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1.
JPEN J Parenter Enteral Nutr ; 39(3): 301-12, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24408035

RESUMO

INTRODUCTION: Death from sepsis in the intensive care unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with ω-3 has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial. METHOD: A randomized control trial investigating the effects of parenteral ω-3 was carried out. Consecutive patients diagnosed with sepsis were entered into the study and randomized to receive either parenteral ω-3 or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), and days free of organ dysfunction/failure. RESULTS: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral ω-3 were associated with a significant reduction in new organ dysfunction (Δ-SOFA 2.2 ± 2.2 vs. 1.0 ± 1.5, P = .005 and maximum-SOFA 10.1 ± 4.2 vs. 8.1 ± 3.2, P = .041) and maximum CRP (186.7 ± 78 vs. 141.5 ± 62.6, P = .019). There was no significant reduction in the length of stay between cohorts. Patients treated with ω-3 in the strata of less severe sepsis had a significant reduction in mortality (P = .042). CONCLUSION: The treatment of critically ill septic patients with parenteral ω-3 is safe. It is associated with a significant reduction in organ dysfunction. It may be associated with a reduction in mortality in patients with less severe sepsis.


Assuntos
Proteína C-Reativa/metabolismo , Estado Terminal/terapia , Ácidos Graxos Ômega-3/uso terapêutico , Inflamação/prevenção & controle , Insuficiência de Múltiplos Órgãos/prevenção & controle , Nutrição Parenteral , Sepse/terapia , Idoso , Estado Terminal/mortalidade , Ácidos Graxos Ômega-3/farmacologia , Feminino , Óleos de Peixe , Humanos , Inflamação/etiologia , Inflamação/mortalidade , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Projetos Piloto , Sepse/complicações , Sepse/mortalidade , Sepse/patologia
2.
JOP ; 15(5): 485-8, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25262717

RESUMO

CONTEXT: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course. CASE REPORT: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels. CONCLUSION: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

3.
Eur J Cancer ; 50(15): 2570-82, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25091797

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis. To date patient outcomes have not improved principally due to the limited number of patients suitable for surgical resections and the radiation and chemotherapy resistance of these tumours. In the last decade, a failure of conventional therapies has forced researchers to re-examine the environment of PDAC. The tumour environment has been demonstrated to consist of an abundance of stroma containing many cells but predominantly pancreatic stellate cells (PSCs). Recent research has focused on understanding the interaction between PSCs and PDAC cells in vitro and in vivo. It is believed that the interaction between these cells is responsible for supporting tumour growth, invasion and metastasis and creating the barrier to delivery of chemotherapeutics. Novel approaches which focus on the interactions between PDAC and PSCs which sustain the tumour microenvironment may achieve significant patient benefits. This manuscript reviews the current evidence regarding PSCs, their interaction with PDAC cells and the potential implication this may have for future therapies. METHODS: A PubMed search was carried out for the terms 'pancreas cancer' OR 'pancreatic cancer', AND 'pancreatic stellate cells', NOT 'hepatic stellate cells'. All studies were screened and assessed for their eligibility and manuscripts exploring the relationship between PSCs and PDAC were included. The studies were subdivided into in vitro and in vivo groups. RESULTS: One hundred and sixty-six manuscripts were identified and reduced to seventy-three in vitro and in vivo studies for review. The manuscripts showed that PDAC cells and PSCs interact with each other to enhance proliferation, reduce apoptosis and increase migration and invasion of cancer cells. The pathways through which they facilitate these actions provide potential targets for future novel therapies. CONCLUSION: There is accumulating evidence supporting the multiple roles of PSCs in establishing the tumour microenvironment and supporting the survival of PDAC. To further validate these findings there is a need for greater use of physiologically relevant models of pancreatic cancer in vitro such as three dimensional co-cultures and the use of orthotopic and genetically engineered murine (GEM) models in vivo.


Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Comunicação Celular , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Apoptose , Movimento Celular , Proliferação de Células , Humanos , Microambiente Tumoral
4.
Surg Laparosc Endosc Percutan Tech ; 24(4): 385-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25077640

RESUMO

PURPOSE: This study compared 2 methods of palliative stent placement, 6-monthly interval stent changes (RS), or a single-stent policy with no planned stent change (SS). RESULTS: A total of 460 patients were identified. There were no significant differences in the proportion of patients requiring unplanned stent changes in the RS or SS group (22.3% vs. 22.8%). Median survival was not significantly different between the RS and SS groups, for both benign disease (96 vs. 92 mo) and malignant disease (9 vs. 6 mo). Patients undergoing unplanned stent changes had the poorest survival and the highest stent change-related complication rate. Patients with a blocked stent episode were more likely to develop further problems with stent patency, within a median interval of 2.5 months. CONCLUSIONS: In carefully selected patients, a single stent may be adequate with no planned change of stent. There appears to be a clearly defined subgroup of patients who have recurrent problems with stent patency; these should have their interval exchange brought forward on a 3-monthly basis, or a self-expanding metal stent should be used.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Icterícia Obstrutiva/cirurgia , Stents , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Seguimentos , Humanos , Incidência , Icterícia Obstrutiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de Tempo , Resultado do Tratamento
5.
J Eval Clin Pract ; 20(3): 203-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24661411

RESUMO

RATIONALE, AIMS AND OBJECTIVES: Chronic pancreatitis (CP) is a progressive inflammatory disorder with pain being the most frequent symptom. It is associated with loss of function, pancreatogenic diabetes and digestive enzyme deficiency. The impact of local complications and loss of pancreatic function results in unknown and unreported costs. This study attempts to identify both the direct and indirect costs associated with CP. METHODS: A MEDLINE literature review was performed for all relevant articles relating to any aspect of direct and indirect costs as a result of CP. RESULTS: In the UK, there are 12,000 admissions per annum of patients with CP at an estimated cost of £55.8 million. The costs for loss of pancreatic function are estimated at £45-90 million and $75.1 million for endocrine and exocrine function, respectively. Chronic pain contributes $638 million per year in costs. The protracted course of CP and paucity of monetary data make quantifying direct and indirect costs difficult. An estimate of direct and indirect costs is at £285.3 million per year. This equates to £79,000 per person per year. CONCLUSIONS: Patients with CP consume a disproportionately high volume of resources.


Assuntos
Efeitos Psicossociais da Doença , Pancreatite Crônica/economia , Humanos , Classe Social , Reino Unido
6.
Langenbecks Arch Surg ; 398(7): 983-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23995711

RESUMO

PURPOSE: Accurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease. METHODS: Retrospective case note review of all patients undergoing staging laparoscopy for radiologically resectable hilar cholangiocarcinoma, identified from the hepatobiliary multidisciplinary team database, was performed. RESULTS: One hundred consecutive patients underwent staging laparoscopy between 1998 and 2011. Of these, 34 patients were found to be irresectable due to metastatic disease, and 11, due to extensive local disease. Fifty patients proceeded to exploratory laparotomy following staging laparoscopy, and 36 % (18/50) of whom were found to have irresectable disease: 12 patients due to advanced local disease and 6 patients due to metastases. The overall yield of laparoscopy was 45 %, and the accuracy was 71 %. There was no significant difference in age, preoperative bilirubin, neutrophil/lymphocyte ratio, Ca19-9 levels or T stage between patients with resectable disease and with irresectable disease on laparoscopy. There was also no change in the yield of laparoscopy over time, despite advances in radiological imaging. CONCLUSION: In this series, staging laparoscopy avoided unnecessary laparotomy in 45 % of patients with radiologically resectable hilar cholangiocarcinoma. No factor was able to predict positive yield, and therefore, all patients with potentially resectable hilar cholangiocarcinoma should undergo staging laparoscopy.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Laparoscopia , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-23647811

RESUMO

INTRODUCTION: Mediators derived from the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid oxidation have been shown to have tumour promoting effects in experimental models, while n-3 PUFAs are thought to be protective. Here we report fatty acid concentrations in hepatic colorectal metastases compared to liver tissue without tumour in humans. METHODS: Twenty patients with colorectal liver metastasis were randomized to receive a 72 h infusion of parenteral nutrition with or without n-3 PUFAs. Histological samples from liver metastases and liver tissue without tumour were obtained from 15 patients at the time of their subsequent liver resection (mean 8 days (range 4-12) post-infusion) and the fatty acid composition determined by gas chromatography. RESULTS: There were no significant differences in fatty acid composition between the two intervention groups. When data from all patients were combined, liver tissue without tumour had a higher content of both n-3 and n-6 PUFAs and a lower content of oleic acid and total n-9 fatty acids compared with tumour tissue (p<0.0001, 0.0002,<0.0001 and <0.0001, respectively). The n-6/n-3 PUFA ratio was found to be higher in tumour tissue than tissue without tumour (p<0.0001). CONCLUSIONS: Hepatic colorectal adenocarcinoma metastases have a higher content of n-9 fatty acids and a lower content of n-6 and n-3 PUFAs than liver tissue without tumour.


Assuntos
Adenocarcinoma/química , Neoplasias Colorretais/química , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Neoplasias Hepáticas/química , Fígado/química , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade
8.
HPB (Oxford) ; 15(6): 428-32, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23458624

RESUMO

BACKGROUND: Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications. METHODS: As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed. RESULTS: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. DISCUSSION: Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen.


Assuntos
Proteínas Angiogênicas/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Citocinas/sangue , Mediadores da Inflamação/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Administração Intravenosa , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Regulação para Baixo , Inglaterra , Ácidos Graxos Ômega-3/administração & dosagem , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Estimativa de Kaplan-Meier , Modelos Lineares , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fatores de Tempo , Resultado do Tratamento , Gencitabina
9.
Artif Organs ; 37(5): 457-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23489088

RESUMO

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments.


Assuntos
Oxigenação por Membrana Extracorpórea , Rim/irrigação sanguínea , Circulação Hepática , Fígado/irrigação sanguínea , Perfusão/métodos , Circulação Renal , Equilíbrio Ácido-Base , Animais , Biomarcadores , Glicemia/metabolismo , Creatinina/sangue , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/instrumentação , Feminino , Homeostase , Concentração de Íons de Hidrogênio , Rim/metabolismo , Fígado/metabolismo , Modelos Animais , Perfusão/efeitos adversos , Perfusão/instrumentação , Suínos , Fatores de Tempo , Sobrevivência de Tecidos
10.
Pancreas ; 42(2): 322-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23407482

RESUMO

OBJECTIVES: Chronic pancreatitis (CP) results in an extremely poor quality of life and substantially increases health care utilization. Few data exist regarding the cost-effectiveness of surgical treatment for CP. METHODS: This article examined the cost-effectiveness of total pancreatectomy (TP) with islet cell autotransplantation (IAT) for CP. RESULTS: Sixty patients undergoing TP + IAT and 37 patients undergoing TP were identified. Surgery resulted in significant reduction in opiate use, frequency of hospital admissions, and length of stay as well as visual analog scale scores for pain. Total pancreatectomy + IAT resulted in longer survival than TP alone (16.6 vs 12.9 years); 21.6% of patients with TP + IAT were insulin-independent, and those requiring insulin have reduced daily requirements compared with those having TP alone (22 vs 35 IU). The cost of TP + IAT with attendant admission and analgesia costs over the 16-year survival period was £110,445 compared with £101,608 estimated 16-year costs if no TP + IAT was undertaken. CONCLUSIONS: Total pancreatectomy + IAT is effective in improving pain and reducing analgesia. Islet cell transplantation offers the chance of insulin independence and results in lower insulin requirements, as well as conferring a survival advantage when compared with TP alone. Total pancreatectomy + IAT is cost-neutral when compared with nonsurgical or segmental surgical therapy.


Assuntos
Custos de Cuidados de Saúde , Transplante das Ilhotas Pancreáticas/economia , Pancreatectomia/economia , Pancreatite Crônica/economia , Pancreatite Crônica/cirurgia , Satisfação do Paciente , Adulto , Idoso , Analgésicos Opioides/economia , Analgésicos Opioides/uso terapêutico , Distribuição de Qui-Quadrado , Análise Custo-Benefício , Custos de Medicamentos , Emprego/economia , Custos Hospitalares , Humanos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Insulina/economia , Insulina/uso terapêutico , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/mortalidade , Estimativa de Kaplan-Meier , Tempo de Internação/economia , Pessoa de Meia-Idade , Dor Pós-Operatória/economia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Pancreatite Crônica/mortalidade , Readmissão do Paciente/economia , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
World J Gastroenterol ; 19(2): 147-54, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23345935

RESUMO

Numerous techniques developed in medicine require careful evaluation to determine their indications, limitations and potential side effects prior to their clinical use. At present this generally involves the use of animal models which is undesirable from an ethical standpoint, requires complex and time-consuming authorization, and is very expensive. This process is exemplified in the development of hepatic ablation techniques, starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies. The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models. Ex vivo non perfused models are less expensive, easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours. In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines. Isolated perfused ex vivo liver models have been used to study drug toxicity, liver failure, organ transplantation and hepatic ablation and combine advantages of both previous models.


Assuntos
Técnicas de Ablação/história , Técnicas de Ablação/métodos , Fígado/cirurgia , Modelos Animais , Direitos dos Animais/história , Animais , Ablação por Cateter/história , Ablação por Cateter/métodos , Crioterapia/história , Crioterapia/métodos , História do Século XX , História do Século XXI
12.
ANZ J Surg ; 83(4): 280-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23043467

RESUMO

BACKGROUND: Preoperative biliary drainage (PBD) for distal bile duct obstruction may increase post-operative complications. This study examined the effect of PBD on positive bile culture (PBC) rates and complications after biliary bypass or pancreaticoduodenectomy. Bilirubin levels in the non-PBD cohort were also analysed to determine the impact on outcome. METHODS: A retrospective case-note analysis from 2005 to the present day was undertaken. Statistical analysis was undertaken using Students's t-test, chi-squared test, receiver operator characteristics, correlation coefficient and relative risk ratios. RESULTS: A total of 422 patients were identified undergoing pancreaticoduodenectomy or biliary bypass for either benign or malignant distal biliary obstruction. One hundred ninety-six patients had complete data regarding PBD and bile cultures. PBD resulted in a significantly higher relative risk of both infectious complications and positive bile cultures. Overall complication rate was greater in patients undergoing PBD. The major complication rate was equivalent between the two groups. Bilirubin levels in the non-PBD cohort did not correlate or predict length of stay, high-dependency stay, and mortality or complication rate. CONCLUSION: There seems to be little value in PBD for patients with distal biliary obstruction other than to defer definitive surgery to a non-emergency setting. For most hepato-pancreato-biliary units, avoidance of PBD will prove logistically difficult.


Assuntos
Colestase/cirurgia , Drenagem/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia , Distribuição de Qui-Quadrado , Colangiopancreatografia Retrógrada Endoscópica , Colestase/mortalidade , Drenagem/métodos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Curva ROC , Estudos Retrospectivos , Stents , Infecção da Ferida Cirúrgica/mortalidade
13.
J Artif Organs ; 16(2): 218-28, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23184259

RESUMO

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.


Assuntos
Circulação Extracorpórea , Falência Hepática Aguda/terapia , Fígado/metabolismo , Fígado/patologia , Perfusão/métodos , Animais , Biópsia , Isquemia Fria , Feminino , Imuno-Histoquímica , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Testes de Função Hepática , Modelos Logísticos , Tamanho do Órgão , Estatísticas não Paramétricas , Suínos , Transdutores , Isquemia Quente
14.
J Vis Exp ; (82): e50567, 2013 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-24378595

RESUMO

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.


Assuntos
Rim/fisiologia , Fígado/fisiologia , Perfusão/métodos , Animais , Oxigenação por Membrana Extracorpórea , Técnicas In Vitro , Rim/irrigação sanguínea , Rim/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Preservação de Órgãos , Suínos
15.
Am J Surg ; 204(4): 518-26, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23010618

RESUMO

BACKGROUND: The ex vivo porcine liver perfused model isolates the organ from extrinsic regulatory mechanisms, facilitating an improved understanding of the organ physiology and reaction to various conditions. We have assessed the influence of the addition of a porcine kidney to the circuit. METHODS: Eight livers were harvested and perfused for 6 hours. In 5 additional experiments a kidney also was connected in parallel. Hourly arterial blood gases were collected to analyze glucose, acid base, and renal parameters. The primary end point was an evaluation of the influence of the kidney on glucose, pH, and electrolyte levels. RESULTS: In the combined porcine liver-kidney circuit all the parameters significantly improved compared with the liver circuit alone. This was particularly evident for glucose values because normoglycemia was reached by the end of the perfusion, and for pH and electrolyte values that were maintained at initial levels. CONCLUSIONS: The addition of a porcine kidney to the perfusion circuit improves the biochemical milieu. This might produce more consistent and reliable results, particularly during studies requiring a steady-state environment.


Assuntos
Equilíbrio Ácido-Base , Glicemia/metabolismo , Transfusão de Sangue Autóloga , Rim/fisiologia , Fígado/fisiologia , Perfusão/métodos , Equilíbrio Ácido-Base/fisiologia , Animais , Eletrólitos/sangue , Técnicas de Cultura de Órgãos , Suínos , Temperatura , Fatores de Tempo
16.
J Gastrointest Surg ; 16(11): 2064-73, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22923210

RESUMO

BACKGROUND: Histological abnormalities in the non-tumour-bearing liver (NTBL) may influence outcome following hepatectomy. Effects will be most pertinent following right trisectionectomy but have yet to be specifically examined in this context. This study aimed to investigate the influence of perioperative factors, including NTBL histology, on outcome following right trisectionectomy. METHODS: Pathological review of the NTBL of 103 consecutive patients undergoing right trisectionectomy between January 2003 and December 2009 was performed using established criteria for steatosis, non-alcoholic steatohepatitis (NASH), sinusoidal injury (SI), fibrosis and cholestasis. Perioperative and pathological factors were correlated with post-operative outcome (morbidity, major morbidity, hepatic insufficiency and mortality). RESULTS: Morbidity, hepatic insufficiency and major morbidity occurred in 37.9 %, 14.6 % and 22.3 % of cases, respectively. Ninety-day mortality rate was 5.8 %. NASH (P = 0.007) and perioperative blood transfusion (P = 0.001) were independently associated with hepatic insufficiency following trisectionectomy. NASH (P = 0.028), perioperative transfusion (P = 0.016), diabetes mellitus (P = 0.047) and coronary artery disease (P = 0.036) were independently associated with major morbidity. Steatosis, SI, fibrosis and cholestasis in the NTBL demonstrated no association with any adverse outcome. CONCLUSION: NASH, but not steatosis or SI, is associated with adverse outcome following right trisectionectomy and caution must be exerted when considering major hepatectomy in patients with NASH.


Assuntos
Fígado Gorduroso/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
Arch Surg ; 147(7): 657-66, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22802063

RESUMO

OBJECTIVES: To compare the morbidity, pain, cosmesis, and cost-effectiveness of single-incision laparoscopic cholecystectomy (SILC) with standard laparoscopic cholecystectomy (SLC). DATA SOURCES: Existing literature in MEDLINE through July 31, 2011. STUDY SELECTION: We reviewed all studies identified through MEDLINE. References were cross-checked to ensure capture of cited pertinent articles. Case reports and series of less than 4 cases were excluded. DATA SYNTHESIS: In total we analyzed 49 studies, including 2336 patients. Seven studies consisted of randomized trials and 11 of case-matched control series (compared with SLC). The technical aspects of SILC were not standardized. Median follow-up time was 4 weeks, although 27 studies (55.1%) reported no follow-up. The overall median complication rate was 7.37% (range, 0-28.6%), and the overall rate of biliary duct complications was 0.39%. Postoperative pain was similar or worse in SILC compared with SLC in 10 of 13 articles reporting pain outcomes (76.9%). Six articles investigating cosmesis after SILC compared outcomes with those of SLC. Three articles demonstrated significantly improved cosmesis after SILC. CONCLUSIONS: The perceived benefits of SILC compared with SLC are improved cosmesis and reduced surgical trauma. No definitive evidence suggests that such improvements can be gained by SILC. Complications are more common, may be underestimated owing to the lack of sufficient follow-up, and may be associated with a shift from safe practice.


Assuntos
Colecistectomia Laparoscópica/métodos , Análise Custo-Benefício , Estética , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde , Medição da Dor , Complicações Pós-Operatórias , Umbigo
18.
Pathol Oncol Res ; 18(4): 1085-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22706978

RESUMO

Electrolytic ablation (EA) destroys the liver by releasing toxic radicles and producing modifications in the local pH without increasing the tissue temperature. We assessed the histological changes produced by EA using an ex-vivo perfused model. Five porcine livers were harvested, preserved in ice and reperfused for six hours in an extracorporeal circuit using autologous normothermic blood. One hour after reperfusion EA was performed and liver biopsies collected at the end of the experiments. The main necrotic zone consisted of coagulative necrosis, sinusoidal dilatation and haemorrhage with an unusual morphological pattern. The coagulative necrosis and haemorrhage affected mainly the peripheral area of the lobule with relative sparing of the area surrounding the centrilobular vein. Contrasting with this sinusoidal dilatation appeared to be more prominent in the centrilobular area. EA produces patterns of tissue destruction that have not been observed with the more commonly used thermal techniques. Further studies should obtain more information about the influence of adjacent biliary and vascular structures so that appropriate clinical trials can be designed.


Assuntos
Eletrocoagulação/métodos , Fígado/patologia , Fígado/cirurgia , Animais , Eletrocoagulação/efeitos adversos , Feminino , Histocitoquímica , Fígado/efeitos da radiação , Necrose , Reperfusão , Suínos
19.
J Artif Organs ; 15(3): 290-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22476783

RESUMO

The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.


Assuntos
Citocinas/sangue , Rim/fisiologia , Fígado/fisiologia , Animais , Perfusão , Suínos
20.
Pancreas ; 41(2): 233-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21946812

RESUMO

OBJECTIVES: The role of laparoscopy in staging periampullary malignancies is to detect small-volume metastatic disease not visible on preoperative imaging. Owing to improvements in preoperative imaging, some centers no longer undertake routine laparoscopic staging, whereas others still find it a useful pre-exploration tool. METHODS: This study investigated the diagnostic yield of staging laparoscopies in 137 consecutive potentially resectable patients with periampullary malignancies. Serology on presentation, tumor size on computed tomography and proinflammatory markers such as C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and Glasgow Prognostic Score were also examined to see if they were able to identify patients more likely to benefit from staging laparoscopy. RESULTS: Laparoscopy identified occult disease in 16.1% of the patients. Only tumor diameter on cross-sectional imaging was related to an increase in diagnostic yield on staging laparoscopy. Area-under-curve values for tumor size and occult disease at laparoscopy were 0.8, with P = 0.0001. CONCLUSION: Staging laparoscopy is a useful adjunct to computed tomography in staging periampullary cancers. Tumor size (especially >45 mm) is the only preoperative marker predictive of unexpected occult disease and may be used to select high-risk patients for laparoscopic staging.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Carcinoma Ductal Pancreático/diagnóstico , Mediadores da Inflamação/sangue , Laparoscopia , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Inglaterra , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Carga Tumoral
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