Comparison of Capillary Zone Electrophoresis with High-pressure Liquid Chromatography in the Evaluation of Hemoglobinopathies

Objective: The capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC) methods were compared in terms of HbA2 measurement for the assessment of hemoglobinopathies. Materials and Methods: CZE was compared with HPLC for the evaluation of patients without hemoglobinopathy (n=321), with ß-thalassemia trait (n=113), and with common (HbD-Punjab, E, C, S/A, and S/S) and rare (HbS/D, O-Arap, Lepore, G-Coushata, Setif, Hamadan, Q-Iran, and H) variants (n=21). The reference range for HbA2 was determined by CZE. Results: Among patients without hemoglobinopathy, the median (2.5th-97.5th percentiles) values were 97.4% (97.0-98.0%) and 97.5% (96.6-98.4%) for HbA (p=0.060) and 2.4% (1.6-3.0%) and 2.5% (1.6-3.1%) for HbA2 (p<0.001) by HPLC and CZE, respectively. The reference range for HbA2 was 1.6-3.1% by CZE. In the comparison of methods for HbA2, there was a constant error of 0.255 (confidence interval: 0.062-0.448) and bias of 0.10% (limit of agreement: 0.33-0.53), and higher values were obtained with CZE. A strong correlation was observed between the methods (r=0.782). Interrater agreement was almost perfect for clinical diagnosis (Ï°=0.911). The two methods detected and identified the common variants similarly. All rare variants, except HbH by HPLC and HbS/D by CZE, were detected as separate peaks by both methods. Conclusion: The two methods were in agreement regarding the preliminary identification of ß-thalassemia patients. Different Hb variants were detected by both methods but with possible methodological interference for HbA2 measurements. CZE is a reliable and simple alternative for the evaluation of hemoglobinopathies. The standardization of HbA2 measurements should be prioritized as more techniques become available in routine laboratory practice.

The effects of facial mask use on ocular surface parameters and tear film cytokine profile in prolonged use.

OBJECTIVE: To compare tear fluid levels of matrix metalloproteinase 9 (MMP-9) and IL-1ß cytokines between healthcare workers wearing facial masks and controls with correlations in clinical findings. METHODS: In a prospective, controlled clinical trial tear fluid was analyzed for MMP-9 and IL-1ß levels using a commercially available test (Invitrogen; Thermo Fisher Scientific Inc. Waltham, Massachusetts, USA). Symptoms and signs of dry eye disease (DED) were evaluated using the ocular surface disease index (OSDI), noninvasive tear break-up time (NIBUT), tear meniscus height (TMH), Oxford corneal staining, meibomiography, and clinical findings of meibomian gland dysfunction (MGD). RESULTS: In the 38 eyes of healthcare workers and 30 eyes of controls, there was no statistically significant difference between the groups in terms of age and sex (p > 0.05). The mean OSDI score, daily mask wear time, meibomiography degree, and rate of positive clinical findings of MGD were higher in group 1 than in group 2, and the mean NIBUT was higher in group 2. (p > 0.05). The mean values of IL-1ß and MMP-9 were higher in group 1 (p = 0.036 and p = 0.001, respectively). The TMH and Oxford score percentages were similar between the two groups (p > 0.05). CONCLUSIONS: Elevated levels of IL-1ß and MMP-9 in the basal tear fluid reveal increased ocular inflammation in healthcare professionals. Lower NIBUT values with higher OSDI and meibomian gland loss scores support ocular surface disturbance depending on regular mask use.

Serum apelin-13 levels and total oxidant/antioxidant status of patients with Alzheimer's disease.

OBJECTIVE: We aimed to evaluate apelin-13 levels, total oxidant/antioxidant status in Alzheimer's disease (AD) and to investigate the relationship between these parameters. METHODS: Patients newly diagnosed with AD were enrolled in the study. The control group consisted of age- and gender-matched healthy individuals. Serum levels of apelin-13, total antioxidant status (TAS), and total oxidant status (TOS) were measured. Oxidative stress index was calculated (TOS/TAS) for each participant. RESULTS: We reported that serum apelin-13 and TAS values were significantly lower in the AD group compared with controls, and they found a fair but insignificant relationship between Apelin-13 and TAS values. CONCLUSION: According to our results, we suggested that insufficient apelin-13 and TAS levels may contribute to the pathogenesis of AD.

Evaluation of the Analytical Properties of the Diagon CoagXL Coagulation Analyzer.

BACKGROUND: This study aims to evaluate the analytical properties of the DIAGON CoagXL (Budapest, Hungary) coagulation system. METHODS: The study includes a total of 212 normal, 49 pathologic plasma samples sent to our laboratory. The par-tial thromboplastin time (PTT) and activated partial thromboplastin time (aPTT) measurements were performed on the Diagon CoagXL and Stago StaR coagulometers. The precision, method comparison, carry-over, activity determination, and reference range verification studies were performed with Diagon CoagXL, the test analyzer. RESULTS: In the precision study performed with normal and pathologic plasma samples for the PT and aPTT tests, the within-day coefficient of variation (CV%) was 1.9 in the normal and 0.68 in the pathologic plasma for the PT, and for the aPTT it was 0.61 in the normal and 0.9 in the pathologic plasma. The between-day CV% was 1.6 in the normal plasma and 5.5 in the pathologic plasma for the PT and 3.7 in the normal plasma and 2.1 in the pathologic plasma for the aPTT. In the comparison study, the entire group mean ± standard deviation (mean ± SD) value for the INR was found to be 3.13 ± 1.26 in the CoagXL and 2.67 ± 0.82 in the StaR analyzer. The difference between these values was statistically significant (p < 0.006). For aPTT, mean ± SD value was found to be 39.44 ± 25.02 seconds (sec) in the CoagXL analyzer and 43.4 ± 27.63 sec in the StaR analyzer. The difference between these values was not statistically significant (p > 0.5). In the carryover study, the carryover value was -0.16 for the PT and 0 for the aPTT, which was under the allowable limit value (< 3 SD). In the percent activity determination study, regression equation of prothrombin activity (%) versus time (sec) was found as y = 341.6567 ± 37.1920x + 1.0913x2 (R2 = 0.97). The reference range verification analyses reveal that the manufacturer ranges were acceptable. CONCLUSIONS: Verification studies of CoagXL analyzer system was acceptable. But in comparison studies of PT we saw that there are still problems with recommended INR system.

Evaluation of new Beckman Coulter 25(OH) Vitamin D assay and potential improvement of clinical interpretation.

INTRODUCTION: The aim of this study was to assess the analytical performances of the newly developed Access2 25-hydroxyvitamin D (25(OH)D) total immunoassay on two analysers, DxI800 and Access2 (Beckman Coulter, Brea, CA, USA), and compare these two and a recalibrated Modular E 170 25(OH)D assay (Roche Diagnostics, Penzberg, Germany) with reference liquid chromatography tandem-mass spectrometry (LC-MS/MS) with special emphasis on clinical diagnosis. MATERIALS AND METHODS: Beckman immunoassays were assessed for imprecision, accuracy, limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, interference, and carryover. One hundred and nineteen samples were run on DxI 800, Access2, and E 170, and agreement with the LC-MS/MS method was evaluated. RESULTS: DxI 800 and Access2 assays showed good performances in terms of LoB, LoD, LoQ, linearity, and interference. All immunoassays showed negative biases ranging from - 8.6% (DxI 800) to - 19.2% (Access2). DxI 800 and Access2 systems had proportional biases, and the E170 system had a constant bias with the largest random error. Concordance correlation coefficient values ranged from 0.941 (CI: 0.917-0.958) for DxI800 to 0.854 (CI: 0.811-0.889) for Access2. Kappa (κ) coefficients were found moderate for Dxl (0.709; CI: 0.581-0.837) and E170 (0.771; CI: 0.587-0.844) and fair for Access2 (0.572; CI: 0.428-0.716). CONCLUSIONS: All immunoassays can be used in routine 25(OH)D measurements, still fairly diagnosing patients' status. Recent standardization attempts seem not to contribute too much to clinical diagnosis. A clinical laboratory must at least be aware of its method to avoid misinterpretation of results.

Can first trimester maternal serum follistatin like 3 levels predict developing gestational diabetes mellitus?

PURPOSE: The purpose of this study is to determine whether the first trimester maternal serum levels of follistatin like 3 (FSTL3) are altered in patients who develop gestational diabetes mellitus (GDM). METHODS: This is a prospective nested case-control study that included 170 singleton pregnant women recruited in their first trimester. All women were followed up until the delivery and 144 of them completed the study. The maternal serum levels of FSTL3 were measured at 11-14 weeks of gestation. The GDM-affected women (n = 19) were compared with the GDM-free control women (n = 125) for potential serum biomarkers including the FSTL3 levels. RESULTS: There were no significant differences in maternal age, maternal pre-pregnancy body mass index, and neonatal birth weight between the GDM group and the GDM-free control group. Women with GDM had significantly greater weight gain during pregnancy than the women without GDM. Serum concentration of glycosylated hemoglobin was significantly higher in women with GDM. There were no significant differences in serum FSTL3 levels (p = 0.578) between the GDM group and the GDM-free control group. CONCLUSIONS: Our results suggest that the first trimester maternal serum FSTL3 levels are not altered in women who develop GDM and thus do not support the use of serum FSTL3 levels for early prediction of GDM.

Effect of ejaculation on Serum Prostate-Specific Antigen concentration.

PURPOSE: To evaluate the effect of ejaculation on serum prostate-specific antigen (PSA) concentrations in patients with lower urinary tract symptom (LUTS). MATERIALS AND METHODS: Our study includes 98 men (62 study and 36 control). After three days of sexual abstinence, blood samples were drawn for the measurement of baseline PSA levels. Then the patients were told to ejaculate. One, 5, 24 and 72 hours after ejaculation, serum total (tPSA), free (fPSA) and complexed PSA (cPSA) levels were measured. Serum PSA sampling was performed at the same intervals in the control group without ejaculation. RESULTS: The mean age in study and control groups patients were 59.03±0.99 years, 61.14±1.30 years, respectively. In the study group, changes in tPSA and fPSA levels after ejaculation were found statistically significant while changes in cPSA levels and f/tPSA ratios were not significant (p=0.016, p=0.0003, p=0.176, and p=0.173, respectively). Baseline values showed significant differences with 1st and 5th hours. No significant changes in tPSA, fPSA, cPSA levels and f/tPSA values were found in control group (p=0.223, p=0.224, p=0.444, and p=0.718, respectively). The changes in the number of patients exceeding the cutoff values after ejaculation were not statistically significant for tPSA, cPSA, and f/tPSA ratio. CONCLUSIONS: In this study, ejaculation increased tPSA and fPSA concentrations but it didn't have a significant effect on serum cPSA levels and f/tPSA ratios. However, recent ejaculation may affect the biopsy indication at least near cut off PSA values. Further studies are needed to explain the mechanisms of alterations in the concentration of PSA.

The effectiveness of BD Vacutainer® Plus Urinalysis Preservative Tubes in preservation of urine for chemical strip analysis and particle counting.

INTRODUCTION: The aim of this study was to evaluate the stability of urine collected in preservative tubes for chemistry strip analyses and particle counting to determine whether the transport of urine samples with all of their constituents is possible. MATERIALS AND METHODS: 275 pathologic urine specimens were included. Each urine sample was evaluated after 4, 8, 12, 24, and 48 hours of storage in BD Vacutainer(®) Plus Urinalysis Preservative (BD UAP) tubes and compared with refrigeration at 4 °C. All analyses were peformed on H-800 and FUS-200 automatic modular urine analyzers (Dirui Industry, Changchun, China). The kappa coefficients (κ), false positive (FP) and false negative (FN) rates were evaluated. κ > 0.8 was accepted as good agreement. RESULTS: Haemoglobin (Hb), leucocyte esterase (LE), and protein (Pro) analyses should be performed within 4 hours, whereas glucose (Glc) was stable until the end of 48 hours in both storage conditions. Nitrite (Nit) was well preserved in BD UAP tubes for 24 hours but was stable only up to 8 hours at 4 °C. Bilirubin (Bil) had very high FN rates even at 4 hours in both conditions. The particle counting showed high FN rates for white blood cells (WBC) and red blood cells (RBC), whereas squamous epithelial cells (EC) were stable up to 8 hours in both conditions. CONCLUSIONS: Preanalytical requirements for both urine chemical strip analyses and particle counting in a unique sample were not met in either condition. Thus, the transfer of urine samples for centralization of urinalysis is not yet feasible.

Effect of ejaculation on serum prostate-specific antigen concentration

ABSTRACT Abstract Purpose:To evaluate the effect of ejaculation on serum prostate-specific antigen (PSA) concentrations in patients with lower urinary tract symptom (LUTS). Materials and Methods Our study includes 98 men (62 study and 36 control). After three days of sexual abstinence, blood samples were drawn for the measurement of baseline PSA levels. Then the patients were told to ejaculate. One, 5, 24 and 72 hours after ejaculation, serum total (tPSA), free (fPSA) and complexed PSA (cPSA) levels were measured. Serum PSA sampling was performed at the same intervals in the control group without ejaculation. Results The mean age in study and control groups patients were 59.03±0.99 years, 61.14±1.30 years, respectively. In the study group, changes in tPSA and fPSA levels after ejaculation were found statistically significant while changes in cPSA levels and f/tPSA ratios were not significant (p=0.016, p=0.0003, p=0.176, and p=0.173, respectively). Baseline values showed significant differences with 1st and 5th hours. No significant changes in tPSA, fPSA, cPSA levels and f/tPSA values were found in control group (p=0.223, p=0.224, p=0.444, and p=0.718, respectively). The changes in the number of patients exceeding the cutoff values after ejaculation were not statistically significant for tPSA, cPSA, and f/tPSA ratio. Conclusions In this study, ejaculation increased tPSA and fPSA concentrations but it didn’t have a significant effect on serum cPSA levels and f/tPSA ratios. However, recent ejaculation may affect the biopsy indication at least near cut off PSA values. Further studies are needed to explain the mechanisms of alterations in the concentration of PSA.

Is galectin-3 associated with urinary albumin excretion in type 2 diabetes?

INTRODUCTION: The relationship between galectin-3 and diabetes mellitus or renal function has recently been investigated. In this study, we tried to evaluate the association of galectin-3 in urinary albumin excretion levels in type 2 diabetic patients. MATERIAL AND METHODS: In a group of 137 type 2 diabetes patients, the mean of the last three urinary microalbumin/creatinine ratios and galectin-3 levels were evaluated. The patient group was divided into three subgroups according to their level of albuminuria calculated with urine microalbumin/creatinine ratio. RESULTS: There was no significant difference between the galectin values of the three subgroups. Significant differences were observed between GFR results of group 1 vs. 3 (p < 0.0001) and group 2 vs. 3 (p = 0.0006), and serum creatinine results of group 1 vs. 3 (p = 0.0003) and group 2 vs. 3 (p < 0.0001). The three subgroups did not reveal any significant difference concerning the age, BMI, duration of DM, FPG, and HbA1c levels. CONCLUSIONS: We concluded that serum galectin-3 values are not affected by the levels of urinary albumin excretion in DM patients. We could not find any relation between galectin-3 and the parameters of DM such as FPG, HbA1c, and duration of the disease. (Endokrynol Pol 2016; 67 (6): 580-584).

Does preeclampsia have any adverse effect on fetal heart?

OBJECTIVE: To determine whether preeclampsia causes fetal cardiac cell damage by assessing umbilical artery NT-proBNP, cardiac troponin I and homocysteine. METHODS: A cross-sectional study with 73 fetuses between 26 and 40 weeks of gestation was performed. Thirty-three healthy mothers' fetuses were control group (Group I). While 12 mildly pre-eclamptic mothers' fetuses constituted Group II, 28 fetuses of severe pre-eclamptic mothers were Group III. RESULTS: Umbilical cord mean NT-proBNP levels of Group I, II and III are 520.8 ± 404.5 pg/ml; 664.2 ± 215.9 pg/ml; and 1932.8 ± 2979.5 pg/ml, respectively (p = 0.0001). The number of neonates with NT-proBNP > 500 pg/mL that indicates severe cardiac damage is higher in Group III (p = 0.001). The mean homocysteine levels are also statistically significantly higher in Group III. Cardiac troponin I levels are not different between the groups (p = 0.46). CONCLUSION: Increased NT-proBNP and homocysteine might not only indicate some degree of in-utero cardiac cell damage but also feto-placental endothelial injury in the fetuses of severe pre-eclamptic mothers. Our finding that shows no evidence of correlation between cardiac troponin I levels with cell damage and endothelial injury requires further research.

A Comparison of Three Widely Used Immunoassay Systems in Cortisol Measurement.

BACKGROUND: Interassay variability is one of the challenging issues of routine clinical laboratory practice. Commercial plasma cortisol immunoassays are also subject to this issue. In this study, we intended to evaluate the interchangeability of cortisol results of three widely used immunoassay systems. METHODS: The cortisol values of 150 serum samples measured by three immunoassay systems, Beckman Coulter DXI 800, Roche Modular E170, and Siemens Immulite 2500, were compared. RESULTS: A degree of proportional biases was observed between all three methods; DXI 800 showed the worst biases with the other two systems (slope values 0.67 and 0.77 with E170 and Immulite 2500, respectively). DXI 800 showed poor agreement with other methods (CCC: 0.83 and 0.87, respectively). There was a moderate agreement between E170 and Immulite 2500 (CCC: 0.92). CONCLUSIONS: All three methods showed a degree of variability among themselves. DXI 800 results were not interchangeable with the other two systems.

Establishing reference intervals for D-dimer to trimesters.

OBJECTIVE: When D-dimer is used to evaluate suspected venous thromboembolism in pregnant patients, the reference interval of common population may cause misinterpretation. The present study aims to determine reference intervals of D-dimer in the three trimesters. METHODS: Four-hundred sixteen pregnant women and 32 non-pregnant women were enrolled in this cross-sectional study. Reference group had comprised 123 pregnant in the first trimester (5-11 week), 164 pregnant in the second trimester (13-20 week) and 126 pregnant women in the third trimester (25-35 week). D-dimer levels were analyzed via immunoturbidimetric assay. RESULTS: If the threshold of 0.50 mg/L for diagnosis of VTE is used, 4.8% of pregnant women in the second trimester and 23.8% of pregnant women in the third trimester would have D-dimer levels exceeding this cut-off value. Reference intervals of D-dimer were determined as 0.11-0.40 mg/L; 0.14-0.75 mg/L and 0.16-1.3 mg/L in first, second and third trimester, respectively. CONCLUSION: The established D-dimer reference intervals for each trimester of pregnancy are different from those used in common population. These reference intervals may assist clinicians in making accurate clinical decisions. Further studies are needed to establish new cut-off values for the D-dimer to rule out VTE in each trimester.

The changing of serum vitamin B12 and homocysteine levels after gastrectomy in patients with gastric cancer: do they associate with clinicopathological factors?

After total (TG) or distal subtotal gastrectomy (DG), patients are at high risk of vitamin B12 (vit-B12) deficiency, which results in elevation of homocysteine levels. The changing of serum vit-B12 and homocysteine levels in patients with gastric cancer is not well known. Seventy-two patients with gastric cancer who had undergone currative gastrectomy and 50 healthy controls were included. Serum vit-B12 and homocysteine levels were analyzed in gastric cancer patients. In addition, these parameters were compared with those of healthy control subjects. While serum vit-B12 levels in gastrectomized patients were significantly lower than that of healthy controls (221.8 ± 125.6 pg/mL vs. 309.9 ± 174.3 pg/mL, p = 0.002), homocysteine levels were significantly higher in patients with gastric cancer (14.2 ± 6.7 µmol/L vs. 12.5 ± 6.1 µmol/L, p = 0.016). Mean serum folate level was found to be high in healthy controls (7.3 ng/mL) compared to patients (9.2 ng/mL, p = 0.027). Out of 72 patients, 40 patients (55.6 %) with gastric cancer developed vit-B12 deficiency after gastrectomy. Vit-B12 deficiency was found to be related with gastrectomy type (p = 0.02) and homocysteine levels (p = 0.014). In patients who underwent TG, the incidence of vit-B12 deficiency was significantly higher compared with those with DG (67.5 vs. 32.5 %). In addition, serum vit-B12 level in patients with DG was significantly higher than that of patients with TG (248.3 ± 122.0 pg/mL vs. 200.8 ± 126.7 pg/mL, p = 0.041), whereas homocysteine levels were significantly lower in DG group compared with TG group (12.1 ± 6.1 µmol/L vs. 15.8 ± 6.9 µmol/L, p = 0.014). A logistic regression analysis showed that the extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency (p < 0.001, odds ratio 1.38). Our results showed that cumulative vit-B12 deficiency rate was significantly higher after TG compared with that after DG, while homocysteine levels were significantly higher in TG group compared with DG group. The extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency. Vit-B12 deficiency and hyperhomocysteinemia are imperious clinical situation for patients with gastric cancer after surgery. Hence, both preoperative and regular postoperative monitoring of vit-B12 and homocysteine levels for all gastrectomized patients with gastric cancer are important and necessary for early detection and prevention of vit-B12 deficiency and hyperhomocysteinemia as a risk factor for cardiovascular diseases.

Effects of ejaculation on serum prostate-specific antigen levels.

OBJECTIVE: The aim of this study is to evaluate the effect of ejaculation on serum total, free and complex prostate-specific antigen (PSA) levels and their effect on biopsy decisions. MATERIAL AND METHODS: Our study includes 47 men older than 45 years with symptomatic benign prostatic hyperplasia (BPH). Patients' PSA levels were under 2.5 ng/mL, and there were no known conditions to preclude ejaculation. Eight patients with similar demographic, and clinical characteristics were chosen as a control group. With three days of sexual abstinence, blood samples were drawn for the measurement of baseline PSA levels, and then the patients were told to ejaculate. One, 5, 24 and 72 hours after ejaculation, serum total, free and complexed PSA levels were measured. Serum PSA sampling was performed at the same intervals in the control group without ejaculation. RESULTS: The mean age of the patients was 59.13±1.38 years in the study group, and 63.75±3.13 years in the control group. The mean international prostate symptom scores (IPSS) were 11.78±1.12 and 11.63±3.32 in the study, and the control groups, respectively. The mean baseline total, free, and complexed PSA values were 1.07±0.09, 0.31±0.03, and 0.71±0.08 ng/mL, respectively. In the study group, total PSA value was found to be 1.29±0.12 ng/mL (p=0.008) at first hour after ejaculation, and this change was statistically significant when compared with baseline values. Mean total PSA level rose up to 1.28±0.13 ng/mL (p=0.05) by the 5(th) hour after ejaculation, but this change was not statistically significant relative to the baseline values. Mean free PSA level rose after the first hour postejaculation to 0.37±0.04 ng/mL (p=0.01) and after the fifth hour postejaculation to 0.37±0.04 ng/mL (p=0.002), and these changes were statistically significant relative to the baseline values. There were no statistically significant changes at the other sampled times as for the total, free or complexed PSA serum levels. When all three values were considered individually, in only 2.12% of the patients, biopsy decisions could be affected by the elevation in PSA levels. CONCLUSION: When the PSA value is borderline with respect to biopsy decisions, the effect of ejaculation on serum PSA levels may be clinically important. In these patients, ejaculation must be questioned, and repeated. PSA levels should be evaluated 24 hours after ejaculation. There were no statistically significant changes in the levels of complex PSA values. Further studies are needed to clarify the relationship between complexed PSA and ejaculation.

The prognostic importance of changing serum M30 and M65 values after chemotherapy in patients with advanced-stage non-small-cell lung cancer.

Although oncological treatments are improving, the prognosis of non-small-cell lung cancer (NSCLC) patients has not. Several biomarkers related to prognosis have been evaluated, and M30 and M65 have been reported to be higher in patients with NSCLC than in healthy people. In the current study, we evaluated the clinical importance of the change in serum M30 and M65 values after chemotherapy in patients with NSCLC. Serum M30 and M65 values were measured before and 48 h after chemotherapy in thirty-two patients with advanced NSCLC. The importance of the change in the levels of these markers after chemotherapy was analyzed by univariate analysis. The median serum M65 and M30 values increased significantly after chemotherapy (p < 0.001). The median M30 value after chemotherapy was an important prognostic factor for both overall survival (OS) (p = 0.002) and progression-free survival (PFS) (p = 0.002). Stage and histopathological type were significant both for PFS and OS. Multivariate analysis showed that the median M30 value after chemotherapy was the only independent prognostic factor for PFS (p = 0.04, HR 5.4) and OS (p = 0.02, HR 11.49). Our results indicated that both serum M30 and M65 values increased after chemotherapy in patients with advanced NSCLC, and an elevated serum M30 value was an independent prognostic factor for both PFS and OS.

The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer.

In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48 h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7 ± 111.5 U/l [pre mean] vs. 983.3 ± 214.1 U/l [post mean], p = 0.01; M65, 2,061.7 ± 431.2 U/l [pre mean] vs. 2,646.3 ± 433.1 U/l [post mean], p = 0.003). Means of the differences of M30 and M65 levels before and 48 h after chemotherapy were 400.5 ± 190 U/l ([M30-difference] M30-D) and 584.6 ± 335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3 months, p = 0.018 and OS, 13.6 vs. 8.1 months, p = 0.029). In addition, median PFS and OS intervals in patients with serum M65-D > 584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4 months for PFS, p = 0.002 and 5.7 vs. 13.6 months for OS, p = 0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (p = 0.02 and p = 0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (p = 0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48 h after chemotherapy and these were poor prognostic factors for both PFS and OS of patients. Moreover, increased serum M65 levels after chemotherapy can be predict tumor response.

Serum M30 and M65 values in patients with advanced stage non-small-cell lung cancer compared with controls.

BACKGROUND: M30 and M65 are derivatives of cytokeratin 18 and released from the epithelial cell during cell death. These markers can be used to evaluate prognosis and chemotherapy response in several tumours. We evaluated serum M30 and M65 values in patients with advanced nonsmall- cell lung cancer (NSCLC) compared with those in a healthy group. MATERIAL AND METHODS: Thirty-two patients with advanced NSCLC and thirty-two healthy people were included in the study. Serum M30 and M65 values were measured by quantitative ELISA method. The best cut-off value for serum M65 was calculated by ROC analysis and then univariate analysis was performed to determine the importance of M65 value in predicting progression-free survival (PFS). RESULTS: There were no differences between mean serum M30 values between patients and controls (445.44±536.17 vs. 340.56±345.07, p=1). The mean serum M65 values were found to be significantly higher in patients than in healthy controls (1421.30±1662.59 vs. 648.85±341.17, p<0.001). The best cut-off value for serum M65 predicting PFS was 1311.64 U/l (AUC 0.58, sensitivity and specificity were 45.5% and 85.7% respectively). The patients with serum M65 values ≥1311.64 U/l had worse PFS than patients with serum M65 values <1311.64 U/l, p=0.01). There was no correlation between serum M30 value and PFS in the patient group (p=0.4). CONCLUSIONS: Our results indicated that serum M65 values elevated in advanced NSCLC compared to a healthy control group and elevated serum M65 level can predict PFS in patients.

Serum concentrations of CA 125, CA 15-3, CA 19-9 and CEA in normal pregnancy: a longitudinal study.

PURPOSE: Although cancer diagnosed during pregnancy is rare, the coexistence of pregnancy and malignancy becomes more common in view of prolongation of reproductive age. Therefore, it is important that the specificity of a tumor marker be evaluated during pregnancy to avoid misinterpretation in the follow-up of a pregnant cancer patient. The present study aims to investigate the serum concentrations of CA-125, CA 15-3, CA 19-9 and CEA in healthy pregnant women through gestation. METHODS: In this prospective study, we followed thirty healthy pregnant women. Blood samples were obtained during each trimester of pregnancy (10-12, 22-24 and 34-36 weeks). The maternal serum levels of CA-125, CA 15-3, CA 19-9 and CEA were measured using electrochemiluminescence immunoassay. RESULTS: There was no difference between the first and second trimester serum levels of CA 125, CEA and CA 19-9. However, serum CA 125 levels in third trimester were found to be significantly elevated in pregnants compared to the second trimester (median values 19.6 vs. 15.6 IU/mL, p = 0,009). Similarly, the serum CEA levels in third trimester were significantly higher than those of second trimester (median values 1.1 vs. 0.7 ng/ml, p = 0.001). It is also found that CEA and CA 19-9 assay values were significantly elevated in the third trimester of pregnancy when compared with the first trimester of pregnancy (CEA median values 1.1 vs. 0.7 ng/ml, p = 0.02 and CA 19-9 median values 11.6 vs. 7.7 IU/mL, p = 0,02). Three trimester had statistically similar levels for serum CA 15-3 (median values 17.5, 19.7 and 18.3 U/mL, respectively). The four tumor markers assay values were found generally within the normal range. CONCLUSIONS: These findings suggest that maternal serum levels of CA 125, CEA and CA 19-9 were increased during third trimester of pregnancy. However, these elevations were within the normal range. CA 15-3 is independent of gestation and reliable tumor markers in monitoring malignancy in pregnant patients.

Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer?

PURPOSE: M30 and M65 are different circulating fragments of cytokeratin 18. They release during apoptotic cell death, so it is believed that they reflect cell death of epithelial tumors. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting of survival for patients with advanced gastric cancer compare with healthy controls. METHODS: Thirty-four patients with advanced gastric cancer and thirty-two healthy controls were included. Plasma M30 and M65 values were measured by quantitative ELISA method. RESULTS: The median age of patients and control groups was 60 and 56 years, respectively. No difference was detected between patient and control groups with respect to plasma median M30 values (390.4 vs. 270.7 U/l, respectively, P = 0.10). The median plasma M65 values of patients were significantly higher than those of control group (1232.1 vs. 580.1 U/l, P < 0.001). The best cut-off values for plasma M30 and M65 for predicting progression-free survival (PFS) were 277.7 and 1434.9 U/l in ROC analysis. The patients whose plasma M30 values were higher than 277.7 U/l had worse PFS than patients with plasma M30 value <277.7 U/l (8.9 vs. 11.2, respectively, P = 0.01). The median PFS of patients whose M65 levels lower than or equal to 1434.9 U/l was better than that of patients whose M65 levels were >1434.9 U/l (12.4 vs. 10.4, respectively, P = 0.04). But plasma M30 and M65 level in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. CONCLUSIONS: These results showed that plasma M65 values were significantly elevated in patients with advanced gastric cancer compared to healthy people. Moreover, both increased plasma M30 and M65 levels can predict PFS in patients with gastric cancer.