OBJECTIVES: The aim of the present study was to propose a methodologically innovative sonographic approach for optimal evaluation of synovial tissues (starting from histopathology). METHODS: Using high-frequency ultrasound probes and high-level ultrasound machines, we matched the histological microarchitecture of synovial tissues with multiple sonographic patterns in physiological and pathological conditions. Likewise, high-sensitive color/power Doppler assessments have also been performed to evaluate the microcirculation. RESULTS: Modern equipment allows for a macroscopic classification of synovial pathologies recognizing different morphological patterns; however, intimal and subintimal layers of the synovium cannot be distinguished from each other on ultrasound. High-sensitive Doppler imaging clearly defines the microvascular pattern, especially in patients with hypertrophic synovial pathologies. CONCLUSIONS: In clinical practice, using adequate technological equipment i.e. high-frequency B-mode and high-sensitive Doppler imaging, detailed sonographic assessment of synovial tissues can be performed - defining the main sono-histological patterns.
PURPOSE: Detrusor muscle (DM) in the resected specimen of patients with pT1 bladder cancer (BCa) is a quality-of-care criteria. We aimed to assess whether obtaining adequate DM is dependent on surgeon's experience, whether is a surrogate for resection quality, and whether the degree of DM thickness is related to postoperative outcomes in en bloc resection for bladder tumors (ERBT). MATERIALS AND METHODS: We retrospectively analyzed the records of 106 pT1 high-grade BCa patients who underwent ERBT at several institutions. All specimens were reviewed by a single pathologist who assessed the presence or absence of DM and its thickness measured by a micrometer, when present. Early recurrence, defined as pathologically confirmed BCa on repeat resection or tumor recurrence at the first follow-up cystoscopy (within 3 months), was the endpoint reflective of the resection quality. RESULTS: Of 106 patients, DM was detected in 99 (93%), and the median DM thickness was 1.8 mm. Large tumor size (>30 mm) was associated with adequate DM sampling (>1.8mm) (odds ratio [OR]: 6.10, 95% confidence intervals [CIs]: 2.08-17.9, P = 0.001), while surgeon's experience was not. DM presence and DM thickness were both not associated with early recurrence, while positive surgical margin was an independent prognosticator for early recurrence (OR: 3.38, 95% CI: 1.12-10.2, P = 0.031). Excessive DM sampling (>2.1 mm) was associated with prolonged urethral catheterization (OR: 28.8, 95% CI: 3.36-248, P = 0.002). CONCLUSIONS: In ERBT, surgeon's experience seems irrelevant to obtain DM. Resection quality relies on surgical margin status, not the degree of DM. Obtaining excessive DM incurs adverse events/unnecessary medical care.
- MeSH
- cystektomie MeSH
- lidé MeSH
- lokální recidiva nádoru * patologie MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- retrospektivní studie MeSH
- svaly patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC). PATIENTS AND METHODS: We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model. CONCLUSION: We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation.
- MeSH
- biologické markery MeSH
- cystektomie MeSH
- karcinom z přechodných buněk * farmakoterapie chirurgie MeSH
- lidé MeSH
- lymfocyty patologie MeSH
- močový měchýř patologie MeSH
- nádory močového měchýře * farmakoterapie chirurgie MeSH
- neoadjuvantní terapie MeSH
- neutrofily patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- svaly patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- MeSH
- anální kanál patologie MeSH
- fyzioterapie (techniky) MeSH
- lidé MeSH
- os pubis patologie MeSH
- palpační vyšetření konečníku metody MeSH
- pánevní dno * patologie MeSH
- spoušťové body patofyziologie MeSH
- svaly patologie MeSH
- syndromy myofasciální bolesti * diagnóza patofyziologie rehabilitace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
CONTEXT: Radiomics is a field of science that aims to develop improved methods of medical image analysis by extracting a large number of quantitative features. New data have emerged on the successful application of radiomics and machine-learning techniques to the prediction of muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the diagnostic performance of radiomic techniques in predicting MIBC. EVIDENCE ACQUISITION: The literature search for relevant studies up to July 2020 was performed in the PubMed and EMBASE databases by two independent reviewers. The meta-analysis was inducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inclusion criteria comprised studies that evaluated the diagnostic accuracy of radiomic models in predicting MIBC and used pathological examination as the reference standard. For bias assessment, Quality Assessment of Diagnostic Accuracy Studies-2 and Radiomic Quality Score were used. Weighted summary proportions were used to calculate pooled sensitivity and specificity. A linear mixed model was implemented to calculate the hierarchical summary receiver-operating characteristic (HSROC). Meta-regression analyses were performed to explore heterogeneity. EVIDENCE SYNTHESIS: Eight studies with a total of 860 patients were included. The summary estimates for sensitivity and specificity in predicting MIBC were 82% (95% confidence interval [CI]: 77-86%) and 81% (95% CI: 76-85%), respectively. The area under HSROC was 0.88. There were no relevant heterogeneity in diagnostic accuracy measures (I2 = 33% and 41% for sensitivity and specificity, respectively), which was confirmed by a subsequent meta-regression analysis. CONCLUSIONS: Radiomics shows high diagnostic performance in predicting MIBC. Despite differences in approaches, radiomic models were relatively homogeneous in their diagnostic accuracy. With further improvements, radiomics has the potential to become a useful adjunct in clinical management of bladder cancer. PATIENT SUMMARY: Rapidly evolving imaging analysis methods using artificial intelligence algorithms, called radiomics, show high diagnostic performance in predicting muscle-invasive bladder cancer.
BACKGROUND: Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU). OBJECTIVE: To examine tumor size as an independent predictor of muscle-invasive and/or non-organ-confined rates of RPUC at RNU. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified nonmetastatic RPUC at RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2-4N0-2) and (2) non-organ-confined (pT3-4N0-2) RPUC at RNU. RESULTS AND LIMITATIONS: Of 4657 patients, 3052 (65.5%) had pT2-4N0-2 and 2382 (51.2%) pT3-4N0-2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5-5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.1) across all registries. Rates of pT2-4N0-2 and pT3-4N0-2 RPUC increased with tumor size. Specifically, for tumor size intervals from 0.1-1.0 cm to 9.1-10.0 cm, the pT2-4N0-2 rate ranged from 45% to 83% and the pT3-4N0-2 rate ranged from 23% to 75%, respectively (both p < 0.001). In multivariable LRMs, tumor size (in 1-cm units) was an independent predictor of pT2-4N0-2 (odds ratio [OR] 1.25; p < 0.001) and pT3-4N0-2 (OR 1.30; p < 0.001) disease at RNU. CONCLUSIONS: Tumor size is a key predictor of muscle-invasive or non-organ-confined RPUC. Greater tumor size directly and virtually linearly predicts a higher rate of invasive or non-organ-confined RPUC at RNU. PATIENT SUMMARY: For patients with cancer in urinary tract cells lining the kidney, larger tumor size predicts worse stage of the disease at surgery.
- MeSH
- karcinom z přechodných buněk * epidemiologie patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * epidemiologie patologie chirurgie MeSH
- nádory močového měchýře * chirurgie MeSH
- nádory močovodu * epidemiologie patologie chirurgie MeSH
- nefroureterektomie metody MeSH
- retrospektivní studie MeSH
- svaly patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. METHODS: We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. RESULTS: Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12-1.32, p < 0.001, and OR1.35, 95%CI 1.23-1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. CONCLUSION: Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.
- MeSH
- cystektomie MeSH
- hepatocytární růstový faktor terapeutické užití MeSH
- lidé MeSH
- nádory močového měchýře * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- svaly patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis. OBJECTIVES: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients. METHODS: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes. RESULTS: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009). CONCLUSIONS: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies.
- MeSH
- biopsie MeSH
- dítě MeSH
- dospělí MeSH
- interleukiny krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myozitida krev metabolismus patologie MeSH
- polymyozitida krev metabolismus patologie MeSH
- senioři MeSH
- svaly metabolismus patologie MeSH
- upregulace MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.
Circulating miRNAs have been proposed as the effective diagnostic biomarkers for muscular fibrosis-associated diseases. However, circulating biomarkers for early diagnosis of contracture muscles are limited in gluteal muscle contracture (GMC) patients. Here we sought to explore the abnormally expressed miRNAs in plasma and contraction bands of GMC patients. The results showed miR-29a-3p expression in plasma and contraction bands tissue was significantly reduced in GMC patients compared with normal control. Cell viability and levels of proliferation-associated protein cyclin D1 and cyclin-dependent-kinase 2 (CDK2) were powerfully inhibited by miR-29a mimics and enhanced by miR-29a inhibitor compared with negative control. Furthermore, miR-29a mimics effectively impeded, while miR-29a inhibitor enhanced the expression of collagen I and collagen III, followed by the secretion of transforming growth factor beta1 (TGF-beta1), TGF-beta3 and connective tissue growth factor (CTGF) in primary human contraction bands (CB) fibroblasts. The miR-29a-3p negatively regulated the expression of TGF-beta1 through binding to the 3´ UTR region of SERPINH1 (encoding heat shock protein HSP47), but had no effect on Smad2 activity. The miR-29a-3p was inversely correlated with HSP47 in contraction bands tissue from GMC patients. Collectively, miR-29a was notably depressed and regulated cell viability and fibrosis by directly targeting HSP47 in GMC, which suggest that circulating miR-29a might be a potential biomarker for early diagnosis and provides a novel therapeutic target for GMC.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- fibroblasty metabolismus patologie MeSH
- fibróza genetika patologie prevence a kontrola MeSH
- hýždě patologie MeSH
- kontraktura genetika patologie prevence a kontrola MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- proteiny tepelného šoku HSP47 genetika metabolismus MeSH
- studie případů a kontrol MeSH
- svaly metabolismus patologie MeSH
- transformující růstový faktor beta1 genetika metabolismus MeSH
- viabilita buněk fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
