Comparative Study Of Several Staging Systems Of Hepatocellular Carcinoma And Experiences Of Lin Lizhu's Treatment?

The First StudyObjectiveBy collecting clinical data of hepatocellular carcinoma patients,one is to verify and compare each staging system,observe the accuracy of prognosis evaluation,and discuss the feasibility of some clinical treatments;the other is to improve and optimize the existing staging system which is widely accepted to remove its main shortcomings.These stages are represented by Barcelona phasing and TNM staging.The modified staging was compared with other stages.Finally,the corresponding conclusions are drawn.The three is to establish a new stage of TCM syndrome type,and try to explore its relationship with the stages of modern medicine.MethodsFrom September 2011 to August 2016,658 cases of hepatocellular carcinoma(HCC)were treated in the hospital or outpatient department of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and Linan People's Hospital.Of them,568 cases were classified according to TCM syndrome differentiation.Kaplan-Meier method was used to analyze single and multiple factors survival,and COX multifactor regression analysis was used to get survival regression equation.On the basis of this equation,TNM staging was improved and a new staging was obtained.The prognostic judgment ability of staging system includes three aspects:homogeneity,that is,the survival time of patients divided into the same group has little difference;discrimination:the survival time of patients in different groups has obvious difference;single trend:the later the staging,the worse the survival situation.SPSS21.0 was used to calculate the cumulative survival rate of patients in each stage,Kaplan-Meier curve was used to represent the cumulative survival rate,and Log rank test was used to compare the Likelihood Ratio x2 of each stage system to show the homogeneity of each stage system;R language(Version 3.3.1)was used to calculate the homogeneity of each stage system.AIC and C-index were used to evaluate their discriminative power and single trend.If the two are inconsistent,C-index is the main method,and the area under the ROC curve of the subjects in each stage can be calculated according to the living conditions of half a year,one year and two years respectively.The prognostic accuracy of the following stages was compared:Child-Pugh liver function classification,Okuda stage,CLIP stage,Barcelona stage,7th Edition TNM stage,old edition(2001 edition)China stage,HKLC stage,new edition China stage(2017 edition),8th Edition TNM stage and new stage.Based on the results,the practicability of each stage is further discussed.According to its shortcomings,the most widely accepted Barcelona stage is further improved.Similarly,according to the Kaplan-Meier method,568 patients were divided into five groups according to TCM syndrome types,and the survival time of each group was compared in pairs.According to the results,the syndrome group with no statistical difference was merged.Finally,the survival time of each group was statistically significant,and a simple staging of TCM syndrome was obtained.Then discuss its relationship with Barcelona staging.Results1.Univariate analysis showed that age,symptoms,drinking history,KPS score,tumor number,tumor maximum diameter,vascular invasion,AFP,CA199,CA125,prothrombin time,international standardized ratio,total bilirubin,direct bilirubin,indirect Bilirubin,alanine aminotransferase,glutamic oxaloacetic aminotransferase,serum albumin,lymph node metastasis,distant metastasis.COX multivariate analysis showed that KPS score,tumor number,tumor maximum diameter,vascular invasion,AFP,CA199,CA125,prothrombin time,total bilirubin,albumin,lymph node metastasis,distant metastasis.And a regression model is obtained.2.On the basis of the above results,we fitted a new staging system,modified JIS staging system,which was composed of the TNM staging system of the 8th Edition and the Child-Pugh score,and compared it with the other 9 staging.The results showed that the AIC of Child-Pugh score,the 7th edition TNM staging system,the 8th edition TNM staging system,the Okuda staging system,CLIP,BCLC,old version(2001 version)Chinese staging system,HKLC,new Chinese staging system(2017 version),and modified JIS staging system were 6613.034,6619.104,6576.420,6722.428,6435.534,6312.684,6415.678,6323.163,6437.79 and 6307.611,respectively.LR x2 were 355.413,349.342,392.026,246.018,532.912,655.763,552.768,736.283,530.657 and 660.835,respectively.C-index were 0.708,0.707,0.709,0.683,0.771,0.761,0.753,0.808,0.771 and 0.784,respectively.The area under the ROC curve of six-month,one-year and two-year survival conditions with the above staging systems were 0.640?0.611?0.580;0.686?0.715?0869;0.677?0.702?0.878;0.564?0.553?0.539;0.780?0.768?0.837;0.628?0.624?0.707;0.647?0.650?0.774;0.825?0.791?0.900;0.716?0.725?0.895;0.764?0.749?0.833 respectively.3.These comparisons suggest that Barcelona' s prognostic assessment is not very effective,but because it is currently the most widely accepted staging,facilitating scientific research and communication,it is considered to optimize its improvement.According to the results of the regression model,the most widely accepted Barcelona staging was refined and improved by using Child-Pugh liver function grading as a related index.The patients in stage C,grade A,and grade B were classified as C1 and C2 respectively,and stage 0 of he 2010 edition of Barcelona stage was introduced.Compared with the above stages,the AIC value was 6251.281,the LR x2 was 717.165,and the C-index value was 0.802.The area under the ROC curve of the six months,1 years and 2 years of survival was 0.775,0.773 and 0.868 respectively.The accuracy of prognostic assessment in 11 stages is ranked 2nd,which is much better than the previous Barcelona stage.The staging method is simple and convenient.4.According to the relationship between TCM syndromes and survival time,a simple staging of TCM syndromes is obtained,that is,liver stagnation and spleen deficiency are the main type in the early stage,liver heat and blood stasis,liver and gallbladder dampness-heat,spleen deficiency and dampness-retention in the middle stage,and liver and kidney yin deficiency in the late stage.The distribution characteristics are related to the Barcelona score.Conclusion1.For Chinese patients with advanced hepatocellular carcinoma(HCC),the prognostic criteria for each staging system with descending ability were:HKLC stage,modified Barcelona stage,modified JIS stage,new Chinese staging system(2017 version),CLIP,BCLC,old version(2001 version)Chinese staging system,the 8th edition TNM staging system,Child-Pugh score,the 7th edition TNM staging system,and Okuda staging system;2.On the basis of the above conclusions,combined with the practicability and guidance of staging,the corresponding conclusion is drawn:for the purpose of clinical evaluation and scientific research exchange,the modified Barcelona staging can be considered,and its specific clinical treatment advice can be mainly referred to the Chinese staging of the 2017 edition.In addition,HKLC staging may also be useful in assessing the prognosis of patients in Guangdong,Hong Kong and Macao.The improved JIS staging and Barcelona staging obtained in this study have further validation and development value.3.The syndrome types of TCM have a certain relationship with the survival time.The staging of TCM obtained in this study also has the value of further verification and development,and has a certain correlation with Barcelona staging.The Second StudyObjectiveTo summarize the use of traditional Chinese medicine in the treatment of hepatocellular carcinoma by Professor Lin Lizhu,and to further explore new prescriptions,so as to provide some ideas and methods for clinical treatment.mexnoasTo collect the prescriptions of traditional Chinese medicine for hepatocellular carcinoma(HCC)from the tutor of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Professor Lin Lizhu,from September 2015 to June 2017.Then,the above prescriptions are analyzed by using the Chinese Medicine Heritage Assistant System(2.5 edition).The software has improved mutual information method,rule analysis,complex system and unsupervised entropy clustering method,which can be used to mine and analyze medical records and prescriptions.Results1.A total of 492 prescriptions of traditional Chinese medicine were obtained,and the frequency of syndrome types was from high to low:337 times of liver depression and spleen deficiency,109 times of liver heat and blood stasis,35 times of liver and gallbladder dampness and heat,7 times of spleen deficiency and dampness retention,4 times of liver and kidney yin deficiency.2.The frequency of use of the top 20 drugs in the following order:licorice,peach kernel,woodlouse bug,Solanum nigrum,arrowhead,Taxus,snail,Sabra,Scutellaria Barbara,Costus,Poria,Fructus aurantii,Rhizoma Atractylodis Macrocephalae,Rhizoma Zedoariae,Rhizoma Pinelliae,Radix Codonopsis,Radix Paeoniae Alba,bupleurum,Alisma orientalis,turtle shell,dandelion.3.Drug category analysis showed that the top 5 drug categories were:heat-clearing drugs,deficiency-tonifying drugs,antiepisodic drugs,Dampness-eliminating drugs,blood-activating and stasis-removing drugs.4.The statistical analysis of four gases of the drug was followed by frequency,followed by cold,flat,warm,cool and hot.The five flavours of drugs are decreased by frequency,sweet,bitter,spicy,sour,astringent and salty.According to the statistics of attributive channel,the descending order of the frequency is liver,spleen,stomach,heart,lung,kidney,large intestine,gallbladder,bladder,triple jiao,small intestine and pericardium.The number of prescription drugs is 14 to 18;5.Based on the analysis of association rules,8 drugs were obtained,licorice,peach kernel,woodlouse worm,Long Kui,arrowhead,Taxus,Herba Scutellariae,and Scutellaria.That is the therapeutic drug used according to the characteristics of this disease.6.Based on the analysis of association rules,according to the different syndrome types,in addition to the above 8 drugs,we can get Codonopsis pilosula,Atractylodes macrocephala,Poria cocos,Radix Paeoniae Alba,Fructus Aurantii,Radix Bupleuri,Rhizoma Typhoniae and Pinellia ternate.Ligustrum lucidum,Lotus tuber,Muxiang,Pinellia ternate,Rhizoma Parthenocissus,Turtle shell,Zedoary rhizome and Rubiae are commonly used drugs for liver-heat and blood stasis.7.Based on the improved mutual information method to analyze drug association degree and complex system entropy clustering analysis of core drug combinations,7 new prescriptions were obtained on the basis of unsupervised entropy hierarchical clustering analysis.The specific composition is as follows:Formuta I:Fructus aurantii Immaturus,Cynanchum paniculate,Magnolia officinalis,Cortex Magnoliae officinalis,arrowhead,Solanum nigrum,woodlouse worm,and aspera glabra;Formula 2:madder,Paris,turtle shell,bupleurum and Herba asperiae;Formuta 3:Codonopsis pilosula,Peony bark,Atractylodes macrocephala,Rehmannia glutinosa;Formula 4:Yinchen,Shancigu,Swollen rhizome,Tianji Huang,Xi Huangcao;Formuta 5:Prepared Rehmannia glutinosa,Mulberry parasitic Ming Zi and mulberry;No.6:Almond,Bombyx mori,Houttuynia cordata,Palace Guardian,Aconite and Cinnamomum twig;No.7 Uncaria,Chuanxiong,Gastrodia elata,Angelica dahurica.Conclusion1.Summarize the medication rule of tutors in treating hepatocellular carcinoma,that is,differentiation and treatment on the basis of differentiation of diseases.The treatment methods used for differentiating diseases are activating blood circulation to dissipate blood stasis,clearing away heat and detoxifying.The specific medication is woodlouse worm,peach kernel,Solanum nigrum,asarum,arrowhead,Scutellaria Barbara,Taxus and licorice.The results of syndrome differentiation and treatment were as follows:the liver depression and spleen deficiency type was modified by Sijunzi Decoction and Sini powder,and if the stomach fullness and stuffy,the stomach fullness and discomfort,then No.1 prescription was added or subtracted to remove the fullness;the Liver heat and blood stasis type treatment with clearing away heat and cooling blood stasis and nourishing yin and kidney,with Erzhi pills add or subtract turtle shell,Ruffy grass,Paris and so on;Liver and gallbladder dampness-heat type is clear heat,dampness and yellowing,add and subtract with No.4 prescription;Spleen deficiency and dampness-trapped with Sijunzi decoction;Liver and kidney yin deficiency,nourishing kidney,nourishing yin and clearing heat,combined with No.3 and 5 prescriptions add or subtract.Such as yin deficiency and fever,can be used for nourishing Yin,clearing heat and cooling blood by prescription No.2 If have a headache at the same time,then add and subtract with No.7 prescription to cool blood and promote blood circulation,remove blood stasis and relieve pain;if spleen deficiency is obvious,phlegm turbidity internal obstruction,then consider invigorating the spleen and removing dampness and phlegm,add and subtract with No.6 prescription.2.The tutor emphasized the treatment concept of integrated TCM and Western medicine,and carried out staging treatment.Taking Barcelona staging as an example,patients of stage A,Zheng Qi is not weak,pathogenic factor is not strong.They were treated radically with western medicine to eradicate disease pathogens,and the main treatment was to nourish soil element and protect the body' s vital energy during the perioperative period.In the stage B and C,most of the cases are of excessive pathogenicity without deficiency of vital energy,and there are many disputes between positive and pathogenic factors.At this time,the purpose of“protecting liver and suppressing tumor”is to deal with adverse reactions and restore the body' s integrity on the basis of local minimally invasive treatment or systematic treatment of eliminating pathogens.Regular function;according to the different syndrome types of liver-heat with dampness,blood stasis or spleen deficiency,TCM syndrome differentiation and treatment;end-stage patients,BCLC staging recommended the best support treatment.At this time,it is that the deficiency of Zheng Qi is obvious,and it is unable to resist pathogenic factors,mostly for nourishing the liver,kidney yin,and protecting the liver function of patients.In the whole course of treatment,we should pay attention to protecting the liver function of patients.For some patients of hepatocellular carcinoma that can not be cured,"survive with tumors" to maintain a dynamic balance between them.In addition,tutor also pays attention to the combination of medical treatment and recuperation.3.On the basis of the above research,the next step is to establish a staging system of integrated traditional Chinese and Western medicine which is suitable for the Chinese people,and to include all the guidance of medical treatment,psychology,diet and exercise into the staging system,so as to achieve a truly comprehensive and detailed guidance for the treatment and regulation of hepatocellular carcinoma patients in China.This is also the true significance of this study lies.