1.Prognostic factors of survival in patients with resectable hilar cholangiocarcinoma
Qian ZHU ; Guoliang QIAO ; Jianjun YAN ; Yiqun YAN
Chinese Journal of Hepatobiliary Surgery 2014;20(9):662-666
Objective To investigate the appropriate cutoff point of CA19-9 in prognosis and to determine other potential prognostic factors which may affect survival of patients with hilar cholangiocarcinoma (HC) after radical surgery.Methods 168 patients who had undergone radical surgery for hilar cholangiocarcinoma with R0 and R1 resection were selected for the study.Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9.CA19-9 and other clinicopathologic factors were analyzed for their influence on survival using multivariate methods.Results The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 of less than 150 IU/L (P <0.001).On univariate analysis,age,differentiation,tumor size,Bismuth-Corlette classification,portal vein invasion,lymph node metastasis,hepatic artery invasion,liver invasion,preoperative biliary drainage,resection margin and preoperative CA19-9 levels were identified as significant prognostic factors.On multivariable analysis,lymph node metastasis,resection margin and preoperative CA19-9 levels were independent prognostic factors of survival.Conclusions A raised preoperative CA19-9 level was an independent prognostic factor of survival for hilar cholangiocarcinoma.The most discriminative cutoff point of CA19-9 for prognosis was at 150 kU/L.
2.Prognosis after resection of early hepatocellular carcinoma in HBV-related cirrhotic patients
Qian ZHU ; Guoliang QIAO ; Jianjun YAN ; Mengchao WU ; Yiqun YAN
Chinese Journal of Hepatobiliary Surgery 2014;20(4):258-264
Objective To identify clinicopathologic factors which predict survival following hepatectomy in HBV-related cirrhotic patients with early hepatocellular carcinoma (HCC).Methods A database was used to identify patients with histologically confirmed early HCC (≤5 cm,no nodal involvement,metastases,or major vascular invasion) who underwent surgical resection (excluding ablation or transplantation).Among 20 700 patients with HCC who were diagnosed at the Eastern Hepatobiliary Surgery Hospital from April 2005 to November 2010,537 (2.6%) patients with early HCC were studied retrospectively.Prognostic factors were evaluated using the Kaplan-Meier curves,Cox proportional hazards models and the receiver operating characteristic (ROC) curves.Results The study included 537 patients.The median tumor size was 2.9 cm,and 33% of patients had tumors ≤2 cm.Most HCC lesions were solitary (63%) and had no evidence of vascular invasion (64%).Following surgery,the overall median and 5-year survival were 45 months and 33% respectively.After adjusting for demographic factors and histological grade,tumor size >2 cm (hazard ratio [HR]:1.56),multifocal tumors (HR:1.34),and vascular invasion (HR:2.03) remained independent predictors of poor survival (all P < 0.05).Based on these findings,a prognostic scoring system was developed that allotted 1 point each for these factors.Patients with early HCC could be stratified into 4 distinct prognostic groups (median and 5-year survival,respectively):0 points (97 months,96%),1 point (85 months,76%),2 points (76 months,54%),3 points (56 months,39%) (P <0.01).Conclusions The present study emphasized the importance of pathologic staging even in patients with small HCC.Anatomical resection of HCC should be the preferred surgical procedure in cirrhotic patients.
3.Risk factors and surgical outcomes for spontaneous rupture of BCLC stage A and stage B hepatocellular carcinoma
Qian ZHU ; Guoliang QIAO ; Jianjun YAN ; Yiqun YAN
Chinese Journal of Hepatobiliary Surgery 2015;21(2):81-85
Objective To investigate the risk factors of spontaneous rupture of BCLC stage A and stage B hepatocellular carcinoma (HCC),and to review the surgical outcomes.Methods From April 2002 to November 2006,89 patients who suffered from spontaneous rupture of HCC of BCLC stage A and stage B were included into this study.A control group of 171 patients was selected by matching the sex,age and BCLC stage.Clinical data and survivals were collected and analysed.Results On multivariate analysis,hypertension (HR 7.38,95%CI:1.91 ~28.58,P<0.05),cirrhosis (HR6.04,95% CI:2.83 ~12.88,P < 0.05) and tumor location in segments Ⅱ,Ⅲ,Ⅵ (HR 5.03,95% CI:2.70 ~ 6.37,P < 0.05) were predictive factors of spontaneous rupture of HCC.In the study group,the median survival and median disease-free survival were 12 months (range,1 ~ 78 months) and 4 months (range,0 ~ 78 months) respectively.The overall survival rates and disease-free survival rates at 1-,3-and 5-year were 66.3%,23.4%,10.1% and 57.0%,16.8%,4.5%,respectively.Only radical resection remained predictive of overall survival (HR 0.32,95% CI:0.08 ~ 0.61,P < 0.05) and disease-free survival (HR 0.12,95% CI:0.01 ~ 0.73,P < 0.05).Conclusions Tumor location,as well as hypertension and cirrhosis were associated with spontaneous rupture of HCC.One-stage hepatic resection should be recommended to patients with ruptured HCC of BCLC stage A and stage B.
4.New perspectives on the natural history and growth pattern of hepatic hemangioma in adults: a cohort study
Qian ZHU ; Guoliang QIAO ; Jianjun YAN ; Yiqun YAN
Chinese Journal of Hepatobiliary Surgery 2015;21(11):721-725
Objective To investigate the natural history and growth pattern of hepatic hemangioma in adults.Methods From April 2010 to March 2013, adult patients with hepatic hemangioma who had no prior treatment were enrolled.A routine follow-up was performed to observe the natural history and complications of these lesions.Results 236 patients were enrolled in the study.The median size of the hemangiomas was 4.5 cm (range 0.6 ~ 19.2 cm).During a median follow-up of 48 months (range 3 ~ 266 months), the hemangiomas increased in size in 61.0% of patients, remained stable in size in 23.7%, decreased in size in 8.5%.The peak growth period was in patients < 30 years age (0.46 ± 0.41 cm/year) and the growth rate decreased significantly after 50 years of age (0.21 ±0.40 cm/year).Hemangiomas with a size <2.0 cm had the lowest growth rate (0.16 ± 0.42 cm/year).The peak growth rate was in hemangiomas 8.0 ~ 10.0 cm (0.80 ± 0.62 cm/year) , but for hemangiomas > 10.0 cm, the growth rate was only (0.47 ±0.91)cm per year.Only 9 patients had severe symptoms caused by the hemangioma.No patients presented with hemangioma-related complications.Conclusions The majority of hepatic hemangiomas have the tendency to increase in size but they rarely caused complications.All the hemangiomas could be safely managed by observation, and surgery should only be considered in patients with complications.
5.Injection of ethanol into the common bile duct to establish a rat model of biliary atresia
Juntao GE ; Long LI ; Yandong WEI ; Haibin WANG ; Guoliang QIAO ; Zhen ZHANG ; Yao LIU ; Anxiao MING
Acta Laboratorium Animalis Scientia Sinica 2014;(3):50-52
Objective To establish a new rat model of biliary atresia by pure ethanol injection into the common bile duct.Methods A catheter was inserted and fixed in the common bile duct in male SD rats .Saline (8 rats) or pure ethanol (16 rats) was injected through the catheter ,respectively, and the biochemical and pathological changes in the rats were examined .Results SD rats in the experimental group were divided into a persistent injury and a restoration of liver dysfunction groups according to pathological and biochemical detection .In the persistent injury group , biochemical impair-ments were significantly higher at 8 weeks after ethanol injection than those in the control group and restoration group .Dis-tinct pathological changes in the liver were observed using HE , SMA, and Masson staining .Conclusions It is a reliable animal model of biliary atresia induced by injection of pure ethanol into the common bile duct in the rat .It will provide a useful tool in future studies of biliary atresia .
6.Effect of combination of ganoderma lucidum polysaccharide and metformin on AGEs and CTGF of cardiac muscle in type 2 diabetic rats and the mechanism
Jin QIAO ; Zhihua DOU ; Feng WU ; Guoliang MENG ; Hui CHEN ; Huihua ZHENG
Chinese Pharmacological Bulletin 2014;(4):536-541
Aim To study the effects of ganoderma lu-cidum polysaccharides and metformin on myocardial fi-brosis of type 2 diabetic rats and its mechanism. Methods SD rats were fed with high fat diet for 4 weeks, and then were injected with streptozotocin (30mg·kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomized into normal control group,diabetes group, ganoderma lucidum polysaccha-rides group ( 600 mg · kg-1 ) , metformin group ( 600 mg·kg-1 ) , and combination group( ganoderma lucid-um polysaccharides 300 mg·kg-1 +metformin 300 mg ·kg-1 ) . After 12 weeks’ treatment,the levels of fast-ing serum glucose were determined and the extent of myocardial fibrosis was observed by Picro-sirius red staining. The contents of AGEs in serum were deter-mined by fluorescence spectrophotometer. The activities of CAT and GSH-Px in myocardium were detected. Im-munohistochemical method and Western blot were used to detect myocardial tissue AGEs and CTGF protein ex-pression. Results Combination group could repress patho-proceeding of myocardial fibrosis efficiently, im-prove the activity of CAT and GSH-Px in myocardium and lower the concentration of AGEs in serum, as well as reduce the expression of AGEs and CTGF in myo-cardium. Conclusions Ganoderma lucidum polysac-charides and metformin could prevent myocardial fibro-sis. The possible mechanism may be related to repress-ing oxidative stress of myocardium, lowering serum AGEs and down regulating AGEs and CTGF of myocar-dium.
7.Effect of Ganoderma Lucidum Polysaccharides Combined with Metformin on Oxidative Stress of Type 2 Diabetic Rats in Vivo
Jin QIAO ; Zhihua DOU ; Zhong SHI ; Feng WU ; Guoliang MENG ; Hui CHEN ; Huihua ZHEN
Herald of Medicine 2015;(6):718-721
Objective To study the effect of ganoderma lucidum polysaccharides combined with metformin on oxidative stress of type 2 diabetic rats. Methods SD rats were fed with high fat diet for 4 weeks and injected with streptozotocin (30 mg·kg-1 ) to produce type 2 diabetic model. The diabetic rats were randomly divided into diabetes model group, ganoderma lucidum polysaccharides group (600 mg·kg-1 ), metformin group (600 mg·kg-1 ), combination group (ganoderma lucidum polysaccharides 300 mg·kg-1+ metformin 300 mg·kg-1 ), After 12 weeks of treatment, the level of fasting blood glucose was determined, and the activity of superoxide dismutase ( SOD), malondialdehyde ( MDA), catalase ( CAT), glutathione peroxidase (GSH-Px), total cholesterol (TC) and triglyceride (TG) were detected. Results The levels of fasting blood glucose in the treatment groups were significantly lower than that in the diabetes model group (P<0. 01). Furthermore, fasting blood glucose in the combination group was significantly lower than that in ganoderma lucidum polysaccharides group and metformin group (P<0. 01). Compared with diabetes model group, serum TC and TG in the treatment groups were significantly lower (P<0. 05, P<0. 01). Serum TC and TG were significantly lower in the combination group than in ganoderma lucidum polysaccharides group and metformin group (P<0. 05, P<0. 01). Compared with diabetes model group, serum SOD levels in the treatment groups were significantly higher (P<0. 01). Compared with ganoderma lucidum polysaccharides group and metformin group, serum SOD levels in the combination group was significantly higher (P<0. 05). Compared with diabetes group, serum MDA levels in the treatment groups were significantly lower (P<0. 01). Serum MDA in the combination group was significantly lower than that in ganoderma lucidum polysaccharides group and metformin group ( P<0. 05). Compared with diabetes model group, serum CAT and GSH-Px in the treatment groups were significantly higher (P<0. 05, P<0. 01). Serum CAT and GSH-Px in the combination group were significantly higher than those in ganoderma lucidum polysaccharides group and metformin group (P<0. 05). Conclusion Ganoderma lucidum polysaccharides combined with metformin could effectively inhibit oxidantion stress in type 2 diabetic rats. The effect was better than ganoderma lucidum polysaccharides or metformin used alone. The possible mechanism may be related to increased activity of SOD, CAT, GSH-Px in vivo and regulation of dyslipidemia.
8.Effect of combination of ganoderma lucidum polysaccharide and metformin on aortic lesions and expression of VEGF in type 2 diabetic rats
Jin QIAO ; Zhihua DOU ; Feng WU ; Guoliang MENG ; Hui CHEN ; Huihua ZHEN
Chinese Pharmacological Bulletin 2014;(8):1079-1084
Aim To investigate the effects and mecha of ganoderma lucidum polysaccharides and metformin on pathological changes of thoracic aorta in diabetic ratsandthemechanisms.Methods SDratswerefed with high fat diet for 4 weeks and injected with strepto-zotocin ( 30 mg · kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomly into diabetes group, ganoderma lucidum polysaccharides group ( 600 mg·kg-1 ) ,metformin group(600 mg·kg-1 ) ,combi-nation group ( ganoderma lucidum polysaccharides 300 mg· kg-1 + metformin 300 mg · kg-1 ) and normal control group. After 12 weeksˊ treatment, the levels of fasting serum glucose, the activity of catalase(CAT), glutathione peroxidase ( GSH-Px ) , total cholesterol (TC)and triglyceride(TG) in serum were detected. Pathological changes of thoracic aorta were observed by HE staining. Immunohistochemy and Western blot were used to detect thoracic aorta VEGF protein expression. Results Combination group could lower fasting serum glucose and blood fat significantly, meanwhile the ac-tivity of CAT and GSH-Px in serum was improved. The expression of VEGF in thoracic aorta was repressed. The result of HE staining suggested that the lipid de-posits in aortic endothelium in combination group were lessthanthoseinthemodelgroup.Conclusions Ga-noderma lucidum polysaccharides combined with met-formin has an obvious prevention on pathological chan-ges of thoracic aorta in diabetic rats. The possible mechanism may be related to repressing oxidative stress of thoracic aorta, regulating the dyslipidemia, and the down regulation of the expression of VEGF in thoracic aorta.
9.Effects of Ganoderma lucidum polysaccharides combined with metformin on myocardial structure and hemodynamics in type 2 diabetic rats
Jin QIAO ; Zhihua DOU ; Feng WU ; Guoliang MENG ; Hui CHEN ; Huihua ZHEN
Chinese Pharmacological Bulletin 2016;32(7):1012-1016
Aim To discuss the effects and mechanism of Ganoderma lucidum polysaccharides and metformin on myocardial structure and hemodynamics in type 2 diabetic rats.Methods High fat diet combined with intraperitoneal injection of low dose streptozotocin 30 mg· kg -1 was applied to establish rat model of type 2 diabetes mellitus .The diabetic rats were randomly into normal control group ,diabetes group , ganoderma lucid-um polysaccharides group (600 mg· kg -1 ) , metformin group ( 600 mg · kg -1 ) , combination group ( ganoder-ma lucidum polysaccharides 300 mg · kg -1 +metform-in 300 mg· kg -1 ) .After 12 weeks′treatment,the lev-els of fasting serum glucose were determined and the hemodynamic parameters (LVSP,LVEDP,dp/dtmax,-dp/dtmax ) were determined.Collagen volume fraction ( CVF ) was detected by Van Gieson . Immunohisto-chemical method and Western blot were used to detect myocardial tissue MMP-2 protein expression .Results The fasting blood glucose was significantly decreased in the combined treatment group .Combined medication could significantly improve hemodynamic parameters in diabetic rats: reduced LVEP and raised LVEDP , dp/dtmax and -dp/dtmax .CVF was significantly decreased in combination group .The expression of MMP-2 in my-ocardial tissue was significantly inhibited .Conclusions The combination of Ganoderma lucidum polysaccha-ride and metformin can significantly improve the hemo-dynamic parameters in type 2 diabetic rats, and have a preventive effect on diabetic cardiomyopathy . The mechanism may be related to the down regulation of the expression of MMP-2.
10.Screening and optimizing the colorectal cancer related tumor markers from multi-tumor markers proteinchip
Jinxuan HOU ; Xueqin YANG ; Chuang CHEN ; Qiao JIANG ; Guoliang YANG ; Yan LI
Cancer Research and Clinic 2008;20(5):303-305,309
Objective To analyze the association between C12 tumor markers and colorectal cancer,in order to screen for colorectal cancer related tumor markers so as to provide theoretical base for the establishment of colorectal cancer diagnostic biochips. Methods The sera of 173 colorectal cancer patients were detected for 12 common tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242), cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), prostate specific antigen (PSA), free-PSA, neuron-specific enolase (NSE),human chorionic gonagotropin-beta (β-HCG), human growth hormone (HGH), and ferritin using the C12tumor markers proteinchip, and colorectal cancer related parameters were analyzed by Kappa test and cost-effectiveness analysis to find the most optimal tumor marker program. Results CEA (36.4 %), CA242(19.7 %), CA19-9 (18.5 %), CA125(9.8 %) were major tumor markers increased among the 173 colorectal cancer patients. Kappa test revealed 7 tumor marker programs having strong consistency with the detection results of C12 tumor markers proteinchip, and CEA singly detected was proved to be the best program by cost-effectiveness analysis. Conclusion C12 tumor markers proteinchip system have limited value in the diagnosis of colorectal cancer, but the design of chip is too complicated and costly for widespread screening among the high risk populations. Searching for new colorectal cancer biomarkers and designing small diagnostic chip could significantly enhance the clinical value of tumor markers in terms of diagnostic rate and practical utility.