Summary. Background Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor type but most patients ultimately experience disease progression. SCLC is associated with alterations in the coagulation system. The present randomized clinical trial (RCT) was designed to determine whether addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) would improve SCLC outcome compared with CT alone. Methods Combination CT consisted of cyclophosphamide, epirubicine and vincristine (CEV) given at 3-weekly intervals for six cycles. Eighty-four patients were randomized to receive either CT alone (n ¼ 42) or CT plus LMWH (n ¼ 42). LMWH consisted of dalteparin given at a dose of 5000 U once daily during the 18 weeks of CT. Results Overall tumor response rates were 42.5% with CT alone and 69.2% with CT plus LMWH (P ¼ 0.07). Median progression-free survival was 6.0 months with CT alone and 10.0 months with CT plus LMWH (P ¼ 0.01). Median overall survival was 8.0 months with CT alone and 13.0 months with CT plus LMWH (P ¼ 0.01). Similar improvement in survival with LMWH treatment occurred in patients with both limited and extensive disease stages. The risk of death in the CT + LMWH group relative to that in the CT group was 0.56 (95% confidence interval 0.30, 0.86) (P ¼ 0.012 by log rank test). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths. Conclusions These results support the concept that anticoagulants, and particularly LMWH, may improve clinical outcomes in SCLC. Further clinical trials of this relatively non-toxic treatment approach are indicated.

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Lack of vasodilator substances, such as nitric oxide (NO), has been implicated in the development of pulmonary hypertension, but the pathogenesis of the disease remains speculative. We hypothesized that NO plays a role in the pathogenesis of primary pulmonary hypertension (PPH), and may serve as a sensitive and specific marker of disease progression and/or severity. To test this, exhaled NO and pulmonary artery pressure were measured in individuals with PPH and secondary pulmonary hypertension (SPH) on various therapies, including the potent vasodilator epoprostenol (prostacyclin), compared with healthy controls. NO in exhaled breath of individuals with PPH was lower than SPH or control (p<0.05). In contrast, exhaled NO of individuals with PPH or SPH receiving epoprostenol was strikingly higher than PPH or SPH individuals not receiving epoprostenol, or controls. Concomitant with higher NO levels, right ventricular systolic pressure of individuals significantly decreased with epoprostenol. Importantly, in paired measures of exhaled NO before and after epoprostenol, NO increased in all pulmonary hypertensive individuals 24 h after initiation of epoprostenol therapy (p<0.05). NO may be a useful noninvasive marker of pulmonary hypertension severity and response to prostacyclin therapy.

In conclusion, the viral etiology (hepatitis B and C infections) in Turkish population is found to be an important factor in HCC development. The Child-Pugh classification, AFP levels, TNM classification, being female and treatment were determined to be important prognostic factors in HCC patients.

In subgroups of breast cancer, the shortest disease-free and overall survival was observed in basaloid and human epidermal growth factor receptor-2 groups. CK5/6 expression is a marker used in diagnosing breast cancers in basaloid group and is associated with a poor prognosis. Similarly, loss of tumor suppressor gene PTEN and a high expression of c-Met has been associated with poor prognosis in breast cancer and many other cancers. In this study, we aimed to determine the effect of CK5/6 and c-Met expressions, and PTEN loss on the disease prognosis in triple-negative breast cancer patients. Ninety-seven patients pathologically diagnosed with triple-negative breast cancer were enrolled. The clinical and pathological characteristics of the patients were recorded. c-Met, PTEN, and CK5/6 expressions were evaluated with immunohistochemical methods from paraffin blocks. The median age of patients was 47 years. CK5/6 positivity was 50.5 %, PTEN loss was 44.3 %, and high c-Met expression was detected in 53.6 %. In multivariate analysis, predictors of the recurrence were loss of PTEN (HR = 2.99; P = 0.004), high c-Met expression (HR = 2.05; P = 0.06), CK5/6 expression (HR = 2.99; P = 0.02), increase in the number of metastatic lymph nodes (HR = 1.11; P = 0.001), and an increase in tumor size (HR = 1.226; P = 0.01). Also, PTEN loss (HR = 2.43; P = 0.05), CK5/6 expression (HR = 3.74; P = 0.01), and N2-3 tumors compared to negatives (HR = 3.63; P = 0.01) were associated with death. PTEN loss correlated with those of lymphovascular invasion. There was a correlation between CK5/6 expression and the number of metastatic lymph nodes. Also, a correlation was found among cancers with highly expressed levels of c-Met, T1-2 tumors, and high-grade tumors. The classical markers, lymph node involvement and tumor size, were found to be of prognostic value; however, high c-Met and CK5/6 expressions, and PTEN loss were found to increase risk of recurrence and death in patients with triple-negative breast cancer.