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
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
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
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
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
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:Low central venous pressure(CVP) affects hemodynamic stability and tissue perfusion.This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma(HCC).METH...BACKGROUND:Low central venous pressure(CVP) affects hemodynamic stability and tissue perfusion.This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma(HCC).METHODS:Ninety-seven patients who underwent partial hepatectomy for HCC had their CVP controlled at a level of 0 to 5 mmHg during hepatic parenchymal transection.The systolic blood pressure(SBP) was maintained,if possible,at 90 mmHg or higher.Hepatitis B surface antigen was positive in 90 patients(92.8%) and cirrhosis in 84 patients(86.6%).Pringle maneuver was used routinely in these patients with clamp/unclamp cycles of 15/5 minutes.The average clamp time was 21.4±8.0 minutes.These patients were divided into 5 groups based on the CVP:group A:0-1 mmHg;B:1.1-2 mmHg;C:2.1-3 mmHg;D:3.1-4 mmHg and E:4.1-5 mmHg.The blood loss per transection area during hepatic parenchymal transection and the arterial blood gas before and after liver transection were analyzed.RESULTS:With active fluid load,a constant SBP ≥90 mmHg which was considered as optimal was maintained in 18.6% in group A(95% CI:10.8%-26.3%);39.2% in group B(95% CI:29.5%-48.9%);72.2% in group C(95% CI:63.2%-81.1%);89.7% in group D(95% CI:83.6%-95.7%);and 100% in group E(95% CI:100%-100%).The blood loss per transection area during hepatic parenchymal transection decreased with a decrease in CVP.Compared to groups D and E,blood loss in groups A,B and C was significantly less(analysis of variance test,P<0.05).Compared with the baseline,the blood oxygenation decreased significantly when the CVP was reduced.Base excess and HCO 3-in groups A and B were significantly decreased compared with those in groups C,D and E(P<0.05).CONCLUSION:In consideration of blood loss,SBP,base excess and HCO 3-,a CVP of 2.1-3 mmHg was optimal in patients undergoing partial hepatectomy for HCC.展开更多
BACKGROUND:Following curative treatment for hepato-cellular carcinoma(HCC),50%-90% of postoperative death is due to recurrent disease.Intra-hepatic recurrence is frequently the only site of recurrence.Thus,any neoadju...BACKGROUND:Following curative treatment for hepato-cellular carcinoma(HCC),50%-90% of postoperative death is due to recurrent disease.Intra-hepatic recurrence is frequently the only site of recurrence.Thus,any neoadjuvant or adjuvant therapy,which can decrease or delay the incidence of intra-hepatic recurrence,or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant,will improve the results of liver resection.This article systematically reviewed the current evidence of neoadjuvant,adjuvant, and chemoprevention in partial hepatectomy of HCC. DATA SOURCES:Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to November 2008 using the keywords "hepatocellular carcinoma","hepatectomy","adjuvant therapy","neoadjuvant therapy",and"regional therapy". Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS:Neoadjuvant transarterial chemoembolization or adjuvant regional transarterial chemotherapy± embolization+systemic chemotherapy did not add benefit. Both adjuvant transarterial radioembolization with 131 I-lipiodol and adjuvant systemic interferon showed promising results.However,there were only a limited number of such studies.CONCLUSIONS:Further randomized controlled studies need to be carried out.Currently,there is no consensus on a standard neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for HCC.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
Under ultrasound guidance, a blunt suture needle was inserted around the Glissonian pedicle and then sutured. This technique significantly reduced the blood loss and facilitated the procedure of partial hepatectomy. W...Under ultrasound guidance, a blunt suture needle was inserted around the Glissonian pedicle and then sutured. This technique significantly reduced the blood loss and facilitated the procedure of partial hepatectomy. We applied this technique in 182 patients who needed partial hepatectomy. We concluded that this method is simple and easy to occlude the vascular inflow and outflow, and allows an accurate delineation of the anatomic zone and therefore, simplifies the procedure of partial hepatectomy.展开更多
BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of t...BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H_2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H_2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH_2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.展开更多
Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury(AKI) should be considered as a...Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury(AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs.展开更多
AIM To identify risk factors for the occurrence of acute kidney injury(AKI) in the postoperative period of partial hepatectomies. METHODS Retrospective analysis of 446 consecutive resections in 405 patients, analyzing...AIM To identify risk factors for the occurrence of acute kidney injury(AKI) in the postoperative period of partial hepatectomies. METHODS Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified. RESULTS Of the total 446 partial liver resections, postoperative AKI occurred in 80 cases(17.9%). Identified predictors of AKI were: Non-dialytic chronic kidney injury(CKI), biliary obstruction, the Model for End-Stage Liver Disease(MELD) score, the extent of hepatic resection, the occurrence of intraoperative hemodynamic instability, post-hepatectomy haemorrhage, and postoperative sepsis. CONCLUSION The MELD score, the presence of non-dialytic CKIand biliary obstruction in the preoperative period, and perioperative hemodynamics instability, bleeding, and sepsis are risk factors for the occurrence of AKI in patients that underwent partial hepatectomy.展开更多
BACKGROUND:The anti-proliferative gene,PC3(pheoch- romocytoma cell 3)/BTG2(B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family.This study aimed to assess t...BACKGROUND:The anti-proliferative gene,PC3(pheoch- romocytoma cell 3)/BTG2(B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family.This study aimed to assess the effects of recombinant human hepatopoietin(HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma(HCC)at different stages of progression. METHODS:After a rat model of partial hepatectomy was established,we investigated gene expression within 1 hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system.The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile,the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization. RESULTS:The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation.HPO rapidly induced the expression of the genes c-fos,LRF-1,and PC3 in primary cultured rat hepatocytes,which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation.Positive BTG2 mRNA expression was detected in 71.19%(42/59)of the HCC samples and in 75%(3/4)of the normal liver tissue samples obtained from the region around the HCC tissues.PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation. CONCLUSIONS:Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/ BTG2 gene.PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation.The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC,so PC3/BTG2 may play an important role in these processes.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
In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and ...In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.展开更多
AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver rege...AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. KaplanMeier method and the log-rank test were used for ahalyzing the survival after PH. Differences in the resultsof immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.CONCLUSION: Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH.展开更多
文摘BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.
基金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.
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
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.
基金supported by a grant from the Guangxi Natural Science(GKZ0447066)
文摘BACKGROUND:Low central venous pressure(CVP) affects hemodynamic stability and tissue perfusion.This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma(HCC).METHODS:Ninety-seven patients who underwent partial hepatectomy for HCC had their CVP controlled at a level of 0 to 5 mmHg during hepatic parenchymal transection.The systolic blood pressure(SBP) was maintained,if possible,at 90 mmHg or higher.Hepatitis B surface antigen was positive in 90 patients(92.8%) and cirrhosis in 84 patients(86.6%).Pringle maneuver was used routinely in these patients with clamp/unclamp cycles of 15/5 minutes.The average clamp time was 21.4±8.0 minutes.These patients were divided into 5 groups based on the CVP:group A:0-1 mmHg;B:1.1-2 mmHg;C:2.1-3 mmHg;D:3.1-4 mmHg and E:4.1-5 mmHg.The blood loss per transection area during hepatic parenchymal transection and the arterial blood gas before and after liver transection were analyzed.RESULTS:With active fluid load,a constant SBP ≥90 mmHg which was considered as optimal was maintained in 18.6% in group A(95% CI:10.8%-26.3%);39.2% in group B(95% CI:29.5%-48.9%);72.2% in group C(95% CI:63.2%-81.1%);89.7% in group D(95% CI:83.6%-95.7%);and 100% in group E(95% CI:100%-100%).The blood loss per transection area during hepatic parenchymal transection decreased with a decrease in CVP.Compared to groups D and E,blood loss in groups A,B and C was significantly less(analysis of variance test,P<0.05).Compared with the baseline,the blood oxygenation decreased significantly when the CVP was reduced.Base excess and HCO 3-in groups A and B were significantly decreased compared with those in groups C,D and E(P<0.05).CONCLUSION:In consideration of blood loss,SBP,base excess and HCO 3-,a CVP of 2.1-3 mmHg was optimal in patients undergoing partial hepatectomy for HCC.
文摘BACKGROUND:Following curative treatment for hepato-cellular carcinoma(HCC),50%-90% of postoperative death is due to recurrent disease.Intra-hepatic recurrence is frequently the only site of recurrence.Thus,any neoadjuvant or adjuvant therapy,which can decrease or delay the incidence of intra-hepatic recurrence,or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant,will improve the results of liver resection.This article systematically reviewed the current evidence of neoadjuvant,adjuvant, and chemoprevention in partial hepatectomy of HCC. DATA SOURCES:Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to November 2008 using the keywords "hepatocellular carcinoma","hepatectomy","adjuvant therapy","neoadjuvant therapy",and"regional therapy". Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS:Neoadjuvant transarterial chemoembolization or adjuvant regional transarterial chemotherapy± embolization+systemic chemotherapy did not add benefit. Both adjuvant transarterial radioembolization with 131 I-lipiodol and adjuvant systemic interferon showed promising results.However,there were only a limited number of such studies.CONCLUSIONS:Further randomized controlled studies need to be carried out.Currently,there is no consensus on a standard neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for HCC.
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.
基金supported by a grant from Scientific and Technological Project of Chongqing city(CSTC2012gg-yyjs10016)
文摘Under ultrasound guidance, a blunt suture needle was inserted around the Glissonian pedicle and then sutured. This technique significantly reduced the blood loss and facilitated the procedure of partial hepatectomy. We applied this technique in 182 patients who needed partial hepatectomy. We concluded that this method is simple and easy to occlude the vascular inflow and outflow, and allows an accurate delineation of the anatomic zone and therefore, simplifies the procedure of partial hepatectomy.
文摘BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H_2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H_2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH_2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.
文摘Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury(AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs.
文摘AIM To identify risk factors for the occurrence of acute kidney injury(AKI) in the postoperative period of partial hepatectomies. METHODS Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified. RESULTS Of the total 446 partial liver resections, postoperative AKI occurred in 80 cases(17.9%). Identified predictors of AKI were: Non-dialytic chronic kidney injury(CKI), biliary obstruction, the Model for End-Stage Liver Disease(MELD) score, the extent of hepatic resection, the occurrence of intraoperative hemodynamic instability, post-hepatectomy haemorrhage, and postoperative sepsis. CONCLUSION The MELD score, the presence of non-dialytic CKIand biliary obstruction in the preoperative period, and perioperative hemodynamics instability, bleeding, and sepsis are risk factors for the occurrence of AKI in patients that underwent partial hepatectomy.
基金supported by grants from the National Natural Science Foundation of China(Nos.30370341and 30570410)the Academic Foundation for Author of National Excellent Doctoral Dissertation of China(No.200261).
文摘BACKGROUND:The anti-proliferative gene,PC3(pheoch- romocytoma cell 3)/BTG2(B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family.This study aimed to assess the effects of recombinant human hepatopoietin(HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma(HCC)at different stages of progression. METHODS:After a rat model of partial hepatectomy was established,we investigated gene expression within 1 hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system.The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile,the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization. RESULTS:The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation.HPO rapidly induced the expression of the genes c-fos,LRF-1,and PC3 in primary cultured rat hepatocytes,which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation.Positive BTG2 mRNA expression was detected in 71.19%(42/59)of the HCC samples and in 75%(3/4)of the normal liver tissue samples obtained from the region around the HCC tissues.PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation. CONCLUSIONS:Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/ BTG2 gene.PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation.The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC,so PC3/BTG2 may play an important role in these processes.
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.
文摘In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.
文摘AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. KaplanMeier method and the log-rank test were used for ahalyzing the survival after PH. Differences in the resultsof immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH.CONCLUSION: Our findings indicate that overexpression of NK2 inhibits liver regeneration after PH.
