Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 308
Filtrar
1.
Am J Case Rep ; 23: e934149, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35115482

RESUMO

BACKGROUND Inverted papilloma is a benign epithelial lesion of the nasal cavities. Although commonly encountered in clinical practice, it rarely presents with extensive ossification and few cases have been described in the literature. CASE REPORT Herein, we describe the case of a 51-year-old man who presented to clinical attention for persistent right nasal obstruction. Magnetic resonance imaging (MRI) and computed tomography (CT) scans of the facial bones showed a lobated lesion with ossification occupying most of the right nasal cavity. The lesion was removed by endoscopic sinus surgery, leaving the surrounding bone structures intact. On pathological examination, mature bone tissue was found within an inverted papilloma. The pathologist contacted the surgeon, who confirmed that no healthy bone tissue was removed during the procedure. Therefore, a diagnosis of inverted papilloma with ossification could be made without the use of ancillary techniques. CONCLUSIONS Inverted papilloma with ossification is a common lesion with a rare feature. Our report investigates the diagnostic difficulties of a paradigmatic case, highlighting the importance of multidisciplinary teamwork in reaching the final diagnosis.


Assuntos
Neoplasias Nasais , Papiloma Invertido , Neoplasias dos Seios Paranasais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/diagnóstico por imagem , Neoplasias Nasais/cirurgia , Osteogênese , Papiloma Invertido/cirurgia , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/cirurgia , Tomografia Computadorizada por Raios X
2.
Int Urol Nephrol ; 54(3): 541-550, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35044553

RESUMO

OBJECTIVE: To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with radical prostatectomy (RP) and staged with extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: ETD was evaluated as the ratio of endogenous testosterone (ET) on prostate volume (PV). HR-PCa was assessed according to the European Association of Urology (EAU) system. The association of ETD and other routinely clinical factors (BPC: percentage of biopsy positive cores; PSA: prostate specific antigen; ISUP: tumor grade system according to the International Society of Urologic Pathology; cT: tumor clinical stage) with the risk of PLNI was assessed by the logistic regression model. RESULTS: Overall, 201 out of 805 patients (24.9%) were classified HR and PLNI occurred in 42 subjects (20.9%). On multivariate analysis, PLNI was independently predicted by BPC (OR 1.020; 95% CI 1.006-1.035; p = 0.019), ISUP > 3 (OR 2.621; 95% CI 1.170-5.869; p = 0.019) and ETD (OR 0.932; 95% CI 0.870-0.999; p = 0.045). After categorizing continuous clinical predictors, the risk of PLNI was independently increased by ETD up to the median (OR 2.379; 95% CI 1.134-4.991; p = 0.022), BPC > 50% (OR 3.125; 95% CI 1.520-6.425; p = 0.002) as well as by ISUP > 3 (OR 2.219; 95% CI 1.031-4.776; p = 0.042). CONCLUSIONS: As ETD measurements decreased, patients were more likely to have PLNI. In HR disease with PLNI, the influence of PCa on ETD should be addressed by higher level studies.


Assuntos
Excisão de Linfonodo , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Testosterona/sangue , Idoso , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pelve , Valor Preditivo dos Testes , Prostatectomia/métodos , Estudos Retrospectivos , Medição de Risco
3.
Urol Int ; : 1-12, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35081537

RESUMO

OBJECTIVE: The aim of this study is to evaluate the influence of endogenous testosterone density (ETD) on features of aggressive prostate cancer (PCa) in intermediate-risk disease treated with radical prostatectomy and extended pelvic lymph node dissection. MATERIALS AND METHODS: Density measurements included the ratio of endogenous testosterone (ET), prostate-specific antigen (PSA), and percentage of biopsy positive cores (BPC) on prostate volume (ETD, PSAD, and BPCD, respectively). The ratio of percentage of cancer invading the gland (tumor load, TL) on prostate weight (TLD) was also calculated. Unfavorable disease (UD) was defined as tumor upgrading (ISUP >3) and/or upstaging (pT >2) and/or lymph node invasion (LNI). Associations of ETD with features of aggressive PCa, including UD and TLD, were evaluated by logistic and linear regression models. RESULTS: Evaluated cases were 338. Subjects with upgrading, upstaging, and LNI were 61/338 (18%), 73/338 (21%), and 25/338 (7.4%), respectively. TLD correlated with UD (Pearson's correlation coefficient, r = 0.204; p < 0.0001), PSAD (r = 0.342; p < 0.0001), BPCD (r = 0.364; p < 0.0001), and ETD (r = 0.214; p < 0.0001), which also correlated with BMI (r = -0.223; p < 0.0001), PSAD (r = 0.391; p < 0.0001), and BPCD (r = 0.407; p < 0.0001). TLD was the strongest independent predictor of UD (OR = 2.244; 95% CI = 1.146-4.395; p = 0.018). In the multivariate linear regression model predicting BPCD, ETD was an independent predictor (linear regression coefficient, b = 0.026; 95% CI: 0.016-0.036; p < 0.0001) together with PSAD (b = 1.599; 95% CI: 0.863-2.334; p < 0.0001) and TLD (b = 0.489; 95% CI: 0.274-0.706; p < 0.0001). According to models, TLD increased as ETD increased accordingly, but mean ET levels were significantly lower for patients with UD. CONCLUSIONS: As ETD measurements incremented, the risk of large tumors extending beyond the prostate increased accordingly, and patients with lower ET levels were more likely to occult UD. The influence of ETD on PCa biology should be addressed by prospective studies.

4.
J Clin Pathol ; 75(1): 39-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33144356

RESUMO

AIMS: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1). METHODS: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed. RESULTS: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC. CONCLUSION: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.


Assuntos
Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores/metabolismo , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Análise Serial de Tecidos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
5.
Immunotherapy ; 14(2): 145-153, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34806404

RESUMO

Background: Combinations based on immune checkpoint inhibitors are the new first-line standard treatment for metastatic renal cell carcinoma. Sarcomatoid renal cell carcinoma (sRCC) has a dismal prognosis but good immunogenicity. Methods: The authors performed a network meta-analysis of Phase III randomized trials of immune checkpoint inhibitor-based combinations versus standard tyrosine kinase inhibitor monotherapy reporting data for sRCC. The end points were overall survival, progression-free survival and objective response rate. Results: Five trials comprising 569 sRCC patients (out of a total of 4409 metastatic renal cell carcinoma patients) were included. Nivolumab-cabozantinib was the highest ranking treatment for overall survival (p-score = 88%) and progression-free survival (p-score = 81%). Atezolizumab-bevacizumab had the highest rank for objective response rate (p-score = 80%). Conclusion: Despite some limitations, nivolumab-cabozantinib might be the preferred first-line option for sRCC in terms of efficacy.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Anilidas/uso terapêutico , Carcinoma de Células Renais/imunologia , Humanos , Neoplasias Renais/imunologia , Metanálise em Rede , Nivolumabe/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico
6.
Mod Pathol ; 35(3): 376-385, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33990704

RESUMO

Eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) is characterized by a solid and cystic architecture with cells showing abundant eosinophilic cytoplasm with hobnail arrangement and a cytokeratin 7-negative/cytokeratin 20-positive immunophenotype. Recent studies have suggested that bi-allelic events affecting TSC genes might play an important role for such tumors. However, only indirect evidence of the clonal origin of TSC mutation has been gathered so far. Therefore, in this paper we aimed to perform multi-regional tumor sampling molecular analysis in four ESC RCC cases that had been completely embedded, three sporadic and one occurring in a patient with tuberous sclerosis complex (TSC). Histologically, the 4 cases showed cystic and solid architecture and cells with abundant eosinophilic cytoplasm with cytoplasmic stippling and round to oval nuclei. Immunohistochemistry showed at least focal expression of cytokeratin 20 in all tissue samples and negative cytokeratin 7, as well as diffuse positivity for S100A1 and at least focal expression of cathepsin K in three out of four cases. The sporadic cases showed the same somatic TSC1 mutations in all tissue samples analyzed, while the TSC-associated case showed the same TSC1 alteration in both normal tissue and all tumor samples analyzed, proving the germline nature of the alteration. In conclusion, our data demonstrate that clonal TSC loss is a key event in ESC RCC and support considering ESC RCC as an entity given its distinct morphologic, immunophenotypical and molecular characteristics.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Esclerose Tuberosa , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carotenoides , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Amostragem , Esclerose Tuberosa/genética , Vitamina A/análogos & derivados
7.
J Robot Surg ; 16(1): 45-52, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33559802

RESUMO

To investigate factors associated with the risk of major complications after radical prostatectomy (RP) by the open (ORP) or robot-assisted (RARP) approach for prostate cancer (PCa) in a tertiary referral center. 1062 consecutive patients submitted to RP were prospectively collected. The following outcomes were addressed: (1) overall postoperative complications: subjects with Clavien-Dindo System (CD) one through five versus cases without any complication; (2) moderate to major postoperative complications: cases with CD < 2 vs. ≥ 2, and 3) major post-operative complications: subjects with CDS CD ≥ 3 vs. < 3. The association of pre-operative and intra-operative factors with the risk of postoperative complications was assessed by the logistic regression model. Overall, complications occurred in 310 out of 1062 subjects (29.2%). Major complications occurred in 58 cases (5.5%). On multivariate analysis, major complications were predicted by PCa surgery and intraoperative estimated blood loss (EBL). ORP compared to RARP increased the risk of major CD complications from 2.8 to 19.3% (OR = 8283; p < 0.0001). Performing ePLND increased the risk of major complications from 2.4 to 7.4% (OR = 3090; p < 0.0001). Assessing intraoperative blood loss, the risk of major postoperative complications was increased by BL above the third quartile when compared to subjects with intraoperative blood loss up to the third quartile (10.2% vs. 4.6%; OR = 2239; 95%CI: 1233-4064). In the present cohort, radical prostatectomy showed major postoperative complications that were independently predicted by the open approach, extended lymph-node dissection, and excessive intraoperative blood loss.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Encaminhamento e Consulta , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Centros de Atenção Terciária , Resultado do Tratamento
8.
Cancer Cytopathol ; 130(2): 96-109, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34478240

RESUMO

Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Biomarcadores Tumorais/metabolismo , Transportador de Glucose Tipo 1/genética , Homozigoto , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Neoplasias Pleurais/diagnóstico , Deleção de Sequência
9.
J Robot Surg ; 16(2): 463-471, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34131882

RESUMO

To evaluate potential factors associated with the risk of perioperative blood transfusion (PBT) with implications on length of hospital stay (LOHS) and major post-operative complications in patients who underwent robot-assisted radical prostatectomy (RARP) as a primary treatment for prostate cancer (PCa). In a period ranging from January 2013 to August 2019, 980 consecutive patients who underwent RARP were retrospectively evaluated. Clinical factors such as intraoperative blood loss were evaluated. The association of factors with the risk of PBT was investigated by statistical methods. Overall, PBT was necessary in 39 patients (4%) in whom four were intraoperatively. Positive surgical margins, operating time and intraoperative blood loss were associated with perioperative blood transfusion on univariate analysis. On multivariate analysis, the risk of PBT was predicted by intraoperative blood loss (odds ratio, OR 1.002; 95% CI 1.001-1.002; p < 0.0001), which was associated with prolonged operating time and elevated body mass index (BMI). PBT was associated with delayed LOHS and Clavien-Dindo complications > 2. In patients undergoing RARP as a primary treatment for PCa, the risk of PBT represented a rare event that was predicted by severe intraoperative bleeding, which was associated with increased BMI as well as with prolonged operating time. In patients who received a PBT, prolonged LOHS as well as an elevated risk of major Clavien-Dindo complications were seen.


Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Transfusão de Sangue , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
10.
Diagn Cytopathol ; 50(1): 34-45, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34677909

RESUMO

BACKGROUND: Digital pathology has widened pathologists' opportunities to examine both surgical and cytological samples. Recently, portable mobile devices like tablets and smartphones have been tested for application with digital technologies including static, dynamic, and more recently whole slide imaging. This study aimed to review the published literature on the impact of mobile devices on cancer diagnoses in cytology. This analysis focused on their diagnostic potential, technical details, critical issues and pitfalls, and economical aspects. METHODS: A systematic search was carried out in the electronic databases Embase and PubMed. Studies dealing with the application of mobile devices for diagnosing cancer on cytological specimens were included. The quality of studies was assessed with the QUADAS-2 tool. The main themes addressed were the comparison of manual examination with light microscopy and the use of mobile tools for primary diagnosis. The technical features of different models of smartphones and tablets, software, and adapters were also studied in terms of feasibility and costs-analysis. RESULTS: Of 2458 retrieved articles, 18 were included. Concordance with light microscopy was good and diagnostic performance comparable with an expert pathologist's diagnosis. The mobile devices studied differed, sometimes significantly, in terms of speed and cost. The utility was improved by employing specifically designed adapters. Image acquisition and transmission represent the main critical points in almost all studies. CONCLUSION: The use of mobile devices demonstrated promising results regarding the digital evaluation of cytological samples. Widespread adoption even in underserved areas is anticipated following validation studies, technology improvements, and reduction in the costs.


Assuntos
Computadores de Mão , Neoplasias , Citodiagnóstico , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia/métodos , Neoplasias/diagnóstico
11.
Phys Rev Lett ; 127(21): 213601, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34860112

RESUMO

In order for non-Hermitian (NH) topological effects to be relevant for practical applications, it is necessary to study disordered systems. Without disorder, a class of driven-dissipative cavity arrays displays directional amplification when associated with a nontrivial winding number of the NH dynamic matrix. In this work, we show analytically that the correspondence between NH topology and directional amplification holds also in the presence of disorder. We first show that a NH topological phase is preserved as long as the size of the point gap, i.e., the minimum distance of the disorderless complex spectrum from the origin, is larger than the maximum amount of disorder; the disorder is assumed to be bounded but otherwise general, i.e., complex and both local (on-site disorder) and nonlocal (disordered couplings). We then derive analytic bounds for the probability distribution of the scattering matrix elements, which show that the key features of nontrivial NH topology, namely, that the end-to-end forward (reverse) gain grows (is suppressed) exponentially with system size, are preserved in disordered systems. Our results prove that NH topology in cavity arrays is robust against disorder.

12.
Expert Opin Ther Targets ; 25(12): 1095-1105, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34873971

RESUMO

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles. RESEARCH DESIGN AND METHODS: The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes. A subgroup of cases, representative of each subtype, was further investigated using transcriptomic analysis. Bioinformatics tools were applied for clustering and pathway analysis and defining the immune composition of the tumor microenvironment. RESULTS: PHCC had more frequent KRAS mutations (p = 0.0047), whereas TP53 mutations were more common in DECC (p = 0.006). Potentially actionable alterations included high-tumor mutational burden and/or microsatellite instability (7.1%), PI3KCA mutations (8.1%), and MYC (10.1%) and ERBB2 amplification (5.1%). The transcriptomic profiles showed the presence of three distinct clusters, which followed the anatomic origin and differed in immune microenvironment. DECC appeared to contain two distinct tumor subgroups, one enriched for druggable alterations and one lacking actionable opportunities. CONCLUSIONS: This study provides new insights into the molecular landscape and the actionable alterations of ECC. Our findings represent a step toward improved ECC molecular taxonomy and therapeutic strategies for precision oncology.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Genômica , Humanos , Mutação , Medicina de Precisão , Transcriptoma , Microambiente Tumoral/genética
13.
Pathologica ; 113(5): 307-315, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34837089

RESUMO

In this manuscript, we summarize the main features of angiomyolipoma highlighting the recognition of epithelioid angiomyolipoma and the discovery of immunohistochemical expression of HMB45 in a group of tumors that now are referred to as as PEComas. In this scenario, Dr. Rosai believed in our intuition, demonstrating his intellectual honesty and motivated us with his experience ("when a tumor seems malignant it is malignant") and enthusiasm for the new entities ("in Verona, you use HMB45 instead of H&E"). He really pushed the improvement of the knowledge in this field.


Assuntos
Angiomiolipoma , Neoplasias Renais , Neoplasias de Células Epitelioides Perivasculares , Angiomiolipoma/diagnóstico , Humanos , Masculino
14.
Cancers (Basel) ; 13(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771680

RESUMO

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients' characteristics.

15.
Int Urol Nephrol ; 53(12): 2505-2515, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34677784

RESUMO

OBJECTIVES: To evaluate preoperative endogenous testosterone (ET) density (ETD), defined as the ratio of ET on prostate volume, and tumor upgrading risk in low-risk prostate cancer (PCa). MATERIALS AND METHODS: From November 2014 to December 2019, 172 low-risk patients had ET (nmol/L) measured. ETD, prostate-specific antigen density (PSAD) and the ratio of percentage of biopsy positive cores (BPC) to prostate volume (PV), defined as BPC density (BPCD), were evaluated. Associations with tumor upgrading in the surgical specimen were assessed by statistical methods. RESULTS: Overall, 121 patients (70.3%) had tumor upgrading, which was predicted by BPCD (odds ratio, OR = 4.640; 95% CI 1.903-11.316; p = 0.001; overall accuracy: 70.3%). On multivariate analysis, tumor upgrading and clinical density factors related to each other for BPCD being predicted by ETD (regression coefficient, b = 0.032; 95% CI 0.021-0.043; p < 0.0001), PSAD (b = 1.962; 95% CI 1.067-2.586; p < 0.0001) and tumor upgrading (b = 0.259; 95% CI 0.112-0.406; p = 0.001). According to the model, as BPCD increased, ETD and PSAD increased, but the increase was higher for upgraded cases who showed either higher tumor load but significantly lower mean levels of either ET or PSA. CONCLUSIONS: As ETD increased, higher tumor loads were assessed; however, in upgraded patients, lower ET was also detected. ETD might stratify low-risk disease for tumor upgrading features.


Assuntos
Neoplasias da Próstata/metabolismo , Testosterona/metabolismo , Idoso , Biópsia com Agulha de Grande Calibre , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Carga Tumoral
16.
Int Urol Nephrol ; 53(12): 2517-2526, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34580803

RESUMO

OBJECTIVE: To test the hypothesis that endogenous testosterone (ET) density could be associated with tumor load (TL) in patients with intermediate risk (IR) prostate cancer (PCa). MATERIALS AND METHODS: Endogenous testosterone density (ETD, ratio between ET and prostate volume [PV]), biopsy positive cores density (BPCD, the ratio between the number of positive cores and PV) and prostate-specific antigen density (PSAD, ratio between total PSA and PV) were retrospectively evaluated on a prospectively collected data on 430 patients with IR PCa submitted to radical prostatectomy (RP). Tumor load (TL) was measured as the percentage of prostatic volume occupied by cancer at final pathology. Unfavorable disease (UD) was defined as tumor upgrading (ISUP grading group 4, 5) and/or upstaging (pT3a or 3b) in prostate specimens. Associations were assessed by the logistic regression and linear regression models. RESULTS: Overall, UD, which was detected in 122 out of 430 IR patients (28.4%), was predicted by BPCD (odd ratio, OR = 1.356; 95% CI 1.048-1.754; p = 0.020) with a sensitivity 98.4% and overall accuracy 71.9%. On multivariate analysis, BPCD was independently predicted by PSAD (regression coefficient, b = 1.549; 95% CI 0.936-2.162; p < 0.0001), ETD (b = 0.032; 95% CI 0.023-0.040; p < 0.0001) and TL (b = 0.009; 95% CI 0.005-0.014; p < 0.0001). As BPCD increased, ETD and ET levels increased accordingly, but patients with BPCD > 1.0%/mL had significantly lower ET levels. CONCLUSIONS: As ETD increased, BPCD and TL increased, accordingly; furthermore, patients with lower ET levels were more likely to have occult UD. The influence of tumor load, and unfavorable disease on ET and ETD needs to be addressed by further studies.


Assuntos
Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Testosterona/metabolismo , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Fatores de Risco , Carga Tumoral
17.
Pathol Res Pract ; 226: 153605, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34530257

RESUMO

Immunohistochemical assessment with combined positive score (CPS) of programmed death-ligand 1 (PD-L1) is the prerequisite for administration of checkpoint inhibitor therapy in head and neck squamous cell carcinoma (HNSCC). Practicing pathologists are required to assess PD-L1 in routinary work and can be faced up with practical issues not always addressed in clinical trials or guidelines, such as choice of specimen to test, the intrinsic heterogeneity in PD-L1 expression in tumors and the potential impact of already administered therapy, given that patients' material can be procured at several times of cancer natural history. In the present work, we review and discuss the recent literature regarding the assessment of PD-L1 in HNSCC from the perspective of the practicing pathologist, providing some evidence on the single issues. It emerges a general trend to an underestimation of PD-L1 expression in biopsies compared to resection specimens and to a higher degree of positivity in metastatic lymph nodes in respect to primary tumors. Moreover, therapy shows to have contrasting effect on PD-L1 expression. Although further studies are needed, taking into account the intrinsic heterogeneity in PD-L1 expression and the conflicting evidences, it may be speculated that the most recent material of patients in respect to the natural history of tumor can be the most reliable to evaluate PD-L1 expression.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico
18.
Int Urol Nephrol ; 53(10): 2027-2039, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34228260

RESUMO

OBJECTIVE: To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2). RESULTS: Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994-1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989-1.000; p = 0.015). CONCLUSIONS: In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.


Assuntos
Excisão de Linfonodo , Metástase Linfática , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Testosterona/sangue , Idoso , Humanos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Pelve , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
19.
Front Immunol ; 12: 680973, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122444

RESUMO

The immune infiltrate within tumors has proved to be very powerful in the prognostic stratification of patients and much attention is also being paid towards its predictive value. In this work we therefore aimed at clarifying the significance and impact of PD-L1 and PD-1 expression on the prognostic value of CD8+ tumor infiltrating lymphocytes (TILs) in a cohort of consecutive patients with primary resected non-small cell lung cancer (NSCLC). Tissue microarrays (TMA) were built using one representative formalin fixed paraffin embedded block for every case, with 5 cores for each block. TMA sections were stained with PD-L1 (clone SP263), PD-1 (clone NAT105) and CD8 (clone SP57). Number of CD8+ cells per mm2 were automatically counted; median, 25th and 75th percentiles of CD8+ cells were used as threshold for statistical clinical outcome analysis and evaluated in patients subgroups defined by expression of PD-L1 and PD-1 within tumors. We found an overall strong prognostic value of CD8+ cells in our cohort of 314 resected NSCLC, especially in PD-L1 negative tumors lacking PD-1+ TILs, and demonstrated that in PD-L1 positive tumors a higher density of CD8+ lymphocytes is necessary to improve the prognosis. Our data strengthen the concept of the importance of the assessment and quantification of the immune contexture in cancer and, similarly to what has been carried on in colorectal cancer, promote the efforts for the establishment of an Immunoscore for NSCLC for prognostic and possibly predictive purposes.


Assuntos
Antígeno B7-H1/genética , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/etiologia , Neoplasias Pulmonares/etiologia , Linfócitos do Interstício Tumoral/metabolismo , Receptor de Morte Celular Programada 1/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
20.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066087

RESUMO

Immune evasion is a key strategy adopted by tumor cells to escape the immune system while promoting their survival and metastatic spreading. Indeed, several mechanisms have been developed by tumors to inhibit immune responses. PD-1 is a cell surface inhibitory receptor, which plays a major physiological role in the maintenance of peripheral tolerance. In pathological conditions, activation of the PD-1/PD-Ls signaling pathway may block immune cell activation, a mechanism exploited by tumor cells to evade the antitumor immune control. Targeting the PD-1/PD-L1 axis has represented a major breakthrough in cancer treatment. Indeed, the success of PD-1 blockade immunotherapies represents an unprecedented success in the treatment of different cancer types. To improve the therapeutic efficacy, a deeper understanding of the mechanisms regulating PD-1 expression and signaling in the tumor context is required. We provide an overview of the current knowledge of PD-1 expression on both tumor-infiltrating T and NK cells, summarizing the recent evidence on the stimuli regulating its expression. We also highlight perspectives and limitations of the role of PD-L1 expression as a predictive marker, discuss well-established and novel potential approaches to improve patient selection and clinical outcome and summarize current indications for anti-PD1/PD-L1 immunotherapy.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Terapia de Alvo Molecular , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Humanos , Neoplasias/fisiopatologia , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Evasão Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...