Ary Serpa Neto

Her-2/neu expression in prostate adenocarcinoma: a systematic review and meta-analysis.

PURPOSE HER-2/neu has been linked to the clinical progression of hormone independent prostate cancer. We performed a meta-analysis to investigate the prognostic impact of HER-2/neu over expression in patients with prostate adenocarcinoma, and its correlation with other pathological and clinical variables. MATERIALS AND METHODS We searched the MEDLINE, Embase, CancerLit and ASCO abstract databases for published studies of HER-2/neu protein expression in primary prostate cancer tissue with a median followup of greater than 2 years and data on survival in patients with and without HER-2/neu over expression. We separately analyzed studies reporting HER-2/neu soluble receptor levels in patients with prostate cancer. RESULTS We included 38 articles with a total of 5,976 patients. The overall RR of death in those with HER-2/neu over expression in the primary tumor was 1.63 (95% CI 1.47-1.82, p <0.0001). In the presence of over expression the recurrence RR was 1.87 (95% CI 1.59-2.21, p <0.0001). High HER-2/neu extracellular domain levels also correlated with death (RR 2.01, 95% CI 1.21-3.35, p = 0.007) and recurrence (RR 1.74, 95% CI 1.41-2.15, p <0.0001). CONCLUSIONS There is a consistent association of HER-2/neu over expression and Gleason less than 7 with a higher RR of death and recurrence in patients with prostate cancer. Further clinical trials should test the hypothesis that HER-2/neu is a marker of a clinically worse outcome in patients with prostate cancer and a potential target for therapy.

A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma

BackgroundOsteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa per se. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT).MethodsThe Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia.ResultsThirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; p < 0.00001) and a higher risk of fractures (RR, 1.17; p < 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (p = 0.031) but it was similar to bone mineral density found in healthy controls (p = 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearmans rho = -0.490 and -0.773; p = 0.028 and 0.001, respectively) and with total hip t score (Spearmans rho = -0.900; p = 0.037).ConclusionWe found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.

Dynamic Sentinel Node Biopsy for Inguinal Lymph Node Staging in Patients with Penile Cancer: A Systematic Review and Cumulative Analysis of the Literature

BackgroundDynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection (ILND). However, a prophylactic bilateral ILND is a procedure with approximately 50% of morbidity. The purpose of this review is to evaluate the accuracy of DSNB in penile cancer.MethodsThis is a systematic review and cumulative analysis of studies published between 1966 and 2010. The Medline, Embase, Cancerlit, and American Society of Clinical Oncology abstract databases were searched for published studies on penile cancer and DSNB. The outcomes assessed were: sensitivity, specificity, likelihood ratios, and summary receiver operating characteristics (ROC) curves.ResultsTen articles covering 519 participants were included in the cumulative analysis. The pooled sensitivities and specificities for sentinel node biopsy for detection of metastasis were 77.1 and 100% versus ILND and 87.9 and 100% versus wait and see program. The false-negative rate founded was 3.1% in the ILND group and 3.5% in the wait and see group.ConclusionsThe use of dynamic sentinel lymph node biopsy to detect lymph node metastasis in specialized centers appears to be justified. Addiction of other techniques to DSNB to reduce false-negative results is awaited and must be confirmed by future studies.

Molecular oncogenesis of prostate adenocarcinoma: role of the human epidermal growth factor receptor 2 (HER-2/ neu )

The potential mechanisms involving the genesis and growth of androgen-independent prostate cancer include super-expression of the androgen receptor (AR), in an attempt to compensate for the low androgenic plasma levels and mutations of this specific receptor, which could determine resistance to anti-androgenic therapy. However, most advanced prostate tumors have no mutations or amplifications of the AR, suggesting a potential role of non-androgenic growth factors, including epidermal growth factor (EGF), transforming growth factor α, insulin-like growth factor (IGF-1) and fibroblast growth factor. More specifically, these factors, and their receptors like EGFR (HER-1) and HER-2/neu, through paracrine and autocrine mechanisms, may contribute to the proliferation and growth of prostate cancer. Free full text available at www.tumorionline.it

Terapia de privación de andrógenos y obesidad mórbida: ¿tienen en común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.

Relation of uric acid with components of metabolic syndrome before and after Roux-en-Y gastric bypass in morbidly obese subjects

OBJECTIVE The purpose of the study was to investigate the prevalence of hyperuricemia in morbidly obese subjects before and after Roux-en-Y gastric bypass (RYGBP) and its relationship with metabolic syndrome abnormalities. SUBJECTS AND METHOD We evaluated 420 morbidly obese patients. Pre and postoperative (8 months after RYGBP) blood samples were drawn. Obese patients underwent laparoscopic RYGBP and after eight months all the tests were repeated. RESULTS The overall prevalence of hyperuricemia was 34.28%. Hyperuricemia was more common in men than in women (51.72 vs. 29.72%; p = 0.0002). Men with hyperuricemia were more likely to have diabetes (p = 0.034) and more elevated fasting plasma glucose levels (p = 0.027). Women with hyperuricemia were more likely to have hypertension (p = 0.003), metabolic syndrome (p = 0.001), elevated triglycerides (p = 0.001) and GGT (p = 0.009), and decreased HDL (p = 0.011). After surgery, uric acid levels decreased from 5.60 ± 1.28 to 4.23 ± 1.20 (p < 0.0001). The prevalence of hyperuricemia decreased from 33.6% to 6.4% (p < 0.0001), in men from 48.3% to 17.2% (p < 0.0001) and in women from 29.7% to 3.6% (p < 0.0001). CONCLUSION Concentrations of uric acid were associated with the prevalence of metabolic abnormalities in this sample of morbidly obese patients. Also, weight loss after RYGBP can reduce uric acid levels and the prevalence of hyperuricemia.

Ten Years of Docetaxel-Based Therapies in Prostate Adenocarcinoma: A Systematic Review and Meta-Analysis of 2244 Patients in 12 Randomized Clinical Trials

BACKGROUND Chemotherapy can reduce serum prostate-specific antigen (PSA) levels and relieve pain in some patients with castration-resistant prostate cancer (CRPC). To improve therapeutic efficacy numerous randomized trials have investigated docetaxel-based combination regimens. The present analysis tries to overcome the statistical limitations of the individual trials and investigates the treatment effects in total and in various combination groups. METHODS The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published randomized placebo-controlled trials evaluating the use of docetaxel-based regimens in patients with CRPC. The outcomes assessed were overall survival, overall response rate, PSA response rate, and adverse effects. RESULTS Twelve articles (2244 participants) were included in the meta-analysis. The analysis demonstrates a higher PSA response rate from docetaxel-based combinations when compared with docetaxel alone (relative risk [RR] = 1.16; P = .010). The estimated median survival in docetaxel-based combinations was statistically significantly longer than in the docetaxel-alone group (22.0 vs. 18.4 months; P = .037). Grade 3 or 4 neutropenia as well as grade 3 or 4 thromboembolic events were similar in both arms (overall RR, 0.87 [confidence interval (CI) 0.71-1.07]; P = .20 and overall RR 1.52 [0.79 - 2.90]; P = .21, respectively). CONCLUSION The analysis of 12 randomized trials provides evidence in favor of docetaxel-based combination chemotherapy for patients with CRPC and good performance status.

Methodological Standardization for the Extraction of Free DNA in Plasma of Peripheral Blood

Background: Biological materials such as cells, DNA, RNA, and proteins can be recovered from blood, urine, feces, pancreatic juice and sputum of patients. Here, we described a method for free plasma DNA extraction used in our laboratory, compared it to one of the most reproduced in the literature, and also verified the effects of short time storage of plasma on DNA quantification. Methods: We assessed DNA concentrations in four samples of peripheral blood one hour, one day and three days after plasma separation (part A). EDTA blood (10 mL) was collected from each individual (10) and the specimen was centrifuged at 1,300 g for 10 min. The supernatant was transferred into polypropylene tubes, with particular attention not to disturb the buffy coat layer and the plasma was microcentrifuged at 2,400 g. DNA extracted from plasma was quantified (part B). Results: Mean DNA concentration after our extraction process was similar to those methods found in literature. Moreover, we found a consistently negative correlation between time after plasma collection and DNA concentrations (r = -0.568; p = 0.022). Conclusion: We showed a new method for DNA extraction. Also, we verified that fast processing after plasma collection was necessary to produce realistic results of plasma DNA.

Predictive performance of 12 equations for estimating glomerular filtration rate in severely obese patients

OBJECTIVE Considering that the Cockcroft-Gault formula and the equation of diet modification in renal disease are amply used in clinical practice to estimate the glomerular filtration rate, although they seem to have low accuracy in obese patients, the present study intends to evaluate the predictive performance of 12 equations used to estimate the glomerular filtration rate in obese patients. METHODS This is a cross-sectional retrospective study, conducted between 2007 and 2008 and carried out at a university, of 140 patients with severe obesity (mean body mass index 44 ± 4.4 kg/m2). The glomerular filtration rate was determined by means of 24-hour urine samples. Patients were classified into one or more of the four subgroups: impaired glucose tolerance (n = 43), diabetic (n = 24), metabolic syndrome (n = 76), and/or hypertension (n = 66). We used bias, precision, and accuracy to assess the predictive performance of each equation in the entire group and in the subgroups. RESULTS In renal disease, Cockcroft-Gaults formula and the diet modification equation are not precise in severely obese patients (precision: 40.9 and 33.4, respectively). Sobhs equation showed no bias in the general group or in two subgroups. Salazar-Corcorans and Sobhs equations showed no bias for the entire group (Bias: -5.2, 95% confidence interval (CI) = -11.4, 1.0, and 6. 2; 95%CI = -0.3, 12.7, respectively). All the other equations were imprecise for the entire group. CONCLUSION Of the equations studied, those of Sobh and Salazar-Corcoran seem to be the best for estimating the glomerular filtration rate in severely obese patients analyzed in our study.

Estudo descritivo da mortalidade por câncer de próstata no Estado de São Paulo no período de 1980-2007

objective: Prostate cancer is the second most common neoplasm among men worldwide. This study aimed to examine the trend in mortality rates of prostate cancer among the population in the State of São Paulo, Brazil, from 1980 to 2007. Methods: a descriptive study of temporal series was conducted using mortality data due to prostate cancer between1980 and 2007 in the State of São Paulo. Mortality rates were obtained from the SUS Information System on Mortality (SIM/SUS – DATASUS). The age-specific mortality rates were calculated as well as linear regression and temporal trend analysis. results: It could be observed that mortality increased according to age, being very similar only between the age group 70-79 years and ≥ 80 years (p = 0.047). The mortality peak in the age group 50-79 years occurred at the same time; however, the drop in mortality rates since then has been much more pronounced in the group of 50-59 years. There was a linear increase and direct association between the number of biopsies and the incidence of prostate cancer (r = 0.714, p = 0.024). Conclusions: Prostate cancer is a major cause of mortality in São Paulo and effective screening and treatment measures should be adopted to improve this scenario.