Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study

Background: Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum. Methods: We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of Sao Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy. Results: We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%. Conclusions: Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered

Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and alpha-, beta- and gamma-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of a-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of a-catenin expression is related to tumor size in upper tract urothelial carcinomas

Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model

Abstract\ud \ud \ud \ud Background\ud Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells.\ud \ud \ud \ud Methods\ud Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis.\ud \ud \ud \ud Results\ud Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher β- and γ-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002).\ud \ud \ud \ud Conclusions\ud A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of β- and γ-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.We thank Mr. Isaque Santana for rendering technical assistance for immunohistochemistry study. This study was supported by FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo)

Underexpression of MMP-2 and its Regulators, TIMP2, MT1-MMP and IL-8, is Associated with Prostate Cancer

Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (>= 7) over-expressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2009/50368-9]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Perception of the population of the city of Passos on the factors that determine the appearance of cancer: myths and truths

Introdução: As neoplasias malignas são responsáveis por inúmeras mortes em todo o mundo, por isso são encaradas pela população com muito temor e curiosidade. Sendo assim muitas pessoas recorrem aos meios de comunicação mais convenientes, que nem sempre abordam corretamente as doenças, para se informar sobre prevenção do câncer, ou então se baseiam na cultura popular passada por gerações sem nenhum embasamento científico. Objetivo: Analisar a percepção da população sobre os fatores de risco para o câncer e classificá-las de acordo com o nível de evidência encontrado nas pesquisas científicas. Metodologia: Foram selecionados 146 participantes, de maneira aleatória, que responderam a um questionário enviado por e-mail o qual indagava o que o pesquisado considera que seja um fator de risco para se desenvolver cânceres. Esses dados foram tabelados e uma pesquisa bibliográfica foi realizada para reconhecer os fatores de risco mencionados pela população como evidentes ou não evidentes cientificamente. Resultados: O estresse e causas psicológicas foram mencionados por 43,84% das pessoas pesquisadas e pelo estudo bibliográfico foi classificado como evidência parcialmente positiva. O cigarro foi mencionado por 39,04% dos participantes e foi classificado como evidência positiva, a herança genética foi indicada por 38,36% e classificada como evidência positiva, sexo sem proteção foi mencionado por apenas uma pessoa e foi classificado como evidência positiva. Conclusão: Com os dados obtidos observamos que, a maioria das respostas possuem relação com evidências científicas publicadas e comprovadas, no entanto, mais estudos e divulgações acerca de formas preventivas devem ser realizados.Introduction: Malignant neoplasms are responsible for a great and increasing number of deaths worldwide, what justify the fear and curiosity which population face these diseases. To learn about cancer prevention, many people search for information in the most convenient means of communication, which do not always show the clinical evidences of the diseases correctly. Moreover, much of the knowledge, are based on popular beliefs inherited from generations without any scientific basis. Objective: Analyze the population’s perception of the risk factors associated with cancer and classify them according to the level of evidence found in scientific literature. Methodology: 146 participants were randomly selected and answered a questionnaire sent by email asking what the respondent considers to be a risk factor for developing cancers. These data were tabulated and a bibliographic search was carried out to recognize the risk factors mentioned by the population as scientifically evident or not evident. Results: Stress and psychological causes were mentioned by 43.84% of the people surveyed and classified as partially positive evidence by the bibliographic study. The cigarette smoking was mentioned by 39.04% of the participants and it was classified as positive evidence, the genetic inheritance was indicated by 38.36% and classified as positive evidence, unprotected sex was mentioned by only one person and was classified as positive evidence. Conclusion: The data obtained showed that the majority of the responses were related to published and proven scientific evidence, however, further studies and more impacting prevention plans hould be carried out

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2009/50368-9]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Comportamentos de proteção contra a infecção por SARS-CoV-2: um estudo de coorte

INTRODUÇÃO: Nós elaboramos um estudo prospectivo com o objetivo de avaliar fatores (adesão ao distanciamento social, uso de EPI’s, etc.) que poderiam ser determinantes no desenvolvimento da COVID-19 que poderá subsidiar o desenvolvimento de estratégias de saúde eficazes no combate da infecção no município de Passos - Minas Gerais, Brasil, seja em ambientes hospitalar ou não-hospitalar. MÉTODOS: Trata-se de um estudo coorte longitudinal onde foram incluídos 343 indivíduos da população que foram selecionados aleatoriamente por conglomerado. Os indivíduos selecionados responderam a um questionário relacionado às características clínicas, medidas preventivas, comorbidades e uso de medicamentos. Na ocasião foi realizado teste rápido nos indivíduos para detecção de anticorpos IgG e IgM. O tempo médio de acompanhamento foi de seis meses e, durante o acompanhamento, manteve-se contato telefônico a cada duas semanas. Ao final do seguimento, novo teste sorológico foi realizado e calculado o risco associado à presença de fatores de risco e à incidência da doença. RESULTADOS: Verificamos que 27,3% dos participantes que se infectaram no seguimento faziam uso ivermectina e hidroxicloroquina como forma de prevenção, enquanto nós não infectados, 11,3% usavam esses medicamentos. Para os indivíduos que apresentaram a doença durante o seguimento 21,2% relataram respeitar o isolamento social, 27,3% relataram que saíram para trabalhar e 42,14% relataram que frequentaram ambientes hospitalares. Entre os participantes que tiveram a infecção, 12,1% relataram contato apenas com familiares, 9,1% com familiares e colegas de trabalho e 75,8% com profissionais de saúde. CONCLUSÕES: Este estudo forneceu dados epidemiológicos de indivíduos infectados pelo COVID-19, que podem contribuir com o sistema de saúde no estabelecimento de medidas preventivas.INTRODUCTION: We designed a prospective study aiming to assess factors (adherence to social distancing, use of PPE, etc.) that could be determinants in the development of COVID-19 that may subsidize the development of effective health strategies to combat the infection in the municipality of Passos - Minas Gerais, Brazil, whether in the hospital or non-hospital settings. METHODS: This is a longitudinal cohort study where 343 individuals from the population were included and randomly selected by clusters. The selected individuals answered a questionnaire related to clinical characteristics, preventive measures, comorbidities, and medication use. A rapid test was performed on the individuals to detect IgG and IgM antibodies. The average follow-up period was six months, and during the follow-up, telephone contact was maintained every two weeks. At the end of the follow-up, a new serological test was performed, and the risk associated with risk factors and disease incidence was calculated. RESULTS: We found that 27.3% of patients who became infected during follow-up were using ivermectin and hydroxychloroquine as a means of prevention, while in non-infected patients, 11.3% used these drugs. (p = 0.024). For patients who had the disease during follow-up, 21.2% reported respecting social isolation, 27.3% reported leaving for work, and 42.14% reported having attended hospital environments (p = 0.004). Among the participants who had the infection, 12.1% reported contact only with family members, 9.1% with family members and co-workers, and 75.8% with health professionals (p = 0.001). CONCLUSIONS: This study provided epidemiological data on patients infected with COVID-19, which can contribute to the health system's establishment of preventive measures

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Evaluation of polymorphisms of matrix metalloproteinases genes in prostate cancer

Introdução: O Câncer de próstata (CaP) é o mais comum do homem brasileiro. É importante a identificação de alterações moleculares que possam prever o seu desenvolvimento e potencial biológico. Polimorfismos de nucleotídeo único (SNP) são alterações da seqüência do DNA onde somente uma base é trocada com uma freqüência superior a 1% na população, que podem levar a modificações estruturais e funcionais na proteína, ou afetar a sua quantidade, e podem constituir marcadores de predisposição e prognóstico de neoplasias. Metaloproteinases (MMP) são proteínas da família de enzimas proteolíticas, que degradam a matriz extracelular, e SNP na sua estrutura têm sido associados ao comportamento de tumores. Objetivos: Avaliar a freqüencia de SNP nos genes das MMP1, 2, 7 e 9, em pacientes com CaP e grupo controle, relacionando com suscetibilidade para o desenvolvimento da doença e previsão de seu potencial biológico. Material e Métodos: A amostra é constituída por tecido não tumoral de 100 indivíduos com CaP, e 100 amostras controle representadas por soro de indivíduos saudáveis, sem câncer de próstata. O DNA foi obtido utilizando protocolos convencionais de extração. Para genotipagem foi utilizada técnica de identificação de base única com uso de sondas marcadas com fluoróforos (Taqman®) pela técnica de reação em cadeia da polimerase em tempo real. As freqüências alélicas foram calculadas e a comparação entre os grupos foi feita utilizando-se o teste de qui-quadrado com valor de significância de 0,05. Resultados: Nos genes das MMP1 a freqüência do genótipo homozigoto polimórfico esteve mais presente no grupo controle que no CaP (p>0,001). No gene da MMP9 o alelo polimórfico esteve mais presente em pacientes com CaP (p>0,001), e em tumores com escore de Gleason6 (p=0,003). No gene da MMP2 de acordo com estadiamento patológico o alelo polimórfico foi mais freqüente em tumores pT3 (p=0,026) e Gleason maior ou igual a 7(p=0,042). Conclusão: Nossos resultados sugerem que o polimorfismo no gene da MMP1 está associado a um caráter de proteção aos indivíduos quanto ao desenvolvimento do CaP. O polimorfismo no gene da MMP9 está associado a um aumento no risco de desenvolvimento desta neoplasia, e quando analisamos as associações com os fatores prognósticos encontramos uma correlação com tumores de melhor prognóstico. Por outro lado o polimorfismo do gene da MMP2 se associa a tumores não órgãoconfinadosIntroduction: Prostate cancer (PCa) is the most frequent tumor in males in Brazil. Research has been directed for the identification of molecular markers that can predict the PCa predisposition and prognosis. Single nucleotide polymorphisms (SNPs) are genome variations, present in a frequency of 1% or more. The matrix metalloproteinases (MMPs) are a family of enzymes responsible for the degradation of extracellular matrix. SNPs have been demonstrated in the promoter region of these genes and have been associated with development and progression of some cancers. Objective: To investigate the correlation between polymorphisms of MMP1, 2, 7, 9 with susceptibility and classical prognostic parameters in PCa. Patients and methods: The sample is constituted by normal tissue of 100 patients with PCa, and 100 healthy men as controls (serum). DNA genomic was extracted from paraffin blocks and serum using conventional protocols. The DNA sequence containing the polymorphic sites was amplified by Real-Time polymerase chain reaction, using fluorescent probes (Taqman®). The allelic frequency was calculated and the comparison between the groups was made using the qui-square test with value of significance of 0.05. Results: The polymorphic homozygote genotype of the MMP1 was more frequent in the control group than in the PCa (p<0.001). The polymorphic allele of MMP9 was more frequent in the PCa group (p<0.001), and in tumors Gleason6 (p=0,003). The polymorphic allele of MMP2 was more frequent in tumors of higher stage (pT3) (p=0.026) and higher Gleason Score (7) (p=0.042). Conclusion: We have shown that MMP1 polymorphism is more frequent in the control group, than in patients with PCa, it may be associated to protection for the development of PCa. The MMP9 polymorphism was related to higher risk for development of this neoplasia, but associated with lower Gleason score. MMP2 polymorphism was associated with non organconfined disease