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1.
Semin Immunol ; 61-64: 101660, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36370672

RESUMEN

Monoclonal antibodies that target specific ligand-receptor signaling pathways and act as immune checkpoint inhibitors have been designed to remove the brakes in T cells and restore strong and long-term antitumor-immunity. Of note, many of these inhibitory receptors are also expressed by Innate Lymphoid Cells (ILCs), suggesting that also blockade of inhibitory pathways in innate lymphocytes has a role in the response to the treatment with checkpoint inhibitors. ILCs comprise cytotoxic NK cells and "helper" subsets and are important cellular components in the tumor microenvironment. In addition to killing tumor cells, ILCs release inflammatory cytokines, thus contributing to shape adaptive cell activation in the context of immunotherapy. Therefore, ILCs play both a direct and indirect role in the response to checkpoint blockade. Understanding the impact of ILC-mediated response on the treatment outcome would contribute to enhance immunotherapy efficacy, as still numerous patients resist or relapse.


Asunto(s)
Inmunidad Innata , Neoplasias , Humanos , Inmunoterapia , Células Asesinas Naturales , Citocinas/metabolismo , Microambiente Tumoral
2.
Artículo en Inglés | MEDLINE | ID: mdl-38632055

RESUMEN

BACKGROUND AND HYPOTHESIS: The decision for acceptance or discard of the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and one-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium. METHODS: The training set was n=620 for DGF and n=711 for 1y-tl, with validation sets n=158 and n=162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology. RESULTS: Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set. CONCLUSION: Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use.

3.
Pathologica ; 116(1): 55-61, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38482675

RESUMEN

Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Antígeno B7-H1 , Nectinas/genética , Vejiga Urinaria/patología , Hibridación Fluorescente in Situ , Biomarcadores de Tumor/análisis
4.
Lab Invest ; 103(11): 100243, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37634845

RESUMEN

Renal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels, and interstitium, causing functional decline and requiring prompt treatment due to its significant morbidity and mortality. Congo red (CR) stain on renal biopsy samples is the gold standard for diagnosis, but the need for polarized light is limiting the digitization of this nephropathology field. This study explores the feasibility and reliability of CR fluorescence on virtual slides (CRFvs) in evaluating the diagnostic accuracy and proposing an automated digital pipeline for its assessment. Whole-slide images from 154 renal biopsies with CR were scanned through a Texas red fluorescence filter (NanoZoomer S60, Hamamatsu) at the digital Nephropathology Center of the Istituto di Ricovero e Cura a Carattere Scientifico San Gerardo, Monza, Italy, and evaluated double-blinded for the detection and quantification through the amyloid score and a custom ImageJ pipeline was built to automatically detect amyloid-containing regions. Interobserver agreement for CRFvs was optimal (k = 0.90; 95% CI, 0.81-0.98), with even better concordance when consensus-based CRFvs evaluation was compared to the standard CR birefringence (BR) (k = 0.98; 95% CI, 0.93-1). Excellent performance was achieved in the assessment of amyloid score overall by CRFvs (weighted k = 0.70; 95% CI, 0.08-1), especially within the interstitium (weighted k = 0.60; 95% CI, 0.35-0.84), overcoming the misinterpretation of interstitial and capsular collagen BR. The application of an automated digital pathology pipeline (Streamlined Pipeline for Amyloid detection through CR fluorescence Digital Analysis, SPADA) further increased the performance of pathologists, leading to a complete concordance with the standard BR. This study represents an initial step in the validation of CRFvs, demonstrating its general reliability in a digital nephropathology center. The computational method used in this study has the potential to facilitate the integration of spatial omics and artificial intelligence tools for the diagnosis of amyloidosis, streamlining its detection process.


Asunto(s)
Amiloidosis , Rojo Congo , Humanos , Reproducibilidad de los Resultados , Inteligencia Artificial , Amiloide/metabolismo , Coloración y Etiquetado , Amiloidosis/diagnóstico por imagen , Amiloidosis/metabolismo
5.
Transpl Int ; 36: 11410, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37470063

RESUMEN

The ESOT TLJ 3.0. consensus conference brought together leading experts in transplantation to develop evidence-based guidance on the standardization and clinical utility of pre-implantation kidney biopsy in the assessment of grafts from Expanded Criteria Donors (ECD). Seven themes were selected and underwent in-depth analysis after formulation of PICO (patient/population, intervention, comparison, outcomes) questions. After literature search, the statements for each key question were produced, rated according the GRADE approach [Quality of evidence: High (A), Moderate (B), Low (C); Strength of Recommendation: Strong (1), Weak (2)]. The statements were subsequently presented in-person at the Prague kick-off meeting, discussed and voted. After two rounds of discussion and voting, all 7 statements reached an overall agreement of 100% on the following issues: needle core/wedge/punch technique representatively [B,1], frozen/paraffin embedded section reliability [B,2], experienced/non-experienced on-call renal pathologist reproducibility/accuracy of the histological report [A,1], glomerulosclerosis/other parameters reproducibility [C,2], digital pathology/light microscopy in the measurement of histological variables [A,1], special stainings/Haematoxylin and Eosin alone comparison [A,1], glomerulosclerosis reliability versus other histological parameters to predict the graft survival, graft function, primary non-function [B,1]. This methodology has allowed to reach a full consensus among European experts on important technical topics regarding pre-implantation biopsy in the ECD graft assessment.


Asunto(s)
Trasplante de Riñón , Trasplante de Órganos , Humanos , Trasplante de Riñón/métodos , Reproducibilidad de los Resultados , Riñón/patología , Biopsia , Donantes de Tejidos , Supervivencia de Injerto
6.
Pediatr Dev Pathol ; 26(1): 5-12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36448447

RESUMEN

Digital imaging, including the use of artificial intelligence, has been increasingly applied to investigate the placenta and its related pathology. However, there has been no comprehensive review of this body of work to date. The aim of this study was to therefore review the literature regarding digital pathology of the placenta. A systematic literature search was conducted in several electronic databases. Studies involving the application of digital imaging and artificial intelligence techniques to human placental samples were retrieved and analyzed. Relevant articles were categorized by digital image technique and their relevance to studying normal and diseased placenta. Of 2008 retrieved articles, 279 were included. Digital imaging research related to the placenta was often coupled with immunohistochemistry, confocal microscopy, 3D reconstruction, and/or deep learning algorithms. By significantly increasing pathologists' ability to recognize potentially prognostic relevant features and by lessening inter-observer variability, published data overall indicate that the application of digital pathology to placental and perinatal diseases, along with clinical and radiology correlation, has great potential to improve fetal and maternal health care including the selection of targeted therapy in high-risk pregnancy.


Asunto(s)
Inteligencia Artificial , Placenta , Femenino , Embarazo , Humanos , Algoritmos , Feto
7.
Cytopathology ; 34(5): 419-422, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36721906

RESUMEN

The COVID-19 pandemic has acted as a powerful change driver in the field of pathology and has had relevant consequences on the practice of cytopathology, in terms of changes in workload, rates of malignancy, and the performance of cytology. At the same time, regulatory authorities have relaxed their requirements for the deployment of digital pathology for remote diagnostic reporting. However, most of these improvements have concerned digital histopathology. Data from a literature search show that experiences in digital cytopathology during the pandemic have concerned mainly educational and academic activities. From a broader point of view, when searching for all published literature on digital pathology, only a minority of papers deal with cytopathology, but a noticeable increase in publications has been seen in the last 10 years, with an upward trend toward a maximum of papers in 2021. Indeed, the pandemic has led to greater awareness of the possibility of digital for cytopathology as well.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Citodiagnóstico , Prueba de COVID-19
8.
Cytopathology ; 34(1): 5-14, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36082410

RESUMEN

Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guideline includes three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been beyond the scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology. A systematic search was carried out in PubMed-MEDLINE and Embase databases up to November 2021 to identify all publications regarding validation of WSI in cytology. Each article was reviewed to determine if SRs and/or GPSs recommended by the CAP guideline were adequately satisfied. Of 3963 retrieved articles, 25 were included. Only 4/25 studies (16%) satisfied all three SRs, with only one publication (1/25, 4%) fulfilling all three SRs and nine GPSs. Lack of a suitable validation dataset was the main missing SR (16/25, 64%) and less than a third of the studies reported intra-observer variability data (7/25, 28%). Whilst the CAP guideline for WSI validation in clinical practice helped the widespread adoption of digital pathology, more evidence is required to routinely employ WSI for diagnostic purposes in cytopathology practice. More dedicated validation studies satisfying all SRs and/or GPSs recommended by the CAP are needed to help expedite the use of WSI for primary diagnosis in cytopathology.


Asunto(s)
Interpretación de Imagen Asistida por Computador , Microscopía , Humanos , Microscopía/métodos , Interpretación de Imagen Asistida por Computador/métodos , Variaciones Dependientes del Observador , Citodiagnóstico/métodos , Laboratorios
9.
Cytopathology ; 34(6): 581-589, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37530465

RESUMEN

OBJECTIVE: Despite an increase in thyroid fine needle aspiration (FNA) and advances in whole slide imaging (WSI) adoption, digital pathology is still considered inadequate for primary diagnosis of these cases. Herein, we aim to validate the utility of WSI in thyroid FNAs employing the Delphi method strategy. METHODS: A panel of experts from seven reference cytology centres was recruited. The study consisted of two consecutive rounds: (1) an open-ended, free-response questionnaire generating a list of survey items; and (2) a consensus analysis of 80 selected shared WSIs from 80 cases by six investigators answering six morphological questions utilising a 1 to 5 Likert scale. RESULTS: High consensus was achieved for all parameters, with an overall average score of 4.27. The broad majority of items (84%) were ranked either 4 or 5 by each physician. Two badly scanned cases were responsible for more than half of the low-ranked (≤2) values (57%). Good to excellent (≥3) diagnostic confidence was reached in more than 95.2% of cases. For most cases (78%) WSI assessment was not limited by technical issues linked to the image acquisition process. CONCLUSION: This systematic Delphi study indicates broad consensus among participating physicians on the application of DP to thyroid cytopathology, supporting expert opinion that WSI is reliable and safe for primary diagnostic purposes.

10.
Pathologica ; 115(6): 318-324, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38180139

RESUMEN

Objective: The use of standardized structured reports (SSR) and suitable terminologies like SNOMED-CT can enhance data retrieval and analysis, fostering large-scale studies and collaboration. However, the still large prevalence of narrative reports in our laboratories warrants alternative and automated labeling approaches. In this project, natural language processing (NLP) methods were used to associate SNOMED-CT codes to structured and unstructured reports from an Italian Digital Pathology Department. Methods: Two NLP-based automatic coding systems (support vector machine, SVM, and long-short term memory, LSTM) were trained and applied to a series of narrative reports. Results: The 1163 cases were tested with both algorithms, showing good performances in terms of accuracy, precision, recall, and F1 score, with SVM showing slightly better performances as compared to LSTM (0.84, 0.87, 0.83, 0.82 vs 0.83, 0.85, 0.83, 0.82, respectively). The integration of an explainability allowed identification of terms and groups of words of importance, enabling fine-tuning, balancing semantic meaning and model performance. Conclusions: AI tools allow the automatic SNOMED-CT labeling of the pathology archives, providing a retrospective fix to the large lack of organization of narrative reports.


Asunto(s)
Procesamiento de Lenguaje Natural , Systematized Nomenclature of Medicine , Humanos , Estudios Retrospectivos
11.
Pathologica ; 115(4): 199-204, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37314869

RESUMEN

A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31st, 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management.


Asunto(s)
Trasplante de Riñón , Nefrología , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Riñón/cirugía , Riñón/patología , Terapia de Inmunosupresión , Biopsia
12.
Mod Pathol ; 35(6): 712-720, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35249100

RESUMEN

Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83-0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms.


Asunto(s)
Neoplasias de la Mama , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Biomarcadores de Tumor/análisis , Proliferación Celular , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Antígeno Ki-67/análisis , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Reproducibilidad de los Resultados
13.
Histopathology ; 80(2): 397-406, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34496080

RESUMEN

AIMS: The introduction of immunotherapy for patients with head and neck squamous cell carcinoma (HNSCC) raises the need for harmonisation between different types of antibody and immunohistochemistry platform for evaluating the expression of PD-L1 by use of the combined positive score (CPS) in this tumour. The aim of this study was to compare the expression of PD-L1 as determined with the CPS and two widely used assays (the 22C3 PharmDx assay and the SP263 assay) in a cohort of HNSCCs. METHODS AND RESULTS: We analysed 43 whole sections of HNSCC with two different anti-PD-L1 antibodies, 22C3 and SP263. The results, expressed as the CPS, were evaluated by 10 trained pathologists and statistical analyses were performed. We found a very similar results for PD-L1 expression between the 22C3 PharmDx assay and the SP263 assay in our cohort, and a strong and significant correlation between the two assays for all specimens (P < 0.0001). The interobserver reliability among pathologists for the continuous scores of CPS with the intraclass correlation coefficient and the correlation between the two assays were both good. Moreover, the rate of agreement between assays was high at all cut-offs and was best for the most relevant cut-off of CPS ≥ 1, and the kappa values were always in the range of almost perfect. CONCLUSIONS: Two different assays (the 22C3 PharmDx assay and SP263 assay) for PD-L1 in HNSCC showed high agreement. These data suggest that these two assays are interchangeable in the selection of patients with HNSCC for immunotherapy.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
14.
Int J Mol Sci ; 23(5)2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35269607

RESUMEN

Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) is receiving more attention as a biomarker for eligibility for immune checkpoint inhibitors in advanced diseases. However, due to high costs and resource limitations, MSI/dMMR testing is not widely performed. Some attempts are in progress to predict MSI/dMMR status through histomorphological features on H&E slides using artificial intelligence (AI) technology. In this study, the potential predictive role of this new methodology was reviewed through a systematic review. Studies up to September 2021 were searched through PubMed and Embase database searches. The design and results of each study were summarized, and the risk of bias for each study was evaluated. For colorectal cancer, AI-based systems showed excellent performance with the highest standard of 0.972; for gastric and endometrial cancers they showed a relatively low but satisfactory performance, with the highest standard of 0.81 and 0.82, respectively. However, analyzing the risk of bias, most studies were evaluated at high-risk. AI-based systems showed a high potential in predicting the MSI/dMMR status of different cancer types, and particularly of colorectal cancers. Therefore, a confirmation test should be required only for the results that are positive in the AI test.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Endometriales , Inteligencia Artificial , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Endometriales/genética , Femenino , Humanos , Inestabilidad de Microsatélites
15.
Pathologica ; 114(4): 322-325, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36136900

RESUMEN

Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adulto , COVID-19/diagnóstico , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Humanos , ARN Mensajero , SARS-CoV-2 , Piel/patología
16.
Liver Transpl ; 27(1): 55-66, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32746498

RESUMEN

The risk of transmission of malignancy from donor to recipient is low. However, this occurrence has dramatic consequences. Many reports of donor-derived cancers in liver transplant recipients have been published, but they have not been systematically summarized into a lucid and unified analysis. The present study is an attempt to provide clarity to this unusual but clinically important problem. We systematically reviewed all patient reports, patient series, and registries published on cancer transmission events through the end of December 2019. We identified a total of 67 publications with 92 transmission events. The most frequently transmitted cancers were lymphomas (30; 32.6%), melanomas (8; 8.7%), and neuroendocrine tumors (8; 8.7%). Most of the melanomas were metastasizing, whereas most of the lymphomas were localized to the graft. The median time to cancer diagnosis after transplantation was 7 months, with 78.1% of diagnoses established in the first year. Melanoma carried the worst prognosis, with no recipients alive at 1 year after cancer diagnosis. Lymphoma recipients had a better outcome, with more than 75% surviving at 2 years. A metastatic cancer carries a worse prognosis for recipients, and recipients with localized cancer can benefit from the chance to undergo transplantation again. The findings confirm the need to pay attention to donors with a history of melanoma but also suggest the need for a more careful evaluation of groups of donors, such as those dying from cerebral hemorrhage. Finally, recipients of organs from donors with cancer should be carefully followed to detect potential transmission.


Asunto(s)
Trasplante de Hígado , Neoplasias , Trasplantes , Supervivencia de Injerto , Humanos , Trasplante de Hígado/efectos adversos , Sistema de Registros , Donantes de Tejidos
17.
J Oral Pathol Med ; 50(9): 864-873, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34157159

RESUMEN

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression with combined positive score (CPS) ≥1 is required for administration of checkpoint inhibitor therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The 22C3 pharmDx Dako immunohistochemical assay is the one approved as companion diagnostic for pembrolizumab, but many laboratories work on other platforms and/or with other clones, and studies exploring the potential interchangeability of assays have appeared. EVIDENCE FROM THE LITERATURE: After review of the literature, it emerges that the concordance among assays ranges from fair to moderate, with a tendence of assay SP263 to yield a higher quota of positivity and of assay SP142 to stain better immune cells. Moreover, pathologists achieve very good concordance in assessing PD-L1 CPS, particularly with SP263. CONCLUSIONS: Differences in terms of platforms, procedures, and study design still preclude a quantitative synthesis of evidence and clearly further work is needed to draw stronger conclusions on the interchangeability of PD-L1 assays in HNSCC.


Asunto(s)
Antígeno B7-H1 , Neoplasias de Cabeza y Cuello , Biomarcadores de Tumor , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Inmunohistoquímica , Recurrencia Local de Neoplasia , Patólogos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico
18.
Cytopathology ; 32(5): 588-595, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33792981

RESUMEN

The application of next generation sequencing (NGS) technology to cytological samples has significantly modified molecular cytopathology practice. Cytological samples represent a valid source of high-quality DNA for NGS analysis, especially for predicting patients' response to targeted treatments and for refining the risk of malignancy in indeterminate cytological diagnoses. However, several pre-analytical factors may influence the reliability of NGS clinical analysis. Here, we briefly review the challenges of NGS in cytology practice, focusing on those pre-analytical factors that may negatively affect NGS success rates and routine diagnostic applications. Finally, we address the future directions of the field.


Asunto(s)
Citodiagnóstico/métodos , Técnicas Citológicas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patología
19.
Int J Mol Sci ; 22(10)2021 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-34066087

RESUMEN

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.


Asunto(s)
Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Terapia Molecular Dirigida , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Humanos , Neoplasias/fisiopatología , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Escape del Tumor
20.
Pathologica ; 113(4): 280-284, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34542544

RESUMEN

Congenital granular cell epulis is a rare benign lesion usually arising as single mass from the alveolar ridge of maxillary bone of female newborns, composed of polygonal granular cells that typically stain negative for S-100, in contrast to the adult counterpart. Larger lesions can disturb breathing and breast-feeding, requiring surgery. Prenatal diagnosis is achieved in few cases, even if this would be important for best management of delivery and therapy. Here we present a case of multiple CGCE in a female newborn discovered at birth, together with a brief review of pathogenesis, differential diagnoses and treatment implications of early diagnosis.


Asunto(s)
Neoplasias Gingivales , Tumor de Células Granulares , Diagnóstico Diferencial , Femenino , Neoplasias Gingivales/diagnóstico por imagen , Neoplasias Gingivales/cirugía , Tumor de Células Granulares/diagnóstico por imagen , Tumor de Células Granulares/cirugía , Humanos , Recién Nacido , Embarazo , Diagnóstico Prenatal
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