Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial

BACKGROUND： Disease recurrence is a main challenge in treatment of hepatocellular carcinoma （HCC）. There is no generally accepted method for preventing recurrence of HCC after resection. OBJECTIVE： To compare the efficacy of a traditional herbal medicine （THM） regimen and transarterial chemoembolization （TACE） in preventing recurrence in post-resection patients with small HCC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a multicenter, open- label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE. MAIN OUTCOME MEASURES： Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure. RESULTS： Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 （P = 0.048）. Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively （P = 0.026）. Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar. CONCLUSION： In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events. TRIAL REGISTRTION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.

Psychosocial and spiritual needs of patients with chronic diseases: validation of the Chinese version of the Spiritual Needs Questionnaire

OBJECTIVE： Even in secular societies, a small portion of patients find their spirituality to help cope with illness. But for the majority of patients, psychosocial and spiritual needs are neither addressed nor even considered a relevant factor by health care professionals. To measure such specific needs, the Spiritual Needs Questionnaire （SpNQ） was developed. The aim of this study was to validate the Chinese version of the SpNQ （SpNQ-Ch） and thus to measure psychosocial and spiritual needs of Chinese patients. METHODS： This was a cross-sectional study among 168 patients with chronic diseases who were recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China using standardized questionnaires. We performed reliability and factor analyses, as well as analyses of variance, first order correlations and regression analyses. RESULTS： The 17-item SpNQ-Ch had a similar factorial structure as the original version with two main and three minor factors which accounted for 64% of variance, and internal consistency estimates （Cronbach＇s a） ranging from 0.51 to 0.81. Included were the 4-item scale Inner Peace Needs, the 5-item scale Giving/Generativity （with 2 sub-constructs, Praying and Sources）, and a Needs, the 5-item scale Religious Needs 3-item scale Reflection/Release Needs. In Chinese patients with cancer （63%）, pain affections （10%）, or other chronic conditions （23%）, the needs for Giving/Generativity （which refer to categories of Connectedness and Meaning） and Inner Peace Needs scored highest, while Religious Needs and the Reflection/Release Needs scored lower. CONCLUSION： The SpNQ-Ch is congruent with its primary version, and can be used in future studies with the mostly nonreligious patients from China. First findings indicate specific psychosocial and spiritual needs which should be addressed by health care professionals to support patients in their struggle with chronic illness in terms of psycho-emotional stabilization, finding hope and meaning, and thus achieving peaceful states of mind despite chronic illness.

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 healthrelated 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 StageⅠto 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 = 0.002vs StageⅠ). 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.

Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine

Traditional Chinese medicine （TCM） is an important part of the treatment of primary liver cancer （PLC） in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical prac-tice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the method- ological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study

Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance HCC.Methods:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and safety.Propensity score matching(PSM)analysis was used to control for possible selection bias from the study group allocation process.Results:Of the 325 patients included,161 received JD Granule and 164 received sorafenib.No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,respectively.Even after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival rates.The most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib group.The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.Conclusion:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

Interpretation of illness in patients with chronic diseases from Shanghai and their associations with life satisfaction, escape from illness, and ability to reflect the implications of illness

The aim of this study is to analyze how patients with chronic diseases from Shanghai interpret their disease, and how these interpretations influence patients＇ life satisfaction, intention to escape from their illness and their ability to reflect on the implications of their illness. METHODS： A cross-sectional study enrolling 142 patients （mean age （50 ±16） years; 63% men, 37% women） with chronic diseases （60% cancer） was recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China and surveyed using standardized questionnaires. RESULTS： Patients with chronic diseases from Shanghai interpreted their illness mostly as an Adverse Interruption of Life （55%）, as a Threat/Enemy （50%）, but also as a Challenge （49%）, and only rarely as a Call for Help （18%） or as a Punishment （13%）. Particularly fatalistic negative （i.e., Threat/Enemy, Adverse Interruption of Life） and strategy-associated disease interpretations （i.e., Relieving Break, Call for Help） were moderately associated with patients＇ intention to escape from illness. In contrast, positive interpretations （i.e., something of Value, Challenge） and also the guilt-associated negative interpretation Failure were moderately related with patients＇ ability to reflect on their illness. However, life satisfaction was weakly associated only with the view that illness might be a Challenge. Interestingly, 58% of those who would see their illness as an Adverse Interruption （AI＋） could see it also as a Challenge （Ch＋）. Detailed analyses showed that AI＋Ch＋ patients differ from their AI＋Chcounterparts significantly with respect to their ability to reflect life and implications of illness （F=9.1 ; P=-0.004）.

Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions

Recombinant adeno-associated virus （rAAV） serotype 2, 3 and 8 vectors are the most promising liver- tropic AAV serotype vectors. Liver diseases are significant problems in China. However, to date, few studies on AAV neutralizing antibodies （Nabs） were working with the Chinese population or with the rAAV3 vectors. The present study aimed to determine the prevalence of Nabs in Chinese population against wild-type AAV2, AAV3 and AAV8 capsids as well as additional two AAV3 variants. In addition, we performed a preliminary analysis to investigate the potential influence of traditional Chinese medicine body constitutions on AAV Nabs. Our work demonstrated that the majority of healthy Chinese subjects were positive for AAV Nabs, with the order of AAV2 〉 AAV3 = AAVLK03 〉 AAV8. There was no difference between： 1）AAV3 and its variants; 2） male and female subjects; and 3） different age cohorts （〈 35, 36- 50, and 〉 51 years old）. People in the Qi-deficiency constitution had significantly increased AAV8 Nabs than people in the Gentleness constitution. Our studies may have impact on the future clinical design of AAV-based gene therapy in the Chinese population.