XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis.

Numerous studies have investigated the association between three polymorphisms (Lys939Gln, Ala499Val and PAT-/+) of Xeroderma pigmentosum group C (XPC) gene and bladder cancer susceptibility; however, the findings are inconclusive. In order to acquire a more precise estimation of the relationship, we performed a meta-analysis based on 10 studies including 3,934 cases and 4,269 controls for Lys939Gln, five studies including 2,113 cases and 2,249 controls for Ala499Val, and seven studies including 2,834 cases and 3,048 controls for PAT-/+ polymorphism. We searched publications from EMBASE, MEDLINE, and Chinese Biomedical. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model according to the between-study heterogeneity. We found that all studied polymorphisms were individually associated with increased overall cancer risks, as shown by ORs (95% CIs) below: the Lys939Gln (Gln/Gln vs. Lys/Lys: OR = 1.39, 95% CI = 1.08-1.79; recessive model: OR = 1.42, 95% CI = 1.11-1.83; and allele comparing: OR = 1.12, 95% CI = 1.003-1.24), the Ala499Val (Val/Val vs. Ala/Ala: OR = 1.82, 95% CI = 1.19-2.79; recessive model: OR = 1.70, 95% CI = 1.18-2.46; and allele comparing: OR = 1.23, 95% CI = 1.01-1.50), and the PAT-/+ (+/+ vs. -/-: OR = 1.36, 95% CI = 1.03-1.79 and recessive model: OR = 1.34, 95% CI = 1.06-1.70). Furthermore, stratification analyses demonstrated an increased risk for Asian populations as to the Lys939Gln and PAT-/+ whereas for Caucasian populations as to the Ala499Val polymorphism in the homozygous and recessive models. Despite some limitations, this meta-analysis suggests that XPC polymorphisms are associated with bladder cancer risk, but this association warrants further validation in well-designed studies with large sample sizes.

Anticancer drug-loaded multifunctional nanoparticles to enhance the chemotherapeutic efficacy in lung cancer metastasis.

BACKGROUND: Inhalation of chemotherapeutic drugs directly into the lungs augments the drug exposure to lung cancers. The inhalation of free drugs however results in over exposure and causes severe adverse effect to normal cells. In the present study, epidermal growth factor (EGF)-modified gelatin nanoparticles (EGNP) was developed to administer doxorubicin (DOX) to lung cancers. RESULTS: The EGNP released DOX in a sustained manner and effectively internalized in EGFR overexpressing A549 and H226 lung cancer cells via a receptor-mediated endocytosis. In vitro cytotoxicity assay showed that EGNP effectively inhibited the growth of A549 and H226 cells in a dose-dependent manner. In vivo biocompatibility study showed that both GNP and EGNP did not activate the inflammatory response and had a low propensity to cause immune response. Additionally, EGNP maintained a high therapeutic concentration in lungs throughout up to 24 h comparing to that of free drug and GNP, implying the effect of ligand-targeted tumor delivery. Mice treated with EGNP remarkably suppressed the tumor growth (~90% tumor inhibition) with 100% mice survival rate. Furthermore, inhalation of EGNP resulted in elevated levels of cleaved caspase-3 (apoptotic marker), while MMP-9 level significantly reduced comparing to that of control group. CONCLUSIONS: Overall, results suggest that EGF surface-modified nanocarriers could be delivered to lungs via inhalation and controlled delivery of drugs in the lungs will greatly improve the therapeutic options in lung cancer therapy. This ligand-targeted nanoparticulate system could be promising for the lung cancer treatment.

The potential relationship between uric acid and the recovery in sudden sensorineural hearing loss.

OBJECTIVE: Serum uric acid is proven to be associated with chronic hearing loss, but its effect on Sudden Sensorineural Hearing Loss (SSNHL) is unclear. This study aims to evaluate the prognostic values of serum uric acid levels in SSNHL patients. METHODS: The clinical records of SSNHL patients were retrospectively reviewed. Patients were divided into different groups based on hearing recovery and audiogram type, and uric acid levels were compared. Based on uric acid levels, patients were categorized into normouricemia and hyperuricemia groups, and clinical features and hearing recovery were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: In total, 520 SSNHL patients were included in this study, including 226 females and 294 males. In female patients, 186 patients were included in the normouricemia group, and 40 patients were enrolled in the hyperuricemia group. Significant differences were observed in uric acid levels, Total Cholesterol (TC), rate of complete recovery, and slight recovery between the two groups. In male patients, 237 subjects were categorized into the normouricemia group, and 57 patients were included in the hyperuricemia group. The rate of complete recovery and slight recovery was lower in the hyperuricemia group compared to the normouricemia group. All patients were further divided into good recovery and poor recovery groups based on hearing outcomes. The uric acid levels, initial hearing threshold, rate of hyperuricemia, and TC were lower in the good recovery group than the poor recovery group both in female and male patients. Binary logistic regression results showed that uric acid levels, initial hearing threshold, and hyperuricemia were associated with hearing recovery. CONCLUSION: Hyperuricemia might be an independent risk factor for hearing recovery in SSNHL patients. Serum uric acid and initial hearing threshold possibly affected the hearing outcome in males and females with SSNHL. LEVEL OF EVIDENCE: Level 4.

S100A2 upregulates GLUT1 expression to promote glycolysis in the progression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor. Among the S100 protein family members, the imbalance of S100 calcium-binding protein A2 (S100A2) was related to the pathogenesis of several types of cancer, and S100A2 has been reported to be upregulated in the plasma of NPC patients; however, its specific role in NPC pathogenesis remains unclear. Thus, this study aims to determine the potential role of S100A2 in NPC to provide novel insights into NPC management. C666-1 and NPC/HK-1 cells were transfected with S100A2 silencing/overexpression (si/oe) constructs. For in vivo investigations, NPC/HK-1 cells were transfected with si/oe-S100A2 to induce tumor formation in nude mice. Cellular viability and apoptosis were assessed using the CCK8 assay, colony-forming assay, and flow cytometry. Glucose uptake and lactate production levels were quantified using biochemical assays. S100A2 expression was measured via RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence were performed to determine the levels of S100A2, PI3K, AKT, p-PI3K, p-AKT, GLUT1, HK-2, LDHA, and ki-67 proteins. S100A2 expression levels were significantly higher in NPC cancer tissues than in adjacent tissues. Similarly, C666-1 and NPC/HK-1 cells exhibited increased S100A2 expression, and silencing S100A2 significantly inhibited NPC cell viability, proliferation, glucose uptake, and lactate production, and induced apoptosis and decreased the protein levels of GLUT1, LDHA, and HK2 in NPC cells. Conversely, S100A2 overexpression enhanced these characteristics in NPC cells but could be mitigated by the PI3K/AKT inhibitor (LY294002). Silencing S100A2 suppressed the tumor formation of NPC/HK-1 cells, while S100A2 overexpression promoted tumor formation and could be hindered by a GLUT1 inhibitor (WZB117). S100A2 is upregulated in cancer tissues of NPC patients and was found to promote proliferation, glycolysis, and tumor formation in NPC cells through its interaction with GLUT1.

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma-a retrospective cohort study.

Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4+ T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker. Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes. Results: The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P<0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085). Conclusions: In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Radiotherapy for Primary Tracheal Carcinoma: Experience at a Single Institution.

BACKGROUND: There is limited understanding of tracheal carcinoma (TC) because of its rarity. We examined the efficacy of radiotherapy (RT) for patients with primary TC. METHODS: We analyzed the records of 32 patients with primary TC who received RT at our center between November 1996 and December 2016. RESULTS: Thirteen patients received adjuvant RT and 18 received definitive RT. Eight patients achieved complete remission (CR) after definitive RT. Among all patients, the 5-year overall survival (OS) rate was 46.9% and the locoregional progression free survival (LRPFS) rate was 68.1%. Univariate analysis indicated the 5-year OS was better in those with adenoid cystic adenocarcinoma than squamous cell carcinoma (P = 0.001); the 5-year LRPFS was better in patients who received surgical resection than those who did not (92.9% vs 46.4%, P = 0.013) and in patients who received postoperative RT than in those who received definitive RT (91.7% vs 50.1%, P = 0.038). A sub-group univariate analysis indicated the 5-year PFS was better for those who received at least 68 Gy of radiation (44.4% vs 13.0%, P = 0.044). Patients who achieved CR had a better 5-year PFS than those who did not (57.1% vs 10%, P = 0.006). No patients had a toxicity of grade 3 or more. CONCLUSIONS: Adjuvant and definitive RT are safe and effective treatments for TC. Patients who received dosages of 68 Gy or more and who had complete tumor regression following definitive RT seemed to have better long-term survival.

Analysis of cervical and retropharyngeal lymph node metastases in the patients with hypopharyngeal carcinoma with computed tomography and magnetic resonance imaging.

BACKGROUND AND OBJECTIVE: Hypopharyngeal carcinoma has a high risk for early regional lymphatic dissemination. However, reports about regional lymph node metastases, especially retropharyngeal lymph node metastases, are rare. This research explored the spread of hypopharyngeal carcinoma, especially metastases of the retropharyngeal lymph nodes by studying computed tomography (CT) and magnetic resonance imaging (MRI) images. METHODS: The CT/MRI images of 88 patients with pathologically confirmed hypopharyngeal carcinomas that were performed at our hospital between August 2000 and March 2009 were analyzed retrospectively. The interrelations among local stage and lymph nodes in various regions were analyzed by Chi2 test and multivariate logistical regression. RESULTS: The rate of regional lymph node metastasis for all patients was 73.9%, and the highest rates of positive lymph nodes were at levels IIa (61.4%), IIb (44.3%), and III (37.5%). Metastases to levels I, IV, V, and VI were rare, as were retropharyngeal lymph-node metastases, which were always combined with metastases at levels II and III. Univariate analysis showed that level-IV metastases correlated to metastases at levels Ib and III; retropharyngeal lymph node metastases were correlated to level IIb and bilateral cervical lymph node metastases. Multivariate analysis showed that level-VI metastases correlated to level IV and that retropharyngeal lymph-node metastases correlated to bilateral cervical lymph node metastases. CONCLUSIONS: Regional lymph node metastases in patients with hypopharyngeal carcinoma follow some regulations, and skip metastasis is rare. The highest rates of positive lymph nodes are at levels II and III. Bilateral lymph node metastases may be a risk factor for retropharyngeal lymph node metastases.

CT-guided needle biopsy through mandibular area for the diagnosis of nasopharyngeal carcinoma in the parapharyngeal space.

BACKGROUND AND OBJECTIVE: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC. METHODS: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus. RESULTS: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment. CONCLUSIONS: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.

Clinical Efficacy of HiPorfin Photodynamic Therapy for Advanced Obstructive Esophageal Cancer.

OBJECTIVE: To explore the clinical efficacy of HiPorfin photodynamic therapy for advanced esophageal cancer and evaluate its impact on survival. METHODS: Retrospective analysis of 32 patients with advanced obstructive esophageal cancer at our institution from September 2013 to December 2016. HiPorfin was infused as the photosensitizer at a dose of 5 mg/kg, and after 48 hours, 630-nm laser irradiation was subsequently performed through an optical fiber that passed through the biopsy channel of a flexible endoscope. RESULTS: The effectiveness rate was 78.1% (25/32), and the significant efficacy rate was 56.3% (18/32). The dysphagia score decreased from 3.43 ± 0.73 to 1.79 ± 0.53 (P < .05). There was no grade 3 or more toxicity. The median overall survival was estimated to be 16 months. Univariate analysis showed higher overall survival with a Karnofsky Performance Status score ≥80 compared with a Karnofsky Performance Status score <80 (hazard ratio: 2.626; 95% CI: 1.091-6.322; P = .024). Overall survival was higher in patients who had received radiation therapy than in patients who did not receive radiation therapy (hazard ratio: 3.574; 95% CI: 1.501-8.510; P = .002). CONCLUSION: Photodynamic therapy is an effective method for advanced esophageal cancer. The side effects are mild, and the short-term effect is good, especially in the relief of dysphagia. Photodynamic therapy can prolong the survival of patients with advanced esophageal cancer, and the Karnofsky Performance Status score and previous radiation therapy have a significant effect on the overall survival.

The potential relationship between uric acid and the recovery in sudden sensorineural hearing loss

Abstract Objective Serum uric acid is proven to be associated with chronic hearing loss, but its effect on Sudden Sensorineural Hearing Loss (SSNHL) is unclear. This study aims to evaluate the prognostic values of serum uric acid levels in SSNHL patients. Methods The clinical records of SSNHL patients were retrospectively reviewed. Patients were divided into different groups based on hearing recovery and audiogram type, and uric acid levels were compared. Based on uric acid levels, patients were categorized into normouricemia and hyperuricemia groups, and clinical features and hearing recovery were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. Results In total, 520 SSNHL patients were included in this study, including 226 females and 294 males. In female patients, 186 patients were included in the normouricemia group, and 40 patients were enrolled in the hyperuricemia group. Significant differences were observed in uric acid levels, Total Cholesterol (TC), rate of complete recovery, and slight recovery between the two groups. In male patients, 237 subjects were categorized into the normouricemia group, and 57 patients were included in the hyperuricemia group. The rate of complete recovery and slight recovery was lower in the hyperuricemia group compared to the normouricemia group. All patients were further divided into good recovery and poor recovery groups based on hearing outcomes. The uric acid levels, initial hearing threshold, rate of hyperuricemia, and TC were lower in the good recovery group than the poor recovery group both in female and male patients. Binary logistic regression results showed that uric acid levels, initial hearing threshold, and hyperuricemia were associated with hearing recovery. Conclusion Hyperuricemia might be an independent risk factor for hearing recovery in SSNHL patients. Serum uric acid and initial hearing threshold possibly affected the hearing outcome in males and females with SSNHL. Level of evidence Level 4.

Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From August 2009 to August 2013, patients with stage III-IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)-residual and gross tumor volume of cervical lymph node (GTVnd)-residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated. RESULTS: A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression-free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively. CONCLUSION: After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy ofradiation dose to the tumorregression field may be feasible and need further investigation.

Increased Expression of Cullin 3 in Nasopharyngeal Carcinoma and Knockdown Inhibits Proliferation and Invasion.

This study aimed to investigate the clinical significance of cullin 3 expression in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism of cullin 3 underlying the growth and metastasis of NPC cells. Our findings showed that the expression levels of cullin 3 were significantly increased in both NPC tissues and cell lines. A strong positive correlation was found between cullin 3 expression and the Ki-67-based proliferation index in NPC tissues. Moreover, cullin 3 overexpression was correlated with local relapse and distant metastasis in NPC patients. In vitro experiments showed that knockdown of cullin 3 caused a significant reduction in the proliferation of NPC cells, probably by inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited colony formation and the migratory and invasive capacities of NPC cells. The expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related proteins were also meditated by cullin 3 in NPC cells. Based on these findings, we demonstrated that cullin 3 plays a promoting role in the malignant progression of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be used as a promising therapeutic target for NPC.

Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro.

Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.

Univariate and multivariate analyses for postoperative bleeding after nasal endoscopic surgery.

CONCLUSIONS: Our study suggested that the major risk factors for postoperative bleeding after nasal endoscopic surgery (NES) included hypertension, long-term non-steroidal anti-inflammatory drugs (NSAIDs), and previous nasal surgery. The use of preoperative corticosteroids is a valuable measure for reducing postoperative bleeding after NES. OBJECTIVES: To explore risk factors for postoperative bleeding after NES and find effective measures to reduce or prevent the condition. METHODS: A total of 641 patients who underwent NES were analyzed retrospectively. Univariate analysis and logistic regression were performed to find potential risk factors. RESULTS: The incidence of postoperative bleeding after NES was 8.4%. Multivariate logistic regression analysis revealed that the occurrence of postoperative bleeding after NES was positively associated with hypertension, long-term NSAIDs, previous NES, and modified submucosal septoplasty, but negatively associated with the use of preoperative corticosteroids.

Prognostic value of tumor volume for patients with nasopharyngeal carcinoma treated with concurrent chemotherapy and intensity-modulated radiotherapy.

PURPOSE: We aimed to analyze prognostic factors in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT); in addition, we aimed to elucidate the value of primary gross tumor volume (GTVp) in predicting prognosis of patients. METHODS: Between February 2001 and December 2008, 321 patients with NPC treated with concurrent chemotherapy and IMRT were analyzed retrospectively. GTVp was calculated from treatment planning computed tomography scans. A receiver operating characteristics (ROC) curve was used to determine the best cutoff point of GTVp. RESULTS: The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) for NPC patients were 93.8, 80.1, 73.0, and 83.7 %, respectively. Univariate and multivariate analyses indicated that GTVp had exhibited a statistically significant correlation with LFFS, DMFS, DFS, and OS (P < 0.05, all), whereas T classification was not an independent prognostic factor. According to ROC curve analysis, 49 and 19 mL were determined as the cutoff points of GTVp for local control and distant metastasis, respectively. Based on this, 321 patients were divided into three volume subgroups. LFFS, DMFS, DFS, and OS demonstrated significant differences among patients in different volume subgroups (P < 0.001, all) and were superior to T classification for predicting prognosis of NPC patients. CONCLUSIONS: Primary gross tumor volume is an independent prognostic factor in local control, distant metastasis, disease-free survival, and overall survival in NPC. An adjusted TNM staging system that includes GTVp as a quantitative indicator to evaluate prognosis is warranted.

[Potential risk factors of excessive epistaxis after endoscopic endonasal surgery].

OBJECTIVE: To investigate the potential risk factors and management of excessive epistaxis after endoscopic endonasal surgery (EES). METHOD: Six hundred and forty-one patients who underwent EES in our hospital from December 2011 to December 2012 were reviewed retrospectively. Factors which potentially affect the incidence of excessive epistaxis after EES were analyzed with univariate and multivariate logistic regression model. RESULT: The incidence rate of excessive epistaxis after EES was 8.4% in our study. Multivariate logistic regression analysis revealed that history of previous EES, along with other four factors, correlated significantly with the occurrence of excessive epistaxis after EES. CONCLUSIONS: Previous EES, along with other three factors, may increase the chance of excessive epistaxis after EES, while pre-operative corticosteroid therapy may reduce the risk to some extent.

Using CT or MRI to assess locoregional spread to determine the radiotherapy target of hypopharyngeal carcinoma.

AIM: To identify the locoregional extension of hypopharyngeal carcinoma (HPC), particularly the invasion of the nasopharynx and skull base, and metastasis of level VI and retropharyngeal lymph node (RPLN) by investigating computed tomography (CT) and magnetic resonance (MR) images; together with the radiotherapy target of HPC. METHODS: CT and MR images of 186 patients with pathologically confirmed HPC between Aug 2000 and Dec 2010 were analyzed retrospectively. We used the χ(2) test and logistic regression to analyze local invasion and regional spread and to determine their relationships. RESULTS: Of the 186 patients, there was only one case of invasion of the nasopharynx without skull base involvement. The rate of regional node metastasis was 79%. There was no significant relationship between T stage and lymph node metastasis (P = 0.1). Level IV metastasis (P = 0.001), RPLN metastasis (P = 0.041) and esophageal invasion (P = 0.003) were significantly correlated with level VI metastasis. Primary tumor subsite (P = 0.024), bilateral cervical node metastasis (P < 0.001) and size of cervical nodes (P = 0.01) significantly contributed to the occurrence of RPLN metastasis. CONCLUSION: The locoregional spread of HPC occurs via certain routes. It is potentially unnecessary to routinely and prophylactically irradiate the nasopharynx and skull base. Patients with early stage HPC should receive bilateral cervical prophylactic irradiation. The decision regarding the administration of prophylactic irradiation to the level VI and RPLN areas should be according to the relative risk factors.

Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer.

Combination of more than one therapeutic strategy is the standard treatment in clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a nanoparticulate system will suppress the tumor growth. In the present study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome to systemically deliver in a lung cancer model (A549). The resulting nanoparticle (lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co-delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226) in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase 3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo-DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable tumor inhibition response was attributed to the synergistic effect of DTX potency and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental results suggest that co-delivery of DTX and siRNA could be promising approach in the treatment of lung cancers.

Prognostic significance of tumor volume in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy.

BACKGROUND: This study was undertaken to analyze the correlation between primary gross tumor volume (GTVp) and prognosis in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). METHODS: Between February 2001 and December 2006, 305 patients with NPC treated with IMRT were analyzed retrospectively. GTVp was calculated from treatment planning CT scans. RESULTS: Univariate and multivariate analyses indicated that GTVp had a statistically significant correlation to local control, distant metastasis, and overall survival in patients with NPC, whereas T classification was not an independent prognostic factor. Among patients classified with N0-1 and N2-3, there were significant differences in the rates of distant metastasis between those with GTVp smaller and larger than 25 mL (p < .001 and p = .002, respectively). CONCLUSIONS: GTVp is highly significant in evaluating local control, distant metastasis, and overall survival of patients with NPC treated with IMRT. Therefore, it is recommended that GTVp be included in the new TNM classification system.

Correlation between nasopharyngeal carcinoma tumor volume and the 2002 International Union Against Cancer tumor classification system.

BACKGROUND: The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system. METHODS: Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis. RESULTS: Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 - 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis. CONCLUSION: Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system.