Bevacizumab in combination with anticancer drugs for previously treated advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Patients with NSCLC often have an advanced disease at the time of diagnosis, with a 1-year survival rate about 10-15% under the best support treatment. As therapeutic methods for lung cancer developed rapidly in recent years, the prognosis of stage IIIB or IV NSCLC also improve to a large extend. Bevacizumab is a monoclonal antibody against VEGFR which inhibits abnormal vascular growth in malignant tumors. In October 2006, bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for first-line use in advanced NSCLC. For patients with advanced NSCLC who failed in previously platinum-based chemotherapy, bevacizumab also showed enhancing efficacy to antitumor drugs recommended by the latest NCCN guideline. This review intends to present the recent progress and prospects of bevacizumab in second- or third-line treatment for patients with refractory NSCLC.

Preoperative platelet/lymphocyte ratio is a superior prognostic factor compared to other systemic inflammatory response markers in ovarian cancer patients.

The aim of the present study was to determine the most meaningful preoperative prognostic factor of cancer-related death in ovarian cancer patients by comparing potentially prognostic systemic inflammatory response (SIR) markers. The levels of fibrinogen, albumin, C-reactive protein (CRP), and serum cancer antigen-125 (CA-125) and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in 190 ovarian cancer patients to identify predictors of overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analyses. Patients with a PLR >203 had a shorter PFS and OS than the patients in PLR ≤203 group (11 vs. 24 months and 28 vs. 64 months). Univariate analyses revealed that tumor stage, postoperative residual tumor mass, ascites, and the levels of all SIR markers were associated with PFS and OS. Multivariate analysis revealed that PLR was independently associated with PFS (hazard ratio [HR] 1.852, 95% confidence interval [CI] 1.271-2.697, P = 0.001) and OS (HR 2.158, 95%CI 1.468-3.171, P < 0.001), as well as tumor stage and postoperative residual tumor mass. In contrast, fibrinogen remained significant only for PFS (HR 1.724, 95%CI 1.197-2.482, P = 0.003). Patients with a PLR >203 were more prone to have advanced tumor stage (P = 0.002), postoperative residual tumor mass >2 cm (P = 0.032), malignant ascites (P < 0.001), and all the other elevated SIR markers (P < 0.001). Preoperative PLR is superior to other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients.

Saracatinib (AZD0530) is a potent modulator of ABCB1-mediated multidrug resistance in vitro and in vivo.

Saracatinib, a highly selective, dual Src/Abl kinase inhibitor, is currently in a Phase II clinical trial for the treatment of ovarian cancer. In our study, we investigated the effect of saracatinib on the reversal of multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters in vitro and in vivo. Our results showed that saracatinib significantly enhanced the cytotoxicity of ABCB1 substrate drugs in ABCB1 overexpressing HeLa/v200, MCF-7/adr and HEK293/ABCB1 cells, an effect that was stronger than that of gefitinib, whereas it had no effect on the cytotoxicity of the substrates in ABCC1 overexpressing HL-60/adr cells and its parental sensitive cells. Additionally, saracatinib significantly increased the doxorubicin (Dox) and Rho 123 accumulation in HeLa/v200 and MCF-7/adr cells, whereas it had no effect on HeLa and MCF-7 cells. Furthermore, saracatinib stimulated the ATPase activity and inhibited photolabeling of ABCB1 with [(125)I]-iodoarylazidoprazosin in a concentration-dependent manner. In addition, the homology modeling predicted the binding conformation of saracatinib within the large hydrophobic drug-binding cavity of human ABCB1. However, neither the expression level of ABCB1 nor the phosphorylation level of Akt was altered at the reversal concentrations of saracatinib. Importantly, saracatinib significantly enhanced the effect of paclitaxel against ABCB1-overexpressing HeLa/v200 cancer cell xenografts in nude mice. In conclusion, saracatinib reverses ABCB1-mediated MDR in vitro and in vivo by directly inhibiting ABCB1 transport function, without altering ABCB1 expression or AKT phosphorylation. These findings may be helpful to attenuate the effect of MDR by combining saracatinib with other chemotherapeutic drugs in the clinic.

Ultra-Widefield Swept-Source Optical Coherence Tomography Angiography in the Assessment of Choroidal Changes in Young Adults With Myopia.

Purpose: To evaluate choroidal changes in young adults with myopia using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: This study enrolled 105 eyes of 105 participants who underwent SS-OCTA imaging (24 mm × 20 mm) centered on the fovea. Eyes were categorized as low myopia, moderate myopia, or high myopia. Choroidal thickness, choroidal capillary plexus (CCP) vessel density, and choroidal Sattler's and Haller's layer (CSHL) vessel density were analyzed in nine grids using built-in angiography analysis software. Results: A significant decrease in choroidal thickness was found in most grids (P < 0.01) in high myopia. The CSHL vessel density also showed a significant decrease in most grids (P < 0.05) in high myopia. Choroidal thickness was negatively correlated with axial length in most grids (P < 0.05). Choroidal thinning was most evident in the macular grid (ß = -22.55, P < 0.001). CSHL vessel density was negatively correlated with axial length in most grids (P < 0.05). Conclusions: Choroidal changes could be quantified using ultra-widefield SS-OCTA. Choroidal thinning with increasing axial length indicated regional differences in eyes with myopia, which were most evident in the macular area. Decreased CSHL vessel density with increasing axial length also indicated regional differences in eyes with myopia. Translational Relevance: This study explored choroidal changes with a wider field of view than has been currently available.

Diagnostic value of semi-quantitative grading of musculoskeletal ultrasound in wrist and hand lesions of subclinical synovitis in rheumatoid arthritis.

We used semi-quantitative grading of musculoskeletal ultrasound to evaluate wrist and hand lesions of subclinical synovitis, in order to make earlier diagnosis of rheumatoid arthritis. A total of 164 patients were included in this study. Physical examination and ultrasound examination were used to evaluate 30 joints of the wrist and hand. According to the clinical symptoms, the patients were divided into subclinical synovitis (SS) group and clinical synovitis (CS) group. The wrist and hand joints of patients with rheumatoid arthritis between the two groups were evaluated by semi-quantitative grading of musculoskeletal ultrasound, including synovitis, Power Doppler signal, joint effusion and bone erosion. We found that the total score of semi-quantitative ultrasound, synovitis score and Power Doppler signal score in the SS group were lower than those in the CS group (P<0.05). There was no significant difference in joint effusion score and bone erosion score (P>0.05). In the analysis of laboratory examination, the value of anti-RA33 antibody and ESR of SS group were decreased than that of CS group, with statistically significant difference (P=0.004), while that of RF, AKA and CCP had no significant difference between the two groups (P>0.05). In this study, the author also compared the tenosynovitis between the two groups. There was statistically significant difference (P=0.033). In conclusions, semi-quantitative grading of musculoskeletal ultrasound has certain diagnostic value for the diagnosis of subclinical synovitis in wrist and hand lesion.

Prognostic value of γ-glutamyl transpeptidase to albumin ratio combined with aspartate aminotransferase to lymphocyte ratio in patients with hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.

Targeted therapy of multiple liver metastases after resected solitary gastric metastasis and primary pulmonary adenocarcinoma.

Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases.

[Multianalysis of short-term prognostic factors in surgical practices for hypertensive intracerebral hemorrhage].

OBJECTIVE: To evaluate and compare the effectiveness of different types of surgical therapy for patients with hypertensive cerebral hemorrhage, and analyze the major risk factors of prognosis. METHODS: 2464 patients with hypertensive cerebral hemorrhage in 92 hospitals in different areas of China underwent different types of surgical treatment: Group I (n = 639), undergoing traditional craniotomy as control; Group II (n = 409), receiving minimally invasive hematoma evacuation; and Group III (n = 1416), receiving CT guided stereotaxic hematoma aspiration. The clinical data were collected and underwent multianalysis. RESULTS: The factors influencing the short-term prognosis were Glasgow coma scale (GCS) score before surgery and the incidence of postoperative complications in Group II; GCS score before surgery and the incidence of postoperative complications and volume of hemorrhage, duration between ictus and surgery, use of urokinase in Group III; and GCS score before surgery, muscle power before surgery, diastolic pressure at admission and postoperative complications in Group III. CONCLUSION: Analysis of prognosis related factors of cerebral hemorrhage plays a very important role in the selection of therapeutic strategy. It may be beneficial for standardizing surgical indications, further designing large scale clinical trial, helping the doctors select appropriate strategy of treatment, and serving the social population better.

A retrospective analysis of cisplatin, pemetrexed, and bevacizumab in previously treated non-small-cell lung cancer.

Patients with non-small-cell lung cancer (NSCLC) often have an advanced disease when firstly diagnosed. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor receptor (VEGFR). In this study, we retrospectively analyzed the efficacy of cisplatin, pemetrexed, and bevacizumab in previously treated advanced NSCLC. Results showed that the objective response rate(ORR) of this novel regimen is 43%, median progression-free survival (PFS) was 5.2 months (95% CI, 3.7 to 6.7 months) and median overall survival (OS) was 11.4 months (95% CI, 8.8 to 13.9 months). Adverse events were generally mild, ranging from grade 1 to grade 3. In conclusion, the combination of cisplatin, pemetrexed, and bevacizumab obtained promising results in selected patients with NSCLC. Randomized clinical trials are needed to further investigate the efficacy of this regimen.

Human telomerase gene and high-risk human papillomavirus infection are related to cervical intraepithelial neoplasia.

Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

[Variation of different carbon sources in the sewage treatment process].

The biodegradability and speciation of organics were studied through long-term analysis of A2/O treatment. The majority of the organic matters were particle organics which accounted for 61% of the total organics. The proportions of rapidly degradable, slowly degradable and refractory organics were 15. 8% , 54. 2% and 30% respectively. Rapidly biodegradable organics were mainly dissolved organics while slowly biodegradable organics were particle organics. The variation of these two kinds of carbon sources was analyzed during the treatment process. It was noted that microbial hydrolysis fermentation took place in the anaerobic and anoxic tanks, which led to the transformation of slowly biodegradable organics and the anaerobic tank had the highest transformation rate. The transformation and utilization of rapidly/slowly biodegradable organics were analyzed through calculation. The results showed that the transformation efficiency of slowly biodegradable organics in the anaerobic and anoxic tanks in two hours was 33% and 20%, respectively. Furthermore, the amount and species of aliphatic acid increased in the anaerobic and anoxic tanks comparing with raw water.

A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.

INTRODUCTION: The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: In this study, 240 NSCLC patients with stage IIIB (with pleural effusion) and stage IV disease were randomly assigned (1: 1) to receive dicycloplatin 450 mg/m(2) or carboplatin AUC = 5, in combination with paclitaxel 175 mg/m(2) (D + P or C + P) every 3 weeks for up to 4 to 6 cycles. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: The response rates for the D + P and C + P arm were 36.44% and 30.51%, respectively (p = 0.33). The median PFS was 5.6 months in the D + P arm and 4.7 months in the C + P arm (p = 0.31). The median OS was 14.9 months for D + P and 12.9 months for C + P (p = 0.37). Adverse events in the two arms were well balanced. The most common grade 3/4 adverse event was hematologic toxicity. CONCLUSIONS: Patients treated with D + P had similar response and survival rates to those treated with C + P, and toxicities of both treatments were generally tolerable.

Treatment strategies and prognostic factors of patients with primary germ cell tumors in the mediastinum.

OBJECTIVE: The aim of this study was to evaluate the clinical characteristics and survival outcomes of patients with primary mediastinal germ cell tumor (PMGCT) by identifying the prognostic factors and efficacies of different treatment modalities. METHODS: Fifty-five patients with PMGCT who were treated consecutively at Cancer Center, Sun Yat-sen University, Guangzhou, from 1988 to 2010 were evaluated retrospectively. RESULTS: Fifty-two men and 3 women with a median age of 25 years were identified, of whom 17 (30.9%) had pure seminomatous, 38 (69.1%) had nonseminomatous histology, 27 (49.1%) had tumor located at mediastinum, 20 (36.4%) had lung metastases and/or effusions, and 8 (14.5%) had distant metastases. Three treatments surgery, chemotherapy, and radiotherapy were performed in 11 (20%) patients, two treatments chemotherapy plus surgery or radiotherapy were performed in 25 (45.6%), and single treatment surgery or chemotherapy was performed in 17 (30.9%). The other two patients (3.6%) received no treatment. After a median follow-up time of 31.4 months, the 5-year survival rate was 52%. The median overall survival time was 87.9 months. Patients who received two treatments had the longest survival time of 118.3 months, P = 0.000. Those who had pure seminoma histology, whose tumor confined to the mediastinum and who achieved complete or partial remission at initial evaluation, who had complete resection and radiotherapy were considered to have better prognosis according to univariate analysis. On multivariate analysis, extension and response rate at initial evaluation were independently predictive of survival. CONCLUSIONS: Primary mediastinal germ cell tumor is rare with a dominant frequency in young male patients. Chemotherapy combined with local therapy like surgery or radiotherapy is a reasonable treatment strategy recommended. Extension and initial remission rate are independent prognostic factors.

[An analysis on the cost of hypertensive outpatient in the community hospital in Shanghai].

OBJECTIVE: To study the cost of the hypertensive outpatients. METHODS: The study randomly selected 460 insured patients with hypertension and investigated their cost on each case in the out-patient department through 2002, based on the electronic system of medical insurance. RESULTS: As a whole, the distribution of hypertensive outpatient expenditure takes on the positively skewed, with the median of 1 567.9 Yuan RMB. With the increase of age, the average expenses in each age group increased accordingly. In the study, the average number of outpatient attendances per patient was 19.5, the average expenses per visit was 115.4 Yuan RMB. In age groups 40 - 49 and 50 - 59, expenses of outpatient in male and female groups are obviously different in 2002 (Wilcoxon W(40 - 49) = 36, P(40 - 49) = 0.037; Wilcoxon W(50 - 59) = 374, P(50 - 59) = 0.023), as well as the number of out-patients (Wilcoxon W(40 - 49) = 52.5, P(40 - 49) = 0.007; Wilcoxon W(50 - 59) = 379, P(50 - 59) = 0.028). When considering the factors of gender and age at one time, the outpatient expenditures in the male group were significantly different between the different age groups (chi(2) = 22.3, P < 0.001), as well as the number of outpatients (chi(2) = 25.4, P < 0.001). In addition, the expenditure of drugs, which took a large proportion of the total expenditure of hypertensive outpatients (about 83.6 percent), was divided into three parts according to the degree of correlation with hypertension: direct expenses related to the with disease, the indirect expenses and the irrespective. The proportions of each part were 19.9 percent, 32.3 percent and 47.8 percent respectively. CONCLUSION: When economic evaluation of community prevention is carried out, the cost and cost-benefit analysis based on the analysis of outpatient expenditure and the proportion of expenses on hypertension should be taken into account. Additionally, to provide appropriate mode of medicare, to impact the behaviors and expenditure of patients, and to provide low-cost but good effective drug are also essential and important factors.