibit the metastatic activity of human NPC cells by downregulating the protein expression of MMP-2 through modulation of the Src signaling pathway, suggesting that EGCG may be a potential candidate for chemoprevention of NPC.

Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo.

Radiation therapy (RT) is the current standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Radioresistance is a major contributor to radiotherapy failure. In this study, we used patient-derived cells and a radiation-resistant cell line in vitro and in vivo for two purposes: evaluate the anti-tumor effects and understand the mechanisms in the dual PI3K/mTOR signaling pathway regulation of radiosensitization. Our findings indicate that in OML1-R cells, the radioresistance phenotype is associated with activation of the PI3K/AKT/mTOR signaling pathway. Compared to a combination of PI3K or mTOR inhibitors and radiation, dual blockade of the PI3K and mTOR kinases significantly improved radiation efficacy in oral cancer and patient-derived OSCC cells. Dual PI3K/mTOR inhibition enhanced the effect of radiation by inhibiting AKT/mTOR signaling pathways and caused G1 phase arrest, which is associated with downregulation of cyclin D1/CDK4 activity, leading to growth inhibition. In nude mice xenografted with radioresistant OML1-R cells, the combined treatment was also more effective than RT alone in reducing tumor growth. This treatment was also demonstrated to be dependent on the inhibition of protein kinase-dependent S6 kinase pathway and eIF4E-mediated cap-dependent translation. These findings indicate that activation of the PI3K/AKT/mTOR signaling pathway has a role in radioresistance of OSCC. We determined that a PI3K/mTOR inhibitor combined with radiation exhibits synergistic inhibition of the AKT/mTOR axis and induces cell cycle arrest. Our results show the therapeutic potential of drugs targeting the PI3K/AKT/mTOR signaling pathway should be new candidate drugs for radiosensitization in radiotherapy.

AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis and Inducing G1/G2/M Cell Cycle Arrest.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models. METHODS: We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression. RESULTS: Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells. CONCLUSIONS: These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.

Predicting three-month and 12-month post-fitting real-world hearing-aid outcome using pre-fitting acceptable noise level (ANL).

OBJECTIVE: Determine the extent to which pre-fitting acceptable noise level (ANL), with or without other predictors such as hearing-aid experience, can predict real-world hearing-aid outcomes at three and 12 months post-fitting. DESIGN: ANLs were measured before hearing-aid fitting. Post-fitting outcome was assessed using the international outcome inventory for hearing aids (IOI-HA) and a hearing-aid use questionnaire. Models that predicted outcomes (successful vs. unsuccessful) were built using logistic regression and several machine learning algorithms, and were evaluated using the cross-validation technique. STUDY SAMPLE: A total of 132 adults with hearing impairment. RESULTS: The prediction accuracy of the models ranged from 61% to 68% (IOI-HA) and from 55% to 61% (hearing-aid use questionnaire). The models performed more poorly in predicting 12-month than three-month outcomes. The ANL cutoff between successful and unsuccessful users was higher for experienced (∼18 dB) than first-time hearing-aid users (∼10 dB), indicating that most experienced users will be predicted as successful users regardless of their ANLs. CONCLUSIONS: Pre-fitting ANL is more useful in predicting short-term (three months) hearing-aid outcomes for first-time users, as measured by the IOI-HA. The prediction accuracy was lower than the accuracy reported by some previous research that used a cross-sectional design.

Comparison of different comorbidity measures for oral cancer patients with surgical intervention: A longitudinal study from a single cancer center.

OBJECTIVE: Several comorbid measures have been developed and demonstrated the predictive ability for cancer mortality. We conducted a retrospective study on oral squamous cell carcinoma (OSCC) patients to compare the Charlson comorbidity index score (CCIS) to the Elixhauser comorbidity index score (ECIS). METHODS: Newly diagnosed OSCC patients (n=232) post major surgery with or without adjuvant therapy were identified from the cancer registry database between 2006 and 2011. Comorbidities present prior to the cancer diagnosis were obtained and adapted to the CCIS and ECIS. The prevalence of comorbid conditions and the influence on disease-specific survival (DSS) rate were calculated and analyzed by Cox regression model. The discriminatory ability of these two comorbid measures was evaluated by using the adjusted hazard ratio and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's c-statistic. RESULTS: Most of the patients (93.5%) were male with a mean age of 54 ± 11 years and 77 of them (33.1%) had at least one comorbid condition. The ECIS was associated DSS, with an additional 10% increased risk observed for mortality for each increased score (HR, 1.10; 95% confidence interval [CI], 1.03-1.18) after adjusting with pathological risk features. However, the CCIS was not an independent prognostic factor for these patients. The ECIS increased discriminatory ability but the CCIS did not improve discrimination. CONCLUSIONS: Comorbid conditions significantly influenced the clinical outcomes of patient with OSCC post major surgery. A higher ECIS was associated with worse disease specific survival indicative of a valuable prognostic indicator. The ECIS may be considered in further clinical trials for a variety of cancers, including head and neck cancers.

The Prognostic Ability of Log Odds of Positive Lymph Nodes in Oral Cavity Squamous Cell Carcinoma.

Recently, log odds of positive lymph nodes (LODDS) was proven a better prediction of outcomes than other methods in gastric cancer, pancreatic cancer, and colon cancer. However, the validity is not yet tested in oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective study to compare the predictive ability of LODDS, traditional pN classification and lymph node ratio (rN) in OSCC patients.In total, 347 OSCC patients receiving surgery with or without adjuvant therapy at the time of diagnosis between 2004 and 2013 were identified from the cancer registry database of the Dalin Tzu Chi Hospital. Cox proportional hazards models were used to compare the disease-specific survival (DSS) rates for pN, rN, and LODDS after adjusting for possible confounding risk factors. The discriminatory ability of different classification systems was evaluated using the adjusted hazard ratio and Akaike information criterion (AIC) by multivariate regression model. The prediction accuracy of the model was assessed by Harrell's c-statistic.The 347 OSCC patients had a mean age of 57 years old. Among them, 322 patients (92.8%) were male and 189 patients (54.5%) were in stages III to IV. LODDS showed better discriminatory ability for patients with <5 pathological cervical metastatic nodes and those with rN < 0.2. The hypothetical T-LODDS-M staging system had higher linear trend Chi-square, lower AIC, and higher prediction accuracy compared with the American Joint Committee on Cancer (AJCC) TNM, or hypothetical T-rN-M system. After adjusting for other factors, the LODDS unfavorable group had the highest adjusted hazard ratio (HR, 5.42; 95% confidence interval [CI], 3.19-9.12) and LODDS-based model lowest AIC of 704, comparing with pN and rN-based model. The LODDS-based system had the highest prediction accuracy for 3-year DSS (Harrell's c-statistic, 0.803).In our series, LODDS shows great promise as a prognostic tool for OSCC. Compared with the AJCC pN classification and the rN classification, LODDS can stratify OSCC patients and help to identify high-risk patients missed by the other systems.

Modified Tumor Classification With Inclusion of Tumor Characteristics Improves Discrimination and Prediction Accuracy in Oral and Hypopharyngeal Cancer Patients Who Underwent Surgery.

Several histopathological characteristics have a significant prognostic impact on recurrence and survival rates in head and neck squamous cell carcinoma (HNSCC). We conducted a retrospective study on patients with HNSCC to compare traditional pathological T (pT) classification to a new T classification system that incorporates these histopathological characteristics.Newly diagnosed patients with HNSCC (n = 349) post major surgery were identified from the cancer registry database between 2004 and 2013. The pT and new T classification systems were compared with respect to recurrence-free survival (RFS), disease-specific survival (DSS), and survival rates using the Cox proportional hazards model with adjustments. The discriminatory ability of these 2 classification systems was evaluated using the adjusted hazard ratio (HR) and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's C-statistic.The new T classification, which incorporated tumor size, extent, and location with histopathological features had better discriminatory ability and monotonicity of gradients than did pT classification. The new T4 classification yielded a higher adjusted HR in RFS (HR, 4.11; 95% confidence interval [CI], 7.75-9.65) and in DSS (HR, 4.39; 95% CI, 1.6-12.03), and a lower AIC in recurrence (927 vs 969) and survival rates (791 vs 833).The new T classification system had better discriminatory ability in RFS and DSS compared with the routinely used American Joint Committee on Cancer (AJCC) pT classification system. Therefore, this new T classification system, which includes tumor size, location, extent, and histopathological features, could be used as an alternative to AJCC pT classification for patients with HNSCC.

MCP1-Induced Epithelial-Mesenchymal Transition in Head and Neck Cancer by AKT Activation.

AIM: To explore whether monocyte chemotactic protein-1 (MCP1) is associated with the epithelial-mesenchymal transition (EMT) and neck metastases in head and neck cancer (HNC). MATERIALS AND METHODS: MCP1 and its related protein were evaluated using western blotting, and a migration assay for HNC cell lines. Thirty-five patients with HNC were recruited for the evaluation of MCP1 expression and pathologically-proven neck metastases from their tissue specimens. RESULTS: MCP1 changed the phenotype of OML-1 cells to a spindle shape, with increased mobility. In OML3 cells, MCP1 knockdown with siRNA blocked EMT. Activation of protein kinase B (AKT) was positively associated with the EMT phenotype, and this transition was abrogated with a phosphoinositide 3 kinase (PI3K) inhibitor. By comparing clinical outcomes, the histological MCP1 score was associated with pathological neck metastases (p=0.027). CONCLUSION: The overexpression of MCP1 in HNC cells may partially induce EMT through the AKT pathway. A high cellular expression of MCP1 was associated with pathological neck metastases.

Treatment of refractory Aspergillus otomycosis with voriconazole: case series and review.

BACKGROUND: Voriconazole is a broad-spectrum azole exhibiting strong anti-Aspergillus activity and good long-term tolerance. However, the evidence for voriconazole efficacy against refractory Aspergillus otomycosis is weak. METHOD: We reviewed the medical records of patients with Aspergillus otomycosis treated with voriconazole from January 2008 to June 2012 in a Taiwanese regional hospital. Demographic data and information regarding underlying diseases, clinical features, treatment and outcome were assessed. RESULTS: In total, 14 cases of Aspergillus otomycosis were treated with voriconazole, including 5 patients with Aspergillus invasive otitis externa. All patients had failed to respond to local treatment, antibiotics or topical agents. One case was lost to follow up. The symptoms of two patients recurred after voriconazole treatment: one patient received a second 12-week course of voriconazole and was cured; and symptoms of the other patient recurred after a second 12-week course of voriconazole, leading to surgical debridement. The remaining 11 patients were cured by voriconazole treatment without extensive surgical debridement. CONCLUSION: This study demonstrates that voriconazole can be a very effective and convenient therapeutic option for the management of refractory Aspergillus otomycosis.

RAD001 enhances the radiosensitivity of SCC4 oral cancer cells by inducing cell cycle arrest at the G2/M checkpoint.

BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) kinase enhances the radiosensitivity of some cancer cells. We investigated the effect of RAD001, an mTOR inhibitor, on irradiated oral cancer cell lines. MATERIALS AND METHODS: Clonogenic assays were performed to determine the radiosensitivity of SCC4 and SCC25 cells after treatment with RAD001. Target protein phosphorylation, apoptosis, and cell-cycle progression were assessed in SCC4 cells treated with RAD001 with and without ionizing radiation. RESULTS: RAD001 increased the radiosensitivity of SCC4 cells without affecting cell death; it also inhibited phosphorylation of mTOR, S6, and factor 4E binding protein 1 and reduced the clonogenic survival of irradiated cancer cells. RAD001 combined with radiation increased G2 arrest by activating CHK1, which phosphorylates CDC25C at Ser216, thereby inhibiting CDC2-cyclin B 1 complex formation. CONCLUSION: RAD001 enhances the radiosensitivity of SCC4 cells by inhibiting mTOR signaling and inducing G2 cell-cycle arrest through disruption of the G2 checkpoint.

Acceptable noise level (ANL) and real-world hearing-aid success in Taiwanese listeners.

OBJECTIVE: The objective of this prospective study was to investigate the relationship between acceptable noise level (ANL), which was measured using Taiwanese and the international speech test signal (ISTS), and real-world hearing-aid success for listeners who were representative of the population commonly seen in clinics. DESIGN: Unaided ANLs were measured pre-hearing-aid fitting. Hearing-aid success was assessed three months post-fitting using the international outcome inventory for hearing aids (IOI-HA) and a hearing-aid use questionnaire. STUDY SAMPLE: Eighty adults with hearing impairment completed the study. RESULTS: Both Taiwanese and ISTS ANLs were significantly associated with hearing-aid success, with higher ANLs suggesting poorer outcomes. However, the ANL's prediction accuracy for the probability of hearing-aid success was either much lower than that suggested by some literature, or was not much different from that of simply predicting all listeners as successful users. CONCLUSIONS: The current study suggested the possibility of using ANL to predict hearing-aid success. However, the usefulness of ANL as a clinical tool is unlikely to be as great as indicated by the literature.

Association between provider volume and healthcare expenditures of patients with oral cancer in Taiwan: a population-based study.

BACKGROUND: Oral cancer requires considerable utilization of healthcare services. Wide resection of the tumor and reconstruction with free flap are widely used. Due to high recurrence rate, close follow-up is mandatory. This study was conducted to explore the relationship between the healthcare expenditure of oncological surgery and one-year follow up and provider volume. METHODS: From the National Health Insurance Research Database published by the Taiwanese National Health Research Institute, the authors selected a total of 1300 oral cancer patients who underwent tumor resection and free flap reconstruction in 2008. Hierarchical linear regression analysis was subsequently performed to explore the relationship between provider volume and expenditures of oncological surgery and one-year follow-up period. Emergency department (ED) visits and 30-day readmission rates were also analyzed. RESULTS: The mean expenditure for oncological surgery was $11080±4645 (all costs are given in U.S. dollars) and $10129±9248 for one-year follow up. For oncological surgery expenditure, oral cancer patients treated by low-volume surgeons had an additional $845 than those in high-volume surgeons in mixed model. For one-year follow-up expenditure, patients in low-volume hospitals had an additional $3439 than those in high-volume hospitals; patient in low-volume surgeons and medium-volume surgeons incurred an additional expenditure of $2065 and $1811 than those in high-volume surgeons. Oral cancer patients treated in low-volume hospitals incurred higher risk of 30-day readmission rate (odds ratio, 6.6; 95% confidence interval, 1.6-27). CONCLUSIONS: After adjusting for physician, hospital, and patient characteristics, low-volume provider performing wide excision with reconstructive surgery in oral cancer patients incurred significantly higher expenditure for oncological surgery and one-year healthcare per patient than did others with higher volumes. Treatment strategies adapted by high-volume providers should be further analyzed.

Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer: a preliminary report.

BACKGROUND: The aim of this study was to determine the influence of inflammation on acute phase protein and epithelial-mesenchymal transition (EMT) in buccal cancer. METHODS: Western blotting was carried out to investigate the expression of haptoglobin and epithelial-mesenchymal transition in oral cancer cell lines with or without IL-6 stimulation. We studied patients with buccal cancer patients without distant metastasis at diagnosis. Correlation between cellular haptoglobin, EMT, and clinical characteristics of buccal cancer was analyzed to assess the prognostic value of cellular haptoglobin level and EMT. The relationship of haptoglobin, and EMT expression with survival was assessed using Cox proportional hazard models. RESULTS: Western blotting analysis showed that increased haptoglobin protein was associated with overexpression of vimentin. Under IL-6 stimulation, overexpression of haptoglobin, EMT-associated motile phenotype was noted in OC2 cell lines. Overexpression of haptoglobin was also associated with an increased risk for locoregional recurrence [hazard ratio (HR) 1.04; p=0.011] after adjusting for age, gender, disease site, stage, and treatment modality. CONCLUSIONS: Increased cellular expression of haptoglobin is associated with EMT in oral cancer cell lines and this phenomenon could be exaggerated with IL-6. Cellular expression of haptoglobin is related to locoregional recurrence rate in buccal cancer patients.

The equivalence of acceptable noise level (ANL) with English, Mandarin, and non-semantic speech: a study across the U.S. and Taiwan.

OBJECTIVE: Acceptable noise level (ANL) determines the maximum noise level that a listener is willing to accept while listening to speech. The objective of this study was to determine the equivalence of ANL measured using different speech stimuli for native speakers who lived in the U.S. and Taiwan. DESIGN: ANLs were measured using English, Mandarin, and the international speech test signal (ISTS) at each site. The same babble noise was used across speech stimuli. The ANLs were considered equivalent if the difference was unlikely to be greater than 3 dB. STUDY SAMPLE: Thirty adults with normal hearing were recruited at each site. RESULTS: For each site, the equivalence test suggested that the native-language and foreign-language ANLs were equivalent. Between the two sites, ANLs measured using the listener's native language were also equivalent. Although the ISTS ANL obtained within each site was equivalent to, and highly correlated to, the native-language ANL, the data were unable to confirm the equivalence of the ISTS ANLs obtained from the two sites. CONCLUSIONS: The results suggested the possibility of directly comparing ANL measures carried out in different countries using different languages. However, it remains unclear if the ISTS can serve as an international ANL stimulus.

Infectious complications in head and neck cancer patients treated with cetuximab: propensity score and instrumental variable analysis.

BACKGROUND: To compare the infection rates between cetuximab-treated patients with head and neck cancers (HNC) and untreated patients. METHODOLOGY: A national cohort of 1083 HNC patients identified in 2010 from the Taiwan National Health Insurance Research Database was established. After patients were followed for one year, propensity score analysis and instrumental variable analysis were performed to assess the association between cetuximab therapy and the infection rates. RESULTS: HNC patients receiving cetuximab (n = 158) were older, had lower SES, and resided more frequently in rural areas as compared to those without cetuximab therapy. 125 patients, 32 (20.3%) in the group using cetuximab and 93 (10.1%) in the group not using it presented infections. The propensity score analysis revealed a 2.3-fold (adjusted odds ratio [OR] = 2.27; 95% CI, 1.46-3.54; P = 0.001) increased risk for infection in HNC patients treated with cetuximab. However, using IVA, the average treatment effect of cetuximab was not statistically associated with increased risk of infection (OR, 0.87; 95% CI, 0.61-1.14). CONCLUSIONS: Cetuximab therapy was not statistically associated with infection rate in HNC patients. However, older HNC patients using cetuximab may incur up to 33% infection rate during one year. Particular attention should be given to older HNC patients treated with cetuximab.

The impact of influenza vaccinations on the adverse effects and hospitalization rate in the elderly: a national based study in an Asian country.

OBJECTIVES: To examine the risk of adverse effects of special interest in persons vaccinated against seasonal influenza compared with unvaccinated persons aged 65 and above. METHODS: We retrospectively observed 41,986 vaccinated elderly persons and 50,973 unvaccinated elderly persons in Taiwan from October 1, 2008, through September 30, 2009, using the National Health Insurance database. Neurological and autoimmune disorders and one-year hospitalization rates and in-hospital mortality rates were analyzed according to the vaccination status. Propensity score analysis was used to assess the relationship between adverse outcomes, hospitalization rates, and vaccination status. RESULTS: 45% of the elderly received influenza vaccination. Multiple logistic regression showed that the probability of being vaccinated was related to more patients visiting for URI symptoms (odds ratio (OR), 1.03; 95% CI, 1.02-1.03), men (OR, 1.15; 95% CI, 1.12-1.17), increased age (OR, 1.02; 95% CI, 1.02-1.03), and more comorbidities (OR, 1.2; 95% CI, 1.17-1.23). There were no statistical differences in neurological and autoimmune diseases between the vaccinated and unvaccinated individuals using propensity score analysis, but vaccinated persons had a reduced hospitalization rate of 19% (odds ratio [OR], 0.81; 95% CI, 0.77-0.84) for the first six-months and 13% for one-year of follow-up (OR, 0.87; 95% CI, 0.85-0.9). CONCLUSIONS: Based on data from the one-year follow-ups among 93,049 elderly persons in Taiwan, reassuring results for selected neurological and autoimmune diseases were found among the vaccinated individuals after adjusting other factors. Influenza vaccination decreased the risk for hospitalization. Public health strategies must continue to improve the influenza vaccination rate among the elderly with information based upon tangible evidence.

Characterizing the major sonographic textural difference between metastatic and common benign lymph nodes using support vector machine with histopathologic correlation.

Sonographic texture analysis can reflect histopathological components and their arrangement in metastatic and common benign lymph nodes. It is helpful in differentiation between metastatic and benign lymph node lesions for target selection during biopsy of multiple lymph nodes and the strategy of the management. Two ultrasound systems, 107 sonographic regions of interest (ROIs) of metastases and 174 sonographic ROIs of common benign lymph nodes, were recruited in the study. Thirteen texture features derived from co-occurrence matrix were used in characterization of above ROI ultrasound images. Support vector machine (SVM) was used as a classifier and a feature selector. The experimental results show that the entropy gains the best cross-validation accuracy of 94.66% and 87.73% in both ultrasound systems 1 and 2 for the classification of metastatic and benign lymph nodes disease. The accuracy can be further increased to 97.86% and 100% by the combination of the sum average in the study. There are significantly higher entropy and sum average values of the metastatic lymph nodes than of the benign lymph nodes, which are due to the heterogeneous compositions and arrangement of larger cancer cells, lymphocytes, and stroma in metastatic lymph nodes that contrast with simple inflammatory cells infiltration in common benign lymph nodes.

Increased risk of vascular events in emergency room patients discharged home with diagnosis of dizziness or vertigo: a 3-year follow-up study.

BACKGROUND: Dizziness and vertigo symptoms are commonly seen in emergency room (ER). However, these patients are often discharged without a definite diagnosis. Conflicting data regarding the vascular event risk among the dizziness or vertigo patients have been reported. This study aims to determine the risk of developing stroke or cardiovascular events in ER patients discharged home with a diagnosis of dizziness or vertigo. METHODOLOGY: A total of 25,757 subjects with at least one ER visit in 2004 were identified. Of those, 1,118 patients were discharged home with a diagnosis of vertigo or dizziness. A Cox proportional hazard model was performed to compare the three-year vascular event-free survival rates between the dizziness/vertigo patients and those without dizziness/vertigo after adjusting for confounding and risk factors. RESULTS: We identified 52 (4.7%) vascular events in patients with dizziness/vertigo and 454 (1.8%) vascular events in patients without dizziness/vertigo. ER patients discharged home with a diagnosis of vertigo or dizziness had 2-fold (95% confidence interval [CI], 1.35-2.96; p<0.001) higher risk of stroke or cardiovascular events after adjusting for patient characteristics, co-morbidities, urbanization level of residence, individual socio-economic status, and initially taking medications after the onset of dizziness or vertigo during the first year. CONCLUSIONS: ER patients discharged home with a diagnosis of dizziness or vertigo were at a increased risk of developing subsequent vascular events than those without dizziness/vertigo after the onset of dizziness or vertigo. Further studies are warranted for developing better diagnostic and follow-up strategies in increased risk patients.

Increased risk of stroke in young head and neck cancer patients treated with radiotherapy or chemotherapy.

BACKGROUND: Chemo-radiotherapy-induced carotid stenosis and cerebrovascular events in head and neck cancer patients can cause severe disability and death. We aimed to estimate the risk of stroke in such patients over a six-year follow-up period. PATIENTS AND METHODS: The study cohort consisted of head and neck cancer patients (n=10,172). Cox proportional hazard model was used to compare the stroke-free survival rate between the patients treated with radiotherapy or chemotherapy, surgery alone, and surgery with adjuvant therapy after adjusting for possible confounding factors. RESULTS: At the end of follow-up, 384 patients had strokes: 126 (4.3%) from the surgery alone group, 167 (3.8%) from the radiotherapy or chemotherapy group, and 91 (3.2%) from the surgery with adjuvant therapy (P=0.222). Head and neck cancer patients aged less than 55 years treated with radiotherapy or chemotherapy conferred a 1.8-fold higher risk for stroke (95% CI, 1.22-2.56; P=0.003) after adjusting for patient characteristics, co-morbidities, geographic region, urbanization level, and socio-economic status. There was no statistical difference in stroke risk between different treatment modalities in head and neck cancer patients aged 55 years and more. CONCLUSIONS: Young head and neck cancer patients treated with radiotherapy or chemotherapy have higher risks for stroke. Different treatment strategies should be considered in such patients.

Increased risk of ischemic stroke in young nasopharyngeal carcinoma patients.

PURPOSE: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. METHODS AND MATERIALS: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n=1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n=4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. RESULTS: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p=0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio=0.87; 95% CI, 0.56-1.33; p=0.524) after adjusting for other factors. CONCLUSIONS: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.