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Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.
Subject(s)
Aortic Valve Stenosis , Aortic Valve , Calcinosis , Computed Tomography Angiography , Fibrosis , Humans , Male , Prospective Studies , Female , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Middle Aged , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/pathology , Aortic Valve Stenosis/surgery , Calcinosis/diagnostic imaging , Calcinosis/pathology , Fibrosis/diagnostic imaging , Computed Tomography Angiography/methods , AgedABSTRACT
BACKGROUND: Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. The aim of this study was to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts. METHODS: This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. RESULTS: A total of 36 patients developed biliary complications (at least one event) - 6 events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7% vs. 43.4% [P=0.11]). No differences were found significant with respect to anastomotic (19.9% vs. 33.7% [P=0.20]) and non-anastomotic strictures (0% vs. 11.1% [P=0.10]) as well as biliary fistulas (11.7% vs. 12.2% [P=0.93]). Survival analysis did not show significantly different result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038). CONCLUSIONS: The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for benefits of dHOPE in low-risk grafts.
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BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.
Subject(s)
Appendectomy , Appendicitis , COVID-19 , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Humans , Cross-Sectional Studies , COVID-19/pathology , COVID-19/immunology , COVID-19/complications , Appendicitis/pathology , Appendicitis/virology , Male , Child , Female , Systemic Inflammatory Response Syndrome/pathology , Child, Preschool , SARS-CoV-2/immunology , Adolescent , Appendix/pathologyABSTRACT
INTRODUCTION: A tumor microenvironment plays an important role in bladder cancer development and in treatment response. PURPOSE: The aim of the study was to assess how the components of the microenvironment affect tumor recurrence and to find the potential biomarkers for immunotherapy in NMIBC. METHODS: The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome. RESULTS: Multivariate analysis confirmed that the CD4 (p = 0.001), CD20 (p = 0.008) and PD-L1 expressed on tumor cells (p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4+ cell infiltration (<4.6%) and severe CD20+ infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group also frequently recurs after 12 months (p = 0.0005). CONCLUSIONS: The evaluation of CD4+ and CD20+ cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates the determination of a group of patients with a low risk of recurrence.
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BACKGROUND/AIM: Data on the prevalence of human papilloma virus (HPV) DNA in different subtypes of endometrial carcinomas (EC) are limited. PATIENTS AND METHODS: We investigated the incidence of HPV16 DNA E6/E7 transcripts in 47 type I (endometrioid-type) tumors and eight type II (non-endometrioid-type) uterine neoplasms applying PCR-based technology. Immunohistochemical staining in HPV16 positive cases was also performed, and seven lymph node metastases were examined for the presence of HPV16 DNA E6/E7. RESULTS: None of the type I ECs was positive for HPV16 E6 gene transcripts; however, four out of 8 (50%) type II ECs (two out of four papillary-serous and two out of four clear-cell carcinomas) were positive for HPV16 E6 transcripts. The difference in HPV16 E6 transcripts between endometrioid and non-endometrioid neoplasms was statistically significant (p=0.0011). Apart from the cancer subtype, none of the EC clinicopathological features were related to HPV16 E6 positivity. None of 55 ECs contained an HPV16 E7 gene transcripts. All slides from gene-positive samples revealed intense immunostaining reactions. Interestingly, the virus was not detected in any of seven lymph node metastases, including four from HPV16-positive primary tumors. CONCLUSION: HPV16 E6 gene transcripts may be present in ECs, primarily in the non-endometrioid (type II) uterine cancer subtypes. HPV E6/E7 DNA transcripts were not found in lymph node metastases, even when the primary tumors harboured HPV DNA.
Subject(s)
Endometrial Neoplasms , Papillomavirus Infections , Female , Humans , Human papillomavirus 16/genetics , Lymphatic Metastasis , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Endometrial Neoplasms/genetics , DNAABSTRACT
OBJECTIVE: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). BACKGROUND: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. METHODS: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054). RESULTS: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. CONCLUSION: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.
Subject(s)
Liver Transplantation , Humans , Brain Death , Organ Preservation , Graft Survival , Tissue Donors , Liver , PerfusionABSTRACT
Bladder cancer (BC) can be divided into two subgroups depending on invasion of the muscular layer: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Its aggressiveness is associated, inter alia, with genetic aberrations like losses of 1p, 6q, 9p, 9q and 13q; gain of 5p; or alterations in the p53 and p16 pathways. Moreover, there are reported metabolic disturbances connected with poor diagnosis-for example, enhanced aerobic glycolysis, gluconeogenesis or haem catabolism.Currently, the primary way of treatment method is transurethral resection of the bladder tumour (TURBT) with adjuvant Bacillus Calmette-Guérin (BCG) therapy for NMIBC or radical cystectomy for MIBC combined with chemotherapy or immunotherapy. However, intravesical BCG immunotherapy and immune checkpoint inhibitors are not efficient in every case, so appropriate biomarkers are needed in order to select the proper treatment options. It seems that the success of immunotherapy depends mainly on the tumour microenvironment (TME), which reflects the molecular disturbances in the tumour. TME consists of specific conditions like hypoxia or local acidosis and different populations of immune cells including tumour-infiltrating lymphocytes, natural killer cells, neutrophils and B lymphocytes, which are responsible for shaping the response against tumour neoantigens and crucial pathways like the PD-L1/PD-1 axis.In this review, we summarise holistically the impact of the immune system, genetic alterations and metabolic changes that are key factors in immunotherapy success. These findings should enable better understanding of the TME complexity in case of NMIBC and causes of failures of current therapies.
Subject(s)
Non-Muscle Invasive Bladder Neoplasms , Urinary Bladder Neoplasms , Humans , BCG Vaccine/therapeutic use , Tumor Microenvironment , Urinary Bladder Neoplasms/pathology , Immunotherapy , Neoplasm Invasiveness , Administration, Intravesical , Adjuvants, ImmunologicABSTRACT
Introduction: Biopsy of facial skin lesions is an important supplement to dermatological diagnostics, especially in doubtful cases or suspected of being malignant. Objectives: The aim of the retrospective study of 2135 histopathological records of lesions on the face was to: establish the most common indications for a skin biopsy in patients with facial lesions, establish the frequency of histopathological diagnoses, evaluate how often clinically suspected inflammatory lesions are identified as tumors in histopathology, evaluate the accuracy of clinical diagnoses of the most common skin tumors and dermatoses. Methods: It was a retrospective study. Histopathological records from the lesions on the face from years 2010-2017 were analyzed. Results: The mean age of patients was 69.3 [7-98]. Fifty-eight percent of the patients were women. Among 2135 clinical diagnoses skin tumors were suspected in 1905 cases. Among 2169 obtained histopathological results (34 biopsies showed 2 diseases), we identified skin tumors in 1940 cases, with 1388 confirmed as malignant. The clinical diagnosis of a specific benign or malignant skin tumor was accurate in 1013/1634 subjects, in comparison to inflammatory lesions, which were correct in 67/148 cases, (P = 0.0001). Among all preliminary inflammatory diagnoses, 33/204 lesions were identified as skin tumors in histopathology. Conclusions: In conclusion in most cases of skin tumors the clinical diagnosis is confirmed by histopathological examination. In case of facial inflammatory lesions, the accuracy of clinical diagnosis is lower, with a significant number of facial lesions appearing inflammatory in clinical evaluation but being diagnosed as skin cancers in pathology.
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Hypopharyngeal cancer is a poorly characterized type of head and neck squamous cell carcinoma (HNSCC) with bleak prognosis and only few studies focusing specifically on the genomic profile of this type of cancer. We performed molecular profiling of 48 HPV (Human Papilloma Virus)-negative tumor samples including 23 originating from the hypopharynx and 25 from the larynx using a targeted next-generation sequencing approach. Among genes previously described as significantly mutated, TP53, FAT1, NOTCH1, KMT2C, and CDKN2A were found to be most frequently mutated. We also found that more than three-quarters of our patients harbored candidate actionable or prognostic alterations in genes belonging to RTK/ERK/PI3K, cell-cycle, and DNA-damage repair pathways. Using previously published data we compared 67 hypopharyngeal cancers to 595 HNSCC from other sites and found no prominent differences in mutational frequency except for CASP8 and HRAS genes. Since we observed relatively frequent mutations of KTM2C (MLL3) in our dataset, we analyzed their role, in vitro, by generating a KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrated that KMT2C loss-of-function mutations resulted in increased colony formation and proliferation, in concordance with previously published results. In summary, our results show that the mutational profile of hypopharyngeal cancers might be similar to the one observed for other head and neck cancers with respect to minor differences and includes multiple candidate actionable and prognostic genetic alterations. We also demonstrated, for the first time, that the KMT2C gene may play a role of tumor suppressor in HNSCC, which opens new possibilities in the search for new targeted treatment approaches.
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PURPOSE: Wilson's disease (WD) is an inherited disorder involving copper accumulation in the liver and brain. An important mechanism responsible for hepatocyte injury in WD is mitochondria destruction, although damage may also be caused by oxidative stress and lipid peroxidation. PATIENTS/METHODS: The study included 54 treated patients with WD without liver cirrhosis and 10 healthy controls. All patients had liver biopsy and immunohistochemical analysis of liver samples was performed using targeted staining for markers of mitochondrial injury (thioredoxin-2 [TRX2], cytochrome c oxidases subunit 2 [COX2], and cytochrome c oxidases complex IV subunit 4 isoform 1 [COX4-1]), of oxidative stress (peroxiredoxin-1 [PRDX1] and 8-hydroxyguanosine [8-OHdG]), and of lipid peroxidation (4-hydroxynonenal [4-HNE]). RESULTS: Expression, measured as mean strengths of intensity (SI) of immunohistochemical reactions per 5 fields of view, was significantly lower in patients with WD compared to controls for COX2 (2.9 vs 8.3), 8-OHdG (0.05 vs 3.8), TRX2 (4.9 vs 10.1), and PRDX1 (4.6 vs 10.1) (all P â< â10-5). COX4-1 expression was undetected in patients with WD but detected in control specimens (8.1) (P â< â10-5). 4-HNE was overexpressed in patients with WD compared to controls (10.1 vs 9.1; P â< â0.07). CONCLUSIONS: Negligible COX4-1 and low COX2 expression in liver specimens may serve as markers of inner mitochondrial membrane injury in treated patients with WD and early stages of liver fibrosis.
Subject(s)
Hepatolenticular Degeneration , Humans , Hepatolenticular Degeneration/metabolism , Hepatolenticular Degeneration/pathology , Copper , Cyclooxygenase 2/metabolism , Cytochromes c/metabolism , Liver/metabolism , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Biomarkers/metabolism , Oxidoreductases/metabolism , Peroxiredoxins/metabolism , Thioredoxins/metabolismABSTRACT
BACKGROUND: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. METHODS: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. RESULTS: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084). CONCLUSIONS: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.
Subject(s)
Takotsubo Cardiomyopathy , Animals , Echocardiography , Female , Humans , Isoproterenol/adverse effects , Male , Myocytes, Cardiac , Rats , Rats, Sprague-Dawley , Takotsubo Cardiomyopathy/chemically induced , Takotsubo Cardiomyopathy/complications , Takotsubo Cardiomyopathy/diagnosisABSTRACT
In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.
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The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH.
Subject(s)
Antioxidants/metabolism , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Hepatitis, Autoimmune/genetics , Liver Cirrhosis/genetics , Mitochondrial Proteins/genetics , Oxidoreductases/genetics , Polymorphism, Genetic/genetics , Polymorphism, Genetic/physiology , Adolescent , Adult , Aged , Child , Female , Genotype , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/metabolism , Hepatitis, Autoimmune/prevention & control , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/metabolism , Liver Cirrhosis/prevention & control , Male , Middle Aged , Phenotype , Young AdultABSTRACT
Resumo Introdução: A microarquitetura dos vasos mucosos e submucosos é crucial para o diagnóstico. A neoangiogênese é um parâmetro biológico confirmado que implica progressão e metástase no câncer de laringe. Objetivo: Investigar a correlação entre as classificações de padrões vasculares por imagem de banda estreita e densidade imuno-histológica de microvasos em diferentes tipos de lesões intraepiteliais da prega vocal. Método: A análise da densidade imuno-histológica de microvasos com o uso de anticorpos CD31 e CD34 foi feita em 77 lesões, inclusive: 20 lesões não displásicas, 20 com displasia de baixo grau, 17 com displasia de alto grau e 20 com câncer invasivo. A avaliação dos padrões vasculares com a imagem de banda estreita, de acordo com as diretrizes de classificação de Ni e da European Laryngological Society, foi feita antes da ressecção cirúrgica. Resultados: O valor médio da densidade imuno-histológica de microvasos com CD31 foi o mais alto para as lesões do Tipo IV de Ni (20,55), enquanto para o padrão longitudinal e perpendicular, de acordo com a classificação da European Laryngological Society, foi de 12,50 e 19,45, respectivamente. O maior valor médio da densidade imuno-histológica de microvasos com CD34 foi identificado nas lesões de Ni Tipo Va (35,43) e nos padrões longitudinal e perpendicular de acordo com a classificação da European Laryngological Society foi de 15,12 e 30,40, respectivamente. Conclusões: As alterações morfológicas microvasculares das lesões laríngeas intraepiteliais observadas na endoscopia por imagem de banda estreita foram positivamente correlacionadas com os índices de angiogênese da avaliação imuno-histológica.
Subject(s)
Laryngeal Neoplasms/diagnostic imaging , Narrow Band Imaging , Vocal Cords/diagnostic imaging , Endoscopy , Microvascular DensityABSTRACT
Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
Subject(s)
Cholangitis, Sclerosing , Fatigue Syndrome, Chronic , Liver Cirrhosis, Biliary , Liver Transplantation , Adult , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/surgery , Female , Humans , Liver Cirrhosis, Biliary/complications , Liver Cirrhosis, Biliary/surgery , Liver Transplantation/adverse effects , Male , Quality of LifeABSTRACT
OBJECTIVES: Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson's disease. To evaluate the accuracy of collagen proportionate area (CPA), transient elastography and shear wave elastography (SWE) in the assessment of liver fibrosis in adult patients with Wilson's disease. METHODS: In this retrospective study of 60 patients with Wilson's disease, results of percutaneous cutting liver biopsy assessed using the Ishak fibrosis score and CPA were compared with liver stiffness measured with transient elastography and SWE. RESULTS: CPA correlated with the Ishak score (r = 0.45; P = 0.001) and transient elastography results correlated with SWE measurements (r = 0.80; P = 0.0001). In contrast, transient elastography or SWE did not significantly correlate with the Ishak score or CPA. CONCLUSION: Collagen content assessment may be useful for estimation of liver fibrosis in patients with Wilson's disease. However, single time-point elastographic liver stiffness measurements have a limited diagnostic value in Wilson's disease.
Subject(s)
Elasticity Imaging Techniques , Hepatolenticular Degeneration , Adult , Biopsy , Hepatolenticular Degeneration/diagnostic imaging , Humans , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Retrospective StudiesABSTRACT
INTRODUCTION: The microarchitecture of the mucosal and submucosal vessels is crucial for diagnosis of vocal fold lesions. Neo-angiogenesis is a confirmed biological parameter that implicates progression and metastasis in laryngeal cancer. OBJECTIVE: This study investigates the correlation between vascular pattern classifications by narrow band imaging and immunohistological microvessel density in different types of intraepithelial vocal fold lesions. METHODS: Analysis of immunohistological microvessel density using CD31 and CD34 antibodies was performed in 77 lesions including: 20 non-dysplastic lesions, 20 with low-grade dysplasia, 17 with high-grade dysplasia and 20 invasive cancers. The evaluation of vascular patterns with narrow band imaging according to the Ni classification and European Laryngological Society guidelines was performed prior to surgical resection. RESULTS: The mean value of CD31 microvessel density was the highest for Ni Type IV lesions (20.55), whereas for the longitudinal and perpendicular patterns according to the European Laryngological Society classification it was 12.50 and 19.45 respectively. The highest mean value of microvessel density with CD 34 was identified in Ni Type Va (35.43) lesions and in the longitudinal and perpendicular patterns according to the European Laryngological Society classification was 15.12 and 30.40 respectively. CONCLUSIONS: The microvascular morphological changes of intraepithelial laryngeal lesions observed under narrow band imaging endoscopy are positively correlated with angiogenesis indexes of immunohistological evaluation.
Subject(s)
Laryngeal Neoplasms , Narrow Band Imaging , Endoscopy , Humans , Laryngeal Neoplasms/diagnostic imaging , Microvascular Density , Vocal Cords/diagnostic imagingABSTRACT
BACKGROUND AND AIMS: Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two-dimensional shear wave elastography (2D-SWE), are used to quantify liver fibrosis. Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D-SWE. Here, we compare liver and spleen 2D-SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH. METHODS: We analysed liver and spleen 2D-SWE in relation to liver TE in 90 patients treated ≥ 6 months for AIH. Liver and spleen 2D-SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18 months follow-up. RESULTS: Liver 2D-SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P < .001) but there was no link between spleen 2D-SWE and ALT. Liver 2D-SWE, but not spleen 2D-SWE, was associated with histopathological inflammatory score (P < .01). When compared to LB, the optimal cut-offs for detecting cirrhosis by liver and spleen 2D-SWE were 16.1 kPa (AUROC 0.93) and 29.8 kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D-SWE had significantly better AUROC for detecting cirrhosis than liver 2D-SWE alone. CONCLUSIONS: Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.
Subject(s)
Elasticity Imaging Techniques , Hepatitis, Autoimmune , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/pathology , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , SpleenABSTRACT
INTRODUCTION: Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. Material and Methods. Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP-sham-operated rats with a placebo (water); SOB-sham-operated rats with an alpha-1 adrenergic antagonist; BOOP-rats with BOO and a placebo; and BOOB-rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study. RESULTS: Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18). CONCLUSIONS: The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.
Subject(s)
Toll-Like Receptor 4/metabolism , Toll-Like Receptor 9/metabolism , Urinary Bladder Neck Obstruction/metabolism , Adrenergic alpha-Agonists/pharmacology , Animals , Body Weight , Disease Models, Animal , Inflammation , Interleukin-18/metabolism , Interleukin-6/metabolism , Male , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-1/metabolism , Tamsulosin/pharmacology , Urinary Bladder/metabolismABSTRACT
OBJECTIVES: The study was designed to evaluate the tissue expression of NRP-1 and serum level of sNRP-1 in the same patients with intraepithelial laryngeal lesions or early staged laryngeal cancer to identify the clinical significance of these biomarkers in the diagnosis of laryngeal lesions. MATERIAL AND METHODS: A prospective analysis of tissue was performed on specimens and blood samples from 49 patients, who were admitted for surgical resection due to suspicious vocal fold lesions and were diagnosed as non-dysplasia, low-grade dysplasia, high-grade dysplasia and invasive cancers. RESULTS: ELISA was conducted on 48 blood samples. The minimum level of sNRP-1 was 0.15 ng/ml and maximum- 37.71 ng/ml. The Kruskal-Wallis one-way analysis of variance revealed no differences in sNRP-1 levels between different histopathological stages of vocal fold lesions (p = 0.234). IHC was conducted in 49 tissue samples. The evaluated mean scores of NRP-1 tissue expression were compared to histopathological stage of the lesion. The Kruskal-Wallis one-way analysis of variance revealed no differences in NRP-1 tissue expression between different histopathological stages of vocal fold lesions (p = 0.536). The correlation of tissue NRP-1 expression and serum levels of NRP-1 within analyzed group was insignificant. The Spearman's rank correlation coefficient was 0.076 (p = 0.606). CONCLUSIONS: The NRP-1 tissue expression and serum levels are unlikely to be a prognostic factor for identification of laryngeal dysplasia or early stage laryngeal cancer. Further studies investigating biomolecules involved in laryngeal carcinogenesis are necessary.