Valente M.,University of Padua |
Valente M.,Institute of Pathological Anatomy |
Furian L.,University of Padua |
Della Barbera M.,University of Padua |
And 6 more authors.
Transplantation Proceedings | Year: 2012
In renal transplant patients, glomerulitis may be present in all types of acute rejection, often accompanied by diffuse C4d staining of peritubular capillaries: C4d3 positivity in more than 50% of peritubular capillaries. It may progress to chronic transplant glomerulopathy, characterized by capillary basement membrane multilayering, proteinuria, and progressive loss of renal function. While C4d3 is a recognized marker of an antibody-mediated reaction, the significance of glomerular C4d (GlC4d) staining is unknown. The aim of this study was to evaluate GlC4d immunoreactivity and its correlation with C4d3 in acute rejection biopsies. Paraffin-embedded acute rejection biopsies from 90 renal transplant patients were evaluated according to the Banff classification. Biopsies showing C4d-positive endothelial cells in more than 50% of glomeruli were considered GlC4d-positive. C4d3-positive staining prevalence was 23%. GlC4d-positive staining showed an 89% concordance rate (r = 0.81, P <.0001; Cohen's k = 0.80, P <.0001). GlC4d detection sensitivity was 0.80 and specificity 0.97. C4d3 and GlC4d immunoreactivity was significantly associated with glomerulitis (P <.006 and P <.03, respectively) and with proteinuria at the time of biopsy (P <.03 and P <.01, respectively). Interestingly, GlC4d positivity correlated better than C4d3 positivity with the presence of posttransplant circulating anti-human leukocyte antigen alloantibodies (P <.04 and P =.7, respectively). Patients with C4d3- or GlC4d-positive acute rejections underwent graft loss due to interstitial fibrosis and tubular atrophy more frequently than those with C4d0- or GlC4d-negative rejections (P <.0001 and P <.005, respectively), whereas no differences were observed in graft loss due to death. In conclusion, C4d3 and GlC4d stains showed a high correlation rate. Compared with C4d3, GlC4d staining demonstrated good sensitivity and excellent specificity. Our results suggested that GlC4d staining may indicate glomerular endothelial damage and be of prognostic value. © 2012 Elsevier Inc. All rights reserved.
PubMed | St Annes University Hospital Of Brno, Institute of Pathological Anatomy, Charles University, Masaryk University and University of Tokyo
Type: Journal Article | Journal: Artificial organs | Year: 2016
Histopathological analysis can provide important information in long-term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF-TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF-TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF-TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 m thick transverse sections were stained with hematoxylin-eosin (HE). Additional staining was done for detection of connective tissue (Masson-Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100 and 500 magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro-particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro-particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments.
Bartos V.,Faculty Hospital |
Pokorny D.,Faculty Hospital |
Zacharova O.,Faculty Hospital |
Haluska P.,Faculty Hospital |
And 5 more authors.
Acta Dermatovenerologica Alpina, Pannonica et Adriatica | Year: 2011
Background. Basal cell carcinoma (BCC) of the skin is now the most common malignancy in the human population. One of the most negative features of this disease is frequent tumor recurrence. Unfortunately, all of the traditional diagnostic criteria have failed to definitively predict which patients should be considered at high risk of recurrence. Objective. The aim of this study was to evaluate the prevalence, topographical localization, and histomorphological features of recurrent BCCs. Methods. Biopsy samples and clinical data from 30 consecutive patients (15 women and 15 men) with 31 recurrent BCCs diagnosed from January 2007 to September 2010 were analyzed retrospectively. The mean age of the individuals at the time of diagnosis of recurrence was 68.2 years (range 32 to 97 years). Histological types and other pathological findings of original and relapsing BCCs, as well as the time between them, were able to be compared in 24 cases. Results. Recurrent carcinomas represented 4.9% of all diagnosed cases during the observed period. Recurrence time varied from 4 to 105 months with a mean time of 31.2 months. The majority of recurrences occurred within 3 years after the primary treatment. The topographic localization of tumors was as follows: auricles (n = 5), cheeks (n = 4), medial canthus (n = 4), periauricular regions (n = 3), temporal areas (n = 3), paranasal regions (n = 3), nose (n = 3), forehead (n = 1), lower eyelid (n = 1), mandible (n = 1), chin (n = 1), neck (n = 1), and back (n = 1). Histologically, 50% of primary and 54.8% of recurrent BCCs demonstrated at least partial aggressive-growth features. Comparing primary and corresponding relapsing BCCs, 50% of them showed an identical type, in 16.7% the recurrent tumor had developed a more aggressive histological picture, and in 20.8% the histomorphology had became more benign. Of all primary tumors previously removed by total extirpation, 54.5% were resected completely and 45.5% incompletely. Conclusions. BCC recurrences may vary considerably with respect to various tumor- and host-related factors, and so it is impossible to predict them precisely. Although aggressive histological types and positive excision margins are considered the strongest predictors, we demonstrated that half of the primary cancers had shown an indolent character, and that more than half of them had appeared to be completely resected. We can conclude that all patients that have had BCCs removed should be re-examined regularly even after microscopically adequate excisions, or lesions with an indolent histomorphology. Careful monitoring must be undertaken for at least 3 years; however, the most appropriate course is a lifetime of regular follow-up.
Grimaldi F.,Endocrinology and Metabolism Unit |
Muser D.,Cardiothoracic Surgery |
Beltrami C.A.,Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine |
Machin P.,Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine |
And 8 more authors.
Frontiers in Endocrinology | Year: 2010
Introduction: Histological distinction between typical and atypical bronchopulmonary car- cinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Materials and Methods: The long-term post-surgical out- come of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conven- tional histology with a panel of immunohistochemical markers of neuroendocrine differen- tiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). Results: Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0-20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67 score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivari- ate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly dif- ferent disease-free survival was found (log-rank test P < 0.0001). Conclusion: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up. © 2011 Grimaldi, Muser, Beltrami, Machin, Morelli, Pizzolitto, Talmassons, Marciello, Colao, Monaco, Monaco and Faggiano.
Quartuccio L.,Rheumatology Clinic |
Maset M.,Rheumatology Clinic |
De maglio G.,Azienda Ospedaliero Universitaria S. Maria della Misericordia |
Pontarini E.,Rheumatology Clinic |
And 6 more authors.
Rheumatology (United Kingdom) | Year: 2012
Objective. Glucocorticoid (GC)-related adverse events greatly contribute to the outcome in giant cell arteritis (GCA). CYC was investigated as a steroid-sparing agent in GCA.Methods. Nineteen patients treated with CYC were retrospectively analysed. CYC was administered in 15 of the 19 patients after failure of high doses of GC or relapse during medium to high doses of GC, with or without MTX, while CYC was used ab initio in 4 of the 19 patients, all with type 2 diabetes. Follow-up ranged from 1 month to nearly 9 years after the end of CYC treatment.Results. The efficacy of CYC was observed in 15 of the 19 patients, and remission was still present 6-12 months after CYC suspension in 12 of the 13 patients. GCs were suspended in 6 of the 15 patients, and they were continued at a dose ≤ 5 mg/day of prednisone in all the remaining responders. Relapse occurred in 4 of the 15 patients, usually >12 months after CYC suspension. Suspension of GC daily dose or reduction to ≤ 5 mg/day of prednisone occurred within the first 6 months of follow-up after the beginning of CYC in 10 of the 15 patients. Ten adverse events were registered in nine patients, with recovery usually soon after the suspension of CYC or dose reduction. However, one death occurred due to acute hepatitis. Disappearance of the inflammatory infiltrate could be demonstrated when temporal artery biopsy was repeated 3 months after CYC in one patient.Conclusion. CYC may represent a useful option for patients requiring prolonged medium- to high-dose GC therapy and at high risk of GC-related side effects. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Rocha C.M.,University of Aveiro |
Carrola J.,University of Aveiro |
Barros A.S.,University of Aveiro |
Gil A.M.,University of Aveiro |
And 12 more authors.
Journal of Proteome Research | Year: 2011
In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management. © 2011 American Chemical Society.
PubMed | Polithecnic University of the Marche Region Ospedali Riuniti, Medical Oncology, Marche Polytechnic University, Clinica di Oncologia Medica and Institute of Pathological Anatomy
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017
388 Background: For the last few years, sunitinib has been considered the standard treatment for first-line metastatic renal cell carcinoma, but in 2010 a new drug pazopanib had been approved for treatment in this setting. Recent data from the COMPARZ and PISCES study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS and a patients preference for pazopanib if we consider quality of life parameters. The aim of our study is to investigate whether polymorphisms of VEGF and VEGFR can influence PFS and OS when patients are treated either with sunitinib or pazopanib as first-line treatment.97 histologic samples of mRCC patients were tested for VEGF-A, VEGF-C, and VEGFR-1, 2, 3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first-line treatment.In patients treated with sunitinib VEGF-A rs833061 resulted significant in PFS (CC+CT vs TT, p < 0.0001) and OS (p < 0.0001). VEGF-A rs699947 was significant for PFS (AA+AC vs. CC) p = 0.0001) and OS (p < 0.0001). VEGF-A rs2010963 was significant in PFS (CC vs. CG vs. GG, p = 0.0001) and in OS (p = 0.0045). VEGR3 rs6877011 was significant in PFS (CC vs. CG, p = 0.0075) and OS (p = 0.0001). At multivariate analysis rs833061, rs2010963, and rs68877011 were significant in PFS. rs833061 and rs68877011 were independent factors in OS. In the pazopanib treated groups of patients VEGF-A rs833061 resulted significant in PFS (TT+CT vs. CC p = 0.027) Conclusions: In our analysis patients with CC or CT polymorphism of rc833061 had a favourable PFS and OS if treated with sunitinib instead patients treated with pazopanib seems to have benefit if CT+TT polymorphism, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line with sunitinib. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first-line therapy with sunitinib. Our data seem to suggest that biology could have a role in the choice of first-line treatment for mRCC patients. Further data will be presented at the Symposium.
Bauerova K.,Slovak Academy of Sciences |
Drafi F.,Slovak Academy of Sciences |
Kuncirova V.,Slovak Academy of Sciences |
Ponist S.,Slovak Academy of Sciences |
And 3 more authors.
Physiological Research | Year: 2015
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact. © 2015 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic.