Statins Prevent Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy: A Single-center Retrospective Study with a Median Follow-up of 51.20 Months.

INTRODUCTION: Prostate cancer is the most commonly diagnosed cancer in men. Radical prostatectomy is a potentially curative alternative for localized disease, although a significant percentage of these patients will suffer a biochemical recurrence with associated mortality. A wide spectrum of anticancer properties of statins has been demonstrated and the role of these drugs in prevention and treatment of other types of cancer is being increasingly studied. OBJECTIVE: The aim of this study was to investigate whether the use of statins is associated with reduced risk of biochemical recurrence among patients submitted to radical prostatectomy. PATIENTS AND METHODS: We retrospectively reviewed 875 patients submitted to radical prostatectomy between January 2009 and December 2018. Approximately 45.7% of the patients were on medication with statins at the time of surgery. We evaluated a possible association between statin use and biochemical recurrence and which patients would benefit the most with statin treatment. RESULTS: Overall, statins were associated with an approximately 40% reduction in risk of biochemical recurrence at a median follow-up time of 51.2 months (HR 0.599, p<0.05). Patients with pT2c staging (HR 0.486, p=0.017) and ISUP ≥3 (HR 0.61, p=0.011) seem to have benefited more from statin use. CONCLUSION: In this cohort, use of statins proved beneficial in reducing the risk of biochemical recurrence among patients submitted to radical prostatectomy. Prospective studies are required to confirm this result and to evaluate its safety profile in those patients.

Aortic valve microcalcification and cardiovascular risk: an exploratory study using sodium fluoride in high cardiovascular risk patients.

18F-sodium fluoride (18F-NaF) has been used to access aortic stenosis in clinical research setting. It is known that its uptake is related with microcalcification. The purpose of this study was to assess the relationship between 18F-NaF uptake by the aortic valve and cardiovascular risk. Twenty-five patients with risk factors for cardiovascular disease, without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD (Atherosclerotic Cardiovascular Disease) risk calculator. Aortic valve 18F-NaF (AoVCUL) uptake was evaluated through the corrected uptake per lesion (CUL = max SUV - mean blood-pool SUV). Calcium score was obtained through cardiac CT. The patients present a mean age of 63.90 ± 8.60 years and 56% males. The mean ASCVD was of 28.76 ± 18.96 (M 25, IQR 38.50). The mean aortic valve calcium score (AoVCaSc) was of 53.24 ± 164.38 (M 6; IQR 29.75) and the AoVCUL was of 0.50 ± 0.10 (M 0.52, IQR 0.15). The patients were classified according to the ASCVD: patients with a risk greater or equal than the 50th percentile of the ASCVD risk and patients with a risk lower than the 50th percentile. The AoVCUL was evaluated in both groups: AoVCUL = 0.56 ± 0.10 vs 0.42 ± 0.15, p = 0.02; AoVCaSc was of 0 in 11 patients (44%) and those with an ASCVD greater or equal than the 50th percentile had a mean AoVCaSc of 8.00 ± 13.80, and those with an ASCVD risk lower than the 50th percentile had a mean AoVCaSc of 95.00 ± 223.45; p = 0.09. In this study microcalcification, evaluated through 18F-NaF on PET-CT, was related with cardiovascular risk. Although the score of calcium seems to be higher in higher cardiovascular risk patients, no significant difference was found between groups.

Renal artery wall 18F-NaF activity and glomerular filtration rate: an exploratory analysis in a high cardiovascular risk population.

OBJECTIVES: Atherosclerotic plaque molecular imaging with F-sodium fluoride (NaF) PET with computed tomography (PET-CT) may identify active unstable microcalcification. We sought to explore renal arteries calcification activity in a group of high cardiovascular (CV) risk subjects without manifest CV disease. METHODS: High CV risk hypertensive individuals from a single centre were prospectively scanned with F-NaF-PET-CT in major vascular territories. Renal arterial wall activity was retrospectively analysed and expressed as the ratio between maximum standard uptake value in the lesion and mean blood pool activity in the superior vena cava [tissue-to-background ratio (TBR)]. We explored renal artery wall F-NaF activity's association to CV risk factors and renal function. RESULTS: Mean age was 64 ± 8.6 years, 56% male, 96% Caucasian and 24% had chronic kidney disease (CKD) (n = 25). Six individuals (24%) showed renal artery wall radiotracer uptake (TBR 1.4 ± 0.4); these subjects were heavier, had higher triglycerides, high-sensitivity C-reactive protein and predicted CV risk (SCORE) compared to the remaining cohort (P < 0.05 for all comparisons). There was a trend toward higher F-NaF uptake in other major vessels and increased thoracic fat volume in subjects with renal artery wall uptake. Glomerular filtration rate (GFR) was lower in subjects with positive renal plaques (93.0 ± 29.7 vs. 65.0 ± 19.7 ml/min, P = 0.04). Renal artery radiotracer uptake and eGFR were inversely correlated (r = -0.42, P = 0.04). CONCLUSION: In a high CV risk group without manifest CV disease, higher renal artery wall F-NaF activity is associated with superior predicted CV risk and lower GFR.

Metabolic tumor burden quantified on [18F]FDG PET/CT improves TNM staging of lung cancer patients.

PURPOSE: The purpose of our study was to test a new staging algorithm, combining clinical TNM staging (cTNM) with whole-body metabolic active tumor volume (MATV-WB), with the goal of improving prognostic ability and stratification power. METHODS: Initial staging [18F]FDG PET/CT of 278 non-small cell lung cancer (NSCLC) patients, performed between January/2011 and April/2016, 74(26.6%) women, 204(73.4%) men; aged 34-88 years (mean ± SD:66 ± 10), was retrospectively evaluated, and MATV-WB was quantified. Each patient's follow-up time was recorded: 0.7-83.6 months (mean ± SD:25.1 ± 20.3). RESULTS: MATV-WB was an independent and statistically-significant predictor of overall survival (p < 0.001). The overall survival predictive ability of MATV-WB (C index: mean ± SD = 0.7071 ± 0.0009) was not worse than cTNM (C index: mean ± SD = 0.7031 ± 0.007) (Z = -0.143, p = 0.773). Estimated mean survival times of 56.3 ± 3.0 (95%CI:50.40-62.23) and 21.7 ± 2.2 months (95%CI:17.34-25.98) (Log-Rank = 77.48, p < 0.001), one-year survival rate of 86.8% and of 52.8%, and five-year survival rate of 53.6% and no survivors, were determined, respectively, for patients with MATV-WB < 49.5 and MATV-WB ≥ 49.5. Patients with MATV-WB ≥ 49.5 had a mortality risk 2.9-5.8 times higher than those with MATV-WB < 49.5 (HR = 4.12, p < 0.001). MATV-WB cutoff points were also determined for each cTNM stage: 23.7(I), 49.5(II), 52(III), 48.8(IV) (p = 0.029, p = 0.227, p = 0.025 and p = 0.001, respectively). At stages I, III and IV there was a statistically-significant difference in the estimated mean overall survival time between groups of patients defined by the cutoff points (p = 0.007, p = 0.004 and p < 0.001, respectively). At stage II (p = 0.365), there was a clinically-significant difference of about 12 months between the groups. In all cTNM stages, patients with MATV-WB ≥ cutoff points had lower survival rates. Combined clinical TNM-PET staging (cTNM-P) was then tested: Stage I < 23.7; Stage I ≥ 23.7; Stage II < 49.5; Stage II ≥ 49.5; Stage III < 52; Stage III ≥ 52; Stage IV < 48.8; Stage IV ≥ 48.8. cTNM-P staging presented a superior overall survival predictive ability (C index = 0.730) compared with conventional cTNM staging (C index = 0.699) (Z = -4.49, p < 0.001). CONCLUSION: cTNM-P staging has superior prognostic value compared with conventional cTNM staging, and allows better stratification of NSCLC patients.

[Superiority of 18F-FNa PET/CT for Detecting Bone Metastases in Comparison with Other Diagnostic Imaging Modalities]. / Superioridade da PET/CT com FNa-F18 na Deteção de Metástases Ósseas quando Comparada com Outros Métodos de Diagnóstico por Imagem.

INTRODUCTION: The 18F-NaF positron emission tomography/computed tomography is being considered as an excellent imaging modality for bone metastases detection. This ability was compared with other imaging techniques. MATERIAL AND METHODS: We retrospectively evaluated 114 patients who underwent 18F-NaF positron emission tomography/ computed tomography. Of these, 49 patients also had bone scintigraphy, 61 18F-FDG positron emission tomography/computed tomography and 10 18F-FCH positron emission tomography/computed tomography. We identified the technique that detected the largest number of bone metastases. For the detection of skeletal metastases with the 18F-NaF positron emission tomography/computed tomography study, the contribution of the positron emission tomography component was compared with the contribution of the computed tomography component. Cases in which 18F-NaF positron emission tomography/computed tomography and bone scintigraphy required further additional tests for diagnosis clarification were registered. RESULTS: The 18F-NaF positron emission tomography/computed tomography was superior to bone scintigraphy in 49% of the patients (p < 0.001); it was superior to 18F-FDG positron emission tomography/computed tomography in 59% of the patients (p < 0.001) and it was superior to 18F-FCH positron emission tomography/computed tomography in 40% of the patients (p < 0.001). None of the compared imaging techniques were superior to 18F-NaF positron emission tomography/computed tomography. The positron emission tomography component was superior to computed tomography in 35% of the cases (p < 0.001). Further investigation was suggested in only 3.5% of patients who underwent 18F-NaF positron emission tomography/computed tomography (45% for bone scintigraphy) (p < 0.001). DISCUSSION: As with other authors, our experience also confirms that 18F-NaF positron emission tomography/computed tomography is an excellent imaging modality for the detection of bone metastases, detecting lesions in more patients and more lesions per patient. CONCLUSION: The 18F-NaF positron emission tomography/computed tomography showed a superior ability for the detection of bone metastases when compared with bone scintigraphy, 18F-FDG positron emission tomography/computed tomography and 18F-FCH positron emission tomography/computed tomography.

Introdução: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 vem sendo considerada como uma modalidade imagiológica com vantagens na pesquisa de metastização óssea. Comparámos a sua capacidade para deteção de metástases ósseas com a de outras técnicas imagiológicas.Material e Métodos: Avaliámos retrospetivamente 114 doentes que realizaram tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Destes, 49 realizaram também cintigrafia óssea, 61 tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e 10 tomografia por emissão de positrões/tomografia computorizada - FCH-F18. Identificámos a técnica que detetou um maior número de metástases ósseas. Comparámos ainda a tomografia por emissão de positrões com a componente tomografia computorizada da tomografia por emissão de positrões/tomografia computorizada - FNa-F18. Registámos as situações  nas quais a tomografia por emissão de positrões/tomografia computorizada FNa-F18 e a cintigrafia óssea necessitaram de exames adicionais para esclarecimento complementar.Resultados: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 foi superior à cintigrafia óssea em 49% dos doentes (p < 0,001); foi superior à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 em 59% dos doentes (p < 0,001) e foi superior à tomografia por emissão de positrões/tomografia computorizada - FCH-F18 em 40% dos doentes (p < 0,001). Nenhuma das técnicas imagiológicas avaliadas lhe foi superior. Na tomografia por emissão de positrões/tomografia computorizada -FNa-F18 a componente tomografia por emissão de positrões foi superior à tomografia computorizada em 35% dos casos (p < 0,001). Foi sugerida investigação complementar em apenas 3,5% dos doentes que realizaram tomografia por emissão de positrões/ tomografia computorizada - FNa-F18 (45% para a cintigrafia óssea) (p < 0,001).Discussão: Em conformidade com o referido por outros autores, a nossa experiência confirma que a tomografia por emissão de positrões/tomografia computorizada - FNa-F18 tem excelente desempenho na deteção de metástases ósseas, sendo capaz de identificar lesões em mais doentes, e em maior número, quando comparada com outras técnicas imagiológicas.Conclusão: A tomografia por emissão de positrões/tomografia computorizada - FNa-F18 revelou superioridade na deteção de metástases ósseas comparativamente à cintigrafia óssea, à tomografia por emissão de positrões/tomografia computorizada - FDG-F18 e à tomografia por emissão de positrões/tomografia computorizada - FCH- F18.

[PET/CT with 18F-Fluorocholine in Patients with Prostatic Cancer in Biochemical Recurrence]. / PET/CT com Fluorocolina-F18 em Doentes com Carcinoma da Próstata em Recidiva Bioquímica.

INTRODUCTION: In prostate cancer, after therapy with curative intent, biochemical recurrence frequently occurs. The purpose of this study was to evaluate the impact of PET/CT with 18F-fluorocholine in restaging these patients and in their orientation, and to analyze the effect of the risk stratification, the values of PSA and the hormone suppression therapy, in the technique sensitivity. MATERIAL AND METHODS: Retrospective analysis of 107 patients with prostate carcinoma in biochemical recurrence who underwent PET/CT with 18F-fluorocholine in our hospital, between December 2009 and May 2014. RESULTS: The overall sensitivity was 63.2% and 80.0% when PSA > 2 ng/mL. It was possible to identify distant disease in 28% of the patients. The sensitivity increased from 40.0%, in patients with low and intermediate risk, to 55.2% in high-risk patients. Without hormonal suppression therapy, the sensitivity was 61.8%, while in the group under this therapy, was 67.7%. DISCUSSION: PET/CT with 18F-fluorocholine provided important information even in patients with low levels of PSA, however, with significantly increased sensitivity in patients with PSA > 2 ng/mL. Sensitivity was higher in high-risk patients compared with low and intermediate risk patients, however, without a statistically significant difference. The hormone suppression therapy does not appear to influence uptake of 18F-fluorocholine in patients resistant to castration. CONCLUSIONS: In this study, PET/CT with 18F-Fluorocholine showed good results in restaging patients with prostate cancer biochemical recurrence, distinguishing between loco regional and systemic disease, information with important consequences in defining the therapeutic strategy.

Introdução: No carcinoma da próstata, é frequente, após terapêutica com intuito curativo, ocorrer recidiva bioquímica. O objectivo deste trabalho foi avaliar o impacto da PET/CT com fluorocolina-F18 no restadiamento e orientação destes doentes e analisar a influência, da estratificação de risco, dos valores do PSA e da terapêutica de supressão hormonal, na sensibilidade da técnica. Material e Métodos: Análise retrospectiva de 107 doentes com carcinoma da próstata em recidiva bioquímica que realizaram PET/CT com fluorocolina-F18 no nosso hospital, entre dezembro de 2009 e maio de 2014. Resultados: A sensibilidade global foi de 63,2% sendo 80,0% quando PSA > 2 ng/mL. Foi possível identificar doença à distância em 28% dos doentes. A sensibilidade aumentou de 40,0% em doentes de risco baixo e intermédio para 55,2% em doentes de alto risco. Sem terapêutica de supressão hormonal, a sensibilidade foi de 61,8% enquanto no grupo sob essa terapêutica, foi de 67,7%. Discussão: A PET/CT com fluorocolina-F18 forneceu informações relevantes, mesmo em doentes com baixos valores do PSA, contudo, com incremento significativo da sensibilidade nos doentes com PSA >2 ng/mL. A sensibilidade foi superior nos doentes de alto risco comparativamente com os de risco baixo e intermédio, contudo, sem uma diferença estatisticamente significativa. A terapêutica de supressão hormonal parece não influenciar a captação de Fluorocolina-F18 nos doentes resistentes à castração. Conclusões: Neste estudo, a PET/CT com fluorocolina-F18 apresentou bons resultados no restadiamento de doentes com carcinoma da próstata em recidiva bioquímica, distinguindo entre doença loco-regional e sistémica, informação com importantes consequências na definição da estratégia terapêutica.

A glimpse from the past: osteoporosis and osteoporotic fractures in a Portuguese identified skeletal sample.

UNLABELLED: The diachronic variation of etiological factors, like longevity or diet, affected the prevalence of osteoporosis and the so-called osteoporotic fractures in the past. As such, it is important to understand the epidemiology of this disease in historical populations; with behaviors and customs that were unalike the modern westernized lifestyle. OBJECTIVES: The main objective of this study is to characterize the epidemiological patterns of osteoporosis and related fractures in an identified Portuguese skeletal sample from the mid 19th - early 20th centuries. MATERIALS AND METHODS: The sample studied comprised 196 skeletal individuals with known sex and age-at-death, housed at the University of Coimbra. Bone mineral density (BMD) was evaluated in the proximal femur through dual X-ray absorptiometry and osteoporotic fractures were recorded according to clinical and paleopathological protocols. RESULTS: BMD decreased significantly with age-at-death, both at the ROI «Total hip¼ and the ROI «Neck¼. At the «Total hip¼, peak bone mass (PBM) was achieved early (20-29 years age group) in both sexes. In the study-group as a whole, BMD was significantly higher in males when compared to females. As expected, the prevalence of osteoporosis in the proximal femur is higher in women and rises steeply with age. Comparisons with two modern Portuguese samples showed an equivalent pattern of BMD reduction. Nonetheless, BMD is usually lower in the skeletal sample. Women with osteoporosis had a much larger probability of showing a fragility fracture than women diagnosed with «normal¼ BMD or osteopenia. CONCLUSIONS: In spite of enormous lifestyle differences, the epidemiological pattern of bone mass decrease in a Portuguese skeletal sample is strikingly similar to the ones observed in modern populations. This study adds further data to the recent notion that osteoporosis is a disease with deep roots in the past.

Prediction of sentinel node status and clinical outcome in a melanoma centre.

Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.