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1.
Medicine (Baltimore) ; 98(51): e18490, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861033

RESUMO

To generate a nomogram to predict posthepatectomy liver failure (PHLF), we attempted to elucidate salient risk factors in patients with hepatocellular carcinoma (HCC).We performed a retrospective review of 665 patients with HCC who received hepatectomy in 2 academic institutions in China. Independent risk factors for PHLF were identified from putative demographic, intrinsic, biochemical, surgery-related, and volumetric data. A predictive nomogram was formulated based on relevant risk factors, and we compared this with existing models.We identified clinical signs of portal hypertension (P = .023), serum total bilirubin (P = .001), serum creatinine (P = .039), and intraoperative hemorrhage (P = .015) as being important risk factors in predicting PHLF. The nomogram had a C-index of 0.906 for the externally validated data. The nomogram displayed better predictive value than 2 of the other most cited models (C-indices of 0.641 and 0.616, respectively) in the current cohort. Additionally, we were able to patients into low- (<10%), intermediate- (10-30%), and high-risk (≥30%) groups based on the nomogram. This allows us to facilitate person-specific management.Here, we constructed a simple nomogram for prediction of PHLF in patients with HCC weighted by independent risk factors. Further prospective studies are required to confirm the predictive ability of our nomogram.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Falência Hepática/epidemiologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , China/epidemiologia , Feminino , Humanos , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Nomogramas , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 98(48): e18166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770264

RESUMO

RATIONALE: Hepatectomy is a treatment to increase survival and curability of patients with intrahepatic lesions or malignant tumors. However, posthepatectomy liver failure (PHLF) can occur. This case is a patient showing acute mental change in postanesthetic care unit (PACU) as an uncommon symptom of PHLF after extended right hepatectomy. PATIENT CONCERNS: A 68-year-old male patient was admitted for surgery of Klatskin tumor. He had hypertension and atrial fibrillation. His model for end-stage liver disease score was 16 pts. His serum bilirubin and ammonia levels were 4.75 mg/dL and 132.8 mcg/dL, respectively. Other laboratory data were nonspecific. He underwent extended right hepatic lobectomy including segments IV-VIII for 9 hours. Weight of liver specimen was 1028 g which was about 58% of total liver volume based on computed tomographic volumetry. The patient was extubated and moved to the PACU with stable vital sign and regular self-breathing. He could obey verbal commands. Fifteen minutes after admission to the PACU, the patient showed abruptly decreasing mental status and self-breathing. DIAGNOSES: Brain computed tomography, blood culture, and sputum culture were performed to diagnose brain lesions and sepsis for evaluating the sudden onset comatous mental status. Results showed nonspecific finding. INTERVENTIONS: He was intubated for securing airway and applying ventilatory care. The patient was moved to the intensive care unit. He received intensive conservative therapy including continuous renal replacement therapy and broad-spectrum antibiotics. OUTCOMES: The patient's condition was worsened. He expired on postoperative day 3. LESSONS: Acute mental change is uncommon and rare as initial symptoms of PHLF. Therefore, clinician may overlook the diagnosis of PHLF in patients with acute mental change after hepatectomy. Thus, clinician should plan an aggressive treatment for PHLF including liver transplantation by recognizing any suspicious symptom, although such symptom is rare.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia , Encefalopatia Hepática , Tumor de Klatskin/cirurgia , Falência Hepática , Fígado , Complicações Pós-Operatórias , Idoso , Neoplasias dos Ductos Biliares/patologia , Tomografia Computadorizada de Feixe Cônico/métodos , Tratamento Conservador/métodos , Evolução Fatal , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/fisiopatologia , Humanos , Tumor de Klatskin/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Falência Hepática/psicologia , Testes de Função Hepática/métodos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/psicologia
3.
Khirurgiia (Mosk) ; (9): 73-79, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532170

RESUMO

Modern surgical and intensive care achievements did not result decrease of mortality in patients with acute small bowel obstruction (ASBO). Direct cause of mortality in ASBO patients is peritonitis followed by multiple organ failure syndrome including acute failure of liver, kidneys, lungs and other organs. Publications devoted to the problem of acute liver failure and its complicationsare reviewed in the article. Mechanisms of pathogenesis and clinical manifestations of multiple organ failure syndrome in patients with acute small bowel obstruction are analyzed.


Assuntos
Obstrução Intestinal/mortalidade , Falência Hepática/mortalidade , Insuficiência de Múltiplos Órgãos/mortalidade , Peritonite/mortalidade , Doença Aguda , Humanos , Obstrução Intestinal/etiologia , Intestino Delgado , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Peritonite/etiologia
4.
Transplant Proc ; 51(7): 2420-2424, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405742

RESUMO

Sepsis causes life-threatening organ dysfunction and is the leading cause of morbidity and mortality in critically ill patients worldwide. Mortality rate of sepsis is close to 30% to 50% despite better understanding of the pathophysiology of sepsis, and advances in antimicrobial therapy, resuscitation strategies, and mechanical ventilation. Liver failure is characterized by accumulation of potentially toxic substances in the systemic circulation of the patient. Toxic effects of these molecules can induce cellular injuries leading to multiorgan dysfunction. Hydrophobic unconjugated bilirubin and bile acids, hydrophilic conjugated bilirubin, and ammonium are the main toxins accumulated in liver failure. We carried out cytokine adsorbtion (CytoSorb) procedure with continuous venovenous hemodialysis in 12-hour sessions. The biochemical values of the patients before and after the use of the filter were recorded. The parameters compared were as follows: total bilirubin, direct bilirubin, C-reactive protein, leukocyte, neutrophil, alanine aminotransferase, aspartate aminotransferase, creatinine, colloid oncotic pressure, ammonia, gamma-glutamyl transferase, alkaline phosphatase, procalcitonin, hematocrit, hemoglobin, pH, albumin, international normalized ratio, fibrinogen, lactate dehydrogenase, platelet, temperature, changes in vasoactive medication requirement, temperature. According to these results, cytokine adsorption systems can be considered as an option to lower bilirubin levels in cases of liver failure. Its inability to lower ammonia level is considered a disadvantage compared with other bilirubin-lowering methods. Although further studies are needed to compare different methods, cytokine adsorption systems may be considered in treatment planning as it contributes to the treatment of sepsis and hyperbilirubinemia in liver failure patients with sepsis.


Assuntos
/métodos , Citocinas/sangue , Hiperbilirrubinemia/sangue , Falência Hepática/terapia , Sepse/sangue , Adsorção , Amônia/sangue , Bilirrubina/sangue , Feminino , Humanos , Hiperbilirrubinemia/complicações , Falência Hepática/sangue , Falência Hepática/etiologia , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Sepse/complicações , Resultado do Tratamento
5.
Acta Med Port ; 32(6): 420-426, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31292022

RESUMO

INTRODUCTION: Excessive portal venous pressure in the liver remnant is an independent factor in the occurrence of posthepatectomy liver failure and small-for-size syndrome. The baseline portal pressure prior to hepatectomy was not considered previously. The aim of this study is to assess the impact of portal pressure change during hepatectomy on the patient outcome. MATERIAL AND METHODS: Prospective observational study including 30 patients subjected to intraoperative measurement of portal pressure before and after hepatectomy. This variation was related to the patient outcome. Control group evaluation was assessed. Patient, disease and procedure features were considered. The optimal cut-off of portal pressure variation was determined. Linear regression or logistic regression was applied to identify predictors of the outcome. RESULTS: The univariate analysis showed that portal pressure increase after hepatectomy was associated with coagulation impairment in the first 30 postoperative days (p < 0.05), and with the occurrence of major complications (p = 0.01), namely hepatic failure (p = 0.041). The multivariate analysis showed that portal venous pressure increase ≥ 2 mmHg is an independent factor for worse outcomes. DISCUSSION: As in previous studies, this study concludes that, after hepatectomy, in addition to the functional liver remnant, other factors are responsible for deterioration of liver function and patient outcome, such as the portal pressure increase and the exposure to chemotherapy prior to hepatectomy. This work may influence the definition of future indications for portal influx modulation. CONCLUSION: Patient outcomes are influenced by the portal venous pressure increase: an increment ≥ 2 mmHg after hepatectomy seems to increase the risk of major complications.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Pressão na Veia Porta/fisiologia , Complicações Pós-Operatórias/etiologia , Idoso , Análise de Variância , Área Sob a Curva , Determinação da Pressão Arterial/métodos , Estudos de Casos e Controles , Feminino , Hepatectomia/mortalidade , Humanos , Hipertensão , Coeficiente Internacional Normatizado , Cuidados Intraoperatórios , Modelos Lineares , Fígado/enzimologia , Falência Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/efeitos dos fármacos , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Tempo de Protrombina , Fatores de Tempo , Resultado do Tratamento
6.
Intern Med ; 58(20): 3039-3043, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31243220

RESUMO

Severe hepatic failure is rarely a cause of death in patients with immunoglobulin light chain (AL) amyloidosis. We herein report a case of AL amyloidosis involving a bleeding tendency due to factor X deficiency and marked hepatic involvement of amyloidosis. The patient died due to severe liver dysfunction two weeks after admission. The diagnosis was confirmed histologically by AL-λ amyloidosis, with the liver and spleen as the main lesions, on an autopsy. As treatment-related toxicity is strong in advanced cases, appropriate treatments are required to improve the prognosis of AL amyloidosis with severe liver dysfunction.


Assuntos
Deficiência do Fator X/etiologia , Cadeias Leves de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Falência Hepática/etiologia , Idoso , Deficiência do Fator X/diagnóstico , Evolução Fatal , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Falência Hepática/diagnóstico
7.
Surgery ; 166(3): 247-253, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31204072

RESUMO

BACKGROUND: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery. METHODS: All patients with complete liver volume data in the associating liver partition and portal vein ligation for staged hepatectomy registry were included in this study. Estimate total liver volume and estimated future remnant liver volume were calculated for 16 published formulas. The median over- or underestimation compared with actual measured volumes were determined for estimate total liver volume and future remnant liver volume. The proportion of patients with an under- or overestimated future remnant liver volume for each formula were compared with each other using a 25% cut-off for each formula. RESULTS: Among 529 studied patients, the formulas ranged from a 19% underestimation to a 63% overestimation of estimate total liver volume. Estimation of future remnant liver volume lead to a 10% underestimation to a 5% overestimation among the formulas. Of all studied formulas, the Vauthey1 formula was the most accurate, generating underestimation of future remnant liver volume in 20% and overestimation of future remnant liver volume in 6% of patients. CONCLUSION: Validation of 16 published total liver volume formulas in a multicenter international cohort of 529 patients that underwent staged hepatectomy revealed that the Vauthey formula (estimate total liver volume = 18.51 × body weight + 191.8) provides the most accurate prediction of the actual future remnant liver volume.


Assuntos
Hepatectomia , Falência Hepática/diagnóstico , Falência Hepática/cirurgia , Idoso , Feminino , Hepatectomia/métodos , Hepatectomia/normas , Humanos , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pré-Operatório , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
8.
Gastroenterol Clin North Am ; 48(2): 183-198, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31046970

RESUMO

Inborn errors of metabolism (IEMs) are usually recognized by characteristic neurologic and metabolic manifestations and sometimes by dysmorphism. However, IEMs can present with a wide variety of gastrointestinal manifestations, whether as the primary or a minor clinical symptom. Regardless, gastrointestinal and hepatic manifestations of IEMs are important clinical features that can help identify an underlying defect; these disorders should be taken into consideration as part of a patient's clinical assessment. It is prudent to include metabolic disorders in the differential diagnosis because in some cases, gastrointestinal symptoms may be the only presenting feature in a patient with an underlying IEM.


Assuntos
Gastroenteropatias/etiologia , Trato Gastrointestinal , Erros Inatos do Metabolismo , Dor Abdominal/etiologia , Doença de Fabry/etiologia , Humanos , Falência Hepática/etiologia , Redes e Vias Metabólicas/genética , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Pancreatite/etiologia , Porfiria Aguda Intermitente/etiologia , Vômito/etiologia
9.
Medicine (Baltimore) ; 98(18): e15458, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045820

RESUMO

Posthepatectomy liver failure (PHLF) is the main cause of perioperative death, and liver cirrhosis is one of the most important risk factors for PHLF. Spleen stiffness (SS) is a novel ultrasonic indicator for liver cirrhosis and portal hypertension, however, it is not clear that whether it has a significant influence on PHLF. Future remnant liver volume (FRLV) is a significant factor for liver regeneration after hepatectomy, spleen volume (SV) could also predict the degree of liver cirrhosis, and recent literatures reported that SV to FRLV ratio (SV/FRLV) could predict small for size syndrome (SFSS) in liver transplantation, however, the relationship between SV/FRLV and PHLF in patients receiving hepatectomy is not known. Systemic inflammatory response (SIR) plays a significant role in the pathogenesis and progression of liver cirrhosis, however, it is not very clear about the exact relationship between SIR and PHLF.We prospectively collected the medical data of consecutive patients diagnosed with hepatocellular carcinoma (HCC) who underwent hepatectomy from August 2015 to February 2016. Preoperative measurements of SS, liver stiffness (LS), SV, FRLV, and SIR were performed on all patients. A univariate analysis was performed to find the risk factors of PHLF and a multivariate analysis was used to identify independent risk factors. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve.Twenty three (23) (14.6%) patients developed PHLF. Univariate analysis found several variables significantly related to PHLF, they were as follows: tumor diameter (P = .01), cirrhosis (P = .001), neutrophil to lymphocyte ratio (NLR) (P = .018), LS (P = .001), SS (P = .001), SV/FRLV (P < .001), operation duration (P = .003), transfusion (P = .009), hepatic inflow occlusion (HIO) (P = .001). Finally, SV/FRLV (P < .001, hazard ratio (HR) = 26.356, 95% confidence interval (CI) 1.627-425.21), SS (P = .009, HR = 1.077, 95%CI 1.017-1.141), and HIO time (P = .002, HR = 1.043, 95%CI 1.014-1.072) were determined as the independent risk factors of PHLF by multivariate analysis.SS and SV/FRLV help to predict the development of PHLF in patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Neoplasias Hepáticas/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Ultrassonografia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Elasticidade , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco , Baço/diagnóstico por imagem , Baço/patologia , Resultado do Tratamento
10.
Transplant Proc ; 51(4): 1121-1126, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30981405

RESUMO

AIM: There is a well-known risk of the emergence of hepatic failure in living donor transplant cases on whom are performed a right donor hepatectomy (RDH). There are different prevalence ratios in literature on this phenomenon. In our study, we aim to depict the prevalence of hepatic failure and risk factors in our cases regarding the most recent description criteria related to hepatic failure. PATIENTS AND METHODS: We included right liver donor hepatectomy cases who fit the donor evaluation algorithm at the Dokuz Eylul University Liver Transplantation Unit between the period of June 2000 and September 2017. The patients were evaluated regarding preoperative data. Liver failure was defined according to the International Study Group of Liver Surgery (ISGLS) criteria. We also included statistical analysis of risk factors that are potentially related to liver failure. RESULTS: We included a total of 276 patients. In 27 (9.7%) patients, we observed posthepatectomy liver failure (PHLF). In 26 (9.4%) patients, we observed Grade A liver failure; in 1 (0.3%) patient, we observed Grade B liver failure. We did not observe any Grade C hepatic failure. In patients with hepatic failure, we observed a significantly longer period of hospitalization (P = .007). Old age (odds ratio = 1.065, 95% confidence interval, 1.135-29.108, P = .035) and preoperatory red blood cell (RBC) transfusion (odds ratio = 5.749, 95% confidence interval, 1.019-1.113, P = .005) were shown as independent risk factors for PHLF. CONCLUSION: Posthepatectomy liver failure is a vital complication of RDH. The risk can be decreased by careful selection of donor candidates. Elderly donor candidates and intraoperative RBC are independent risk factors for PHLF.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Transplante de Fígado , Doadores Vivos , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Idoso , Feminino , Hepatectomia/métodos , Humanos , Incidência , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Coleta de Tecidos e Órgãos/métodos
11.
Langenbecks Arch Surg ; 404(3): 301-308, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30929063

RESUMO

BACKGROUND: Iatrogenic injuries to vital structures of the liver and posthepatectomy liver failure are associated with high mortality. The current donor situation in Norway allows liver transplantation of patients beyond conventional criteria. METHODS: From 1984 to 2017, a total of 1510 liver transplantations were performed. In this retrospective study, we report the results of 13 patients undergoing liver transplantation due to iatrogenic injuries to the liver vasculature or posthepatectomy liver failure. RESULTS: Twelve men and one woman with a median age of 55 years (range 22-69) were included. Seven patients underwent radical surgery for cancer prior to transplantation. The median follow-up time was 70.5 months (range 2.2-177). Three of the patients with malignant disease did not experience disease recurrence, whereas four patients had cancer recurrence and died 7, 24, 45, and 78 months after transplantation. Five of six patients with non-malignant disease fully recovered, but one patient died after 9 months due to infectious complications. CONCLUSIONS: Liver transplantation for liver failure due to portal vein and hepatic artery injury in patients with non-malignant disease seems justified. However, it may be questioned whether patients with malignant disease beyond established criteria should be offered liver transplantation.


Assuntos
Hepatectomia , Falência Hepática/etiologia , Falência Hepática/cirurgia , Transplante de Fígado/métodos , Fígado/lesões , Fígado/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Feminino , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Noruega , Estudos Retrospectivos
12.
Eur Radiol ; 29(11): 5861-5872, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30899977

RESUMO

OBJECTIVES: Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14 days and 28 days after PVE as well as 10 days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis. RESULTS: RE of the left lobe prior to PVE versus 14 days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040). CONCLUSIONS: Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14 days after PVE. KEY POINTS: • To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. • Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. • A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity.


Assuntos
Embolização Terapêutica/efeitos adversos , Gadolínio DTPA/farmacologia , Hepatectomia/efeitos adversos , Falência Hepática/diagnóstico , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética/métodos , Idoso , Feminino , Humanos , Falência Hepática/etiologia , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Veia Porta , Curva ROC
13.
J Surg Res ; 239: 191-200, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30844633

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice. METHODS: Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process. Transgenic GFP-MSCs were administered i.p. 24 h after 70% hepatectomy in BALB/c nude mice, whereas control mice received phosphate-buffered saline. Mice were sacrificed 2, 3, and 5 d after partial hepatectomy. Blood and organs were harvested and metabolic alterations as well as liver regeneration subsequently assessed by liver function tests, multianalyte profiling immunoassays, histology, and immunostaining. RESULTS: Hepatocyte and sinusoidal endothelial cell proliferation were significantly increased after partial hepatectomy in mice receiving MSC compared to control mice (Hepatocyte postoperative day 3, P < 0.01; endothelial cell postoperative day 5, P < 0.05). Hepatocyte fat accumulation correlated inversely with hepatocyte proliferation (r2 = 0.4064, P < 0.01) 2 d after partial hepatectomy, with mice receiving MSC being protected from severe fat accumulation. No GFP-positive cells could be detected in the samples. Serum levels of IL-6, HGF, and IL-10 were significantly decreased at day 3 in mice receiving MSC when compared to control mice (P < 0.05). Relative body weight loss was significantly attenuated after partial hepatectomy in mice receiving MSC (2 d and 3 d, both P < 0.001) with a trend toward a faster relative restoration of liver weight, when compared to control mice. CONCLUSIONS: Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/prevenção & controle , Regeneração Hepática , Transplante de Células-Tronco Mesenquimais , Complicações Pós-Operatórias/prevenção & controle , Animais , Proliferação de Células , Modelos Animais de Doenças , Hepatectomia/métodos , Hepatócitos , Humanos , Fígado/citologia , Fígado/fisiologia , Fígado/cirurgia , Falência Hepática/etiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Complicações Pós-Operatórias/etiologia , Transplante Heterólogo
14.
Nat Rev Gastroenterol Hepatol ; 16(5): 269-281, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30850822

RESUMO

Cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, are highly specialized cells residing in a complex anatomic niche where they participate in bile production and homeostasis. Cholangiocytes are damaged in a variety of human diseases termed cholangiopathies, often causing advanced liver failure. The regulation of cholangiocyte transport properties is increasingly understood, as is their anatomical and functional heterogeneity along the biliary tract. Furthermore, cholangiocytes are pivotal in liver regeneration, especially when hepatocyte regeneration is compromised. The role of cholangiocytes in innate and adaptive immune responses, a critical subject relevant to immune-mediated cholangiopathies, is also emerging. Finally, reactive ductular cells are present in many cholestatic and other liver diseases. In chronic disease states, this repair response contributes to liver inflammation, fibrosis and carcinogenesis and is a subject of intense investigation. This Review highlights advances in cholangiocyte research, especially their role in development and liver regeneration, their functional and biochemical heterogeneity, their activation and involvement in inflammation and fibrosis and their engagement with the immune system. We aim to focus further attention on cholangiocyte pathobiology and the search for new disease-modifying therapies targeting the cholangiopathies.


Assuntos
Doenças dos Ductos Biliares/patologia , Ductos Biliares/patologia , Células Epiteliais/patologia , Regeneração Hepática , Imunidade Adaptativa , Doenças dos Ductos Biliares/complicações , Doenças dos Ductos Biliares/imunologia , Doenças dos Ductos Biliares/fisiopatologia , Ductos Biliares/fisiologia , Ductos Biliares/fisiopatologia , Células Epiteliais/imunologia , Células Epiteliais/fisiologia , Fibrose , Humanos , Imunidade Inata , Inflamação , Falência Hepática/etiologia , Falência Hepática/fisiopatologia
15.
Surg Oncol ; 28: 78-85, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851917

RESUMO

OBJECTIVES: To develop and validate a radiomics-based nomogram for the preoperative prediction of posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve consecutive HCC patients who underwent hepatectomy were included in the study pool (training cohort: n = 80, validation cohort: n = 32), and another 13 patients were included in a pilot prospective analysis. A total of 713 radiomics features were extracted from portal-phase computed tomography (CT) images. A logistic regression was used to construct a radiomics score (Rad-score). Then a nomogram, including Rad-score and other risk factors, was built with a multivariate logistic regression model. The discrimination, calibration and clinical utility of nomogram were evaluated. RESULTS: The Rad-score could predict PHLF with an AUC of 0.822 (95% CI, 0.726-0.917) in the training cohort and of 0.762 (95% CI, 0.576-0.948) in the validation cohort; however, the approach could not completely outmatch the existing methods (CP [Child-Pugh], MELD [Model of End Stage Liver Disease], ALBI [albumin-bilirubin]). The individual predictive nomogram that included the Rad-score, MELD and performance status (PS) showed better discrimination with an AUC of 0.864 (95% CI, 0.786-0.942), which was higher than the AUCs of the conventional methods (nomogram vs CP, MELD, and ALBI at P < 0.001, P < 0.005, and P < 0.005, respectively). In the validation cohort, the nomogram discrimination was also superior to those of the other three methods (AUC: 0.896; 95% CI, 0.774-1.000). The calibration curves showed good agreement in both cohorts, and the decision curve analysis of the entire cohort revealed that the nomogram was clinically useful. A pilot prospective analysis showed that the radiomics nomogram could predict PHLF with an AUC of 0.833 (95% CI, 0.591-1.000). CONCLUSIONS: A nomogram based on the Rad-score, MELD, and PS can predict PHLF.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Falência Hepática/diagnóstico , Neoplasias Hepáticas/cirurgia , Nomogramas , Tomografia Computadorizada por Raios X/métodos , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Falência Hepática/diagnóstico por imagem , Falência Hepática/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco
16.
J Surg Res ; 239: 253-260, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30856518

RESUMO

BACKGROUND: Pringle maneuver (PM) is used for inflow vascular control during hepatectomy, but its use remains controversial. We aimed to report its pattern of use and association with postoperative outcomes. METHODS: We identified hepatectomy patients using the liver-targeted National Surgical Quality Improvement Program database (2014-2016). Associations between PM and posthepatectomy liver failure (PHLF), receipt of blood transfusion, and total hospital length of stay (LOS) were evaluated. RESULTS: We identified 7870 patients (74.9%) with no Pringle maneuver and 2632 (25.1%) with PM. PM patients were older (median age 61 versus 60 y, P = 0.002) and had higher ASA scores (76.1% versus 71.4% were ASA 3-4, P < 0.001). PM had more malignancy (83.0% versus 73.0%, P < 0.001), neoadjuvant therapy (37.7% versus 28.8%, P < 0.001), total lobectomy (30.6% versus 23.2%, P < 0.001), open resection (90.8% versus 74.9%, P < 0.001), and longer operations (246 min versus 212 min, P < 0.001). PM was associated with longer LOS (0.36 d, 95% confidence interval [CI] 0.11-0.60) and increased risk of PHLF (odds ratio [OR] 1.36, 95% CI 1.11-1.66), although not clinically significant grade B/C PHLF (OR 0.82, 95% CI 0.57-1.19), but was not associated with receipt of perioperative blood transfusions (OR 1.00, 95% CI 0.69-1.64). CONCLUSIONS: PM is associated with similar clinically significant PHLF and transfusion requirements but longer LOS compared with no Pringle maneuver.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/epidemiologia , Neoplasias Hepáticas/terapia , Complicações Pós-Operatórias/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Feminino , Hepatectomia/métodos , Hepatectomia/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/estatística & dados numéricos , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
17.
BMJ Case Rep ; 12(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30796069
18.
BMC Med Imaging ; 19(1): 20, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808320

RESUMO

BACKGROUND: One of the major causes of perioperative mortality of patients undergoing major hepatic resections is post-hepatectomy liver failure (PHLF). For preoperative appraisal of the risk of PHLF it is important to accurately predict resectate volume and future liver remnant volume (FLRV). The objective of our study is to prospectively evaluate the accuracy of hemihepatectomy resectate volumes that are determined by computed tomography volumetry (CTV) when compared with intraoperatively measured volumes and weights as gold standard in patients undergoing hemihepatectomy. METHODS: Twenty four patients (13 women, 11 men) scheduled for hemihepatectomy due to histologically proven primary or secondary hepatic malignancies were included in our study. CTV was performed using a semi-automated module (S, hereinafter) (syngo.CT Liver Analysis VA30, Siemens Healthcare, Germany). Conversion factors between CT volumes on the one side and intraoperative volumes and weights on the other side were calculated using the method of least squares. Absolute and relative disagreements between CT volumes and intraoperative volumes were determined. RESULTS: A conversion factor of c = 0.906 most precisely predicted intraoperative volumes of exsanguinated hemihepatectomy specimens from CT volumes in all patients with mean absolute and relative disagreements between CT volumes and intraoperative volumes of 57 ml and 6.3%. The use of operation-specific conversion factors yielded even better results. CONCLUSIONS: CTV performed with S accurately predicts intraoperative volumes of hemihepatectomy specimens when applying conversion factors which compensate for exsanguination. This allows to precisely estimate the FLRV and thus minimize the risk of PHLF in patients undergoing major hepatic resections.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fígado/cirurgia , Falência Hepática/etiologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Resultado do Tratamento , Carga Tumoral
19.
Pediatr Dev Pathol ; 22(4): 356-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30722724

RESUMO

Autopsy reports of 78 stillbirths and early infant deaths (up to age 8 weeks) were reviewed to investigate the prevalence of extrahepatic nonreticuloendothelial siderosis (EHNRS) in the context of neonatal liver failure. Of these, 10 liveborns (12.8%), M:F 3:2, with mean gestational age 37.6 weeks (range: 35-39) and mean age at the time of demise 19.1 days (range: 7-42), showed significant liver injury: infection (n = 7, viral > fungal), congenital malformations (n = 2), and ischemia (n = 1). None had maternal history of gestational alloimmune liver disease (GALD) or previous fetal/neonatal death due to liver failure. Seven of 10 cases (70%) showed EHNRS: pancreas (n = 6), kidneys (n = 4), thyroid and adrenal glands (n = 3), and bronchial glands and heart (n = 2). Iron deposition was most frequent in the pancreas (60%), most diffuse in the kidneys, and seen in at least 2 organs, with pancreas and kidney being the most frequent combination. Hepatic C5b-9 expression was variable (1+ to 4+) except 1 case (100% necrosis). The duration of illness and the mean age at the time of demise tended to be higher in those with EHNRS. In summary, hepatic and EHNRS, with or without C5b-9 expression, are not specific for GALD. Other causes of liver failure should be investigated as clinically and pathologically appropriate.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Morte Fetal/etiologia , Doenças do Recém-Nascido/etiologia , Ferro/metabolismo , Falência Hepática/etiologia , Siderose/etiologia , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Doenças do Recém-Nascido/patologia , Fígado/metabolismo , Fígado/patologia , Falência Hepática/complicações , Falência Hepática/patologia , Assistência Perinatal , Gravidez , Estudos Retrospectivos , Siderose/patologia , Natimorto
20.
Clin Sci (Lond) ; 133(1): 153-166, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30606815

RESUMO

Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis, and when PVP is reduced, rates of liver dysfunction decrease. The aim of the present study was to characterize the hemodynamic, biochemical, and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects. Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80% hepatectomy, and were maintained under terminal anesthesia for 8 h. The primary outcome was changed in PVP. Secondary outcomes included portal venous flow (PVF), hepatic arterial flow (HAF), and biochemical and histological markers of liver injury. Hepatectomy increased PVP (9.3 ± 0.4 mmHg pre-hepatectomy compared with 13.0 ± 0.8 mmHg post-hepatectomy, P<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g, P<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min, P=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg, P=0.046 and PCS = 8.3 ± 1.2 mmHg, P=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min, P<0.0001 and PCS = 488.4 ± 106.4 ml/min, P=0.002) compared with control. Treatment with terlipressin increased HAF (73.2 ± 11.3 ml/min) compared with control (40.3 ± 6.3 ml/min, P=0.026). The results of the present study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.


Assuntos
Hepatectomia , Artéria Hepática/efeitos dos fármacos , Circulação Hepática/efeitos dos fármacos , Falência Hepática/prevenção & controle , Fígado/irrigação sanguínea , Derivação Portocava Cirúrgica , Pressão na Veia Porta/efeitos dos fármacos , Veia Porta/efeitos dos fármacos , Terlipressina/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Artéria Hepática/fisiopatologia , Fígado/patologia , Falência Hepática/etiologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Masculino , Veia Porta/fisiopatologia , Sus scrofa
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