Purpose: Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. Radioresistance is a major challenge in the treatment of brain tumors. The development of several types of tumors, including GBM, involves the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Upon activation, this pathway induces radioresistance. In this study, we investigated whether additional use of selective inhibitors of PI3K isoforms would enhance radiosensitivity in GBM. Materials and Methods: We evaluated whether radiation combined with PI3K isoform selective inhibitors can suppress radioresistance in GBM. Glioma 261 expressing luciferase (GL261-luc) and LN229 were used to confirm the effect of combination of radiation and PI3K isoform inhibitors in vitro. Cell viability was confirmed by clonogenic assay, and inhibition of PI3K/AKT signaling activation was observed by Western blot. To confirm radiosensitivity, the expression of phospho-γ-H2AX was observed by immunofluorescence. In addition, to identify the effect of a combination of radiation and PI3K-α isoform inhibitor in vivo, an intracranial mouse model was established by implanting GL261-luc. Tumor growth was observed by IVIS imaging, and survival was analyzed using Kaplan–Meier survival curves. Results: Suppression of the PI3K/AKT signaling pathway increased radiosensitivity, and PI3K-α inhibition had similar effects on PI3K-pan inhibition in vitro. The combination of radiotherapy and PI3K-α isoform inhibitor suppressed tumor growth and extended survival in vivo. Conclusion This study verified that PI3K-α isoform inhibition improves radiosensitivity, resulting in tumor growth suppression and extended survival in GBM mice.

Objectives: . Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). Methods: . We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. Results: . Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780). Conclusion . A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Objectives: . Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). Methods: . We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. Results: . Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780). Conclusion . A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Purpose: To evaluate the incidence and presentation of osteoporotic sequential bilateral hip fractures (SBHF) in Center for Joint Disease, Chonnam National University Hwasun Hospital as there are limited studies with variable results reported in Korea. Materials and Methods: Records of 507 patients aged >60 years old presenting with osteoporotic hip fractures between 2009 and 2015 were retrospectively reviewed to document the occurrence and presentation of sequential hip fractures; mean post-treatment follow-up was 48 months. Additionally, any correlations between sequential fractures and initial fracture and risk factors were assessed. Bone mineral density (BMD) was measured before and after sequential hip fracture for comparison. Results: There were 246 femoral neck (Group A) and 261 intertrochanteric (Group B) fractures. The cumulative incidence of SBHF was 8.2% (42 patients total; 29 in Group A and 13 in Group B). Average interval of SBHF for Group A and Group B were 37.4 months and 29.9 months, respectively. There was significant correlation between the initial fracture type and sequential fractures, particularly the trochanteric and subgroup of those with neck fractures. Hypertension as a co-morbidity and female sex have been identified as risk factors for SBHF. No significant findings were noted regarding BMD and risk factors in both groups. Conclusion The clinical presentations of SBHF noted here concur with other worldwide studies and may guide efforts to develop relevant programs to prevent SBHF.

PURPOSE: The use of immediate breast reconstruction (IBR) has been debated because it may be a causative factor in adjuvant treatment delay and may subsequently increase the probability of recurrence. We investigated whether IBR was related to adjuvant treatment delay and survival outcomes. METHODS: We retrospectively analyzed the duration from operation to adjuvant treatment administration and survival outcomes according to IBR status among patients with breast cancer who underwent mastectomy followed by adjuvant chemotherapy from January 2005 to December 2014. Propensity score matching was performed to balance the clinicopathologic baseline characteristics between patients who did and did not undergo IBR. RESULTS: Of 646 patients, 107 (16.6%) underwent IBR, and the median follow-up was 72 months. The median duration from surgery to adjuvant chemotherapy was significantly longer in patients who underwent IBR than in those who did not (14 vs. 12 days, respectively, p = 0.008). Based on propensity score matching, patients who underwent IBR received adjuvant therapy 3 days later than those who did not (14 vs. 11 days, respectively, p = 0.044). The duration from surgery to post-mastectomy radiation therapy (PMRT) did not significantly differ between the 2 groups. Local recurrence-free survival, regional recurrence-free survival, systemic recurrence-free survival, and overall survival were also not significantly different between the 2 groups (p = 0.427, p = 0.445, p = 0.269, and p = 0.250, respectively). In the case-matched cohort, survival outcomes did not change. CONCLUSION: IBR was associated with a modest increase in the duration from surgery to chemotherapy that was statistically but not clinically significant. Moreover, IBR had no influence on PMRT delay or survival outcomes, suggesting that it is an acceptable option for patients with non-metastatic breast cancer undergoing mastectomy.
Breast Implants ; Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Cohort Studies ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Mammaplasty ; Mastectomy ; Propensity Score ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies

The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines (TNF-α, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, TNF-α and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, TNF-α, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.
Blotting, Western ; Chemokines ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Helminths ; Humans ; Interleukin-4 ; Mast Cells ; Nitric Oxide ; Toxoplasma

BACKGROUND/AIMS: Little evidence is available about the effect of change in nonalcoholic fatty liver disease (NAFLD) status on risk of diabetes mellitus (DM) development. In this study, we tried to analyze the DM risk according to change in NAFLD status over time. METHODS: Among a total of 10,141 individuals for whom routine healthcare assessment was performed, 2,726 subjects were selected according to the inclusion/exclusion criteria. NAFLD status change was determined by using serial abdominal ultrasonography and fatty liver index (FLI) during the follow-up period. RESULTS: Subjects were categorized according to change in NAFLD status as follows: 670 subjects in the persistent NAFLD group, 155 subjects in the resolved NAFLD group, 498 subjects in the incident NAFLD group, and 1,403 subjects in the no NAFLD group. Multivariate Cox regression analysis revealed that incident NAFLD (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.08 to 3.50; p=0.026) and persistent NAFLD (HR, 3.59; 95% CI, 2.05 to 6.27; p<0.001) were independent risk factors for predicting DM development, whereas the risk with resolved NAFLD was not significantly different from that with no NAFLD. FLI could reproduce the results acquired by ultrasonography. CONCLUSIONS: This study demonstrated that future DM risk could be influenced by changes in NAFLD status over time. Resolution of NAFLD could reduce the risk of future DM development, while the development of new NAFLD could increase the risk of DM development.
Delivery of Health Care ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fatty Liver ; Follow-Up Studies ; Non-alcoholic Fatty Liver Disease ; Obesity ; Risk Factors ; Ultrasonography

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.
Advisory Committees ; Consensus ; Counseling ; Drug Therapy ; Glottis ; Humans ; Laryngeal Neoplasms* ; Neck*

Most men infected with Trichomonas vaginalis are asymptomatic and can remain undiagnosed and untreated. This has been hypothesized to result in chronic persistent prostatic infection. Adhesion of the protozoan organisms to mucosal cells is considered a first and prerequisite step for T. vaginalis infection. Adhesion of T. vaginalis to prostate epithelial cells has not yet been observed; however, there are several reports about inflammation of prostate epithelial cells induced by T. vaginalis. The aim of this study was to investigate whether adhesion and cytotoxicity of T. vaginalis are involved in inflammation of prostate epithelial cells. When RWPE-1 cells were infected with T. vaginalis (1:0.4 or 1:4), adhesion of T. vaginalis continuously increased for 24 hr or 3 hr, respectively. The cytotoxicity of prostate epithelial cells infected with T. vaginalis (RWPE-1: T. vaginalis=1:0.4) increased at 9 hr; at an infection ratio of 1:4, cytotoxicity increased after 3 hr. When the RWPE-1 to T. vaginalis ratio was 1:0.4 or 1:4, production of IL-1β, IL-6, CCL2, and CXCL8 also increased. Epithelial-mesenchymal transition (EMT) was verified by measuring decreased E-cadherin and increased vimentin expression at 24 hr and 48 hr. Taken together, the results indicate that T. vaginalis adhered to prostate epithelial cells, causing cytotoxicity, pro-inflammatory cytokine production, and EMT. Our findings suggest for the first time that T. vaginalis may induce inflammation via adhesion to normal prostate epithelial cells.
Cadherins ; Cell Adhesion ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Epithelium* ; Humans ; Inflammation ; Interleukin-6 ; Male ; Prostate* ; Trichomonas vaginalis* ; Trichomonas* ; Vimentin

Proximal femoral cephalomedullary nailing is one of the treatments of choice for intertrochanteric fracture. Zimmer Natural Nail® (ZNN; Zimmer) is one of the alternatives. We report two cases of broken tail portion of the ZNN lag screw during the removal procedure. This may be the first reported cases in scientific literature with this pattern of failure. We report these cases to highlight one of the possible problems that could occur during removal of this implant which can possibly prolong the operation time significantly if the required device is not prepared.
Hip Fractures ; Tail*