Mutlu Dogan

Venous Thromboembolism in Patients with Cancer and Its Relationship to the Coagulation Cascade and Vascular Endothelial Growth Factor

Venous thromboembolism (VTE) is a well-recognized problem in malignancy. Patients with cancer who have VTE have a worse prognosis than other patients with cancer. Hypercoagulability in patients with cancer is related to malignancy itself and its treatment. These patients have multiple risk factors for thromboembolism, such as being immobilized, having central venous catheters, and receiving chemoradiation therapy. Cancer procoagulant, tissue factor, factor VIII, and thrombin have important roles in causing cancer-associated thromboembolism. Tumors require neovascularization for delivering oxygen and other nutrients. Therefore, angiogenesis facilitates tumor growth, invasion, and metastasis. New blood vessels formed by angiogenesis are thrombogenic. Hypercoagulability and tumor growth are closely related. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that may also cause VTE in patients with cancer. The relationship between cancer, angiogenesis, VEGF, and thrombosis is reviewed herein. Studies are ongoing to enhance our understanding of this complex interaction.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer.

BACKGROUND Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. RESULTS A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ≥3.24) and PNI (<49.5 or ≥49.5). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). CONCLUSIONS NLR (≥3.24) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer

SummaryBackgroundIt was reported that hematological markers of systemic inflammatory response might be prognostic in various cancer types. We aimed to evaluate the platelet/lymphocyte ratio (PLR) as a prognostic factor and its effect on overall survival in non-small cell lung cancer (NSCLC).MethodsClinicopathological characteristics and basal (pretreatment) PLR of 145 patients with NSCLC were evaluated retrospectively. The preoperative or pretreatment blood count data were obtained from the recorded computerized database. PLR was defined as the absolute platelet count divided by the absolute lymphocyte count.ResultsA total of 145 patients were enrolled. Median age was 57 years(range 26–83). Receiver operating characteristic curves for overall survival prediction were plotted to verify the optimum cut-off point for PLR. The recommended cut-off values for PLR was 198.2 with a sensitivity of 65.0 % and a specificity of 71.4 %. Median overall survival was 34.0 (95 % confidence interval (CI) 14.7–53.3) months in the group with low PLR (< 198.2), while it was 11.0 (95 % CI 5.6–16.3) months in the group with high PLR (≥ 198.2). The difference between the groups was statistically significant (p < 0.0001).ConclusionsOur study supports the view that a high basal PLR is a poor prognostic factor in NSCLC. However, the validity of the cut-off values for PLR identified in our study needs further prospective trials.

The effect of venous thromboembolism on survival of cancer patients and its relationship with serum levels of factor VIII and vascular endothelial growth factor: a prospective matched-paired study.

BACKGROUND Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascu-lar endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND METHODS Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were hav-ing the same malignancy, stage, metastatic site, performance status and age (5 years) as patients in the VT group. RESULTS Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). CONCLUSION There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.

The relationship between platelet-lymphocyte ratio, neutrophil-lymphocyte ratio, and survival in metastatic gastric cancer on firstline modified docetaxel and cisplatinum plus 5 Fluorourasil Regimen: A single institute experience.

Background/Aims: The association between platelet–lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), and survival with response rates were evaluated in metastatic gastric cancer (MGC). Patients and Methods: MGC patients on firstline modified docetaxel/cisplatinum/5-fluorourasil [mDCF; docetaxel 60 mg/m2 (days 1–5), cisplatin 60 mg/m2 (day 1), 5FU 600 mg/m2 (days 1–5), q3w] were evaluated retrospectively. The cutoff values were 160 for PLR and 2.5 for NLR. Progression-free survival (PFS) and overall survival (OS) were estimated for group I (PLR >160), group II (PLR ≤ 160), group III (NLR ≥ 2.5), group IV (NLR < 2.5), group V (PLR > 160 and NLR ≥ 2.5), group VI (PLR ≤ 160 and NLR <2.5), and group VII [VIIa (PLR > 160 and NLR < 2.5) and VIIb (PLR ≤160 and NLR ≥ 2.5)]. Results: One hundred and nine MGC patients were evaluated for basal hematological parameters and survival analysis, retrospectively. Most of the patients were male in their fifties with grade III adenocarcinoma (62.9%) and liver metastasis (46.7%). Patients with PLR > 160 and/or NLR ≥ 2.5 had significantly shorter PFS and OS (P = 0.04, 0.01, 0.019, and P = 0.003, 0.002, 0.000, respectively). Conclusion: High PLR (> 160) and/or NLR (≥ 2.5) seem to be poor prognostic factors in MGC.

A rare gastric neoplasm: gastric medullary carcinoma

A 57-year-old female patient with early stage gastric medullary carcinoma is presented with review of the literature.

Is plasma caveolin-1 level a prognostic biomarker in metastatic pancreatic cancer?

Background/Aims: To evaluate the prognostic significance of plasma caveolin (CAV)-1 and its association with survival and treatment response rates in metastatic pancreatic cancer (MPC). Patients and Methods: Plasma samples were prospectively collected from 41 patients with newly diagnosed MPC. Moreover, plasma samples were collected from 48 patients with chronic pancreatitis and 41 healthy individuals (control groups) for assessing Cav-1 levels. Plasma Cav-1 levels were evaluated at baseline and after three cycles of chemotherapy in the patients with MPC. Results: The median Cav-1 level was 13.8 ng/mL for the patients with MPC and 12.2 ng/mL for healthy individuals (P = 0.009). The Cav-1 cut-off level was calculated as 11.6 ng/mL by using the receiver operating characteristic curve. The median overall survival and progression-free survival rates were 5 and 2.4 months, respectively, for participants with a high basal plasma Cav-1 level; the corresponding values were 10.5 and 9.4 months for participants with a low plasma Cav-1 level (P = 0.011 and P= 0.003, respectively). Of the 41 patients with MPC, 23 completed at least three cycles of chemotherapy. The median Cav-1 level was 13 ng/mL for post-treatment MPC (r2: 0.917; P= 0.001). High basal plasma caveolin-1 level have continued to remain at high levels even after chemotherapy, showing a trend toward worse response rates (P = 0.086). Conclusion: High basal plasma Cav-1 levels seem to be associated with poor survival and tend to yield worse therapeutic outcomes in patients with MPC. This study is the first to evaluate the prognostic significance of plasma Cav-1 levels as a prognostic factor in patients with MPC. However, larger prospective clinical trials are warranted.

Evaluation of the effects of red blood cell distribution width on survival in lung cancer patients

Aim of the study Data are available indicating that red blood cell distribution width (RDW) is higher in cancer patients compared to healthy individuals or benign events. In our study, we aimed to investigate the influence of different RDW levels on survival in lung cancer patients. Material and methods Clinical and laboratory data from 146 patients with lung cancer and 40 healthy subjects were retrospectively studied. RDW was recorded before the application of any treatment. Patients were categorised according to four different RDW cut-off values (median RDW, RDW determined by ROC curve analysis, the upper limit at the automatic blood count device, and RDW cut of value which used in previous studies). Kaplan-Meier survival analysis was used to examine the effect of RDW on survival for each cut-off level. Results The median age of patients was 56.5 years (range: 26–83 years). The difference in median RDW between patients and the control group was statistically significant (14.0 and 13.8, respectively, p = 0.04). There was no difference with regard to overall survival when patients with RDW ≥ 14.0 were compared to those with RDW < 14.0 (p = 0.70); however, overall survival was 3.0 months shorter in low values of its own group in each of the following cut-off values: ≥ 14.2 (p = 0.34), ≥ 14.5 (p = 0.25), ≥ 15 (p = 0.59), although no results were statistically significant. Discussion We consider that the difference between low and high RDW values according to certain cut-off values may reflect the statistics of larger studies although there is a statistically negative correlation between RDW level and survival.

Oxaliplatin-induced acute thrombocytopenia.

Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular deoxyribonucleic acid (DNA) by leading covalent bifunctional DNA adducts with cellular DNA. Major side effects of oxaliplatin are neurotoxicity (peripheral neuropathy), myelosuppression with moderate thrombocytopenia and gastrointestinal toxicity (diarrhea). Thrombocytopenia might be related to myelosuppression and/or drug-induced immune thrombocytopenia (DIIT). In here, oxaliplatin-induced thrombocytopenia is discussed with review of the literature.

Molecular Spectrum of PIK3CA Gene Mutations in Patients with Nonsmall-Cell Lung Cancer in Turkey

AIMS The aim of the present study was to obtain the first data for the phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutation frequency among nonsmall-cell lung cancer (NSCLC) patients in Turkey. All exons of the PIK3CA gene were investigated by sequence analysis in 40 NSCLC tumor tissue samples. RESULTS The 1634A>C mutation, which has previously been identified in many cancers including NSCLC, was identified in three tumor tissue samples in the present study. Interestingly, a second mutation (1658_1659delGTinsC) was also identified in these patients. The concurrence of these two mutations has been reported as the Cowden syndrome, which is known to be a cancer predisposition syndrome. This finding is important since it may be an indicator of the underlying cancer predisposition syndrome in NSCLC patients. Moreover, four novel mutations were identified in the present study. However, in vitro studies are required to evaluate the effects of these mutations on kinase activation. CONCLUSIONS The high frequency of PIK3CA mutations exerts important clinical implications for targeted therapy. This finding indicates that therapeutic agents targeting the phosphatidylinositol 3-kinase (PI3K) would be beneficial in the NSCLC subpopulation.