Review Of Traditional Chinese Medicine Literature Of Hepatocellular Carcinoma And Wu Yu 's Physician' S Experience In Syndrome Differentiation

According to a paper published in 2012, named" Traditional Chinese Medicine Zheng in the Era of Evidence-Based Medicine:A Literature Analysis", indicates in the early time, the majority of Chinese Medicine Research publication is from the perspective of TCM syndromes "Zheng" to research medical issues. However, in the recent years, the Chinese Medicine Research publication from perspective of "Zheng" in application with pathology to research medical issue gradually increase. Such trend demonstrates Chinese Medicine Research has gradually applied the research efforts of the modern pathology and physiology. This paper attempts to introduce the methodology (systematic review) of the evidence-based medicine to research the relationship between Zhengs of Liver Cancer and objective indicators, which can be laboratory or imaging results.The document retrieval method for this paper is to search the full contents of documents in the China Journal CNKI digital library database with the keywords of "Zheng", "Objective Indicator" and "Liver Cancer". The search result is that 1331 documents are obtained. By preliminarily screening the aforesaid documents obtained,109 documents are identified that includes the research the relationship between Zheng of liver cancer and objective indicators. By reading the full text of the search results,46 documents are identified.9 out of 46 documents are the animal-based experiments research based documents and 37 out of 46 are the clinical observation documents.46 documents contain a total of 33 different Zhengs, and a total of 98 different objective indicators. The top 3 of 33 Zhengs are the spleen-deficiency Zheng, yin-deficient of liver and kidney Zheng, stagnation of qi and blood stasis Zheng.The first part of this paper:the discussion on the potential application of methodology (systematic review) of evidence-based medicine in the objectivization of Zheng diagnosis system.Traditionally, the Zheng diagnosis for Chinese Medicine Doctor is based on the different symptom or sign of each patient. Hence, Zheng diagnosis is subjective. However, in order to response the modern pathology and advanced imaging technology, a reach topic is addressed how to reasonably and objectively apply the objective indicators of laboratory or imaging results into Zheng diagnosis system. In order to discuss the possibility of objectivization of Zheng diagnosis system, this part tries to introduce the concepts and methodology of evidence-base medicine on the Zheng research concerning the relationship between Zheng and objective indicators. Furthermore, a concept of Systematic Review shall be mentioned, which is an approach of EBM that uses methods systematically to evaluate the literature search results in order to obtain the best evidence among all available publication. Because of the different study design of each document, some concepts shall be addresses, such as the identification of documents, search strategy, quality evaluation, and the heterogeneity.Therefore, the following concepts will be addressed:1. Search method (how to program the search formula, including which databases shall be searched, what kind of keyword shall be used; how to identify the documents); 2. Critical evaluation (what kind of critical evaluation shall be applied; how to evaluate the documents obtained); 3. Literature heterogeneity problem (what is the Literature heterogeneity; how to appropriately address the heterogeneity of documents); and 4 Descriptive Analysis (how to choose appropriate analysis method for the document with clinical heterogeneity).Part 2:Literature Survey on the documents concerning the relationship between Zheng of Liver Cancer and objective indicators.BACKGROUND:The more research efforts focus on the combination of Traditonal and Western Medicine in treating HCC. In response to such trend, we can discover that the research paper on the relationship between HCC Zheng and objective indicators increases graduatually. However,the rearch results of being inconstistcy is concerned by various researcher. In order to clatify such inconstistcy, we apply the literature survey to research and analyze the documents concerning the relationship between types of syndromes ("Zheng") of Liver Cancer and objective indicators.OBJECTIVE:Traditionally, the Zheng diagnosis is based on the collection of symptom(s) or sign(s) of each patient. Because the characteristics of early stage of liver cancer patient is that there is no obvious signs or symptoms expressed, the purpose of this research is that how to reasonably identify the relsationship between the objective indicators of the modern pathology and advanced imaging technology and Zheng.METHOD: ① Database:CNKI Chinese Journal Database (Web version);② Inclusion Criteria:All documents concern the relationship between Zhengs of Liver cancer and the objective indicators.③ Selection and Evaluation methods: one person independent filters documents twice, and conducts the evaluation on literature publication bias and on document quality.④ In case of clinical heterogeneity of documents obtained:Descriptive Statistical Analysis is applied to such documents.RESULT:① Data collection:After preliminarily filtering the database,1331 documents are collected. There is no document in English version. After screening the aforesaid 1331 documents,109 documents are identified. After reading full context of 109 documents,47 documents are obtained. 9 documents are the animal-based experiment research documents and 37 documents are the clinical observation documents.37 clinical observation documents are analyzed descriptively.② Publication bias analysis:There are 17 different observation or research institutions of total 46 documents. The institutions in Shanghai, Guangzhou, and Hunan are published majority of the doucments obtained. Three research institutions published 9 animal-based experiments research documents, which 7 out of 9 documents were published by Shanghai First Medical College.37 Clinical observation documents are published by 15 research institutions, and 9 of 37 documents were published by Guangzhou University of Chinese Medicine. While only Shanghai First Medical literature published both animal-based experiment research documents and clinical observation documents, which includes 7 animal-based experiments research documents and 3 clinical observation documents.③ QUADAS:Domain 1 (case selection) indicates 57% of documents is at low risk. Domain 2 (the objectivity of CM doctor to make Zheng diagnosis) indicates 63% of documents is at low risk. Domain 3 (The objectivity of evaluation between the relationship between Zheng and objective indicator) indicates 60% of documents is at low risk.④ Descriptive statistical analysis:The method applies to 37 Clinical Observation documents, which include a total of 86 objective indicators. The most popular objective indicators of documents are γ-glutamyl transpeptidase (γ-GT), alpha-fetoprotein (AFP), CD4+8 documents apply r-GT as one of objective indicators to discuss the relationship between Zheng of Liver Cancer and Objective indicator and include 12 different Zhengs. However, only 4 documents express r-GT has significant influence in Zheng diagnosis:γ-GT expresses significant abnormality in stagnation of blood stasis Zheng with qi or spleen deficiency Zheng. 9 documents apply AFP as one of objective indicators to discuss the relationship between Zheng of Liver Cancer and Objective indicator and include 19 different Zhengs. However, only 5 documents express AFP has significant influence in Zheng diagnosis:AFP expresses significant abnormality in qi deficiency and blood stasis Zheng (the figure of AFP is between 200 and 400); the spleen deficiency and blood stasis Zheng (the figure of AFP is more than 400ug/l), and heat Zheng (the figure of AFP is more than 1751ug/l).5 documents apply the immune factors as one of objective indicators to discuss the relationship between Zheng of Liver Cancer and Objective indicator and include 10 different Zhengs. All documents express the immune factors have significant influence in Zheng diagnosis:the immune factors express significant abnormality in the deficiency Zheng.⑤ Because of the heterogeneity among documents obtained, it is very difficult in integrating all the results published by different centers concerning the same medical issues by using the method of meta-analysis. Therefore, it is unable to reasonably integrate data of documents obtained to research the relationship between Zhengs and objective indicators. However, the descripve analysis can be applied.DISCUSSION:First, reluctant to apply the golden standard in the event of diagnosis: currently the golden standard for the diagnosis of liver cancer is histopathological examination of liver tissue. However, only 10 documents express to partially or fully apply such standard to diagnose patients with liver cancer.Second, without written down the Diagnosis Standard and Chinese Medicine Zheng Diagnosis Standard in documents:The patient selection process is based on specific diagnosis or Zheng diagnosis standards to ensure reliability and repeatability studies. However,17 out of 37 the clinical observation documents obtained have not stated a diagnosis standard; and12 have not stated a Zheng diagnosis standard.Third, without written down the patient inclusion and exclusion criteria in documents:each patient has his/her own unique characteristics, such as patient condition, complications, prior treatment and other interventions. Therefore, when a research discusses specific interventions, the outcome of the research will be influenced by unique characteristic of each patient included. Hence, the purpose for the development of inclusion and exclusion criteria is to include the patients with similar characteristics. With such patients, the impact of non-research factors can be eliminated when researcher conducts the effect analysis of interventional treatment. The research more likely can be reproducible. In this paper,6 out of 37 the clinical observation documents obtained state clearly inclusion and exclusion criteria. Clinically, patients with primary liver cancer are often under critical condition. Hence, it is hard to establish the feasibility of the exclusion criteria. However, the research develops an inclusion criterion and details the unique characteristics of each patient selected can improve the practicality of research findings. Therefore, the inclusion criteria shall not be strict and shall be more flexible can bring more benefit on practicality on the research outcome of the relationship between Zheng and objective indicators.Fourth, the relationship between the specific Zheng and objective indicators:there are 31 different Zhengs and 87 objective indicators described in the 37 clinical observation documents obtained. If the research focuses on the relationship between the most popular 5 Zhengs of Liver Cancer and the most popular 3 objective indicators, the outcome of this research indicates AFP expresses significant abnormality in spleen deficiency Zheng. In contrast, the outcomes of the research on the relationship between any Zheng of liver cancer and the most popular 3 objective indicators are (1) γ-GT expresses significant abnormality in stagnation of qi and blood stasis Zheng; (2) AFP expresses significant abnormality in qi deficiency and blood staisi, spleen deficiency and blood stasis Zheng, and heat Zheng; and (3) immuse factors express significant abnormality in deficiency Zheng. In response to such different outcome, it is reasonable to conclude that the research only controls objective indicators can observe more outcomes from the research.Fifth, according to the current conclusion, the specific objective indicators can express significant abnormality in certain Zheng (A=B), but this does not mean that the significant abnormality of a specific objective indicators means a particular Zheng (B><A).Third Part:Case AnalysisAfter reviewing the case reports of clinical patients of Xiyuan Hospial between 2013 and 2014, there are 7 cases elected because of the suffieicnt information of the AFP level in the case reports. In response to the search result of the Second Part, the AFP leverl of the case with the same treatment of search result is relative stable than that with the different one.Fourth Part:Conclusion and DiscussionRegard to the relationship between Zheng and objective indicators of the documents obtained in this paper, there are 33 different Zhengs and 98 different kinds of objective indicators. For the clinical observation documents, there are 31 different Zheng and 87 different objective indicators. With the application of the search result, when the treatment method is in line with the search result, the AFP level is relativelt stable. The diversity topics among documents can be found, such as diagnosis standard, Zheng diagnosis standard, inclusion criteria, etc. Consequently, we are unable to carry out the integration analysis of the results published by different research centers. Therefore, for the designation future research, we learn from the conclusion of this paper. Before designing studies, the designer of each research shall clarify the research methods of the study. The research method can be either (1) observation on the variation of single objective indicator corresponding different symptoms; or (2) the observation on the variation of single symptom corresponding to different objective indicators. Another feature of Chinese Medicine publication is heterogeneity, therefore, how to come up a reasonable methodology allows research results published by different center to be integrated and analyzed.In future studies, the designer shall consider all elements, such as doctors experience, patents preference, current clinical practice, economic issues, etc., in order to select a suitable objective indicator. After an objective indicator is chosen, the observation shall be made on the variation of the quantity or quality of the objective indicator in correspondance with various symptoms (an objective-symptom-Zheng), vice versa. The Zheng may be idenfied according to the results of aforesaid observation. Furthermore, the use of appropriate methodology to explore the Zheng associated with objective indicators potentially provides objective evidence of Zheng diagnosis.