Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

AIM: To evaluate outcomes of radiofrequency ablation(RFA) therapy for early hepatocellular carcinoma(HCC) and identify survival- and recurrence-related factors. METHODS: Consecutive patients diagnosed with early HCC by computed tomography(CT) or magnetic resonance imaging(MRI)(single nodule of ≤ 5 cm, or multi-(up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Cancer do Estado de S o Paulo, Brazil were enrolled in the study. RFA of the liver tumors(with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response(absence of enhancing tissue at the tumor site) or incomplete response(enhancing tissue remaining at the tumor site). Overall survival and diseasefree survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model. RESULTS: A total of 38 RFA sessions were performed during the study period on 34 patients(age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo(range, 1-33). The study population showed predominance of male sex(76%), less severe liver disease(Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor(65%). The maximum tumor diameters ranged from 10 to 50 mm(median, 26 mm). The initial(immediately post-procedure) rate of RFAinduced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule(vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema(resolved with intervention) and intestinal perforation(led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis(HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1-and 2-year cumulative disease-free survival rates were 65% and 36%, respectively. CONCLUSION: RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.     

Comparison between reference values for FVC,FEV1, and FEV1/FVC ratio in White adults in Brazil and those suggested by the Global Lung Function Initiative 2012

OBJECTIVE:

To evaluate the spirometry values predicted by the 2012 Global Lung Function Initiative (GLI) equations, which are recommended for international use, in comparison with those obtained for a sample of White adults used for the establishment of reference equations for spirometry in Brazil.

METHODS:

The sample comprised 270 and 373 healthy males and females, respectively. The mean differences between the values found in this sample and the predicted values calculated from the GLI equations for FVC, FEV₁, and VEF₁/FVC, as well as their lower limits, were compared by paired t-test. The predicted values by each pair of equations were compared in various combinations of age and height.

RESULTS:

For the males in our study sample, the values obtained for all of the variables studied were significantly higher than those predicted by the GLI equations (p < 0.01 for all). These differences become more evident in subjects who were shorter in stature and older. For the females in our study sample, only the lower limit of the FEV₁/FVC ratio was significantly higher than that predicted by the GLI equation.

CONCLUSIONS:

The predicted values suggested by the GLI equations for White adults were significantly lower than those used as reference values for males in Brazil. For both genders, the lower limit of the FEV₁/FVC ratio is significantly lower than that predicted by the GLI equations.     

Study of intestinal malabsorption diseases as cause of monosymptomatic short stature

OBJECTIVE: This study was carried out in order to evaluate the etiology of monosymptomatic childhood short stature (below the third percentile or with growth rate of less than 5 cm/year) with emphasis on causes due to intestinal malabsorption. METHODS: Each patient was submitted to endocrinological, biochemical and hematological investigation. Determination of serum anti-gliadin antibodies, fecal fat, chloride levels in sweat, jejunal biopsy and bone age was also obtained.RESULTS: A total of 51 children was studied, most of them belonging to the group of normal variants. Four children had abnormally high sweat chloride, compatible with the diagnosis of cystic fibrosis. These children were asymptomatic regarding respiratory and gastrointestinal tract. CONCLUSIONS: We conclude that cystic fibrosis, besides celiac disease, must be included in the differential diagnosis of short stature in childhood.     

ACE activity is modulated by kinin B2 receptor

Angiotensin-converting enzyme (ACE) is an ectoprotein able to modulate the activity of a plethora of compounds, among them angiotensin I and bradykinin. Despite several decades of research, new aspects of the mechanism of action of ACE have been elucidated, expanding our understanding of its role not only in cardiovascular regulation but also in different areas. Recent findings have ascribed an important role for ACE/kinin B(2) receptor heterodimerization in the pharmacological properties of the receptor. In this work, we tested the hypothesis that this interaction also affects ACE enzymatic activity. ACE catalytic activity was analyzed in Chinese hamster ovary cell monolayers coexpressing the somatic form of the enzyme and the receptor coding region using as substrate the fluorescence resonance energy transfer peptide Abz-FRK(Dnp)P-OH. Results show that the coexpression of the kinin B(2) receptor leads to an augmentation in ACE activity. In addition, this effect could be blocked by the B(2) receptor antagonist icatibant. The hypothesis was also tested in endothelial cells, a more physiological system, where both proteins are naturally expressed. Endothelial cells from genetically ablated kinin B(2) receptor mice showed a decreased ACE activity when compared with wild-type mice cells. In summary, this is the first report showing that the ACE/kinin B(2) receptor interaction modulates ACE activity. Taking into account the interplay among ACE, ACE inhibitors, and kinin receptors, we believe that these results will shed new light into the arena of the controversial search for the mechanism controlling these interactions.     

Differential Effects of Thalidomide on Angiogenesis and Tumor Growth in Mice

Thalidomide, clinically used as an antiinflammatory and antitumoral drug, inhibited sponge-induced angiogenesis when administered systemically (100 mg/kg^–1) in mice. However, it failed to inhibit solid Ehrlich tumor in the same mouse strain. We have used functional, biochemical and histological parameters to assess neovascularization and fibrovascular tissue infiltration of the mice sponge granuloma. The neovascularization growth as detected by development of blood flow and hemoglobin content extracted from the implants showed that thalidomide inhibited fibrovascular tissue formation by 40%. The functional and biochemical parameters correlated well with the histological study. Thalidomide had no inhibitory effect in the development of Ehrlich tumor. The detection of this selective action using the same animal strain bearing two different processes, supports the hypothesis that rather than species specificity, thalidomide is tissue specific. This approach may be used to identify the specificity of other therapeutic agents against distinct angiogenesis-dependent diseases.