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BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.
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Carcinoma Hepatocelular , Células Estreladas do Fígado , Interleucina-17 , Neoplasias Hepáticas , Animais , Humanos , Masculino , Ratos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Endopeptidases/metabolismo , Endopeptidases/genética , Regulação Neoplásica da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Interleucina-17/metabolismo , Interleucina-17/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Ratos Sprague-Dawley , Microambiente TumoralRESUMO
OBJECTIVE: Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: The clinical data of 1,602 patients with hepatitis B-related HCC who underwent partial hepatectomy in our department were retrospectively studied. The patients were divided into three groups according to their preoperative HBV DNA levels: group A <200 IU/mL, group B 200-20,000 IU/mL, and group C >20,000 IU/mL. The rates of postoperative complications, especially the rate of postoperative liver failure, were compared. RESULTS: There were significant differences among the three groups in the rates of postoperative liver failure. On multivariate logistic regression analysis, a high preoperative HBV DNA level was an independent risk factor for postoperative liver failure. CONCLUSIONS: Preoperative HBV DNA level was a significant risk factor for postoperative hepatic dysfunction.
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Carcinoma Hepatocelular/cirurgia , DNA Viral/sangue , Hepatectomia/efeitos adversos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Falência Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Falência Hepática/prevenção & controle , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: This study aimed to clarify the incidence of hepatitis B virus (HBV) reactivation and its significance on long-term survival after partial hepatectomy in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative low HBV-DNA level of less than 2000 IU/mL. BACKGROUND: HBV reactivation is a frequent complication of systemic chemotherapy in hepatitis B surface antigen-positive patients. Surgery and anesthesia result in a generalized state of immunosuppression in the immediate postoperative period. Data on HBV reactivation and its significance after partial hepatectomy are unclear. PATIENTS AND METHODS: Consecutive patients from January 2006 to December 2007 were retrospectively studied. RESULTS: HBV reactivation happened in 19.1% of patients in 1 year. There were 28 patients whose HBV reactivation was detected after the diagnosis of HCC recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity, preoperative HBV-DNA above the lower limit of quantification (≥200 IU/mL), Ishak inflammation score of greater than 3, preoperative transarterial chemoembolization (TACE), operation time of more than 180 minutes, blood transfusion, and without prophylactic antiviral therapy were significantly associated with an increased risk of HBV reactivation. HBV reactivation negatively influenced postoperative hepatic functions. The posthepatectomy liver failure rate in patients with HBV reactivation was significantly higher than in those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free survival (DFS) rate and overall survival (OS) rates after resection in patients with HBV reactivation were significantly lower than those without reactivation (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score, preoperative TACE, long operation time, and blood transfusion were independent risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL or more, tumor diameter greater than 5 cm, presence of satellite nodules, presence of portal vein tumor thrombus, blood transfusion, and resection margin less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200 IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater than 5 cm, the presence of satellite nodules, the presence of portal vein tumor thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy, and HBV reactivation were independent risk factors for OS. CONCLUSIONS: HBV reactivation was common after partial hepatectomy for HBV-related HCC with a preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic antiviral treatment should be given before partial hepatectomy.
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Carcinoma Hepatocelular/virologia , Hepatectomia , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/mortalidade , Medição de Risco , Ativação Viral , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , China/epidemiologia , DNA Viral/análise , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Carga ViralRESUMO
PURPOSE: To correlate early HBV-DNA suppression by antiviral treatment with posthepatectomy long-term survivals in patients with HBV-related hepatocellular carcinoma (HCC). METHODS: A retrospective study was conducted on patients with a baseline HBV-DNA load of >2,000 IU/ml. The cumulative rates of HBV-DNA undetectability at weeks 24 and 48, as well as long-term tumor recurrence and overall survivals were determined. RESULTS: Of 1,040 patients with a high baseline HBV-DNA load, 865 patients received antiviral treatment. At a median follow-up of 42 months, 616 patients (59.2 %) had developed HCC recurrence and 482 patients (46.3 %) had died. The median time to recurrence was 25 months. In patients who received antiviral treatment, the cumulative rates of HBV-DNA undetectability (<200 IU/ml) were 54.3 and 88.1 % at weeks 24 and 48, respectively. There was no significant difference between the two groups of patients who received antiviral treatment or not for disease-free survival. On multivariate analyses, tumor size >5 cm, blood transfusion, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak inflammation score were significant risk factors of HCC recurrence. Also, tumor size >5 cm, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak fibrosis score were significant factors associated with poor postoperative overall survival. On the other hand, an undetectable HBV-DNA level before week 24 was a significant protective factor of disease-free survival and overall survival. CONCLUSIONS: Early HBV-DNA suppression with antiviral treatment improved prognosis of patients with HBV-related HCC.
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Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/virologia , Carga Viral , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/patologia , DNA Viral/sangue , Intervalo Livre de Doença , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Humanos , Estimativa de Kaplan-Meier , Lamivudina/uso terapêutico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Organofosfonatos/uso terapêutico , Veia Porta/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND/AIMS: Our aim was to compare the postoperative outcomes of partial hepatectomy using Pringle maneuver and selective main portal vein clamping. METHODOLOGY: From January 2004 to December 2006, 169 consecutive patients received liver resection by the same surgical team. The surgical techniques were the same for all patients except for the hepatic vascular inflow occlusion techniques during liver parenchymal transection. Patients either received clamping of the portal triad (PTC group, n=118) or selective main portal vein clamping (PVC group, n=51). RESULTS: Operative time to carry out PVC was significantly longer than PTC (110.6±21.8 vs. 129.6±29.8min), however intraoperative blood loss was the same. There was no significant difference in operative mortality or morbidity rates, although the liver function recovered quicker in the PVC group. Significantly more patients in the PTC group developed HCC recurrence at postoperative one year than the PVC group (60.2% vs. 33.3%). There was no significant difference in overall survival between the 2 groups. Univariate analysis showed that clamping method, tumor size and BCLC grade were risk factors for disease-free survival (DFS) at one year, and multivariate analyses demonstrated clamping method and AFP level as independent risk factors for DFS. CONCLUSIONS: Patients subjected to selective portal vein clamping did better than those to Pringle maneuver in the postoperative outcomes. The underlying mechanism may be I/R injury of the liver remnant which might also contribute to an increase in tumor recurrence after liver resection.
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Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/terapia , Veia Porta , Adulto , Antineoplásicos/administração & dosagem , Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/terapia , Constrição , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado/fisiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/prevenção & controle , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , Neoplasias da Coluna Vertebral/secundário , Fatores de TempoRESUMO
OBJECTIVE: To investigate the application of an improved method of hepatic vein occlusion with Satinsky clamp when resecting the liver tumor involving second hepatic portal. METHODS: From January 2003 to December 2010, there were totally 330 patients with liver tumor admitted, who underwent liver resection with Pringle maneuver plus hepatic vein occlusion with Satinsky clamp. Data regarding the intra-operative and post-operative course of the patients were analyzed. There were 245 male and 85 female patients, with a mean age of (50 ± 11) years. The diameter of tumor was (9 ± 6) cm. Among the 330 patients, there were 271 patients with viral hepatitis B, 215 patients with liver cirrhosis; 321 patients were in Child class A of liver function and 9 in class B. Pringle maneuver plus hepatic vein occlusion with Satinsky clamp was used to occlude the blood flow in the liver resection. The liver transection was performed with clamp-crushing technique. RESULTS: Hepatic vein occlusion with Satinsky clamp was successful in all 330 patients. The operation time was (132 ± 29) minutes, while (7 ± 3) minutes for dissecting hepatic vein and (22 ± 7) minutes for inflow blood occlusion. The blood loss in operation was (480 ± 265) ml, with 20% of patients receiving blood transfusion. No patient had large hemorrhage and air embolism due to hepatic vein laceration. No patient died in the perioperative period. The complications included 31 patients of pleural effusion, 14 patients of seroperitoneum, 10 patients of biliary fistula, 2 patients of massive blood loss during liver resection and 2 patients of re-bleeding after operation. CONCLUSION: The method of hepatic vein occlusion with Satinsky clamp was safe and effective.
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Veias Hepáticas/cirurgia , Neoplasias Hepáticas/cirurgia , Instrumentos Cirúrgicos , Adulto , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Oclusão TerapêuticaRESUMO
BACKGROUND: Due to the rarity of primary hepatic malignant fibrous histiocytoma (MFH), the natural history, optimal management and prognosis are poorly characterized. METHODOLOGY: Between January 2003 and December 2008, we treated 12 consecutive patients with primary hepatic MFH. The patient demographics, tumor characteristics, type of treatment and actuarial survival were analyzed. RESULTS: The mean +/- SD tumor size was 8.4 +/- 3.2cm. Four patients had satellite lesions. R0, R1 and R2 resection of the liver tumor were achieved in 5, 2 and 5 patients, respectively. There was no hospital mortality and the complication rate was 8.3%. At a median follow-up of 11.3 months, local recurrence had occurred in 6 patients and local recurrence + distant metastases in 3 patients. Most patients (8/12) died of the tumor within a year after surgery, with a median survival of 6.1 months. For the remaining 4 patients, 2 patients had undergone surgery for less than 1 year previously, one patient who had a R0 liver resection with extrahepatic metastasis survived for 14 months with multiple metastases, and another patient who had a R0 liver resection but without extrahepatic metastasis survived for 60 months and was disease free. The median survival for the R0 liver resection group carried out in patients without extrahepatic metastases was 8.5 months, while the median survival of the debulking group (R0 liver resection with extrahepatic metastasis/ R1 or R2 liver resection) was 7 months. There was no significant difference in survival between the two groups. CONCLUSION: Hepatic resection was safe for patients with primary MFH with a poor prognosis. Complete resection offers the only hope of long-term disease free survival.
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Histiocitoma Fibroso Maligno/cirurgia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Hepatectomia , Histiocitoma Fibroso Maligno/diagnóstico , Histiocitoma Fibroso Maligno/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To predict patient survival in early-stage hepatocellular carcinoma (HCC) following hepatic resection. We evaluated the prognostic potential of the aspartate aminotransferase to platelet ratio index (APRI) in order to use it to model a nomogram. PATIENTS AND METHODS: We randomized 901 early-stage HCC patients treated with hepatic resection at our center into training and validation cohorts that were followed from January 2009 to December 2012. X-tile software was used to establish the APRI cut-off threshold in the training cohort. The validation cohort was subsequently assessed to determine threshold value accuracy. Data generated from the multivariate analysis in the training cohort were used to design a prognostic nomogram. Decision curve analyses (DCA), concordance index values (C-index) and calibration curves were used to determine the performance of the nomogram. RESULTS: X-tile software revealed that the optimal APRI cut-off threshold in the training cohort that distinguished between patients with different prognoses was 0.9. We, therefore, validated its prognostic value. Multivariate analyses showed that poor overall survival was associated with APRI above 0.9, blood loss of more than 400 mL, liver cirrhosis, multiple tumors, tumor size greater than 5 cm, microvascular invasion and satellite lesions. When the independent risk factors were integrated into the prognostic nomogram, it performed well with accurate predictions. Indeed, the performance was better than comparative prognosticators (P<0.05 for all) with 0.752 as the C-index (95% CI: 0.706-0.798). These results were verified by the validation cohort. CONCLUSION: APRI was a noninvasive and accurate predictive indicator for patients with early-stage HCC. Following hepatic resection to treat early-stage HCC, individualized patient survival predictions can be aided by the nomogram based on APRI.
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BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare condition. The aim of the present study was to evaluate the clinical characteristics and surgical outcomes for IMT of the liver in our large cohort of patients. METHODS: From January 2001 to December 2007, all patients with a pathological diagnosis of IMT of the liver who underwent partial hepatectomy were retrospectively analyzed. RESULTS: During the study period, 64 patients underwent partial hepatectomy for IMT of the liver in our tertiary referral center. The commonest clinical presentation was abdominal pain (53%), followed by fever (41%); 15.6% of patients were asymptomatic. Preoperative diagnosis of IMT was suspected in only five patients (8%). The indications for surgery included suspicion of malignancy (60.9%), uncertain diagnosis (40.6%), symptomatic disease (26.6%), and spontaneous rupture (3.1%). The postoperative complication rate was low (17.2%). There was no hospital mortality. After a median follow-up of 30 months, no patient developed recurrence. CONCLUSIONS: Although there are various treatment options for IMT of the liver, surgical resection for good risk patients is preferred.
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Granuloma de Células Plasmáticas/cirurgia , Neoplasias Hepáticas/cirurgia , Idoso , Estudos de Coortes , Diagnóstico por Imagem , Feminino , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Objective: To evaluate the importance of preoperative blood platelet to lymphocyte ratio (PLR) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver surgery and to examine the connection with CD8+ lymph cell infiltration. Methods: Between 2009 and 2014, consecutive HCC patients who received curative liver surgery were included into this retrospective study. Baseline clinicopathological characteristics were analyzed to identify predictors of recurrence-free and overall patient survival rate after liver resection. The samples of all patients were under Tissue Microarray (TMA) construction and immunohistochemical staining for CD8+.The association of the number of CD8+T-cells in the cancer nests and peritumoral stroma with PLR level was analyzed. Results: A total of 1,174 HBV-related HCC patients who received a liver resection without any peri-operative adjuvant therapy were enrolled into this retrospective study. Univariate and Multivariate analysis using Cox regression model showed that PLR was an independent factor affecting recurrence and overall survivals. The optimal cutoff of PLR using the receiver operating characteristic curve was 150. There were 236 patients (20.1%) who had a PLR of 150 or more. The 5-year survival rate after liver resection was 71.8% in patients with a PLR of < 150 and it was 57.2% in those with a PLR of 150 or more (P < 0.001). Both 5-year recurrence-free and overall survival rates in liver cancer stage A patients at Barcelona Clinic with different PLR group were also significantly different (P = 0.007 for recurrence and P = 0.001 for overall survival). Similar results were also observed in stage B patients (P < 0.001 for recurrence and P = 0.033 for overall survival). To determine the association between PLR and the severity of liver inflammation, an immuno-histological examination using CD8+ staining was performed on the liver specimens of 1,174 patients. Compared with low PLR (<150) group, more CD8+T-cells were found in the peritumoral tissue in high PLR (≥ 150) group. Conclusions: PLR played as an independent factor for predicting the survival after hepatectomy for HCC patients. A high PLR was associated with an accumulation of CD8+ T-cells in the peritumoral stroma.
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OBJECTIVE: To evaluate the effect of preoperative transarterial chemoembolization (TACE) for resectable large hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Resection of HCC is potentially curative, but local recurrence is very common. There is currently no effective neoadjuvant or adjuvant therapy. METHODS: From July 2001 to December 2003, 108 patients (hepatitis B carrier = 98.1%) with resectable HCC (> or =5 cm) was randomly assigned to preoperative TACE treatment (n = 52) or no preoperative treatment (control group) (n = 56). RESULTS: Five patients (9.6%) in the preoperative TACE group did not receive surgical therapy because of extrahepatic metastasis or liver failure. The preoperative TACE group had a lower resection rate (n = 47, 90.4% vs. n = 56, 100%; P= 0.017), and longer operative time (mean, 176.5 minutes vs. 149.3 minutes; P= 0.042). No significant difference was found between the 2 groups in operative blood loss, surgical morbidity, and hospital mortality.At a median follow-up of 57 months, 41 (78.8%) of 52 patients in the preoperative TACE group and 51 (91.1%) of 56 patients in the control group had recurrent disease (P= 0.087). The 1-, 3-, and 5-year disease-free survival rates were 48.9%, 25.5%, and 12.8%, respectively, for the preoperative TACE group and 39.2%, 21.4%, and 8.9%, respectively, for the control group (P= 0.372). The 1-, 3-, and 5-year overall survival rates were 73.1%, 40.4%, and 30.7%, respectively, for the preoperative TACE group and 69.6%, 32.1%, and 21.1%, respectively, for the control group (P= 0.679). CONCLUSIONS: Preoperative TACE did not improve surgical outcome. It resulted in drop-out from definitive surgery because of progression of disease and liver failure.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To report our experience on the safety and efficacy of hepatic resection under selective hepatic vascular exclusion (SHVE). METHODS: SHVE was used in 246 consecutive patients undergoing major or complex liver resection in our center. Preoperative demographic and clinical data, details of the surgical procedure, pathologic diagnosis, postoperative course, and complications were collected prospectively. RESULTS: From January 2000 to July 2007, liver resections were performed under SHVE in 246 patients; total SHVE, right partial SHVE, and left partial SHVE in 145, 54, and 47 patients, respectively. SHVE was converted to total hepatic vascular exclusion in 3 patients because the tumor invaded the wall of the inferior vena cava. Hemodynamic tolerance to SHVE was excellent, with only a slight increase in systemic and pulmonary vascular resistance during clamping. There were no deaths and the morbidity rate was 24.8%. The mean hospital stay was 9.6 days (range, 8-18). CONCLUSION: Our study showed that SHVE was safe, efficacious, and it was applicable to liver tumors which were near, but had not invaded into the inferior vena cava.
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Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia Cirúrgica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/irrigação sanguínea , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Constrição , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/prevenção & controle , Fígado/cirurgia , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios/métodos , Probabilidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Veia Cava Inferior , Adulto JovemRESUMO
BACKGROUND: Most liver resections require clamping of the hepatic pedicle (Pringle maneuver) to avoid excessive blood loss. But Pringle maneuver can not control backflow bleeding of hepatic vein. Resection of liver tumors involving hepatic veins may cause massive hemorrhage or air embolism from the injuries of the hepatic veins. Although total hepatic vascular exclusion can prevent bleeding of the hepatic veins effectively, it also may result in systemic hemodynamic disturbance because of the inferior vena cava being clamped. Hepatic venous occlusion, a new technique, can control the inflow and outflow of the liver without clamping the vena cava. METHODS: A total of 71 cases of liver tumors underwent resection with occlusion of more than one of the main hepatic veins. All tumors involved the second porta hepatis and at least one main hepatic vein. Ligation or occlusion with serrefines, tourniquets and auricular clamps were used in hepatic venous occlusion. RESULTS: Of the 71 patients, ligation of the hepatic veins was used in 28 cases, occlusion with a tourniquet in 26, and occlusion with a serrefine in 17. Right hepatic veins were occluded in 38 cases, both right and middle hepatic veins in 2, the common trunk of the left and middle hepatic veins in 24, branches of the left and middle hepatic veins in 2, and all three hepatic veins in 5. Thirty-five cases underwent hemihepatic vascular occlusion, 4 alternate hemihepatic vascular occlusion, 23 portal triad clamping plus selective hepatic vein occlusion, and 9 portal triad clamping plus total hepatic vein occlusion. The third porta hepatis was isolated in 26 cases. The amount of intraoperative blood loss averaged (540 +/- 283) (range 100 to 1000) ml in the group of total hemihepatic vascular occlusion and in the group of alternate hemihepatic vascular occlusion, (620 +/- 317) (range 200 - 6000) ml in the group of portal triad clamping plus selective or total hepatic vein occlusion. All tumors were completely removed. CONCLUSIONS: Hepatic venous occlusion applied in hepatectomy can prevent bleeding and air embolism, and is safe and effective with stable hemodynamics.
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Hepatectomia/métodos , Veias Hepáticas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Hemorragia/etiologia , Hepatectomia/efeitos adversos , Humanos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVE: To compare the effects of selective hepatic vascular exclusion (SHVE) and Pringle maneuver in resecting the liver tumors involving the second porta hepatis. METHODS: From January 2000 to October 2005, 2100 liver tumors were resected, among which 235 tumors adhered to or were very close to one or more hepatic veins. Both SHVE and Pringle maneuver were used to control the blood loss during the hepatectomy. They were divided into two groups: SHVE group (125 cases) and Pringle group (110 cases). Data regarding the intra-operative and postoperative courses of the patients were analyzed. SHVE group included total SHVE (clamping of the porta hepatis and all major hepatic veins) in 25 cases and partial SHVE (clamping of the porta hepatic and one or two hepatic veins) in 100 cases. Three methods were used to occlude hepatic veins: be ligated with suture, be encircled and occluded with tourniquets and be clamped with Shatinsky clamps directly. RESULTS: There was no difference between the 2 groups regarding the age, sex, tumor size, cirrhosis and HBsAg positive rate, ischemia time and operating time (P > 0.05). Intra-operative blood loss and transfusion requirements were decreased significantly in the SHVE group. Hepatic veins ruptured with massive blood loss in 14 and air embolism in 3 in Pringle group, but there was no massive blood loss and air embolism in SHVE group. Postoperative bleeding, reoperation, liver function failure and mortality rate were higher in Pringle group (P < 0.05), ICU stay and hospital stay were longer in Pringle group (P < 0.05). CONCLUSIONS: SHVE is much more effective than Pringle maneuver for controlling intraoperative bleeding. It can prevent massive blood loss and air embolism resulting from hepatic veins ruptured and can reduce the postoperative complications rate and mortality rate. Clamping the hepatic veins with Shatinsky clamp is safer and easier than encircled and occluded with tourniquets.
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Hepatectomia/métodos , Veias Hepáticas/cirurgia , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controleRESUMO
Zinc finger protein X-linked (ZFX) is frequently upregulated in multiple human malignancies and also plays a critical role in the maintenance of self-renewal in embryonic stem cells. However, the role of ZFX in liver cancer stem cells (CSCs) remains obscure. We observed that the elevated expression of both ZFX and epithelial cell adhesion molecule (EpCAM) was associated with aggressive clinicopathological features and indicated poor prognosis in patients with hepatocellular carcinoma (HCC). ZFX was commonly enriched in liver EpCAM+ CSCs. Knockdown of ZFX decreased the proportion of EpCAM+ CSCs in HCC cells and suppressed their expression of stemness-related genes, self-renewal capacity, chemoresistance, metastatic potential, and tumorigenicity. Conversely, upregulation of ZFX in CSCs rescued these inhibitory effects and enhanced stem-like properties. Mechanistically, depletion of ZFX reduced nuclear translocation and transactivation of ß-catenin, thereby inhibiting the self-renewal capacity of EpCAM+ CSCs. Moreover, knockdown of ß-catenin attenuated the self-renewal of EpCAM+ HCC cells stably expressing ZFX, further indicating that ß-catenin is required for ZFX-mediated expansion and maintenance of EpCAM+ CSCs. Taken together, our findings indicate that ZFX activates and maintains EpCAM+ liver CSCs by promoting nuclear translocation and transactivation of ß-catenin. Furthermore, combination of ZFX and EpCAM may serve as a significant indicator for prognosis of patients with HCC.
Assuntos
Carcinoma Hepatocelular/patologia , Molécula de Adesão da Célula Epitelial/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/metabolismo , Dedos de Zinco , Idoso , Análise de Variância , Animais , Carcinoma Hepatocelular/metabolismo , Autorrenovação Celular/fisiologia , Resistencia a Medicamentos Antineoplásicos , Molécula de Adesão da Célula Epitelial/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Prognóstico , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Despite the therapeutic advances that have been achieved during the past decade, the molecular pathogenesis underlying HCC remains poorly understood. In this study, we discovered that increased expression eukaryotic translation initiation factor 5B (eIF5B) was significantly correlated with aggressive characteristics and associated with shorter recurrence-free survival (RFS) and overall survival (OS) in a large cohort. We also found that eIF5B promoted HCC cell proliferation and migration in vitro and in vivo partly through increasing ASAP1 expression. Our findings strongly suggested that eIF5B could promote HCC progression and be considered a prognostic biomarker for HCC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Fatores de Iniciação em Eucariotos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Intervalo Livre de Doença , Seguimentos , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Fígado/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Análise Serial de Tecidos , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Zinc finger CCCH-type containing 15 (ZC3H15), also known as DRG family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein that associates with active translation machinery. The aim of our study was to explore the clinical relevance and intrinsic functions of ZC3H15 in hepatocellular carcinoma (HCC). We constructed a cohort with 261 tumor and matched normal tissues from HCC patients. ZC3H15 protein and mRNA levels were determined using immunohistochemistry, western blot analysis, and quantitative polymerase chain reaction. ZC3H15 was highly expressed in the majority of HCC cases, and high ZC3H15 levels were significantly associated with high serum a-fetoprotein (AFP) levels (>20 ng/mL) and vascular invasion. Kaplan-Meier and Cox regression data indicated that elevated ZC3H15 was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.789; 95% confidence interval [95% CI], 1.298-2.466 [P=0.0004]) and overall survival (HR, 1.613; 95% CI, 1.120-2.322 [P=0.0101]). Interaction of ZC3H15 with TRAF2 increased activation of NFκB signaling. These results suggest ZC3H15 is an independent prognostic marker in HCC patients that is clinicopathologically associated with tumor invasion and serum AFP levels.
Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Proteínas de Transporte/genética , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Invasividade Neoplásica , Prognóstico , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , Análise Serial de Tecidos , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: Complete caudate lobectomy using the anterior hepatic parenchymal transection approach is a proper but technically demanding operation for tumors situated in or involving the paracaval portion of the caudate lobe. This study was intended to share our experience on this operation. METHOD: Forty-nine consecutive patients who received complete caudate lobectomy using the anterior hepatic parenchymal transection approach were studied. The clinicopathologic and perioperative data, complications, and survival were analyzed. RESULTS: Of the 49 patients, 15 (30.6 %) received isolated complete caudate lobectomy and 34 (69.4 %) received complete caudate lobectomy associated with segmentectomy IV. The median tumor size was 7.3 cm (2.4-18.0 cm), the operating time was 200 min (120-370 min), and the operative blood loss was 700 ml (200-3000 ml). The postoperative complication rate was 36.7 %. There was no perioperative death. Patients in the associated complete caudate lobectomy group had larger tumors (P<0.001), higher platelet counts (P=0.033), shorter operation time (P=0.004), and less patients with residual tumor (P=0.03) than those in the isolated complete caudate lobectomy group. There were no significant differences in cirrhosis, surgical resection margin, blood loss, postoperative complications, and prognosis between the two groups. CONCLUSION: Complete caudate lobectomy using the anterior hepatic parenchymal transection approach was technically feasible and safe for patients with tumors situated in or involving the paracaval portion of the caudate lobe. Associated resection of segment IV can be used to facilitate the surgery and decrease the chance of local residual tumor.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica , Feminino , Humanos , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Duração da Cirurgia , Complicações Pós-Operatórias , PrognósticoRESUMO
Massive blood loss remains a problem during resection for giant liver hemangioma. This present study was designed to compare selective hepatic vascular exclusion (SHVE) versus Pringle maneuver in surgery for liver hemangioma compressing the major (right, middle, or left) hepatic veins. From January 2003 to December 2011, 589 consecutive patients with hemangioma underwent liver resection in our department, and 273 patients had their tumors compressing at least one of the three major hepatic veins (right, middle, or left). Either SHVE (n = 120 patients) or Pringle maneuver (n = 153 patients) was used to minimize blood loss during resection. Data regarding the intraoperative and postoperative courses of these patients were retrospectively analyzed. There was no significant difference between the two groups of patients regarding age, sex, tumor size, types of hepatectomy, and extent of tumor involvement of the major hepatic veins. Intraoperative blood loss, transfusion requirements, and transfusion volume were significantly less in the SHVE group (P < 0.01). For the Pringle group, major hepatic veins were lacerated in 19 patients during hepatic parenchymal transection. For the SHVE group, a major hepatic vein was lacerated during extrahepatic dissection of the hepatic vein in two patients and during hepatic parenchymal transection in 14 patients. SHVE was more efficacious in minimizing intraoperative bleeding during liver resection for hemangiomas compressing the major hepatic veins. It prevented intraoperative major bleeding and air embolism and significantly decreased postoperative liver failure and in-hospital mortality.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemangioma/cirurgia , Hepatectomia/métodos , Veias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Hemangioma/diagnóstico , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Veias Hepáticas/cirurgia , Mortalidade Hospitalar , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: Based on a large series of histopathologically confirmed hepatic angiomyolipomas, we retrospectively studied the typical diagnostic features of hepatic angiomyolipoma and proposed a treatment strategy for this disease. MATERIALS AND METHODS: From December 1997 to December 2007, 74 consecutive patients who received definitive treatment for hepatic angiomyolipoma, at a single tertiary center, were studied. RESULTS: There was a marked female predominance (54 females vs. 20 males) and the mean age was 42 years. Forty patients had no symptoms and the tumors were detected incidentally during a medical check-up. From this study, we proposed the typical diagnostic features of hepatic angiomyolipoma to be the absence of risk factors for malignancy, normal tumor marker levels, and typical imaging features on ultrasound (USG), abdominal contrast computed tomography (CT), or magnetic resonance imaging (MRI). Only 23% of patients could have been diagnosed before surgery using these features. One patient (1.4%) had a malignant angiomyolipoma, and died with distant metastases 14 months after surgery. After a median follow-up of 64 months, there was no recurrence in the other 73 patients. CONCLUSION: Patients with typical diagnostic features suggestive of hepatic angiomyolipoma could be observed with regular surveillance. Definitive treatment should be performed when the tumor has symptoms/complications, when the tumor is enlarging, or when a malignant lesion cannot be ruled out.