RESUMO
PURPOSE: We aimed to investigate controversial pediatric urolithiasis issues systematically, integrating expert consensus and comprehensive guidelines reviews. METHODS: Two semi-structured online focus group meetings were conducted to discuss the study's need and content, review current literature, and prepare the initial survey. Data were collected through surveys and focus group discussions. Existing guidelines were reviewed, and a second survey was conducted using the Delphi method to validate findings and facilitate consensus. The primary outcome measures investigated controversial issues, integrating expert consensus and guideline reviews. RESULTS: Experts from 15 countries participated, including 20 with 16+ years of experience, 2 with 11-15 years, and 4 with 6-10 years. The initial survey identified nine main themes, emphasizing the need for standardized diagnostic and treatment protocols and tailored treatments. Inter-rater reliability was high, with controversies in treatment approaches (score 4.6, 92% agreement), follow-up protocols (score 4.8, 100% agreement), and diagnostic criteria (score 4.6, 92% agreement). The second survey underscored the critical need for consensus on identification, diagnostic criteria (score 4.6, 92% agreement), and standardized follow-up protocols (score 4.8, 100% agreement). CONCLUSION: The importance of personalized treatment in pediatric urolithiasis is clear. Prioritizing low-radiation diagnostic tools, effectively managing residual stone fragments, and standardized follow-up protocols are crucial for improving patient outcomes. Integrating new technologies while ensuring safety and reliability is also essential. Harmonizing guidelines across regions can provide consistent and effective management. Future efforts should focus on collaborative research, specialized training, and the integration of new technologies in treatment protocols.
Assuntos
Guias de Prática Clínica como Assunto , Urolitíase , Humanos , Criança , Urolitíase/terapia , Urolitíase/diagnóstico , Consenso , Técnica DelphiRESUMO
AIMS: Tumour necrosis factor (TNF)-alpha induces death or cell proliferation by activation of nuclear factor (NF)-kappaB, also activated by interleukin (IL)-1 alpha. The aim was to investigate upstream and downstream components of NIK transduction pathway in normal (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC). METHODS AND RESULTS: Immunohistochemistry and Western blotting were performed. In NP, the cytoplasm of epithelial cells was intensely immunoreactive to IL-1 receptor-associated kinase (IRAK), TNF receptor-associated factor (TRAF)-6, NF-kappaB inducing kinase (NIK), I kappa kappa alpha/beta, I kappaB alpha and p-I kappaB; weakly to NF-kappaB-p50; and negative to NF-kappaB-p65. BPH samples were intensely immunoreactive to IRAK, TRAF-6, NIK, I kappa kappa alpha/beta, I kappaB alpha, p-I kappaB; weakly to NF-kappaB-p50 and NF-kappaB-p65. Whereas low-grade PIN showed intermediate results between NP and BPH, results in high-grade PIN were similar to those found in PC (low Gleason). In PC, immunoreactivity was intense for IRAK, TRAF-6, NIK, I kappa kappa alpha/beta (increasing with Gleason), I kappaB alpha, p-I kappaB (decreasing with Gleason); weak for NF-kappaB-p50 and NF-kappaB-p65 (decreasing with Gleason). Nuclear NF-kappaB was observed in PC. CONCLUSIONS: NF-kappaB enhances cell proliferation, but also ATF-2 or Elk-1. Since IL-1 and TNF-alpha are related to inflammation and their immunoexpression increases in PC, inhibition of these cytokines might be a possible target for PC treatment, because they decrease the activity of all transduction pathway members that activate transcription factors such as NF-kappaB, Elk-1 or ATF-2.
Assuntos
Carcinoma/enzimologia , Interleucina-1/fisiologia , NF-kappa B/fisiologia , Hiperplasia Prostática/enzimologia , Neoplasias da Próstata/enzimologia , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Transporte Proteico/fisiologia , Transdução de Sinais/genética , Quinase Induzida por NF-kappaBRESUMO
INTRODUCTION: NF-kB (p50/p65) is a transcription factor involved in TNF-α-induced cell death resistance by promoting several antiapoptotic genes. We intend to relate the expression of NF-kB (p50 and p65) with serum levels of prostate-specific antigen (PSA), both in normal males and in those with pathologic conditions of the prostate. MATERIALS AND METHODS: this study was carried out in 5 normal, 24 benign prostatic hyperplastic (BPH) and 19 patients with prostate cancer (PC). Immunohistochemical and Western blot analyses were performed on tissue and serum PSA was assayed by PSA DPC Immulite assays (Diagnostics Products Corporation, Los Angeles, CA). RESULTS: in controls, p65 NF-kB was not found and p50 was scantly detected in 60% normal samples in the cytoplasm of epithelial cells. Both p50 and p65 were expressed in 62.5% of the samples with BPH and in 63.2% of those with PC. Both increased its frequency of expression with higher PSA serum levels. CONCLUSIONS: Activation of NF-kB revealed by its nuclear translocation in prostate cancer could be related to cancer progression and elevated seric PSA levels. A better understanding of the biologic mechanism by which circulating PSA levels increase and its relation with NF-kB expression is needed. Possibly, NF-kB blockage could be used as a therapeutic target to counteract proliferation in prostate cancer.