| Part I:Clinical Study of Liver Regeneration after Hemi-HepatectomyObjective:To investigate the ratio of liver regeneration and the factors affecting the degree of liver regeneration in patients with Hepatocellular Carcinoma(HCC)after hemi-hepatectomy,and to establish a preoperative prediction model of liver regeneration and evaluate its predictive efficacy.Methods:Between the September 2013 to December 2017 in the Affiliated Tumor Hospital of Guang Xi Medical University,A total of 125 HCC patients whom suffer hemi-hepatectomy were clinical analysize.The volumes of preoperative Total Liver Volume(TLV),Tumor size,Tumor Volume(TV),resected of Liver Volume(r-LV)and Remnant Liver Volume(RLV)by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.After hemi-hepatectomy,the 1st,5th,9th and 13th CT examination were measured respectively,at the same time,Future Liver Remnant Volume,FLRV were measured after hemi-hepatectomy by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.According to the degree of liver regeneration volume after hemi-hepatectomy,all the HCC patients were divided into the liver regeneration significant group and liver regeneration not significant group.The clinical risk factors of the liver regeneration degree were evluated by using univariate analysis and logistics multivariate analysis after hemi-hepatectomy.The preoperative predicte liver regeneration model were construct by using nomogram basing the results of the multivariate analysis after hemi-hepatectomy.The accurcy and effieiciency of the predicte liver regeneration model were verified by using its own control validation.Results:A total of 125 patients with hemi-hepatectomy were enrolled,including 72(57.6%)patients with right hemi-hepatectomy and 53(42.4%)patients with left hemi-hepatectomy.Thirteen patients suffered Post-Hepatectomy Liver Failure(PHLF)after hemi-hepatectomy,and 1 patient died of PHLF within 90 days.According to the median liver volume regeneration rate of 21.3%at the first week after hemi-hepatectomy,the patients were divided into two groups:liver regeneration significant group(liver volume regeneration rate>21.3%)and liver regeneration insignificant group(liver volume regeneration rate<21.3%).The research results showed:(1)The univariate analysis showed:gender,age,BMI,BSA,diabetes,HBV-DNA level,whether the antiviral treatment perioperative,AFP level,total bilirubin,albumin,alanine aminotransferase,aspertate aminotransferase,prothrombin time,blood platelet count,model for end-stage liver disease score,portal venous tumor emboli,operation time,blood loss,resected liver volume,spleen volume were no statistical difference by comparison in the two groups(P>0.05).There were statistically significant differences in cirrhosis,portal vein occlusion,postoperative complications degree,FLV,TV,RLV and%RLV by using the univariate analysis(P<0.05).(2)The results of logistic regression multivariate analysis showed that:RLV<601 cm~3(OR=0.230,95%CI:0.074-0.717,P=0.011),%RLV(OR=0.271,95%CI:0.077-0.960,P=0.043)and cirrhosis(OR=7.740,95%CI:2.748--21.798,P<0.001)were the risk factors for liver regeneration after hemihepatectomy.According to the multivariate analysis results,a Nomogram model for predicting postoperative liver regeneration was successfully established.The Area Under the curve(AUC=0.889,95%CI:0.831-0.948)of ROC was verified by the calibration curve.The difference between the predicted value and the true value was small.(3)The Growth Ratio(GR)of the median FLRV at 1st,5th,9th and 13th weeks after hemi-hepatectomy were21.3%,30.9%,34.6%and 37.1%,respectively.The liver regeneration rate in the right hemichorectomy group,PHLF group,no cirrhosis group and severe postoperative complications group were significantly higher than those patients in the left hemi-hepatectomy group,none PHLF group,cirrhosis group and mild postoperative complications group(all P<0.05).There was no statistically significant difference between the age groups(P>0.05).The median Net growth ratio(?GR)of liver volume at 1st,5th,9th and 13th weeks after hemi-hepatectomy were 26.6%,7.4%,3.6%and 1.3%,respectively.(4)There was no significant difference in liver function indexes between the liver regeneration significant group and the liver regeneration non-significant group before liver resection and the 9th and 13th weeks after hemi-hepatectomy(P>0.05).Compared with the liver regeneration non-significant group,the levels of TBil and PT were higher in the liver regeneration significant group at week 1and weeks 5,while the levels of ALB and PA were lower(P<0.05)between the two groups.However,There was no significant difference in AST and ALT between the two groups(P>0.05).Conclusion:(1)The liver volume regeneration was obviously after hemi-hepatectomy,especially in the first week after the liver resection.And then the liver regeneration ratio decreased gradually as time goes on.The liver volume regeneration was not obvious and tended to be stable after the fifth week postoperative.(2)The degree of liver regeneration after hemi-hepatectomy is closely related to RLV,%RLV and cirrhosis.The establishment of a nomogram model can accurately predict the incidence of postoperative significant liver regeneration preoperative.(3)Liver volume regeneration is not equal to the function regeneration of cell.With the occurrence of liver regeneration and the maturation of cell function,liver function gradually recovered after hemi-hepatectomy.Part Ⅱ: Clinical Study of Post-Hepatectomy Liver Failure after Hemi-HepatectomyObjective: To investigate the influencing factors of liver failure(PHLF),construct the preoperative model to predict the occurance of PHLF,and compare the efficacy of different liver volume assessment indexes in predicting PHLF in patients with Hepatocellular Carcinoma(HCC)after hemihepatectomy.Methods: Between the September 2013 to December 2017 in the Affiliated Tumor Hospital of Guang Xi Medical University,A total of 125 HCC patients whom suffer hemi-hepatectomy were clinical analysize.The volumes of preoperative Total Liver Volume(TLV),Tumor size,Tumor Volume(TV),resected of Liver Volume(r-LV)and Remnant Liver Volume(RLV)by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.After hemi-hepatectomy,the 1st,5th,9th and 13 th CT examination were measured respectively,at the same time,Future Liver Remnant Volume(FLRV)were measured after hemi-hepatectomy by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.The risk factors of PHLF under different diagnostic criteria were compared by univariate and multivariate analysis.The preoperative predicte PHLF model underent different diagnostic criteria were construct by using nomogram basing the results of the multivariate analysis after hemi-hepatectomy.The cut-off value,sensitivity and specificity of %RLV,RLV/SLV,RLV/BW,SRLV and SV/RLV in predicting PHLF after hemi-hepatectomy were calculated.The ROC curves of the five predictors were compared to evaluate the efficacy of predicting PHLF after hemihepatectomy.Results: A total of 125 patients with hemi-hepatectomy were enrolled,including 72(57.6%)patients with right hemi-hepatectomy and 53(42.4%)patients with left hemi-hepatectomy.One case died due to PHLF within 90 days after hemi-hepatectomy.(1)The diagnostic criteria of liver failure: "50-50criteria" was used to divide the patients into PHLF50-50 group(n = 13)and no-PHLF50-50 group(n = 112).The univariate results of the two groups showed statistically significant differences in total bilirubin,SSV,FLV,SRLV and SV/RLV(all P < 0.05).Multivariate results showed that total bilirubin(TBIL)(OR:0.814,95% CI:0.715-0.927,P = 0.002),SRLV(OR:1.020,95% CI:1.003-1.037,P = 0.021),SSV(OR:0.984,95% CI:0.970-0.998,P = 0.023)were risk factors for PHLF after hemi-hepatectomy.Based on the multivariate analysis results,a Nomogram prediction model for PHLF based on the "50-50criterion" was successfully constructed.The AUC was 0.927(95% CI: 0.857-1.000)by using the ROC curve.The difference was small between the predicted value and the true value by by the calibration curve verifing.RLV/SLV(cut-off value: 48.83%,AUC = 0.808,sensitivity 84.6%,specificity 65.8%,95% CI:0.728-0.873),and SRLV(cut-off value:345.6 ml/m2,AUC = 0.808,sensitivity84.6%,specificity 65.8%,95% CI: 0.728-0.873)were better than %RLV(cut-off value: 61.64%,AUC = 0.690,sensitivity 84.6%,specificity57.7%,95% CI: 0.6-0.77),RLV/BW(cut-off value: 9.77,AUC = 0.770,sensitivity 84.6%,specificity 61.3%,95% CI: 0.686-0.841),SV/RLV(cut-off value: 0.44,AUC=0.821,sensitivity 69.2%,specificity 87.4%,95% CI: 0.741-0.884).Comparison of ROC curves showed that SRLV vs RLV/BW and RLV/SLV vs RLV/BW showed statistically significant differences(P = 0.029).Pairwise comparison of other indicators showed no statistical significance(all P > 0.05).(2)The patients were divided into PHLFNON +A group(no liver failure+ grade A liver failure)and PHLFB+C group(grade B+C liver failure)using the "ISGLS criterion".A total of 48 patients(48/125,38.4%)developed grade B or C PHLF,among which 1 patient with grade C PHLF died within 3 months after hemi-hepatectomy.The univariate analyse results of the two groups showed statistically significant differences in liver cirrhosis,AST,blood loss,tumor size,SSV,r LV,SRLV,APRI,SV/RLV(all P < 0.05).Multivariate analyse results showed that AST(OR:0.980,95% CI: 0.961-0.999,P = 0.040),blood loss(OR:0.998,95% CI: 0.997-0.999,P = 0.001),SRLV(OR : 1.013,95%CI:1.007-1.019,P = 0.001),SSV(OR:0.983,95% CI: 0.972-0.994,P=0.002),rLV(OR:0.998,95% CI: 0.996-1.000,P=0.039)and liver cirrhosis(OR:0.983,95% CI: 0.972-0.994,P=0.002)were risk factors for PHLF after hemihepatectomy(all P < 0.05).Based on the multivariate analysis results,a Nomogram prediction model for PHLF based on the "ISGLS criterion" was successfully constructed.The AUC was 0.877(95% CI: 0.817 – 0.936)by using the ROC curve.The difference was small between the predicted value and the true value by by the calibration curve verifing.RLV/SLV(cut-off value 50.94%(AUC=0.755,sensitivity 68.7%,specificity 75.3%,95% CI: 0.67-0.827)and SRLV(cut-off value 360.6ml/m2(AUC=0.755,sensitivity 68.7%,specificity75.3%,95%CI: 0.67-0.827)were better than %RLV(cut-off value 54.65%(AUC=0.751,sensitivity 64.6%,specificity 77.9%,95%CI: 0.665-0.824)in predicting PHLF,RLV/BW(cut-off value 9.46(AUC=0.726,sensitivity 62.5%,specificity 75.3%,95% CI: 0.639--0.802),SV/RLV(cut-off value 0.302(AUC=0.736,sensitivity 62.5%,specificity 74%,95% CI: 0.665-0.811).Comparison of ROC curves showed that SRLV vs RLV/BW and RLV/SLV vs RLV/BW had statistical significance(P < 0.01).Pairwise comparison of other indicators showed no statistical significance(P > 0.05).Conclusion: SRLV and SSV are key stable risk factors for predicting PHLF under different diagnostic criteria,and also can accurately predict the occurrence of PHLF after hemi-hepatectomy.%RLV,RLV/SLV,RLV/BW,SRLV and SV/RLV are all effective predictors of PHLF after hemihepatectomy,and RLV/SLV and SRLV are more effective than other indexes in predicting PHLF after hemi-hepatectomy.Part Ⅲ: Clinical Study of Portal Hypertension and its Relation with Liver Regeneration and Post-Hepatectomy Failure after Hemi-HepatectomyObjective: To investigate the changes of portal venous pressure in patients with Hepatocellular Carcinoma(HCC)after hemichorectomy at different stages and its influencing factors in patients with Hepatocellular Carcinoma(HCC)after hemihepatectomy.Constructing a preoperative prediction model of increased portal venous pressure after hemi-hepatectomy and exploring the correlation between portal venous pressure change in the first week after hemichorectomy and postoperative liver regeneration and liver failure.Methods: Between the September 2013 to December 2017 in the Affiliated Tumor Hospital of Guang Xi Medical University,A total of 125 HCC patients whom suffer hemi-hepatectomy were clinical analysize.The volumes of preoperative Total Liver Volume(TLV),Tumor size,Tumor Volume(TV),resected of Liver Volume(r-LV)and Remnant Liver Volume(RLV)by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.After hemi-hepatectomy,the 1st,5th,9th and 13 th CT examination were measured respectively,at the same time,Future Liver Remnant Volume(FLRV)were measured after hemi-hepatectomy by using the Myrian three-dimensional surgery planning system software for all the HCC pateients.According to the increase degree of postoperative Hepatic Venous Pressure Gradient(HVPG),the patients were divided into ?HVPG increased significantly group and the ?HVPG increased insignificantly grooup.The risk factors affecting the increase of ?HVPG after hemi-hepatectomy were analyzed by univariate analysis and logistic regression multivariate analysis.The preoperative prediction model of the increase of ?HVPG after hemihepatectomy was established by nomogram.Correlation analysis and ROC curve were used to analyze the correlation between the increase of ?HVPG and liver regeneration,as well as the correlation between the increase of ?HVPG and postoperative PHLF.Results: A total of 125 patients with hemi-hepatectomy were enrolled,including 72(57.6%)patients with right hemi-hepatectomy and 53(42.4%)patients with left hemi-hepatectomy.Thirteen patients suffered Post-Hepatectomy Liver Failure(PHLF)after hemi-hepatectomy,and 1 patient died of PHLF within 90 days.According to the median increase of 4.86 mm Hg in the first week after hemi-hepatectomy,the patients were divided into two groups: ?HVPG increased significantly(?HVPG > 4.86 mm Hg)group and ?HVPG increased insignificantly(?HVPG < 4.86 mm Hg)group.The results showed:(1)The median spleen volume(minimum and maximum)increased from 168.5(46-474)preoperatively to 168.5(46-474),226(72-582),210(54.8-588),217(60-591),and 210(59-596)at 1st,5th,9th,and 13 th weeks after hemi-hepatectomy,with statistical differences compared with preoperatively(all P < 0.05).Median platelet count(minimum and maximum)decreased from 240.6(86.1-336)before surgery to 181(36-294),183(75-295),186(77.8-291)and 191(76-292)at 1st,5th,9th,and 13 th weeks after hemi-hepatectomy,with statistical significance while compared with that preoperative(all P < 0.05).(2)The median(minimum and maximum)HVPG at preoperative,the 1st,5th,9th and 13 th weeks on post-operative were 8.41(2.85-13.65)mm Hg,13.04(4.91-19.83)mm Hg,10.99(5.03-17.39)mm Hg,11.09(5.36-18.76)mm Hg and10.93(5.37-18.39)mm Hg,respectively.HVPG at 1st,5th,9th and 13 th weeks after hemi-hepatectomy increased by 4.85(-0.18-10.08),2.30(-0.77-7.28),2.37(-0.78-6.19)and 2.35(-1.21-6.80),respectively,compared to the preoperative,with statistical significance(all P < 0.05).Subgroup analysis results indicate that the ? HVPG differences were statistically significant(all P < 0.05)while compared the right hemi-hepatectomy group,PHLF group,liver cirrhosis group,severe complications group compared to the left hemi-hepatectomy,none-PHLF group,none-liver cirrhosis group,mild complications.However,while compare liver regeneration significantly group,elder age groups to the no significant liver regeneration and younger group,the ?HVPG differences had no statistical difference(P > 0.05)on postoperative 1th week after hemi-hepatectomy.(3)There were no statistical significant differences in age,BSA,diabetic,HBV DNA level,whether the antiviral treatment,AFP,INR,bilirubin,albumin,alanine aminotransferase,aspertate aminotransferase,prothrombin time,blood platelet count,ascites,esophageal gastric varices,portal vein diameter,operation method,operation duration,the first door block,blood loss,liver tumor size,tumor size,RLV and preoperative spleen volume(all P > 0.05).There were significant differences in gender,MELD score,cirrhosis,BMI and resected liver volume(all P < 0.05).Logistics multivariate regression analysis showed that the resected liver volume(>820cm3)(OR=4.424,95% CI: 1.106-17.692,P=0.035),cirrhosis of the liver(OR=84.843,95%CI: 20.175-356.788,P < 0.001)and RLV(OR=3.415,95% CI: 1.183-14.271,P = 0.029)were risk factors for increasing HVPG after hemi-hepatectomy.(4)A Nomogram model for predicting postoperative increasing HVPG was successfully constructed based on multivariate analysis.The area under the ROC curve(AUC)was 0.951(95% CI 0.917-0.984).(5)The liver regeneration rates of ?HVPG significant increasing group and with no significant increasing group were 31.48%±22.09%,21.25±19.51%,respectively.The difference was statistically significant(P=0.007)in these 2 groups.Correlation analysis showed that liver regeneration rate was positively correlated with ?HVPG(r=0.283,P=0.002).According to the 50-50 criterion,patients were divided into PHLF group and non-PHLF group.Postoperative liver regeneration rates of the two groups were 42.6% ± 21.1%and 22.3% ± 18.5%,respectively.And the difference between the two groups was statistically significant(P < 0.001).?HVPG were 7.02 ± 1.44 mm Hg and4.44 ± 2.43 mm Hg in PHLF group and non-PHLF group,respectively.The difference was statistically significant(P=0.001).The cut-off value of ?HVPG,which resulted in PHLF,was 5.83 mm Hg on the first week.(AUC=0.81,95%CI: 0.729-0.892).Conclusion :(1)Hemi-hepatectomy can lead to increased spleen volume,decreased platelet count and increased HVPG,and the changes were most significant at first week postoperatively.The most significant change was observed at the first week after hemi-hepatectomy.Compared to the 1st week postoperatively,the spleen volume and HVPG decreased on 5th weeks postoperatively,while platelet counts increased somewhat.These changes were tended to be stable at 9th and 13 th weeks postoperatively.(2)Resected liver volume(>820cm3),liver cirrhosis and RLV are risk factors for increasing HVPG after hemihepatectomy.The construction of preoperative nomogram model can accurately predict the occurrence risk of significantly increased HVPG after hemi-hepatectomy.(3)HVPG increased after hemihepatectomy,which can promote liver regeneration,but while ?HVPG > 5.83 mm Hg,the risk of postoperative PHLF was significantly increased. |
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