RESUMO
Squamous cell carcinoma (SCC) of the esophagus and adenocarcinoma of the esophago-gastric junction (AEG) are diseases with poor prognosis. Despite radical surgery having been carried out, many patients are at risk of cancer recurrence, especially with the presence of metastases in the lymph nodes. The study involved 60 patients suffering from SCC and AEG who had lymph nodes surgically removed between 2012 and 2018. Only lymph nodes with N0 status were subjected to immunohistochemistry examination. Histopathological criteria were used for the diagnosis of micrometastases (MM), defined as tumor cells or cell clusters of 0.2-2 mm diameter in the lymph node and tumor cell microinvolvement defined as free-floating neoplastic cells or cell clusters within the sub-capsular sinus or intramedullary sinuses of the lymph node. A total of 1130 lymph nodes were removed during surgery, with an average of 22 lymph nodes per patient (range 8-58). Micrometastases were found in 7 (11.66%) patients: 6 (10.0%) with AEG and 1 (1.66%) with SCC, representing a statistically significant difference p = 0.017. Multivariate analysis of the study group did not confirm the dependence of the MM on the T features ( p = 0.7) or G ( p = 0.5). In a Cox regression analysis, MM were not a risk factor for death, HR: 2.57 (0.95; 7.00), p = 0.064. There was no difference in overall survival for patients with MM (N (+)) and those without (N0), p = 0.055, but there was a statistically significant difference in time of relapse between patients with and without MM ( p = 0.049). Patients with the N (+) status are at high risk of cancer recurrence, and therefore we believe that complementary treatment should be considered in this group.
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Prognóstico , Micrometástase de NeoplasiaRESUMO
It is unknown whether fibrosis-associated microRNAs: miR-21, miR-26, miR-29, miR-30 and miR-133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. METHODS: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end-point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR-26 and miR-29 as well as myocardial miR-133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12-month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end-point; however, myocardial miR-133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14-2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14-2.17; P < .005). The best cut-off value for the miR-133a level for the prediction of the combined end-point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.
Assuntos
Cardiomiopatia Dilatada/genética , Fibrose/genética , Ventrículos do Coração/metabolismo , MicroRNAs/genética , Biomarcadores/sangue , Biópsia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/fisiopatologia , Matriz Extracelular/genética , Feminino , Fibrose/sangue , Fibrose/fisiopatologia , Ventrículos do Coração/patologia , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
BACKGROUND: The dynamics of the extracellular matrix (ECM) fibrosis process in dilated cardiomyopathy (DCM) may be assessed non-invasively by means of serum markers of fibrosis. AIM: To explore the kinetics of serum markers of fibrosis during a 12-month follow-up in DCM. METHODS: We included 70 consecutive DCM patients (pts) (48±12.1years, EF 24.4±7.4%) with new-onset (n=35, duration <6months) and chronic DCM (n=35, >6months). Markers of collagen type I and III synthesis - procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, PIIINP), and ECM metabolism controlling factors - tumor growth factor beta-1 (TGF1-ß), and connective tissue growth factor (CTGF) - were measured in serum at baseline, and at 3- and 12-month follow-up. All pts underwent endomyocardial biopsy to determine the presence and extent of ECM fibrosis. RESULTS: Markers of collagen type I synthesis (PICP and PINP) were almost homogenously increased over the 3- and 12-month period, whereas PIIINP values decreased and PIIICP levels were unchanged in new-onset and chronic DCM, and in pts with and without ECM fibrosis. Both TGF-ß and CTGF levels decreased over the observation period. Kinetics of serum markers of collagen synthesis and fibrosis controlling factors did not differ between DCM pts categorized according to disease duration and fibrosis status. CONCLUSIONS: The kinetics of collagen type I and III synthesis in DCM move in opposite directions, with production of collagen type I consistently increasing, and the synthesis of collagen type III decreasing. Levels of TGF and CTGF, which are proven fibrosis-stimulating factors, had a tendency to decrease. Regardless of disease duration or fibrosis status, the kinetics of serum markers of collagen synthesis, TGF and CTGF were similar in DCM. A better understanding of the kinetics of serum markers of fibrosis in DCM may help to develop more tailored therapeutic approaches to fibrosis.
Assuntos
Cardiomiopatia Dilatada/sangue , Colágeno Tipo III/sangue , Colágeno Tipo I/sangue , Fator de Crescimento do Tecido Conjuntivo/sangue , Fibrose Endomiocárdica/sangue , Fibrose/sangue , Fatores de Crescimento Transformadores/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/complicações , Colágeno Tipo I/biossíntese , Colágeno Tipo III/biossíntese , Fibrose Endomiocárdica/complicações , Feminino , Fibrose/terapia , Seguimentos , Humanos , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
Left ventricular reverse remodeling (LVRR) is reported in dilated cardiomyopathy (DCM) patients (pts). However, numerous definitions of LVRR exist. Measurements of serum markers of fibrosis provide insight into myocardial fibrosis. The relationship between LVRR and fibrosis is poorly understood. From July 2014 until October 2015, we included 63 consecutive DCM pts (48 ± 12.1 years, EF 24.4 ± 7.4%) with completed baseline and 3-month follow-up echocardiograms. LVRR was assessed on the basis of four differing definitions. Procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, and PIIINP), collagen 1, ostepontin, tumor growth factor beta-1, connective tissue growth factor, and matrix metalloproteinases (MMP-2, MMP-9), and their tissue inhibitor (TIMP-1) were measured in serum. In addition, all pts underwent right ventricular endomyocardial biopsy. Depending on the definition chosen, LVRR could be diagnosed in between 14.3 and 50.8% pts. Regardless of the LVRR definition used, the frequency of LVRR was similar in fibrosis negative and positive DCM. Minor differences of markers of fibrosis were detected between pts with and without LVRR. For every LVRR definition, adjusted and unadjusted models were constructed to evaluate the predictive value of serum fibrosis parameters. Only an increase of TIMP-1 by 1 ng/ml was found to independently increase the probability of LVRR by 0.016%. The choice of a particular definition of LVRR determines the final diagnosis, and this has a profound impact on subsequent management. LVRR is unrelated to biopsy-detected ECM fibrosis. Serum markers of fibrosis are only weakly related to LVRR, and are not of use in the prediction of LVRR.
Assuntos
Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/patologia , Matriz Extracelular/patologia , Remodelação Ventricular , Adulto , Biópsia , Ecocardiografia , Feminino , Fibrose , Humanos , Modelos Logísticos , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Polônia , Inibidor Tecidual de Metaloproteinase-1/sangue , Função Ventricular EsquerdaRESUMO
BACKGROUND: Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood. OBJECTIVE: To investigate whether enhanced metabolism of ECM occur in DCM. METHODS: Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-ß), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis. RESULTS: The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p < 0.01]. The levels of PIIINP [4.41 (2.17-6.08) vs. 3.32 (1.69-5.02) ng/ml, p < 0.001], CTGF [3.82 (0.48-23.87) vs. 2.37 (0.51-25.32) ng/ml, p < 0.01], MMP-2 [6.06 (2.72-14.8) vs. 4.43 (2.27-7.4) ng/ml, p < 0.001], MMP-9 [1.98 (0.28-9.25) vs. 1.01 (0.29-3.59) ng/ml, p < 0.002)], and TIMP-1 [15.29 (1.8-36.17) vs. 2.61 (1.65-24.09) ng/ml, p < 0.004] were significantly higher in DCM, whereas levels of col-1 [57.7 (23.1-233.4) vs. 159.4 (31.2-512.9) pg/ml, p < 0.001] were significantly lower in DCM compared to controls. There were no differences in all measured serum markers of ECM metabolism between newonset and chronic DCM and as well as fibrosis positive and negative pts. Fibrosis was weakly correlated only with the duration of DCM (r = 0.23, p < 0.05), however, not a single serum marker of fibrosis correlated with fibrosis. Neither unadjusted nor adjusted models, constructed from serum markers of ECM metabolism, predicted the probability of myocardial fibrosis. CONCLUSIONS: Dynamics of ECM turnover in DCM is high, which is reflected by the increased levels CTGF and degradation enzymes. Synthesis of collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM.
Assuntos
Cardiomiopatia Dilatada/patologia , Matriz Extracelular/patologia , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/sangue , Feminino , Fibrose , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
The evaluation of ß-catenin expression in adenocarcinoma of the esophagogastric junction and its influence on cancer progression. Sixty-one patients who were diagnosed with adenocarcinoma of the esophagogastric junction were examined. We evaluated ß-catenin distribution in the cell membrane and the cell nucleus in adenocarcinoma of the esophagogastric junction type 1 and type 3. Our findings showed lack of a statistically significant difference in evaluation of adenocarcinoma type 1 and type 3 aggressiveness. However, we found a statistically significant association with the T and N stage, although we did not find an effect of them on patient survival. Patients with cellular membrane and cell nucleus staining comprise a group of patients with higher risk of malignancy progression in adenocarcinoma of the esophagogastric junction types 1 and 3.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/patologia , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Primary melanoma of the esophagus (PME) represents a rare type of gastrointestinal malignancy with an exceptionally poor diagnosis. So far, only few descriptions of PME which satisfactorily summarize their clinical characteristics and prognosis have been published. OBJECTIVES: The aim of our study was to summarize our experience with PME patients. MATERIAL AND METHODS: In a group of 1387 patients who underwent esophagectomy due to neoplastic process in the years 2000-2020 in 2 high-volume university thoracic surgery centers, we identified those with confirmed PME diagnosis. Subsequently, their clinical characteristics, imaging and histopathological results were compared. The data regarding the long-term survival were obtained from the Polish National Death Registry. RESULTS: The PME was identified in 4 (0.29%) patients. Three of them (75%) were males. The mean age on admission was 64.3 ±17.5 years. The main symptom in all patients was dysphagia. In 1 patient with the most advanced PME, the clinically relevant weight loss was noted. In 3 patients, Ivor Lewis esophagectomy was performed, and 1 patient underwent McKeown resection. Histopathologic examination revealed a metastasis of lymph nodes only in 1 patient. The average maximum size of tumor was 6.9 ±4.7 cm and all tumors were located in distal part of the esophagus. Two out of those 4 patients are still alive and the longest survival time is 17 years. One patient died due to postoperative massive gastrointestinal bleeding complicated with cardiac arrest and the other one due to progression of PME systemic dissemination 6 months after surgical treatment. CONCLUSION: The PME is an extremely rare diagnosis. A long-term survival can be achieved with the complete resection. Clinical scenarios of surgically treated PME patients may significantly differ.
Assuntos
Neoplasias Esofágicas , Melanoma , Cirurgia Torácica , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , UniversidadesRESUMO
UNLABELLED: Coeliac disease (gluten enteropathy) is a chronic inflammatory disease of the gastrointestinal (GI) tract of autoimmune etiology in genetically predisposed individuals. It is the most frequent enteropathy with frequency of 1/100 and 1/300 in the adult population in America and Europe respectively. Typical form of celiac disease including abdominal pain, weight loss, nausea is quite rare in adults. In some coeliac patients, symptoms persist in spite of strict gluten free diet. One of the reasons of this is interference of the autoimmune diseases. Results of our studies revealed in the group of 110 patients with diagnosed gluten enteropathy, coexistence of autoimmune disease, such as diabetes mellitus type 1 in 7.2% cases, hyperthyreosis on 1.8% of cases, vitiligo in 0.9% of cases, primary biliary cirrhosis in 2% of cases and rheumatoidal arthritis in 0,9 of cases. In the group of 80 ulcerative colitis patients, coexistence of celiac disease basing on serological histopatological investigation was found in 4 patients (5%). CONCLUSIONS: Coexistence of coeliac disease with other autoimmune diseases is quite frequent. Gluten enteropathy symptoms may be interpreted as originating from other autoimmune disease. It can delay the diagnosis of celiac disease and introduction of gluten free diet, which improves the quality of life and protects from dangerous GI complications.
Assuntos
Doenças Autoimunes/epidemiologia , Doença Celíaca/epidemiologia , Adolescente , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Colite Ulcerativa/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Hipertireoidismo/epidemiologia , Cirrose Hepática Biliar/epidemiologia , Masculino , Pessoa de Meia-Idade , Vitiligo/epidemiologia , Adulto JovemRESUMO
Celiac disease is increasingly recognized autoimmune enteropathy caused by a permanent gluten intolerance. Gluten is the main storage protein of wheat, in genetically predisposed individuals. Celiac disease risk in first degree relatives is about 10%. Diarrhea and changes of bowel movement, observed as well in celiac disease as in IBS, may lead to misdiagnosis of IBS basing on the Rome criteria or may be associated with coexistence of both diseases. The aim of the study was to assess the celiac disease prevalence in patients with irritable bowel syndrome. The study group comprised 200 patients (120 women and 80 men) aged 18-78 years (mean: 46.7 years) with diarrhoeal form of irritable bowel syndrome (IBS), according to the Rome criteria II. At the beginning and after a three month period anti tissue transglutaminase antibodies (IgA tTG) were estimated. Gastroscopy with biopsy where performed in those with IgA tTG titre above 1/200. 40 patients were immunologically positive and 14 of them have histopathologically proven celiac disease. In the group of patients with detected celiac disease, gluten free diet was applied besides the treatment with trimebutin or mebewerin, recommended for IBS. After 6 months the decrease of IgA tTG titre in the serum was observed. In 5 of these patients IgA tTG level was negative. It was associated with the significant decrease of clinical symptoms, such as diarrhea and flatulence. The remaining symptoms, such as abdominal pain, feeling of incomplete defecation demanded continuation of IBS treatment. With regard to often atypical celiac disease symptoms--adult active searching should be performed to differentiate from irritable bowel syndrome.
Assuntos
Doença Celíaca/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Adulto , Idoso , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Comorbidade , Progressão da Doença , Feminino , Gastroscopia , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/patologia , Síndrome do Intestino Irritável/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
BACKGROUND: Angiogenesis is a basic process that enables neoplasms to thrive. Microvessel density (MVD) evaluation is an accepted parameter for assessing the angiogenesis process within a tumor. The aim of the present study has been to assess the number of microcapillaries in both invasive ductal breast cancer with the presence of metastases in regional lymph nodes and in invasive ductal breast cancer without such metastases. METHODS: The CD34 antigen immunoreactivity level was assessed by immunohistochemistry in both types of invasive ductal breast cancer. Tissue samples were obtained from 40 patients and were divided into two groups according to whether or not there were lymph node metastases. RESULTS: The patients with lymph node metastases exhibited statistically significantly higher numbers of stained microcapillaries than the patients who did not have lymph node metastases. CONCLUSION: Thus the number of stained microcapillaries as evaluated by using the CD34 immunoreactivity level seems to be a useful predictor for the development of local lymph node metastases in female invasive ductal breast cancer.
Assuntos
Antígenos CD34/análise , Neoplasias da Mama , Carcinoma Ductal de Mama , Linfonodos/patologia , Metástase Linfática/patologia , Neovascularização Patológica , Adulto , Idoso , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/irrigação sanguínea , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/metabolismo , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
INTRODUCTION: Serum markers of fibrosis provide an insight into extracellular matrix (ECM) fibrosis in heart failure (HF) and dilated cardiomyopathy (DCM). However, their role as predictors of cardiovascular (CV) events in DCM is poorly understood. METHODS: This is an observational, prospective cohort study. 70 DCM patients (48±12.1years, ejection fraction - EF 24.4±7.4) were recruited. Markers of collagen type I and III synthesis - procollagen type I and III carboxy- and amino-terminal peptides (PICP, PIIICP, PINP, PIIINP), fibrosis controlling factors - ostepontin (OPN), transforming growth factor (TGF1-ß) and connective tissue growth factor (CTGF), and matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor (TIMP-1), were measured in serum. All patients underwent endomyocardial biopsy. The end-point was combined with CV death and urgent HF hospitalization. Patients were divided into two groups: those who did (group 1, n=45) and did not reach (group 2, n=25) an end-point. RESULTS: Over a 12-month period of observation, 6 CV deaths and 19 HF hospitalizations occurred. Qualitative and quantitative measures of ECM fibrosis were similar in both groups. The levels of all of the markers of collagen synthesis, TGF1-ß, MMP-9 and TIMP-1 were similar, however, OPN, CTGF and MMP-2 were significantly lower in group 1. CONCLUSIONS: Invasively-determined fibrosis levels were not related with CV outcomes in DCM. Out of the 11 markers of fibrosis under study, only OPN was found to be related to CV outcomes. OPN is not only the pivotal protein controlling fibrosis, but may also serve as a biomarker associated with prognosis.
Assuntos
Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Osteopontina/sangue , Intervalo Livre de Doença , Determinação de Ponto Final , Matriz Extracelular/metabolismo , Feminino , Fibrose , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Resultado do TratamentoRESUMO
BACKGROUND: The relationship between right ventricle (RV), extracellular matrix (ECM) fibrosis and fibrosis-linked, circulating microRNAs in dilated cardiomyopathy (DCM) is unknown. AIM: The aim of the study was to uncover the associations between serum markers of ECM metabolism and circulating microRNAs with RV morphological and functional parameters. METHODS: The study population consisted of 70 consecutive DCM patients (ejection fraction 24.4 ± ± 7.4%). Based on detailed echocardiographic assessment - 15 patients had normal RV, whereas 55 patients had RV dilatation (RVD) and/or RV systolic dysfunction (RVSD). Procollagens type I and III carboxy- and amino-terminal peptides, osteopontin (OPN), TGF1-b1, connective tissue growth factor (CTGF), MMP-2, MMP-9 and TIMP-1 were measured in serum as well as expression of miR-21, miR-26, miR-29, miR-30 and miR-133a. All patients underwent endomyocardial biopsy. RESULTS: Biopsy-proven fibrosis was evenly distributed in two groups. Serum levels of fibrosis markers did not differ between groups. OPN, CTGF, MMP-2, and TIMP-1 correlated with RV parameters. Only miR-133 a was differently expressed in both groups. MiR-21, miR-26, miR-30, and miR-133a cor-related with RV morphological but without functional parameters. Not a single marker of fibrosis was independently associated with RV. MiR-30 was associated with RV impairment in the logistic regression model adjusted for age, sex, body mass index, and disease duration; however, lost its significance in the more comprehensive model. CONCLUSIONS: Right ventricle structural and functional abnormalities are common in DCM. ECM fibrosis and serum markers are not associated with RV impairment. The prognostic value of studied microRNAs on RV is limited in DCM.
Assuntos
Cardiomiopatia Dilatada/fisiopatologia , MicroRNA Circulante/genética , Regulação da Expressão Gênica , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Função Ventricular Direita/fisiologia , Biópsia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , MicroRNA Circulante/biossíntese , Ecocardiografia Doppler de Pulso , Feminino , Fibrose/patologia , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , SístoleRESUMO
One of the prognostic and predictive factors in invasive breast carcinomas is determination of the HER2/neu proto-oncogene amplification or HER2 protein overexpression. HER2 amplification/overexpression is associated with a more aggressive disease course, greater likelihood of recurrence and generally poor prognosis. The authors compared the specificity, simplicity of a given procedure and method standardization, the simplicity of evaluation the results of each in situ hybridization method and time needed for performing the test. Sixty-three cases of infiltrating breast carcinoma from surgically excised tumors and core needle biopsies were included in the study. The first step was the determination of HER2 status by immunohistochemistry. The patients with moderate (2+) and strong (3+) overexpression of HER2 protein were chosen for determining HER2 amplification by three methods of in situ hybridization: FISH, CISH and in situ hybridization with silver autometallography. The statistical analysis revealed a good agreement between IHC and ISH methods and among ISH methods. The results indicate that all in situ hybridization methods are equivalent tools for evaluating HER2 gene amplification in archival material. There is no clear answer which method is the best assay to determine HER2 marker status, although the authors present some advantages and disadvantages of all the described techniques and a proposed algorithm for choosing a method for a given laboratory.
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Neoplasias da Mama/genética , Hibridização In Situ/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Amplificação de Genes , Genes erbB-2 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proto-Oncogene Mas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
In the present study on animal model of ulcerative colitis the influence of fungal colonization on the severity of inflammatory lesions in the colon and the course of their healing was evaluated. The results of our studies revealed, that significant fungal colonization (over 10(4) CFU/ml) delayed ulcer healing in the colon. It corresponded with the decrease of colonic blood flow (CBF) in the region of lesions and increase of interleukin (IL)-1beta, tumor necrosis factor(TNF)-alpha level in the serum. Introduction of antifungal therapy (fluconazole) or probiotic in rats inoculated with Candida accelerated the process of ulcer healing in the colon, expressed through the reduction of macro- and microscopic lesions in the colon and decrease of MPO, IL-beta TNF-alpha serum level.
Assuntos
Candida/isolamento & purificação , Candidíase/diagnóstico , Candidíase/microbiologia , Colite Ulcerativa/microbiologia , Animais , Antifúngicos/uso terapêutico , Candidíase/sangue , Candidíase/tratamento farmacológico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Colo/irrigação sanguínea , Colo/microbiologia , Modelos Animais de Doenças , Fluconazol/uso terapêutico , Interleucina-1beta/sangue , Masculino , Probióticos/uso terapêutico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
Present-day methods of successful treatment of inflammatory bowel diseases (IBD) result from a better understanding of their pathophysiology due to advances in preclinical studies in this area of knowledge. Until recently microbiological studies have been focused on the bacterial aspects in pathogenesis of GI disorders, however in the last years an interest in the presence of fungi in the gastrointestinal tract has also increased. In this study using an animal model of ulcerative colitis, the impact of fungal colonization of the colon on the intensity of inflammatory changes in the colonic mucosa and the course of their healing was carried out. The macroscopic and microscopic criteria relating to the changes of weight of examined fragments of the colon were evaluated while assessing differences between groups tested. The intensity of intestinal inflammatory changes was determined by assessment of such parameters, as colonic blood flow (CBF), the level of MPO as a marker of colonic neutrophil infiltration intensity and the plasma levels of IL-1beta; and TNF-alpha concentrations. Results at the 3rd day after TNBS rectal administration revealed an increase of weight of isolated segments of inflammed colon, a decrease of CBF and the 4-5 fold increase of plasma MPO activity. Candida colonization of colon mucosa of rats delayed healing of colonic ulcers, induced by TNBS and this was associated with the increased expression of plasma IL-1beta and TNF-alpha levels. Administration of antifungal (fluconazole) or probiotic (Lacidofil) treatment to C. albicans infected rats exerted favorable effect on healing of inflammatory changes in the colon because the area of ulcerations in groups of rats treated with fluconazole or Lacidofil was significantly smaller in comparison with those inoculated with Candida solution only. Administration of fluconazole or Lacidofil significantly decreased the weight of colon segments, the MPO activity and the plasma IL-1beta and TNF-alpha levels, as compared with respective values in the group receiving Candida only. The results of our studies indicate the deteriorating influence of Candida on the healing process of inflamed colon in the animal model of ulcerative colitis. Concomitant therapy with probiotic or antifungal treatment improved healing of colonic lesions, decreased the weight of inflamed colonic tissue and also attenuated the MPO activity and plasma proinflammatory cytokines IL-1beta and TNF-alpha levels.
Assuntos
Candidíase/complicações , Candidíase/fisiopatologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Cicatrização/efeitos dos fármacos , Administração Retal , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Fluconazol/uso terapêutico , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-1beta/sangue , Masculino , Probióticos/uso terapêutico , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/sangueRESUMO
INTRODUCTION There are no widely accepted standards for the diagnosis of sarcoidosis. OBJECTIVES The aim of this study was to assess the relative diagnostic yield of endobronchial ultrasound fine-needle aspiration (EBUS -FNA) and endoscopic ultrasound fine needle aspiration (EUS -FNA), and to compare them with standard diagnostic techniques such as endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA), and mediastinoscopy. PATIENTS AND METHODS This was a prospective randomized study including consecutive patients with clinical diagnosis of stage I or II sarcoidosis. EBB, TBLB, and TBNA were performed at baseline in all patients. Subsequently, patients were randomized to group A (EBUS -FNA) or group B (EUS -FNA). Next, a crossover control test was performed: all patients with negative results in group A underwent EUS -FNA and all patients with negative results in group B underwent EBUS -FNA. If sarcoidosis was not confirmed, mediastinoscopy was performed. RESULTS We enrolled 106 patients, of whom 100 were available for the final analysis. The overall sensitivity and accuracy of standard endoscopic methods were 64% each. When analyzing each of the standard endoscopic methods separately, the diagnosis was confirmed with EBB in 12 patients (12%), with TBLB in 42 patients (42%), and with TBNA in 44 patients (44%). The sensitivity and accuracy of each endosonographic technique were significantly higher than those of EBB+TBLB+TBNA (P = 0.0112 vs P = 0.0134). CONCLUSIONS The sensitivity and accuracy of EBUS -FNA and EUS -FNA are significantly higher than those of standard endoscopic methods. Moreover, the sensitivity and accuracy of EUS -FNA tend to be higher than those of EBUS -FNA.
Assuntos
Biópsia por Agulha Fina/métodos , Sarcoidose/diagnóstico , Adulto , Idoso , Confiabilidade dos Dados , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Sensibilidade e Especificidade , Adulto JovemRESUMO
Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread.
Assuntos
Apoptose/imunologia , Decídua/imunologia , Tolerância Imunológica/imunologia , Pólipos Nasais/imunologia , Neoplasias/imunologia , Placenta/imunologia , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Decídua/metabolismo , Endometriose/imunologia , Endometriose/metabolismo , Feminino , Humanos , Imunidade Celular/fisiologia , Metástase Linfática/imunologia , Ciclo Menstrual/imunologia , Ciclo Menstrual/metabolismo , Metalotioneína/imunologia , Metalotioneína/metabolismo , Pólipos Nasais/metabolismo , Neoplasias/metabolismo , Placenta/metabolismoRESUMO
INTRODUCTION: The generation of proper immune response in the tumor environment seems to be essential in antitumor defense. RCAS1 expression has been shown to participate in the regulation of immune cytotoxic activity, metallothionein participates in the protection of cells against immune mediated apoptosis. Since MT and RCAS1 expression is observed within healthy tumor environment we aimed to focus on the proteins expression in tumor and its healthy adjacent tissue in invasive ductal breast cancer regarding the immune cells presence and activity. MATERIAL AND METHODS: RCAS1, metallothionein, CD3, CD56, CD4, CD25, CD69, CD68 and CD16 antigens expression was assessed by immunohistochemistry in invasive ductal breast cancer. Tissue samples were obtained from 45 patients and were grouped according to the presence of lymph nodes metastases. Two groups were obtained: with and without lymph nodes metastases. RESULTS: Significant differences were observed in RCAS1 and metallothionein expression in tumor and significant differences in metallothionein expression in healthy stroma regarding the presence of lymph nodes metastases. The significantly higher RCAS1 expression was noticed in tumor in comparison to stroma in patients with the presence of lymph nodes metastases. No such difference was observed in patients without the metastases. Significantly higher metallothionein expression was identified in tumor than in stroma in both groups of patients, with and without lymph nodes metastases. These changes in RCAS1 and metallothionein expression were significantly related with the changes in the number and activity of immune cells. CONCLUSION: RCAS1 and metallothionein expression in breast cancer healthy stroma seems to be essential for the coexistence of cytotoxic immune cells and normal epithelial cells. The loss of the ability to compensate the growing cytotoxic immune response in the environment might participate in the development of tumor spread.
Assuntos
Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Carcinoma Ductal de Mama/imunologia , Metalotioneína/metabolismo , Análise de Variância , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Apoptose/imunologia , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Tolerância Imunológica/imunologia , Imunidade Celular/fisiologia , Metástase Linfática/imunologia , Glândulas Mamárias Humanas/imunologia , Glândulas Mamárias Humanas/metabolismo , Metalotioneína/imunologia , Estatísticas não ParamétricasRESUMO
UNLABELLED: The influence of microbiological factor is taken into consideration in the pathogenesis of ulcerative colitis (UC). The aim of studies was to: 1.evaluate the presence of significant fungal colonization, over 10(5) CFU/ml in patients with UC and the control group (irritable colon syndrome, IBS); 2. estimate the influence of antifungal treatment in the activity of UC. MATERIAL AND METHODS: We evaluated 72 patients aged from 18-72 years, 60 patients with UC, 12 with IBS. Clinical investigation: initially and after 4 weeks interview and colonoscopy with colon biopsies for histology and mycology were taken. Activity of UC was evaluated according to: clinical, endoscopic and histological IACH criteria. 13 patients with significant fungal colonization were given antifungal treatment. Biopsies for histology were stained with hematoxylin-epsin (H-E). Qualitative and quantitative mycolo-gical evaluation was performed according to Muller method. RESULTS: 1. Significant fungal colonization was more frequent in patients with UC history over 5 years, in comparison with shorter disease history and IBS, in 33.3%, 13.8% and 1.3% respectively. 2. Candida albicans was most often isolated in 91.7% of cases. 3. Initial analysis of the activity index of UC in patients with significant and non-significant fungal colonization did not revealed differences between these groups, 13.84 and 14.0 respectively. 3. After 4 weeks stronger decrease of the UC activity index was observed in patients with significant fungal colonization treated with antifungal treatment, in comparison with patients not given antifungal therapy: 8.0 and 10.41 respectively, p<0.01. Differences were significant according to clinical 2.23 (C) -3.33 (D), p<0.05 and endoscopic cryteria: 3.46 (C) -4.84 (D), p<0.01. CONCLUSIONS: 1. Significant fungal colonization of colon may influence the activation of UC. 2. Longer disease history may be the risk factor of significant fungal colonization in colon. 3. Antifungal treatment in patients with significant colonization caused clinical improvement of UC.