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BACKGROUND: Penile cancer is high in some underdeveloped countries. Signal transducer and activator of transcription 3 (STAT3) and CD44, CD24, and SOX2+ are known to be markers of diagnosis and prognosis in other cancers, but without studies in penile cancer. METHODS: A cross-sectional study was conducted at the Hospital de Cancer de Pernambuco from March 2015 to December 2017. We performed SOX2, STAT3, CD24, and CD44 analyses in blood and tumor tissue by flow cytometry. RESULTS: High levels of CD44highCD24low, CD44highCD24lowpSTAT3+ and CD44hig hCD24low in the blood of patients compared to the controls (p < 0.05). Low of SOX2+ T cells in blood of patients compared to controls. High CD44highCD24low levels in patients with perineural invasion (PNI), tumor size > 3 cm, and pT2 stage (p < 0.05). High T cell levels in the blood and tumor tissue of patients with tumor ≤3 cm (p < 0.05). Increased SOX2+ T cells in blood of patients with PNI (-) and pT1 stage (p < 0.05). CD44highCD24lowpSTAT3+ (r = 0.669; p = 0.024) and SOX2+T cells (r = 0.404, p = 0.029) correlation were observed between blood and tumor tissue in penile cancer patients. CONCLUSION: CD44, CD24, and SOX2 molecules were markers of advanced disease associated with the worst prognosis in CaPe. However, pSTAT3 and T cells were associated with a more favorable prognosis in this study.

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BACKGROUND: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells. METHODS: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion. RESULTS: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells. CONCLUSION: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC.

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Recent advancements in image analysis and interpretation technologies using computer vision techniques have shown potential for novel applications in clinical microbiology laboratories to support task automation aiming for faster and more reliable diagnostics. Deep learning models can be a valuable tool in the screening process, helping technicians spend less time classifying no-growth results and quickly separating the categories of tests that deserve further analysis. In this context, creating datasets with correctly classified images is fundamental for developing and improving such models. Therefore, a dataset of urine test Petri dishes images was collected following a standardized process, with controlled conditions of positioning and lighting. Image acquisition was conducted by applying a hardware chamber equipped with a led lightning source and a smartphone camera with 12 MP resolution. A software application was developed to support image classification and handling. Experienced microbiologists classified the images according to the positive, negative, and uncertain test results. The resulting dataset contains a total of 1500 images and can support the development of deep learning algorithms to classify urine exams according to their microbial growth.

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PURPOSE: Penile cancer has a high incidence in developing countries. The standard treatment is removal of the primary tumor and, when necessary, inguinal lymphadenectomy. Currently, the most important prognostic factor is lymph node disease, however, the available staging methods are inaccurate, and the high morbidity rate of lymphadenectomy has stimulated the study of predictive biomarkers of lymph node metastasis for selecting the patients who need lymphadenectomy. SOX2, STAT3 and CD44high/CD24low were chosen because they have provided good predictive results in other squamous cell carcinoma (SCC), although there are no studies for penile cancer. Thus, the expression of SOX2, STAT3, CD24+, and CD44+ in the penile cancer tumor microenvironment was investigated for correlation with tumor behavior in SCC. METHODS: This observational, prospective, translational study included 34 men and investigated the expression of SOX2, STAT3, CD24+, and CD44+ in tumor tissue by flow cytometry. RESULTS: The median age of the 38 evaluated patients with penile cancer was 61 (37-80) years. Most patients presented a tumor located on the glans penis (82.3%), with the usual histological type (79.4%) and 61.7% of patients presented stage pT2. No metastasis was found in 85.3% of patients. The expression of SOX2, STAT3 and CD44high/CD24low in the microenvironment of penile SCC treated with lymphadenectomy was significantly associated with aggressive tumor behavior (p < 0.05). STAT3 expression shows discrepant points when evaluated in context of angiolymphatic vascular invasion. CONCLUSION: SOX2, STAT3 and CD44high/CD24low in penile SCC can be indicators of prognosis, allowing for selection of more aggressive treatment when necessary.

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INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

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BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

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BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Eleven questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reducing colectomy, gastrectomy, and thyroidectomy, a major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO and it should serve as an important reference for the management of families with cancer predisposition.

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BACKGROUND: Considering the socioeconomic disparities and inequalities observed in the healthcare resources among the Brazilian regions, we aimed to analyze the mortality trends of urological cancers in Brazil to identify areas with differential risks. METHODS: Deaths related to prostate (PCa), bladder (BCa), kidney (KC), penile (PeC), and testis (TCa) cancers from 1996 to 2019 were retrieved from the Mortality Information System database (Brazil). Geographic and temporal patterns were analyzed using age-standardized mortality rates (ASMRs). A joinpoint regression model was used to identify changes in the trends and calculate the average annual percentage change (AAPC) for each region. RESULTS: In Brazil, the ASMRs (per 100,000 persons/year) were 11.76 for PCa; 1.37, BCa; 1.13, KC; 0.33, and PeC; 0.26, TCa over the period. Increasing mortality trends were registered for BCa (AAPC = 0.45 in men; 0.57 in women), KC (AAPC = 2.03 in men), PeC (AAPC = 1.01), and TCa (AAPC = 2.06). The PCa mortality presented a significant reduction after 2006. The Northeast and North regions showed the highest increases in the PCa mortality. The South registered the highest ASMRs for BCa and KC, but the highest increasing trends occurred in the men from the Northeast. The North presented the highest ASMR for PeC, while the South registered the highest ASMR for TCa. CONCLUSION: Differences among regions may be partly explained by disparities in the healthcare systems. Over the study period, the North and Northeast regions presented more discrepant mortality rates. Efforts should be made to ensure access to the healthcare resources for people at risk, particularly in these regions.

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OBJECTIVES: Self-assembling peptide P11-4 is amphiphilic and pH-triggered, effective on repairing early enamel carious lesions and dentin remineralization. However, P11-4 effects on dentin biomineralization and repair ability remain unexplored. Thus, cytocompatibility and effectiveness of P11-4 on inducing mineralization and migration of odontoblast-like cells (MDPC-23) were investigated. METHODS: MDPC-23 were seeded in contact with P11-4 (0.5 and 1 µg/ml), Dentin Matrix Protein 1 (DMP1 0.5 and 1 µg/ml) or Calcium hydroxide (Ca(OH)2 100 µg/ml) solutions. Cell viability was verified using MTT (n = 6/group). Mineral deposition was tested using Alizarin Red (n = 4/group). Cell migration was assessed by light microscopy (n = 2/group). MTT and Alizarin Red data were compared using Kruskal-Wallis and Mann-Whitney (α=0.01). RESULTS: P11-4 (0.5 and 1 µg/ml) and DMP1 (0.5 and 1 µg/ml) resulted the highest cell viability; Ca(OH)2 presented the lowest. 1 µg/ml DMP1 and 1 µg/ml P11-4 promoted the highest mineral deposition. Ca(OH)2 presented lower values of mineral deposits than DMP1 1 µg/ml (p < 0.01), but similar to P11-4 1 µg/ml. P11-4 and DMP1 at 0.5 µg/ml induced lesser mineral precipitation than P11-4 and DMP1 at 1 µg/ml (p < 0.01), with no difference to Ca(OH)2. All materials stimulated cell migration, however, lower concentrations of DMP1 and P11-4 demonstrated a higher migration potential. CONCLUSION: P11-4 did not affect cell viability, induces mineral deposition and MDPC-23 migration like DMP1. CLINICAL SIGNIFICANCE: Self-assembling peptide P11-4 does not affect the cell viability and induces mineral deposition comparable to native protein involved in biomineralization. Combined with its ability to bind type I collagen, P11-4 is a promising bioinspired molecule that provides native-tissue conditions and foster further studies on its ability to form dentin bridges in pulp-capping strategies.

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The methylation and expression of DNA repair system genes has been studied in several tumor types. These genes have been associated with resistance to chemotherapy treatments by epigenetic regulation. Studies have yet to show the effects of combined therapy using an epigenetic drug (5-aza-2CdR) and cisplatin (CDDP) on DNA repair genes in oral squamous cell carcinoma (OSCC). This study proposed to investigate the effects of CDDP in combination with 5-aza-2CdR on the methylation of MGMT and MLH1 genes in oral cancer cells. Oral squamous cell carcinoma cell lineages (SCC-9, SCC-15, and SCC-25) were submitted to 72 hours of treatment: 0.1 µM CDDP (or 4.44 µM SCC-9), 0.1 µM and 0.3 µM 5-aza-2CdR (or 1 µM and 3 µM SCC-9), and the drugs in combination. Cell viability was assessed by MTT, DNA methylation of MGMT and MLH1 genes by Methylation Sensitivity High-Resolution Melting (MS-HRM), and the relative expression of the genes by RT-qPCR. The results show that all treatments reduced cell viability; however, in SCC-15 and SCC-9 (IC50 value), 5-aza-2CdR promotes cell sensitization to cytotoxic effect of cisplatin. The MGMT promoter region was 100% demethylated in the SCC-15 and SCC-25 cells but partially (50%) methylated in SCC-9 before drug treatment. Treatment with IC50 CDDP value kept the methylation status and decreased MGMT expression in SCC-9; MGMT gene in SCC-15 and SCC-25 cells became downregulated after treatment with 5-aza-2CdR. MLH1 was demethylated, but the treatments with low-doses and combined drugs decreased the expression in SCC-9 and SCC-25; however high doses of 5-aza-2CdR and drug combination with IC50 value CDDP increased expression of MLH1 in SCC-9. The data presented suggest that epigenetic drugs associated with chemotherapy have clinical translational potential as a therapy strategy to avoid or reverse cancer resistance, requiring further investigation.

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ABSTRACT Purpose: To analyze the association between obesity and urinary incontinence rate in men submitted to robot-assisted radical prostatectomy (RARP) in a high-volume cancer center. Materials and Methods: We reported 1.077 men who underwent RARP as the primary treatment for localized prostate cancer from 2013 to 2017. Patients were classified as non-obese (normal BMI or overweight) or obese men (BMI ≥30kg/m2). They were grouped according to the age, PSA level, D'Amico risk group, Gleason score, ASA classification, pathological stage, prostate volume, salvage/adjuvant radiotherapy, perioperative complications, and follow-up time. Urinary continence was defined as the use of no pads. For the analysis of long-term urinary continence recovery, we conducted a 1:1 propensity-score matching to control confounders. Results: Among the obese patients, mean BMI was 32.8kg/m2, ranging 30 - 45.7kg/m2. Only 2% was morbidly obese. Obese presented more comorbidities and larger prostates. Median follow-up time was 15 months for the obese. Complications classified as Clavien ≥3 were reported in 5.6% of the obese and in 4.4% of the non-obese men (p=0.423). Median time for continence recovery was 4 months in both groups. In this analysis, HR was 0.989 for urinary continence recovery in obese (95%CI=0.789 - 1.240; p=0.927). Conclusions: Obese can safely undergo RARP with similar continence outcomes comparing to the non-obese men when performed by surgeons with a standardized operative technique. Future studies should perform a subgroup analysis regarding the association of obesity with other comorbidities, intending to optimize patient counseling.

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Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

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PURPOSE: To analyze the association between obesity and urinary incontinence rate in men submitted to robot-assisted radical prostatectomy (RARP) in a high-volume cancer center. MATERIALS AND METHODS: We reported 1.077 men who underwent RARP as the primary treatment for localized prostate cancer from 2013 to 2017. Patients were classified as non-obese (normal BMI or overweight) or obese men (BMI ≥30kg/m2). They were grouped according to the age, PSA level, D'Amico risk group, Gleason score, ASA classification, pathological stage, prostate volume, salvage/adjuvant radiotherapy, perioperative complications, and follow-up time. Urinary continence was defined as the use of no pads. For the analysis of long-term urinary continence recovery, we conducted a 1:1 propensity-score matching to control confounders. RESULTS: Among the obese patients, mean BMI was 32.8kg/m2, ranging 30 - 45.7kg/m2. Only 2% was morbidly obese. Obese presented more comorbidities and larger prostates. Median follow-up time was 15 months for the obese. Complications classified as Clavien ≥3 were reported in 5.6% of the obese and in 4.4% of the non-obese men (p=0.423). Median time for continence recovery was 4 months in both groups. In this analysis, HR was 0.989 for urinary continence recovery in obese (95%CI=0.789 - 1.240; p=0.927). CONCLUSIONS: Obese can safely undergo RARP with similar continence outcomes comparing to the non-obese men when performed by surgeons with a standardized operative technique. Future studies should perform a subgroup analysis regarding the association of obesity with other comorbidities, intending to optimize patient counseling.

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INTRODUCTION: Prostate cancer is one of the most common malignancies among men worldwide. Prostate-specific antigen (PSA) screening shows uncertain benefits and harms from clinical and economic perspectives, resulting in an important impact on healthcare systems. Because of nonstandardized studies and substantial differences among populations, data are still inconclusive. OBJECTIVE: The objective of this study was to carry out long-term cost-effectiveness and cost-utility analysis on the PSA-screened population from the service provider's perspective in the Brazilian population. METHODS: We performed a cost-effectiveness and cost-utility analysis using clinical outcomes obtained from 9692 men enrolled in the PSA screening program. Prostate cancer treatments, 5-year follow-up outcomes, and all related costs were examined. Data were compared with a nonscreened prostate cancer population to calculate incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). ICER and ICUR were compared with the Brazilian-established willingness-to-pay (WTP) threshold (WTP = R$ 114 026.55). RESULTS: A total of 251 of 9692 men had a diagnosis of prostate cancer (2.6%), of which 90% had localized disease. Two hundred and five patients were treated as follows: surgery (45.37%); radiation therapy (11.22%); radiation plus androgen deprivation therapy (21.95%); active surveillance (13.17%); exclusive androgen deprivation therapy (7.32%); and watchful waiting (0.98%). Two simulated cohorts were compared based on screening and nonscreening groups. Values obtained were-ICER of R$ 44 491.39 per life saved and ICUR of R$ 10 851.56 per quality-adjusted life year (QALY) gained-below the Brazilian WTP threshold and showed cost-effectiveness and cost-utility advantages. CONCLUSION: According to the Brazilian WTP, PSA screening is a cost-effective policy from a hospital and long-term perspective and should have more standardized studies developed in different populations and economies.

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ABSTRACT Purpose: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. Materials and Methods: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. Results: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. Conclusions: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

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PURPOSE: To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS: Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS: Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION: Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

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PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

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PURPOSE: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

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Acute myeloid leukemia (AML) is a complex hematological disorder characterized by blockage of differentiation and high proliferation rates of myeloid progenitors. Anthracycline and cytarabine­based therapy has remained the standard treatment for AML over the last four decades. Although this treatment strategy has increased survival rates, patients often develop resistance to these drugs. Despite efforts to understand the mechanisms underlying cytarabine resistance, there have been few advances in the field. The present study developed an in vitro AML cell line model resistant to cytarabine (HL­60R), and identified chromosomal aberrations by karyotype evaluation and potential molecular mechanisms underlying chemoresistance. Cytarabine decreased cell viability, as determined by MTT assay, and induced cell death and cell cycle arrest in the parental HL­60 cell line, as revealed by Annexin V/propidium iodide (PI) staining and PI DNA incorporation, respectively, whereas no change was observed in the HL­60R cell line. In addition, the HL­60R cell line exhibited a higher tumorigenic capacity in vivo compared with the parental cell line. Notably, no reduction in tumor volume was detected in mice treated with cytarabine and inoculated with HL­60R cells. In addition, western blotting revealed that the protein expression levels of Bcl­2, X­linked inhibitor of apoptosis protein (XIAP) and c­Myc were upregulated in HL­60R cells compared with those in HL­60 cells, along with predominant nuclear localization of the p50 and p65 subunits of NF­κB in HL­60R cells. Furthermore, the antitumor effect of LQB­118 pterocarpanquinone was investigated; this compound induced apoptosis, a reduction in cell viability and a decrease in XIAP expression in cytarabine­resistant cells. Taken together, these data indicated that acquired cytarabine resistance in AML was a multifactorial process, involving chromosomal aberrations, and differential expression of apoptosis and cell proliferation signaling pathways. Furthermore, LQB­118 could be a potential alternative therapeutic approach to treat cytarabine­resistant leukemia cells.

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PURPOSE: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. MATERIALS AND METHODS: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. RESULTS: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. CONCLUSIONS: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

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