BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data ...BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.展开更多
INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can ...INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can be induced to proliferatequickly by partial hepatectomy (PH),and,to somedegree,they stop dividing and re-differentiate intocells functioning as hepatocytes.This shows展开更多
The effects of pHGF on the changes of hepatocyte proliferative cycle and liver regenerative capacity after partial hepatectomized rats were observed by flow cytometry (FCM). The results were as follows:1)S phase fract...The effects of pHGF on the changes of hepatocyte proliferative cycle and liver regenerative capacity after partial hepatectomized rats were observed by flow cytometry (FCM). The results were as follows:1)S phase fraction (SPF) in group of normal rats (group A) accounted for 9. 89% and increased gradually within 6 h, following a peak at 12th h or 36th h after operation, but in the group of pHGF-treated rats (group B) the peak appeared at 24th h after operation; 2 )Proliferatioll index (PI) of group A was 19. 6 % before partial hepatectomy, increased to 34. 91% within 6 h and reached a peaks at 12th or 36th h after operation, and in group B the peak appeared at 48th h after operation. There were significant differences between two groups in SPF and PI (P<0. 01). The weight of liver began to increase 12 h after operation, and almost reached the preoperative weight 5 days after operation. These findings suggest that PHGF can promote the DNA synthesis and segmentation of hepatocyte.展开更多
AIM:To study the expression of tumor necrosis factor- alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo. METHODS: Male SD rats underwent 70% partial h...AIM:To study the expression of tumor necrosis factor- alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo. METHODS: Male SD rats underwent 70% partial hepatec- tomy. The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy. TACE expression was investigated by Western blotting, immunohistochemistry, and serial section immunostaining. RESULTS: Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration, reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h. TACE protein was localized to mononuclear cells (MNC), which infiltrated the liver from the spleen after hepatectomy. The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α (TGFα). In addition, TACE-staining MNC partially overlapped with CD3+ T lymphocytes. CONCLUSION: TACE may be involved in liver regenera- tion by pathway mediated with TGFα-EGFR in the cell- cycle progressive phase in vivo. TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.展开更多
Summary: The effects of pro-hepatocyte growth factor (pHGF) on the changes of renal cellular proliferative cycle of partial hepatectomized rats were observed by flow cytometry (FCM). S phase fraction (SPF) of control ...Summary: The effects of pro-hepatocyte growth factor (pHGF) on the changes of renal cellular proliferative cycle of partial hepatectomized rats were observed by flow cytometry (FCM). S phase fraction (SPF) of control rats (group A) accounted for 7.58 % and increased gradually within 6 h, following a peak at 12th or 36th h after operation, but in pHGF-treated rats (group B) the peak appeared at 24th h after operation. Proliferation index (PI) of group A was 13. 2 % before partial hepatectomy, increased within 6 h and reached a peak at 12th or 36th h after operation, and in group B the peak appeared at 48th h after operation. There were significant differences in SPF and PI between two groups (P<0. 01 ). These findings suggest that PHGF may nonspecifically promote the DNA synthesis of renal cells.展开更多
AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells duri...AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cellsduring liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.CONCLUSION: HRC liver provides a tool for investigating human liver regeneration in a humanized animal model.展开更多
BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finge...BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20(ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2(ZHX2), ZBTB20, alpha-fetoprotein(AFP) and glypican 3(GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.展开更多
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been adopted by liver surgeons in recent years.However,high morbidity and mortality rates have limited the promotion of ...BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been adopted by liver surgeons in recent years.However,high morbidity and mortality rates have limited the promotion of this technique.Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant(FLR)similar to a complete split with better postoperative safety profiles.However,some others have suggested that ALPPS can induce more rapid and adequate FLR growth,but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS(p-ALPPS).AIM To perform a systematic review and meta-analysis on ALPPS and p-ALPPS.METHODS A systematic literature search of PubMed,Embase,the Cochrane Library,and ClinicalTrials.gov was performed for articles published until June 2019.Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included.Our main endpoints were the morbidity,mortality,and FLR hypertrophy rates.We performed a subgroup analysis to evaluate patients with and without liver cirrhosis.We assessed pooled data using a random-effects model.RESULTS Four studies met the inclusion criteria.Four studies reported data on morbidity and mortality,and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis.In the non-cirrhotic group,p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPStreated patients[odds ratio(OR)=0.2;95%confidence interval(CI):0.07–0.57;P=0.003 and OR=0.16;95%CI:0.03-0.9;P=0.04].No significant difference in the FLR hypertrophy rate was observed between the two groups(P>0.05).The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups.In contrast,ALPPS seemed to have a better outcome in the cirrhotic group.CONCLUSION The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.展开更多
To the editor:We read with great interest the article entitled "Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats" by Ulmer et al.[1]...To the editor:We read with great interest the article entitled "Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats" by Ulmer et al.[1].The aim of this study was to analyse the impact of terlipressin ver-展开更多
AIM: To reveal the liver regeneration (LR) and its controlas well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers.MET...AIM: To reveal the liver regeneration (LR) and its controlas well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers.METHODS: Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. RESULTS: Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of themshowed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressedin 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. CONCLUSION: In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR.展开更多
Objective To discuss the value of partial hepatectomy in patients with hilar cholangiocarcinoma.Methods English articles related to hilar cholangiocarcinoma were screened from January 1,1990 to May 12,2019 in the Pub ...Objective To discuss the value of partial hepatectomy in patients with hilar cholangiocarcinoma.Methods English articles related to hilar cholangiocarcinoma were screened from January 1,1990 to May 12,2019 in the Pub Med,MEDLINE,EMBASE,and Cochrane Library databases.Information on postoperative radical cure,survival,morbidity,and mortality after surgery were extracted from articles that met the inclusion criteria for the meta-analysis.Results Twenty-two articles that met the inclusion criteria were classified into 4 study groups: the hepatectomy radical cure group(19 articles),the hepatectomy survival group(16 articles),the hepatectomy morbidity group(9 articles),and the hepatectomy mortality group(17 articles).We found that the rate of radical cure after partial hepatectomy(odds ratio [OR] 0.32,95% confidence interval [CI] 0.20-0.51) and the survival rate(hazard ratio [HR] 0.67,95% CI 0.58-0.79) were significantly higher than after simple bile duct resection,but that morbidity(OR 1.99,95% CI 1.37-2.90) and mortality(OR 2.71,95% CI 1.47-4.98) in patients within the partial hepatectomy group were also higher than in the simple bile duct resection group,taking into account the significant heterogeneity in the articles pertaining to the hepatectomy radical cure group(I^2=68.3%,P=0.000),a sub-group analysis was subsequently conducted.Its results showed that when the branches of the secondary bile ducts were not involved during hilar cholangiocarcinoma,then a bile duct resection had a similar radical cure outcome as combined partial hepatectomy(OR 0.94,95% CI 0.54-1.65).Conclusion Partial hepatectomy can increase the proportion of radical cure in patients with hilar cholangiocarcinoma and extend the survival time after surgery.However,the morbidity and mortality after surgery are higher than those in simple bile duct resections.Therefore,simple bile duct resection is still a relevant and efficient tool in the treatment of Bismuth-Corlette Type Ⅰ and Ⅱ hilar cholangiocarcinomas.展开更多
In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and ...In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.展开更多
AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver rege...AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. KaplanMeier method and the log-rank test were used for ahalyzing the survival after PH. Differences in the resultsof immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.CONCLUSION: Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH.展开更多
AIM: To analyze the effects of NF-κB inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS: Saline, PDTC or P...AIM: To analyze the effects of NF-κB inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS: Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups). RESULTS: Compared to saline injected controls, NF-κB activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF-κB activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH. CONCLUSION: These data strongly suggest that (1) NF-κB p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF-κB. In conclusion, NF-κB activation is not critically required for the process of liver regeneration after PH.展开更多
pH and volatile fatty acids both might affect the further hydrolysis of particulate solid waste, which is the limiting-step of anaerobic digestion. To clarify the individual effects of pH and volatile fatty acids, bat...pH and volatile fatty acids both might affect the further hydrolysis of particulate solid waste, which is the limiting-step of anaerobic digestion. To clarify the individual effects of pH and volatile fatty acids, batch experiments were conducted at fixed pH value (pH 5-9) with or without acetate (20 g/L). The hydrolysis efficiencies of carbohydrate and protein were evaluated by carbon and nitrogen content of solids, amylase activity and proteinase activity. The trend of carbohydrate hydrolysis with pH was not affected by the addition of acetate, following the sequence ofpH 7〉pH 8〉pH 9〉pH 6〉pH 5; but the inhibition of acetate (20 g/L) was obvious by 10%-60 %. The evolution of residual nitrogen showed that the effect of pH on protein hydrolysis was minor, while the acetate was seriously inhibitory especially at alkali condition by 45%-100 %. The relationship between the factors (pH and acetate) and the response variables was evaluated by partial least square modeling (PLS). The PLS analysis demonstrated that the hydrolysis of carbohydrate was both affected by pH and acetate, with pH the more important factor. Therefore, the inhibition by acetate on carbohydrate hydrolysis was mainly due to the corresponding decline of pH, but the presence of acetate species, while the acetate species was the absolutely important factor for the hydrolysis of protein.展开更多
BACKGROUND The phenomenon of liver regeneration after partial hepatectomy(PH)is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand,and on the other h...BACKGROUND The phenomenon of liver regeneration after partial hepatectomy(PH)is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand,and on the other hand,new surgical approaches which allow removal of massive space-occupying hepatic tumors,which earlier was considered as inoperable.Interestingly,the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ.Because of this,the question“How does the structure of regenerated liver differ from normal,regular liver?”has not been fully answered yet.Furthermore,almost without any attention is left the liver's structural transformation after repeated hepatectomy(of the re-regenereted liver).ATM To compare the architectonics of the lobules and circulatory bed of normal,regenerated and re-regenerated livers.METHODS The livers of 40 adult,male,albino Wistar rats were studied.14 rats were subjected to PH-the 1st study group(SG1);10 rats underwent repeated PH–the 2nd study group(SG2);16 rats were subjected to sham operation-control group(CG);The livers were studied after 9 months from PH,and after 6 months from repeated PH.Cytological(Schiff reaction for the determination of DNA concentration),histological(H&E,Masson trichrome,CK8 Immunohistochemical marker,transparent slides after Indian Ink injection,),morphometrical(hepatocytes areas,perimeters and ploidy)and Electron Microscopical(Scanning Electron Microscopy of corrosion casts)methods were used.RESULTS In the SG1 and SG2,the area of hepatocytes and their perimeter are increased compared to the CG(P<0.05).However,the areas and perimeters of the hepatocytes of the SG1 and SG2 groups reveal a lesser difference.In regenerated(SG1)and re-regenerated(SG2)livers,the hepatocytes form the remodeled lobules,which size(300-1200μm)exceeds the sizes of the lobules from CG(300-600μm).The remodeled lobules(especially the“mega-lobules”with the sizes 1000-1200μm)contain the transformed meshworks of the sinusoids,the part of which is dilated asymmetrically.This meshwork might have originated from the several portal venules(interlobular and/or inlet).The boundaries between the adjacent lobules(including mega-lobules)are widened and filled by connective tissue fibers,which gives the liver parenchyma a nodular look.In SG2 the unevenness of sinusoid diameters,as well as the boundaries between the lobules(including the mega-lobules)are more vividly expressed in comparison with SG1.The liver tissue of both SG1 and SG2 is featured by the slightly expressed ductular reaction.CONCLUSION Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.展开更多
文摘BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.
基金China-France Scientific end Technical Cooperation (No.1996-134)Bioengineering Key Laboratory of Henan Province
文摘INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can be induced to proliferatequickly by partial hepatectomy (PH),and,to somedegree,they stop dividing and re-differentiate intocells functioning as hepatocytes.This shows
文摘The effects of pHGF on the changes of hepatocyte proliferative cycle and liver regenerative capacity after partial hepatectomized rats were observed by flow cytometry (FCM). The results were as follows:1)S phase fraction (SPF) in group of normal rats (group A) accounted for 9. 89% and increased gradually within 6 h, following a peak at 12th h or 36th h after operation, but in the group of pHGF-treated rats (group B) the peak appeared at 24th h after operation; 2 )Proliferatioll index (PI) of group A was 19. 6 % before partial hepatectomy, increased to 34. 91% within 6 h and reached a peaks at 12th or 36th h after operation, and in group B the peak appeared at 48th h after operation. There were significant differences between two groups in SPF and PI (P<0. 01). The weight of liver began to increase 12 h after operation, and almost reached the preoperative weight 5 days after operation. These findings suggest that PHGF can promote the DNA synthesis and segmentation of hepatocyte.
文摘AIM:To study the expression of tumor necrosis factor- alpha converting enzyme (TACE) and evaluate its significance in liver regeneration after partial hepatectomy in vivo. METHODS: Male SD rats underwent 70% partial hepatec- tomy. The remaining liver and spleen tissue samples were collected at indicated time points after hepatectomy. TACE expression was investigated by Western blotting, immunohistochemistry, and serial section immunostaining. RESULTS: Expression of TACE in liver and spleen tissues after partial hepatectomy was a time-dependent alteration, reaching a maximal level between 24 and 48 h and remaining elevated for more than 168 h. TACE protein was localized to mononuclear cells (MNC), which infiltrated the liver from the spleen after hepatectomy. The kinetics of TACE expression was in accordance with the number of TACE-staining MNCs and synchronized with those of transforming growth factor-α (TGFα). In addition, TACE-staining MNC partially overlapped with CD3+ T lymphocytes. CONCLUSION: TACE may be involved in liver regenera- tion by pathway mediated with TGFα-EGFR in the cell- cycle progressive phase in vivo. TACE production and effect by paracrine may be a pathway of involvement in liver regeneration for the activated CD3+ T lymphocytes.
文摘Summary: The effects of pro-hepatocyte growth factor (pHGF) on the changes of renal cellular proliferative cycle of partial hepatectomized rats were observed by flow cytometry (FCM). S phase fraction (SPF) of control rats (group A) accounted for 7.58 % and increased gradually within 6 h, following a peak at 12th or 36th h after operation, but in pHGF-treated rats (group B) the peak appeared at 24th h after operation. Proliferation index (PI) of group A was 13. 2 % before partial hepatectomy, increased within 6 h and reached a peak at 12th or 36th h after operation, and in group B the peak appeared at 48th h after operation. There were significant differences in SPF and PI between two groups (P<0. 01 ). These findings suggest that PHGF may nonspecifically promote the DNA synthesis of renal cells.
基金Supported by The National Natural Science Foundation of China, No. 30271177 and No. 39870676the Major Scienceand Technology Projects of Guangdong Province, No. B602+4 种基金the Natural Science Foundation of Guangdong Province, No.021903the Science and Technology Planning Project of Guangdong Province, No. 2009B060300008the Science and Technology Projects of Guangzhou City, No. 2002Z2E0121the Medical Scientific Research Foundation of Guangdong Province, No. A2007359the Science and Technology Talented Man Foundation of Outstanding Young and Middle-aged People of Southern Medical University,the Special Fund of Scientific Instrument Collaborative Share-net in Guangzhou, No. 2006176
文摘AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cellsduring liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.CONCLUSION: HRC liver provides a tool for investigating human liver regeneration in a humanized animal model.
基金supported by a grant from the Shanghai Municipal Commission of Education Scientific Research and Innovation Project(11zz107)
文摘BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20(ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2(ZHX2), ZBTB20, alpha-fetoprotein(AFP) and glypican 3(GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.
文摘BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been adopted by liver surgeons in recent years.However,high morbidity and mortality rates have limited the promotion of this technique.Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant(FLR)similar to a complete split with better postoperative safety profiles.However,some others have suggested that ALPPS can induce more rapid and adequate FLR growth,but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS(p-ALPPS).AIM To perform a systematic review and meta-analysis on ALPPS and p-ALPPS.METHODS A systematic literature search of PubMed,Embase,the Cochrane Library,and ClinicalTrials.gov was performed for articles published until June 2019.Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included.Our main endpoints were the morbidity,mortality,and FLR hypertrophy rates.We performed a subgroup analysis to evaluate patients with and without liver cirrhosis.We assessed pooled data using a random-effects model.RESULTS Four studies met the inclusion criteria.Four studies reported data on morbidity and mortality,and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis.In the non-cirrhotic group,p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPStreated patients[odds ratio(OR)=0.2;95%confidence interval(CI):0.07–0.57;P=0.003 and OR=0.16;95%CI:0.03-0.9;P=0.04].No significant difference in the FLR hypertrophy rate was observed between the two groups(P>0.05).The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups.In contrast,ALPPS seemed to have a better outcome in the cirrhotic group.CONCLUSION The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.
文摘To the editor:We read with great interest the article entitled "Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats" by Ulmer et al.[1].The aim of this study was to analyse the impact of terlipressin ver-
基金Supported by the National Natural Science Foundation of China,No. 30270673
文摘AIM: To reveal the liver regeneration (LR) and its controlas well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers.METHODS: Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. RESULTS: Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of themshowed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressedin 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. CONCLUSION: In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR.
基金Supported by a grant from the Science and Technology Research and Development Project of Chengde(No.201804A023)
文摘Objective To discuss the value of partial hepatectomy in patients with hilar cholangiocarcinoma.Methods English articles related to hilar cholangiocarcinoma were screened from January 1,1990 to May 12,2019 in the Pub Med,MEDLINE,EMBASE,and Cochrane Library databases.Information on postoperative radical cure,survival,morbidity,and mortality after surgery were extracted from articles that met the inclusion criteria for the meta-analysis.Results Twenty-two articles that met the inclusion criteria were classified into 4 study groups: the hepatectomy radical cure group(19 articles),the hepatectomy survival group(16 articles),the hepatectomy morbidity group(9 articles),and the hepatectomy mortality group(17 articles).We found that the rate of radical cure after partial hepatectomy(odds ratio [OR] 0.32,95% confidence interval [CI] 0.20-0.51) and the survival rate(hazard ratio [HR] 0.67,95% CI 0.58-0.79) were significantly higher than after simple bile duct resection,but that morbidity(OR 1.99,95% CI 1.37-2.90) and mortality(OR 2.71,95% CI 1.47-4.98) in patients within the partial hepatectomy group were also higher than in the simple bile duct resection group,taking into account the significant heterogeneity in the articles pertaining to the hepatectomy radical cure group(I^2=68.3%,P=0.000),a sub-group analysis was subsequently conducted.Its results showed that when the branches of the secondary bile ducts were not involved during hilar cholangiocarcinoma,then a bile duct resection had a similar radical cure outcome as combined partial hepatectomy(OR 0.94,95% CI 0.54-1.65).Conclusion Partial hepatectomy can increase the proportion of radical cure in patients with hilar cholangiocarcinoma and extend the survival time after surgery.However,the morbidity and mortality after surgery are higher than those in simple bile duct resections.Therefore,simple bile duct resection is still a relevant and efficient tool in the treatment of Bismuth-Corlette Type Ⅰ and Ⅱ hilar cholangiocarcinomas.
文摘In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.
文摘AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. KaplanMeier method and the log-rank test were used for ahalyzing the survival after PH. Differences in the resultsof immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.CONCLUSION: Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH.
基金Supported by a grant from Glaxo-Smithkline, Belgium, a grant from Astra Zeneca, Belgium, and a grant (3-4598) of FRSM,Belgium
文摘AIM: To analyze the effects of NF-κB inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS: Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups). RESULTS: Compared to saline injected controls, NF-κB activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF-κB activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH. CONCLUSION: These data strongly suggest that (1) NF-κB p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF-κB. In conclusion, NF-κB activation is not critically required for the process of liver regeneration after PH.
文摘pH and volatile fatty acids both might affect the further hydrolysis of particulate solid waste, which is the limiting-step of anaerobic digestion. To clarify the individual effects of pH and volatile fatty acids, batch experiments were conducted at fixed pH value (pH 5-9) with or without acetate (20 g/L). The hydrolysis efficiencies of carbohydrate and protein were evaluated by carbon and nitrogen content of solids, amylase activity and proteinase activity. The trend of carbohydrate hydrolysis with pH was not affected by the addition of acetate, following the sequence ofpH 7〉pH 8〉pH 9〉pH 6〉pH 5; but the inhibition of acetate (20 g/L) was obvious by 10%-60 %. The evolution of residual nitrogen showed that the effect of pH on protein hydrolysis was minor, while the acetate was seriously inhibitory especially at alkali condition by 45%-100 %. The relationship between the factors (pH and acetate) and the response variables was evaluated by partial least square modeling (PLS). The PLS analysis demonstrated that the hydrolysis of carbohydrate was both affected by pH and acetate, with pH the more important factor. Therefore, the inhibition by acetate on carbohydrate hydrolysis was mainly due to the corresponding decline of pH, but the presence of acetate species, while the acetate species was the absolutely important factor for the hydrolysis of protein.
基金the Shota Rustaveli National Science Foundation of Georgia,No.DP2016_22[New Interfaculty Interdisciplinary Structured Doctoral Programme“Translational Biomedicine”(Direction–“Hepatology”)].
文摘BACKGROUND The phenomenon of liver regeneration after partial hepatectomy(PH)is still a subject of considerable interest due to the increasing frequency of half liver transplantation on the one hand,and on the other hand,new surgical approaches which allow removal of massive space-occupying hepatic tumors,which earlier was considered as inoperable.Interestingly,the mechanisms of liver regeneration are extensively studied after PH but less attention is paid to the architectonics of the regenerated organ.Because of this,the question“How does the structure of regenerated liver differ from normal,regular liver?”has not been fully answered yet.Furthermore,almost without any attention is left the liver's structural transformation after repeated hepatectomy(of the re-regenereted liver).ATM To compare the architectonics of the lobules and circulatory bed of normal,regenerated and re-regenerated livers.METHODS The livers of 40 adult,male,albino Wistar rats were studied.14 rats were subjected to PH-the 1st study group(SG1);10 rats underwent repeated PH–the 2nd study group(SG2);16 rats were subjected to sham operation-control group(CG);The livers were studied after 9 months from PH,and after 6 months from repeated PH.Cytological(Schiff reaction for the determination of DNA concentration),histological(H&E,Masson trichrome,CK8 Immunohistochemical marker,transparent slides after Indian Ink injection,),morphometrical(hepatocytes areas,perimeters and ploidy)and Electron Microscopical(Scanning Electron Microscopy of corrosion casts)methods were used.RESULTS In the SG1 and SG2,the area of hepatocytes and their perimeter are increased compared to the CG(P<0.05).However,the areas and perimeters of the hepatocytes of the SG1 and SG2 groups reveal a lesser difference.In regenerated(SG1)and re-regenerated(SG2)livers,the hepatocytes form the remodeled lobules,which size(300-1200μm)exceeds the sizes of the lobules from CG(300-600μm).The remodeled lobules(especially the“mega-lobules”with the sizes 1000-1200μm)contain the transformed meshworks of the sinusoids,the part of which is dilated asymmetrically.This meshwork might have originated from the several portal venules(interlobular and/or inlet).The boundaries between the adjacent lobules(including mega-lobules)are widened and filled by connective tissue fibers,which gives the liver parenchyma a nodular look.In SG2 the unevenness of sinusoid diameters,as well as the boundaries between the lobules(including the mega-lobules)are more vividly expressed in comparison with SG1.The liver tissue of both SG1 and SG2 is featured by the slightly expressed ductular reaction.CONCLUSION Regenerated and re-regenerated livers in comparison with normal liver contain hypertrophied hepatocytes with increased ploidy which together with transformed sinusoidal and biliary meshworks form the remodeled lobulli.