Liver regeneration(LR)following partial hepatectomy(PH)is a unique and complex physiological response that restores hepatic mass and function through tightly orchestrated cellular and molecular events.Traditionally vi...Liver regeneration(LR)following partial hepatectomy(PH)is a unique and complex physiological response that restores hepatic mass and function through tightly orchestrated cellular and molecular events.Traditionally viewed as a proliferation-driven process,LR is now understood to involve both hepatocyte hyperplasia and hypertrophy,triggered primarily by hemodynamic alterations such as increased portal pressure and shear stress.These promote LR through endothelial–hepatocyte communication via activation of Piezo1-a mechanosensitive ion channel highly expressed in vascular endothelial cells.This channel is considered one of the potential upstream activators of molecular cascades including the interleukin(IL)-6/signal transducer and activator of transcription 3,tumour necrosis factor-alpha/nuclear factor-kappa B,Wnt/β-catenin,Hippo/YAP,transforming growth factor-beta,and Notch pathways,which contribute variably to the proliferation,differentiation,or suppression of hepatic cells.Novel insights into the IL-22 and IL-33 signaling axes,bile acid and glutamine metabolism,and the role of intestinal microbiota are also presented as promising emerging targets.This review synthesizes current insights into the interplay between mechanical cues,key signaling pathways,and metabolic reprogramming that govern early regenerative responses.We explore the mechanisms dictating the balance between hyperplasia and hypertrophy,noting that hypertrophy predominates after minor resections,while proliferation is dominant in larger resections.Polyploidization emerges as a significant adaptive mechanism,contributing to hepatocyte survival and tissue remodeling.The importance of ductular reactions,microvascular adjustments,and extracellular matrix dynamics in lobular architecture remodeling is also highlighted.The study explores the occurrence of ductular reactions in both minor and major resections,particularly within the granulation tissue near dissection areas.The paper also examines structural remodeling in regenerated liver tissue,demonstrating ongoing transformations in hepatocyte morphology and sinusoidal architecture even months after PH,and emphasizing that the termination of liver mass regrowth does not equate to the cessation of LR.展开更多
To the Editor:Liver transplantation is widely regarded as the definitive treat-ment for patients with end-stage liver disease.However,the per-sistent shortage of cadaveric liver grafts has driven the develop-ment of l...To the Editor:Liver transplantation is widely regarded as the definitive treat-ment for patients with end-stage liver disease.However,the per-sistent shortage of cadaveric liver grafts has driven the develop-ment of living-donor liver transplantation(LDLT).Despite its ben-efits,LDLT raises substantial concerns regarding donor morbid-ity,as the procedure involves operating on a healthy individual.Complications associated with donor hepatectomy include abdom-inal trauma,chronic wound pain,physical stress,and psycholog-ical burdens[1,2].In light of these challenges,minimally inva-sive approaches,including laparoscopic and robotic donor hepa-tectomy,have been introduced to mitigate risks and enhance re-covery[3].However,the impact of these techniques on male sex-ual function-a critical aspect of donor quality of life-remains underexplored.Several retrospective studies have highlighted sex-ual dysfunction and altered spousal relationships following open donor hepatectomy[4-6].For instance,9%of donors reported a de-crease in sexual activity,and a significant proportion experienced low body image perceptions.展开更多
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
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
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 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
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
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
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 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
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
AIM： To analyze the effects of NF-kB inhibition by antioxidant pyrrolidine dithiocarbamate （PDTC） or TNF inhibitor pentoxifylline （PTX） on liver regeneration after partial hepatectomy （PH）. METHODS： Saline, PD...AIM： To analyze the effects of NF-kB 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-kB 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-kB activation at 0.5 h. Signal transducer and activator of transcription 3 （Stat3） acUvatJon 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-kB p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, （2） star3 activation is a stress response unrelated to the activation of NF-kB. In conclusion, NF-kB activation is not critically required for the process of liver regeneration after PH.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
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
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
AIM： To elucidate the metabolism and the effect of the cyclosporin A （CyA） as a representative immuno- suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS： CyA was administere...AIM： To elucidate the metabolism and the effect of the cyclosporin A （CyA） as a representative immuno- suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS： CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; （group I） water, （group 2） 5 mg/kg CyA, （group 3） 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS： The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION： These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.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
A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is...A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it;control pig II 24% and 4%;control pig III 27% and 7%. The test group presented no significant liver regeneration since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.展开更多
文摘Liver regeneration(LR)following partial hepatectomy(PH)is a unique and complex physiological response that restores hepatic mass and function through tightly orchestrated cellular and molecular events.Traditionally viewed as a proliferation-driven process,LR is now understood to involve both hepatocyte hyperplasia and hypertrophy,triggered primarily by hemodynamic alterations such as increased portal pressure and shear stress.These promote LR through endothelial–hepatocyte communication via activation of Piezo1-a mechanosensitive ion channel highly expressed in vascular endothelial cells.This channel is considered one of the potential upstream activators of molecular cascades including the interleukin(IL)-6/signal transducer and activator of transcription 3,tumour necrosis factor-alpha/nuclear factor-kappa B,Wnt/β-catenin,Hippo/YAP,transforming growth factor-beta,and Notch pathways,which contribute variably to the proliferation,differentiation,or suppression of hepatic cells.Novel insights into the IL-22 and IL-33 signaling axes,bile acid and glutamine metabolism,and the role of intestinal microbiota are also presented as promising emerging targets.This review synthesizes current insights into the interplay between mechanical cues,key signaling pathways,and metabolic reprogramming that govern early regenerative responses.We explore the mechanisms dictating the balance between hyperplasia and hypertrophy,noting that hypertrophy predominates after minor resections,while proliferation is dominant in larger resections.Polyploidization emerges as a significant adaptive mechanism,contributing to hepatocyte survival and tissue remodeling.The importance of ductular reactions,microvascular adjustments,and extracellular matrix dynamics in lobular architecture remodeling is also highlighted.The study explores the occurrence of ductular reactions in both minor and major resections,particularly within the granulation tissue near dissection areas.The paper also examines structural remodeling in regenerated liver tissue,demonstrating ongoing transformations in hepatocyte morphology and sinusoidal architecture even months after PH,and emphasizing that the termination of liver mass regrowth does not equate to the cessation of LR.
文摘To the Editor:Liver transplantation is widely regarded as the definitive treat-ment for patients with end-stage liver disease.However,the per-sistent shortage of cadaveric liver grafts has driven the develop-ment of living-donor liver transplantation(LDLT).Despite its ben-efits,LDLT raises substantial concerns regarding donor morbid-ity,as the procedure involves operating on a healthy individual.Complications associated with donor hepatectomy include abdom-inal trauma,chronic wound pain,physical stress,and psycholog-ical burdens[1,2].In light of these challenges,minimally inva-sive approaches,including laparoscopic and robotic donor hepa-tectomy,have been introduced to mitigate risks and enhance re-covery[3].However,the impact of these techniques on male sex-ual function-a critical aspect of donor quality of life-remains underexplored.Several retrospective studies have highlighted sex-ual dysfunction and altered spousal relationships following open donor hepatectomy[4-6].For instance,9%of donors reported a de-crease in sexual activity,and a significant proportion experienced low body image perceptions.
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.
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 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 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.
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-
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 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.
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-kB 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-kB 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-kB activation at 0.5 h. Signal transducer and activator of transcription 3 （Stat3） acUvatJon 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-kB p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, （2） star3 activation is a stress response unrelated to the activation of NF-kB. In conclusion, NF-kB activation is not critically required for the process of liver regeneration after PH.
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.
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.
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.
文摘AIM： To elucidate the metabolism and the effect of the cyclosporin A （CyA） as a representative immuno- suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS： CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; （group I） water, （group 2） 5 mg/kg CyA, （group 3） 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS： The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION： These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.
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.
文摘A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it;control pig II 24% and 4%;control pig III 27% and 7%. The test group presented no significant liver regeneration since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.
