Pattern characteristics in patients with primary liver cancer in different clinical stages.

OBJECTIVE: To explore the characteristics of primary liver cancer in terms of Traditional Chinese Medicine (TCM) by analyzing the variations of the patterns along with the clinical stages. METHODS: The patients who were hospitalized in the Changhai Hospital of Traditional Chinese Medicine dated from March 1999 to December 2008 were included in this retrospective study. The patients were grouped according to their cancer stages, and their patterns were judged and quantified according to the "Standard diagnosis and quantitative criteria of the common patterns in primary liver cancer" formulated by the Changhai Hospital of Traditional Chinese Medicine. Statistics methods included ANOVA and nonparametric test, among others. RESULTS: The data of the 398 newly diagnosed pa- tients showed that Qi Stagnation, Blood Stasis, and Dampness patterns were more frequent than the other basic patterns with relatively high scores; patterns of Liver Qi Stagnation, Liver Blood Stasis, and Dampness Heat were more than the other complex patterns and scored relatively high. Scores of Dampness and Liver Qi Stagnation patterns varied among the groups at different stages and the differences were statistically significant (P(Dnampness) = 0.002, P(Liver Qi Stagnation) = 0.020). The highest scores of Dampness pattern and Liver Qi Stagnation pattern corresponded with Stage IIIb, and Stage IIIa, respectively. Dampness pattern frequency was higher (P = 0.001) in the Stage IIIb group than in other groups. CONCLUSION: Pattern characteristics in patients with primary liver cancer of different clinical stages might manifest in the variations of the Dampness pattern along the process of the disease and the major pathogenic factor of primary liver cancer might be Dampness.

Study on TCM Syndrome Differentiation of Primary Liver Cancer Based on the Analysis of Latent Structural Model.

Primary liver cancer (PLC) is one of the most common malignant tumors because of its high incidence and high mortality. Traditional Chinese medicine (TCM) plays an active role in the treatment of PLC. As the most important part in the TCM system, syndrome differentiation based on the clinical manifestations from traditional four diagnostic methods has met great challenges and questions with the lack of statistical validation support. In this study, we provided evidences for TCM syndrome differentiation of PLC using the method of analysis of latent structural model from clinic data, thus providing basis for establishing TCM syndrome criteria. And also we obtain the common syndromes of PLC as well as their typical clinical manifestations, respectively.

Metabolic profiling study of yang deficiency syndrome in hepatocellular carcinoma by h1 NMR and pattern recognition.

This study proposes a (1)H NMR-based metabonomic approach to explore the biochemical characteristics of Yang deficiency syndrome in hepatocellular carcinoma (HCC) based on serum metabolic profiling. Serum samples from 21 cases of Yang deficiency syndrome HCC patients (YDS-HCC) and 21 cases of non-Yang deficiency syndrome HCC patients (NYDS-HCC) were analyzed using (1)H NMR spectroscopy and partial least squares discriminant analysis (PLS-DA) was applied to visualize the variation patterns in metabolic profiling of sera from different groups. The differential metabolites were identified and the biochemical characteristics were analyzed. We found that the intensities of six metabolites (LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars) in serum of Yang deficiency syndrome patients were lower than those of non-Yang deficiency syndrome patients. It implies that multiple metabolisms, mainly including lipid, amino acid, and energy metabolisms, are unbalanced or weakened in Yang deficiency syndrome patients with HCC. The decreased intensities of metabolites including LDL/VLDL, isoleucine, lactate, lipids, choline, and glucose/sugars in serum may be the distinctive metabolic variations of Yang deficiency syndrome patients with HCC. And these metabolites may be potential biomarkers for diagnosis of Yang deficiency syndrome in HCC.

MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA.

MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

A traditional Chinese herbal medicine compound preparation versus interventional therapy after resection of small hepatocellular carcinoma: 22-year follow-up.

OBJECTIVE: To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy (IT) in patients after resection of small hepatocellular carcinoma (HCC). in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimally Invasive Surgery, First Affiliated Hospital of Guangxi Medical University. Four groups were based on different therapy modes: a TCM-only (TCMO) group, a TCM combined with interventional therapy (TCM-IT) group, an interventional therapy-only (ITO) group, and a simple operation (SO) group. Prognostic factors were correlated with overall survival (OS) and OS rates were calculated with the Kaplan-Meier method, and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model. RESULTS: The median OS was 151.20 months in the TCM-IT group, 43.87 months in the ITO group, and 20.77 months in the SO group. All survival rates of the TCMO group were higher than those of the other three groups (>50%). The 5-, 10-, and 15-year OS in the TCMO and ITO patients were 83.94%, 45.50%, and 71.22% and 33.34%, 55.58%, and 9.26%, respectively (risk ratio, 0.209; 95% confidence interval, 0.126-0.347; P = 0.000). Multivariate analysis revealed that the independent risk factors were therapy mode (P = 0.000), sex (P = 0.005), family history (P = 0.011), TNM classification of malignant tumor staging (P = 0.000), medical care-seeking behavior (P = 0.021), and maximum diameter (P = 0.030). CONCLUSION: Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma.

AIM: To investigate and evaluate the change in health-related quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM Stage I to Stage II, Stage IIIA, Stage IIIB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage I to Stage IIIB (P = 0.002 vs Stage I; P = 0.032 vs Stage II; P = 0.033 vs Stage IIIA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage II; P = 0.032 vs Stage IIIA). For the social and family well-being subscale, only Stage IIIB scores were significantly lower as compared with Stage I scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages IIΙ, IIIA and IIIB (P = 0.002 vs Stage I). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

Preventive effects of jiedu granules combined with cinobufacini injection versus transcatheter arterial chemoembolization in post-surgical patients with hepatocellular carcinoma: a case-control trial.

OBJECTIVE: To investigate the therapeutic effects of Jiedu granules, a Chinese medicine (CM) compound, plus cinobufacini injection, which was extracted from skin of Bufo bufo gargarizans Cantor, to prevent the recurrence of hepatocellular carcinoma (HCC) after surgical resection. METHODS: In this case-control trial, a total of 120 patients who stayed in Changhai Hospital were enrolled from December 2001 to December 2006. Sixty patients were treated with Jiedu granules plus cinobufacini injection to prevent tumor recurrence after operation (CM group) and 60 patients were treated with transcatheter arterial chemoembolization (TACE) after operation (TACE group). Progression-free survival (PFS) and overall survival (OS) rates were determined to evaluate the therapeutic effects of post-operative management of patients with HCC. RESULTS: PFS in the CM group was 18.07 months [95% confidence interval (CI): 12.49-23.65] and the 1-, 2-, 3-, 4- and 5-year PFS rates were 61%, 39%, 26%, 22% and 12%, respectively. PFS in the TACE group was 8.03 months (95% CI: 6.63-9.44) and the 1-, 2-, 3-, 4- and 5-year PFS rates were 34%, 11%, 7%, 2% and 0%, respectively. There was significant difference in survival rate between the two groups (P<0.01). The mean survival time (MST) of patients in the CM group was 49.53 months versus 39.90 months of the TACE group. The 1-, 2-, 3-, 4- and 5-year survival rates were 90%, 82%, 80%, 70% and 63%, respectively, in the CM group, and 79%, 70%, 60%, 60% and 36%, respectively, in the TACE group. There was significant difference in survival time between the two groups (P=0.045). CONCLUSIONS: Jiedu granules plus cinobufacini injection, a combination that is commonly used for post-operation management of HCC, can postpone tumor recurrence and metastasis, prolong the survival time and increase the survival rate of post-surgical patients with HCC. However, these findings need to be confirmed in a prospective, randomized controlled trial.

[Investigation on traditional Chinese medicine syndrome distribution of 4 618 hepatitis B virus infection subjects in Qidong of Jiangsu Province, China].

OBJECTIVE: To study the traditional Chinese medicine (TCM) syndrome distribution in patients with hepatitis B virus (HBV) infection in Qidong region of Jiangsu Province, China. METHODS: A cross-sectional survey was performed. Subjects from Qidong of Jiangsu Province of China were screened among the locally enrolled residents by detecting hepatitis B surface antigen (HBsAg) from May 2007 to May 2011 and were assigned to HBsAg-negative cohort or HBsAg-positive cohort. Then, the subjects were diagnosed according to alanine aminotransferase, alpha-fetoprotein and B ultrasound. The syndrome of the subjects was determined using a TCM questionnaire consisting of signs and symptoms. RESULTS: A total of 5 908 subjects were enrolled in this survey, among whom, 4 718 were diagnosed with HbsAg infection (positive result of HbsAg detection) and 1 147 were negative. 143 subjects were excluded for not receiving the blood examination. The final diagnoses of the subjects were non-HBV infection (n=1128), HBV carrier (n=4019), chronic hepatitis B (n=225), posthepatitic cirrhosis (n=263) or liver cancer (n=111). The TCM syndrome differentiation results showed that there were differences in syndrome distribution between HBV-infected and non-HBV-infected patients. The main syndromes of the HBV-infected patients were qi deficiency, qi stagnation, blood stasis and dampness heat, related to the Zang of liver and spleen. The distribution principles of TCM syndrome among patients of HBV carrier, chronic hepatitis B and cirrhosis were similar. Moreover, with the progression of the patients' condition, the scores of syndromes increased, and the number of accompanying syndromes increased as well. The main syndromes of patients with liver cancer were blood stasis and excess heat, which was slightly different from that of the other HBV-infected patients. CONCLUSION: The TCM syndrome distribution in patients of HBV infection in Qidong region of Jiangsu Province shows regularity. The disorder is mainly due to qi stagnation and blood stasis and is also related to deficiency of healthy qi, especially deficiency of spleen qi.

Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival. METHODS: A retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc. RESULTS: The median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006). CONCLUSION: Combination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula: a retrospective study.

Transcatheter arterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) because of its survival benefit, although its clinical effect is still far from satisfactory. In China, there has been a long history of using traditional Chinese medicine in the treatment of liver cancer and other malignancies. In this study, the authors evaluated the effect of combined therapy with TACE and JDF granule preparation (a traditional Chinese herbal medicine formula) in the treatment of patients with unresectable HCC on survival. Clinical data, including baseline, performance status change, and survival time of 165 patients with unresectable HCC seen between January 2002 and December 2007 were retrospectively analyzed. Among the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and 85 patients (control group) received TACE alone. The survival rate of both groups was calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model. The median overall survival was 9.2 months (95% confidence interval [95% CI], 6.94-1.46) in the study group versus 5.87 months (95% CI, 4.21-7.52) in the control group. In the study group (TACE + JDF), 1-year, 2-year, and 3-year survival rates were 41.2%, 18.4%, and 9.6%, respectively. The Cox regression analysis revealed the therapy model to be an independent predictor of patient prognosis. Current study data demonstrated that TACE combined with JDF granule preparation could improve the prognosis of patients. TACE combined with JDF granule preparation may prolong survival of patients with unresectable HCC.

Relationship between abnormal characteristics of sublingual collateral and portal vein hemodynamic changes in patients with primary hepatic carcinoma.

OBJECTIVE: To investigate the relationship between the abnormal characteristics of sublingual collateral (SC) and portal vein hemodynamic changes in patients with primary hepatic carcinoma (PHC). METHODS: A total of 123 patients of PHC with abnormal SC were enrolled. The SC characteristics were classified and evaluated. The principal components (PC) of SC extracted from them by principal component analysis and the relationship between PC and the dynamic changes of portal vein flow were analyzed by correlation analysis. RESULTS: Three groups of PC were extracted, namely PC-1 (length, width, presentation type of visualization), PC-2 (circuitous, vesicular change), and PC-3 (color, collateral hemostasis, petechiae, ecchymosis). Their total accumulative contribution degree reached 56.803%. Correlation analysis shows that PC-1 was significantly positively correlated with the hemodynamic parameters of the portal vein (P<0.01), while PC-2 and PC-3 were not (P>0.05). CONCLUSION: Length, width and presentation type of SC could be used for predicting the changes of portal venous pressure in PHC patients.

[Evaluation of Chinese version of the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire].

OBJECTIVE: To evaluate the effectiveness of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire in measuring the quality of life in patients with primary hepatic carcinoma (PHC) in China. METHODS: FACT-Hep questionnaire was translated into Chinese and revised properly. From September 2005 to April 2006, one hundred and eighty patients with primary liver carcinoma were admitted and measured by using the Chinese version of FACT-Hep questionnaire, and the reliabilities, validities and responsibilities of the questionnaire were assessed. RESULTS: Correlation coefficient was higher between items and dimension of their corresponding domain (0.5933+/-0.1652) than that between the items and other domains (0.2749+/-0.1922). Six principal constituents were extracted by factor analysis and represented all domains of the questionnaire. The combinations of components were consistent with what was expected. The correlation coefficient of criterion-related validity was 0.828. The test-retest reliability correlation coefficients of physical, social/family, emotion, function, symptom and total questionnaire were 0.731, 0.334, 0.953, 0.786, 0.785 and 0.801 respectively, and the values of Cronbach's alpha were 0.7397, 0.4193, 0.7914, 0.8250, 0.8399 and 0.9161, respectively. There were statistical differences in scores of FACT-Hep questionnaire in different PHC stages or in different Child-Pugh classes (P<0.05). CONCLUSION: The FACT-Hep questionnaire can measure the quality of life in patients with PHC with good reliability, validity and responsiveness; it can be used in assessing the disease-specific health-related quality of life of patients with hepatobiliary cancers.

[Construction of a therapeutic effect evaluation system for patients with primary liver cancer based on syndrome differentiation in traditional Chinese medicine].

OBJECTIVE: To construct a system of therapeutic effect evaluation for patients with primary liver cancer according to the theory of syndrome differentiation in traditional Chinese medicine (TCM), and to examine its reliability. METHODS: Analytic hierarchy process and 100 mm surveyor's rod method were applied to obtain bottom layer and top level syndromes, which were used to construct the method of therapeutic effect evaluation, and its reliability was verified in clinical practice by comparing with some evaluation criteria in Western medicine, such as cancer severity scale; Karnofsky performance scale; Child-Pugh classification, cancer staging classification, and quality of life scale, etc. RESULTS: A system of therapeutic effect evaluation was constructed, and it could reflect the progress of tumor, changes of hepatic function and constitution. The evaluation scores acquired from the system were highly associated with the quality of life of the patients. CONCLUSION: The system of therapeutic effect evaluation can reflect the severity of disease and the characteristics of TCM treatment.

[Study on diagnostic standard for dampness syndrome in patients with chronic gastritis].

OBJECTIVE: To consummate the standard of macroscopic syndrome differentiation for diagnosis of dampness syndrome in patients with chronic gastritis (CG), based on the essentials of syndrome differentiation in TCM diagnostics and combined with the multivariant mathematical statistic method. And try to find out the methods and approaches for establishing standard for TCM syndrome differentiation. METHODS: Clinical investigation on CG patients was carried out adopting clinical epidemiological method. RESULTS: The meaningful symptoms for making diagnosis of Pi-Wei damp-heat syndrome in frequency order, were red tongue with yellow and greasy fur, sticky and greasy sensation in mouth, brown urine, constipation, dry stool, flushed face and ponderous extremities. Those for Pi deficiency with damp retention syndrome were swollen tongue with teeth-print, greasy fur, sticky and greasy sensation in mouth, tastelessness, and poor appetite. CONCLUSION: By combining the integrative medical theory with multivariant statistic method, the meaningful essentials for diagnosis of dampness syndrome can be screened out.