Publications by authors named "Yaojun Zhang"

81 Publications

Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Oct 12. Epub 2021 Oct 12.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively.

Objective: This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC.

Methods: A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes.

Results: Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy.

Conclusions: Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
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http://dx.doi.org/10.1245/s10434-021-10903-4DOI Listing
October 2021

Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin.

Phys Rev Lett 2021 Jun;126(25):258102

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that cross-linked chromatin can mechanically suppress droplets' coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.
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http://dx.doi.org/10.1103/PhysRevLett.126.258102DOI Listing
June 2021

Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients.

BMC Cancer 2021 Jul 4;21(1):775. Epub 2021 Jul 4.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.

Background: Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy.

Methods: A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS.

Results: Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006).

Conclusion: Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
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http://dx.doi.org/10.1186/s12885-021-08428-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254996PMC
July 2021

Rainfall increasing offsets the negative effects of nighttime warming on GHGs and wheat yield in North China Plain.

Sci Rep 2021 03 22;11(1):6505. Epub 2021 Mar 22.

School of Environmental Engineering, Nanjing Institute of Technology, Nanjing, 210000, Jiangsu, China.

The effects of nighttime warming and rainfall increasing on crop productivity and soil greenhouse gas emissions are few studied. This study was conducted with a field experiment to investigate the effects of nighttime warming, rainfall increasing and their interaction on wheat grain yield, methane (CH) and nitrous oxide (NO) emissions during a winter wheat growing season in the North China Plain (NCP). The results showed that nighttime warming and rainfall increasing significantly altered soil temperature and moisture, and thus the CH and NO emissions from the soil. Nighttime warming significantly promoted soil CH uptake by 21.2% and increased soil NO emissions by 22.4%. Rainfall increasing stimulated soil NO emissions by 15.7% but decreased soil CH uptake by 18.6%. Nighttime warming significantly decreased wheat yield by 5.5%, while rainfall increasing enhanced wheat yield by 4.0%. The results indicate that the positive effect of nighttime warming on CH uptake and negative effect on wheat yield can be offset by rainfall increasing in the NCP. Generally, rainfall increasing significantly raised the global warming potential and greenhouse gas intensity induced by CH and NO emissions. Overall, this study improves our understanding of agroecosystem C and N cycling in response to nighttime warming and rainfall increasing under future climate change.
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http://dx.doi.org/10.1038/s41598-021-86034-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985485PMC
March 2021

Decoding the physical principles of two-component biomolecular phase separation.

Elife 2021 Mar 11;10. Epub 2021 Mar 11.

Department of Molecular Biology, Princeton University, Princeton, United States.

Cells possess a multiplicity of non-membrane-bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon - for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.
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http://dx.doi.org/10.7554/eLife.62403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952089PMC
March 2021

Effect of prior cancer on survival of hepatocellular carcinoma: implications for clinical trial eligibility criteria.

BMC Cancer 2021 Feb 9;21(1):147. Epub 2021 Feb 9.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Background: Patients with cancer history are usually excluded from hepatocellular carcinoma (HCC) clinical trials. However, whether previous malignancy affects the oncological outcomes of HCC patients has not been fully assessed. This study aimed to evaluate whether prior cancer compromised the survival of HCC patients.

Methods: Patients with HCC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015, and then they were classified into groups with and without prior cancer. The Kaplan-Meier and multivariate Cox regression analysis were adopted to evaluate whether prior cancer impacted clinical outcomes after propensity score matching (PSM) adjusting baseline differences. Validation was performed in the cohort from our institution.

Results: We identified 2642 HCC patients with prior cancer. After PSM, the median overall survival (OS) time were 14.5 and 12.0 months respectively for groups with and without prior cancer. Prior cancer did not compromise prognosis in patients with HCC (p = 0.49). The same tendency was found in subgroups stratified by tumor stages and cancer interval period: OS was similar between groups with and without prior cancer (both p values> 0.1). In the multivariate Cox regression model, prior cancer did not adversely impact patients' survival (HR: 1.024; 95% CI: 0.961-1.092). In the validation cohort from our institution, prior cancer had no significant association with worse outcomes (p = 0.48).

Conclusion: For HCC patients, prior cancer did not compromise their survival, regardless of tumor stage and cancer interval period. Exclusion criteria for HCC clinical trials could be reconsidered.
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http://dx.doi.org/10.1186/s12885-021-07870-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871582PMC
February 2021

Lack of Response to Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: Abandon or Repeat?

Radiology 2021 03 19;298(3):680-692. Epub 2021 Jan 19.

From the Division of Interventional Ultrasound (S.C., M.K.), Cancer Center (S.C., M.K.), Department of Radiation Oncology (Z.P.), Clinical Trial Unit (Z.P., B.L., J.M.), Institute of Precision Medicine (Z.P., M.K.), Department of Interventional Oncology (Jiaping Li), Department of Radiology (S.F.), and Department of Liver Surgery (M.K.), The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, China 510080; Department of Hepatobiliary Surgery, Cancer Centre, Sun Yat-sen University, Guangzhou, China (Y.Z., M.C., R.G.); and Department of Liver Surgery, Dongguan People's Hospital, Dongguan, China (Jiali Li).

Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). It is unknown whether conventional TACE (cTACE) should be continued or abandoned after initial nonresponse for intermediate-stage HCC. The optimal number of sessions before abandoning cTACE remains debated. Purpose To define the number of sessions that patients who do not respond to treatment (hereafter, nonresponders, with stable disease [SD] or progressive disease [PD]) should undergo before abandoning cTACE. Materials and Methods Patients with intermediate-stage HCC and Child-Pugh A liver function who underwent consecutive cTACE sessions between January 2005 and December 2012 were retrospectively included from three centers. Radiologic response rate to each session and its correlation with overall survival were evaluated. Response was assessed by modified Response Evaluation Criteria in Solid Tumors. A nomogram constructed by using tumor size, tumor capsule, and α-fetoprotein to predict patients who responded to treatment (hereafter, responders) was validated with sensitivity and specificity. Results This study evaluated 4154 patients (mean age, 58 years ± 6 [standard deviation]; 3777 men; primary cohort, 3442 patients [mean age, 58 years ± 6; 3129 men]; validation cohort, 712 patients [mean age, 58 years ± 7; 648 men]). Response rate to first cTACE was 35.6% (1227 of 3442, primary cohort) and 36.7% (261 of 712, validation cohort). For patients with SD who were nonresponders to first cTACE, the response rates after second cTACE were 46.1% (719 of 1560) and 48.4% (147 of 304); for patients with SD who were nonresponders to the second cTACE session, the response rates after the third cTACE session were 58.3% (591 of 1014) and 48.5% (98 of 202). For patients with SD who were nonresponders to third, fourth, and fifth cTACE sessions, response rates after fourth, fifth, and sixth cTACE sessions were less than 10%. All response rates in patients with PD who were nonresponders to the next cTACE were less than 5%. Responders to first, second, and third cTACE had higher 5-year overall survival than nonresponders (all < .001) but responders to the fourth cTACE did not ( = .21). The sensitivity and specificity of a nomogram predicted responders to third cTACE: 75.0% and 79.4% (internal validation) and 78.6% and 87.0% (external validation), respectively. Conclusion Three sessions were recommended before abandoning conventional transarterial embolization (cTACE) for intermediate-stage hepatocellular carcinoma. The nomogram developed in this study identified responders to third cTACE. © RSNA, 2021 See also the editorial by Georgiades in this issue.
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http://dx.doi.org/10.1148/radiol.2021202289DOI Listing
March 2021

Can Immediately Treating Subcentimeter Hepatocellular Carcinoma Improve the Survival of Patients?

J Hepatocell Carcinoma 2020 16;7:377-384. Epub 2020 Dec 16.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China.

Background: With the development of imaging technology, an increasing number of subcentimeter hepatocellular carcinoma (HCC) has been detected. How to manage these lesions remains controversial and lacks evidence. We aimed to explore whether timely treating subcentimeter HCC is necessary considering the risks of false-positives and treatment failure.

Methods: In this retrospective study, we reviewed HCC patients treated with hepatectomy or ablation in our institution. Then, we enrolled 439 HCC patients with solitary lesion measuring up to 2 cm from November 1, 2009 to June 30, 2019. The baseline and clinical characteristics of these patients were collected. The patients were classified into primary and recurrent groups. The Kaplan-Meier method with Log-rank test was performed to compare the overall survival (OS) and recurrence-free survival (RFS) between patients with subcentimeter HCC and those with HCC measuring 1-2 cm. Univariate and multivariate analyses were adopted to identify prognostic factors for survival.

Results: The OS and RFS did not differ significantly between patients with subcentimeter HCC and those with HCC measuring 1-2 cm in the primary group (p = 0.12 and 0.75). Similar results were found in the recurrent group. In multivariate analysis, the albumin-bilirubin (ALBI) grade and serum alpha fetoprotein (AFP) level were significantly associated with OS and RFS in the primary group. The serum AFP level was the only factor that correlated with OS and RFS in the recurrent group.

Conclusion: Routine screening for subcentimeter HCC is feasible. Considering uncertain diagnosis and treatment difficulties, it is more considerable to follow patients until lesions are larger than 1 cm and then provide curative treatments.
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http://dx.doi.org/10.2147/JHC.S287641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751727PMC
December 2020

Baseline HBV Loads Do Not Affect the Prognosis of Patients with Hepatocellular Carcinoma Receiving Anti-Programmed Cell Death-1 Immunotherapy.

J Hepatocell Carcinoma 2020 1;7:337-345. Epub 2020 Dec 1.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.

Background: A high hepatitis B virus (HBV) load is a common exclusion criterion in hepatocellular carcinoma (HCC) clinical trials for anti-programmed cell death (PD)-1 immunotherapy. However, the validity of this criterion is barely verified. This study aimed to evaluate the impact of baseline HBV DNA levels and antiviral therapy on the oncological outcomes and liver functions of patients with HCC receiving anti-PD-1 immunotherapy.

Methods: We reviewed HCC trials related to anti-PD-(L)1 immunotherapy and whether they ruled out patients with increased HBV loads on clinicaltrials.gov. Then, for this retrospective study, we enrolled 253 HCC patients treated with anti-PD-1 blockade in our institution. Baseline information was compared between patients with low and high HBV loads. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncological outcomes and hepatic impairment.

Results: Among 76 HCC clinical trials including 13,927 patients receiving anti-PD-(L)1 blockade, 41 (53.9%) excluded patients with relatively high baseline HBV loads. The PFS and OS did not differ significantly between patients with baseline HBV loads ≤ 2000 IU/mL and those with viral loads >2000 IU/mL (p=0.615 and 0.982). The incidence of hepatic impairment showed no association with the baseline HBV load (p=0.319). Patients receiving antiviral therapy had a better OS than those without antiviral therapy in the high baseline HBV load group (p= 0.001).

Conclusion: High HBV loads did not compromise the clinical outcomes of HCC patients receiving anti-PD-1 blockade. Antiviral therapy could improve the OS of HCC patients with high HBV loads.
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http://dx.doi.org/10.2147/JHC.S278527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718972PMC
December 2020

Biochar addition alleviate the negative effects of drought and salinity stress on soybean productivity and water use efficiency.

BMC Plant Biol 2020 Jun 22;20(1):288. Epub 2020 Jun 22.

School of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.

Background: Environmental stress is a crucial factor restricting plant growth as well as crop productivity, thus influencing the agricultural sustainability. Biochar addition is proposed as an effective management to improve crop performance. However, there were few studies focused on the effect of biochar addition on crop growth and productivity under interactive effect of abiotic stress (e.g., drought and salinity). This study was conducted with a pot experiment to investigate the interaction effects of drought and salinity stress on soybean yield, leaf gaseous exchange and water use efficiency (WUE) under biochar addition.

Results: Drought and salinity stress significantly depressed soybean phenology (e.g. flowering time) and all the leaf gas exchange parameters, but had inconsistent effects on soybean root growth and WUE at leaf and yield levels. Salinity stress significantly decreased photosynthetic rate, stomatal conductance, intercellular CO concentration and transpiration rate by 20.7, 26.3, 10.5 and 27.2%, respectively. Lower biomass production and grain yield were probably due to the restrained photosynthesis under drought and salinity stress. Biochar addition significantly enhanced soybean grain yield by 3.1-14.8%. Drought stress and biochar addition significantly increased WUE by 27.5 and 15.6%, respectively, while salinity stress significantly decreased WUE by 24.2%. Drought and salinity stress showed some negative interactions on soybean productivity and leaf gaseous exchange. But biochar addition alleviate the negative effects on soybean productivity and water use efficiency under drought and salinity stress.

Conclusions: The results of the present study indicated that drought and salinity stress could significantly depress soybean growth and productivity. There exist interactive effects of drought and salinity stress on soybean productivity and water use efficiency, while we could employ biochar to alleviate the negative effects. We should consider the interactive effects of different abiotic restriction factors on crop growth thus for sustainable agriculture in the future.
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http://dx.doi.org/10.1186/s12870-020-02493-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310043PMC
June 2020

Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Cohort Study.

J Oncol 2020 28;2020:4835653. Epub 2020 May 28.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China.

Residual tumor tissue after radiofrequency ablation (RFA) is inevitable in clinical practice, and the optimal management of residual tumor after RFA has not been established. To evaluate the efficiency and toxicity of stereotactic body radiotherapy (SBRT) as a salvage therapy after incomplete RFA for hepatocellular carcinoma (HCC), we retrospectively included 32 HCC patients with an initial incomplete response (iIR) to RFA from May 2011 to August 2018. An iIR was defined as the presence of residual enhancement on CT or MRI one month after RFA treatment. The primary endpoint was local tumor control (LTC); the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. All patients fulfilled 6 fractions of SBRT as planned, with dosages ranging from 30 Gy to 54 Gy. The objective response rate (ORR) was 50.0%. The 1- and 2-year LTC rates were 86.6% (95% CI, 74.3% to 98.9%) and 74.7% (95% CI, 55.9% to 93.5%), respectively. Fewer times of prior treatments was associated with better LTC (HR = 11.7, =0.026). The 1- and 2-year PFS rate were 69.9% (95% CI, 53.4% to 86.4%) and 52.7% (95% CI, 33.1% to 72.3%), respectively. A higher Child-Pugh score was the only independent risk factor for tumor progression (HR = 5.17, =0.012). The 1- and 3-year OS rate were 85.6% and 67.1%, respectively. Only two patients suffered grade 3 adverse events, and none experienced grade 4 or 5 events. In conclusion, for HCC patients confirmed to have an iIR to prior RFA, with compensated liver function, SBRT provided favorable LTC and OS along with acceptable toxicity.
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http://dx.doi.org/10.1155/2020/4835653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275213PMC
May 2020

Single versus multiple port laparoscopic left lateral sectionectomy for hepatocellular carcinoma: A retrospective comparative study.

Int J Surg 2020 May 13;77:15-21. Epub 2020 Mar 13.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, PR China; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, PR China. Electronic address:

Background: Single port laparoscopic hepatectomy has been applied in some surgeries. We aimed to describe our experience with single port laparoscopic left lateral sectionectomy (SPLS) and to compare the safety and feasibility of this technique with those of conventional multi-port laparoscopic left lateral sectionectomy (MPLS) in the treatment of hepatocellular carcinoma (HCC).

Methods: A total of 72 consecutive patients who underwent SPLS (n = 33) and MPLS (n = 39) for HCC were enrolled. The peri-operative parameters of safety and feasibility, as well as the short-term oncological outcomes were compared.

Results: The length of postoperative hospital stay (LOS) was significantly shorter in the SPLS group than in the MPLS group (4.12 vs. 4.59 days, P = 0.043). No significant difference between the two groups was found in the operation time (104.58 vs. 95.69 min in the SPLS group and MPLS group respectively, P = 0.353) or the amount of blood loss (62.73 vs. 68.46 ml, P = 0.595). The 1-year recurrence-free survival rate was 77.9% in the SPLS group and 70.7% in the MPLS group (P = 0.82). Subgroup analysis showed that for patients without cirrhosis, the LOS was shorter in the SPLS group than in the MPLS group (P = 0.033), while for patients with cirrhosis, the LOS was not significantly different between the two groups (P = 0.201), although it was shorter in the SPLS group.

Conclusions: SPLS was a feasible and safe surgical approach for the treatment of HCC on left lateral section.
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http://dx.doi.org/10.1016/j.ijsu.2020.03.003DOI Listing
May 2020

Expression of hepatitis B surface antigen in liver tissues can serve as a predictor of prognosis for hepatitis B virus-related hepatocellular carcinoma patients after liver resection.

Eur J Gastroenterol Hepatol 2021 01;33(1):76-82

Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center.

Background: Hepatitis B surface antigen (HBsAg) is a detectable index after hepatitis B virus (HBV) infection, which is a risk factor of hepatocellular carcinoma (HCC). However, few studies have focused on the expression of HBsAg in HCC patients' liver tissues. This study aimed to explore the potential utility of using HBsAg protein expression in normal liver tissues as a prognostic factor for HCC patients who underwent liver resection.

Study Design: The study enrolled 100 HCC patients with seropositivity for HBsAg. The liver tissues were collected, and tissue microarrays were constructed. The expression of HBsAg in liver tissues were measured by immunohistochemistry (IHC). Relevant clinical data and follow-up records were collected for analysis.

Results: HBsAg expressions was detected in 29 patients (positive group) and was unable to be detected in the remaining 71 patients (negative group). The patients in the positive group had higher HBV DNA levels (P < 0.05) than the patients in the negative group. The overall survival (OS) rate of the positive group was worse than the OS rate of the negative group (P = 0.013). The OS rates after resection at 1 and 2 years in negative group were 90.1% and 85.7%, respectively, while the value in the positive group were 79.3% and 65.5%, respectively. Multivariate analysis showed that HBsAg expression in liver tissues, ascites and alpha-fetoprotein levels were independent factors influencing OS. Similarly, after propensity score matching (PSM), the OS was worse in the positive group than in the negative group, and HBsAg expression could also serve as a predictor for OS (P = 0.039). The OS rates after resection and PSM at 1 and 2 years were 93.2% and 85.9% in the negative group, while the value in the positive group were 79.3% and 65.5%.

Conclusion: As determined according to grouping based on immunohistochemistry staining results for HBsAg, this study indicated that HBsAg expression in liver tissues could predict the OS of HBV-related HCC patients after liver resection.
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http://dx.doi.org/10.1097/MEG.0000000000001698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704243PMC
January 2021

One-year clinical results of the NANO registry: A multicenter, prospective all-comers registry study in patients receiving implantation of a polymer-free sirolimus-eluting stent.

Catheter Cardiovasc Interv 2020 02 21;95 Suppl 1:658-664. Epub 2020 Jan 21.

Department of Cardiology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, China.

Objectives: We aimed to evaluate the safety and efficacy of Nano+™ (Lepu Medical, Beijing, China) stent implantation in all-comer patients at the 1-year follow-up.

Background: The Nano+™ stent is a novel polymer-free sirolimus-eluting stent polymer that employs nanoporous stent surface technology to control drug-delivery. The Nano+™ stent is one of the most widely used drug-eluting stent (DES) in China.

Methods: A total of 2,481 consecutive patients were included in the multicenter and prospective NANO registry. In this study, the primary endpoint was target lesion failure (TLF) at 1-year follow-up, defined as a composite of cardiac death, target vessel nonfatal myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). The safety endpoint was the occurrence of definite or probable stent thrombosis (ST).

Results: Up to 40.2% of patients presented with acute myocardial infarction (AMI). A total of 63.9% of the 2,904 lesions were American College of Cardiology/American Heart Association (ACC/AHA) type B2 or C lesions. One-year follow-up data were available for 98.4% of patients. The 1-year rate of TLF was 3.1% with rates of 1.3, 1.8, and 0.4% for clinically driven TLR, cardiac death, and TV-MI, respectively. ST occurred in 0.4% of patients. Diabetes mellitus, AMI, left ventricular ejection fraction <40% and long lesions (>40 mm) were independent predictors of 1-year TLF.

Conclusions: The 1-year clinical outcomes were excellent for Nano+™ polymer-free SES implantation in an all-comer patient population. Follow-up will be extended up to 5 years, to further elucidate the potential long-term clinical benefits.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.
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http://dx.doi.org/10.1002/ccd.28734DOI Listing
February 2020

Transarterial Chemoembolization Combined with Radiofrequency Ablation in the Treatment of Stage B1 Intermediate Hepatocellular Carcinoma.

J Oncol 2019 16;2019:6298502. Epub 2019 Sep 16.

Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou 510080, China.

Background: Due to the heterogeneity of patients with Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC), Bolondi criteria were proposed and patients were divided into four substages. The purpose of this study was to compare the survival of substage B1 patients who were initially treated with a combination of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (TACE-RFA) or TACE alone.

Methods: 404 patients with stage B1 HCC were retrospectively analyzed from January 2005 to December 2012. 209 patients received TACE-RFA, and 195 received TACE alone as initial treatment. The overall survival (OS) and progression-free survival (PFS) rates were estimated by the Kaplan-Meier method and compared by the log-rank test.

Results: 1-, 3-, and 5-year OS rates were 83.7%, 45.8%, and 24.8% in the TACE-RFA group and 80.7%, 26.4%, and 16.7% in the TACE group, respectively (=0.003). The corresponding PFS rates were 71.8%, 26.6%, and 13.0% and 59.1%, 11.0%, and 2.2% in the TACE-RFA group and TACE group, respectively ( < 0.001). Multivariate regression analysis indicated that tumor size (OS: hazard ratio (HR) = 0.683, =0.001; PFS: HR = 0.761, =0.013), along with treatment allocation (OS: HR = 0.701, =0.003; PFS: HR = 0.620, < 0.001), was the independent prognostic factor for both OS and PFS.

Conclusions: Combination TACE and RFA treatment yielded better survival than TACE alone for patients with stage B1 HCC according to the Bolondi criteria.
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http://dx.doi.org/10.1155/2019/6298502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766138PMC
September 2019

Single-Port Laparoscopic Hepatectomy for Liver Tumor: Operative Steps (With Video).

Surg Laparosc Endosc Percutan Tech 2019 Dec;29(6):e98-e101

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center.

Background: The single-port laparoscopic technique has been widely applied in abdominal surgery. We introduce a single-port laparoscopic hepatectomy for liver tumor in a single center.

Materials And Methods: This study included 37 patients who underwent single-port laparoscopic liver resection for liver tumor in the segments II, III, IV, and V between October 2017 and November 2018. Their perioperative course and operative techniques were retrospectively evaluated.

Results: All patients underwent single-port laparoscopic hepatectomy for liver tumor. None of the cases was converted to open surgery. The median procedure duration was 100 minutes (39 to 240 min), and the median blood loss volume was 50 mL (30 to 300 mL). No postoperative complications >3 grades were observed during the perioperative period. The median postoperative hospital stay was 4 days (3 to 7 d).

Conclusions: Single-port laparoscopic hepatectomy is a safe, feasible, and minimal incision, especially for tumors in the left lobe.
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http://dx.doi.org/10.1097/SLE.0000000000000724DOI Listing
December 2019

The Optimal Management for Sub-Centimeter Hepatocellular Carcinoma: Curative Treatments or Follow-Up?

Med Sci Monit 2019 Jul 4;25:4941-4951. Epub 2019 Jul 4.

Department of Minimally Invasive Interventional Radiology, Center of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China (mainland).

BACKGROUND The optimal strategy for dealing with sub-centimeter hepatic nodules has not yet been established. This study aimed to assess whether there was a need to provide curative treatments for sub-centimeter hepatocellular carcinomas (HCCs) to patients at risk for high false positives. MATERIAL AND METHODS We identified patients with primary pathologically diagnosed HCC ≤2 cm from 2004 to 2015 in the Surveillance, Epidemiology and End Results (SEER) database. They were divided according to the interventions they received: local ablation, surgical resection, or liver transplantation. In each group, overall survival and cancer-specific survival were used as endpoints to compare the prognoses between patients with sub-centimeter HCC and patients with HCC measuring 1 to 2 cm by Kaplan-Meier. Propensity score matching was performed to reduce bias. We also compared the survival of patients with a primary solitary HCC based on interventions, in the different tumor size groups. Bootstrapping was performed to validate the findings. RESULTS Overall, 10.4% of patients (197 out of 1894) had HCCs <1 cm, and 89.6% of patients (1697 out of 1894) had HCCs in the 1 to 2 cm range. There was no significant difference in overall and cancer-specific survival between patients with HCCs <1 cm and those with HCCs in the 1 to 2 cm range, in all treatment groups. After adjusting confounding factors, no significant correlation was found between tumor size and survival time. In patients with HCCs measuring ≤2 cm, overall survival and cancer-specific survival were superior in liver transplantation compared with surgical resection and local ablation. Surgical resection provided better survival than local ablation. CONCLUSIONS Compared to patients with HCCs measuring 1 to 2 cm, the survival rates of patients with sub-centimeter HCCs was not improved through curative treatments, risking high false positives.
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http://dx.doi.org/10.12659/MSM.916451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625578PMC
July 2019

Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions.

Nat Commun 2019 06 24;10(1):2771. Epub 2019 Jun 24.

Division of Biological Sciences, 0377, Department of Molecular Biology, University of California, San Diego, La Jolla, CA, 92093, USA.

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (V), diversity (D) and joining (J) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track V-DJ motion in B-lymphocytes. We find that V and DJ segments are trapped in configurations that allow only local motion, such that spatially proximal segments remain in proximity, while spatially remote segments remain remote. Within a subset of cells, however, abrupt changes in V-DJ motion are observed, plausibly caused by temporal alterations in chromatin configurations. Comparison of experimental and simulated data suggests that constrained motion is imposed by a network of cross-linked chromatin chains characteristic of a gel phase, yet poised near the sol phase, a solution of independent chromatin chains. These results suggest that chromosome organization near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.
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http://dx.doi.org/10.1038/s41467-019-10628-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591236PMC
June 2019

Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

Cancer Med 2019 08 17;8(9):4200-4213. Epub 2019 Jun 17.

Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE.

Methods: Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center.

Results: No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple-drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single-drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple-drug chemotherapy benefit versus single-drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller).

Conclusions: Triple-drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single-drug TACE.
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http://dx.doi.org/10.1002/cam4.2355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675716PMC
August 2019

Regulation of T cell expansion by antigen presentation dynamics.

Proc Natl Acad Sci U S A 2019 03 8;116(13):5914-5919. Epub 2019 Mar 8.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544;

An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher-affinity clones can suppress the proliferation of lower-affinity clones, thereby promoting the specificity of the response. Using the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.
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http://dx.doi.org/10.1073/pnas.1812800116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442601PMC
March 2019

MiR-139-5p, miR-940 and miR-193a-5p inhibit the growth of hepatocellular carcinoma by targeting SPOCK1.

J Cell Mol Med 2019 04 1;23(4):2475-2488. Epub 2019 Feb 1.

Cancer Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

The study was aimed to screen out miRNAs with differential expression in hepatocellular carcinoma (HCC), and to explore the influence of the expressions of these miRNAs and their target gene on HCC cell proliferation, invasion and apoptosis. MiRNAs with differential expression in HCC were screened out by microarray analysis. The common target gene of these miRNAs (miR-139-5p, miR-940 and miR-193a-5p) was screened out by analysing the target genes profile (acquired from Targetscan) of the three miRNAs. Expression levels of miRNAs and SPOCK1 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The target relationships were verified by dual luciferase reporter gene assay and RNA pull-down assay. Through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide,thiazolyl blue tetrazolium bromide (MTT) and transwell assays and flow cytometry, HCC cell viability, invasion and apoptosis were determined. In vivo experiment was conducted in nude mice to investigate the influence of three miRNAs on tumour growth. Down-regulation of miR-139-5p, miR-940 and miR-193a-5p was found in HCC. Overexpression of these miRNAs suppressed HCC cell viability and invasion, promoted apoptosis and inhibited tumour growth. SPOCK1, the common target gene of miR-139-5p, miR-940 and miR-193a-5p, was overexpressed in HCC. SPOCK1 overexpression promoted proliferation and invasion, and restrained apoptosis of HCC cells. MiR-139-5p, miR-940 and miR-193a-5p inhibited HCC development through targeting SPOCK1.
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http://dx.doi.org/10.1111/jcmm.14121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433657PMC
April 2019

Association of Sustained Response Duration With Survival After Conventional Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

JAMA Netw Open 2018 10 5;1(6):e183213. Epub 2018 Oct 5.

Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Importance: Defining early reliable surrogate end points for survival in patients with hepatocellular carcinoma (HCC) after conventional transarterial chemoembolization (cTACE) is of great value.

Objective: To evaluate the association between sustained response duration (SRD) and overall survival (OS) after cTACE for intermediate HCC.

Design, Setting, And Participants: This multicenter cohort study enrolled 2403 consecutive patients in China with naive intermediate HCC between June 1, 2000, and December 31, 2008, as the primary cohort, and 331 consecutive patients with intermediate naive HCC between January 1, 2011, to June 30, 2012, as the validation cohort. All patients received cTACE as an initial treatment. Initial response and best response were defined as the radiological response after first cTACE or best radiological response after 2 or more sessions of cTACE, respectively. Responders were those who experienced complete response or partial response. Sustained response duration was defined as the time between the date when complete response, partial response, or stable disease was achieved and the date progressive disease occurred after cTACE. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors. Information about patients in the study was collected from January 1, 2018, to March 31, 2018, and analysis of these data was performed in April 2018.

Main Outcomes And Measures: Overall survival.

Results: A total of 2734 total patients (2499 of 2734 [91.4%] male; median [range] age, 56.5 [18-75] years) were included in the analysis. In the primary cohort, SRD of 6 months or more was found to have the strongest association with 5-year OS after cTACE among different durations of sustained response. Patients with SRD of 6 months or more (387 of 430 male; median [range] age, 57 [18-75] years) had the longest median (range) OS (67.7 [64.8-72.1] months), followed by initial responders (760 of 874 male; median [range] age, 56 [18-75] years; median [range] OS, 55.8 [55.0-57.7] months) and best responders (939 of 1032 male; median [range] age, 57 [18-75] years; median [range] OS, 53.2 [52.2-54.6] months). Response duration of 6 months or more was found to be an independent prognostic factor for OS (hazard ratio, 0.145; 95% CI, 0.124-0.170; P < .001). The significance of SRD as a factor associated with OS was confirmed in the validation cohort.

Conclusions And Relevance: Sustained response duration of 6 months or more was associated with OS and may serve as an early surrogate end point after cTACE for intermediate HCC.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.3213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324454PMC
October 2018

Tumor Location Influences Oncologic Outcomes of Hepatocellular Carcinoma Patients Undergoing Radiofrequency Ablation.

Cancers (Basel) 2018 Oct 10;10(10). Epub 2018 Oct 10.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, China.

Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients ( = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively ( = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients ( = 0.013). The OS, RFS, and dRFS were not significantly different between groups.

Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.
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http://dx.doi.org/10.3390/cancers10100378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210710PMC
October 2018

A novel inflammation-based nomogram system to predict survival of patients with hepatocellular carcinoma.

Cancer Med 2018 10 27;7(10):5027-5035. Epub 2018 Sep 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer, Guangzhou, China.

Background And Aim: The existed staging systems were limited in the accuracy of prediction for overall survival (OS) of hepatocellular carcinoma (HCC) patients. The aim of this study is to establish a novel inflammation-based prognostic system with nomogram for HCC patients.

Methods: A prospective cohort of patients was recruited and assigned to the training cohort (n = 659) and validation cohort (n = 320) randomly. Different inflammation-based score systems were evaluated to select the best one predicting overall survival (OS). The inflammation-based score system with the highest predicting value and the parameters best reflecting tumor burden identified by multivariate analysis were selected to construct a novel predicting nomogram system. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C-index) and calibration curve and compared with conventional staging systems.

Results: With a highest C-index and areas under the receiver operating characteristic curve (AUC), C-reactive protein/albumin ratio (CAR) was selected to construct the novel system, along with tumor number, tumor size, macrovascular invasion and extra-hepatic metastases. The C-index of the nomogram was 0.813 (95% CI, 0.789-0.837) in the training cohort and 0.794 (95% CI, 0.756-0.832) in the validation cohort. The calibration curve for predicting probability of survival showed that the nomogram had a high consistency with follow-up data. The C-index of the novel system was higher than other conventional staging systems (P < 0.001).

Conclusions: The novel inflammation-based nomogram, developed from prospectively collected data in the present study, predicted the OS of HCC patients.
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http://dx.doi.org/10.1002/cam4.1787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198220PMC
October 2018

High expression of TACC2 in hepatocellular carcinoma is associated with poor prognosis.

Cancer Biomark 2018 ;22(4):611-619

Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.

Background: Transforming acidic coiled-coil protein 2 (TACC2) is a member of TACC family proteins which is mainly involved in the stabilization of spindles and regulation of microtubule dynamics through interactions with molecules involved in centrosomes/microtubules. TACC2 is involved in tumorigenesis of variety of cancers but the clinical significance of TACC2 protein in hepatocellular carcinoma (HCC) is still unclear.

Objective: This study aims to investigate the expression of TACC2 in HCC and determine if clinical significance and prognostic relevance exists.

Methods: We performed quantitative PCR (qPCR) and western blot to examine TACC2 mRNA and protein expression in paired HCC tissues and matched adjacent non-cancerous tissues. Immunohistochemistry was performed in 106 postoperative HCC samples.

Results: There was higher expression of TACC2 protein and mRNA in HCC tissue. Immunohistochemistry analysis showed high expression of TACC2 in HCC tissue and was significantly associated with the capsular extension, tumor recurrence and shortened overall and disease free survival. The Cox regression analysis suggested that a high expression of TACC2 was an independent prognostic factor for HCC patients.

Conclusion: This finding suggests that TACC2 may be a useful tool as a candidate biomarker to predict the recurrence and prognosis of HCC.
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http://dx.doi.org/10.3233/CBM-170091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130418PMC
November 2018

Sorafenib Monotherapy Versus Sorafenib Combined with Regional Therapies for Hepatocellular Carcinoma Patients with Pulmonary Oligometastases: A Propensity Score-matched Analysis.

J Cancer 2018 19;9(10):1745-1753. Epub 2018 Apr 19.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.

Sorafenib has been recommended as the standard therapy for advanced HCC with extrahepatic metastasis. The purpose of this retrospective study was to investigate the difference in overall survival (OS) between treatments with sorafenib combined with regional therapies versus sorafenib monotherapy in hepatocellular carcinoma (HCC) patients with pulmonary oligometastases. The study retrospectively enrolled 95 consecutive patients who underwent sorafenib therapy. A combined group (CG) of 40 patients received regional therapy in addition to sorafenib, and a monotherapy group (MG) of 55 patients received only sorafenib. OS was the primary endpoint, and time to progression (TTP) was the secondary endpoint. Subgroup analysis was further performed to evaluate the differences between the two groups. A propensity score-matched analysis was performed to overcome the bias. Median OS was significantly longer in the CG than in the MG (18.37 vs. 7.13 months; = 0.002). Multivariate analysis identified three baseline characteristics that were prognostic indicators of OS: macrovascular invasion, regional therapy, and alpha-fetoprotein. Median TTP was significantly longer in the CG than in the MG (2.93 vs. 2.23 months; = 0.004). Further multivariate analysis showed alpha-fetoprotein, total bilirubin, and regional therapy as prognostic indicators of TTP. After propensity score matching, 34 paired patients constituted each group. Patients in the adjusted CG showed a longer OS and TTP than those in the adjusted MG (OS: 18.37 vs. 7.37 months, = 0.015; TTP: 3.12 vs. 2.265 months, = 0.009). Multivariate analysis showed that combining regional therapies was still a prognostic indicator of OS ( = 0.01) and TTP ( = 0.001). Sorafenib combined with regional therapies may be associated with prolonged OS and TTP in HCC patients with pulmonary oligometastases compared with sorafenib monotherapy.
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http://dx.doi.org/10.7150/jca.24568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968762PMC
April 2018

The mutation of hepatitis B virus and the prognosis of hepatocellular carcinoma after surgery: a pilot study.

Cancer Manag Res 2018 27;10:599-611. Epub 2018 Mar 27.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Although hepatitis B virus (HBV) is still one of the most common etiological factors for hepatocellular carcinoma (HCC), the association between the HBV mutations and the clinical characteristics and prognosis of HBV-related HCC patients (HBV-HCC) after surgical resection remains largely unknown.

Materials And Methods: A cohort of 131 consecutive patients who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV genotype and 14 genomic mutations, which have been reported to relate to HCC in liver samples, were sequenced. The associations between the genomic mutations and clinical characteristics and outcomes were analyzed.

Results: Both A1762T/G1764A mutation and Pre S deletion related to worse overall survival (OS, =0.040 and <0.001, respectively) and disease-free survival (DFS, =0.040 and <0.001, respectively), G1899A mutation related to worse OS (=0.030), A1762T/G1764A mutation correlated with tumor size (=0.204, =0.019), G1899A mutation correlated with vascular invasion (=0.332, <0.001), and Pre S deletion correlated with alpha-fetoprotein (AFP; =0.254, =0.003) positively. Multivariate analysis with Cox proportional hazards model revealed that both A1762T/G1764A mutation and Pre S deletion were independent prognostic factors for OS (hazard ratio [HR]=3.701, 95% CI=1.390-9.855, =0.009, and HR=4.816, 95% CI=2.311-10.032, <0.001, respectively) and DFS (HR=3.245, 95% CI=1.400-7.521, =0.006, and HR=2.437, 95% CI=1.311-4.530, <0.001, respectively), and patients with dual mutations were found to have the worst OS and DFS (<0.001 and <0.001, respectively). Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have early recurrence (=0.042 and =0.019, respectively).

Conclusion: HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were associated with worse prognoses and early recurrence for HBV-HCC patients after surgery.
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http://dx.doi.org/10.2147/CMAR.S160047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877868PMC
March 2018

Overexpression of LAMC1 predicts poor prognosis and enhances tumor cell invasion and migration in hepatocellular carcinoma.

J Cancer 2017 25;8(15):2992-3000. Epub 2017 Aug 25.

Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.

LAMC1 encodes an extracellular matrix protein, laminin γ1 chain, which is involved in several biological and pathological processes including tissue development, tumor cell invasion and metastasis. In present study, we demonstrated that both LAMC1 protein and mRNA levels were elevated in HCC tissue samples compared with non-cancerous tissue samples according to western blot analyses, immunohistochemistry (IHC) and microarray. Moreover, high LAMC1 expression was positively correlated with incomplete encapsulation (=0.014), poor overall (OS, =0.02) and disease-free survival (DFS, =0.014). Using cell lines, we demonstrated that the levels of LAMC1 mRNA and protein were significantly higher in HCC cell lines than that in LO2 cell line. After the expression of LAMC1 was depressed by siRNA technique, the cell proliferation, migration and invasion were depressed significantly. Taken together, these data suggest that LAMC1 is enriched in HCC; overexpression of LAMC1 predicts poor prognosis, and enhances tumor cell invasion and migration. LAMC1 might be a new biomarker predictive of HCC prognosis and might also be a useful treatment target.
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http://dx.doi.org/10.7150/jca.21038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604451PMC
August 2017

Transcatheter arterial chemoembolization (TACE) versus hepatectomy in hepatocellular carcinoma with macrovascular invasion: a meta-analysis of 1683 patients.

J Cancer 2017 25;8(15):2984-2991. Epub 2017 Aug 25.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.

For hepatocellular carcinoma (HCC) patients with macrovascular invasion (MaVI), hepatectomy and transcatheter arterial chemoembolization (TACE) remain the main treatment options in Asia. However, which could achieve better survivals remains controversial. In present study, we conducted a meta-analysis to clarify the survival benefits and safety of hepatectomy versus TACE in HCC patients with MaVI. The PubMed, Cochrane Library and Web of Science databases were searched for eligible studies. There were no prospective studies identified. 8 retrospective studies from Asia with 1683 patients met our inclusion criteria were included in meta-analysis. The overall survival (OS) is higher in hepatectomy group than TACE group (HR=1.61, 95%CI=1.23-2.10, =0.0005). Hepatectomy was superior over TACE in 1-year (OR=2.27, 95%CI=1.26-4.08, =0.006) and 3-year (OR=3.04, 95%CI=2.17-4.26, <0.00001) respectively, but not in 5-year (OR=7.34, 95%CI=0.78-68.16, =0.08) survival rate. Subgroup analysis demonstrated that hepatectomy was superior over TACE for patients with PVTT (HR=1.50, 95%CI=1.14-1.98, =0.004), but not for patients with HVTT/IVC (HR=2.39, 95%CI=0.88-6.49, =0.09). There was not significantly difference between two groups in peri-operative mortality. Our results indicated that, compared to TACE, hepatectomy might be a better treatment option for resectable HCC patients with MaVI. Being lack of high-quality studies, more well-designed multi-center randomized trials are needed to confirm our finding.
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http://dx.doi.org/10.7150/jca.20978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604450PMC
August 2017
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