LMP2-DC Vaccine Elicits Specific EBV-LMP2 Response to Effectively Improve Immunotherapy in Patients with Nasopharyngeal Cancer.

OBJECTIVE: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). METHODS: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 5 LMP2-DCs by intradermal injection at week 0 and after the second and fourth weeks. Specific responses to LMP2 were detected by enzyme-linked immunospot (ELISPOT) assay at week 0 and at the fifth and eighth weeks. Local clinicians performed the follow-up and tracking of patients. RESULTS: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. CONCLUSION: In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.

A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC).

BACKGROUND: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients. METHODS: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated. RESULTS: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode. CONCLUSION: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

Correlation of metastasis-associated protein expression with prognosis and chemotherapy in nasopharyngeal carcinoma.

The aim of this study was to elaborate the correlation between metastasis-associated protein (MTA) family and the occurrence, progression, prognosis and chemotherapy efficiency in nasopharyngeal carcinoma (NPC).The expression of MTA1, MTA2 and MTA3 protein were detected by immunohistochemistry in a tissue microarray (TMAs) which contains tissue samples of 152 NPC patients embedded by formalin-fixed paraffin. The MTA proteins were mainly expressed in the nuclei of NPC tissues and the correlations between MTAs expression and clinical parameters as well as prognosis of NPC patients showed ethnical differences according to statistically analysis. The results showed that in Han ethnic group, MTA1 expression was positively correlated with N staging, while the expression of MTA2 was negatively correlated with age, and the expression of MTA3 was positively correlated with gender. Patients with high MTA1 expression had poorprognosis. In Zhuang ethnic group, only MTA3 expression was positively correlated with age, recurrence and metastasis of NPC patients; neither MTA1 nor MTA2 expression had any correlation with clinical indexes. Patients with high MTA3 expression had unfavorable prognosis. In addition, our results showed that overall survival among Zhuang NPC patients with low expression of MTA2 increased significantly owing to "carboplatin + fluorouracil" chemotherapy. This therapeutic success, however, did not translate to longer overall survival among Han NPC patients. The biological function of MTA protein family in NPC patients was different among different ethnic groups. In conclusion, we demonstrated that MTAs had a certain tumor promoting function in patients with NPC, and the biological functions of MTAs might be ethnic differences, which suggesting MTAs to be important markers for guiding clinical treatment of NPC.

Influence of endoscopic sinus surgery on the quality of life of patients with early nasopharyngeal carcinoma and the analysis of prognosis-related factors.

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ2 = 4.403, p = 0.036; χ2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

Management of intractable epistaxis in patients who received radiation therapy for nasopharyngeal carcinoma.

To report clinical manifestations, bleeding point localization, and outcomes of management in 16 patients with 16 instances of intractable epistaxis after radiation therapy for nasopharyngeal carcinoma. Retrospective chart review of 16 patients with nasopharyngeal carcinoma (mean age 52.06 ± 14.37 years) with 16 instances of intractable epistaxis during the past 5 years, whose diagnosis was confirmed by angiography (n = 10) or MRI/CT imaging studies and clinical manifestations (n = 6). The mean radiation dose to the affected carotid artery was 101.37 ± 34.85 Gy. Bleeding points were detected in the internal carotid artery (n = 8) or external carotid artery (n = 8). Detachable balloons were used in one affected artery for vascular occlusion; six were treated using an absorbable gelatin sponge (n = 4) or microcoils (diameter 1 mm) (n = 2). Endovascular embolization was successful in seven radiation carotid blowout syndromes with cessation of hemorrhage. One patient underwent external carotid artery ligation and one patient recovered without treatment. The clinical follow-up was 3 months. Therapeutic endovascular embolization of intractable epistaxis is both efficient and safe. It should be considered as the primary treatment modality in intractable epistaxis of nasopharyngeal carcinoma.

[Management of intractable epistaxis and bleeding points localization of post-therapy nasopharyngeal carcinoma].

OBJECTIVE: To investigate the bleeding points and the management of post-therapy nasopharyngeal carcinoma intractable epistaxis. METHODS: The bleeding points, treatment as well as its effects were studied retrospectively in 16 cases of post-therapy nasopharyngeal carcinoma intractable epistaxis. Among them 7 cases had been treated once, 9 cases recurred and received second treatment. Nasopharynx area had received radiotherapy from 70-160 Gy. Nasopharyngeal carcinoma intractable epistaxis occurred in 1-204 months (median time 13 months) after radiotherapy. RESULTS: The bleeding points were found in the following different sites: internal carotid artery 8 patients, the internal maxillary artery of external carotid artery 7 patients, the arteriae pharyngea ascendens of external carotid artery 1 patient. All patients were tally by oronasal packing or intranasal balloons, 9 cases were carried out emergency tracheotomy. Post-therapy nasopharyngeal carcinoma intractable epistaxis was well controlled by transcatheter internal carotid artery balloon embolization in 1 case, transcatheter maxillary artery embolization in 6 cases, external carotid artery ligation in 1 case. Voluntarily stopping bleeding in 1 case. Seven cases among internal carotid artery 8 patients died, 1 case recovery. Seven patients of the internal maxillary artery of external carotid artery and 1 patient of the arteriae pharyngea ascendens of external carotid artery was recovery. There were no complications during a followed-up for 1-3 months after treatment. CONCLUSIONS: After determined the points of post-therapy nasopharyngeal carcinoma epistaxis by angiography mainly the key factors in treatment of epistaxis of post-therapy nasopharyngeal carcinoma were vigorous applicated intractable endovascular treatment, nasal packing and tracheostomy. Internal carotid artery bleeding of post-therapy nasopharyngeal carcinoma still have the high mortality rate at present.

[Choice of surgical approaches for salvage surgery of primary lesion recurrence and residual cases of nasopharyngeal carcinoma].

OBJECTIVE: The choice of surgical approaches for salvage surgery based on the location and invasion of recurrent and residual lesions of nasopharyngeal carcinoma (NPC), surgical results, complications, and survival were assessed. METHODS: Thirty-seven cases with recurrent and residual lesions of NPC underwent salvage surgery between March 1991 and January 2005 were analysed retrospectively. Of 37 patients, 23 were men and 14 women, with a median age of 46.5 years (26 - 57 years); 4 were at stage I, 10 at stage II, 14 at stage III, and 9 at stage IV; 5 cases were with cervical metastasis, including 3 cases of N1 and 2 cases N2. All recurrent and residual lesions of NPC were determined by biopsy. On the location and invasion of recurrent and residual lesions of NPC, 8 cases underwent endoscopic resection of lesions, 12 cases of the palate nasopharyngectomy, 5 cases of maxillary swing, 4 cases of maxillary swing plus prerenal approach, 2 cases of lateral rhinotomy plus coronal flap approach, and 6 cases transfacial plus nasal pyramid swing approach. Five cases with cervical metastasis received neck dissection in addition to the operations for recurrent and residual lesions of NPC. Postoperatively 31 cases received radiotherapy with dosage of 60 Gy, among them 15 cases with concurrent chemoradiation therapy, and 6 cases with clear surgical margin did not received radiotherapy or chemotherapy. The cases were followed up for 12 - 72 months, with a median of 45 months. RESULTS: Total resection for the recurrent and residual lesions of NPC accounted for 91.8% (34/37) and subtotal resection for 8.2% (3/37). The accident of perioperative complications was 24.3% (9/37). The 3- and 5-year overall disease-free survival rates (DFSR) were 62.1% and 43.3%, respectively. The 3- and 5-year overall survival rates (OSR) were 72.9% and 51.3%, respectively. The 5 year DFSR of cases at stage I-IV were 100%, 40%, 28% and 11% (χ(2) = 10.0, P < 0.01), respectively. The 5 year OSR were 100%, 70%, 35% and 28% (χ(2) = 11.5, P < 0.01), respectively. CONCLUSIONS: Salvage surgery is a justified treatment for the recurrent and residual lesions of NPC, by which some patients with recurrent and residual lesions of NPC can be salvaged.

[Plasma resistin level in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the changes and clinical implications of plasma resistin level in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Plasma resistin level was measured by radioimmunoassay in 30 obese OSAHS patients (obese OSAHS group), 7 in the low apnea hypopnea index (AHI) subgroup, 9 in the medium AHI subgroup, and 14 in the high AHI subgroup, 30 obese subjects (obese group), and 28 normal healthy adults (control group). Stepwise multiple linear regression analysis was conducted to determine the correlation of plasma resistin level with body mass index (BMI), body fat percentage, waist to hip ratio (WHR), fasting blood glucose (FBG), blood lipid, AHI, and lowest arterial oxygen saturation (LSaO(2)). RESULTS: The plasma resistin levels of the obese OSAHS group and obese group were (8.48 +/- 1.44) and (7.60 +/- 1.53) microg/L respectively, both significantly higher than that of the control group [(5.78 +/- 1.62) microg/L, both P < 0.05], and that of the obese OSAHS group was significantly higher than that of the obese group (P < 0.05). The plasma resistin level of the high AHI obese OSAHS subgroup was (9.60 +/- 0.51) microg/L, significantly higher than those of the medium and low AHI obese OSAHS subgroups [(7.96 +/- 1.06) and (6.90 +/- 1.32) microg/L respectively, both P < 0.01]. Correlation analysis demonstrated that the fasting plasma resistin level was positively correlated with BMI, neck circumference, waist circumference, WHR, FBG, total cholesterol, triglyceride, and AHI (r = 0.52, 0.66, 0.74, 0.52, 0.59, 0.48, 0.46, and 0.80, all P < 0.05); and negatively correlated with high-density lipoprotein cholesterol and LSaO(2) (r = -0.52, r = -0.60, both P < 0.01). A stepwise multiple linear regression analysis showed that AHI was the most significant contributing factor for the increased plasma resistin level in the obese OSAHS group (R(2) = 0.618). CONCLUSIONS: Plasma resistin level in obese OSAHS patients are increased, and are positively correlated with AHI. It may be used as an important biological index to evaluate the severity of OSAHS.

[Relationship between expression of multidrug-resistant genes in nasopharyngeal carcinoma tissue and sensitivity to chemotherapy].

OBJECTIVE: To study the relationship between multidrug-resistant (MDR) expression in nasopharyngeal carcinoma (NPC) and its sensitivity to chemotherapy. METHODS: The specimens of 23 NPC cases were studied by immunohistochemistry with monoclonal antibody of P-glycoprotein (P-gp), multidrug resistance relation protein (MRP), lung-resistance related protein (LRP), topoisomerase II (Topo II), thymidylate synthase (TS), glutathione-S-transferase (GST-pi). Among them, 20 specimens were taken from primary NPC lesion which were treated with two course of cisplatin (DDP) and 5-fluorouracil (5-FU), 3 specimens were taken from cervical lymph-node of recurrent NPC patients who were treated by radical dissection. RESULTS: Various MDR parameters were expressed differently in 22 cases except for 1 clear cell carcinoma case. The difference was statistically significant (P < 0.05). However, there were no significant difference of MDR expression either among various carcinoma pathomorphology cell groups or among different clinical stage groups. Expression of LRP and TS were found in 10 and 14 cases respectively and the chemotherapy responders rates were 20% (2/10) and 28.5% (4/14) respectively. While the chemotherapy responders rates were 70% (7/10) and 5/6 in cases without expression. There was significant difference (P < 0.001, and P < 0.05). CONCLUSION: The NPC patients with LRP and TS expression may be less sensitive to chemotherapy with DDP + 5-FU.