Objective To validate the mechanism of effect of hepatic artery ischemia on biliary fibrosis after liver transplantation and the prevention method. Methods Eighteen male dogs were established into the concise auto orthotopic liver transplantation models and assigned into three groups randomly: hepatic artery ischemia (HAI) group, TBB group (transferred the blood by a bridge duct ) and control group, each group contained 6 dogs. After opening portal vein, the samples were cut from liver in each group at the time of 6 h, 3 d and 14 d. The pathological modifications of intrahepatic bile ducts were observed and expression of transforming growth factor-β1 (TGF-β1) were detected in the three times. Expressions of Smad3 and phosphate-Smad3 as well as mRNA of α-smooth muscle actin (α-SMA) in intrahepatic bile ducts were detected 14 d after opening portal vein.Results Compared with control group, the collagen deposition and lumens stenosis in biliary vessel wall were more obviously in HAI group. In TBB group, the pathological modifications were slighter compared with HAI group. The positive cell index of TGF-β1 reached peak on day 3 after opening portal vein, then decreased in TBB group, and which in HAI group kept increase and was significantly higher than that in TBB group （Plt;0.05）. The expression level of phosphate-Smad3 and transcriptional level of α-SMA mRNA were 1.04±0.13 and 1.12±0.55 in TBB group on day 14 after opening portal vein, which were significantly higher than those in control group (0.59±0.09 and 0.46±0.18) and lower than those in HAI group (1.82±0.18 and 1.86±0.73), the diversities among three groups were significant (Plt;0.05). There was not significant difference of expression of Smads among three groups (Pgt;0.05). Conclusions Hepatic artery ischemia could increase the deposition of collagen fibers and the transdifferentiation of myofibroblast in bile duct and result in the biliary fibrosis by activating the TGF-β1/Smads signaling pathway. The bridging bypass device could lessen the biliary fibrosis caused by hepatic artery ischemia by inhibiting the activation of TGF-β1/Smads signal transduction passageway.
Objective To evaluate hepatic functional reserve and investigate the clinical value through measuring hepatic functional blood flow by D-sorbitol clearance rate and liver volume changes with CT. Methods Ninety-two patients with portal hypertension due to posthepatic cirrhosis were investigated (cirrhosis group). Twenty healthy volunteers were used as control group. D-sorbitol was infused intravenously at a steady rate. Blood and urine were collected and recorded once before infusion and at 120, 150 and 180 min after infusion, and their concentrations of D-sorbitol were examined by enzyme spectrophotometry. From pharmacokinetic equations, hepatic clearance rate of D-sorbitol (CLH) was calculated. Total hepatic blood flow (QTOTAL) was measured by Doppler sonography, intrahepatic shunt rate (RINS) was obtained. The liver volume change rate was obtained in patients with cirrhosis through the abdominal CT scan. The relations among the indicators, Child classification and postoperative complications were studied. Results After D-sorbitol was infused intravenously for 120 min, the plasma concentration was at the steady state. The plasma concentration was (0.189±0.05) mmol/L in control group and (0.358±0.06) mmol/L in cirrhosis group (Plt;0.01). CLH was (1 248.3±210.5) ml/min in control group and (812.7±112.4) ml/min in cirrhosis group (Plt;0.01). Although QTOTAL in cirrhosis group was declined, compared with the control group 〔(1 280.6±131.4) ml/min vs. (1 362.4±126.9) ml/min〕, Pgt;0.05, while RINS increased markedly 〔(36.54±10.65)% vs. (8.37±3.32)%, Plt;0.01〕. In cirrhosis group, the mean liver volume of Child A, B and C patients were (1 057±249) cm3, (851±148) cm3 and (663±77) cm3 respectively. There were significant differences among the mean liver volume (Plt;0.05). The liver volume was significantly smaller in Child B and C patients than that in Child A (Plt;0.05, Plt;0.01). When CLH was less than 600 ml/min, and liver volume decreased by more than 40%, postoperative complications increased significantly. CLH and the liver volume change rate were not in absolutely good accordance with Child classification. Conclusion The hepatic clearance of D-sorbitol and the quantitative determination of the liver volume with CT can be an objective evaluation of the liver metabolism of the inherent capacity and the hepatic functional blood flow changes. It contributes to the correct understanding of the hepatic functional reserve and lay the foundation for determining a reasonable treatment plan, surgical methods and time.
Objective To summarize the effect of the splenectomy in patients with portal hypertension on the occurrence and recurrence of hepatocellular carcinoma. Methods The related literatures about the splenectomy in patients with hepatocirrhosis combined with portal hypertension or patients with hepatocellular carcinoma combined with portal hypertension in recent years were reviewed. Results At present, most academics considered that, for patients with hepatocirrhosis combined with portal hypertension, splenectomy could reduce the occurrence of hepatocellular carcinoma. For patients with hepatocellular carcinoma combined with portal hypertension, splenectomy+hepatectomy didn’t increase the perioperative mortality, and it could reduce the recurrence rate of hepatocellular carcinoma. Conclusion Splenectomy for patients with portal hypertension is safe, and it can inhibit the occurrence and progress of hepatocellular carcinoma, however, the specific mechanism remain needs further study.
ObjectiveTo explore the effects of hypoxia inducible factor-1 alpha (HIF-1α) on the reverse differentiation of hepatocellular carcinoma cells into liver cancer stem cells, and the maintenance of malignant biological behavior in hypoxic environment.MethodsCD133-negative cells in HepG2 cells were separated by immunomagnetic beads and divided into two groups. The cells of siRNA group were transfected with siRNA-HIF-1α to silence the expression of HIF-1α gene, while cells of the blank control group did not transfect any siRNA fragments. The two groups of cells were cultured under normal and hypoxic conditions respectively. MTT, cloning and Transwell chamber experiments were used to detect the proliferation and invasion ability of cells. Western blot and real-time PCR (RT-PCR) were used to detect the expressions of HIF-1α, CD133, CD90, and CD44 protein and mRNA in cells.ResultsMTT results showed that the cell proliferation rate increased with the prolongation of hypoxia in four groups. Compared with the blank control group at 24, 32, 40, and 48 hours, the cell proliferation rate decreased significantly after siRNA-HIF-1a transfection, on both two kinds of cultured conditions (P<0.05). The results of plate cloning experiment showed that the number of cell-forming clones increased significantly after hypoxic culture (there were significant differences between the transfected normoxic group and transfected hypoxic group, blank control normoxic group and blank control hypoxic group, P<0.05); and the formation of transfected hypoxic condition group at the same time of hypoxia was also significant (P<0.05). The number of clones were significantly less than that of the blank control group at the hypoxic condition (P<0.05). Transwell lab experiment showed that after hypoxic culture, the number of cells migrated to the inferior chamber in the transfection group was significantly reduced compared with that of the blank control group (P<0.05). Western blot and RT-PCR results showed that the expression levels of HIF-1α protein and tumor stem cell markers (CD133, CD90, and CD44 protein) in the blank control hypoxic condition group were significantly higher than those in the other three groups (P<0.05); after siRNA-HIF-1a transfection, HIF-1α mRNA and tumor stem cell markers mRNA (CD133, CD90, and CD44 mRNA) in the transfected hypoxic condition group were significantly lower than those in the transfected normal condition group and the blank control normal condition group (P<0.05).ConclusionsIn hypoxia environment, HIF-1α can promote hepatocellular carcinoma cells to differentiate into liver cancer stem cells and enhance their malignant biological behavior.
【Abstract】Objective The injury induced by hepatic artery ischemia (HAI) in the liver transplantation procedure and the protective effects of using hepatic artery bridge-conduit (HABC) technique were studied. Methods Thirtytwo dogs were randomly divided into 4 groups: control, HAI 30 min, HAI 2 h and HABC groups. We observed the pathological changes of hepatocytes and biliary tract tissues and the microstructure of chondriosome, which were based on the model of auto-orthotopic liver transplantation in dogs. Biochemical and spectrophotometric methodswere used to evaluate the content of MDA and SOD, SDH activities in the graft liver tissue respectively. Results The pathologic and electrical microscopic changes of hepatocytes and epithelial cells of bile ducts were found in HAI 30 min and HAI 2 h groups,while the content of MDA increased to （1.652±0.222） nmol/mg prot and (2.379±0.526) nmol/mg prot, and SOD activity decreased to (11.15±3.9) U/mg prot and (9.47±3.4) U/mg prot. At the same time, SDH activity was also down-regulated to 0.362±0.019 and 0.281±0.029. Compared with control group, the differences were significant (Plt;0.05, Plt;0.01). But these changes of functional index caused by HAI injury were not significant in HABC group. Conclusion The HABC technique can not only avoid HAI injury during operation but also alleviate the occurrence of complication after transplantation, especially the biliary tract complication.
【Abstract】Objective To investigate the influence of hepatectomy combined with splenectomy on curative effect of primary hepatocellular carcinoma patients associated with hypersplenism.Methods Twenty three cases of primary hepatocellular carcinoma associated with hypersplenism were analyzed retrospectively and divided into hepatectomy combined with splenectomy group (n=10) and hepatectomy combined with ligation of splenic artery (n=13). Peripheral blood samples were collected 1 week before operation and 3 monthes after operation respectively. The levels of CD4, CD8, CD16, CD4/CD8, WBC and PLT in the blood were detected. Survival rate between the two groups was compared. Results There were not significant differences in the expressional levels of CD4, CD8, CD16, CD4/CD8,WBC and PLT before operation, bleeding quantity during the operation and rate of severe complications after operation in the two groups. The expressional levels of CD4, CD16, CD4/CD8, WBC and PLT of hepatectomy combined with splenectomy group were much higher in 3 months after operation than those in 1 week before operation and in hepatectomy combined with ligation of splenic artery group (P＜0.01) and the latter with no distinct changes of the above indexes. There was no difference of survival rate between the two groups. But in the hepatectomy combined with ligation of splenic artery group, 7 patients of 13 patients were compelled to terminate chemotherapy because of their low WBC while not a single patient was forced to do so in the hepatectomy combined with splenectomy group. Conclusion Hepatectomy combined with splenectomy is useful for patients with hepatocellular carcinoma associated with hypersplenism to restore the immunological function and the application of chemotherapy after operation.
Objective Establishing Nomogram to predict the overall survival (OS) rate of patients with gastric adenocarcinoma by utilizing the database of the Surveillance, Epidemiology, and End Results (SEER) Program. Methods Obtained the data of 3 272 gastric adenocarcinoma patients who were diagnosed between 2004 and 2014 from the SEER database. These patients were randomly divided into training (n=2 182) and validation (n=1 090) cohorts. The Cox proportional hazards regression model was performed to evaluate the prognostic effects of multiple clinicopathologic factors on OS. Significant prognostic factors were combined to build Nomogram. The predictive performance of Nomogram was evaluated via internal (training cohort data) and external validation (validation cohort data) by calculating index of concordance (C-index) and plotting calibration curves. Results In the training cohort, the results of Cox proportional hazards regression model showed that, age at diagnosis, race, grade, 6th American Joint Committee on Cancer (AJCC) stage, histologic type, and surgery were significantly associated with the survival prognosis (P<0.05). These factors were used to establish Nomogram. The Nomograms showed good accuracy in predicting OS rate, with C-index of 0.751 ［95%CI was (0.738, 0.764)］ in internal validation and C-index of 0.753 ［95% CI was (0.734, 0.772)］ in external validation. All calibration curves showed excellent consistency between prediction by Nomogram and actual observation. Conclusion Novel Nomogram for patients with gastric adenocarcinoma was established to predict OS in our study has good prognostic significance, it can provide clinicians with more accurate and practical predictive tools which can quickly and accurately assess the patients’ survival prognosis individually, and can better guiding clinicians in the follow-up treatment of patients.
The background of abdominal computed tomography (CT) images is complex, and kidney tumors have different shapes, sizes and unclear edges. Consequently, the segmentation methods applying to the whole CT images are often unable to effectively segment the kidney tumors. To solve these problems, this paper proposes a multi-scale network based on cascaded 3D U-Net and DeepLabV3+ for kidney tumor segmentation, which uses atrous convolution feature pyramid to adaptively control receptive field. Through the fusion of high-level and low-level features, the segmented edges of large tumors and the segmentation accuracies of small tumors are effectively improved. A total of 210 CT data published by Kits2019 were used for five-fold cross validation, and 30 CT volume data collected from Suzhou Science and Technology Town Hospital were independently tested by trained segmentation models. The results of five-fold cross validation experiments showed that the Dice coefficient, sensitivity and precision were 0.796 2 ± 0.274 1, 0.824 5 ± 0.276 3, and 0.805 1 ± 0.284 0, respectively. On the external test set, the Dice coefficient, sensitivity and precision were 0.817 2 ± 0.110 0, 0.829 6 ± 0.150 7, and 0.831 8 ± 0.116 8, respectively. The results show a great improvement in the segmentation accuracy compared with other semantic segmentation methods.