Background:To protect neurological tissues,underdosing occurs in most cases ofT4 nasopharyngeal carcinoma (NPC) with intracranial extension.In this study,we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy.Methods:We prospectively enrolled patients who had non-metastatic T4 NPC with intracranial extension treated between January 2009 and November 2013.The prescribed dose was 66.0-70.4 Gy to the primary planning target volume (primary gross tumor volume [GTVp;i.e.,the nasopharyngeal tumor] + 5.0 mm).Dose-volume histogram parameters were calculated,including minimum point dose (Dmin) and dose to 95％ of the target volume (D9s).All patients received chemotherapy with the cisplatin,5-fluorouracil,and docetaxel regimen.Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test.Results:In total,41 patients were enrolled.The local partial response rate was 87.8％ after induction chemotherapy.With a median follow-up of 51 months,7 patients experienced failure in the nasopharynx;the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4％ and 90.2％,respectively.The actual mean Dmin to the GTVp was 55.2 Gy (range 48.3-67.3 Gy),and D9s was 61.6 Gy (range 52.6-69.0 Gy).All doses received by neurological organs remained well within their dose constraints.No patients developed temporal lobe necrosis or other neurological dysfunctions.Conclusions:With relative underdosed IMRT plus effective chemotherapy,the patients achieved satisfactory local control with few late toxicities of the central nervous system.Determining the acceptable extent of dosimetric inadequacy requires further exploration.

OBJECTIVETo investigate the incidence, MRI characteristics and invasion route of nasopharyngeal carcinoma (NPC) infiltrating the cavernous sinus.

METHODSThe data of 141 patients with histologically proven NPC collected from May 2003 to June 2004 were reviewed. All patients were examined by 1.5-tesla superconducting MR unit to evaluate the tumor extent. MR FSE technique was used for T1 WI and T2WI images in the axial plane, followed by FSPGR fat-suppressed gadolinium-enhancement for T1WI images in the axial and coronal sections. All MR images were interpreted and evaluated by two diagnostic radiologists, paying particular attention to the nasopharynx and cavernous sinus infiltration.

RESULTSMR imaging showed infiltration of 49 cavernous sinuses in 39 patients (27.7%). The most common MRI features were enlargement of cavernous sinus with unconventional enhancement (22/49, 44.9%), even with formation of mass inside the sinus (9/49, 18.4%). The other MRI image features were local or diffuse dura mater thickening of cavernous sinus and presence of obscure structure as intra-sinus blurs and hazies inside. The most common infiltration route is through the foramen ovale (18/49, 36.7%), or through both the foramen ovale and foramen lacerum (6/49, 12.2%).

CONCLUSIONIn NPC patients, MRI invasion is characteristically and clearly shown as changes in the cavernous sinus. Possession of this information is crucial for giving correct treatment. The main infiltrtion route is through foramen ovale.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cavernous Sinus ; pathology ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; Neoplasm Invasiveness ; Reproducibility of Results ; Vascular Neoplasms ; pathology

BACKGROUND AND OBJECTIVEConcurrent chemoradiation therapy (CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma (NPC). The effect of neoadjuvant chemotherapy followed by CCRT has not been determined. Therefore, we conducted 2 phase II studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel, cisplatin, and 5 fluorouracil (5-Fu) (TPF) followed by radiotherapy and concurrent cisplatin in patients with stage III and IV(A - B) NPC. This article is the preliminary report on treatment related toxicities and response.

METHODSGraded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria, only patients with stage III or IV(A-B) poorly differentiated or undifferentiated NPC (World Health Organization type II/III) were included. We planned to recruit 52 patients with stage III disease and 64 patients with stage IV(A - B) disease. All patients received neoadjuvant chemotherapy with TPF (docetaxel 75 mg/m(2), day 1; cisplatin 75 mg/m(2), day 1; 5 Fu 500 mg/(m2 x day), continuous intravenous infusion for 120 h), every 3 weeks for 3 cycles, followed by weekly cisplatin (40 mg/m(2)) concurrent with radiotherapy. Three dimensional conformal radiotherapy (3D CRT) and intensity modulated radiotherapy (IMRT) were used. Gross disease planning target volume (PTV), high risk and low risk subclinical PTV doses were prescribed at 70-76 Gy, 66-70 Gy, and 60-61.25 Gy at 1.75-2.0 Gy per fraction. The lower neck or supraclavicular fields may be treated with conventional AP/PA fields for a total of 54 Gy at 1.8 Gy per fraction. Patients were evaluated for tumor response after the completion of neoadjuvant chemotherapy, and at 3 months after radiation according to the Response Evaluation Criteria In Solid Tumors (RECIST). The latest version of the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE 3.0) was used for grading all adverse events.

RESULTSFifty nine patients were evaluable for treatment response. Thirty patients had stage III disease and 29 patients had stage IV(A-B). All patients completed RT to the prescribed dose and 2 cycles of neoadjuvant chemotherapy, with 51 patients (86.4%) completing 3 cycles. A total of 50 (84.7%) and 39 patients (66.1%) completed 4 weeks and 5 weeks of cisplatin during CCRT, respectively. The overall response rate in the primary site and the neck region were 94.9% [complete response (CR) in 25.4%] and 100% (CR in 19.6%) after completing neoadjuvant chemotherapy. At 3 months after RT, the CR rates increased to 96.6% and 90.2%, respectively. After a median follow up of 14.3 months, we observed 5 treatment failures and 2 deaths. The 1 year overall survival, distant metastasis free survival, and locoregional relapse free survival rates were 100%, 95.7%, and 97.7%, respectively. The rates of grade 3/4 myelosuppression and anorexia/nausea/vomiting during neoadjuvant chemotherapy were 55.9% and 16.9%, respectively. The corresponding rates were 11.9% and 23.7% during CCRT. Grade 3/4 mucositis, skin desquamation, and xerostomia occurred in 6.8%, 44.1%, and 27.1% of patients, respectively. There were no treatment related deaths.

CONCLUSIONSNeoadjuvant chemotherapy with TPF followed by CCRT was well tolerated with a manageable toxicity profile. Preliminary results are encouraging and warrant further investigation.

Adult ; Aged ; Anemia ; chemically induced ; etiology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Chemoradiotherapy ; adverse effects ; Chemotherapy, Adjuvant ; adverse effects ; Cisplatin ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; etiology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Nausea ; chemically induced ; etiology ; Neoadjuvant Therapy ; adverse effects ; Neoplasm Staging ; Neutropenia ; chemically induced ; etiology ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Remission Induction ; Survival Rate ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVEAim of our study was to compare hematological parameters in Tibetan natives with those in Han migrants living on the Tibet plateau in order to determine the potential effects of age, gender, and ethnicity on hematological response to hypoxia.

METHODSBlood hemoglobin (Hb, g/dl), hematocrit (Hct, %), red blood cells (RBC,10(6)/mm3) were measured in 3 588 healthy Tibetan natives and 3 371 Han migrants ranging in age from 5 to 72 years, living at a mean altitudes of 2 664 m, 3 813 m, 4 525m and 5 226 m.

RESULTSHemoglobin (Hb) concentration analysis was made by multiple regression equations relating hemoglobin to altitude and age. For 2 093 Han males, Hb = 9.612+ 0.001440xaltitude+ 0.06148xage. For 1 948 Tibetan males, Hb =12.202+ 0.000462xaltitude+ 0.02893xage. For 1 278 Han females, Hb = 10.858+ 0.000939xaltitude+ 0.02632xage. For 1 640 Tibetan females, Hb = 11.402+ 0.000626xaltitude+ 0.00412xage. Each of the four equations was statistically significant (P < 0.001), and had variance (r2) of 0.86 or more, indicating that altitude and age accounted for at least 85% of the variation in hemoglobin levels. The coefficients for altitude and for age were higher (P < 0.05) in Han males than in Tibetan males and higher (P < 0.05) in Han females than in Tibetan females. The Tibetan postmenopausal females had higher Hb values than premenopausal females only presented at altitude above 4 000 m while this phenomenon was beginning at altitude of 2 664 m among Han females.

CONCLUSIONWe conclude that gender and increasing age in Tibetans are associated with lower hemoglobin values than those in Han at high altitude, and we speculate that genetic factors seems to be important.

Adolescent ; Adult ; Aged ; Altitude ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Ethnic Groups ; Female ; Hematocrit ; Hemoglobins ; analysis ; Humans ; Hypoxia ; ethnology ; Male ; Middle Aged ; Tibet ; Transients and Migrants ; Young Adult

OBJECTIVETo discuss the method, the safety, the advantages and disadvantages of endoscopic thyroidectomy via chest and breasts.

METHODSFrom Mar. 2002 to Dec. 2006, endoscopic thyroidectomy via anterior chest and breast approach was performed in 500 patients, including 76 cases of Grave's disease (1 case had an opened operation history), 111 cases of thyroid adenoma, 291 cases of nodular goiter (10 cases have 1-2 opened thyroidectomy history, 2 cases secondary of hyperthyroidism), and 22 cases of thyroid carcinoma.

RESULTSThe endoscopic thyroidectomy was successfully carried out in 492 cases, including tumor enucleation in 50 cases, partial lobectomy in 210 cases, subtotal thyroidectomy in 212 cases (including 73 cases of Graves' disease), and lobectomy in 16 cases of thyroid carcinoma. The operative time length ranged from 40 to 270 min (mean 74.5 min). Mean operative blood loss was 5.5 ml (3-250 ml), no cases underwent blood transfusion. The drainage was taken out in the second or third days postoperatively. Postoperative hospital stay ranged from 3 to 8 days (mean 4.2 days). There were some complications including subcutaneous bleeding (3 cases), burn of the epidermal (1 case), inflammation of the incision (2 cases), subcutaneous bruising (3 cases), subcutaneous effusion (6 cases), thyroid crisis (1 case), and temporarily hoarseness of 2 cases. There were no complications such as permanence damage to recurrent laryngeal nerve or parathyroid glands. The complication rate was 3.6% (18/492). The hospital charges ranged from 7600 to 13,500 RM yuan. The average cost of endoscopic thyroidectomy was 10,510 RM yuan, in contrast to 5700 RM yuan for the open thyroidectomy patients. The post-operative following-up was 3 to 57 months (mean 27 months). All the patients were satisfied with the cosmetic results and the same curative effects as conventional surgery were obtained. However, 3 cases of nodular goiter, 1 case of thyroid carcinoma, and 1 case of Grave's disease were recurrence. The operations were converted into open surgery in 8 cases. The 22 cases with carcinoma were survival until now.

CONCLUSIONSEndoscopic thyroidectomy is a safe and effective method of thyroid surgery. Since all the minimal incisions are on concealed parts of the body, the obvious cosmetic effect of this method is guaranteed. Some disadvantages such as complications and more costs are needed to be improve.

Adolescent ; Adult ; Aged ; Breast ; surgery ; Child ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Thoracic Wall ; surgery ; Thyroidectomy ; methods ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the effects of myrrh extract on biological characteristics of human dermal fibroblasts (Fb), and to explore its possible mechanisms in promoting wound healing.

METHODSNormal Fb was isolated from human foreskin tissue and cultured in vitro. The third to fifth passages of Fb were used in the experiment. (1) Fb were planted onto 96-well plate and divided into control group, and 1 × 10(-4), 1 × 10(-3), 1 × 10(-2), 1 × 10(-1), 1, 10, 1 × 10(2) g/L myrrh water extract groups and myrrh ethanol extract groups according to the random number table. Fb in control group were cultured with DMEM medium containing 0.25% calf serum (briefly called low-concentration serum medium), and those in various concentrations of myrrh water extract and myrrh ethanol extract groups respectively with low-concentration serum medium containing corresponding concentration of 2 kinds of myrrh extract. After being cultured for 48 h, cell morphology was observed with inverted-phase contrast microscope, and Fb proliferation activity (denoted as absorbance value) was determined with MTT method. (2) Fb were respectively planted into flasks and dishes and divided into two groups according to the random number table. Fb in control group were cultured with low-concentration serum medium, and that in 1 g/L myrrh water extract group with low-concentration serum medium containing 1 g/L myrrh water extract. After being cultured for 72 h, Fb cell cycle and the type I and III collagen mRNA expression were respectively determined by flow cytometry and real-time fluorescent quantitative PCR. Data were processed with LSD-t test.

RESULTS(1) Fb in all groups grew in long-spindle shape, but the cell fusion was much obvious in 1 g/L myrrh water extract group than in control group. Fb absorbance value in 1 × 10(-3), 1 × 10(-2), 1 × 10(-1), 1, 10 g/L myrrh water extract groups was respectively 0.378 ± 0.032, 0.402 ± 0.007, 0.390 ± 0.038, 0.453 ± 0.036, 0.390 ± 0.037, all higher than that in control group (0.332 ± 0.044, with t value respectively 2.24, 2.93, 2.69, 5.73, 2.71, P values all below 0.05). Compared with that in control group, Fb absorbance value in 1 × 10(-4) g/L myrrh water extract group was not statistically different (0.312 ± 0.048, t = 2.84, P > 0.05), while that in 1 × 10(2) g/L myrrh water extract group was significantly lower (0.154 ± 0.009, t = 7.17, P < 0.05). Fb absorbance values in 1 × 10(-3), 1 × 10(-1), 1, 10, 1 × 10(2) g/L myrrh ethanol extract groups were significantly lower than that in control group (with t values from 2.30 to 24.79, P values all below 0.05). (2) Compared with those in control group [(82.2 ± 7.9)% and (13.3 ± 2.3)%, (4.5 ± 0.8)%], the percentage of cells in G0/G1 phase in 1 g/L myrrh water extract group was obviously decreased [(74.3 ± 6.3)%, t = 6.77, P < 0.05], while those in S and G2/M phases increased [(16.6 ± 3.4)%, (9.1 ± 1.6)%, with t value respectively 7.53, 6.34, P values below 0.05]. Compared with those in control group (1.00 ± 0.05, 1.00 ± 0.06), the mRNA level of collagen III in 1 g/L myrrh water extract group was significantly up-regulated (1.38 ± 0.12, t = 3.81, P < 0.01), while that of collagen I was not statistically different (0.89 ± 0.08, t = 1.17, P > 0.05).

CONCLUSIONSMyrrh water extract can notably promote the proliferation of Fb, accelerate the cell cycle of Fb, and up-regulate the mRNA expression of type III collagen in Fb, which may be related to its mechanisms in promoting wound healing.

Cell Cycle ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Collagen Type III ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Plant Extracts ; pharmacology ; RNA, Messenger ; genetics ; Terpenes ; pharmacology

BACKGROUND AND OBJECTIVEEarly diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC.

METHODSA proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later.

RESULTSEight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples.

CONCLUSIONSELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

Adult ; Aged ; Algorithms ; Antibodies, Viral ; blood ; Antigens, Viral ; blood ; Biomarkers, Tumor ; blood ; Capsid Proteins ; blood ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; Neoplasm Proteins ; blood ; Proteomics ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

BACKGROUNDAsthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma.

METHODSThirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group: control group, asthma group, ovalbumin (OVA) + OVA group, lipopolysaccharide (LPS) group and LPS + OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge 14 days later. The OVA + OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS + OVA group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin (IL)-4, interferon-gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Th1 and Th2 cells.

RESULTSThe pathological changes in the LPS + OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS + OVA groups were higher than in the control group and the OVA + OVA group (P < 0.05). The level of IgE was higher in the asthma, LPS and LPS + OVA groups than in the control group and the OVA + OVA group (P < 0.05). By flow cytometry analysis, the Th1/Th2 ratio was lower in the LPS + OVA and asthma groups than in other groups (P < 0.05).

CONCLUSIONSThe experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

Animals ; Bronchi ; pathology ; Cell Count ; Cytokines ; physiology ; Disease Models, Animal ; Epithelial Cells ; pathology ; Hypersensitivity ; etiology ; Immunoglobulin E ; blood ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Lipopolysaccharides ; toxicity ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Wistar

Objective To assess the dosimetric impact on the target volumes and organs at risk ( OARs) using simultaneous integrated boost ( SIB ) for the hypoxic regions of the pancreatic cancer patients treated with stereotactic body radiotherapy ( SBRT ) , and to predict an optimal way of SIB. Methods The setup corrections guided by 100 sets of CBCT scans of 10 patients previously treated with SBRT were imported to the treatment planning system ( TPS ) to recalculate the dose to the target and OARs. Two tumor control probability ( TCP ) models were applied to calculate the TCP under various hypoxic situations. The correlations between the TCP and target dose were analyzed. Results Without setup corrections, the PTV and ITV were underdosed by 8. 9％ and 9. 2％ on average respectively relative to planed dose. With setup corrections, the mean dose to PTV and ITV coverage were 1. 6％ and 1. 3％lower than planned respectively. The mean deviations of OAR dose were between -0. 11 Gy and 0. 26 Gy for all plans. The predictive values of Dmean on hypoxic regions were 31. 4, 34. 0 and 37. 2 Gy (Niemierko model) or 31. 6, 33. 9 and 37. 2 Gy (Poisson model) when the oxygen enhancement ratios (OERs) were 1, 1. 5 and 3 respectively. Conclusions With CBCT setup corrections, the dosimetric impacts of setup errors on the target and OARs can be neglected. Significant deviations of TCP calculation were observed without accounting for tumor hypoxia. To counteract the impacts of hypoxia, the mean dose to the hypoxic regions should be at least 1. 24 times of prescribed dose.