RESUMO
BACKGROUND/AIM: Orthotopic Liver Transplantation (OLT) is the treatment of choice for patients with end stage liver disease, acute liver failure, hepatocellular carcinoma and metabolic disorders. As a result of improvement in surgical and anesthesiological skills, advanced understanding of transplant immunology and better critical care management of complications, patients survive longer after liver transplantation. It has been gradually achieved one-year survival rates of 80-90%. During the early post-operative period, all patients undergoing OLT are admitted to the intensive care unit, as they need a management of both preexisting patient's conditions and post-operative complications, usually due to either adverse intra-operative or post-operative events. The purpose of this review is the detailed recording, understanding and interpretation of immediate post-operative complications occurred in patients undergoing OLT, in intensive care unit. This could help to improve patient's treatment and reduce the incidence of complications, with further reduction of morbidity-mortality and cost. We also present our experience from the first 32 OLT patients from Liver Transplantation Unit of Laiko General Hospital, the only Liver Transplantation Unit in Athens. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database. The key words were; Orthotopic liver transplantation; intensive care unit; post-operative complications; outcomes. One hundred-sixteen articles published in English until 2018 were used. We also use all the results from our 32 patients from our Liver Transplantation Unit during the period 07/2006 to 07/2009. RESULTS: All patients undergoing OLT admitted to the intensive care unit for a period of time, depending on the occurrence of post-operative complications. The incidence of primary failure ranges between 2-14%, whereas post-operative bleeding ranges between 7-15%. The treatment is usually conservative, although surgical repair may need in 10-15%. Acute renal failure post-operative is not an infrequent problem too, and has been reported to occur in 9% to 78% of cases. Acute rejection normally occurs 7-14 days after OLT. Additionally, the delay of the weaning from mechanical ventilation in the immediate post-operative period could increase the complications. Infectious complications are quite common almost from the first post-operative day in intensive care unit. CONCLUSIONS: Prolonged intensive care stay could increase the complications post-operative Infectious complications, renal and respiratory impairment are among the most common causes of early post-transplant morbidity and mortality.
Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Transplante de Fígado , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Doenças Biliares/epidemiologia , Doenças Biliares/etiologia , Feminino , Rejeição de Enxerto , Artéria Hepática , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Infecções , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Tamanho do Órgão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Respiração Artificial , Trombose/epidemiologia , Trombose/etiologia , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
OBJECTIVE: Diabetic retinopathy is the leading cause of irreversible blindness in the western world, among the working-age people. Its exact pathogenesis, however, remains obscure. Systemic inflammation is regarded to play a significant role in diabetes by contributing, among others, to the development of diabetic retinopathy. This review focuses on the possible involvement of the systemic inflammatory markers in the pathogenesis of diabetic retinopathy. PATIENTS AND METHODS: We performed a systematic search of the literature of published papers until August 2017 using the PubMed search engine. RESULTS: We demonstrated that many systemic inflammatory markers contribute to the pathogenesis and progression of retinopathy, while we highlighted in several occasions their usefulness as a key tool in the monitoring of the disease progression and the treatment efficacy. CONCLUSIONS: To the best of our knowledge this is the first review in the literature that elaborates the possible association of serum inflammatory markers and diabetic retinopathy, a disease that may cause irreversible loss of vision.
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Biomarcadores/metabolismo , Cegueira/etiologia , Retinopatia Diabética/patologia , Progressão da Doença , Humanos , Inflamação/complicaçõesRESUMO
OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.
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Antineoplásicos/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Inibidores de Histona Desacetilases/metabolismo , Histona Desacetilases/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/genética , Humanos , Ácidos Hidroxâmicos/metabolismo , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Hidroxilaminas/metabolismo , Hidroxilaminas/farmacologia , Hidroxilaminas/uso terapêutico , Quinolinas/metabolismo , Quinolinas/farmacologia , Quinolinas/uso terapêuticoRESUMO
BACKGROUND: Serum creatinine (S-Cr) is the most commonly used marker for the assessment of renal function in kidney transplantation (KTx). Cystatin-C (Cys-C) has been proposed as an alternative marker of renal function for the estimated glomerular filtration rate (eGFR), which seems to be more accurate than S-Cr. The aim of this study was to investigate the relationship between changes in S-Cr, Cys-C, and eGFR measurements in KT patients during the early post-transplantation (post-Tx) period. METHODS: Fifty consecutive patients, aged 15 to 70 years, were subjected to KT. Blood samples were collected at stable time-points on pre-Tx and post-Tx days 2, 6, and 14 and in the third month. Cys-C and S-Cr levels were measured, and GFR was estimated at all time-points using the Cockcroft-Gault and Le Bricon equations. RESULTS: S-Cr and Cys-C levels decreased significantly post-Tx in all time-point determinations compared with pre-Tx levels. Both markers showed a parallel decrease, reaching normal levels in the third month. Estimated GFR post-Tx by S-Cr and Cys-C exhibited a parallel progressive increase without significant difference between the calculations. Correlation between S-Cr and Cys-C in all time-point determinations was positive and of high significance using Pearson's correlation (r = 0.969, P < .01; r = 0.951, P < .01; r = 0.969, P < .01; r = 0.701, P < .01). Also, the correlation between the eGFR by Cys-C and S-Cr was positive and of high significance in all post-Tx calculations (r = 0.896, P < .01; r = 0.935, P < .01; r = 0.929, P < .01; r = 0.861, P < .01). Ten recipients had acute rejection and were treated successfully with antirejection therapy. Their S-Cr, cys-C, and eGFR results were analyzed separately and showed a significant difference from no-rejection patients, with Cys-C being more sensitive to earlier eGFR changes. CONCLUSION: Cystatin-C is an alternative and accurate marker of renal function in KT patients showing similar diagnostic characteristics to S-Cr. However, Cys-C appears superior to S-Cr in reflecting early GFR temporary changes, which is critical for the early detection of acute rejection.
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Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Transplante de Rim , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/fisiopatologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: The loss or damage of an organ or tissue is one of the most common and devastating problems in healthcare today. Tissue engineering applies the principles of engineering and biology toward the development of functional biological replacements that are able to maintain, improve, or restore the function of pathological tissues. The aim of the overall project is to study an already existing method for the decellularization of homograft vascular grafts for use in vascular surgery. MATERIALS AND METHODS: The biomechanical integrity of native and decellularized rat aortas was assessed under uniaxial tension tests. For this purpose, 36 male rats (12 Wistar and 24 Dark Agouti [DA]) were used to excise their abdominal aortas. Twelve of the aortas were tested fresh (Wistar and DA rats), within 24 hours from euthanasia, and the rest were decellularized using a modified protocol (DA rats only). Fresh and decellularized samples (n = 12) were subjected to uniaxial tensile loading to failure, and the recorded stress-strain behaviour of each specimen was assessed in terms of 6 biomechanical parameters. RESULTS: No statistically significant differences were found in any of the biomechanical parameters studied between the decellularized DA rat aorta group and both the native DA and Wistar rat aorta groups (P > .05). Also, no significant difference was shown between the native DA and native Wistar rat aorta groups. CONCLUSIONS: The results from this study have shown that the decellularization protocol did not affect the mechanical properties of the native rat aorta. In addition to this, both native Wistar and native/decellularized DA rat aorta groups shared similar mechanical properties.
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Aorta Abdominal/fisiologia , Fenômenos Biomecânicos/fisiologia , Aloenxertos/fisiologia , Animais , Bioprótese , Prótese Vascular , Masculino , Ratos , Ratos Wistar , Engenharia TecidualRESUMO
Previous studies have shown that intracellular adenosine triphosphate (iATP) in activated CD4 T cells in vitro may identify patients at risk of infection or rejection post-transplantation. In this study, we evaluated whether this test could identify the level of risk in 656 renal transplant recipients (RTRs) with good and stable graft function. Therefore, 1095 blood samples from RTRs and 200 from healthy blood donors (normal controls [NCs]) were collected in 2 years and analyzed using the Cylex(®) ImmuKnow™ assay (Cylex, Inc., Columbia, MD, USA). The classification of T cell responses into strong, moderate, and low revealed significant differences between patients and NCs in low and strong responses (P < .001 and P = .021, respectively). The majority of patient samples exhibited moderate immune response (72.2%) in comparison with NC (75%). One hundred twenty-eight patients had fluctuated T cell responses between the three response zones. All patients were clinically stable for at least 1 month after the test. T cell response was increased after time post-transplantation (P < .001) and was found higher in protocols using azathioprine versus other immunosuppression (P < .001) and cyclosporine instead of tacrolimus (P = .012). According to the results of this study, we are not able to support this assay as an immune monitoring test post-transplantation in clinically stable RTRs. In contrast, measuring of iATP in CD4 T cells is a valuable tool for estimating T cell activation capacity. Because T cell activation is mainly affected by immunosuppression, this test may give information regarding the strength of different immunosuppressive protocols or the strength of immunosuppression as it is associated with longer follow-up periods.
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Trifosfato de Adenosina/metabolismo , Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Insuficiência Renal/sangue , Insuficiência Renal/cirurgia , Adolescente , Adulto , Idoso , Azatioprina/uso terapêutico , Linfócitos T CD4-Positivos/metabolismo , Feminino , Humanos , Imunoensaio , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Risco , Transplantados , Adulto JovemRESUMO
BACKGROUND: The aim of this study was a prospective assessment and determination of risk factors for infections among renal transplant recipients (Rtr) during the 1st year after renal transplantation (Rtx). METHODS: From June 2004 to October 2005, we performed 133 Rtx in 88 men and 45 women of overall mean age of 46 ± 14 years (range; 13-75). RESULTS: During the first year post-Rtx, 88 (58 men and 30 women) infectious episodes were observed in 60 patients (45%). Thirty-nine (65%) required ≥1 hospitalization. Most common was urinary tract infections (UTI; 54 episodes; 61%). The causative organism was identified in 61 of the 88 (69%) episodes: In 51 it was bacterial, in 8 cytomegalovirus (CMV), and in 2 fungi. Forty-three episodes (49%) were observed during the first 3 months; 22 (25%) between 3 and 6 months and 23 (26%) between 6 and 12 months post-Rtx. There were no significant differences between patients with versus without hospitalization owing to infections with regard to recipient gender and age, duration of dialysis pre-Rtx, donor kidney source, acute rejection episodes, donor age, or arterial hypertension. Diabetes was a significant risk factor for infections (odds ratio [OR], 1.154; 95% confidence interval [CI], 1.045-1.274; P = .001], as well as an immunosuppressive regimen that included tacrolimus, mammalian target of rapamycin inhibitor, corticosteroids, and anti-interleukin-2 monoclonal antibody as initial treatment (OR, 3.053; 95% CI, 1.007-9.349; P = .043). There was an increased prevalence of CMV infections after the chemoprophylaxis period (OR, 0.456; 95% CI, 0.358-0.580; P = .002). Mean duration of hospitalization was 11.5 days (range, 2-109). In 3 of 133 (5%) Rtr, the outcome was fatal. CONCLUSION: The frequency of infections during the 1 st year post-Rtx is influenced by the primary disease of the Rtr as well by the choice of immunosuppressive regimen. UTI remains the commonest infection, accounting for half of all infections in the first 3 months post-Rtx. There was an increased risk for CMV infection after the chemoprophylaxis period.
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Infecções/etiologia , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Infecções/microbiologia , Infecções/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatory-related pathways in apolipoprotein E knockout (apoE(-/-)) mice with diabetic atherosclerosis. Forty-five male apoE(-/-) mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorized-treadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339 ± 75.613 x10(3)µm(2)) compared to the control (325.485 ± 72.302 x10(3)µm(2)) and sedentary (340.188 ± 159.108 x 10(3)µm(2)) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE-/- mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.
Assuntos
Apolipoproteínas E , Diabetes Mellitus Experimental , Interleucina-6/sangue , Metaloproteinases da Matriz/sangue , Condicionamento Físico Animal , Placa Aterosclerótica , Inibidor Tecidual de Metaloproteinase-2/sangue , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Inflamação/terapia , Masculino , Camundongos , Camundongos Knockout , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapia , Fatores de TempoRESUMO
OBJECTIVE: Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima-media thickness in patients with Type 2 diabetes mellitus. METHODS: One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self-controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60-75% of maximum heart rate); (3) a resistance training group (60-80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA(1c) levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima-media thickness measurements were obtained at baseline and at the end of the study, after 6 months. RESULTS: At baseline, there were non-significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P < 0.05). Aerobic training further improved lipids, systolic blood pressure and exercise capacity compared with the resistance training and the control groups (P < 0.05). Moreover, high-sensitivity C-reactive protein and visfatin decreased, while vaspin and apelin circulating levels increased within the aerobic exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P < 0.05). Within- and between-group comparisons showed negligible alterations in ghrelin serum levels and body weight after all exercise modalities. Finally, aerobic training attenuated the carotid intima-media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129 ± 0.042 mm, P < 0.001). That effect was independently associated with visfatin and amelioration of peak oxygen uptake. CONCLUSIONS: In subjects with Type 2 diabetes, all exercise training modalities improved metabolic profile. Importantly, aerobic training predominantly ameliorated adipokines concentrations and carotid intima-media thickness progression.
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Anti-Inflamatórios/metabolismo , Glicemia/metabolismo , Doenças das Artérias Carótidas/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Exercício Físico , Hemoglobinas Glicadas/metabolismo , Adipocinas/metabolismo , Análise de Variância , Apelina , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/terapia , Progressão da Doença , Jejum , Feminino , Grelina/metabolismo , Humanos , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/metabolismo , Treinamento Resistido , Fatores de Risco , Serpinas/metabolismoRESUMO
INTRODUCTION: The coexistence of liver cirrhosis with hepatocellular carcinoma (HCC) and colon cancer (Ca), which is a rare clinical condition, was treated in a liver transplant recipient. PATIENTS AND METHODS: A 46-year-old man, diagnosed incidentally during an ultrasound (US) examination with a 3.5-cm HCC in segment VII related to chronic hepatitis C virus (HCV), was referred for liver resection. He underwent a laparoscopic protocol evaluation for liver cirrhosis. Liver appearance and biopsy of the left lobe showed Child B/C liver cirrhosis. Because he fulfilled the Milan criteria, we suggested an orthotopic liver transplantation (OLT). During protocol colonoscopy, we discovered an ulcerative sigmoid colon Ca. Three weeks after completing the pre-OLT assessment he underwent an OLT and was discharged home on day 9 on an immunosuppressive regimen of Everolimus, Myfortic, and Prezolone. Two months after transplantation, the patient underwent a sigmoidectomy and for nearly 1 month thereafter received chemotherapy for colon Ca (6 cycles of FOLFOX:Folinic Acid+Fluorouracil+Oxaliplatin). One and a half years after OLT, patient was in good condition but presented with an increased alpha fetoprotein (a-FP) without other findings. A couple of months later we discovered a colon Ca recurrence and 3 small liver metastases. Patient underwent a bowel resection with Hartmann's procedure. Almost immediately after the last operation, he was found to suffer multiple myeloma. He underwent chemotherapy for both malignancies with good responses, but a few months later died of severe sepsis. DISCUSSION: The relevant literature regarding treatment of liver cirrhosis complicated with HCC and synchronous colon Ca reveals poor and controversial outcomes. Our patient underwent chemotherapy immediately after colon resection in the presence of with a good functioning liver. Although his condition was satisfactory after OLT, the optimal treatment of such complicated patients is as yet uncertain.
Assuntos
Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Colectomia , Neoplasias do Colo/cirurgia , Hepatite C Crônica/complicações , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias Primárias Múltiplas , Protocolos de Quimioterapia Combinada Antineoplásica , Biópsia , Carcinoma Hepatocelular/diagnóstico , Quimioterapia Adjuvante , Neoplasias do Colo/diagnóstico , Colonoscopia , Evolução Fatal , Fluoruracila , Hepatite C Crônica/diagnóstico , Humanos , Achados Incidentais , Leucovorina , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Recidiva Local de Neoplasia , Compostos Organoplatínicos , Sepse/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To correlate the expression of E-cadherin and beta-catenin with alterations of expression of Smad4 in advanced colorectal cancer (CRC). METHODS: Tissue specimens from 75 colorectal cancer cases (Dukes stage C and D) were tested for Smad4, E-cadherin and beta-catenin by the Avidin-Biotin immunoperoxidase method. The results were correlated with patients' clinicopathological parameters. RESULTS: Smad4 expression was lost or reduced in roughly 1 out of every 3 Dukes C and D CRCs. Association of Smad4 expression with other clinicopathological parameters was not noted. Association of expression of E-cadherin with other clinicopathological parameters was not noted, apart from tumor location. Expression of beta-catenin was not associated with clinicopathological parameters. Lack of expression of Smad4 was associated with lack of expression of both E-cadherin (<0.000) and beta-catenin (p<0.000). As regards the relation between E-cadherin and beta-catenin, the expression of each seemed to parallel the expression of the other (p<0.000). Beta-catenin was overexpressed in 68.5% of the specimens studied. CONCLUSION: Clinically advanced CRC is associated with a reduced or complete lack of expression of Smad4. Ecadherin and beta-catenin are expressed in parallel with each other and also with Smad4. This tumor suppressor role of Smad4 by affecting both E-cadherin and beta-catenin may indicate a novel pathway for metastatic tumor via cellular reshaping. The precise underlined mechanism(s) and the clinical significance of these findings remain to be determined.
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Caderinas/análise , Neoplasias Colorretais/química , Proteína Smad4/análise , beta Catenina/análise , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the effectiveness of different therapeutic managements in relation to clinical disease stage, the location of the lesion and to register the rate of disease recurrence of patients with glottic and supraglottic laryngeal cancer, and to also study some specific epidemiologic characteristics. METHODS: A series of 164 patients with laryngeal glottic and supraglottic squamous cell cancer (SCC) treated surgically, with radiation therapy (RT), chemotherapy or combination of these was analysed. After treatment, all patients were followed up for an average of 58 months. All data concerning the primary lesion, therapeutic management, recurrence, staging, 5-year overall survival and epidemiological characteristics such as smoking and alcohol abuse were recorded and analysed in combination with the follow up data. RESULTS: The therapeutic approach most commonly used was RT for stage I tumors and surgery for stages II, III and IV. Stage I and II patients treated with RT had high recurrence rate (60%). Patients with recurrence had 45.3% 5-year overall survival rate and average survival time 80 months, whereas patients with no recurrence had 77.4% 5-year overall survival rate and average survival time 173 months (p=0.0001). There was significant difference in survival between stage I and III (p=0.035), stage I and IV (p=0.0038) and stage II and IV (0.0156). The average overall survival time for non smokers was 195 months (median 1707rpar;, while for smokers it was 99 months (median 100; p=0.0047). The average overall survival time for alcohol abusers was 79 months (median 54), while for those who did not use alcohol it was 153 months (median 150; p=0.016). CONCLUSION: The 5-year overall survival rate was 61.3%. RT alone in stages I and II proved inferior in decreasing re-currences compared with surgery. Smokers had significantly shorter overall survival.
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Glote , Neoplasias Laríngeas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
Between 2000 and 2010, 4241 sera from 597 renal transplant (RTx) recipients were monitored for DSA development. The patients were selected in the absence of immunological memory to donor HLA before RTx and were divided into two groups: the historic group, consisting of patients transplanted before December 1996 and the study group, consisting of those transplanted after December 1996. Ninety-two out of 597 (15.4%) patients developed de novo DSA post-RTx, while 196 had third party anti-HLA antibodies. DSA were more frequent in the historic group compared with the study group (P < 0.001). Anti-HLA class-III DSA predominated in both groups (84.6% vs. 69.7%) and were directed preferentially against donor HLA-DQ (65/92,70.6%). Recipients of class II-incompatible grafts developed DSA more frequently than those receiving class II-compatible grafts (P = 0.003). DSA production was not different between pre-sensitized and non-sensitized patients (P = 0.842). DSA class I (HR = 31.78), DSA class II (HR = 20.92), and non-DSA (HR = 5.94) were the only independent predictors for graft failure. In conclusion, this study shows the results of long-term post-transplant alloantibody monitoring, and confirm the strong association of DSA and graft loss. Protocols that remove anti-HLA antibodies from RTx recipients may benefit allograft survival.
Assuntos
Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim/imunologia , Monitorização Imunológica , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Grécia , Histocompatibilidade/efeitos dos fármacos , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Tolerância ao Transplante , Resultado do TratamentoRESUMO
AIM: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. MATERIALS AND METHODS: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. CONCLUSIONS: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.
Assuntos
Antígeno Ki-67/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Proteína Supressora de Tumor p53/metabolismo , Idoso , Proliferação de Células , Feminino , Grécia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , PrognósticoAssuntos
Transplante de Rim/patologia , Adulto , Biópsia , Biologia Celular , Cromatografia em Camada Fina/métodos , Feminino , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Urinálise/métodosRESUMO
Renal transplantation is the treatment of choice for end-stage renal disease. Vascular complications in renal transplantation are not uncommon and may often lead to allograft loss. The most common vascular complications are transplant renal artery stenosis, transplant renal artery thrombosis, transplant renal vein thrombosis, biopsy-induced vascular injuries, pseudoaneurysm formation, and hematomas. Transplant renal artery and vein thrombosis have an early onset and a dramatic clinical manifestation and usually lead to allograft loss. In contrast, transplant renal artery stenosis has better treatment possibilities, whereas the rest do not occur so often. In our institution, 1367 renal transplantations were performed from September 1980 to April 2005. During this period, we encountered 38 major vascular complications leading to graft loss and 19 transplant renal artery stenoses with successful treatment in the majority of cases. According to these data, we can conclude that renal transplantation is a safe therapeutic procedure for renal failure.
Assuntos
Transplante de Rim/efeitos adversos , Doenças Vasculares/epidemiologia , Falso Aneurisma/epidemiologia , Falso Aneurisma/patologia , Cadáver , Hematoma/epidemiologia , Hematoma/patologia , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Transplante de Rim/mortalidade , Doadores Vivos , Artéria Renal/patologia , Obstrução da Artéria Renal/epidemiologia , Obstrução da Artéria Renal/patologia , Veias Renais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Trombose/epidemiologia , Trombose/patologia , Doadores de TecidosRESUMO
This study was conducted to determine kidney transplantation (KTx) outcomes for Greek patients with renal failure caused by lupus nephritis (LN) compared with matched controls, kidney recipients with other causes of end-stage renal disease (ESRD). Twenty-six patients with systemic lupus erythematosus (SLE) subjected to 26 kidney transplants were studied. For comparative purposes a case-control group was selected, matched for gender, source of donor, age and time of KTx. Patient and graft survival estimates were calculated with the Kaplan-Meier product limit estimator and survival estimates were compared with the log-rank test. All patients received cyclosporine or tacrolimus in combination with azathioprine or mycophenolate mofetil for chronic immunosuppression in addition to steroids. Fourteen transplants were from living-related donors and 12 were from deceased donors. The graft survival rates for lupus patients were 88% at 1 year, 67% at 5 years, 38% at 10 years, poorer than the control survival rates of 92%, 92% and 84% (P=0.004). Patient survival in the lupus group did not differ from that of the controls. Survival in the lupus group was 92% at 1 year, 77% at 5 years and 77% at 10 years vs. 96%, 92% and 92% (P=0.26). Chronic allograft nephropathy was the major cause of graft loss. Recurrent LN was detected in two patients, but only one lead to graft failure. SLE patients compared with controls had significantly higher rates of hypertension, cardiovascular disease, infections and malignancies. Compared with matched controls, SLE patients had inferior but still satisfactory graft survival rates, whereas patient survival rates were similar.
Assuntos
Transplante de Rim , Lúpus Eritematoso Sistêmico/cirurgia , Nefrite Lúpica/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Sobrevivência de Enxerto , Grécia , Humanos , Estimativa de Kaplan-Meier , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/etiologia , Nefrite Lúpica/fisiopatologia , Masculino , Resultado do TratamentoRESUMO
Urological complications after renal transplantation increase morbidity, delay graft function, and occasionally lead to graft and/or patient loss. The aim of this study was to analyze the causes of and therapeutic approaches to urological complications in renal transplantation as they related to patient outcomes. A series of 1525 consecutive renal transplantations were performed over a 24-year period. Renal grafts were obtained in 814 cases from living-related and in 711 from cadaveric donors. A Lich-Gregoire ureterovesical reimplantation technique with minimal bladder wall dissection was employed in all cases. Ureteral stents were routinely used in cadaveric transplants and exceptionally among living-related grafts. Urological complications were classified according to the mechanism and site of urinary tract involvement: graft ureteropelvic junction obstruction/stenosis (A), ureteral obstruction/stenosis (B), ureterovesical anastomosis obstruction/stenosis (C), urinary leakage (D), and other (E). Overall, we encountered 96 urological complications (6.3%). Group C complications occurred in 29 cases (30.2%), followed by 27 cases (28.1%) for group B patients, 25 cases (26.0%) for group D, 12 cases (12.5%) for group A, and 3 cases (3.1%) for group E patients. Surgical intervention was required in 49 (51.0%) of all urological complications. The others (n = 47, 49.0%) were treated either conservatively or by minimally invasive procedures. A rapid diagnosis of urological complications, assisted by early posttransplant DTPA scans, routine ultrasonography, and especially prompt treatment, resulted in compensation of renal graft dysfunction in the vast majority (n = 90, 93.8%) of cases. Surgical techniques of graft retrieval and reimplantation are of utmost importance to minimize the incidence of urological complications.
Assuntos
Transplante de Rim/efeitos adversos , Doenças Urológicas/epidemiologia , Feminino , Grécia , Humanos , Doadores Vivos , Masculino , Estudos Retrospectivos , Stents , Obstrução Ureteral/epidemiologia , Obstrução Ureteral/cirurgia , Doenças Urológicas/cirurgiaRESUMO
PURPOSE: To evaluate the efficacy of percutaneous angioplasty and stenting in cases of artery stenosis of the transplanted kidney or proximal iliac artery stenosis causing transplant dysfunction and/or increase of the arterial blood pressure. MATERIALS AND METHODS: Between January 1999 and June 2007, we evaluated 24 patients who had undergone renal transplantation and subsequently were diagnosed with refractory hypertension and transplant dysfunction for signs of possible renal transplant artery stenosis. Color Doppler ultrasonography and magnetic resonance angiography preceded the intrarterial angiographic investigation, with false-negative results in 18.2% and 13.6% of patients, respectively. In 2 of the 24 patients, angiography did not reveal arterial stenosis affecting the transplanted kidney. Two patients had severe ipsilateral iliac artery stenosis and the remaining 20 had transplant artery stenosis. Successful angioplasty and stenting were performed in these 22 patients. RESULTS: The method was technically feasible in 100%. The procedure-related morbidity was 0%. During the follow-up period (range: 3 to 104 months), two patients died with normal transplant function, two suffered transplant failure, and the remaining 18 still have normal transplant function and easily controlled hypertension. CONCLUSION: Percutaneous angioplasty and stenting in cases of arterial stenosis affecting the renal transplant function are safe and effective procedures. Even more, the strong clinical suspicion must lead to angiographic investigation regardless of the results of other imaging approaches.
Assuntos
Angioplastia , Transplante de Rim/efeitos adversos , Obstrução da Artéria Renal/epidemiologia , Obstrução da Artéria Renal/cirurgia , Stents , Angioplastia Coronária com Balão , Cadáver , Creatinina/sangue , Humanos , Hipertensão/etiologia , Doadores Vivos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Doadores de Tecidos , Resultado do TratamentoRESUMO
Colorectal cancer is one of the most frequent malignant neoplasms causing approximately 10% of cancer deaths. Up to 30% of patients with primary colorectal cancer have already liver metastatic disease at the time of diagnosis. Untreated patients with liver metastases share a poor prognosis with an average survival of 12 months. In contrast, patients whose metastatic lesions are surgically treated have an average 5-year survival rate of 40%. Only 10-15% of initial colorectal liver metastases are considered as being resectable. In the remaining patients, the current trend is to downstage initially unresectable metastases by neoadjuvant therapy (systemic or regional chemotherapy, portal vein embolization - PVE - or hepatic artery chemoembolization), tumor ablation and two-stage hepatectomy, alone or in combinations. This study reviews the current therapeutic options for colorectal liver metastases and their contribution to improve survival rates.