Erkan Topuz

Oxidative stress in breast cancer.

The present study was undertaken to evaluate the place of oxidative stress on breast cancer. Lipid peroxidation as evidenced by malondialdehyde (MDA) and the status of the antioxidants superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were estimated in tissues of 10 fibroadenoma and 40 breast cancer patients. Lipid peroxidation in breast cancer tissues was enhanced compared to nonmalignant tissues (p<0.001). Similarly, antioxidants SOD (p<0.001) and GPx (p=0.007) in tumor tissues significantly were increased. On the contrary, CAT activity was found significantly decreased (p<0.001). We found that oxidant/antioxidant status was independent from any prognostic factors concerning breast cancer. The results of our study have shown higher oxygen-free-radical production and decreased CAT activity support the oxidative stress hypothesis in breast carcinogenesis.

Prognostic factors in pancreatic carcinoma: Serum LDH levels predict survival in metastatic disease

In this study, our aim was to investigate the impact of various prognostic factors on survival in patients with pancreatic carcinoma. The group consisted of 127 cases with adenocarcinoma histologically. The patients had a median age of 58 years, and 81 (64%) were male. The median survival time of the whole group was 7 months, and the 4-year survival rate was 18%. The median survival duration of the patients without metastases was 8 months, and the survival rate at 1 year was 37.5% and 7.2% at 5 years. It was associated with improved survival compared with the cases with metastatic disease (p < 0.0001). In univariate analysis, decreased performance status (p = 0.0009) and unresectability of tumor (p < 0.0001) were associated with poor outcome. However, only surgery was found to be a statistically significant parameter in multivariate analysis (p = 0.002). The median survival duration of patients with metastases was 5 months, and the 1-year survival rate was 10%. Age younger than 60 years (p = 0.04), decreased serum hemoglobin levels (p = 0.04), and elevated lactic dehydrogenase (LDH) levels (p = 0.0001) were associated with a significantly shorter survival rate. In the Cox model, a high serum LDH level was the only independent unfavorable prognostic factor (p = 0.001). In conclusion, surgical intervention in the group without metastases and serum LDH levels in the group with metastases were the most important prognostic factors influencing survival. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced pancreatic cancer.

Anemia in oncology practice: relation to diseases and their therapies.

Anemia is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. In this study, we investigated the incidence and severity of chemotherapy-induced anemia caused by the most common chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults. Five hundred fifty-two patients with histologically proven carcinoma originating from breast (n = 165), lung (n = 128), colon (n = 75), ovary (n = 84), and malignant lymphoma (n = 100) were included in this study. Hemoglobin levels for each patient were measured with an automatic counter during both pretreatment and before each chemotherapy cycle during therapy. To document the incidence of anemia, the National Cancer Institute grading system was used. Before chemotherapy, 44% of patients with breast carcinoma had anemia. There was a 16% increase in the incidence of anemia after chemotherapy. Severe anemia was observed in less than 1% of patients. No difference was found in the incidence of anemia between the fluorouracil, doxorubicin, cyclophosphamide (FAC) and cyclophosphamide, methotrexate, fluorouracil (CMF) regimens used in the adjuvant setting. However, single-agent chemotherapy with newer generation caused more anemia when compared with the FAC regimen (p < 0.005). Chemotherapy resulted in a significant decrease in hemoglobin levels when compared with pretreatment values in patients with lung cancer (p < 0.001). During treatment, the increase in the incidence of grade II anemia was associated with a parallel decrease in the incidence of grade I anemia. The incidence of severe anemia did not exceed 15%. The incidence of anemia was equivalent in both patients with small-cell lung cancer and those with non–small-cell lung cancer treated with the etoposide and cisplatin (EP) combination. Seventy-one percent of patients with colon cancer had anemia before initiation of chemotherapy. No difference was observed in posttreatment hemoglobin values compared with pretreatment values. Patients treated with irinotecan and fluorouracil and leucovorin (FUFA) combination showed similar rates of anemia. Incidence of anemia in patients with ovarian cancer at admission was 68%. Chemotherapy resulted in a prominent increase in incidence of anemia, which increased to 91.5%. There was an increase in grade II anemia, which corresponded to the decrease in grade I anemia. Less than 10% of patients developed severe anemia. No difference in the incidence of anemia was observed in patients with ovarian cancer treated with either cisplatin and cyclophosphamide or cisplatin combination. Showing a high incidence of anemia (82%) at presentation, hemoglobin levels in patients with malignant lymphoma were unaltered with chemotherapy. Severe anemia occurred in less than 3% of patients. There was a higher incidence of anemia in patients with non-Hodgkin’s lymphoma receiving the cyclophosphamide, epirubicin, vincristine, prednisone (CEOP) regimen in contrast to patients with Hodgkin’s lymphoma treated with the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination. There was a prominent decline in the hemoglobin levels with cisplatin-based combinations in contrast to combinations including noncisplatin agents (p < 0.001). In this study, we have observed equivalent rates of treatment-related anemia when compared with previous data in patients with specific tumor types. The incidence of pretreatment anemia was high in various malignancies. The mechanisms underlying the propensity for a higher risk of pretreatment anemia in patients with malignant disorders and its influence on the outcome has to be elucidated by further population-based and molecular studies.

The prevalence and determinants of the use of complementary and alternative medicine in adult Turkish cancer patients.

A study was undertaken to analyze the extent of using complementary alternative medicine (CAM) and to compare sociodemographic and medical characteristics of users and non-users of CAM in Turkish oncology patients. A total of 615 patients with cancer who attended ambulatory patient care units answered the questionnaires. Medical information was reviewed from chart data. Some 291 patients (47.3%) had used at least one type of CAM since the time of initial diagnosis. CAMs almost always consisted of herbal agents (95%). Nettle (Urticae herba) used in conjunction with (88%) or without (56%) various herbal agents were the most popular and prominent CAMs used by patients. Univariate and multivariate comparisons of users and non-users of CAM were performed. In multivariate analysis, female sex (p=0.0006), high income (p=0.0008), advanced stage at diagnosis (p=0.02), and usage of multiple chemotherapy applications (p=0.03) were determined as independent factors for CAM use.

Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-α, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-α immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-α (p<0.001) and CRP (p<0.001), and lower leptin (p=0.021) levels in patients than in controls. Serum IL-6 cytokine (p=0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-α, and CRP were all similar in lung cancer patients independently from severity of weight loss (p>0.05). A direct relationship was found between serum IL-6 and TNF-α levels (r=0.530, p=0.004). We found that both serum leptin (p=0.046) and IL-6 (p=0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-α and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p=0.06) related to a worse prognosis.

Multiple primary neoplasms at a single institution: differences between synchronous and metachronous neoplasms.

During the 10-year period (1987-1996) of our study, 26,255 patients with cancer were admitted to our clinic and, of these, 271 (1%) patients had multiple primary malignant tumors. Ninety-two (34%) patients had synchronous tumors (synchronous group), and 179 (66%) patients had metachronous tumors (metachronous group). The mean age at first diagnosis was higher in the former group. The ratio of men to women was 1.36 in the synchronous group and 0.74 in the metachronous group (p = 0.018). Smokers and drinkers were more common in the synchronous group. Breast cancer and lung cancer were most prevalent, and associations between head/neck and lung cancer and between breast and breast cancer were the most frequent associations in both the synchronous and the metachronous group. The frequency of aerodigestive tumors was higher and that of mesenchymal tumors was lower in the synchronous group than in the metachronous group. Localization in the medial region and in the head/neck was more frequent in the synchronous group than in the case of metachronous secondary tumors.

Serum Vascular Endothelial Growth Factor (VEGF) and Interleukin-8 (IL-8) Levels in Small Cell Lung Cancer

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.

Serum IL-8 and IL-12 levels in breast cancer

Interleukins (ILs) are known to play a fundamental role in cancer. We investigated the serum levels of IL-8 and IL-12, in breast cancer patients, and their relationship with the prognostic parameters and therapy. Fortyeight patients with pathologically verified breast carcinoma and 21 healthy controls were enrolled into the study. Serum samples were obtained at baseline and after two cycles of chemotherapy. Serum IL-8 and IL-12 levels were determined using enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the baseline serum IL-8 and IL-12 levels between breast cancer patients and healthy controls (p = 0.365 andp = 0.871, respectively), no significant correlation between the prognostic parameters and the serum IL-8, IL-12 levels. However, in the subgroup consisting of metastatic breast cancer patients, baseline serum IL-8 levels were significantly higher compared with non-metastatic disease (p = 0.047). Anthracycline-based chemotherapy and the addition of taxane did not change the levels of both serum IL-8 and IL-12. Serum IL-8 level may be useful in determining metastatic breast cancer. Larger studies are needed to confirm this finding.

The value of serum levels of IL-6, TNF-alpha, and erythropoietin in metastatic malignant melanoma: serum IL-6 level is a valuable prognostic factor at least as serum LDH in advanced melanoma.

In order to study the relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of IL-6, TNF-alpha, and erythropoietin (EPO) and metastatic distribution and survival in 16 patients with metastatic malignant melanoma. IL-6 and TNF-alpha immunoassay (R&D Systems, Inc. Minneapolis, USA) employs the quantitative sandwich enzyme immunoassay technique. The Quantikine IVD EPO ELISA (R&D Systems, Inc.) is based on the double-antibody sandwich method. The baseline serum IL-6 and EPO levels were significantly higher in patients with metastatic malignant melanoma than in the control group (p=0.009 and p=0.033, respectively). Serum IL-6 levels were higher in patients with weight loss (p=0.02), who were anemic (p=0.026), with elevated serum LDH levels (p=0.028), and who were chemotherapy nonresponding (p=0.016). The relationship of serum IL-6 concentration to the tumor burden was not determined. Only serum EPO level was influenced by hemoglobin status (p=0.001). No difference was shown among these three parameters. Elevated serum IL-6 concentration (p=0.002) was found to be an adverse prognostic factor in patients with poor performance status, weight loss, low serum hemoglobin, elevated serum LDH, and unresponsive to chemotherapy. On the other hand, both serum TNF-alpha and EPO levels were of no prognostic value. Serum levels of IL-6 were found to be prognostic factors as valuable as serum LDH levels in patients with metastatic malignant melanoma. Their prognostic value should be further evaluated in a larger patient population.

Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer.

&NA; Serum lactate dehydrogenase (LDH) is a biochemical parameter that is elevated in the majority of extensive‐stage small‐cell lung cancer (SCLC). In this study, distribution and prognostic importance of serum LDH in limited‐disease SCLC were investigated. Serum concentrations of LDH were measured in 184 patients at initial examination. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. Significant positive association was found between LDH levels and weight loss, performance status, response to chemotherapy, and albumin but not between age, gender, and hemoglobin values. Patients with high concentrations of LDH had a significantly worse prognosis than did patients with normal levels. The probability of overall survival at 1 year was 60.2% in patients with normal serum LDH levels and 33.1% in patients with higher values (p = 0.0017). Also, the prognostic value of LDH on overall survival was shown in multivariate analysis (p = 0.05). At the time of diagnosis, serum levels of LDH appear to have a significant relation to outcome in patients with limited‐stage SCLC.