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1.
Medicine (Baltimore) ; 103(14): e37632, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579088

RESUMO

Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (P < .001), RLV/body weight (P = .027), RLV/TLV (P < .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.


Assuntos
Regeneração Hepática , Transplante de Fígado , Humanos , Doadores Vivos , Hepatectomia , Estudos Retrospectivos , Fígado/cirurgia , Hepatomegalia
2.
HPB (Oxford) ; 26(4): 521-529, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185541

RESUMO

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.


Assuntos
Gadolínio DTPA , Neoplasias Hepáticas , Regeneração Hepática , Ratos , Animais , Ratos Wistar , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/irrigação sanguínea , Hepatectomia/métodos , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Veia Porta/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Ligadura/métodos
3.
Acta Cir Bras ; 34(11): e201901103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939502

RESUMO

PURPOSE: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. METHODS: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. RESULTS: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. CONCLUSION: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.


Assuntos
Artéria Hepática/cirurgia , Regeneração Hepática/fisiologia , Fígado/diagnóstico por imagem , Veia Porta/cirurgia , Animais , Hepatomegalia/diagnóstico por imagem , Hepatomegalia/fisiopatologia , Imageamento Tridimensional/métodos , Imuno-Histoquímica , Ligadura , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Tamanho do Órgão/fisiologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
5.
J Invest Surg ; 33(1): 69-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29846099

RESUMO

Background: Liver regeneration is a complex procedure in which insulin metabolism has been implicated. The aim of this experimental study was to evaluate the role of insulin in rat hepatic regeneration following major hepatectomy (70%), employing an isolated perfused rat liver (IPRL) model to assess the extraction of insulin from the regenerating liver. Methods: Eighty-six male rats were randomized in 9 groups. A group of rats was studied at postoperative day (POD) 1 having a sham operation while control rats had no operation. All other animals were subjected to 70% hepatectomy. In phase B, at POD 1, 2, 3, 5, 7, and 14, the IPRL was applied. The regenerating liver was perfused with insulin (450 mu/ml) at a flow of 1.4 ml/gr liver/min for 20 min. Animal weight, liver weight, glucose, lactate, aspartate transferase (AST), alanine transferase (ALT), total bilirubin, albumin, prothrombin time (PT), insulin clearance, and tissue proliferating cell nuclear antigen (PCNA) expression were recorded. Results: We observed reduction of the liver's biochemical activities resulting in increase of AST (684%), ALT (532%), PT (27.7%), international normalized ratio (72%), and total bilirubin (82.8%) at first POD, while a normalization of the essential liver's functions occurs at fifth POD. Endogenous insulin concentration increased, while insulin extraction by the liver was reduced at the first POD in animals who underwent hepatectomy (13.94 ± 0.8 vs 7.97 ± 1.80 u/ml, p = 0.0005 and 71 ± 9.9 vs 165.88 µU/gr liver/min, respectively, p = 0.0005). Conclusions: Insulin seems to take part in hepatic regeneration, as the pancreas increases insulin production and the liver absorbs less despite the reduced hepatic mass and function.


Assuntos
Insulina/metabolismo , Regeneração Hepática , Fígado/metabolismo , Animais , Hepatectomia , Insulina/administração & dosagem , Insulina/análise , Fígado/cirurgia , Testes de Função Hepática , Masculino , Modelos Animais , Pâncreas/metabolismo , Perfusão/métodos , Período Pós-Operatório , Ratos
6.
Acta cir. bras ; 34(11): e201901103, Nov. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1054680

RESUMO

Abstract Purpose: To evaluate liver regeneration after selective ligation of portal vein and hepatic artery by 3D Computed Tomography in an experimental model. Methods: Sixteen Wistar rats were randomized into four equal groups: Group I- control (sham), Group II- isolated selective ligation of the hepatic artery, Group III- isolated selective ligation of the portal vein and Group IV- combined ligation of portal vein and hepatic artery. Before procedure and five days after a 3D CT Scan was performed to analyze the hypertrophy, weight and function of the remnant liver. Results: The largest regeneration rate and increase of weight in the hypertrophied lobe was detected in group IV, the first with an average of 3.99 (p=0.006) and the last varying from 6.10g to 9.64g (p=0.01). However, total liver weight and the R1 ratio (Hypertrophied Lobe Weight/Total Liver Weight) was higher in group III (P<0.001) when compared with groups I, II and IV and showed no difference between them. The immunohistochemical examination with PCNA also found higher percentages with statistical significance differences in rats of groups III and IV. It was possible to confirm a strong correlation between hypertrophied lobe weight and its imaging volumetric study. Liver function tests only showed a significant difference in serum gamma-glutamyltransferase and phosphorous. Conclusion: There is a largest liver regeneration after combined ligation of portal vein and hepatic artery and this evidence may improve the knowledge of surgical treatment of liver injuries, with a translational impact in anima nobile.


Assuntos
Animais , Masculino , Veia Porta/cirurgia , Artéria Hepática/cirurgia , Fígado/diagnóstico por imagem , Regeneração Hepática/fisiologia , Tamanho do Órgão/fisiologia , Imuno-Histoquímica , Distribuição Aleatória , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Wistar , Imageamento Tridimensional/métodos , Hepatomegalia/fisiopatologia , Hepatomegalia/diagnóstico por imagem , Ligadura , Fígado/irrigação sanguínea , Fígado/patologia
7.
Int J Mol Sci ; 20(16)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416247

RESUMO

In modern hepatology, diseases of the biliary epithelium, currently termed cholangiopathies, represent one of the main gaps in knowledge, both on experimental and clinical grounds, though they started to draw attention since the late 80s [...].


Assuntos
Doenças Biliares/etiologia , Doenças Biliares/metabolismo , Comunicação Celular , Suscetibilidade a Doenças , Animais , Ductos Biliares/metabolismo , Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Humanos , Fígado/metabolismo , Fígado/patologia , Regeneração Hepática , Cicatrização
8.
Transplant Proc ; 51(4): 1172-1179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101194

RESUMO

AIM: Small-for-size grafts have become more important, especially in living donor liver transplants. The Pringle maneuver, used to reduce blood loss, and the immunosuppressive medications used to prevent graft rejection in liver transplants have different side effects on liver regeneration. We researched the effect of situations where tacrolimus and the Pringle maneuver were applied or not on liver regeneration in rats with partial hepatectomy. MATERIAL AND METHODS: This study was completed with 35 Wistar Albino rats. The subjects were randomly divided into 5 groups: Group 1 had the abdomen opened and no other procedure was performed; Group 2 underwent a 70% hepatectomy; Group 3 underwent a 15-minute Pringle maneuver + 70% hepatectomy; Group 4 underwent a 70% hepatectomy + 5 days of 1 mg/kg/day intraperitoneal tacrolimus; and Group 5 underwent a 150 minute Pringle maneuver + 0% hepatectomy + 5 days of 1 mg/kg/day intraperitoneal tacrolimus. All rats were sacrificed on the seventh postoperative day, remaining liver tissue was weighed, and weight indices created. The remaining liver tissue was stained with phosphohistone H3 and the mitotic index calculated. RESULTS: The groups that underwent the Pringle maneuver, 70% hepatectomy, and tacrolimus administration were compared with the control group in terms of mitotic index and weight index, but no statistically significant differences were identified. CONCLUSION: Suppression of regeneration forms a risk after liver transplantation with small-volume grafts. As a result, research on the effect of tacrolimus combined with the Pringle maneuver is important, especially for transplantations using segmented liver grafts. In our study, we showed that the use of tacrolimus had no negative effect on liver regeneration.


Assuntos
Imunossupressores/farmacologia , Regeneração Hepática/efeitos dos fármacos , Transplante de Fígado/métodos , Tacrolimo/farmacologia , Animais , Modelos Animais de Doenças , Hepatectomia/métodos , Transplante de Fígado/efeitos adversos , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia
9.
HPB (Oxford) ; 21(2): 187-194, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30057122

RESUMO

BACKGROUND: The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. METHODS: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3-6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). RESULTS: 16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 µm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. CONCLUSION: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.


Assuntos
Embolização Terapêutica , Hepatectomia , Circulação Hepática , Microcirculação , Veia Porta/fisiopatologia , Idoso , Velocidade do Fluxo Sanguíneo , Embolização Terapêutica/efeitos adversos , Feminino , Hepatectomia/efeitos adversos , Humanos , Regeneração Hepática , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica , Veia Porta/diagnóstico por imagem , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
10.
Exp Cell Res ; 369(2): 335-347, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29864400

RESUMO

The continuously decreasing willingness for liver donation aggravates treatment of end-stage liver diseases requiring organ transplantation as the only curative strategy. Cell therapy approaches using human hepatocytes or stem cell-derived hepatocyte-like cells may be a therapeutic option out of this dilemma. ABCB5-positive mesenchymal stromal cells from human skin featured promising potential to treat immune-mediated diseases. Since most of chronic liver diseases involve exaggerating immune mechanisms, it was the aim to demonstrate in this study, whether ABCB5+ stem cells may serve as a resource to generate hepatocytic cells for application in liver cell transplantation. Using an established single-step protocol, which had been successfully applied to differentiate mesenchymal stromal cells into the hepatocytic lineage, ABCB5+ skin-derived stem cells did not gain significant characteristics of hepatocytes. Yet, upon culture in hepatocytic differentiation medium, ABCB5+ stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others. Hepatic transplantation of ABCB5+ stem cells, which had been prior cultured in hepatocytic differentiation medium, did not cause any obvious deterioration of liver architecture suggesting their safe application. Thus, human ABCB5+ skin-derived stem cells secreted putative hepatotropic factors after culture in hepatocytic differentiation medium.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pele/citologia , Pele/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Biomarcadores/metabolismo , Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Linhagem da Célula , Meios de Cultura , Hepatectomia , Hepatócitos/transplante , Humanos , Regeneração Hepática , Transplante de Fígado , Masculino , Camundongos , Camundongos Knockout , Modelos Animais , Transplantes/citologia , Transplantes/metabolismo
11.
Eur Surg Res ; 59(1-2): 72-82, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719286

RESUMO

BACKGROUND: There is limited knowledge about the mechanisms behind the unparalleled growth of the future liver remnant (FLR) linked to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). In this study, liver regenerative markers were examined in patients subjected to ALPPS. METHODS: Ten patients with colorectal liver metastases treated with neoadjuvant chemotherapy and ALPPS were included. Plasma was sampled at 6 time points and biopsies from both liver lobes were collected at both stages of ALPPS. The levels of interleukin (IL)-6, hepatocyte growth factor (HGF), tumor necrosis factor-α, epidermal growth factor, and vascular endothelial growth factor in plasma were measured at each time point. Expression of mRNA for markers of proliferation and apoptosis was studied in the biopsies from both liver lobes taken at both stages. RESULTS: ALPPS resulted in a peak of IL-6 after stage 1 (p = 0.004), which decreased rapidly and did not increase again after stage 2. HGF also increased after stage 1 (p = 0.048), and the HGF levels correlated significantly with the degree of growth of the FLR before stage 2 (p = 0.02, r2 = 0.47). There was a correlation between peak levels of IL-6 and HGF (p = 0.03, r2 = 0.84). CONCLUSIONS: IL-6 and HGF seem to be early mediators of hypertrophy after stage 1 in the ALPPS procedure. The peak HGF plasma level correlates with the degree of FLR growth in patients subjected to ALPPS.


Assuntos
Hepatectomia/métodos , Regeneração Hepática , Veia Porta/cirurgia , Adulto , Idoso , Fator de Crescimento Epidérmico/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Ligadura , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Mensageiro/análise , Fator A de Crescimento do Endotélio Vascular/sangue
12.
Gastroenterol Clin North Am ; 47(2): 297-311, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29735025

RESUMO

This article reviews the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). The findings show that the number of adult-to-adult living donor liver transplants is consistently increasing. Living donor liver transplantation has an important benefit for patients with acute liver failure, does not compromise donor safety, and has lower rates of acute cellular rejection in biologically related donor and recipient. The conclusions from the A2ALL consortium have been critical in transplant advancement, supporting increased use to help decrease waitlist death and improve long-term survival of transplant recipients.


Assuntos
Hepatopatias/cirurgia , Transplante de Fígado/estatística & dados numéricos , Doadores Vivos/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Adulto , Estudos de Coortes , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Regeneração Hepática , Transplante de Fígado/efeitos adversos , Transplante de Fígado/economia , Transplante de Fígado/tendências , Doadores Vivos/psicologia , Estudos Multicêntricos como Assunto , Taxa de Sobrevida , Coleta de Tecidos e Órgãos/efeitos adversos , Estados Unidos
13.
Int J Surg ; 52: 74-81, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29425829

RESUMO

Post hepatectomy liver failure (PHLF) remains a significant cause of morbidity and mortality after major liver resection. Although the etiology of PHLF is multifactorial, an inadequate functional liver remnant (FLR) is felt to be the most important modifiable predictor of PHLF. Pre-operative evaluation of FLR function and volume is of paramount importance before proceeding with any major liver resection. Patients with inadequate or borderline FLR volume must be considered for volume optimization strategies such as portal vein embolization (PVE), two stage hepatectomy with portal vein ligation (PVL), Yttrium-90 radioembolization, and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). This paper provides an overview of assessing FLR volume and function, and discusses indications and outcomes of commonly used volume optimization strategies.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Fígado/fisiopatologia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Ligadura/efeitos adversos , Ligadura/métodos , Fígado/cirurgia , Regeneração Hepática , Masculino , Veia Porta/cirurgia , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/métodos , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
14.
Am J Surg ; 215(1): 131-137, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28859921

RESUMO

BACKGROUND: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) and conventional staged hepatectomy (CSH) are options for patients with unresectable liver tumors due to insufficient future liver remnant (FLR). METHODS: A retrospective comparison of clinical data, liver volumetry and surgical outcomes between 10 ALPPS and 29 CSH patients was performed. RESULTS: Patient demographics and disease characteristics were similar between both groups. ALPPS induced superior FLR growth (ALPPS vs. CSH, 48.1% (IQR 39.4-96.9%) vs. 11.8% (IQR 4.3-41.9%), p = 0.013). However, post-operative day 5 international normalized ratio (INR) (ALPPS vs. CSH, 1.6 (IQR 1.5-1.8) vs. 1.4 (IQR 1.3-1.6), p = 0.015) and rate of post-hepatectomy liver failure (ALPPS vs. CSH, 25 vs. 0%, p = 0.032) was higher in the ALPPS group. 90-day mortality (ALPPS vs. CSH, 12.5% vs. 0%, p = 0.320) was similar in both groups. CONCLUSION: ALPPS was superior in inducing FLR growth but associated with increased post-hepatectomy liver failure compared to CSH.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Veia Porta/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Ligadura , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Falência Hepática/prevenção & controle , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento
15.
HPB (Oxford) ; 20(4): 305-312, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29046260

RESUMO

BACKGROUND: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) in assessing liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) compared with portal vein ligation (PVL). METHODS: Thirty rats were divided into the ALPPS, PVL, and control groups. DKI and DWI were performed before and 7 days after surgery. Corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC) were calculated and compared, radiologic-pathologic correlations were evaluated. RESULTS: The volume of the right median lobe increased significantly after ALPPS. There were larger cellular diameters after ALPPS and PVL (P = 0.0003). The proliferative indexes of Ki-67 and hepatocyte growth factor were higher after ALPPS (P = 0.0024/0.0433). D, K and ADC values differed between the groups (P = 0.021/0.0015/0.0008). A significant correlation existed between D and the hepatocyte size (r = -0.523), no correlations existed in ADC and K (P = 0.159/0.111). The proliferative indexes showed moderate negative correlations with ADC (r = -0.484/-0.537) and no correlations with D and K (P = 0.100-0.877). DISCUSSION: Liver regeneration after ALPPS was effective and superior to PVL. DKI, especially the D map, may provide added value in evaluating the microstructure of liver regeneration after ALPPS, but this model alone may perform no better than the standard monoexponential model of DWI.


Assuntos
Hepatectomia/métodos , Regeneração Hepática , Fígado/cirurgia , Veia Porta/cirurgia , Animais , Proliferação de Células , Imagem de Difusão por Ressonância Magnética , Hepatectomia/efeitos adversos , Hepatócitos/patologia , Ligadura , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/fisiopatologia , Masculino , Tamanho do Órgão , Ratos Sprague-Dawley , Fatores de Tempo
16.
World J Gastroenterol ; 23(2): 297-305, 2017 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-28127203

RESUMO

AIM: To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS: We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS: A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION: Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Cirrose Hepática/tratamento farmacológico , Regeneração Hepática/efeitos dos fármacos , Fígado/patologia , Nucleosídeos/análise , Nucleotídeos/análise , Administração Oral , Adulto , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Doença Hepática Terminal/diagnóstico , Feminino , Seguimentos , Humanos , Imageamento Tridimensional/métodos , Fígado/diagnóstico por imagem , Fígado/virologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologia , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Nucleosídeos/administração & dosagem , Nucleosídeos/uso terapêutico , Nucleotídeos/administração & dosagem , Nucleotídeos/uso terapêutico , Tamanho do Órgão/efeitos dos fármacos , Estudos Retrospectivos , Albumina Sérica/análise , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
17.
J Surg Res ; 204(1): 75-82, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27451871

RESUMO

BACKGROUND: Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours. MATERIALS AND METHODS: A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining. RESULTS: Retrospective analysis indicated that body condition scores ≤5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes. CONCLUSIONS: Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration.


Assuntos
Técnicas de Apoio para a Decisão , Indicadores Básicos de Saúde , Hepatectomia/mortalidade , Falência Hepática/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Animais , Feminino , Estimativa de Kaplan-Meier , Falência Hepática/etiologia , Falência Hepática/mortalidade , Regeneração Hepática , Transplante de Fígado/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos
18.
Ann Surg Oncol ; 22(13): 4149-57, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25845431

RESUMO

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH. METHODS: Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score. RESULTS: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10(3)/mm(3) vs. 25.3 % if 100-200 × 10(3)/mm(3) vs. 11.9 % if >200 × 10(3)/mm(3); p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes. CONCLUSIONS: NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/cirurgia , Hiperplasia Nodular Focal do Fígado/etiologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Terapia Combinada , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Prognóstico , Fatores de Risco
19.
Surgery ; 157(2): 194-201, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25282528

RESUMO

BACKGROUND: Meticulous selection of patients who can undergo the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure safely will be paramount to minimize the associated morbidity and mortality. METHODS: We collected data prospectively on 14 consecutive patients who underwent the ALPPS procedure for planned resection of colorectal liver metastases at London Health Sciences Centre, Canada, between April 2012 and November 2013. RESULTS: The median relative increase of the standardized future liver remnant after the ALPPS procedure was 93 ± 28%. The standardized future liver remnant rate of volume increase was 35 ± 13 mL/day. Biopsies of the FLR were taken during stage 1 and 2. These biopsies showed a mean preregeneration Ki-67 index of 0% and a postregeneration index of 14 ± 3%. All 14 ALPPS patients completed the 2-stage hepatectomy. No complications occurred after ALPPS stage 1. After ALPPS stage 2, 5 patients had complications (36%), with 2 patients (14%) having a severe complication (Clavien-Dindo ≥ IIIB). Median follow-up was 9 months. Overall survival at the time of follow-up was 100%. Recurrence developed in 2 patients. One patient had recurrence in the liver and lungs 5 months after stage 2 and was offered more chemotherapy. The other patient developed recurrence in the liver remnant 9 months after stage 2 and underwent additional chemotherapy with a possible future resection of the recurrence. CONCLUSION: Low morbidity and negligible mortality can be achieved with the ALPPS procedure, and the high rates published in previous reports can be improved with refinements in technique and patient selection. The ALPPS approach may be a valid option to enable resection in selected patients with colorectal liver metastases considered unresectable previously by standard techniques.


Assuntos
Neoplasias Colorretais , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Ligadura/efeitos adversos , Ligadura/métodos , Regeneração Hepática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Seleção de Pacientes , Projetos Piloto , Veia Porta/cirurgia , Estudos Prospectivos , Resultado do Tratamento
20.
BMC Cancer ; 14: 980, 2014 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-25523036

RESUMO

BACKGROUND: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer. METHODS/DESIGN: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. DISCUSSION: The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02041871.


Assuntos
Suplementos Nutricionais , Nutrição Enteral/métodos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Cuidados Pré-Operatórios , Infecção da Ferida Cirúrgica/imunologia , Antibacterianos/uso terapêutico , Suplementos Nutricionais/economia , Método Duplo-Cego , Ingestão de Alimentos , Nutrição Enteral/efeitos adversos , Humanos , Imunocompetência , Análise de Intenção de Tratamento , Tempo de Internação , Regeneração Hepática , Estado Nutricional , Cooperação do Paciente , Cuidados Pré-Operatórios/economia , Estudos Prospectivos , Projetos de Pesquisa , Sarcopenia/imunologia , Infecção da Ferida Cirúrgica/prevenção & controle
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