Search

The aim of this study was to evaluate coagulation disorders in patients with metastatic colorectal cancer treated with bevacizumab by using rotation thrombelastogram (ROTEM(®)) and correlate ROTEM(®) parameters with routine coagulation tests. A total of 18 colorectal cancer patients who received bevacizumab combined with chemotherapy were included. There was no statistically significant difference between results of platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen, and D-Dimer obtained at baseline and on day 1 of chemotherapy cycles 4, 8, and 12. CFT value was significantly increased on day 1 of cycle 12 compared with baseline value by both INTEM and EXTEM assays while CT and MCF showed no significant difference. Correlation analysis revealed significant correlation between laboratory parameters and ROTEM(®) parameters. Platelet count showed a positive correlation with MCF in INTEM (r = 0.627) and EXTEM (r = 0.699) assays while showed a negative correlation with CFT in EXTEM (r = -603). There was a significant negative correlation between fibrinogen levels and CFT in INTEM (r = -0.617) and EXTEM (r = -0.512). Our data demonstrated the value of TEG over conventional coagulation tests in evaluating antiangiogenesis agents-induced coagulation disorders.

Aims and Background: The aim of the study was to investigate the alteration in serum matrix metalloproteinase-9 (MMP-9) levels after chemotherapy and the association between the changes in serum levels of MMP-9 and response to chemotherapy in patients with advanced stage non-small cell lung cancer., Methods and Study Design: Twenty-eight consecutive patients with advanced non-small cell lung cancer and 24 healthy controls were enrolled in the study. The patients were treated with cisplatin-based combination chemotherapy. After two cycles, the response was evaluated. Before and after two cycles of chemotherapy, serum samples were collected from the patients., Results: Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001). Prechemotherapy MMP-9 levels were elevated compared to postchemotherapy levels as well (7.2 ± 2.8 vs 5.2 ± 3.3, P = 0.005). Prechemotherapy MMP-9 levels were significantly higher than postchemotherapy MMP-9 levels in patients with partial response (7 patients) (8.2 ± 1.8 and 3.2 ± 2.3, respectively; P = 0.018), but the pre- and postchemotherapy MMP-9 levels were no different in patients with stable disease or progressive disease (21 patients) (7 ± 3.1 and 5.9 ± 3.3, respectively; P = 0.08)., Conclusions: The difference between pre- and postchemotherapy MMP-9 levels in responders was more prominent than that in nonresponders. Whether the decline in serum MMP-9 levels might be used as a marker of response to chemotherapy should be investigated in larger studies.

Purpose: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients., Methods: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves., Results: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease., Conclusion: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

The goal of this study was laboratory testing for hypercoagulability in patients with solid tumors using rotation thrombelastogram (ROTEM) and correlate ROTEM parameters with routine coagulation tests. A total of 78 untreated patients with cancer were included: 28 gastrointestinal system tumors (group 1), 27 respiratory system tumors (group 2), and 23 miscellaneus group of ovarian, renal, nasopharyngeal, mesothelioma, and unknown origin (group 3). Platelet count was significantly increased in group 2 in respect to group 3 (P < 0.05) and fibrinogen level was significantly increased in group 2 in respect to group 1 (P < 0.05). There was no statistically significant difference between subgroups in respect to TEG parameters. Tumor-node-metastasis (TNM) stages of patients was not also associated with either of TEG parameters. Correlation analysis revealed significant correlation between laboratory parameters and ROTEM parameters. Fibrinogen showed the strongest correlation with MCF (r > 0.7) and CFT in all assays (INTEM, EXTEM, FIBTEM, APTEM). There were also statistically significant correlations between platelet number and other ROTEM parameters (INTEM-CFT, -MCF, EXTEM-CFT, -MCF, FIBTEM-MCF, APTEM-CFT, -MCF). In conclusions, our data demonstrates thromboelastographic signs of hypercoagulability in patients with solid tumors. ROTEM is able to identify the contribution of fibrinogen and platelets to clot strength in this patient population.

Objectives: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown., Methods: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique., Results: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis., Conclusions: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.

Rhabdomyosarcoma (RMS) is rare disease in adults (age >or= 16 years). The data from randomized prospective trials are scarce; the clinical outcome of these patients seems poor with the currently available treatment strategies. In this study, we report a single institution's experience in the treatment of adult RMS. We reviewed the medical records of patients with RMS who were >or= 16 years and have been treated in our institution between 1988 and 2003 retrospectively. We analyzed the survival outcome of these patients and the prognostic impact of clinical/pathological factors on their survival. In total, 23 patients with RMS were identified. Median age was 26 years (range, 16-72 years). Majority of patients were male (n: 17, 73.9%), and had large tumors (>or= 5 cm, n: 13, 56.5%), localized disease (N0, M0, n: 12, 52.2%), and embryonal histology (n: 10, 43.5%). Median overall survival was 31.3 months, and the 3-year progression-free survival and overall survival rates were 19.9% and 34.94%, respectively. Patients with smaller tumors (< 5 cm) (p < 0.04), local disease (p < 0.01), and normal lactic dehydrogenase (LDH) level (p < 0.01) at the time of diagnosis were found to have better survival outcome. The tumor size, serum LDH level, and metastatic disease at the time of diagnosis are potential predictors of outcome in patients with adult RMS. Adult RMS is an aggressive disease with poor survival despite treatment. The data from prospective, randomized multicenter trials are necessary in order to improve the clinical outcome of adult RMS patients.

Background: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (mCRC). In this non-randomized pilot study, we investigated the efficacy and safety of sequentially administered XELOX and XELIRI regimens or the reverse sequence in patients with advanced colorectal cancer., Patients and Methods: Entry criteria were histologically confirmed mCRC, ECOG performance status (PS) < or =2 and adequate bone marrow, renal and hepatic function. All patients consecutively received XELOX followed by XELIRI at disease progression or vice versa., Results: In multivariate analysis, independent prognostic factors with worse overall survival were: lower PS (p = 0.0001), multiple metastatic sites (p = 0.016) and high tumor grade. Higher serum levels of alkaline phosphatase and worse ECOG PS were associated with a shorter progression-free survival. Grade 3/4 mucositis, nausea/vomiting, grade 3/4 alopecia and grade 3 diarrhea were more frequent with XELIRI, whereas major toxicity events with XELOX were grade 3 neutropenia, thrombocytopenia and grade 2/3 neurotoxicity., Conclusion: Capecitabine appears to be an acceptable alternative to continuous-infusion fluorouracil (FU)/leucovorin (LV) in combination therapy and offers an effective, but more convenient alternative to continuous infusion FU/LV in the first-line treatment of patients with mCRC., (2008 S. Karger AG, Basel.)

Background: Expression of neuroectodermal markers is a key feature of small cell lung carcinoma (SCLC). Although immune responses against a number of these proteins have been associated with paraneoplastic neuronal disease (PND), most patients with SCLC have anti-neuroectodermal antibodies in the absence of PND. Whether these immune responses affect the clinical outcome in SCLC is critical in understanding the potential value of these proteins as cancer vaccine targets as well as in the pathogenesis of PND., Methods: The authors investigated the frequency of immunoglobulin G autoantibodies against Sry-like high-mobility group box (SOX)1, 2, 3 and Zinc-finger gene of the cerebellum (ZIC)2 proteins in stored serum samples from 90 patients utilizing the lambda-phage plaque assay. Data obtained from patient records were utilized to measure clinical correlates of seroreactivity., Results: Antibodies to SOX1 were present in 28% of patients and another 28% had anti-ZIC2 antibodies, classifying these as some of the most frequent antibody responses observed in SCLC. None had autoimmune paraneoplastic disease. Antibody titers were frequently as high as > or = 1:10(6) and were stable for < or = 6 months after diagnosis. Seroreactivity against either SOX1 or ZIC2 correlated with younger age, lower lactate dehydrogenase levels, and better response to initial therapy., Conclusions: The frequent and stable presence of SOX Group B and/or ZIC2 antibodies in SCLC, but not in healthy individuals examined, indicates they are serological markers of SCLC. However, the correlation between known clinical parameters of less aggressive disease and seroreactivity suggests that these antibodies are indicators of better prognosis in SCLC and warrants further studies to clarify the nature of the underlying immune responses., (Copyright 2005 American Cancer Society.)

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.

Background: Primary hepatocellular carcinoma (HCC) is common in Turkey and its prognosis is poor. In the current study the authors analyzed the prognostic factors and survival in Turkish patients with inoperable HCC with cirrhosis., Methods: Clinical and demographic data of 91 patients consecutively admitted to the authors' institute from 1988 to 2000 were reviewed. A univariate analysis was performed using the Kaplan-Meier method to identify predictors of survival and were compared using the Mantel log-rank test. Independent factors correlated with survival were determined using the Cox regression analysis., Results: Cirrhosis was diagnosed in all patients. Coinfections with HCV and HBV were not observed. Overall median survival was 16.9 months. On univariate analysis, poor performance status (Eastern Cooperative Group); high alpha-fetoprotein (AFP); low albumin; high bilirubin; high alkaline phosphatase; high lactic dehydrogenase; high alanine and aspartate aminotransferase; high gamma-glutamyl transpeptidase; high platelet count; low prothrombin activity; hepatitis B surface antigen positivity; the presence of ascites, encephalopathy, and portal vein thrombosis; poor differentiation and diffuse type of tumor; and no treatment were associated with shorter survival. Multivariate analysis showed that only independent risk factors were related to performance status (Eastern Cooperative Group) at initial presentation and with pathologic characteristic of the tumor: abnormal AFP level., Conclusion: HCC occurred only in patients with liver cirrhosis. Survival time can be predicted from information collected by the physician at the initial assessment.

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.

Serum protein S100 and melanoma-inhibitory protein (MIA) have been described as useful tumor markers for malignant melanoma. In this study, these two serum proteins were compared in 48 patients with melanoma at different stages of disease. Serum concentrations of S100 and MIA were measured by immunoradiometric and enzyme-linked immunosorbent assays, respectively. We found that the cut-off values were 17.4 ng/ml for MIA and 0.09 microg/l for S100. Five patients had stage I-II, 22 had stage III, and 21 had stage IV disease. Serum levels of two markers were elevated with metastatic disease (p < 0.05). Sensitivities of the MIA were found higher compared with S100 in patients with extensive (M1c) metastatic disease and with chemotherapy nonresponders (p > 0.05). We showed a trend for worsened outcome in patients with elevated MIA level in univariate analysis. MIA was found to be more sensitive and is a potential prognostic marker for patients with metastatic malignant melanoma in comparison with S100.

In Western literature, there are few studies investigating the predictors of early versus late recurrence after curative gastrectomy for gastric cancer. The current study analyzed (1) patients who died of recurrent gastric cancer and (2) prognostic factors, which can be applied to timing of death from tumor recurrence. Of 492 patients who underwent curative resection (R0) for gastric cancer in the Department of Surgery, Medical Faculty of Istanbul between 1994 and 2000, 142 patients who died of recurrence were included into study. None of the patients had received postoperative adjuvant treatment. The patients were divided into 2 groups: an early recurrence group that included 102 patients who recurred and died within 2 years after surgery, and a late recurrence group, which included 40 patients who died of recurrence more than 2 years after surgery. Clinicopathologic findings were compared between the early and late recurrence groups. Multivariate analysis was performed to investigate the independent factors, which are predictive for early versus late recurrence, and prognostic factors independently associated with the survival period. In multivariate analysis, the early recurrence group, when compared with the late recurrence group, was characterized by lymph node metastasis (N1-3 versus N0; P = 0.002). Overall survival was influenced by nodal status (N1-3 versus N0; P = 0.003), type of operation performed (radical total versus radical subtotal gastrectomy; P = 0.003), Eastern Cooperative Oncology Group performance status (PS 3-4 versus PS 1-2; P = 0.004), and tumor localization (cardia versus corpus and antrum; P = 0.046). In contrast, T stage of the disease was not prognostic for survival, although it was close to statistical significance (P = 0.066). Multivariate analysis showed that poorer performance status at initial presentation (P = 0.001) and lymph node metastasis (P = 0.032) independently correlated with overall survival (P = 0.002). Lymph node status was the most important factor predictive for early versus late recurrence and patients with lymph node metastases were at more risk of death within 2 years after curative operation for gastric cancer. Postoperative chemoradiotherapy should be especially recommended for patients at high risk of recurrence of adenocarcinoma of the stomach or who have undergone curative resection.

Docetaxel has been the only single active agent against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of docetaxel combined with gemcitabine, another effective drug, in patients with NSCLC previously treated with platinum-based chemotherapy. Thirty-three patients were enrolled. Prior chemotherapy was cisplatin combined with etoposide in 24 patients and vinorelbine in 9 patients. Tumors were sensitive (n = 15), resistant (n = 9), and refractory (n = 9) to front-line chemotherapy. Treatment was docetaxel 85 mg/m(2) on d 1, and gemcitabine 1200 mg/m(2) on d 1 and 8, with cycles repeated every three weeks. Ten patients (30.3%, 95% CI: 15.6-48.7) achieved a partial response and 15 (45.5%) stable disease. Responses were similar frequencies in platinum-sensitive and platinum-resistant/refractory tumors. With a median follow-up period of 5.7 mo (range 1.6-20.0), the median and 6-mo event-free survival were 5.5 mo, 40.6%, respectively. Median and 6-mo overall survival were 7.3 mo and 52.7%. Patients with progressive disease to chemotherapy (p = 0.0008), higher LDH (p = 0.005), and NSE levels (p = 0.03) survived shorter than other patients. In patients refractory to prior chemotherapy, survival was poor as borderline significantly (p = 0.06). The major hematological toxicity was neutropenia. Grade III-IV neutropenia was noted in 14 (42%) patients, with three episodes of febrile neutropenia in 111 cycles. Docetaxel combined with gemcitabine is an active and safe second-line therapy for patients with NSCLC.

The aim of this study is prospectively to evaluate the serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels in detection of acute appendicitis in patients with right iliac fossa pain. Data were collected in prospective manner on 102 consecutive patients with right iliac fossa pain. Laparotomy was performed for suspected acute appendicitis for 55 of the 102 patients, of whom 49 patients had appendicitis, 6 patients non-appendicitis (NA), and the other 47 patients had nonspecific abdominal pain (NSAP) and they did not undergo operation. Among those with appendicitis 31 had acute appendix (AA), 8 had gangrenous appendix (GA), and 10 had perforated appendix (PA). The WBC and CRP the mean (SEM) values were significantly different in AA, GA, and PA groups compared with NSAP and NA groups (P < 0.05). Although the mean IL-6 levels were significantly different only in PA group than the others groups (P < 0.05). The sensitivity and specificity of serum CRP measurements were calculated as 96% and 87%, respectively whereas these were 33% and 83% for IL-6 levels for the diagnosis of the acute appendicitis. As a result, measurement of the CRP levels and WBC have an additional diagnostic value on the diagnosis of the acute appendicitis but determination of IL-6 levels which added to the test combination of WBC and CRP, the sensitivity for the diagnosis of the acute appendicitis was not changed whereas the specificity was decreased to 66%.