Preoperative D-dimers as an independent prognostic marker in cervical carcinoma.

Activation of coagulation and fibrinolysis has been observed in many tumors. Our study aimed to investigate the clinical and prognostic significance of various plasma coagulation tests in patients with cervical cancer. A total of 296 patients with cervical cancer were included in the analysis. Patients were followed up for at least 60 months until death. Pretreatment parameters including activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time, thrombin time, lactate dehydrogenase, and squamous cell carcinoma antigen were evaluated. Prothrombin time (hazard ratio = 1.825; P = 0.006) and plasma D-dimer levels (hazard ratio = 2.179; P = 0.036) were identified as significant independent predictors of overall survival. Patients with elevated D-dimer levels had a significantly shorter overall survival compared with those with low-D-dimer levels (<0.5 µg/ml) in the stage I subgroup (n = 98, P = 0.019) and stage II subgroup (n = 77, P = 0.044). D-dimer levels differed significantly according to mortality (P < 0.001), stage I versus stage II (P = 0.030), and stage I versus stage III/IV (P = 0.038). DD level of patients with chemotherapy and/or radiotherapy was higher than patients with other treatment (P < 0.001). Patients with a low-D-dimer level (<0.5 µg/ml) showed a significantly better 5-year overall survival (OS) compared with patients with an increased D-dimer level for different histological typing of squamous cell carcinoma (SCC) (P = 0.001) and non-SCC (P < 0.043). In conclusion, the pretreatment plasma D-dimer level is a potential prognostic factor for cervical cancer.

Inflammation scores predict survival for hepatitis B virus-related hepatocellular carcinoma patients after transarterial chemoembolization.

AIM: To compare the prognostic ability of inflammation scores for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Data of 224 consecutive patients who underwent TACE for unresectable HBV-related HCC from September 2009 to November 2011 were retrieved from a prospective database. The association of inflammation scores with clinicopathologic variables and overall survival (OS) were analyzed, and receiver operating characteristic curves were generated, and the area under the curve (AUC) was calculated to evaluate the discriminatory ability of each inflammation score and staging system, including tumor-node-metastasis, Barcelona Clinic Liver Cancer, and Cancer of the Liver Italian Program (CLIP) scores. RESULTS: The median follow-up period was 390 d, the one-, two-, and three-year OS were 38.4%, 18.3%, and 11.1%, respectively, and the median OS was 390 d. The Glasgow Prognostic Score (GPS), modifed GPS, neutrophil-lymphocyte ratio, and Prognostic Index were associated with OS. The GPS consistently had a higher AUC value at 6 mo (0.702), 12 mo (0.676), and 24 mo (0.687) in comparison with other inflammation scores. CLIP consistently had a higher AUC value at 6 mo (0.656), 12 mo (0.711), and 24 mo (0.721) in comparison with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems. Multivariate analysis revealed that alanine aminotransferase, GPS, and CLIP were independent prognostic factors for OS. The combination of GPS and CLIP (AUC = 0.777) was superior to CLIP or GPS alone in prognostic ability for OS. CONCLUSION: The prognostic ability of GPS is superior to other inflammation scores for HCC patients undergoing TACE. Combining GPS and CLIP improved the prognostic power for OS.

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene.

AIM: To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS: A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS: Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION: We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.

[Value of percentage of highly fluorescent lymphocytic cells for rapidly assessing septicemia in tumor patients].

OBJECTIVE: To evaluate the value of percentage of highly fluorescent lymphocytic cells (HFLC%) for rapidly assessing septicemia in tumor patients. METHODS: Blood samples were collected from 130 patients with tumors (60 septicemia patients and 70 non-septicemia patients) and 80 healthy controls. HFLC% was analyzed with Sysmex XE-5000, the level of C-reactive protein (CRP) measured with a commercially available turbidimetric immunoassay kit and the level of procalcitonin (PCT) determined with a semiquantitative chromatographic immunoassay kit. The diagnostic values of HFLC% and CRP in septicemia were evaluated with ROC analysis. RESULTS: The values of HFLC% and CRP were significantly higher in the septicemia group than those in the non-septicemia and healthy groups (0.30% (0.10%-0.70%) vs 0.10% (0-0.20%), 0.10% (0-0.20%) ; 80.3 (28.5-129.5) vs 3.3 (1.4-41.4) , 1.4 (0.6-2.5) mg/L, all P < 0.01) . The ROC-AUCs for HFLC% and CRP for a diagnosis of septicemia were 0.72 (sensitivity 71.7%, specificity 58.7%) and 0.92 (sensitivity 96.7%, specificity 82.0%). Both of them could judge septicemia better. Additionally, HFLC% was correlated with the levels of PCT and CRP (r = 0.637, 0.241, both P < 0.01). CONCLUSIONS: HFLC% may be used as a rapid and simple auxiliary indicator in the diagnosis of septicemia in patients with tumors. And it is conducive to make an early diagnosis of septicemia and avoid unnecessary use of antibiotics.

EA-D p45-IgG as a potential biomarker for nasopharyngeal carcinoma diagnosis.

AIM: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit. METHODS: Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity visually assigned to the protein bands. The markers which showed statistical differences between the NPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparison with established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. RESULTS: Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative predictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively. CONCLUSIONS: EA-D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA-IgA positive subjects.

[Assessment of detection assays of Epstein-Barr viral Rta-IgG, VCA-IgA, EA-IgA and Epstein-Barr viral DNA at different clinical stages in the diagnosis of nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the values of combined detection method of EB viral Rta-IgG, VCA-IgA, EA-IgA and EB viral DNA in the diagnosis of nasopharyngeal carcinoma (NPC). METHODS: Serum and plasma samples from 131 untreated NPC patients, 52 non-NPC patients with NPC-like symptoms and 148 healthy donors from January to December 2012 were collected. Immunoenzymatic staining was used to detect VCA-IgA and EA-IgA in sera. ELISA was performed to detect Rta-IgG antibody in sera and real-time fluorescent quantitative PCR for measuring EBV DNA in plasma. The clinical characteristics of 3 groups were compared. ROC curve and correlation analyses were performed to assess the detection assays for the diagnosis of NPC. RESULTS: The positive rates of EBV Rta-IgG, VCA-IgA, EA-IgA and EBV DNA in untreated NPC patient group were higher than those in other two groups. The differences were statistically significant (all P < 0.01). The differences of Rta-IgG antibody positive rates, EBV-DNA levels and EBV-DNA positive rates at different clinical stages were statistically significant (all P < 0.05). The positive rates of VCA-IgA and EA-IgA were not related with clinical stages (P > 0.05). Areas under ROC curve for Rta-IgG and EBV-DNA were 0.901 and 0.827 respectively. All four diagnostic assays demonstrated excellent efficiency. The sensitivity and specificity of individual assays were as follows: Rta-IgG: 77.9%, 92.5%; VCA-IgA 93.1%, 91.5%; EA-IgA: 74.8%, 99.5%; EBV-DNA 64.9%, 97.0%. The sensitivity and specificity of combined assays were 97.7% and 83.5% respectively. CONCLUSION: Combined detection method of EB viral Rta-IgG, VCA-IgA, EA-IgA and EB viral DNA are efficient for the diagnosis of NPC.

[Comparison of testing methods for reticulated platelets].

OBJECTIVE: To compare the accuracy, stability and sample cross-contamination of two independent methods of detecting the percentage of reticulated platelets in peripheral blood and establish a local normal reference range so as to provide methodological rationales in clinical laboratory. METHODS: The percentages of reticulated platelets in peripheral blood of a healthy population were measured by Sysmex XE-5000 blood cell analyzer with polymethyl oxazine staining and flow cytometer with thiazole orange staining respectively. The correlation between the results of two methods was analyzed by Spearman's nonparametric correlation. Information about stability was obtained from measurements of the percentages of reticulated platelets in peripheral blood at designated time points. The analyses of accuracy, sample cross contamination and local normal reference range were performed routinely. RESULTS: The coefficient of variation (CV) of data was lower (16.2%) than that from flow cytometer (35.1%). The sample cross-contaminations of two methods were the same at around 5%. The percentage of reticulated platelets in peripheral blood was stable and consistent whereas the results of flow cytometer fluctuated at different time points within 4 h after blood sampling. The correlation of results obtained from two methods was significant (P < 0.01, r(2) = 0.923). The local normal reference range was 1.0% - 7.5% for Sysmex XE-5000 versus 3.0% - 10.5% for flow cytometer. CONCLUSIONS: Fully automatic blood cell analyze is more advanced than flow cytometer for its simple operation and stable data. And the former is an ideal first-choice for detecting the percentage of reticulated platelets in peripheral blood.

Combined determination of Epstein-Barr virus-related antibodies and antigens for diagnosis of nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: With the development of molecular biology in recent years, many indexes for detecting Epstein-Barr virus (EBV) have been developed. This study was to evaluate the diagnostic value of combined determination of EBV-related antibodies and antigens, including VCA-IgA, EA-IgA, EBV-DNase antibody and EBV-DNA, in diagnosing nasopharyngeal carcinoma (NPC). METHODS: Serum and plasma samples from 160 untreated NPC patients and 76 healthy donors were collected. VCA-IgA and EA-IgA in the serum samples were detected by immunoenzyme staining method. Raji cells were stimulated by ortho-butanoic acid and croton oil to detect EBV-DNase antibody. The content of EBV-DNA in the plasma samples was detected by real-time fluorescence quantitative polymerase chain reaction (RQ-PCR). The diagnostic values of the indexes for NPC were evaluated. RESULTS: The sensitivity and specificity for diagnosing NPC were 90.0% and 89.5% for VCA-IgA, 75.0% and 94.7% for EA-IgA, 76.3% and 90.8% for EBV-DNase antibody, 68.8% and 88.2% for EBV-DNA, and 98.8% and 84.2% for combined determination. The positive rates of VCA-IgA and EA-IgA had no relationship with clinical stage of NPC (p > 0.05); nevertheless, the positive rates of EBV-DNase antibody and EBV-DNA were related with clinical stage (p < 0.05). CONCLUSIONS: The sensitivity of VCA-IgA and the specificity of EA-IgA are the highest while detecting solely. Combined determination could improve the diagnostic sensitivity and accuracy for NPC. EBV-DNase antibody and EBV-DNA could be helpful to evaluate the course of disease and classify the clinical stage of NPC.