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Prostate cancer (PC) is one of the most common cancers in males. A significant proportion of PCs bear TMPRSS2-ETS translocation and overexpress ERG transcription factor, allowing classification into ERG+ and ERG- groups, which differ in several features including the tumor microenvironment. The aim of the study was to verify whether they differ in expression of the miRNA in the microenvironment. The material consisted of 150 radical prostatectomies. Immunohistochemistry (IHC) for ERG was done using a routine method. FISH for TMPRSS2-ETS translocation was done with a ZytoLight SPEC ERG/TMPRSS2 TriCheck Probe. From each case, a representative section was selected, and tumor and non-tumor were microdissected with the LMD7000 device. RNA was isolated using the RNeasy Mini Kit system (Qiagen) and miRNA libraries were prepared with the NEBNext Multiplex Small RNA Library Prep Set for Illumina and their sequencing was performed on the NexSeq 500. Statistical analysis was done with Statistica and R software. When analyzing the expression of miRNAs some differences could be seen, but after correction for multiple comparisons was applied, these were found to be non- significant.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Transativadores , Regulador Transcricional ERG/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Translocação Genética , Microambiente TumoralRESUMO
Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a "genetic wasteland", and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.
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Doença de Alzheimer/genética , Cromossomos Humanos Y , Mosaicismo , Neoplasias da Próstata/genética , Linfócitos T CD4-Positivos/metabolismo , Regulação da Expressão Gênica , Humanos , Células Matadoras Naturais/metabolismo , Leucócitos/metabolismo , MasculinoRESUMO
AIM: To investigate the safety, surgical efficiency and patients' ability to recover from urinary continence as a result of a single absorbable running suture versus single-knot running suture for vesicourethral anastomosis (VUA) during laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: In a prospective randomised study, we evaluated 162 consecutive patients who underwent LRP with VUA using the single running suture technique or the single-knot running suture technique. Perioperative patients' characteristics, morbidity and urinary continence were analysed. RESULTS: The baseline characteristics were similar between the 2 groups. The single running suture technique was related to decreased anastomotic and total operative times compared with the Van Velthoven technique (13.17 ± 5.74 min vs. 28.49 ± 6.45 min, p = 0.0001, and 174.41 ± 62.97 min and 184.94 ± 46.16 min, p = 0.04, respectively). Overall, urinary continence rates at 3, 6 and 12 months in groups 1 and 2 were 49.4 and 69.1%, 81.5 and 86.4%, and 91.4 and 93.8%, respectively (all with p > 0.05 except the follow-up assessment at 3 months following surgery, p = 0.011). CONCLUSIONS: Both methods ensure satisfactory rates of urinary leakage and bladder neck stricture, as well as continence after LRP. However, since the single running suture VUA technique is easier to perform, and the mean anastomosis time of the single running suture VUA technique is shorter than that of the Van Velthoven technique, it appears, therefore, preferable.
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Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Técnicas de Sutura/instrumentação , Suturas , Uretra/cirurgia , Bexiga Urinária/cirurgia , Idoso , Anastomose Cirúrgica/métodos , Desenho de Equipamento , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos ProspectivosRESUMO
PURPOSE: To evaluate the value of examination under anesthesia (EUA) in the assessment of bladder resectability during cystectomy. MATERIALS AND METHODS: This prospective study included consecutive patients undergoing cystectomy for bladder cancer at a single center between June 2017 and October 2020. EUA was conducted before cystectomy by two urologists who assessed the bladder for limited mobility. One examiner was blinded to the imaging results. Soft tissue surgical margin status in the pathological evaluation of a cystectomy specimen served as a measure of resectability. We used multivariable logistic regression models to assess whether EUA performed by blinded or non-blinded examiners is associated with soft tissue positive surgical margins (PSMs) and to calculate the fraction of new information added by such an examination in addition to selected clinical variables. RESULTS: Among the 134 patients analyzed, limited bladder mobility was indicated by the blinded and non-blinded examiners in 23 (17.2%) and 21 (15.7%) cases, respectively. PSMs were identified in 22 (16.4%) patients, more often in patients with limited bladder mobility as assessed by the blinded (odds ratio [OR] 6.7; 95% confidence interval [CI], 1.9-24.2) and non-blinded examiners (OR 12.9; 95% CI, 2.9-57.5). The fraction of new information added by the blinded and non-blinded examiners was 48.6% and 57.7%, respectively. The enrichment of patients who underwent pure laparoscopic cystectomy (nâ¯=â¯102; 76%) and the inclusion of patients for emergent surgery may limit the generalizability of our findings. CONCLUSIONS: The identification of limited bladder mobility during preoperative EUA yielded prognostic information on surgical margin status. Our findings suggest that EUA has the potential to provide valuable insights in the assessment of bladder resectability. However, further research in a larger cohort of patients is warranted to validate and expand on these findings.
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Cistectomia , Laparoscopia , Palpação , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Estudos Prospectivos , Feminino , Masculino , Idoso , Laparoscopia/métodos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The quality of vesicourethral anastomosis (VUA) in laparoscopic radical prostatectomy (LRP) is associated with complications that could significantly affect quality of life. AIM: To compare different types of sutures (Chlosta's versus Van Velthoven versus V-Loc), used for VUA in LRP in terms of complication rates and continence recovery. MATERIAL AND METHODS: Patients who underwent LRP between 2014 and 2018 in a tertiary center were enrolled in the study. Data were extracted from medical records. Urinary continence was assessed at 3, 6, 12 and 18 months after LRP. Propensity score weighted regression models were used to estimate the effect of sutures on outcomes. RESULTS: A sample of 504 patients was analyzed, of which 109 patients underwent Chlosta's suture VUA, 117 patients had Van Velthoven suture VUA, and 278 patients had V-Loc VUA. Median time of anastomosis was 13 (IQR - interquartile range: 10-16) min using Chlosta's suture, 28 (IQR: 24-30) using Van-Velthoven suture and 12 (IQR: 11-16) min using V-Loc suture (p < 0.001). There were no significant differences between groups concerning complications and urinary continence at 12 and 18 months after surgery. The time of urinary continence recovery was on average 19 days (95% CI: 5-33) and 31 days (95% CI: 16-45) shorter during 1 year of observation when the V-Loc suture was used compared to the Van-Velthoven and Chlosta's suture, respectively. CONCLUSIONS: The study showed comparable results considering urinary continence recovery at 12 and 18 months after LRP in all VUA groups. Van Velthoven VUA was more time-consuming and continence recovery was faster in the V-Loc group.
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Introduction: Radical prostatectomy (RP) is the standard surgical treatment for localized prostate cancer (PCa), with excellent oncologic outcomes; however, complications such as post-prostatectomy incontinence could significantly affect quality of life. Aim: To provide data on long-term urinary functional outcomes of bladder neck preservation (BNP) combined with distal urethral length preservation (DULP) in patients treated with videolaparoscopic prostatectomy. Material and methods: In this retrospective study, data were analysed from 619 consecutive patients who underwent laparoscopic radical prostatectomy (LRP) due to localized prostate cancer between November 2014 and December 2018 in a single tertiary care centre in Poland. Of these patients, 227 had BNP and DULP during the procedure. Urinary continence status was assessed in patients at 3, 6, 12, and 18 months after LRP. Cancer resection was assessed by surgical margin status. Results: In the group with BNP and DULP, urinary continence recurred earlier than it did in the control group up to 3 months after surgery: 204 (89.8%) patients in this group were fully continent compared with 283 (72.2%) in the control group (p < 0.001). The difference was also significant after 6 months (95.1% vs. 80.6%, respectively; p < 0.001). Despite these early promising results, there was no difference in urinary continence recovery after 12 and 18 months. There was also no difference between the 2 groups regarding surgical margin status of the resected tissue. Conclusions: Our study showed that BNP combined with DULP is a safe procedure that helps to improve early urinary continence rates after surgery without altering the risk of positive surgical margin.
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The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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Neoplasias da Mama , Carcinoma , Neoplasias Colorretais , Bancos de Espécimes Biológicos , Neoplasias da Mama/genética , Variação Genética , Humanos , Masculino , Mastectomia , Neoplasias Pancreáticas , Neoplasias PancreáticasRESUMO
INTRODUCTION: The aim of this study was to establish at the population level the treatment patterns for lower urinary tract symptoms (LUTS) and overactive bladder (OAB) in Poland. MATERIAL AND METHODS: We used data from LUTS POLAND, a survey representative of the entire Polish population classified by age, sex, and place of residence. The treatment patterns we considered were lifestyle changes, physiotherapy, non-prescription drugs, prescription drugs, and surgical treatment. RESULTS: We obtained 6,005 completed interviews. About one-third of respondents who reported LUTS or OAB were seeking treatment, and many of these persons received treatment. Men were more proactive in seeking treatment than women, and men more often received treatment. Management with prescription drugs was the most common treatment modality of LUTS and OAB respondents. There were some disparities in distribution of other treatment options between LUTS and OAB persons, but, disappointingly, non-invasive and low-cost management strategies were rarely reported as being used. Specialists (mainly urologists) provided most of the treatments. We did not identify differences between urban and rural areas in treatment seeking, treatment receiving, and the treatment methods that were used. CONCLUSIONS: In Poland, the scale was low for seeking treatment for LUTS and OAB. As well, there was little reliance on non-invasive and low-cost management strategies for LUTS and OAB. Our findings underline the need for education of patients and physicians about LUTS and OAB, and for greater healthcare and financial resources for LUTS and OAB patients.
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Renal carcinoma is the 20th most common cancer worldwide. Clear cell renal cell carcinoma is the most frequent type of renal cancer. Even in patients diagnosed at an early stage, characteristics of disease progression remain heterogeneous. Up-to-date molecular classifications stratify the ccRCC samples into two clusters. We analyzed gene expression in 23 T1 or T3 ccRCC samples. Unsupervised clustering divided this group into three clusters, two of them contained pure T1 or T3 samples while one contained a mixed group. We defined a group of 36 genes that discriminate the mixed cluster. This gene set could be associated with tumor classification into a higher stage and it contained significant number of genes coding for molecular transporters, channel and transmembrane proteins. External data from TCGA used to test our findings confirmed that the expression levels of those 36 genes varied significantly between T1 and T3 tumors. In conclusion, we found a clustering pattern of gene expression, informative for heterogeneity among T1 and T3 tumors of clear cell renal cell carcinoma.