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
Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions,with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis.The preo...Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions,with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis.The preoperative albumin-bilirubin(ALBI)score,encompassing serum albumin and bilirubin levels,can be determined via blood analysis,effectively mitigating human error and providing an accurate depiction of liver function.The hepatectomy ratio,which is the proportion of the liver volume removed to the total liver volume,is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation,minimize surgical complications,and reduce mortality rates.Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy.The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.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 d...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 cells during liver regeneration were examined by flow oytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis positive cells in hepatic demonstrated human Aluparenchyma 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
Objective To investigate the efficacy and safety of continuous local anesthetic wound infiltration following open abdominal partial hepatectomy. Methods We performed a prospective, non-randomized, concurrent and con...Objective To investigate the efficacy and safety of continuous local anesthetic wound infiltration following open abdominal partial hepatectomy. Methods We performed a prospective, non-randomized, concurrent and controlled study. Patients undergoing open abdominal partial hepatectomy, according to their willingness, accepted one of the following managements for the postoperative pain: continuous wound catheter (CWC) infiltration, patient-controlled epidural analgesia (PCEA), patient-controlled intravenous analgesia of morphine (PCIAM), and patient-controlled intravenous analgesia of sufentanil (PCIAS). The primary outcome was postoperative visual analogue scale (VAS) scores at rest and on movement. Secondary outcomes included consumption of rescue medication, side effects, and complications associated with postoperative pain management. Results From August 2013 to December 2013, 80 patients were allocated to receive CWC (n=10), PCEA (n=22), PCIAM (n=29), or PCIAS (n=19). After adjusting for age, sex, body mass index, percentage of resected liver, operation time, and Amsterdam Preoperative Anxiety and Information Scale, there was no significant difference in the VAS scores at rest or on movement between Group CWC and the other groups, namely PCEA, PCIAM, and PCIAS, at 4, 12, 48, and 72 hours postoperatively (all P〉0.05). The need for rescue medication was not significantly different between Group CWC and the other three groups at 48 and 72 hours postoperatively (all P〉0.05). There was no significant difference in the incidence of postoperative nausea and vomiting or anal exsufflation time between group CWC and the other three groups (all P〉0.05). No severe adverse effects associated with continuous wound infiltration were observed during the study period. Conclusions CWC has a comparable analgesic effect compared with traditional analgesia methods at most time points postoperatively. CWC is a safe alternative for the postoperative analgesic management of open liver surgery.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
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
AIM: To explore the mechanism of intestinal endotoxemia (IETM) formation and its changes in partially hepatectomized (PH) rats. METHODS: One-hundred and two adult male Wistar rats were randomly divided into thre...AIM: To explore the mechanism of intestinal endotoxemia (IETM) formation and its changes in partially hepatectomized (PH) rats. METHODS: One-hundred and two adult male Wistar rats were randomly divided into three groups: normal control (NC) group, partially hepatectomized (PH) group and a sham-operated (SO) group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation ( 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h). NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin (ET) and diamine oxidase (DAO) levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells (KCs) in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS: Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation (r = 0.757, P 〈 0.05) between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum (La) particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION: The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,展开更多
AIM: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.METHODS: Cirrhosis was induced in rats by administrati...AIM: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.METHODS: Cirrhosis was induced in rats by administration of thioacetarnide. Untreated rats were used as controls. The control rats as well as the cirrhotic rats were subjected to 70% partial hepatectorny. At different time points after hepatectorny, the livers were collected and the levels of cytokines, growth factors and cell cycle proteins were analyzed.RESULTS: After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy. Significantly lower levels of cyclin A and cdk2 were also observed while the cdk inhibitor, p27 was significantly higher. In addition, the cirrhotic group had lower IL-6 levels than the control group at all time points up to 72 h following resection.CONCLUSION: The data from our study shows that impaired liver regeneration in cirrhotic remnants is associated with low expression of cyclins and cdks. This might be the consequence of the low IL-6 levels in cirrhotic liver remnant which would in turn influence the actions of transcription factors that regulate genes involved in cell proliferation and metabolic homeostasis during the regeneration process.展开更多
AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. T...AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liverregeneration 24 h after the damage might be not successful.展开更多
AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wist...AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wistar rats were randomly divided into five groups:Ⅰ=controls,Ⅱ=sham operated,Ⅲ=partial hepatectomy 70%(PHx),Ⅳ=PHx+ BBS(30μg/kg per day),Ⅴ=PHx+NT(300μg/kg per day).Forty eight hours after liver resection,portal en-dotoxin levels and hepatic glutathione redox state were determined.α-fetoprotein(AFP)mRNA(in situ hybridisation),cytokeratin-19 and Ki67 antigen expression (immunohistochemistry)and apoptosis(TUNEL)were evaluated on liver tissue samples.Cells with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was recorded.In addition,the proliferation and apoptotic rates of hepatocytes were determined.RESULTS:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(P<0.001).The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(P<0.001).In addition,BBS and NT induced a significant increase of hepatocyte proliferation(P<0.001),whereas it decreased their apoptotic activity(P<0.001)compared to groupⅢ.BBS and NT significantly decreased portal endotoxemia (P<0.001)and increased the hepatic GSH:GSSG ratio (P<0.05 and P<0.001,respectively)compared to groupⅢ.CONCLUSION:BBS and NT stimulated oval cell proliferation in a model of liver regeneration,without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli,and improved the hepatocyte regenerative response.This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.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. Live...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. Kaplan Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of 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-co (TNF-c0 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
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
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.
文摘Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions,with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis.The preoperative albumin-bilirubin(ALBI)score,encompassing serum albumin and bilirubin levels,can be determined via blood analysis,effectively mitigating human error and providing an accurate depiction of liver function.The hepatectomy ratio,which is the proportion of the liver volume removed to the total liver volume,is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation,minimize surgical complications,and reduce mortality rates.Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy.The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.
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 cells during liver regeneration were examined by flow oytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis positive cells in hepatic demonstrated human Aluparenchyma 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.
文摘Objective To investigate the efficacy and safety of continuous local anesthetic wound infiltration following open abdominal partial hepatectomy. Methods We performed a prospective, non-randomized, concurrent and controlled study. Patients undergoing open abdominal partial hepatectomy, according to their willingness, accepted one of the following managements for the postoperative pain: continuous wound catheter (CWC) infiltration, patient-controlled epidural analgesia (PCEA), patient-controlled intravenous analgesia of morphine (PCIAM), and patient-controlled intravenous analgesia of sufentanil (PCIAS). The primary outcome was postoperative visual analogue scale (VAS) scores at rest and on movement. Secondary outcomes included consumption of rescue medication, side effects, and complications associated with postoperative pain management. Results From August 2013 to December 2013, 80 patients were allocated to receive CWC (n=10), PCEA (n=22), PCIAM (n=29), or PCIAS (n=19). After adjusting for age, sex, body mass index, percentage of resected liver, operation time, and Amsterdam Preoperative Anxiety and Information Scale, there was no significant difference in the VAS scores at rest or on movement between Group CWC and the other groups, namely PCEA, PCIAM, and PCIAS, at 4, 12, 48, and 72 hours postoperatively (all P〉0.05). The need for rescue medication was not significantly different between Group CWC and the other three groups at 48 and 72 hours postoperatively (all P〉0.05). There was no significant difference in the incidence of postoperative nausea and vomiting or anal exsufflation time between group CWC and the other three groups (all P〉0.05). No severe adverse effects associated with continuous wound infiltration were observed during the study period. Conclusions CWC has a comparable analgesic effect compared with traditional analgesia methods at most time points postoperatively. CWC is a safe alternative for the postoperative analgesic management of open liver surgery.
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.
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a grant from the fund for key scientific and technical programs of Shanxi, No. 051094-9,Shanxi Province,China
文摘AIM: To explore the mechanism of intestinal endotoxemia (IETM) formation and its changes in partially hepatectomized (PH) rats. METHODS: One-hundred and two adult male Wistar rats were randomly divided into three groups: normal control (NC) group, partially hepatectomized (PH) group and a sham-operated (SO) group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation ( 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h). NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin (ET) and diamine oxidase (DAO) levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells (KCs) in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS: Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation (r = 0.757, P 〈 0.05) between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum (La) particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION: The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,
基金Supported by a research grant from the National Medical Research Council,Singapore(awarded to T.M.C.Tan as PI and C.K.Leow as co-PI).
文摘AIM: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.METHODS: Cirrhosis was induced in rats by administration of thioacetarnide. Untreated rats were used as controls. The control rats as well as the cirrhotic rats were subjected to 70% partial hepatectorny. At different time points after hepatectorny, the livers were collected and the levels of cytokines, growth factors and cell cycle proteins were analyzed.RESULTS: After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy. Significantly lower levels of cyclin A and cdk2 were also observed while the cdk inhibitor, p27 was significantly higher. In addition, the cirrhotic group had lower IL-6 levels than the control group at all time points up to 72 h following resection.CONCLUSION: The data from our study shows that impaired liver regeneration in cirrhotic remnants is associated with low expression of cyclins and cdks. This might be the consequence of the low IL-6 levels in cirrhotic liver remnant which would in turn influence the actions of transcription factors that regulate genes involved in cell proliferation and metabolic homeostasis during the regeneration process.
文摘AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liverregeneration 24 h after the damage might be not successful.
文摘AIM:To investigate the effect of the neuropeptides bombesin(BBS)and neurotensin(NT)on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS:Seventy male Wistar rats were randomly divided into five groups:Ⅰ=controls,Ⅱ=sham operated,Ⅲ=partial hepatectomy 70%(PHx),Ⅳ=PHx+ BBS(30μg/kg per day),Ⅴ=PHx+NT(300μg/kg per day).Forty eight hours after liver resection,portal en-dotoxin levels and hepatic glutathione redox state were determined.α-fetoprotein(AFP)mRNA(in situ hybridisation),cytokeratin-19 and Ki67 antigen expression (immunohistochemistry)and apoptosis(TUNEL)were evaluated on liver tissue samples.Cells with morphological features of oval cells that were cytokeratin-19 (+)and AFP mRNA(+)were scored in morphometric analysis and their proliferation was recorded.In addition,the proliferation and apoptotic rates of hepatocytes were determined.RESULTS:In the control and sham operated groups,oval cells were significantly less compared to groups Ⅲ,ⅣandⅤ(P<0.001).The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to groupⅢ(P<0.001).In addition,BBS and NT induced a significant increase of hepatocyte proliferation(P<0.001),whereas it decreased their apoptotic activity(P<0.001)compared to groupⅢ.BBS and NT significantly decreased portal endotoxemia (P<0.001)and increased the hepatic GSH:GSSG ratio (P<0.05 and P<0.001,respectively)compared to groupⅢ.CONCLUSION:BBS and NT stimulated oval cell proliferation in a model of liver regeneration,without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli,and improved the hepatocyte regenerative response.This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.
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. Kaplan Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of 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-co (TNF-c0 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.
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-