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      • Analyses of Multiple Factors for Determination of "Selected Patients" Who Should Receive Rechallenge Treatment in Metastatic Colorectal Cancer: a Retrospective Study from Turkey

        Ozaslan, Ersin,Duran, Ayse Ocak,Bozkurt, Oktay,Inanc, Mevlude,Ucar, Mahmut,Berk, Veli,Karaca, Halit,Elmali, Ferhan,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

        Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy ${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ${\geq}12months$ PFS onreceiving first line therapy.

      • Factors Affecting Prognosis in Metastatic Colorectal Cancer Patients

        Eker, Baki,Ozaslan, Ersin,Karaca, Halit,Berk, Veli,Bozkurt, Oktay,Inanc, Mevlude,Duran, Ayse Ocak,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

        Background: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Patients and Methods: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. Findings: Median age was 56 (32-82) years and the male/female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. Conclusions: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.

      • Positive Effects of Oral β-Glucan on Mucositis and Leukopenia in Colorectal Cancer Patients Receiving Adjuvant FOLFOX-4 Combination Chemotherapy

        Karaca, Halit,Bozkurt, Oktay,Ozaslan, Ersin,Baldane, Suleyman,Berk, Veli,Inanc, Mevlude,Duran, Ayse Ocak,Dikilitas, Mustafa,Er, Ozlem,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

        The present study aimed to determine the effect of oral ${\beta}$-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received ${\beta}$-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the ${\beta}$-glucan group were $7,300/mm^3$ and $3,800/mm^3$, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was $264,000/mm^3$ after chemotherapy in the ${\beta}$-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the ${\beta}$-glucan group. We conclude that ${\beta}$-glucan can be used to reduce the adverse effects of chemotherapy.

      • KCI등재

        Association of Early Favipiravir Use with Reduced COVID-19 Fatality among Hospitalized Patients

        Ercan Karatas,Lacin Aksoy,Ersin Ozaslan 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.2

        Background: The antiviral agent favipiravir is an RNA-dependent RNA polymerase (RdRp) inhibitor. Materials and Methods: We examined patients with a clinical, laboratory, and radiological diagnosis of severe coronavirus disease 2019 (COVID-19) pneumonia. We investigated the effect of administering enteral favipiravir at a 2 × 1,600 mg loading dose and 2 × 600 mg maintenance dose for 5 days in addition to the standard COVID-19 treatment. Results: In total, 180 patients, who were hospitalized at the Istanbul Tuzla State Hospital and received favipiravir treatment between March 20, 2020 and May 30, 2020, were examined. Of these, 47 patients died. Thirty-three of the patients who died were aged over 65 years (70%), indicating that fatality was higher in elderly patients. Most of those who died had at least one comorbidity. Of the 101 patients who initiated favipiravir within ≤3 days of hospitalization, 17 died (17%). Of the 79 patients who initiated favipiravir after >3 days of hospitalization, 30 died (38%) (P = 0.002). Conclusion: We found that initiation of favipiravir within the first 72 h after the onset of disease symptoms reduced fatality in patients with COVID-19.

      • Predictive Significance of VEGF and HIF-1α Expression in Patients with Metastatic Colorectal Cancer Receiving Chemotherapy Combinations with Bevacizumab

        Berk, Veli,Deniz, Kemal,Bozkurt, Oktay,Ozaslan, Ersin,Karaca, Halit,Inanc, Mevlude,Duran, Ayse Ocak,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

        Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

      • Haematologic Parameters in Metastatic Colorectal Cancer Patients Treated with Capecitabine Combination Therapy

        Inanc, Mevlude,Duran, Ayse Ocak,Karaca, Halit,Berk, Veli,Bozkurt, Oktay,Ozaslan, Ersin,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

        Background: The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. Materials and Methods: A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX)${\pm}$Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. Results: After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabine-based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.

      • Lack of Prognostic Value of Mean Corpuscular Volume with Capecitabine Therapy in Metastatic Breast Cancer

        Bozkurt, Oktay,Berk, Veli,Kaplan, Muhammed Ali,Cetin, Bulent,Ozaslan, Ersin,Karaca, Halit,Inanc, Mevlude,Duran, Ayse Ocak,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

        Background: Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ${\geq}100$ fl was considered as macrocytosis. Capecitabine was given at a dose of $2500mg/m^2$ daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ${\Delta}MCV$ level (post-treatment values at sixth week - baseline) was 6.4. Whilst ${\Delta}MCV$ was ${\geq}6.4$ in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ${\Delta}MCV$ ${\geq}6.4$ and in 30 (75%) of 40 patients with ${\Delta}MCV$ <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ${\Delta}MCV$ ${\geq}6.4$ and the group with ${\Delta}MCV$ <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.

      • Albumin-globulin Ratio for Prediction of Long-term Mortality in Lung Adenocarcinoma Patients

        Duran, Ayse Ocak,Inanc, Mevlude,Karaca, Halit,Dogan, Imran,Berk, Veli,Bozkurt, Oktay,Ozaslan, Ersin,Ucar, Mahmut,Eroglu, Celalettin,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

        Background: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. Materials and Methods: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/(total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. Results: The mean survival time for each tertile was: for the $1^{st}$ 9.8 months (95%CI:7.765-11.848), $2^{nd}$ 15.4 months (95%CI:12.685-18.186), and $3^{rd}$ 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. Conclusions: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.

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