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1.
Hum Gene Ther ; 31(1-2): 103-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31802713

RESUMO

Liver fibrosis is a chronic liver disease that could further develop to cirrhosis and liver carcinoma. Hepatic stellate cells (HSCs) are primary effector cells to initiate liver fibrosis. We aimed to explore the function and underlying mechanisms of mitochondrial fusion protein Mitofusin-2 (MFN2) in liver fibrosis. First, we utilized an alpha-smooth muscle actin promoter to overexpress MFN2 specifically in HSCs using adeno-associated virus (AAV) vector (AAV-MFN2). Overexpression of MFN2 was specifically achieved in HSC-T6 cells, but not in murine bone marrow-derived macrophages or hepatocyte AML-12 cells. We found that high expression of MFN2 induced apoptosis of HSC-T6 cells. Mechanistically, we demonstrated that high level of MFN2 inhibited TGF-ß1/Smad signaling pathway, triggered downregulation of type I, type III, and type IV collagen, and antagonized the formation of factors associated with liver fibrosis. Furthermore, we found that overexpression of MFN2 using AAV-MFN2 ameliorated CCl4-induced liver fibrosis in vivo with significantly decreased immune cell infiltration. Taken together, our findings indicate that MFN2 is critical in regulating apoptosis and liver fibrosis in HSCs, which might be a useful therapeutic target to treat liver fibrosis.

2.
Gut Liver ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31694365

RESUMO

Background/Aims: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not be fully elucidated, and the lack of therapeutic strategies for NAFLD is an urgent health problem. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) participates in several biological processes, but its relationship with lipid metabolism and NAFLD has not yet been reported. We aimed to determine the function of GNAI3 in the development of NAFLD. Methods: Mice were fed a methionine and choline-deficient diet to induce NAFLD. An NAFLD model in HepG2 cells was induced by free fatty acid treatment. GNAI3 levels in HepG2 cells were downregulated by shRNA. Protein levels of related proteins were evaluated by Western blotting, and mRNA levels were determined by quantitative reverse transcription polymerase chain reaction. Hematoxylin and eosin and Oil Red O staining were used to observe histological changes in liver tissue. Results: The dysregulated hepatic lipid metabolism in the NAFLD mouse model was enhanced by GNAI3 knockout, which also provoked worse liver damage. In the NAFLD model in HepG2 cells, the downregulation of GNAI3 promoted cellular lipid accumulation and enhanced the changes in lipid metabolic enzyme levels. Conclusions: This study demonstrates that GNAI3 participates in the development of NAFLD in both cellular and mouse models. The data indicate that GNAI3 is a potential new target for the treatment of NAFLD in humans.

3.
World J Surg Oncol ; 17(1): 167, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590665

RESUMO

BACKGROUND: To evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC) METHODS: From December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded. RESULTS: In the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively. CONCLUSION: SOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.

4.
Naunyn Schmiedebergs Arch Pharmacol ; 392(12): 1551-1560, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31359090

RESUMO

Hepatocellular carcinoma (HCC) patients have low 5-year survival due to the delayed diagnosis, so it is necessary to develop an alternative treatment. Preferentially expressed antigen of melanoma (PRAME) has a high expression in HCC patients, and the effects of evodiamine on HCC are less characterized, although evodiamine has anti-tumor activities in several tumor types. To investigate the effects of evodiamine on PRAME expression, the in vitro PRAME expression in HepG2 cells after incubated with evodiamine was determined by RT-PCR and western blot. Cell viability, migration, invasion, and apoptosis of evodiamine-incubated HepG2 cells were evaluated by Cell Counting Kit-8, wound healing, transwell assay, and Annexin V-FITC/PI double-staining assay, respectively. To evaluate the mechanism of the regulation of evodiamine on the PRAME expression, chromatin immunoprecipitation coupled with quantitative PCR was employed. Xenograft model was used to evaluate the effects of evodiamine on tumor growth, survival rate, and the PRAME expression. The PRAME expression was inhibited in evodiamine-treated HepG2 cells in vitro and in vivo. The tumor metastasis and growth were inhibited resulting from evodiamine incubation. The evodiamine inhibited the PRAME expression through trimethylation of H3K27. In this study, evodiamine contributes to in vitro and in vivo tumor cell growth inhibition. To achieve this inhibition, the PRAME expression may be repressed through trimethylation resulting from epigenetic regulation of evodiamine.

5.
J Vasc Surg Cases Innov Tech ; 5(1): 4-6, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30619981

RESUMO

We report the case of a 61-year-old man with pancreatectomy with arterial resection and reconstruction and extended lymph node dissection because of locally advanced pancreatic cancer. Surgery revealed the tumor invading the root part of the superior mesenteric artery, so we cut off and reconstructed the artery root through end-to-end anastomosis of the left gastric artery and superior mesenteric artery. The left gastric artery is a reasonable choice to reconstruct the superior mesenteric artery, and to the best of our knowledge, only a few reports describe locally advanced pancreatic cancer as an indication for our surgical procedure.

6.
Clin Exp Med ; 19(1): 149-157, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30498929

RESUMO

The study aimed to evaluate the effectiveness of the first-line chemotherapy FOLFIRINOX in treating pancreatic cancer. Pertinent studies were derived from the PubMed, Cochrane Library and EMBASE. The outcomes were analyzed according to resection rate and radical (R0) resection rate. Data were expressed as weighted commix proportions with 95% confidence intervals (CIs). Twenty-three studies, involving 968 patients with locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), were examined. After treatment, 55% (95% CI 52-58%) of the patients underwent resection and 40% (95% CI 37-43%) underwent R0 resection, and the median overall survival ranged from 15.5 to 35.4 months, with a 10.0-27.1 months' median progression-free survival. The meta-analysis shows that FOLFIRINOX, as the first-line therapy, has significant down-staging effects in patients with LAPC or BRPC, with a 40% R0 resection rate and the adverse events under control.


Assuntos
Antineoplásicos/administração & dosagem , Tratamento Farmacológico/métodos , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Oxaliplatina , Análise de Sobrevida , Resultado do Tratamento
7.
J Formos Med Assoc ; 118(1 Pt 2): 268-278, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29798819

RESUMO

BACKGROUND/PURPOSE: Robotic approach has improved the ergonomics of conventional laparoscopic distal pancreatectomy (LDP), but whether patients benefit more from robot assisted distal pancreatectomy (RADP) is still controversial. This meta-analysis aims to compare the perioperative and economic outcomes of RADP with LDP. METHODS: A systematic review of the literature was carried out on PubMed, EMBASE, and the Cochrane Library between January 1990 and March 2017. All eligible studies comparing RADP versus LDP were included. Perioperative and economic outcomes constituted the end points. RESULTS: 13 English studies with 1396 patients were included. Regarding to intraoperative outcomes, RADP was associated with a significant decrease in conversion rate (OR = 0.52; 95%CI: 0.34, 0.78; P = 0.002). Although the spleen-preserving rates were comparable between RADP and LDP, a significant higher splenic vessels conservation rate was observed in the RADP group (OR = 4.71; 95%CI: 1.77, 12.56; P = 0.002). No statistically significant differences were found at operation time, estimated blood loss and blood transfusion rate. Concerning postoperative outcomes, pooled data indicated the overall morbidity, pancreatic fistula and the length of hospital stay did not differ significantly between the RADP and LDP groups. And concerning pathological outcomes, positive margin rate and the number of lymph nodules harvested were comparable between the two groups. The operative cost of RADP was almost double that of LDP (WMD = 2350.2 US dollars; 95%CI: 1165.62, 3534.78; P = 0.0001). CONCLUSION: RADP showed a slight technical advantage. But whether this benefit is worth twofold cost should be considered by patient's individuation.


Assuntos
Laparoscopia/métodos , Pancreatectomia/economia , Pancreatectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Perda Sanguínea Cirúrgica , Conversão para Cirurgia Aberta , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Duração da Cirurgia , Tratamentos com Preservação do Órgão , Fístula Pancreática/epidemiologia , Período Pós-Operatório , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Baço/cirurgia , Resultado do Tratamento
8.
Cell Physiol Biochem ; 45(3): 1121-1135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29439259

RESUMO

BACKGROUND/AIMS: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. METHODS: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry. RESULTS: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect. CONCLUSIONS: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC.


Assuntos
Antígenos de Neoplasias/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Neoplasias Hepáticas/patologia , Proteína Supressora de Tumor p53/metabolismo , Adulto , Animais , Antígenos de Neoplasias/química , Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67/metabolismo , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais
10.
Asian Pac J Trop Med ; 10(4): 409-413, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28552111

RESUMO

OBJECTIVE: To evaluate the detection accuracy of the biomarkers dickkopf-1, DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers. METHODS: The study was composed of three groups, one with HCC patients, one with non-HCC liver diseases and one with healthy controls. Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA. The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel. RESULTS: The HCC group showed higher levels of dickkopf-1, DCP and AFP than the other two groups (P < 0.05). Dickkopf-1 showed better sensitivity (73.26% vs. 58.13%, P < 0.05) and better specificity (44.0% vs. 29.0%, P < 0.05) than AFP. DCP also had better sensitivity (74.42% vs. 58.13%, P < 0.05) than AFP, but their specificity was similar (30.00% vs. 29.00%, P > 0.05). The combination of the biomarkers as a serum panel produced much better sensitivity (93.02%) and specificity (78.00%) than each of the markers individually (P < 0.05). CONCLUSION: The combination of AFP, DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone. The tests are convenient and inexpensive, and may serve as a valuable addition to current options for the diagnosis of HCC.

11.
Biomed Pharmacother ; 88: 684-688, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28152477

RESUMO

BACKGROUND: The patients with huge (≥10cm) or multiple hepatocellular carcinoma (HCC) in the right liver and insufficient size of the remnant left liver can not be performed an operation of right hemihepatectomy because of that liver failure will occur post operation. We designed anatomic trisegmentectomy in right liver to increase the ratio of future liver remnant volume (%FLRV), thus increasing resectability of huge or multiple HCC. METHODS: Thirteen patients were analyzed by preoperative CT scan for liver and tumor volumetries. If the right hemihepatectomy was done, %FLRV would be at the range of 29.6%-37.5%. However, if trisegmentectomy was done, %FLRV would increase by an average of 14.0%. So patients will not undergo postoperative liver failure due to sufficient %FLRV. Therefore, we designed anatomic trisegmentectomy, with retention of segment 5 or segment 8, to increase %FLRV and increase the resectability for huge or multiple HCC. RESULTS: After trisegmentectomy, the inflow and outflow of remnant liver were maintained well. Severe complications and mortality were not happened post operation. Of the 13 patients, 10 survived up to now. Of the 10 living cases, postoperative lung metastasis was found in 2 and intrahepatic recurrence was found in 1. These 3 patients survive with tumor after comprehensive therapies including oral administration of Sorafenib. CONCLUSION: Compared to right hemihepatectomy, anatomic trisegmentectomy in right liver guarantees the maximum preservation of %FLRV to increase the resectability of huge or multiple HCC, thus improving the overall resection rate.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Fígado/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Resultado do Tratamento
12.
World J Gastroenterol ; 21(12): 3564-70, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25834321

RESUMO

AIM: To evaluate the feasibility of hepatectomy and primary closure of common bile duct for intrahepatic and extrahepatic calculi. METHODS: From January 2008 to May 2013, anatomic hepatectomy followed by biliary tract exploration without biliary drainage (non-drainage group) was performed in 43 patients with intrahepatic and extrahepatic calculi. After hepatectomy, flexible choledochoscopy was used to extract residual stones and observe the intrahepatic bile duct and common bile duct (CBD) for determination of biliary stricture and dilatation. Function of the sphincter of Oddi was determined by manometry of the CBD. Primary closure of the CBD without T-tube drainage or bilioenteric anastomosis was performed when there was no biliary stricture or sphincter of Oddi dysfunction. Dexamethasone and anisodamine were intravenously injected 2-3 d after surgery to prevent postoperative retrograde infection due to intraoperative bile duct irrigation, and to maintain relaxation of the sphincter of Oddi, respectively. During the same period, anatomic hepatectomy followed by biliary tract exploration with biliary drainage (drainage group) was performed in 48 patients as the control group. Postoperative complications and hospital stay were compared between the two groups. RESULTS: There was no operative mortality in either group of patients. Compared to intrahepatic and extrabiliary drainage, hepatectomy with primary closure of the CBD (non-drainage) did not increase the incidence of complications, including residual stones, bile leakage, pancreatitis and cholangitis (P > 0.05). Postoperative hospital stay and costs were nevertheless significantly less in the non-drainage group than in the drainage group. The median postoperative hospital stay was shorter in the non-drainage group than in the drainage group (11.2 ± 2.8 d vs 15.4 ± 2.1 d, P = 0.000). The average postoperative cost of treatment was lower in the non-drainage group than in the drainage group (29325.6 ± 5668.2 yuan vs 32933.3 ± 6235.1 yuan, P = 0.005). CONCLUSION: Hepatectomy followed by choledochoendoscopic stone extraction without biliary drainage is a safe and effective treatment of hepatolithiasis combined with choledocholithiasis.


Assuntos
Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Hepatectomia , Litíase/cirurgia , Hepatopatias/cirurgia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Coledocolitíase/complicações , Coledocolitíase/diagnóstico , Coledocolitíase/economia , Redução de Custos , Análise Custo-Benefício , Dexametasona/administração & dosagem , Drenagem , Estudos de Viabilidade , Feminino , Glucocorticoides/administração & dosagem , Hepatectomia/efeitos adversos , Hepatectomia/economia , Custos Hospitalares , Humanos , Tempo de Internação , Litíase/complicações , Litíase/diagnóstico , Litíase/economia , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/economia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Alcaloides de Solanáceas/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
World J Gastroenterol ; 20(36): 13200-4, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25278718

RESUMO

Surgery such as digestive tract reconstruction is usually required for pancreatic trauma and severe pancreatitis as well as malignant pancreatic lesions. The most common digestive tract reconstruction techniques (e.g., Child's type reconstruction) for neoplastic diseases of the pancreatic head often encompass pancreaticojejunostomy, choledochojejunostomy and then gastrojejunostomy with pancreaticoduodenectomy, whereas these techniques may not be applicable in benign pancreatic diseases due to an integrated stomach and duodenum in these patients. In benign pancreatic diseases, the aforementioned reconstruction will not only increase the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the risks of traction, twisting and angularity of the jejunal loop. In addition, postoperative complications such as mixed fistula are refractory and life-threatening after common reconstruction procedures. We here introduce a novel pancreaticojejunostomy, hepaticojejunostomy and double Roux-en-Y digestive tract reconstruction in two cases of benign pancreatic disease, thus decreasing not only the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the possibility of postoperative complications compared to common reconstruction methods. Postoperatively, the recovery of these patients was uneventful and complications such as bile leakage, pancreatic leakage and digestive tract obstruction were not observed during the follow-up period.


Assuntos
Anastomose em-Y de Roux , Jejunostomia/métodos , Pancreatopatias/cirurgia , Pancreaticojejunostomia , Procedimentos Cirúrgicos Reconstrutivos , Ferimentos e Lesões/cirurgia , Doença Aguda , Colangiopancreatografia por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/diagnóstico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ferimentos e Lesões/diagnóstico
14.
Indian J Surg ; 76(2): 159-61, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24891787

RESUMO

Anatomic liver resection not only enables enough tumor-free resection margin but also guarantees maximum preservation of remaining normal liver tissue. We report herein a hepatocellular carcinoma patient who underwent successful anatomic liver resection of segments 6, 7, and 8 by the method of selective occlusion of hepatic inflow. Multiple tumors were found in segments 6, 7, and 8 by computed tomographic (CT) scanning. CT volumetry analyzed that his left hemi-liver volume was less than the minimal limit of safe survival. Therefore, we planned to perform segment 5 remaining, anatomic liver resection of segments 6, 7, and 8 to guarantee the maximum preservation of remaining normal liver tissue. Selective occlusion of hepatic inflow was creatively used twice in this case to divide right hemi-liver Glissonean pedicle and segments 6 and 7 Glissonean pedicle, respectively. Thus, the resection line was determined, and anatomic liver resection of segments 6, 7, and 8 was completed. Selective right hemi-liver Glissonean pedicle occlusion was used, while parenchymal transection was between segments 6 and 5 and between segments 8 and 5. Therefore, liver ischemia reperfusion injury and homodynamic instability were maximally reduced during operation.

15.
World J Gastroenterol ; 20(15): 4433-9, 2014 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-24764684

RESUMO

AIM: To report the devised anatomic liver resection of segments 6, 7 and 8 to improve the resection rate for patients with right liver tumors. METHODS: We performed anatomic liver resection of segments 6, 7 and 8 to guarantee the maximum preservation of the remaining normal liver tissue. Segment 5 was determined by two steps of Glissonean pedicle occlusion. And a "┏┛" shaped broken resection line was marked upon the diaphragmatic surface of the liver. Selective right hemihepatic inflow occlusion was used to reduce blood loss during parenchymal transection between segments 6 and 5 and between segments 8 and 5. If needed, total hepatic Glissonean pedicle occlusion was used during parenchymal transection between segment 8 and the left liver. RESULTS: Compared to right hemihepatectomy, the percentage of future liver remnant volume was increased by an average of 13.9% if resection of segments 6, 7 and 8 was performed. Resection of segments 6, 7 and 8 was completed uneventfully. After hepatectomy, the inflow and outflow of segment 5 were maintained. There was no perioperative mortality, postoperative abdominal bleeding or bile leakage in this group. Alpha-fetoprotein (AFP) returned to the normal range within 2 mo after the operation in all the patients. One patient died 383 d postoperatively due to obstructive suppurative cholangitis. One patient suffered from severe liver dysfunction shortly after surgery and had intrahepatic recurrence 4 mo postoperatively. Postoperative lung metastasis was found in one patient. No tumor recurrence was found in the other patients and the parameters including liver function and AFP level were in the normal range. CONCLUSION: Anatomic liver resection of segments 6, 7 and 8 can be a conventional operation to improve the overall resection rate for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Adulto , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Tomografia Computadorizada por Raios X
16.
Turk J Gastroenterol ; 23(5): 546-51, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23161300

RESUMO

BACKGROUND/AIMS: We aimed to analyze the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of primary hepatic neuroendocrine tumor. MATERIALS AND METHODS: We retrospectively analyzed the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of 9 patients with primary hepatic neuroendocrine tumor treated in our hospital from January 2003 to January 2010. RESULTS: The clinical manifestations were nonspecific and variable. The most common clinical manifestation was distention or right upper quadrant pain. Radiological findings are not specific and cannot distinguish primary hepatic neuroendocrine tumor from hepatocellular carcinoma. Diagnosis of primary hepatic neuroendocrine tumor was confirmed immunohistochemically and by the absence of extrahepatic primary sites. No extrahepatic primary lesions were found by ultrasonography, computed tomography, magnetic resonance imaging or positron emission tomography scan either preoperatively or during the follow-up period in our research. Immunohistologically, synaptophysin, chromogranin A and CD56 should be used as markers to precisely diagnose primary hepatic neuroendocrine tumor. The outcome of primary hepatic neuroendocrine tumor is mostly related to its resectability. Total resection of the neoplasm is most commonly proposed. A multimodality of treatments, including chemotherapy, transarterial chemoembolization and radiofrequency ablation, should be used preor postoperatively to improve the survival. CONCLUSIONS: Primary hepatic neuroendocrine tumor is a rare entity, and its diagnosis is difficult. Preoperative fine needle biopsy is strongly recommended, and primary surgery integrated with chemotherapy, transarterial chemoembolization or radiotherapy is considered to be an effective modality for primary hepatic neuroendocrine tumor.


Assuntos
Antineoplásicos/uso terapêutico , Ablação por Cateter/métodos , Quimioembolização Terapêutica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Adulto , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/terapia , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
J Thromb Thrombolysis ; 34(1): 135-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22350625

RESUMO

Hepatic artery thrombosis (HAT) remains one of the major causes of graft failure and mortality in liver transplant recipients. But it is a very rare in non-transplantation patient with the complication of HAT. We reported herein a case of successful urokinase intra-arterial thrombolytic treatment for HAT in an essential polycythemia vera patient following pancreato-biliary surgery. This patient underwent debridement and T-tube drainage in common bile duct for severe pancreatitis and acute suppurative obstructive cholangitis. Significant elevation of liver transaminases and white blood cell counts was noted 30 days after operation and HAT was confirmed by CT-angiography and digital subtracted angiography. Apart from malena and malaise, this patient had scarcity of evident symptoms. The only obvious risk factor relating to HAT is thrombocytosis. This patient was continuously characterized by an excess of platelets from its admission to the onset of HAT. This patient was treated successfully with continuous transcatheter arterial thrombolysis using urokinase. The symptom including malena and malaise disappeared 3 days after thrombolysis. And the patient was treated with hydroxyurea for polycythemia vera thereafter. In conclusion, physicians should be alerted that HAT can be happened in non-transplantation patients especially in those of having hypercoagulability.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Artéria Hepática , Pancreatite/cirurgia , Policitemia Vera/cirurgia , Complicações Pós-Operatórias , Trombose/etiologia , Ductos Biliares/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Policitemia Vera/complicações , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem
18.
Med Oncol ; 29(1): 70-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21190094

RESUMO

Mitochondrial GTPase mitofusin-2 (Mfn2) is a novel gene that remarkably suppresses the injury-mediated proliferation of vascular smooth muscle cells (VSMCs) and has a potential apoptotic effect via the mitochondrial apoptotic pathway. Hepatocellular carcinoma (HCC) tissues and matched normal tissues were examined for mfn2 expression. HCC cells were infected with adenovirus carrying Mfn2 (Ad-mfn2) or green fluorescent protein (Ad-GFP), used as a control. Short hairpin RNA (shRNA) was formed by shR-mfn2 and shR-Bax to repress mfn2 and Bax transcription, respectively. The effects of mfn2 on cell cycle distribution and apoptosis were measured by flow cytometric analysis. Significant downregulation of mfn2 was observed in HCC tissues compared with nearby normal tissues. Overexpression of mfn2 inhibited HCC cell proliferation and induced apoptosis by increasing the level of active caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of mfn2 also induced cytochrome c release to the cytoplasm by enhancing Bax translocation from the cytoplasm to the mitochondrial membrane. Upregulation of mfn2 promoted apoptosis of HCC cells, and this was dramatically suppressed by shR-Bax. Our results show that the mfn2 gene is a potential tumor suppressor target that may significantly promote apoptosis via Bax and may inhibit proliferation in HCC cells. This gene may be an important therapeutic target for the treatment of tumors or hyperproliferative diseases.


Assuntos
Apoptose/genética , Carcinoma Hepatocelular/genética , GTP Fosfo-Hidrolases/genética , Genes Supressores de Tumor/fisiologia , Neoplasias Hepáticas/genética , Proteínas Mitocondriais/genética , Transdução de Sinais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Separação Celular , Citometria de Fluxo , GTP Fosfo-Hidrolases/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Mitocondriais/metabolismo , RNA Interferente Pequeno , Transfecção , Proteína X Associada a bcl-2/metabolismo
19.
Expert Rev Gastroenterol Hepatol ; 5(1): 105-21, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21309676

RESUMO

Liver regeneration is known to be a process involving highly organized and ordered tissue growth triggered by the loss of liver tissue, and remains a fascinating topic. A large number of genes are involved in this process, and there exists a sequence of stages that results in liver regeneration, while at the same time inhibitors control the size of the regenerated liver. The initiation step is characterized by priming of quiescent hepatocytes by factors such as TNF-α, IL-6 and nitric oxide. The proliferation step is the step during which hepatocytes enter into the cell cycle's G1 phase and are stimulated by complete mitogens including HGF, TGF-α and EGF. Hepatic stimulator substance, glucagon, insulin, TNF-α, IL-1 and IL-6 have also been implicated in regulating the regeneration process. Inhibitors and stop signals of hepatic regeneration are not well known and only limited information is available. Furthermore, the effects of other factors such as VEGF, PDGF, hypothyroidism, proliferating cell nuclear antigen, heat shock proteins, ischemic-reperfusion injury, steatosis and granulocyte colony-stimulating factor on liver regeneration are also systematically reviewed in this article. A tissue engineering approach using isolated hepatocytes for in vitro tissue generation and heterotopic transplantation of liver cells has been established. The use of stem cells might also be very attractive to overcome the limitation of donor liver tissue. Liver-specific differentiation of embryonic, fetal or adult stem cells is currently under investigation.


Assuntos
Proliferação de Células , Hepatócitos/citologia , Regeneração Hepática/fisiologia , Animais , Hepatócitos/fisiologia , Humanos , Modelos Animais , Ratos , Transdução de Sinais/fisiologia , Transplante de Células-Tronco , Engenharia Tecidual
20.
Biochem Biophys Res Commun ; 400(4): 587-92, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20804729

RESUMO

The tumor suppressor p53 modulates transcription of a number of target genes involved in cell cycle arrest, apoptosis, DNA repair, and other important cellular responses. Mitofusin-2 (Mfn2) is a novel suppressor of cell proliferation that may also exert apoptotic effects via the mitochondrial apoptotic pathway. Through bioinformatics analysis, we identified a p53 binding site in the Mfn2 promoter. Consistent with this, we showed that the p53 protein binds the Mfn2 promoter directly both in vitro and in vivo. Additionally, we found that Mfn2 mRNA and protein levels are up-regulated in a p53-dependent manner. Furthermore, luciferase assays revealed that the activity of the wild-type Mfn2 promoter, but not a mutated version of the promoter, was up-regulated by p53. These results indicate that Mfn2 is a novel p53-inducible target gene, which provides insight into the regulation of Mfn2 and its associated activities in the inhibition of cell proliferation, promotion of apoptosis, and modulation of tumor suppression.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Imunoprecipitação da Cromatina , Sequência Consenso , Doxorrubicina/farmacologia , GTP Fosfo-Hidrolases , Humanos , Regiões Promotoras Genéticas
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