BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned ...BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.展开更多
Objective:To observe the effect of Kupfler cells on immune tolerance in liver transplantation. Methods:The rats were randomly divided into A,B and C groups.A group was sham operation group.The donor rats of group B ha...Objective:To observe the effect of Kupfler cells on immune tolerance in liver transplantation. Methods:The rats were randomly divided into A,B and C groups.A group was sham operation group.The donor rats of group B had intraperitoneal injection of 1 nmol Kuppffer cells every other day for three days before liver transplantation.Rats of group C were injected with equal saline.The rat liver transplantation models were established by modified Kamada’s two-cuff technique.The rats were sacrificed after 24 hours.The concentrations of ALT and AST in serum were measured with the biochemical analyzer.The level of IL-2 and TNF- a in serum were measured by ELISA method.The apoptotic indexes were detected by immunohistochemical assay. Results:The concentration of ALT,AST,IL-1 and TNF- a in A,B and C groups were increased successively.The levels of group C were significantly higher than that of group B and A(P【0.05), and the levels of group B were significantly higher than that of group A(P【0.05).The apoptotic indexes of three groups were 3.40±0.37,14.70±2.54 and 26.33±3.65,respectively,with significant difference among three groups(P【0.05).Conclusions:Pretreatment with Kupfler cells can reduce liver injury and raise liver transplantation immune tolerance.展开更多
AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two g...AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two groups: normal control group ( n =6) and GdCl 3 treated group ( n =8). Sixteen hours before the experiment, rats of GdCl 3 treated group were injected GdCl 3 by the tail vein to eliminate the Kupffer cell function in the periportal region selectively. LPS at a dose of 20μg/100g body weight was injected to rats of both groups by the portal vein. Zero, 2, 5, 10, 30, 60 minutes after LPS injection, liver samples were obtained and distribution of LPS in Kupffer cells was observed by the immunofluorescent method using a monoclonal antibody specific to LPS with a confocal laser scanning microscope. RESULTS In normal control group, positive reactions to LPS were found in Kupffer cells in the periportal region with the peak at 2 minutes after LPS injection. Kupffer cells in the pericentral region showed the peak at 5 minutes after LPS injection, but its fluorescent intensity to LPS at the peak time in the cytoplasm was significantly lower than that of Kupffer cells in the pericentral region at the peak point. In GdCl 3 treated group, Kupffer cells in the pericentral region showed the peak at 2 minutes after LPS injection, and its fluorescent intensity to LPS showed no significant difference from that of the normal control rats at the peak point. No significant changes of fluorescent intensities to LPS were found in Kupffer cells in the periportal region at various time points after LPS injection in GdCl 3 treated rats. CONCLUSION Kupffer cells in the periportal and pericentral regions showed difference to uptake LPS in the portal vein.展开更多
AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, parti...AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.展开更多
AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the ...AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.展开更多
INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping ...INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .展开更多
基金the National Natural Science Foundation of China,No.8190111624Guangxi Natural Science Foundation of China,No.2018JJB140382Guangxi University Young and Middle-Aged Teachers’Basic Scientific Research Ability Improvement Project,No.2019KY0123.
文摘BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been elucidated.The correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been reported.AIM To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after ALPPS.METHODS Clinical data and specimens were collected from 37 patients who developed massive HCC treated with ALPPS.Flow cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after ALPPS.To analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver volume.RESULTS The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 ALPPS.Patients with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than 0.70.CONCLUSION CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’livers.Treg percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.
文摘Objective:To observe the effect of Kupfler cells on immune tolerance in liver transplantation. Methods:The rats were randomly divided into A,B and C groups.A group was sham operation group.The donor rats of group B had intraperitoneal injection of 1 nmol Kuppffer cells every other day for three days before liver transplantation.Rats of group C were injected with equal saline.The rat liver transplantation models were established by modified Kamada’s two-cuff technique.The rats were sacrificed after 24 hours.The concentrations of ALT and AST in serum were measured with the biochemical analyzer.The level of IL-2 and TNF- a in serum were measured by ELISA method.The apoptotic indexes were detected by immunohistochemical assay. Results:The concentration of ALT,AST,IL-1 and TNF- a in A,B and C groups were increased successively.The levels of group C were significantly higher than that of group B and A(P【0.05), and the levels of group B were significantly higher than that of group A(P【0.05).The apoptotic indexes of three groups were 3.40±0.37,14.70±2.54 and 26.33±3.65,respectively,with significant difference among three groups(P【0.05).Conclusions:Pretreatment with Kupfler cells can reduce liver injury and raise liver transplantation immune tolerance.
文摘AIM To reveal the difference of Kupffer cells in the periportal and pericentral regions in the liver to uptake lipopolysaccharides (LPS) injected by the portal vein. METHODS Male Wistar rats were divided into two groups: normal control group ( n =6) and GdCl 3 treated group ( n =8). Sixteen hours before the experiment, rats of GdCl 3 treated group were injected GdCl 3 by the tail vein to eliminate the Kupffer cell function in the periportal region selectively. LPS at a dose of 20μg/100g body weight was injected to rats of both groups by the portal vein. Zero, 2, 5, 10, 30, 60 minutes after LPS injection, liver samples were obtained and distribution of LPS in Kupffer cells was observed by the immunofluorescent method using a monoclonal antibody specific to LPS with a confocal laser scanning microscope. RESULTS In normal control group, positive reactions to LPS were found in Kupffer cells in the periportal region with the peak at 2 minutes after LPS injection. Kupffer cells in the pericentral region showed the peak at 5 minutes after LPS injection, but its fluorescent intensity to LPS at the peak time in the cytoplasm was significantly lower than that of Kupffer cells in the pericentral region at the peak point. In GdCl 3 treated group, Kupffer cells in the pericentral region showed the peak at 2 minutes after LPS injection, and its fluorescent intensity to LPS showed no significant difference from that of the normal control rats at the peak point. No significant changes of fluorescent intensities to LPS were found in Kupffer cells in the periportal region at various time points after LPS injection in GdCl 3 treated rats. CONCLUSION Kupffer cells in the periportal and pericentral regions showed difference to uptake LPS in the portal vein.
基金Supported by the Major Scientific and Technological Project of Zhejiang Province,China,No.2015C03026
文摘AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.
基金Surported by the Funds of Hundred Outsdanding Persons project of Shanghai(97BR029)Science and Technology Commission of Shanghai(984419067)
文摘AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.
基金This work was supported partly by Grant 90089102 from the Scientific Research Fund of the Ministry of Education,Japan
文摘INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .
