Publications by authors named "Zhang Boheng"

22 Publications

  • Page 1 of 1

Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition).

Liver Cancer 2020 Dec 11;9(6):682-720. Epub 2020 Nov 11.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people.

Summary: Since the publication of in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years.

Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019.
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http://dx.doi.org/10.1159/000509424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768108PMC
December 2020

Albumin-to-Alkaline Phosphatase Ratio is an Independent Prognostic Indicator in Combined Hepatocellular and Cholangiocarcinoma.

J Cancer 2020 29;11(17):5177-5186. Epub 2020 Jun 29.

Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education.

The clinical significance of Albumin-to-Alkaline Phosphatase Ratio (AAPR) has been discussed in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The aim of this study is to clarify the prognostic value of AAPR in patients with combined hepatocellular and cholangiocarcinoma (cHCC-CCA). A total of 267 patients pathologically diagnosed as Allen type C cHCC-CCA in our institution were retrospectively enrolled and randomly divided into the training (N=187) cohort and validation (N=80) cohort. The prognostic value of AAPR was evaluated and validated. An AAPR-based nomogram was constructed and its prediction performance was assessed. We identified 0.43 as the optimal threshold value of AAPR by the X-tile software. In the training cohort, the median overall survival (OS) of patients with AAPR < 0.43 was significant shorter than that of those with AAPR ≥ 0.43(15.8 months vs 35 months, respectively, P < 0.001). Univariate and multivariate analyses demonstrated that AAPR was a strong indicator of OS. The concordance index (C-index), receiver operating characteristic (ROC) curves, likelihood ratio tests (LAT), Akaike information criteria (AIC) and decision curve analysis (DCA) demonstrated that AAPR outperformed the Child-Pugh (CP) grade and albumin-bilirubin (ALBI) grade in predicting OS. These findings were further verified in the validation cohort. The AAPR-based nomogram achieved C-index values of 0.76 (95%CI: 0.71-0.81) in the training cohort and 0.69 (95%CI: 0.60-0.78) in the validation cohort, which presented significant superiority to TNM stage. Preoperative AAPR is an independent prognostic predictor in cHCC-CCA. The AAPR-based nomogram contributes to personalized prognosis prediction and clinical decision making for cHCC-CCA.
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http://dx.doi.org/10.7150/jca.45633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378922PMC
June 2020

Comparative performance of inflammation-based prognostic scores in patients operated for intrahepatic cholangiocarcinoma.

Cancer Manag Res 2019 30;11:9107-9119. Epub 2019 Oct 30.

The Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.

Objective: Prognostic performance of inflammation-based prognostic scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI) has been explored in patients with varied types of cancer, though little data is available in intrahepatic cholangiocarcinoma (ICC). This study sought to evaluate the impact of systemic inflammation on the overall survival (OS) of ICC patients, and to identify more optimal prognostic indices.

Patients And Methods: The prognostic power of all the scores mentioned above was compared in 123 patients underwent curative surgery for ICC using Kaplan-Meier curves, COX regression models and the receiver operating characteristics (ROC) curves. The results were validated in a cohort of 95 ICC patients.

Results: Multivariate analysis identified LMR as the only independent inflammation-based predictor for OS in the training cohort (=0.007, HR 2.082, 95% CI 1.218-3.558). More importantly, the combined score of LMR and pTNM designated the inflammation-based pathological stage (IPS) outperformed other established scores in terms of discriminatory ability, monotonicity and homogeneity in the training and validation cohorts.

Conclusion: This study reveals that preoperative LMR is an independent predictor of OS in ICC patients after hepatectomy, and the IPS can be applied as a novel prognostic indicator in these patients.
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http://dx.doi.org/10.2147/CMAR.S198959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831984PMC
October 2019

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

Int J Clin Oncol 2019 Sep 10;24(9):1151-1160. Epub 2019 Jun 10.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients.

Methods: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables.

Results: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years.

Conclusions: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.
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http://dx.doi.org/10.1007/s10147-019-01455-5DOI Listing
September 2019

Differential responses of MET activations to MET kinase inhibitor and neutralizing antibody.

J Transl Med 2018 09 12;16(1):253. Epub 2018 Sep 12.

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.

Background: Aberrant MET tyrosine kinase signaling is known to cause cancer initiation and progression. While MET inhibitors are in clinical trials against several cancer types, the clinical efficacies are controversial and the molecular mechanisms toward sensitivity remain elusive.

Methods: With the goal to investigate the molecular basis of MET amplification (MET) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring MET (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo.

Results: We find that cancer cells driven by MET are more sensitive to INC280 than are those driven by HGF-autocrine activation. In MET cells, INC280 induced a DNA damage response with activation of repair through the p53BP1/ATM signaling pathway. Although MetMab failed to inhibit MET cell proliferation and tumor growth, both INC280 and MetMab reduced HGF-autocrine tumor growth. In addition, we also show that HGF stimulation promoted human HUVEC cell tube formation via the Src pathway, which was inhibited by either INC280 or MetMab. These observations suggest that in HGF-autocrine tumors, the endothelial cells are the secondary targets MET inhibitors.

Conclusions: Our results demonstrate that MET and HGF-autocrine activation favor different molecular mechanisms. While combining MET TKIs and ATM inhibitors may enhance the efficacy for treating tumors harboring MET, a combined inhibition of MET and angiogenesis pathways may improve the therapeutic efficacy against HGF-autocrine tumors.
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http://dx.doi.org/10.1186/s12967-018-1628-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134500PMC
September 2018

S100A11 promotes TGF-β1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma.

Future Oncol 2018 Apr 23;14(9):837-847. Epub 2018 Mar 23.

Liver Cancer Institute & Zhongshan Hospital of Fudan University, Shanghai 200032, PR China.

Aim: Our previous study found S100A11 was significantly raised in intrahepatic cholangiocarcinoma cells, but the relationship between S100A11 and intrahepatic cholangiocarcinoma remains unclear.

Methods: We investigated the effect of silencing S100A11 on TGF-β1-induced epithelial-mesenchymal transition (EMT), cell migration and invasion.

Results: Our results demonstrated silencing S100A11 inhibited TGF-β1-induced cell migration, invasion and EMT, expression of EMT markers E-cadherin, N-cadherin, β-catenin, vimentin, Slug and Snail was reversed. Furthermore, TGF-β1-induced p-SMAD2 and 3 were also inhibited due to low S100A11 expression.

Conclusion: Our present study indicated that S100A11 promotes EMT through accumulation of TGF-β1 expression, and TGF-β1-induced upregulation of p-SMAD2 and 3.
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http://dx.doi.org/10.2217/fon-2017-0534DOI Listing
April 2018

S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway.

Future Oncol 2017 Oct 6;13(23):2053-2063. Epub 2017 Oct 6.

Department of Hepatic Oncology, Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai 20032, PR China.

Aim: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC).

Methods: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions.

Results: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK.

Discussion:  S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients.
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http://dx.doi.org/10.2217/fon-2017-0199DOI Listing
October 2017

Prognostic significance of serum procalcitonin in patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A retrospective analysis of 509 cases.

Medicine (Baltimore) 2017 Jul;96(28):e7438

Liver Cancer Institute and Zhongshan Hospital Department of Epidemiology and Biostatistics, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.

Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, its accuracy in hepatocellular carcinoma (HCC) patients is unknown. The aim of this study was to investigate the prognostic significance of PCT in patients with unresectable HCC treated with transcatheter arterial chemoembolization (TACE).A total of 509 patients with unresectable HCC initially treated with TACE were enrolled in this retrospective study. According to quartile of the PCT values, all patients were divided into 4 groups. Overall survival (OS) was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for evaluating the significance of the prognostic factor.The median follow-up period was 18 months and there were significant differences in the survival rates between the 4 groups. The HR (95% CI) for all-cause mortality comparing patients with PCT Quartile2-4 to patient with Quartile1 (HR = 1.00) were 1.353 (1.023-1.791), 1.799 (1.354-2.390), 1.960 (1.455-2.639), respectively, (P < .001). PCT level was an important prognostic factor for predicting the prognosis of patients with unresectable HCC treated with TACE.
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http://dx.doi.org/10.1097/MD.0000000000007438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515752PMC
July 2017

Treatment with the herbal formula Songyou Yin inhibits epithelial-mesenchymal transition in hepatocellular carcinoma through downregulation of TGF-β1 expression and inhibition of the SMAD2/3 signaling pathway.

Oncol Lett 2017 Apr 8;13(4):2309-2315. Epub 2017 Feb 8.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

It was previously reported that treatment with the herbal formula Songyou Yin (SYY) may serve a role in attenuating epithelial-mesenchymal transition (EMT). In the present study, the effect of treatment with SYY on transforming growth factor-β1 (TGF-β1)-induced EMT was investigated and the potential underlying molecular mechanisms were evaluated. MHCC97H cells were pretreated with SYY for 4 weeks and subsequently named MHCC97HSYY cells. Simultaneously, MHCC97H cells were cultured for 4 weeks without SYY and used as a negative control. Western blot analysis and enzyme-linked immunosorbent assays demonstrated that treatment with SYY inhibited EMT-associated changes and TGF-β1 expression in MHCC97H cells. MHCC97H and MHCC97HSYY cells were treated with 10 ng/ml TGF-β1 to induce EMT. The results of the present study demonstrated that pretreatment with SYY markedly inhibited TGF-β1-induced morphological changes, and reversed the expression of the EMT markers E-cadherin and N-cadherin. In addition, expression levels of the TGF-β1 downstream proteins, phosphorylated mothers against decapentaplegic homologs (p-SMAD)2 and 3, were reduced. Transwell assays indicated that pretreatment with SYY inhibited TGF-β1-induced cancer cell invasion and migration. The results of the present study indicate that SYY inhibited EMT through attenuation of TGF-β1 expression, and downregulation of p-SMAD2 and 3.
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http://dx.doi.org/10.3892/ol.2017.5700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403382PMC
April 2017

Incidence and outcomes of acute kidney injury in patients with hepatocellular carcinoma after liver transplantation.

J Cancer Res Clin Oncol 2017 Jul 13;143(7):1337-1346. Epub 2017 Mar 13.

Liver Cancer Institute, Shanghai, 200032, People's Republic of China.

Purpose: To describe the incidence and outcomes linked with acute kidney injury (AKI) after liver transplantation (LT) in hepatocellular carcinoma (HCC) patients.

Methods: From January 2003 to February 2011, HCC patients undergoing LT were retrospectively enrolled. Patient with a glomerular filtration rate (GFR) <60 mL/min/1.73 m was excluded. AKI was defined and classified according to the AKIN criteria.

Results: Of the 566 eligible patients, AKI was found in 109 (19.26%) patients (stage I, 66 cases; stage II, 15 cases; and stage III, 28 cases). Risk factors for AKI were the long anhepatic time (OR = 3.59, P = 0.009) and prolonged duration of systolic blood pressure (SBP) < 90 mmHg (OR = 1.07, P < 0.0001). Post-LT AKI was an independent risk factor associated with 30-day mortality (HR = 4.05, P = 0.047). Complete recovery occurred in 84 (77.06%) of all AKI episodes within 1 month after operation, while 25 patients (22.94%) suffered from prolonged AKI. Patients with prolonged AKI had a poorer 1-year survival than those with transient AKI (40 vs 86.90%; P < 0.0001). Patients with severe AKI more often developed prolonged AKI. 13 patients (52%) of the prolonged AKI progressed to chronic kidney disease (CKD) defined as eGFR <60 mL/min/1.73 m after 1 year post-operation.

Conclusions: Post-LT AKI is not an uncommon complication. Intra-operative hemodynamic instability is crucial in the development of post-LT AKI and deserves more attention. Most post-LT AKI is transient and reversible, while the prolonged form may predict a decrease survival.
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http://dx.doi.org/10.1007/s00432-017-2376-8DOI Listing
July 2017

Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study.

J Vasc Interv Radiol 2016 Dec 21;27(12):1829-1836. Epub 2016 Aug 21.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai 200032, China. Electronic address:

Purpose: To compare outcomes of transarterial chemoembolization with radiofrequency (RF) ablation in treatment of recurrent hepatocellular carcinoma (HCC) after resection within Barcelona Clinic Liver Cancer (BCLC) stage 0/A.

Materials And Methods: From January 2007 to December 2011, 110 consecutive patients with recurrent HCC meeting BCLC stage 0/A criteria underwent transarterial chemoembolization (n = 78; mean tumor size, 1.9 cm ± 1.0) or RF ablation (n = 32; mean tumor size, 1.9 cm ± 0.6) as initial treatment. The primary outcome was overall survival (OS). Kaplan-Meier method was used to construct survival curves, which were compared by log-rank test. Prognostic factors for OS were analyzed using univariate and multivariate Cox proportional hazard models.

Results: No significant differences between baseline clinical characteristics of the 2 treatment groups were identified. The 1-, 3-, and 5-year OS rates were 89.7%, 61.0%, and 36.6% for the transarterial chemoembolization group and 90.1%, 72.8%, and 60.0% for the RF ablation group. There was no significant difference in OS rates between the groups (P = .159). Subgroup analysis indicated that RF ablation achieved better survival than transarterial chemoembolization among patients ≤ 55 years old and patients with BCLC stage 0 (P = .036 and P = .045). Multivariate analysis revealed that serum albumin (≤ 35 g/L) (hazard ratio = 2.797; 95% confidence interval, 1.366-2.726; P = .005) and α-fetoprotein (> 400 ng/mL) (HR = 2.336; 95% CI, 1.210-4.508; P = .011) levels before treatment were 2 significant risk factors for poor prognosis.

Conclusions: Transarterial chemoembolization might provide a similar OS as RF ablation in patients with recurrent BCLC stage A HCC. However, RF ablation could provide better OS in patients with recurrent BCLC stage 0 HCC.
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http://dx.doi.org/10.1016/j.jvir.2016.06.010DOI Listing
December 2016

Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study.

Med Oncol 2015 Mar 15;32(3):64. Epub 2015 Feb 15.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.

Patients with huge hepatocellular carcinoma >10 cm in diameter represent a special subgroup for treatment. To date, there are few data and little consensus on treatment strategies for huge hepatocellular carcinoma. In this study, we summarized the effects and safety of transarterial chemoembolization for huge hepatocellular carcinoma. A retrospective study was performed based on a large cohort of patients (n = 511) with huge hepatocellular carcinoma who underwent serial transarterial chemoembolization between January 2008 to December 2011 and were followed up until March 2013. We found median survival time was 6.5 months. On multivariate analysis, Child-Pugh class (A versus B) (p < 0.0001), alpha-fetoprotein (≤400 µg/L) (p = 0.002), Barcelona Clinic Liver Cancer stage (B versus C) (p = 0.013), and other treatments after transarterial chemoembolization such as surgical resection (p = 0.008), radiation (p = 0.018), and local radiofrequency ablation (p = 0.002) were factors significantly associated with better overall patient survival after chemoembolization. Twenty-nine percent of these patients showed a tumor response after serial transarterial chemoembolization. Severe complications were few (4.9%), including oncolytic syndrome (n = 3), tumor rupture (n = 3), gastrointestinal bleeding (n = 4), deep venous thrombosis (n = 3), acute cholecystitis (n = 4), femoral artery pseudoaneurysm (n = 1), acute pancreatitis (n = 1), and acute hepatic failure (n = 6). In conclusion, transarterial chemoembolization is a safe and effective treatment for selected patients with huge hepatocellular carcinoma and is recommended as a component of combination therapy. In addition, patients with good liver function and low alpha-fetoprotein levels may acquire greater survival benefits from transarterial chemoembolization.
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http://dx.doi.org/10.1007/s12032-015-0504-3DOI Listing
March 2015

Comparison of Plastic Surgery Residency Training in United States and China.

Ann Plast Surg 2015 Dec;75(6):672-8

From the *Resident Training Program and †Department of Surgery at Zhongshan Hospital, Fudan University, Shanghai, China; ‡Department of Surgery, University of Mississippi Medical Center, Jackson, MS; §Joseph M. Still Burn and Reconstructive Center, Jackson, MS; and ∥Department of Orthopedic Surgery at Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Residency training is internationally recognized as the only way for the physicians to be qualified to practice independently. China has instituted a new residency training program for the specialty of plastic surgery. Meanwhile, plastic surgery residency training programs in the United States are presently in a transition because of restricted work hours. The purpose of this study is to compare the current characteristics of plastic surgery residency training in 2 countries.

Methods: Flow path, structure, curriculum, operative experience, research, and evaluation of training in 2 countries were measured. The number of required cases was compared quantitatively whereas other aspects were compared qualitatively.

Results: Plastic surgery residency training programs in 2 countries differ regarding specific characteristics. Requirements to become a plastic surgery resident in the United States are more rigorous. Ownership structure of the regulatory agency for residency training in 2 countries is diverse. Training duration in the United States is more flexible. Clinical and research training is more practical and the method of evaluation of residency training is more reasonable in the United States. The job opportunities after residency differ substantially between 2 countries. Not every resident has a chance to be an independent surgeon and would require much more training time in China than it does in the United States.

Conclusions: Plastic surgery residency training programs in the United States and China have their unique characteristics. The training programs in the United States are more standardized. Both the United States and China may complement each other to create training programs that will ultimately provide high-quality care for all people.
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http://dx.doi.org/10.1097/SAP.0000000000000226DOI Listing
December 2015

γ-Glutamyltranspeptidase is a prognostic marker of survival and recurrence in radiofrequency-ablation treatment of hepatocellular carcinoma.

Ann Surg Oncol 2014 Sep 21;21(9):3084-9. Epub 2014 Apr 21.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China,

Purpose: Serum γ-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC.

Methods: This retrospective study included 254 patients with small liver cancer (tumor of ≤5 cm in diameter and nodule of ≤3 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors.

Results: After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence.

Conclusions: Serum GGT is a convenient prognostic biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.
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http://dx.doi.org/10.1245/s10434-014-3724-4DOI Listing
September 2014

Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy.

Genes Cancer 2013 Jul;4(7-8):247-60

Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, MI, USA.

Hepatitis B virus (HBV) is a well-known cause of hepatocellular carcinoma (HCC), but the regulators effectively driving virus production and HCC progression remain unclear. By using genetically engineered mouse models, we show that overexpression of hepatocyte growth factor (HGF) accelerated HCC progression, supporting the genomic analysis that an up-regulated HGF signature is associated with poor prognosis in HBV-positive HCC patients. We show that for both liver regeneration and spontaneous HCC development there is an inclusive requirement for MET expression, and when HGF induces autocrine activation the tumor displays sensitivity to a small-molecule Met inhibitor. Our results demonstrate that HGF is a driver of HBV-induced HCC progression and may serve as an effective biomarker for Met-targeted therapy. MET inhibitors are entering clinical trials against cancer, and our data provide a molecular basis for targeting the Met pathway in hepatitis B-induced HCC.
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http://dx.doi.org/10.1177/1947601913501075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807646PMC
July 2013

Delivery of hydrophilic drug doxorubicin hydrochloride-targeted liver using apoAI as carrier.

J Drug Target 2013 May 19;21(4):367-74. Epub 2013 Apr 19.

School of Pharmacy, Fudan University, Shanghai, China.

High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the scavenger receptor class B type 1 (SR-B1) receptor on the surface of hepatocytes. Therefore, ApoA1 can be potentially used to target drugs to the liver. In this study, we successfully loaded doxorubicin hydrochloride (Dox or Dox-HCl), which is a hydrophilic drug used in a wide variety of clinical applications, into the core of reconstituted HDL (rHDL prepared by apoAI and egg phospholipids) to form a doxorubicin-HDL complex (rHDL-Dox). The MTT assays showed that rHDL-Dox particles also had higher cytotoxicity against several cells lines compared to free drug or Dox encapsulated into liposomes. A cellular uptake assay demonstrated that rHDL-Dox had higher absorption in SR-BI receptor positive liver cells. Importantly, in vivo experiments showed that rHDL-Dox can reduce tumor growth more effectively than liposomes. In addition, an in vitro hemolysis assay showed that rHDL-Dox caused only limited hemolysis in the case of high doses. Taken together, our findings indicate that rHDL is a safe and effective drug delivery system for targeting liver.
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http://dx.doi.org/10.3109/1061186X.2012.757769DOI Listing
May 2013

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection.

J Cancer Res Clin Oncol 2013 May 3;139(5):773-81. Epub 2013 Feb 3.

Liver Cancer Institute, Shanghai, China.

Purpose: To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods: One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results: There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion: Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.
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http://dx.doi.org/10.1007/s00432-012-1343-7DOI Listing
May 2013

Oral traditional Chinese medication for adhesive small bowel obstruction.

Cochrane Database Syst Rev 2012 May 16(5):CD008836. Epub 2012 May 16.

Department of General Surgery, Zhongshan Hospital, Institute of General Surgery, Fudan University, Shanghai, China.

Background: Small bowel obstruction (SBO) is one of the most common emergent complications of general surgery. Intra-abdominal adhesions are the leading cause of SBO. Because surgery can induce new adhesions, non-operative management is preferred in the absence of signs of peritonitis or strangulation. Oral traditional Chinese herbal medicine has long been used as a non-operative therapy to treat adhesive SBO in China. Many controlled trials have been conducted to investigate its therapeutic value in resolving adhesive SBO.

Objectives: The aim of this review was to assess the efficacy and safety of oral traditional Chinese medicine (TCM) for adhesive small bowel obstruction.

Search Methods: We searched the following databases, without regard to language or publishing restrictions: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure/Chinese Academic Journals full-text Database (CNKI), and VIP (a full-text database of Chinese journals). The searches were conducted in November 2011.

Selection Criteria: Randomised controlled trials and quasi-randomised controlled trials comparing Chinese medicines administered orally, via the gastric canal, or both with a placebo or conventional therapy in participants diagnosed with adhesive SBO were considered. We also considered trials of TCM (oral administration, gastric tube perfusion, or both) plus conventional therapy compared with conventional therapy alone for patients with adhesive SBO. Studies addressing the safety and efficacy of oral traditional Chinese medicinal agents in the treatment of adhesive SBO were also considered.

Data Collection And Analysis: Two authors collected the data independently. We assessed the risk of bias according to the following methodological criteria: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other sources of bias. Dichotomous data are presented as risk ratios (OR) and 95% confidence intervals (CI); continuous outcomes are presented as mean differences (MD) and 95% CIs. The data analyses were carried out using Review Manager 5.1. For cases in which necessary information was not reported in the paper, we contacted the primary authors for additional information.

Main Results: Five randomised trials involving 664 participants were analysed. Five different herbal medicines were tested in these trials, including Huo-Xue-Tong-Fu decoction, Xiao-Cheng-Qi-Tang decoction, a combination of Xiao-Cheng-Qi-Tang and Si-Jun-Zi-Tang decoctions, Chang-Nian-Lian-Song-Jie-Tang decoction, and Fufang-Da-Cheng-Qi-Tang decoction. There were variations in the tested herbal compositions and methods of medicine administration. The main outcomes reported in the trials were effects on abdominal pain, abdominal distension, constipation defection, time of first defecation after treatment, and reoperation rate during the course of the disease. Secondary outcomes selected for this review were not available, including complications such as small bowel perfusion (bowel resection, system complications, and other possible complications), length of hospital stay, cost of hospitalisation, and time from admission to surgical intervention. The results of five trials showed that patients receiving TCM combined with conventional therapy seemed to have improved outcomes compared with patients receiving conventional treatment alone (OR 4.24, 95% CI 2.83 to 6.36).However, we cannot conclusively determine the efficacy of TCM in this review due to inadequate reporting, low methodological quality, and the prevalence of various biases in the reviewed studies. Furthermore, because none of the reviewed trials discussed adverse events, we could not evaluate the safety of TCM for adhesive SBO patients. All trials were conducted and published in China.

Authors' Conclusions: Although many studies have assessed the use of TCM products for adhesive SBO, most were excluded from this review due to their methodological limitations. This systematic review did not find sufficient evidence to support the objective efficacy and safety of TCM for patients with adhesive SBO. The positive evidence should be interpreted with caution given the insufficient number of studies with large sample sizes, the absence of well-designed, high-quality trials, and the lack of safety information. Therefore, further studies with larger sample sizes and high-quality, randomised, and controlled trials are necessary to produce more accurate and meaningful data on the efficacy of Chinese herbal medicines for adhesive SBO.
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http://dx.doi.org/10.1002/14651858.CD008836.pub2DOI Listing
May 2012

Prognostic significance of alpha-fetoprotein status in the outcome of hepatocellular carcinoma after treatment of transarterial chemoembolization.

Ann Surg Oncol 2012 Oct 25;19(11):3540-6. Epub 2012 Apr 25.

Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, People's Republic of China.

Background: Alpha-fetoprotein (AFP) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its prognostic significance is not well defined. This study was performed to classify the prognostic significance of AFP status in HCC patients after transarterial chemoembolization (TACE).

Methods: Four hundred forty-one HCC patients from a prospective maintained database with pathologic confirmation including 139 with normal AFP levels and 302 with elevated AFP levels were retrospectively studied for prognostic significance of AFP in treatment response and survival after TACE. Univariate and multivariate analyses were used to identify the prognostic factors.

Results: There were significant differences in overall survival (OS) after TACE between AFP-negative and AFP-positive HCC patients when the AFP cutoff value was defined as 20 ng/ml (P < 0.0001). Among the AFP-positive patients, different AFP levels had no significantly prognostic effects on OS after TACE (P = 0.093). Multivariate analysis revealed that AFP status for AFP-negative or positive was an independent prognostic factor for HCC patients after TACE (P = 0.001), along with γ-glutamyltransferase (GGT) level (P = 0.004) and tumor diameter (P < 0.0001). In addition, there were significant differences in clinicopathologic features between AFP-positive and AFP-negative patients with regard to age, gender, alanine transferase level, GGT level, tumor diameter, and Barcelona Clinic Liver Cancer stage.

Conclusions: Compared with AFP-positive HCC patients, patients with AFP-negative status have a better treatment response and prognosis after TACE.
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http://dx.doi.org/10.1245/s10434-012-2368-5DOI Listing
October 2012

Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta-analysis.

BMC Cancer 2012 Jan 16;12:17. Epub 2012 Jan 16.

Live Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Backgrounds: There have been conflicting reports about serum golgi protein 73 (GP73) as one of the most promising serum markers for the diagnosis of hepatocellular carcinoma (HCC). This study was to make a systematic review about the diagnostic accuracy of serum GP73 versus alpha-fetoprotein (AFP) for HCC.

Methods: After a systematic review of related studies, sensitivity, specificity and other measures about the accuracy of serum GP73 and AFP in the diagnosis of HCC were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance.

Results: Eight studies were included in our meta-analysis. The summary estimates for serum GP73 and AFP in diagnosing HCC in the studies included were as follows: sensitivity, 76% (95% confidence interval (CI) 51-91%) vs. 70% (47-86%); specificity, 86% (95%CI 65-95%) vs. 89% (69-96%); diagnostic odds ratio (DOR), 18.59 (95%CI 5.33-64.91) vs. 18.00(9.41-34.46); and area under sROC, 0.88 (95%CI 0.77-0.99) vs. 0.86 (95%CI 0.84-0.87).

Conclusions: The current evidence indicates that serum GP73 has a comparable accuracy to AFP for the diagnosis of HCC, while the value of serum GP73 in combination with AFP for HCC detection deserves further investigation.
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http://dx.doi.org/10.1186/1471-2407-12-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292967PMC
January 2012

Prognostic significance of serum gamma-glutamyl transferase in patients with intermediate hepatocellular carcinoma treated with transcatheter arterial chemoembolization.

Eur J Gastroenterol Hepatol 2011 Sep;23(9):787-93

Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory for Carcicnogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, People's Republic of China.

Objectives: Not every unresectable hepatocellular carcinoma (HCC) could receive survival benefits from transcatheter arterial chemoembolization (TACE), even for intermediate HCC (Barcelona Clinic Liver Cancer stage B). The aim of this study was to investigate prognostic significance of serum γ-glutamyl transferase (GGT) in patients with intermediate HCC treated with TACE.

Methods: A total of 277 patients with intermediate HCC were consecutively treated with TACE and overall survival (OS) was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method according to GGT value before treatment. Univariate and multivariate analyses were used for the study of significance of prognostic factor.

Results: The median follow-up period was 18.7 months. The 1-year and 3-year OS rates were 71.6 and 38.5% in patients with normal GGT and 48.8 and 16.9% in patients with high GGT (P=0.002). High GGT, correlating with higher tumor size, α-fetoprotein (AFP), and alanine aminotrasferase, was an independent prognostic factor for OS (P=0.009). Others included tumor size and ascites. Furthermore, in small HCC and normal AFP subgroup, serum GGT was also correlated with OS (P=0.013 and 0.041, respectively). The combination of GGT and AFP had a better power to predict the TACE effects.

Conclusion: GGT level was an important prognostic factor to predict prognosis of patients with intermediate HCC treated with TACE.
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http://dx.doi.org/10.1097/MEG.0b013e32834902ddDOI Listing
September 2011

Risk factors for recurrence of small hepatocellular carcinoma after long-term follow-up of percutaneous radiofrequency ablation.

Eur J Radiol 2011 Aug 19;79(2):196-200. Epub 2010 Mar 19.

Liver Cancer Institute and Zhongshan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China.

Radiofrequency ablation (RFA) as a local therapy for liver cancer is widely used. The study is to evaluate the therapeutic efficacy of RFA on hepatocellular carcinoma (HCC) and identify the risk factors for recurrence. Clinical records of 124 patients with 135 small HCC with percutaneous RFA as a first-line treatment modality were evaluated in Liver Cancer Institute, Zhongshan Hospital from October 2001 to December 2006. With a median follow-up period of 46 months after RFA therapy, the 1-, 2-, 3-, 4-, and 5-year cumulative survival rates and disease-free survival rates were 91, 70, 61, 48 and 40% and 64, 44, 31, 24 and 24%, respectively. The total recurrence and metastasis rates were 50 and 6.5%, respectively. Independent risk factors for recurrence after RFA included tumor with diameter more than 3 cm, located near the intrahepatic blood vessels, subcapsular locations and PT prolonged more than 3s. Severe complications occurred in 2 cases (1.6%), including biliary tract hemorrhage and subphrenic effusion. RFA appears to be a safe and effective treatment for HCC. It will benefit the efficacy of RFA therapy if those risk factors are considered during the clinical practice.
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http://dx.doi.org/10.1016/j.ejrad.2010.02.010DOI Listing
August 2011